FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Gaddam, S
Rizvi, M
Nimmagadda, KC
Gala, B
Nagrani, T
Ghavami, F
McCord, D
Lafferty, J
AF Gaddam, Sainath
Rizvi, Muniba
Nimmagadda, Krishna Chaitanya
Gala, Bhavesh
Nagrani, Tarun
Ghavami, Foad
McCord, Donald
Lafferty, James
TI Proximal atherosclerotic lesion as a cause of very late stent thrombosis
SO MEDICAL HYPOTHESES
LA English
DT Article
ID SIROLIMUS-ELUTING STENT; BARE-METAL STENTS; CORONARY-ARTERY;
IMPLANTATION
AB Very late stent thrombosis is defined as in-stent thrombosis occurring after 1 year of an intra-coronary artery stent placement. Drug eluting stents have lately been criticized for increased reports of very late stent thrombosis. The exact cause of these very late stent thromboses is not clearly understood. Virchow's triad describes the three main factors of thrombus formation to be stasis of blood flow, endothelial injury and hypercoagulability. Based on Virchow's triad, we propose the cause of very late stent thrombosis to be formation of a de novo atherosclerotic lesion in the proximal segment of a stented artery. The de novo atherosclerotic lesion narrows the vessel lumen and causes stasis of blood flow in the distal stent. The de novo lesion can also cause myocardial ischemia creating a prothrombotic environment in the stented region. Stasis of blood flow and prothrombotic environment in the stented region can lead to the formation of very late stent thrombosis. Since atherosclerosis is a dynamic aging process in humans, we propose de novo proximal lesions in the coronary arteries can predispose to very late stent thrombosis. Published by Elsevier Ltd.
C1 [Gaddam, Sainath; Rizvi, Muniba] Staten Isl Univ Hosp, Dept Internal Med, Staten Isl, NY 10305 USA.
[Gala, Bhavesh; Nagrani, Tarun; Ghavami, Foad; McCord, Donald; Lafferty, James] Staten Isl Univ Hosp, Div Cardiol, Staten Isl, NY 10305 USA.
[Nimmagadda, Krishna Chaitanya] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Gaddam, S (reprint author), Staten Isl Univ Hosp, Dept Internal Med, 475 Seaview Ave, Staten Isl, NY 10305 USA.
EM gaddamsainath@gmail.com
NR 16
TC 3
Z9 3
U1 0
U2 1
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
J9 MED HYPOTHESES
JI Med. Hypotheses
PD APR
PY 2011
VL 76
IS 4
BP 500
EP 502
DI 10.1016/j.mehy.2010.11.036
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 742FK
UT WOS:000288926500012
PM 21185657
ER
PT J
AU Han, B
Xu, XG
Chen, GTY
AF Han, Bin
Xu, X. George
Chen, George T. Y.
TI Proton radiography and fluoroscopy of lung tumors: A Monte Carlo study
using patient-specific 4DCT phantoms
SO MEDICAL PHYSICS
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; RANGE VERIFICATION; RADIATION-THERAPY; ANIMAL
PATIENT; RECONSTRUCTION; PARAMETERS; EXPERIENCE; PARTICLES; BEAMS
AB Purpose: Monte Carlo methods are used to simulate and optimize a time-resolved proton range telescope (TRRT) in localization of intrafractional and interfractional motions of lung tumor and in quantification of proton range variations.
Methods: The Monte Carlo N-Particle eXtended (MCNPX) code with a particle tracking feature was employed to evaluate the TRRT performance, especially in visualizing and quantifying proton range variations during respiration. Protons of 230 MeV were tracked one by one as they pass through position detectors, patient 4DCT phantom, and finally scintillator detectors that measured residual ranges. The energy response of the scintillator telescope was investigated. Mass density and elemental composition of tissues were defined for 4DCT data.
Results: Proton water equivalent length (WEL) was deduced by a reconstruction algorithm that incorporates linear proton track and lateral spatial discrimination to improve the image quality. 4DCT data for three patients were used to visualize and measure tumor motion and WEL variations. The tumor trajectories extracted from the WEL map were found to be within similar to 1 mm agreement with direct 4DCT measurement. Quantitative WEL variation studies showed that the proton radiograph is a good representation of WEL changes from entrance to distal of the target.
Conclusions: MCNPX simulation results showed that TRRT can accurately track the motion of the tumor and detect the WEL variations. Image quality was optimized by choosing proton energy, testing parameters of image reconstruction algorithm, and comparing to ground truth 4DCT. The future study will demonstrate the feasibility of using the time resolved proton radiography as an imaging tool for proton treatments of lung tumors. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3555039]
C1 [Han, Bin; Xu, X. George] Rensselaer Polytech Inst, Troy, NY 12180 USA.
[Chen, George T. Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Xu, XG (reprint author), Rensselaer Polytech Inst, Troy, NY 12180 USA.
EM hanbinthu@gmail.com; xug2@rpi.edu
OI Han, Bin/0000-0001-8179-5762
FU NIH NCI [CA02139]; Rensselaer Polytechnic Institute
FX Dr. G. T. Y. Chen was supported, in part, by NIH NCI Grant No. CA02139
Proton Radiotherapy Research and Mr. B. Han was supported by a Van Auken
Fellowship from Rensselaer Polytechnic Institute. Dr. X. G. Xu performed
this work during his sabbatical leave at MGH. Dr. F. Sauli provided the
detail detector design and experimental data. The authors would like to
acknowledge information and technical assistance provided by Dr. S.
Mori, Dr. H. Paganetti, Dr. G. Sharp, Dr. B. Bednarz, and Mr. A. Ding
and the patient data from IRB approved study at MDAH courtesy of Dr. L.
Dong. In addition, the authors would like to thank the reviewers for
their helpful comments, which have improved the presentation and quality
of this paper.
NR 38
TC 7
Z9 8
U1 2
U2 6
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD APR
PY 2011
VL 38
IS 4
BP 1903
EP 1911
DI 10.1118/1.3555039
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 745GI
UT WOS:000289153500017
PM 21626923
ER
PT J
AU Fuchs, BB
Bishop, LR
Kovacs, JA
Mylonakis, E
AF Fuchs, Beth Burgwyn
Bishop, Lisa R.
Kovacs, Joseph A.
Mylonakis, Eleftherios
TI Galleria mellonella are Resistant to Pneumocystis murina Infection
SO MYCOPATHOLOGIA
LA English
DT Article
DE Galleria mellonella; Infection model; Pneumocystis murina
ID IMMUNE-RESPONSE; CARINII; VIRULENCE; LARVAE; MODEL; MICE; PATHOGENICITY;
EXPRESSION
AB Studying Pneumocystis has proven to be a challenge from the perspective of propagating a significant amount of the pathogen in a facile manner. The study of several fungal pathogens has been aided by the use of invertebrate model hosts. Our efforts to infect the invertebrate larvae Galleria mellonella with Pneumocystis proved futile since P. murina neither caused disease nor was able to proliferate within G. mellonella. It did, however, show that the pathogen could be rapidly cleared from the host.
C1 [Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Bishop, Lisa R.; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Fuchs, BB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA.
EM hfuchs@partners.org; emylonakis@partners.org
FU Intramural NIH HHS [ZIA CL000146-19]
NR 18
TC 6
Z9 6
U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-486X
J9 MYCOPATHOLOGIA
JI Mycopathologia
PD APR
PY 2011
VL 171
IS 4
BP 273
EP 277
DI 10.1007/s11046-010-9368-4
PG 5
WC Mycology
SC Mycology
GA 738TJ
UT WOS:000288664900006
PM 20922567
ER
PT J
AU Schunkert, H
Konig, IR
Kathiresan, S
Reilly, MP
Assimes, TL
Holm, H
Preuss, M
Stewart, AFR
Barbalic, M
Gieger, C
Absher, D
Aherrahrou, Z
Allayee, H
Altshuler, D
Anand, SS
Andersen, K
Anderson, JL
Ardissino, D
Ball, SG
Balmforth, AJ
Barnes, TA
Becker, DM
Becker, LC
Berger, K
Bis, JC
Boekholdt, SM
Boerwinkle, E
Braund, PS
Brown, MJ
Burnett, MS
Buysschaert, I
Carlquist, JF
Chen, L
Cichon, S
Codd, V
Davies, RW
Dedoussis, G
Dehghan, A
Demissie, S
Devaney, JM
Diemert, P
Do, R
Doering, A
Eifert, S
El Mokhtari, NE
Ellis, SG
Elosua, R
Engert, JC
Epstein, SE
de Faire, U
Fischer, M
Folsom, AR
Freyer, J
Gigante, B
Girelli, D
Gretarsdottir, S
Gudnason, V
Gulcher, JR
Halperin, E
Hammond, N
Hazen, SL
Hofman, A
Horne, BD
Illig, T
Iribarren, C
Jones, GT
Jukema, JW
Kaiser, MA
Kaplan, LM
Kastelein, JJP
Khaw, KT
Knowles, JW
Kolovou, G
Kong, A
Laaksonen, R
Lambrechts, D
Leander, K
Lettre, G
Li, MY
Lieb, W
Loley, C
Lotery, AJ
Mannucci, PM
Maouche, S
Martinelli, N
McKeown, PP
Meisinger, C
Meitinger, T
Melander, O
Merlini, PA
Mooser, V
Morgan, T
Muhleisen, TW
Muhlestein, JB
Munzel, T
Musunuru, K
Nahrstaedt, J
Nelson, CP
Nothen, MM
Olivieri, O
Patel, RS
Patterson, CC
Peters, A
Peyvandi, F
Qu, L
Quyyumi, AA
Rader, DJ
Rallidis, LS
Rice, C
Rosendaal, FR
Rubin, D
Salomaa, V
Sampietro, ML
Sandhu, MS
Schadt, E
Schafer, A
Schillert, A
Schreiber, S
Schrezenmeir, J
Schwartz, SM
Siscovick, DS
Sivananthan, M
Sivapalaratnam, S
Smith, A
Smith, TB
Snoep, JD
Soranzo, N
Spertus, JA
Stark, K
Stirrups, K
Stoll, M
Tang, WHW
Tennstedt, S
Thorgeirsson, G
Thorleifsson, G
Tomaszewski, M
Uitterlinden, AG
van Rij, AM
Voight, BF
Wareham, NJ
Wells, GA
Wichmann, HE
Wild, PS
Willenborg, C
Witteman, JCM
Wright, BJ
Ye, S
Zeller, T
Ziegler, A
Cambien, F
Goodall, AH
Cupples, LA
Quertermous, T
Marz, W
Hengstenberg, C
Blankenberg, S
Ouwehand, WH
Hall, AS
Deloukas, P
Thompson, JR
Stefansson, K
Roberts, R
Thorsteinsdottir, U
O'Donnell, CJ
McPherson, R
Erdmann, J
Samani, NJ
AF Schunkert, Heribert
Koenig, Inke R.
Kathiresan, Sekar
Reilly, Muredach P.
Assimes, Themistocles L.
Holm, Hilma
Preuss, Michael
Stewart, Alexandre F. R.
Barbalic, Maja
Gieger, Christian
Absher, Devin
Aherrahrou, Zouhair
Allayee, Hooman
Altshuler, David
Anand, Sonia S.
Andersen, Karl
Anderson, Jeffrey L.
Ardissino, Diego
Ball, Stephen G.
Balmforth, Anthony J.
Barnes, Timothy A.
Becker, Diane M.
Becker, Lewis C.
Berger, Klaus
Bis, Joshua C.
Boekholdt, S. Matthijs
Boerwinkle, Eric
Braund, Peter S.
Brown, Morris J.
Burnett, Mary Susan
Buysschaert, Ian
Carlquist, John F.
Chen, Li
Cichon, Sven
Codd, Veryan
Davies, Robert W.
Dedoussis, George
Dehghan, Abbas
Demissie, Serkalem
Devaney, Joseph M.
Diemert, Patrick
Do, Ron
Doering, Angela
Eifert, Sandra
El Mokhtari, Nour Eddine
Ellis, Stephen G.
Elosua, Roberto
Engert, James C.
Epstein, Stephen E.
de Faire, Ulf
Fischer, Marcus
Folsom, Aaron R.
Freyer, Jennifer
Gigante, Bruna
Girelli, Domenico
Gretarsdottir, Solveig
Gudnason, Vilmundur
Gulcher, Jeffrey R.
Halperin, Eran
Hammond, Naomi
Hazen, Stanley L.
Hofman, Albert
Horne, Benjamin D.
Illig, Thomas
Iribarren, Carlos
Jones, Gregory T.
Jukema, J. Wouter
Kaiser, Michael A.
Kaplan, Lee M.
Kastelein, John J. P.
Khaw, Kay-Tee
Knowles, Joshua W.
Kolovou, Genovefa
Kong, Augustine
Laaksonen, Reijo
Lambrechts, Diether
Leander, Karin
Lettre, Guillaume
Li, Mingyao
Lieb, Wolfgang
Loley, Christina
Lotery, Andrew J.
Mannucci, Pier M.
Maouche, Seraya
Martinelli, Nicola
McKeown, Pascal P.
Meisinger, Christa
Meitinger, Thomas
Melander, Olle
Merlini, Pier Angelica
Mooser, Vincent
Morgan, Thomas
Muehleisen, Thomas W.
Muhlestein, Joseph B.
Muenzel, Thomas
Musunuru, Kiran
nahrstaedt, Janja
Nelson, Christopher P.
Noethen, Markus M.
Olivieri, Oliviero
Patel, Riyaz S.
Patterson, Chris C.
Peters, Annette
Peyvandi, Flora
Qu, Liming
Quyyumi, Arshed A.
Rader, Daniel J.
Rallidis, Loukianos S.
Rice, Catherine
Rosendaal, Frits R.
Rubin, Diana
Salomaa, Veikko
Sampietro, M. Lourdes
Sandhu, Manj S.
Schadt, Eric
Schaefer, Arne
Schillert, Arne
Schreiber, Stefan
Schrezenmeir, Juergen
Schwartz, Stephen M.
Siscovick, David S.
Sivananthan, Mohan
Sivapalaratnam, Suthesh
Smith, Albert
Smith, Tamara B.
Snoep, Jaapjan D.
Soranzo, Nicole
Spertus, John A.
Stark, Klaus
Stirrups, Kathy
Stoll, Monika
Tang, W. H. Wilson
Tennstedt, Stephanie
Thorgeirsson, Gudmundur
Thorleifsson, Gudmar
Tomaszewski, Maciej
Uitterlinden, Andre G.
van Rij, Andre M.
Voight, Benjamin F.
Wareham, Nick J.
Wells, George A.
Wichmann, H-Erich
Wild, Philipp S.
Willenborg, Christina
Witteman, Jaqueline C. M.
Wright, Benjamin J.
Ye, Shu
Zeller, Tanja
Ziegler, Andreas
Cambien, Francois
Goodall, Alison H.
Cupples, L. Adrienne
Quertermous, Thomas
Maerz, Winfried
Hengstenberg, Christian
Blankenberg, Stefan
Ouwehand, Willem H.
Hall, Alistair S.
Deloukas, Panos
Thompson, John R.
Stefansson, Kari
Roberts, Robert
Thorsteinsdottir, Unnur
O'Donnell, Christopher J.
McPherson, Ruth
Erdmann, Jeanette
Samani, Nilesh J.
CA CARDIoGRAM Consortium
TI Large-scale association analysis identifies 13 new susceptibility loci
for coronary artery disease
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION; HEART-DISEASE; VARIANTS;
DESIGN; RISK; EXPRESSION; GENETICS; ATHEROSCLEROSIS; POLYMORPHISMS
AB We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
C1 [Schunkert, Heribert; Preuss, Michael; Aherrahrou, Zouhair; Diemert, Patrick; Freyer, Jennifer; Lieb, Wolfgang; Loley, Christina; Maouche, Seraya; nahrstaedt, Janja; Tennstedt, Stephanie; Willenborg, Christina; Erdmann, Jeanette] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Koenig, Inke R.; Preuss, Michael; Loley, Christina; nahrstaedt, Janja; Schillert, Arne; Willenborg, Christina; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany.
[Kathiresan, Sekar; Musunuru, Kiran] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar; Musunuru, Kiran] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kathiresan, Sekar; Musunuru, Kiran; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar; Altshuler, David; Musunuru, Kiran; Voight, Benjamin F.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Assimes, Themistocles L.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Holm, Hilma; Gretarsdottir, Solveig; Gulcher, Jeffrey R.; Kong, Augustine; Thorleifsson, Gudmar; Stefansson, Kari; Thorsteinsdottir, Unnur] DeCODE Genet, Reykjavik, Iceland.
[Stewart, Alexandre F. R.; Roberts, Robert; McPherson, Ruth] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada.
[Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Gieger, Christian; Doering, Angela; Illig, Thomas; Meisinger, Christa; Peters, Annette; Wichmann, H-Erich] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Absher, Devin] Hudson Alpha Inst, Huntsville, TX USA.
[Allayee, Hooman] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Altshuler, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Anand, Sonia S.] McMaster Univ, Hamilton, ON, Canada.
[Anand, Sonia S.] Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Andersen, Karl; Thorgeirsson, Gudmundur] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland.
[Andersen, Karl; Gudnason, Vilmundur; Smith, Albert; Thorgeirsson, Gudmundur; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Anderson, Jeffrey L.; Carlquist, John F.; Horne, Benjamin D.; Muhlestein, Joseph B.] Univ Utah, Div Cardiol, Cardiovasc Dept, Intermt Med Ctr, Salt Lake City, UT 84112 USA.
[Ardissino, Diego] Univ Parma, Div Cardiol, Azienda Osped, I-43100 Parma, Italy.
[Ball, Stephen G.] Univ Leeds, LIGHT Res Inst, Fac Med & Hlth, Leeds, W Yorkshire, England.
[Ball, Stephen G.; Hall, Alistair S.] Univ Leeds, Div Cardiovasc & Neuronal Remodelling, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England.
[Balmforth, Anthony J.; Nelson, Christopher P.] Univ Leeds, Div Cardiovasc & Diabet Res, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England.
[Barnes, Timothy A.; Braund, Peter S.; Codd, Veryan; Kaiser, Michael A.; Tomaszewski, Maciej; Goodall, Alison H.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England.
[Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA.
[Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany.
[Bis, Joshua C.; Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Resarch Unit, Seattle, WA 98195 USA.
[Bis, Joshua C.; Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Boekholdt, S. Matthijs; Kastelein, John J. P.; Sivapalaratnam, Suthesh] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
[Brown, Morris J.] Univ Cambridge, Clin Pharmacol Unit, Cambridge, England.
[Burnett, Mary Susan; Devaney, Joseph M.; Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, Medstar Hlth Res Inst, Washington, DC 20010 USA.
[Buysschaert, Ian] Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium.
[Buysschaert, Ian; Lambrechts, Diether] Katholieke Univ Leuven VIB, Vesalius Res Ctr, Louvain, Belgium.
[Chen, Li] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada.
[Cichon, Sven; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
[Cichon, Sven] Inst Neurosci & Med INM 1, Res Ctr Juelich, Julich, Germany.
[Dedoussis, George] Harokopio Univ, Dept Dietetics Nutr, Athens, Greece.
[Dehghan, Abbas; Hofman, Albert; Uitterlinden, Andre G.; Witteman, Jaqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Demissie, Serkalem; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Do, Ron; Engert, James C.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Eifert, Sandra; Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[El Mokhtari, Nour Eddine] Kreiskrankenhaus Rendsburg, Innere Med Klin, Rendsburg, Germany.
[Ellis, Stephen G.; Tang, W. H. Wilson] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
[Elosua, Roberto] Ciber Epidemiol & Salud Publ CIBERSP, Cardiovasc Epidemiol & Genet Grp, Inst Municipal Invest Med, Barcelona, Spain.
[Engert, James C.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[de Faire, Ulf; Gigante, Bruna; Leander, Karin] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden.
[de Faire, Ulf; Gigante, Bruna] Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
[Fischer, Marcus; Stark, Klaus; Hengstenberg, Christian] Klin & Poliklin Innere Med II, Regensburg, Germany.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth ARF, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Girelli, Domenico; Martinelli, Nicola; Olivieri, Oliviero] Univ Verona, Dept Med, I-37100 Verona, Italy.
[Gudnason, Vilmundur; Smith, Albert] Iceland Heart Assoc, Kopavogur, Iceland.
[Halperin, Eran] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel.
[Halperin, Eran] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel.
[Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA.
[Hammond, Naomi; Rice, Catherine; Soranzo, Nicole; Stirrups, Kathy; Ouwehand, Willem H.; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, S Cambs, England.
[Hazen, Stanley L.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA.
[Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Jones, Gregory T.; van Rij, Andre M.] Univ Otago, Dunedin Sch Med, Dept Surg, Dunedin, New Zealand.
[Jukema, J. Wouter] Leiden Univ, Dept Cardiol C5 P, Med Ctr, Leiden, Netherlands.
[Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England.
[Kolovou, Genovefa] Onassis Cardiac Surg Ctr, Cardiol Dept 1, Athens, Greece.
[Laaksonen, Reijo] Tampere Univ Hosp, Sci Ctr, Tampere, Finland.
[Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Lettre, Guillaume] Univ Montreal, Dept Med, Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada.
[Lotery, Andrew J.] Univ Southampton, Clin Neurosci Div, Sch Med, Southampton, Hants, England.
[Lotery, Andrew J.] Southampton Gen Hosp, Southampton Eye Unit, Southampton SO9 4XY, Hants, England.
[Mannucci, Pier M.] Osped Maggiore Policlin, Sci Direct, IRCCS, Fdn Ca Granda, Milan, Italy.
[McKeown, Pascal P.; Patterson, Chris C.] Queens Univ Belfast, Ctr Publ Hlth, Inst Clin Sci, Belfast, Ireland.
[Meitinger, Thomas] Deutsch Forschungszentrum Umwelt & Gesundheit, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany.
[Melander, Olle] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Scania Univ Hosp, Malmo, Sweden.
[Merlini, Pier Angelica] Azienda Osped Niguarda CaGranda, Div Cardiol, Milan, Italy.
[Mooser, Vincent] GlaxoSmithKline Inc, Genet Div, King Of Prussia, PA USA.
[Mooser, Vincent] GlaxoSmithKline Inc, Drug Discovery, King Of Prussia, PA USA.
[Morgan, Thomas] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[Muenzel, Thomas; Wild, Philipp S.; Zeller, Tanja; Blankenberg, Stefan] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin, Univ Med Mainz, Mainz, Germany.
[Patel, Riyaz S.; Quyyumi, Arshed A.] Emory Univ, Sch Med, Atlanta, GA USA.
[Patel, Riyaz S.] Cardiff Univ, Cardiff, S Glam, Wales.
[Peyvandi, Flora] Univ Milan, Osped Maggiore Policlin, A Bianchi Bonomi Hemophilia & Thrombosis Ctr, Dept Med & Med Specialties,Fdn IRCCS Ca Granda, Milan, Italy.
[Peyvandi, Flora] Luigi Villa Fdn, Milan, Italy.
[Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Rallidis, Loukianos S.] Univ Athens, Sch Med, Attikon Hosp, Dept Cardiol 2, GR-11527 Athens, Greece.
[Rosendaal, Frits R.; Snoep, Jaapjan D.] Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands.
[Rosendaal, Frits R.] Leiden Univ, Dept Thrombosis & Haemostasis, Med Ctr, Leiden, Netherlands.
[Rosendaal, Frits R.] Leiden Univ, Einthoven Lab Expt Vasc Med, Med Ctr, Leiden, Netherlands.
[Rubin, Diana] Univ Klinikum Schleswig Holstein, Med Klin 1, Kiel, Germany.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Chron Dis Epidemiol & Prevent Unit, Dept Chron Dis Prevent, Helsinki, Finland.
[Sampietro, M. Lourdes] Leiden Univ, Dept Human Genet & Cardiol, Med Ctr, Leiden, Netherlands.
[Sandhu, Manj S.] Wellcome Trust Sanger Inst, Genet Epidemiol Grp, Cambridge, England.
[Sandhu, Manj S.] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England.
[Schadt, Eric] Pacific Biosci, Menlo Pk, CA USA.
[Schadt, Eric] Sage Bionetworks, Palo Alto, CA USA.
[Schaefer, Arne; Schreiber, Stefan] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany.
[Schrezenmeir, Juergen] Max Rubner Inst, Inst Physiol & Biochem Nutr, Kiel, Germany.
[Schrezenmeir, Juergen] Kiel Innovat & Technol Ctr, Clin Res Ctr Kiel, Kiel, Germany.
[Sivananthan, Mohan] Leeds Teaching Hosp Natl Hlth Serv Trust, Cardiol Div, Leeds, W Yorkshire, England.
[Smith, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA.
[Spertus, John A.] Mid Amer Heart Inst, Kansas City, KS USA.
[Stoll, Monika] Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany.
[Tomaszewski, Maciej; Goodall, Alison H.; Samani, Nilesh J.] Glenfield Gen Hosp, Leicester Natl Inst Hlth Res, Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Voight, Benjamin F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Wareham, Nick J.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Sci Biometry & Epidemiol, Munich, Germany.
[Wright, Benjamin J.] Univ Leicester, Dept Cardiovasc Surg, Leicester, Leics, England.
[Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA.
[Ye, Shu] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
[Cambien, Francois] Univ Paris 06, INSERM, UMRS 937, Fac Med Pierre & Marie Curie, Paris, France.
[Maerz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, Heidelberg, Germany.
[Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Maerz, Winfried] Univ Heidelberg, Inst Publ Hlth Social & Prevent Med, Med Fac Manneim, Heidelberg, Germany.
[Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England.
[Ouwehand, Willem H.] NHS Blood Transplant, Cambridge, England.
[Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[McPherson, Ruth] Univ Ottawa, Inst Heart, Atherogen Lab, Ottawa, ON, Canada.
RP Schunkert, H (reprint author), Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
EM heribert.schunkert@uk-sh.de; njs@le.ac.uk
RI Leander, Karin/C-7261-2017; Erdmann, Jeanette/P-7513-2014; Cichon,
Sven/B-9618-2014; Mannucci, Pier/C-3102-2014; Meisinger,
Christine/B-5358-2014; Laaksonen, Reijo/D-6323-2014; Boekholdt,
Matthijs/G-7562-2014; Peters, Annette/A-6117-2011; Boehm,
Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Meitinger,
Thomas/O-1318-2015; Smith, Albert/K-5150-2015; Martinelli,
Nicola/J-5622-2016; Konig, Inke/A-4544-2009; Erdmann,
Jeanette/A-4417-2009; Stark, Klaus/D-3813-2009; Library, Woodruff
Health/A-6096-2012; Lieb, Wolfgang/C-1990-2012; Morgan, Tom/C-3478-2012;
Stewart, Alexandre/A-5677-2011; Willenborg, Christina/D-2668-2012;
Verdrengh, Evelien/H-4571-2012; Gigante, Bruna/I-9252-2012; Deloukas,
Panos/B-2922-2013; Tang, Wai Hong/I-1238-2013; Schreiber,
Stefan/B-6748-2008; Voight, Benjamin/F-1775-2011; Altshuler,
David/A-4476-2009; Cichon, Sven/H-8803-2013
OI Leander, Karin/0000-0002-1404-9222; Cupples, L.
Adrienne/0000-0003-0273-7965; Soranzo, Nicole/0000-0003-1095-3852;
Stewart, Alexandre/0000-0003-2673-9164; Meisinger,
Christa/0000-0002-9026-6544; ELOSUA, ROBERTO/0000-0001-8235-0095;
Erdmann, Jeanette/0000-0002-4486-6231; Cichon, Sven/0000-0002-9475-086X;
Gudnason, Vilmundur/0000-0001-5696-0084; Smith,
Albert/0000-0003-1942-5845; Martinelli, Nicola/0000-0001-6465-5119;
Peyvandi, Flora/0000-0001-7423-9864; Gieger,
Christian/0000-0001-6986-9554; Ziegler, Andreas/0000-0002-8386-5397;
Nothen, Markus/0000-0002-8770-2464; Jones, Gregory
T/0000-0002-6950-4210; Ouwehand, Willem/0000-0002-7744-1790; Dehghan,
Abbas/0000-0001-6403-016X; Stark, Klaus/0000-0002-7832-1942; Willenborg,
Christina/0000-0001-5217-6882; Deloukas, Panos/0000-0001-9251-070X;
Schreiber, Stefan/0000-0003-2254-7771; Altshuler,
David/0000-0002-7250-4107; Cichon, Sven/0000-0002-9475-086X
FU British Heart Foundation [RG/09/012/28096, PG/08/094/26019]; Medical
Research Council [G0401527, G0801566, G1000143, MC_U106179471]; NHLBI
NIH HHS [HL087647, N01 HC025195, R01 HL087647, R01HL089650-02]
NR 39
TC 734
Z9 742
U1 8
U2 97
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 2011
VL 43
IS 4
BP 333
EP U153
DI 10.1038/ng.784
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 741YL
UT WOS:000288903700013
PM 21378990
ER
PT J
AU Chaturvedi, S
Greenberg, SM
AF Chaturvedi, Seemant
Greenberg, Steven M.
TI Intracerebral hematoma expansion Making predictions (about the future)
SO NEUROLOGY
LA English
DT Editorial Material
ID HEMORRHAGE
C1 [Chaturvedi, Seemant] Wayne State Univ, Dept Neurol, Detroit, MI 48201 USA.
[Chaturvedi, Seemant] Wayne State Univ, Stroke Program, Detroit, MI 48201 USA.
[Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA.
[Greenberg, Steven M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Chaturvedi, S (reprint author), Wayne State Univ, Dept Neurol, 8C-UHC,4201 St Antoine, Detroit, MI 48201 USA.
EM SChaturv@med.wayne.edu
NR 8
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR
PY 2011
VL 76
IS 14
BP 1204
EP 1205
DI 10.1212/WNL.0b013e31821435d0
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 745CV
UT WOS:000289142500005
PM 21346224
ER
PT J
AU Elman, MJ
Bressler, NM
Qin, HJ
Beck, RW
Ferris, FL
Friedman, SM
Glassman, AR
Scott, IU
Stockdale, CR
Sun, JK
AF Elman, Michael J.
Bressler, Neil M.
Qin, Haijing
Beck, Roy W.
Ferris, Frederick L., III
Friedman, Scott M.
Glassman, Adam R.
Scott, Ingrid U.
Stockdale, Cynthia R.
Sun, Jennifer K.
TI Expanded 2-Year Follow-up of Ranibizumab Plus Prompt or Deferred Laser
or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema
SO OPHTHALMOLOGY
LA English
DT Article
AB Objective: To report expanded 2-year follow-up of a previously reported randomized trial evaluating intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME).
Design: Multicenter, randomized clinical trial.
Participants: A total of 854 study eyes of 691 participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea.
Methods: Continuation of procedures previously reported for the randomized trial.
Main Outcome Measures: Best-corrected visual acuity and safety at the 2-year visit.
Results: At the 2-year visit, compared with the sham + prompt laser group, the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab + prompt laser group (95% confidence interval adjusted for multiple comparisons [aCI], -0.4 to +7.7), 5.8 letters greater in the ranibizumab + deferred laser group (95% aCI, +1.9 to +9.8), and 1.5 letters worse in the triamcinolone + prompt laser group (95% aCI, -5.5 to +2.4). After the 1- to 2-year visit in the ranibizumab + prompt or deferred laser groups, the median numbers of injections were 2 and 3 (potential maximum of 13), respectively. At the 2-year visit, the percentages of eyes with central subfield thickness >= 250 mu m were 59% in the sham + prompt laser group, 43% in the ranibizumab + prompt laser group, 42% in the ranibizumab + deferred laser group, and 52% in the triamcinolone + prompt laser group. No systemic events attributable to study treatment were apparent. Three eyes in 3 (0.8%) of 375 participants had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group.
Conclusions: The expanded 2-year results reported are similar to results published previously and reinforce the conclusions originally reported: Ranibizumab should be considered for patients with DME and characteristics similar to those of the cohort in this clinical trial, including vision impairment with DME involving the center of the macula.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118:609-614 (C) 2011 by the American Academy of Ophthalmology.
C1 [Qin, Haijing; Beck, Roy W.; Glassman, Adam R.; Stockdale, Cynthia R.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
[Elman, Michael J.] PA, Elman Retina Grp, Baltimore, MD USA.
[Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA.
[Ferris, Frederick L., III] NIH, Bethesda, MD 20892 USA.
[Friedman, Scott M.] Florida Retina Consultants, Lakeland, FL USA.
[Scott, Ingrid U.] Penn State Univ, Coll Med, Hershey, PA USA.
[Sun, Jennifer K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Qin, HJ (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA.
EM drcrstat3@jaeb.org
FU National Eye Institute; National Institute of Diabetes and Digestive and
Kidney Diseases; National Institutes of Health; Department of Health and
Human Services [EY-14231, EY-14229, EY-18817]; Genentech; Allergan,
Inc.; Pfizer; Alcon; Allergan; Office of Research Administration; Bausch
Lomb; Carl Zeiss Meditec; EMMES Corporation; Lumenis; Notal Vision;
Novartis; QLT; Regeneron; Steba Biotech; Abbott Medical Optics; ForSight
Labs; LLC; Genzyme Corporation
FX Supported through cooperative agreements from the National Eye
Institute, National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health, and Department of Health and
Human Services EY-14231, EY-14229, EY-18817; The funding organization
(National Institutes of Health) participated in oversight of the conduct
of the study and review of the article but not directly in the design or
conduct of the study; the collection, management, analysis, or
interpretation of the data; or in the preparation of the article.
Genentech provided the ranibizumab for the study, and Allergan, Inc.,
provided the triamcinolone for the study. In addition, Genentech and
Allergan, Inc., provided funds to DRCR.net to defray the study's
clinical site costs. As described in the DRCR.net Industry Collaboration
Guidelines (available at www.drcr.net), the DRCR.net had complete
control over the design of the protocol, ownership of the data, and all
editorial content of presentations and publications related to the
protocol. A complete list of all DRCR.net investigator financial
disclosures can be found at www.drcr.net. Writing Committee financial
disclosures: Michael J. Elman: Genentech (consultant); Scott M.
Friedman: Pfizer (financial support); Alcon (financial support);
Allergan (financial support); Genentech (financial support); Ingrid U.
Scott: Genentech (consultant); Eyetech (consultant); Jennifer K. Sun:
Novartis (lecturer); Neil M. Bressler: Grants to investigators at The
Johns Hopkins University are negotiated and administered by the
institution (e.g., the School of Medicine) that receives the grants,
typically through the Office of Research Administration. Individual
investigators who participate in the sponsored project(s) are not
directly compensated by the sponsor but may receive salary or other
support from the institution to support their effort on the projects(s).
Dr. Neil Bressler is Principal Investigator of grants at The Johns
Hopkins University sponsored by the following entities (not including
the National Institutes of Health): Allergan, Bausch & Lomb, Carl Zeiss
Meditec, EMMES Corporation, Genentech, Lumenis, Notal Vision, Novartis,
QLT, Regeneron, Steba Biotech, Abbott Medical Optics, ForSight Labs,
LLC, and Genzyme Corporation. A complete list of all DRCR. net
investigator financial disclosures can be found at www.drcr.net.
NR 3
TC 202
Z9 209
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2011
VL 118
IS 4
BP 609
EP 614
DI 10.1016/j.ophtha.2010.12.033
PG 6
WC Ophthalmology
SC Ophthalmology
GA 744DS
UT WOS:000289075200002
PM 21459214
ER
PT J
AU Sen, HN
Sangave, AA
Goldstein, DA
Suhler, EB
Cunningham, D
Vitale, S
Nussenblatt, RB
AF Sen, H. Nida
Sangave, Amit A.
Goldstein, Debra A.
Suhler, Eric B.
Cunningham, Denise
Vitale, Susan
Nussenblatt, Robert B.
TI A Standardized Grading System for Scleritis
SO OPHTHALMOLOGY
LA English
DT Article
ID UVEITIS; INFLAMMATION; AGREEMENT
AB Objective: This study evaluated the performance of a standardized grading system for scleritis using standard digital photographs.
Design: Cross-sectional interobserver agreement study.
Participants: Photo archives from the National Eye Institute.
Methods: Three uveitis specialists from 3 different centers graded 79 randomly arranged images of the sclera with various degrees of inflammation. Grading was done using standard screen resolution (1024x768 pixels) on a 0 to 4+ scale in 2 sessions: (1) without using reference photographs and (2) with reference to a set of standard photographs (proposed grading system). The graders were masked to the order of images, and the order of images was randomized. Interobserver agreement in grading the severity of inflammation with and without the use of grading system was evaluated.
Main Outcome Measures: Interobserver agreement.
Results: The proposed grading system for assessing activity in scleritis demonstrated a good interobserver agreement. Interobserver agreement (pooled kappa) was poor (0.289) without photographic guidance and improved substantially when the "grading system" with standardized photographs was used (kappa = 0.603).
Conclusions: This system of standardized images for scleritis grading provides significantly more consistent grading of scleral inflammation in this study and has clear applications in clinical settings and clinical research.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118:768-771 (C) 2011 by the American Academy of Ophthalmology.
C1 [Sen, H. Nida; Sangave, Amit A.; Cunningham, Denise; Vitale, Susan; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA.
[Goldstein, Debra A.] Univ Illinois, Chicago, IL USA.
[Suhler, Eric B.] Oregon Hlth & Sci Univ, Portland, OR USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Room 10N112, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
FU Celgene; Abbott; Genentech; Novartis; Department of Veterans' Affairs;
National Eye Institute
FX Dr Eric Suhler receives financial support from Celgene, Abbott,
Genentech, Novartis, and the Department of Veterans' Affairs, and
institutional support from Research to Prevent Blindness.; Supported by
the National Eye Institute Intramural research program support (HNS,
RBN, AS, SV).
NR 9
TC 13
Z9 15
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD APR
PY 2011
VL 118
IS 4
BP 768
EP 771
DI 10.1016/j.ophtha.2010.08.027
PG 4
WC Ophthalmology
SC Ophthalmology
GA 744DS
UT WOS:000289075200025
PM 21093921
ER
PT J
AU Rosen, BR
Napadow, V
AF Rosen, Bruce R.
Napadow, Vitaly
TI Quantitative Markers for Neuropsychiatric Disease: Give It a Rest
SO RADIOLOGY
LA English
DT Editorial Material
ID MILD COGNITIVE IMPAIRMENT; FUNCTIONAL CONNECTIVITY; ALZHEIMERS-DISEASE;
SENSORY STIMULATION; NETWORKS; CORTEX; MRI
C1 [Rosen, Bruce R.; Napadow, Vitaly] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Rosen, BR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,MNR Ctr 2301, Charlestown, MA 02129 USA.
EM bruce@nmr.mgh.harvard.edu
FU NCCIH NIH HHS [P01-AT002048, R01 AT004714, P01AT002048, R01-AT004714,
P01 AT002048]; NCRR NIH HHS [P41RR014075, P41 RR014075]; NIBIB NIH HHS
[R01 EB002066, R01EB002066]
NR 19
TC 3
Z9 3
U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD APR
PY 2011
VL 259
IS 1
BP 17
EP 19
DI 10.1148/radiol.10102253
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 741FM
UT WOS:000288848800005
PM 21436093
ER
PT J
AU Boland, GWL
Dwamena, BA
Sangwaiya, MJ
Goehler, AG
Blake, MA
Hahn, PF
Scott, JA
Kalra, MK
AF Boland, Giles W. L.
Dwamena, Ben A.
Sangwaiya, Minal Jagtiani
Goehler, Alexander G.
Blake, Michael A.
Hahn, Peter F.
Scott, James A.
Kalra, Mannudeep K.
TI Characterization of Adrenal Masses by Using FDG PET: A Systematic Review
and Meta-Analysis of Diagnostic Test Performance
SO RADIOLOGY
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; CONTRAST-ENHANCED CT; F-18-FDG PET/CT;
PUBLICATION BIAS; CANCER-PATIENTS; TEST ACCURACY; LUNG-CANCER; IMAGING
CHARACTERIZATION; MALIGNANT LESIONS; META-REGRESSION
AB Purpose: To perform a systematic review and meta-analysis of published data to determine the diagnostic utility of adrenal fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing benign from malignant adrenal disease.
Materials and Methods: Data on FDG PET assessment in MEDLINE and other electronic databases (from inception to November 2009) and in subject matter-specific journals were evaluated and compared with histologic diagnoses and/or established clinical and imaging follow-up results. Methodologic quality was assessed by using Quality Assessment of Diagnostic Accuracy Studies criteria. Bivariate random-effects meta-analytical methods were used to estimate summary and subgroup-specific sensitivity, specificity, and receiver operating characteristic curves and to investigate the effects of study design characteristics and imaging procedure elements on diagnostic accuracy.
Results: A total of 1391 lesions (824 benign, 567 malignant) in 1217 patients from 21 eligible studies were evaluated. Qualitative (visual) analysis of 841 lesions (in 14 reports) and quantitative analyses based on standardized uptake values (SUVs) for 824 lesions (in 13 reports) and standardized uptake ratios (SURs) for 562 lesions (in eight reports) were performed. Resultant data were highly heterogeneous, with a model-based inconsistency index of 88% (95% confidence interval [CI]: 79%, 98%). Mean sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio values for differentiating between benign and malignant adrenal disease were 0.97 (95% CI: 0.93, 0.98), 0.91 (95% CI: 0.87, 0.94), 11.1 (95% CI: 7.5, 16.3), 0.04 (95% CI: 0.02, 0.08), and 294 (95% CI: 107, 805), respectively, with no significant differences in accuracy among the visual, SUV, and SUR analyses.
Conclusion: Meta-analysis of combination PET-computed tomography (CT) reports revealed that FDG PET was highly sensitive and specific for differentiating malignant from benign adrenal disease. Diagnostic accuracy was not influenced by the type of imaging device (PET vs PET/CT), but specificity was dependent on the clinical status (cancer vs no cancer). (C) RSNA, 2011
C1 [Boland, Giles W. L.; Sangwaiya, Minal Jagtiani; Goehler, Alexander G.; Blake, Michael A.; Hahn, Peter F.; Scott, James A.; Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Dwamena, Ben A.] Univ Michigan, Sch Med, Dept Radiol, Ann Arbor, MI USA.
[Dwamena, Ben A.] VA Ann Arbor Healthcare Syst, Nucl Med Serv, Ann Arbor, MI USA.
RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White Bldg 270C, Boston, MA 02114 USA.
EM gboland@partners.org
FU GE Healthcare
FX G.W.L.B. No potential conflicts of interest to disclose. B. A. D. No
potential conflicts of interest to disclose. M.J.S. No potential
conflicts of interest to disclose. A. G. G. No potential conflicts of
interest to disclose. M. A. B. No potential conflicts of interest to
disclose. P. F. H. No potential conflicts of interest to disclose.
J.A.S. No potential conflicts of interest to disclose. M. K. Financial
activities related to the present article: none to disclose. Financial
activities not related to the present article: is a member of the board
of GE Healthcare; is a paid consultant for GE Healthcare; received a
grant or grants are pending from GE Healthcare; received payment from GE
Healthcare for the development of educational presentations. Other
relationships: none to disclose.
NR 66
TC 75
Z9 79
U1 1
U2 6
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD APR
PY 2011
VL 259
IS 1
BP 117
EP 126
DI 10.1148/radiol.11100569
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 741FM
UT WOS:000288848800016
PM 21330566
ER
PT J
AU Flaherty, KT
AF Flaherty, Keith T.
TI Taking Aim at MELANOMA
SO SCIENTIST
LA English
DT Article
ID METASTATIC MELANOMA; PHASE-I/II; INHIBITION; RESISTANCE; TRIAL
C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Flaherty, KT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
NR 11
TC 0
Z9 0
U1 0
U2 0
PU SCIENTIST INC
PI PHILADELPHIA
PA 400 MARKET ST, STE 1250, PHILADELPHIA, PA 19106 USA
SN 0890-3670
J9 SCIENTIST
JI Scientist
PD APR
PY 2011
VL 25
IS 4
BP 32
EP 37
DI 10.3410/M3-8
PG 6
WC Information Science & Library Science; Multidisciplinary Sciences
SC Information Science & Library Science; Science & Technology - Other
Topics
GA 739SL
UT WOS:000288738200016
ER
PT J
AU Halassa, MM
AF Halassa, Michael M.
TI Thalamocortical dynamics of sleep: Roles of purinergic neuromodulation
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE Sleep; Thalamocortical circuitry; Oscillations; Memory; Astrocytes; ATP;
Adenosine
ID SLOW-WAVE SLEEP; ADENOSINE A(1) RECEPTOR; IN-VIVO; HOMEOSTATIC
REGULATION; PROLONGED WAKEFULNESS; HIPPOCAMPAL RIPPLES; NETWORK
ACTIVATION; GENETIC-VARIATION; MEMBRANE-FUSION; BARREL CORTEX
AB Thalamocortical dynamics, the millisecond to second changes in activity of thalamocortical circuits, are central to perception, action and cognition. Generated by local circuitry and sculpted by neuromodulatory systems, these dynamics reflect the expression of vigilance states. In sleep, thalamocortical dynamics are thought to mediate "offline" functions including memory consolidation and synaptic scaling. Here, I discuss thalamocortical sleep dynamics and their modulation by the ascending arousal system and locally released neurochemicals. I focus on modulation of these dynamics by electrically silent astrocytes, highlighting the role of purinergic signaling in this glial form of communication. Astrocytes modulate cortical slow oscillations, sleep behavior, and sleep-dependent cognitive function. The discovery that astrocytes can modulate sleep dynamics and sleep-related behaviors suggests a new way of thinking about the brain, in which integrated circuits of neurons and glia control information processing and behavioral output. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Halassa, Michael M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Halassa, Michael M.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
RP Halassa, MM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,WACC 805, Boston, MA 02114 USA.
EM mhalassa@partners.org
FU NINDS NIH HHS [F31 NS059091, F31 NS059091-01]
NR 101
TC 14
Z9 14
U1 1
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1084-9521
J9 SEMIN CELL DEV BIOL
JI Semin. Cell Dev. Biol.
PD APR
PY 2011
VL 22
IS 2
BP 245
EP 251
DI 10.1016/j.semcdb.2011.02.008
PG 7
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 744CP
UT WOS:000289071500017
PM 21329763
ER
PT J
AU Narla, A
Vlachos, A
Nathan, DG
AF Narla, Anupama
Vlachos, Adrianna
Nathan, David G.
TI Diamond Blackfan Anemia Treatment: Past, Present, and Future
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID RED-CELL APLASIA; ERYTHROID HYPOPLASTIC ANEMIA;
TREACHER-COLLINS-SYNDROME; MYELODYSPLASTIC SYNDROME; CYCLOSPORINE
THERAPY; GENE-TRANSFER; PROTEIN; PROLIFERATION; DIFFERENTIATION;
ERYTHROPOIESIS
AB Despite significant improvements in our understanding of the pathophysiology of Diamond Blackfan anemia (DBA), there have been few advances in therapy. The cornerstones of treatment remain corticosteroids, chronic red blood cell transfusions, and hematopoietic stem cell transplantation, each of which is fraught with complications. In this article, we will review the history of therapies that have been offered to patients with DBA, summarize the current standard of care, including management of side effects, and discuss novel therapeutics that are being developed in the context of the research into the roles of ribosomal haplo-insufficiency and p53 activation in Diamond Blackfan anemia. Semin Hematol 48:117-123. (C) Published by Elsevier Inc.
C1 [Narla, Anupama; Nathan, David G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Narla, Anupama; Nathan, David G.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Narla, Anupama; Nathan, David G.] Childrens Hosp, Boston, MA 02115 USA.
[Vlachos, Adrianna] Steven & Alexandra Cohen Childrens Med Ctr New Yo, New Hyde Pk, NY USA.
[Vlachos, Adrianna] Hofstra N Shore LIJ Sch Med, New Hyde Pk, NY USA.
RP Nathan, DG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana 1644, Boston, MA 02115 USA.
EM david_nathan@dfci.harvard.edu
FU NHLBI NIH HHS [K08 HL078818, K08 HL078818-05, R01 HL082945]
NR 63
TC 10
Z9 11
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD APR
PY 2011
VL 48
IS 2
BP 117
EP 123
DI 10.1053/j.seminhematol.2011.01.004
PG 7
WC Hematology
SC Hematology
GA 743SA
UT WOS:000289037800007
PM 21435508
ER
PT J
AU Blay, JY
Demetri, GD
AF Blay, Jean-Yves
Demetri, George D.
TI The Evolution of a Revolutionary Class: Extending Benefits of Tyrosine
Kinase Inhibitors-Introduction
SO SEMINARS IN ONCOLOGY
LA English
DT Editorial Material
C1 [Blay, Jean-Yves] Univ Lyon 1, Ctr Leon Berard, Dept Med, F-69365 Lyon, France.
[Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Blay, JY (reprint author), Univ Lyon 1, Ctr Leon Berard, Dept Med, F-69365 Lyon, France.
RI Blay, Jean-Yves/N-3966-2016
OI Blay, Jean-Yves/0000-0001-7190-120X
NR 0
TC 1
Z9 1
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD APR
PY 2011
VL 38
IS 2
SU 1
BP S1
EP S2
DI 10.1053/j.seminoncol.2011.01.017
PG 2
WC Oncology
SC Oncology
GA 743JA
UT WOS:000289013400001
PM 21419930
ER
PT J
AU Demetri, GD
AF Demetri, George D.
TI Differential Properties of Current Tyrosine Kinase Inhibitors in
Gastrointestinal Stromal Tumors
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID CHRONIC MYELOID-LEUKEMIA; GROWTH-FACTOR RECEPTORS; IMATINIB MESYLATE;
SELECTIVE INHIBITOR; ACQUIRED-RESISTANCE; BCR-ABL; ANTITUMOR-ACTIVITY;
PHASE-II; IN-VITRO; KIT
AB During the past decade, tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of gastrointestinal stromal tumors (GIST), providing new treatment options with unprecedented clinical benefit. Recognition of the key role played by the receptor tyrosine kinases KIT and platelet-derived growth factor receptor alpha (PDGFR alpha) in the pathogenesis of GIST led to the development of imatinib, the first TKI for this indication and the current first-line standard of care for unresectable or metastatic GIST. However, the clinical efficacy of imatinib is limited by two concerns: the rare patient-specific intolerance to the drug, and the fact that the majority of patients will eventually develop treatment-refractory disease that is resistant to this selective TKI Although sunitinib has been approved worldwide as second-line therapy for GIST following failure of imatinib, the benefits of sunitinib in treating GIST following imatinib failure are most often more limited than first-line therapy, with emergence of treatment-resistant disease in less than 1 year. Other TKIs studied in clinical trials for GIST include a wide range of different agents, such as sorafenib, dasatinib, pazopanib, regorafenib, masitinib, and nilotinib. Each agent differs in its selectivity for individual tyrosine kinases, conferring each with distinct properties that determine clinical safety and efficacy. No agent has yet reached regulatory approval for management of GIST following the failure of both imatinib and sunitinib. This review highlights relevant differences and similarities in the structures and functions, including kinase selectivity and mechanisms of binding, of the currently approved TKIs and certain others in development for the treatment of advanced GIST. In addition, the ability of some TKIs to inhibit alternative targets with potency similar to or greater than their intended primary target (pleiotropic effects) is also discussed. Semin Oncol 38 (Suppl 1):S10-S19 (c) 2011 Elsevier Inc. All rights reserved.
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Demetri, GD (reprint author), Dana Farber Canc Inst, Dana 1212,44 Binney St, Boston, MA 02115 USA.
EM gdemetri@partners.org
FU Novartis Pharmaceuticals Corporation; Novartis Pharmaceuticals
FX Publication of this article was supported by an educational grant from
Novartis Pharmaceuticals Corporation.; Financial support for medical
editorial assistance was provided by Novartis Pharmaceuticals. The
author thanks Angelo Russo, PhD, for his medical editorial assistance
with the manuscript. Dr Demetri took full responsibility for the final
writing and was responsible for fair balance of data and conclusions in
the manuscript.
NR 45
TC 35
Z9 35
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 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD APR
PY 2011
VL 38
IS 2
SU 1
BP S10
EP S19
DI 10.1053/j.seminoncol.2011.01.018
PG 10
WC Oncology
SC Oncology
GA 743JA
UT WOS:000289013400003
PM 21419931
ER
PT J
AU Gokcay, F
Arsava, EM
Baykaner, T
Vangel, M
Garg, P
Wu, O
Singhal, AB
Furie, KL
Sorensen, AG
Ay, H
AF Gokcay, Figen
Arsava, Ethem Murat
Baykaner, Tuna
Vangel, Mark
Garg, Priya
Wu, Ona
Singhal, Aneesh B.
Furie, Karen L.
Sorensen, A. Gregory
Ay, Hakan
TI Age-Dependent Susceptibility to Infarct Growth in Women
SO STROKE
LA English
DT Article
DE cerebral infarct; diffusion-weighted imaging; gender; magnetic resonance
imaging; outcome; perfusion-weighted imaging; women & minorities
ID SEX-DIFFERENCES; EXPERIMENTAL STROKE; MAGNETIC-RESONANCE;
ISCHEMIC-STROKE; ESTROGEN; DIFFUSION; MRI; VOLUME; OUTCOMES; RISK
AB Background and Purpose-It is not known if there is a relationship between gender and tissue outcome in human ischemic stroke. We sought to identify whether the proportion of initially ischemic to eventually infarcted tissue was different between men and women with ischemic stroke.
Methods-We studied 141 consecutive patients with acute ischemic stroke who had a baseline MRI obtained within 12 hours of symptom onset, a follow-up imaging on Day 4 or later, and diffusion-weighted imaging/mean transmit time mismatch on initial MRI. Lesion growth was calculated as percentage of mismatch tissue that underwent infarction on follow-up (percentage mismatch lost). Multivariable analyses explored the effect of gender and other predictors of tissue outcome on percentage mismatch lost.
Results-There was no difference in median percentage mismatch lost between men (19%) and women (11%; P=0.720). There was, however, an interaction between gender and age; median percentage mismatch lost was 7% (0% to 12%) in women and 18% (1% to 35%) in men younger than the population median (71 years, P=0.061). The percentage mismatch lost was not different between men and women >= 71 years old (25% in both groups). The linear regression model revealed gender (P=0.027) and the interaction between age and gender (P=0.023) as independent predictors of percentage mismatch lost.
Conclusions-There is an age-by-gender interaction in tissue outcome after ischemic stroke; brain infarcts in women < 70 years grow approximately 50% less than infarcts in their male counterparts. These findings extend the well-known concept that there is a differential age-by-gender effect on stroke incidence, mortality, and functional outcome to the tissue level. (Stroke. 2011;42:947-951.)
C1 [Ay, Hakan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging,Dept Neurol, Charlestown, MA 02129 USA.
[Gokcay, Figen; Arsava, Ethem Murat; Baykaner, Tuna; Vangel, Mark; Garg, Priya; Wu, Ona; Sorensen, A. Gregory; Ay, Hakan] Harvard Univ, Sch Med, Dept Radiol, AA Martinos Ctr Biomed Imaging,Massachusetts Gen, Boston, MA 02115 USA.
[Singhal, Aneesh B.; Furie, Karen L.; Ay, Hakan] Harvard Univ, Sch Med, Dept Neurol, Stroke Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Ay, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging,Dept Neurol, 149 13th St,Room 2301, Charlestown, MA 02129 USA.
EM hay@partners.org
RI Arsava, Ethem Murat/I-9197-2013
OI Arsava, Ethem Murat/0000-0002-6527-4139
FU National Institutes of Health (NIH) [R01-NS051412, P50-NS051343,
R01-NS038477, R01-NS063925, R01-NS059710]
FX A.B.S. received National Institutes of Health (NIH) grants R01-NS051412
and P50-NS051343, K.L.F. received NIH grant P50-NS051343, A.G.S.
received NIH grants R01-NS038477 and R01-NS063925
(www.biomarkers.org/NewFiles/disclosures.html lists full disclosures),
and H. A. received NIH grant R01-NS059710.
NR 30
TC 10
Z9 10
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD APR
PY 2011
VL 42
IS 4
BP 947
EP 951
DI 10.1161/STROKEAHA.110.603902
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 741IK
UT WOS:000288857200025
PM 21311058
ER
PT J
AU Wu, O
Batista, LM
Lima, FO
Vangel, MG
Furie, KL
Greer, DM
AF Wu, Ona
Batista, Leonardo M.
Lima, Fabricio O.
Vangel, Mark G.
Furie, Karen L.
Greer, David M.
TI Predicting Clinical Outcome in Comatose Cardiac Arrest Patients Using
Early Noncontrast Computed Tomography
SO STROKE
LA English
DT Article
DE coma; outcomes; cardiac arrest; CT; prognosis
ID WHITE-MATTER; SURVIVORS; RESUSCITATION; HYPOTHERMIA; PROGNOSIS; BRAIN;
SCALE; DENSITY; SYSTEM; ATLAS
AB Background and Purpose-Early assessment of the likelihood of neurological recovery in comatose cardiac arrest survivors remains challenging. We hypothesize that quantitative noncontrast computed tomography (NCCT) combined with neurological assessments, are predictive of outcome.
Methods-We analyzed data sets acquired from comatose cardiac arrest patients who underwent CT within 72 hours of arrest. Images were semiautomatically segmented into anatomic regions. Median Hounsfield units (HU) were measured regionally and in the whole brain (WB). Outcome was based on the 6-month modified Rankin Scale (mRS) score. Logistic regression was used to combine Glasgow Coma Scale (GCS) score measured on Day 3 post arrest (GCS_Day3) with imaging to predict poor outcome (mRS>4).
Results-WB HU (P=0.02) and the ratio of HU in the putamen to the posterior limb of the internal capsule (PLIC) (P=0.004) from 175 datasets from 151 patients were univariate predictors of poor outcome. Thirty-three patients underwent hypothermia treatment. Multivariate analysis showed that combining median HU in the putamen (P=0.0006) and PLIC (P=0.007) was predictive of poor outcome. Combining WB HU and GCS_Day3 resulted in 72% [61% to 80%] sensitivity and 100% [73% to 100%] specificity for predicting poor outcome in 86 patients with measurable GCS_Day3. This was an improvement over prognostic performance based on GCS_Day3 <= 8 (98% sensitive but 71% specific).
Discussion-Combining density changes on CT with GCS_Day3 may be useful for predicting poor outcome in comatose cardiac arrest patients who are neither rapidly improving nor deteriorating. Improved prognostication with CT compared with neurological assessments can be achieved in patients treated with hypothermia. (Stroke. 2011;42:985-992.)
C1 [Wu, Ona; Vangel, Mark G.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Batista, Leonardo M.; Lima, Fabricio O.; Furie, Karen L.; Greer, David M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Vangel, Mark G.] Harvard Univ, Harvard Clin & Translat Sci Ctr, Cambridge, MA 02138 USA.
RP Wu, O (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,CNY 2301, Charlestown, MA 02129 USA.
EM ona@nmr.mgh.harvard.edu
RI Lima, Fabricio/E-6507-2015
OI Lima, Fabricio/0000-0002-0383-4145
FU National Institutes of Health [R01NS59775, P50NS051343, R01NS051412,
NCRR [P41RR14075]]
FX This research was supported in part by the National Institutes of Health
(grants R01NS59775, P50NS051343, R01NS051412, and NCRR [P41RR14075]).
Its contents are solely the responsibility of the authors and do not
necessarily represent the official views of the NIH.
NR 36
TC 42
Z9 43
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD APR
PY 2011
VL 42
IS 4
BP 985
EP 992
DI 10.1161/STROKEAHA.110.594879
PG 8
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 741IK
UT WOS:000288857200031
PM 21330629
ER
PT J
AU Walvick, RP
Bratane, BT
Henninger, N
Sicard, KM
Bouley, J
Yu, ZY
Lo, E
Wang, XY
Fisher, M
AF Walvick, Ronn P.
Bratane, Bernt T.
Henninger, Nils
Sicard, Kenneth M.
Bouley, James
Yu, Zhanyang
Lo, Eng
Wang, Xiaoying
Fisher, Marc
TI Visualization of Clot Lysis in a Rat Embolic Stroke Model Application to
Comparative Lytic Efficacy
SO STROKE
LA English
DT Article
DE acute stroke; animal models; ischemia; MRI; thrombolysis
ID MAGNETIC-RESONANCE ANGIOGRAPHY; FOCAL CEREBRAL-ISCHEMIA; ANNEXIN-II;
PLASMINOGEN; REPERFUSION; DIFFUSION; OCCLUSION; MEDIATOR; THERAPY;
SYSTEM
AB Background and Purpose-The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model and to compare tissue plasminogen activator (tPA)-based clot lysis with and without recombinant Annexin-2 (rA2).
Methods-In experiment 1 we used in vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50 mu L in 250 mu L blood. In experiment 2, we used in vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot imaging were conducted before and during treatment with vehicle (n=6), tPA (n=8), or rA2 plus tPA (n=8) at multiple time points. Brains were removed for ex vivo clot localization.
Results-Clots created with 25 mu L Magnevist were the most stable and provided the highest contrast-to-noise ratio. In the vehicle group, clot length as assessed by T1-weighted imaging correlated with histology (r=0.93). Clot length and cerebral blood flow-derived ischemic lesion volume were significantly smaller than vehicle at 15 minutes after treatment initiation in the rA2 plus tPA group, whereas in the tPA group no significant reduction from vehicle was observed until 30 minutes after treatment initiation. The rA2 plus tPA group had a significantly shorter clot length than the tPA group at 60 and 90 minutes after treatment initiation and significantly smaller cerebral blood flow deficit than the tPA group at 90 minutes after treatment initiation.
Conclusions-We introduce a novel MRI-based clot imaging method for in vivo monitoring of clot lysis. Lytic efficacy of tPA was enhanced by rA2. (Stroke. 2011; 42: 1110-1115.)
C1 [Bratane, Bernt T.; Henninger, Nils; Sicard, Kenneth M.; Bouley, James; Fisher, Marc] Univ Massachusetts Med Sch, Dept Neurol, Worcester, MA USA.
[Walvick, Ronn P.] Univ Massachusetts Med Sch, Dept Radiol, Worcester, MA USA.
[Yu, Zhanyang; Lo, Eng; Wang, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA.
[Yu, Zhanyang; Lo, Eng; Wang, Xiaoying] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA.
Harvard Univ, Program Neurosci, Sch Med, Charlestown, MA USA.
RP Bratane, BT (reprint author), 303 Belmont St, Worcester, MA 01604 USA.
EM Bernt.Bratane@umassmed.edu
OI Henninger, Nils/0000-0002-3883-5623
FU NIH
FX This study was supported by institutional grants. X. W. was supported by
a NIH grant.
NR 23
TC 12
Z9 12
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD APR
PY 2011
VL 42
IS 4
BP 1110
EP 1115
DI 10.1161/STROKEAHA.110.602102
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 741IK
UT WOS:000288857200051
PM 21372305
ER
PT J
AU Haynes, AB
Regenbogen, SE
Weiser, TG
Lipsitz, SR
Dziekan, G
Berry, WR
Gawande, AA
AF Haynes, Alex B.
Regenbogen, Scott E.
Weiser, Thomas G.
Lipsitz, Stuart R.
Dziekan, Gerald
Berry, William R.
Gawande, Atul A.
TI Surgical outcome measurement for a global patient population: Validation
of the Surgical Apgar Score in 8 countries
SO SURGERY
LA English
DT Article
ID SURGERY; HEALTH; CARE
AB Background. Surgical care is a vital component. of health care worldwide, yet there is no clinically meaningful measure of operative outcomes that could be applied globally. The Surgical Apgar Score, a simple metric derived from 3 intraoperative parameters, has been shown in U.S. academic medical centers to predict 30-day patient. outcomes after operation, but. has not been validated more broadly.
Methods. We collected the components of the Surgical Apgar Score at the time of operation for 5,909 adult patients undergoing noncardiac operative procedures under general anesthesia at 8 hospitals in diverse international settings and evaluated the relationship between patients' scores and the incidence of inpatient postoperative morbidity and mortality, using generalized estimating equations to adjust for clustering within sites.
Results. During the first 30 days of postoperative hospitalization, 544 patients (9.2%) experienced >= 1 complications. Compared with patients with the median score of 7-whose complication rate was 9.1%-those with a Surgical Apgar Score <5 (n = 302) had an adjusted complication rate of 32.9% (relative risk [RR], 3.6; 95% CI, 2.9-4.5), whereas those with a score of 10 (n = 238) had a 3.0% adjusted complication. rate (RR, 0.3; 95% CI, 0.1-1.1). The score's c-statistic for prediction of any complication is 0.70; for death. it is 0.77.
Conclusion. The Surgical Apgar Score is easily calculated, predictive, and moderately discriminative for major complications among adults undergoing inpatient noncardiac operative procedures. Such. a score could provide objective indication, of relative postoperative, risk for inpatients and provide a potential target for quality improvement efforts, particularly in resource-limited settings. (Surgery 2011;149:519-24.)
C1 [Haynes, Alex B.; Regenbogen, Scott E.; Weiser, Thomas G.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Haynes, Alex B.; Regenbogen, Scott E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Weiser, Thomas G.; Lipsitz, Stuart R.; Berry, William R.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Dziekan, Gerald] WHO, Patient Safety Programme, CH-1211 Geneva, Switzerland.
RP Gawande, AA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave,Kresge 401, Boston, MA 02115 USA.
EM agawande@partners.org
RI Haynes, Alex/K-1446-2013;
OI Haynes, Alex/0000-0002-5731-329X; Gawande, Atul/0000-0002-1824-9176
FU World Health Organization
FX Funded by the World Health Organization.
NR 18
TC 38
Z9 39
U1 0
U2 4
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 2011
VL 149
IS 4
BP 519
EP 524
DI 10.1016/j.surg.2010.10.019
PG 6
WC Surgery
SC Surgery
GA 743KP
UT WOS:000289017500007
PM 21216419
ER
PT J
AU Dave, BR
Sharma, A
Kalva, SP
Wicky, S
AF Dave, Bhavika R.
Sharma, Ashish
Kalva, Sanjeeva P.
Wicky, Stephan
TI Nine-Year Single-Center Experience With Transcatheter Arterial
Embolization for Hemoptysis: Medium-Term Outcomes
SO VASCULAR AND ENDOVASCULAR SURGERY
LA English
DT Article
DE hemoptysis; bronchial arteries; embolization
ID LIFE-THREATENING HEMOPTYSIS; SELECTIVE BRONCHIAL ARTERIOGRAPHY; MASSIVE
HEMOPTYSIS; CYSTIC-FIBROSIS; MAJOR HEMOPTYSIS; PLATINUM COILS;
MANAGEMENT; EMBOLOTHERAPY; IMMEDIATE; DISEASES
AB Purpose: To determine the medium-term efficacy of transcatheter arterial embolization (TAE) for hemoptysis. Materials and Methods: A total of 128 TAE were performed from April 1999 to April 2008 in 58 patients (30:28 F:M) with mean age of 49 (range: 16-89). Major causes of hemoptysis included cystic fibrosis/bronchiectasis (24 of 58); lung metastasis (8 of 58); lung cancer (7 of 58); fungal infection (4 of 58). Follow-up was available in 57 of 58 for a median of 1.28 years. Primary and secondary efficacy of TAE for hemoptysis was calculated using Kaplan-Meier estimates. Results: Technical and clinical successes were estimated at 58 (100%) of 58 and 57(98%) of 58, respectively. Recurrent hemoptysis occurred in 40% (23 of 58). In all, 34% (20 of 58) died during follow-up. Kaplan-Meier estimates for primary and secondary efficacy of TAE at 2, 4, 6, and 8 years were 0.82, 0.46, 0.17, and 0.09 (benign disease) and 0.30, 0, 0, and 0 (malignant disease), respectively. Conclusion: TAE is an effective treatment for hemoptysis in both short- and medium-terms, especially in benign lung disease.
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Dave, BR (reprint author), Univ Mississippi, Dept Radiol, Med Ctr, Jackson, MS 39216 USA.
EM bhavikadave@msn.com
NR 45
TC 5
Z9 6
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1538-5744
J9 VASC ENDOVASC SURG
JI Vasc. Endovasc. Surg.
PD APR
PY 2011
VL 45
IS 3
BP 258
EP 268
DI 10.1177/1538574410395036
PG 11
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 740XJ
UT WOS:000288827400008
PM 21444351
ER
PT J
AU Zapawa, LM
Hughes, JR
Benowitz, NL
Rigotti, NA
Shiffman, S
AF Zapawa, Lisa M.
Hughes, John R.
Benowitz, Neal L.
Rigotti, Nancy A.
Shiffman, Saul
TI Cautions and warnings on the US OTC label for nicotine replacement:
What's a doctor to do?
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Nicotine replacement therapy; Smoking cessation; Substance use disorder;
Tobacco use disorder; Tobacco use cessation
ID RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION; TRANSDERMAL NICOTINE;
TOBACCO DEPENDENCE; DOUBLE-BLIND; GUM USE; PERSISTENT USE; PATCH
THERAPY; QUIT SMOKING; REDUCTION
AB Background: FDA-approved labeling for over-the-counter (OTC) nicotine replacement therapy (NRT) limits duration of use to a relatively short period of time (10-12 weeks) and explicitly advises against NRT use while smoking or with additional forms of NRT.
Objective: To consider and summarize evidence accumulated since the OTC label was created regarding the safety and efficacy of longer-term and concomitant use to provide recommendations regarding these uses.
Method: Literature searches were conducted on Medline, journal websites, and Internet search engines, with findings reviewed by six smoking cessation researchers.
Results: Persistent (i.e., long-term) use of NRT does not appear harmful and self-selected persistent use is primarily driven by concerns about relapse to smoking, not addiction. Similarly, continued use of NRT and tobacco during a lapse or relapse and combination NRT treatment do not appear harmful and appear to enhance efficacy.
Conclusions: Persistent users of NRT should be counseled to reduce and stop NRT only when they are not concerned about relapsing to smoking. Use of NRT with return to smoking during a lapse or relapse should not be automatically discontinued. Combination NRT therapy should be considered for all smokers, especially those who are unable to quit smoking using a single form of NRT. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Zapawa, Lisa M.; Shiffman, Saul] Pinney Associates Inc, Bethesda Metro Ctr 3, Bethesda, MD 20814 USA.
[Hughes, John R.] Univ Vermont, Dept Psychiat, Univ Hlth Ctr, Burlington, VT 05401 USA.
[Benowitz, Neal L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94110 USA.
[Benowitz, Neal L.] Univ Calif San Francisco, Dept Psychiat & Biopharmaceut Sci, San Francisco, CA 94110 USA.
[Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Shiffman, Saul] Univ Pittsburgh, Smoking Res Grp, Pittsburgh, PA 15260 USA.
RP Zapawa, LM (reprint author), 7864 Secretariat Dr, Saline, MI 48176 USA.
EM lzapawa@pinneyassociates.com; john.hughes@uvm.edu;
nbenowitz@medsfgh.ucsf.edu; nrigotti@partners.org;
shiffman@pinneyassociates.com
RI Shiffman, Saul/K-7337-2012
FU National Institute on Drug Abuse (NIDA) [DA000490, DA-11557, DA-17825,
DA-02277]; National Heart Lung and Blood (NHLBI) [K24-04440]; National
Institute on Health; Pfizer; Abbot Pharmaceuticals; Acrux; Aradigm;
American Academy of Addiction Psychiatry; American Psychiatric
Association; Begbies Traynor; Cambridge Hospital; Cline; Davis and Mann;
Constella Group; Consultants in Behavior Change; Dean Foundation; DLA
Piper; EPI-Q European Respiratory Society; Evotec; Exchange Limited;
Fagerstrom Consulting; Free and Clear; Glaxo-Smith Kline; Golin Harris;;
Healthwise; Insyght; Informed; Invivodata; Johns Hopkins University;
Reckner; Maine Medical Center; McGill University Medical School; McNeil
Pharmaceuticals; Novartis Pharmaceuticals; Oglivy Health PR; Ottawa
Heart Institute; Pfizer Pharmaceuticals; Pinney Associates; Propagate
Pharmaceuticals; Reuters; Scientia; Selecta; Temple University of Health
Sciences; University of Arkansas; University of California-San
Francisco; University of Cantabria; University of Kentucky; University
of New Mexico; US National Institutes on Health; Wolters Publishing;
Xenova; GSKCH; Nabi Biopharmaceuticals
FX Dr. Hughes's work on this paper was supported by National Institute on
Drug Abuse (NIDA) Senior Scientist Award DA000490 and NIDA grants
DA-11557 and DA-17825. NIDA had no role in the study design, collection,
analysis or interpretation of the data, writing the manuscript, or the
decision to submit the paper for publication.; Dr. Benowitz's work in
preparing this manuscript was supported in part by NIDA grant DA-02277.
NIDA had no role in the study design, collection, analysis or
interpretation of the data, writing the manuscript, or the decision to
submit the paper for publication.; Dr. Rigotti's efforts on this
manuscript were supported in part by a National Heart Lung and Blood
(NHLBI) grant K24-04440. NHLBI had no role in the study design,
collection, analysis or interpretation of the data, writing the
manuscript, or the decision to submit the paper for publication.; Dr.
Hughes is currently employed by The University of Vermont and Fletcher
Allen Health Care. Since 7/1/2007, he has received research grants from
the National Institute on Health, Pfizer; the latter two develops and
sells smoking cessation medications. During this time, he has accepted
honoraria or consulting fees from several non-profit and for-profit
organizations and companies that develop, sell or promote smoking
cessation products or services or educate/advocate about smoking
cessation, including: Abbot Pharmaceuticals; Acrux; Aradigm; American
Academy of Addiction Psychiatry; American Psychiatric Association;
Begbies Traynor; Cambridge Hospital; Cline, Davis and Mann; Constella
Group; Consultants in Behavior Change; Dean Foundation; DLA Piper, EPI-Q
European Respiratory Society, Evotec; Exchange Limited; Fagerstrom
Consulting; Free and Clear; Glaxo-Smith Kline; Golin Harris; Healthwise;
Insyght; Informed; Invivodata; Johns Hopkins University; J L Reckner;
Maine Medical Center; McGill University Medical School; McNeil
Pharmaceuticals; Novartis Pharmaceuticals; Oglivy Health PR; Ottawa
Heart Institute, Pfizer Pharmaceuticals; Pinney Associates; Propagate
Pharmaceuticals; Reuters; Scientia; Selecta; Temple University of Health
Sciences; University of Arkansas; University of California-San
Francisco; University of Cantabria; University of Kentucky; University
of New Mexico; US National Institutes on Health; Wolters Publishing; and
Xenova.; Dr. Benowitz has served as a paid consultant for several
pharmaceutical companies, including GSKCH Pfizer and McNeil, that market
and/or are developing nicotine and other medications for smoking
cessation. Within the past five years, Dr. Benowitz has received
research grant support from GSKCH. His family formerly held stock in
Pfizer and Johnson and Johnson. Dr. Benowitz has served as a paid expert
witness in litigation against tobacco companies.; In the past three
years, Dr. Rigotti's institution has received research grant funding
from Pfizer and Nabi Biopharmaceuticals to test marketed or
investigational smoking cessation products. She has consulted (without
honoraria since 2008) for Pfizer and Free and Clear.
NR 59
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U1 4
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD APR
PY 2011
VL 36
IS 4
BP 327
EP 332
DI 10.1016/j.addbeh.2010.12.003
PG 6
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 734PC
UT WOS:000288346700008
PM 21220188
ER
PT J
AU Melanson, SEF
Stevenson, K
Kim, H
Antin, JH
Court, MH
Ho, VT
Ritz, J
Soiffer, RJ
Kuo, FC
Longtine, JA
Jarolim, P
AF Melanson, Stacy E. F.
Stevenson, Kristen
Kim, Haesook
Antin, Joseph H.
Court, Michael H.
Ho, Vincent T.
Ritz, Jerome
Soiffer, Robert J.
Kuo, Frank C.
Longtine, Janina A.
Jarolim, Petr
TI The importance of correct assignment of CYP2B6 genetic variants with
respect to cyclophosphamide metabolizer status Response
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Letter
C1 [Melanson, Stacy E. F.; Kuo, Frank C.; Longtine, Janina A.; Jarolim, Petr] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Stevenson, Kristen; Kim, Haesook; Antin, Joseph H.; Ho, Vincent T.; Ritz, Jerome; Soiffer, Robert J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Court, Michael H.] Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02115 USA.
RP Melanson, SEF (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
NR 4
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD APR
PY 2011
VL 86
IS 4
BP 384
EP 384
DI 10.1002/ajh.21997
PG 1
WC Hematology
SC Hematology
GA 740JW
UT WOS:000288790200015
ER
PT J
AU Gripp, KW
Hopkins, E
Sol-Church, K
Stabley, DL
Axelrad, ME
Doyle, D
Dobyns, WB
Hudson, C
Johnson, J
Tenconi, R
Graham, GE
Sousa, AB
Heller, R
Piccione, M
Corsello, G
Herman, GE
Tartaglia, M
Lin, AE
AF Gripp, Karen W.
Hopkins, Elizabeth
Sol-Church, Katia
Stabley, Deborah L.
Axelrad, Marni E.
Doyle, Daniel
Dobyns, William B.
Hudson, Cindy
Johnson, John
Tenconi, Romano
Graham, Gail E.
Sousa, Ana Berta
Heller, Raoul
Piccione, Maria
Corsello, Giovanni
Herman, Gail E.
Tartaglia, Marco
Lin, Angela E.
TI Phenotypic Analysis of Individuals With Costello Syndrome due to HRAS
p.G13C
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Costello syndrome; genotype-phenotype correlation; loose anagen hair;
rasopathy
ID LOOSE ANAGEN HAIR; NOONAN-LIKE-SYNDROME; ACTIVATING MUTATIONS; ORIGIN;
ABNORMALITIES; DISORDERS; SPECTRUM
AB Costello syndrome is characterized by severe failure-to-thrive, short stature, cardiac abnormalities (heart defects, tachyarrhythmia, and hypertrophic cardiomyopathy (HCM)), distinctive facial features, a predisposition to papillomata and malignant tumors, postnatal cerebellar overgrowth resulting in Chiari 1 malformation, and cognitive disabilities. De novo germline mutations in the proto-oncogene HRAS cause Costello syndrome. Most mutations affect the glycine residues in position 12 or 13, and more than 80% of patients share p.G12S. To test the hypothesis that subtle genotype-phenotype differences exist, we report the first cohort comparison between 12 Costello syndrome individuals with p.G13C and individuals with p.G12S. The individuals with p.G13C had many typical findings including polyhydramnios, failure-to-thrive, HCM, macrocephaly with posterior fossa crowding, and developmental delay. Subjectively, their facial features were less coarse. Statistically significant differences included the absence of multifocal atrial tachycardia (P-value = 0.033), ulnar deviation of the wrist (P<0.001) and papillomata (P = 0.003), and fewer neurosurgical procedures (P = 0.024). Fewer individuals with p.G13C had short stature (height below -2 SD) without use of growth hormone (P<0.001). The noteworthy absence of malignant tumors did not reach statistical significance. Novel ectodermal findings were noted in individuals with p.G13C, including loose anagen hair resulting in easily pluckable hair with a matted appearance, different from the tight curls typical for most Costello syndrome individuals. Unusually long eye lashes requiring trimming are a novel finding we termed dolichocilia. These distinctive ectodermal findings suggest a cell type specific effect of this particular mutation. Additional patients are needed to validate these findings. (C) 2011 Wiley-Liss, Inc.
C1 [Gripp, Karen W.; Hopkins, Elizabeth] Alfred I DuPont Hosp Children, Div Med Genet, Wilmington, DE 19803 USA.
[Sol-Church, Katia; Stabley, Deborah L.] Nemours Childrens Clin, Dept Biomed Res, Wilmington, DE USA.
[Axelrad, Marni E.] Texas Childrens Hosp, Baylor Coll Med, Psychol Serv, Sect Psychol,Dept Pediat, Houston, TX 77030 USA.
[Doyle, Daniel] Alfred I DuPont Hosp Children, Div Endocrinol, Wilmington, DE 19803 USA.
[Dobyns, William B.] Seattle Childrens Res Inst, Seattle, WA USA.
[Hudson, Cindy; Johnson, John] Shodair Childrens Hosp, Helena, MT USA.
[Tenconi, Romano] Univ Padua, Dept Pediat, Clin Genet Unit, Padua, Italy.
[Graham, Gail E.] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada.
[Sousa, Ana Berta] Hosp Santa Maria, Serv Genet Med, Lisbon, Portugal.
[Heller, Raoul] Klinikum Univ Koln, Inst Humangenet, Cologne, Germany.
[Piccione, Maria; Corsello, Giovanni] Univ Palermo, Mother & Child Dept, Palermo, Italy.
[Herman, Gail E.] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA.
[Tartaglia, Marco] Ist Super Sanita, Dept Haematol Oncol & Mol Med, I-00161 Rome, Italy.
[Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA.
RP Gripp, KW (reprint author), Alfred I DuPont Hosp Children, Div Med Genet, 1600 Rockland Rd, Wilmington, DE 19803 USA.
EM kgripp@nemours.org
OI Sousa, Ana Berta/0000-0001-5889-2492; Tartaglia,
Marco/0000-0001-7736-9672; Dobyns, William/0000-0002-7681-2844
FU Nemours Foundation; NIH [4P20 RR020173-01]; Telethon-Italy [GGP10020];
National Center for Research Resources
FX We thank the patients and their families for allowing us to share this
information. We thank Dr. Peter Herkenrath from the Children's Hospital
at the University of Cologne for sharing clinical data. This report was
supported by The Nemours Foundation, funds to KSC from NIH grant number
4P20 RR020173-01 from the National Center for Research Resources, and
Telethon-Italy (GGP10020) to MT.
NR 26
TC 23
Z9 23
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD APR
PY 2011
VL 155A
IS 4
BP 706
EP 716
DI 10.1002/ajmg.a.33884
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 740KP
UT WOS:000288792700005
PM 21438134
ER
PT J
AU Lin, AE
Singh, KE
Strauss, A
Nguyen, S
Rawson, K
Kimonis, VE
AF Lin, Angela E.
Singh, Kathryn E.
Strauss, Arthur
Son Nguyen
Rawson, Kristyn
Kimonis, Virginia E.
TI An Additional Patient with Mycophenolate Mofetil Embryopathy: Cardiac
and Facial Analyses
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE cardiovascular malformation; congenital heart defect; conotruncal;
microtia; mycophenolate mofetil; teratogen
ID FETAL MALFORMATIONS; KIDNEY-TRANSPLANTATION; PREGNANCY; EXPOSURE;
NEWBORN; EAR; DIAGNOSIS; ANOMALIES
AB We describe an infant male of Cambodian background who has typical craniofacial features of mycophenolate mofetil (MMF) embryopathy and a complex congenital heart defect (CHD) (double outlet right ventricle, mitral atresia, pulmonic stenosis, and total anomalous pulmonary venous return). Together with four case reports and the 20 patients included in two recent reviews, we report 24 (19 affected, five normal) patients with this pattern of anomalies. Eight (33%) have a CHD, most commonly, conotruncal or aortic arch defects (6/8, 75%). This would support the hypothesis that disturbance of cranial neural crest migration occurs in exposed infants, and may predict which additional anomalies will be observed in the future. We also attempted to score the severity of the facial anomalies in each MMF patient using a system created by plastic surgeons for patients with hemifacial microsomia. This classification had modest utility in comparing severity and correlating facial to extracranial defects. The findings are viewed with caution because of the preliminary methodology. Finally, since several exposed infants have been reported to be minimally affected, we remind clinicians to be sensitive to the potential mild expression of the effects of this teratogen. This awareness may influence clinical management of apparently normal MMF-exposed individuals. (C) 2011 Wiley-Liss, Inc.
C1 [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA 02114 USA.
[Singh, Kathryn E.; Rawson, Kristyn; Kimonis, Virginia E.] Univ Calif Irvine, Div Genet & Metab, Irvine, CA USA.
[Strauss, Arthur; Son Nguyen] Miller Childrens Hosp, Long Beach Mem Med Ctr, Long Beach, CA USA.
RP Lin, AE (reprint author), MassGen Hosp Children, Genet Unit, 185 Cambridge St,CPZN 2222, Boston, MA 02114 USA.
EM lin.angela@mgh.harvard.edu; vkimonis@uci.edu
NR 34
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U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD APR
PY 2011
VL 155A
IS 4
BP 748
EP 756
DI 10.1002/ajmg.a.33934
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 740KP
UT WOS:000288792700012
PM 21594997
ER
PT J
AU de Gonzalez, AB
Kim, KP
Knudsen, AB
Lansdorp-Vogelaar, I
Rutter, CM
Smith-Bindman, R
Yee, J
Kuntz, KM
van Ballegooijen, M
Zauber, AG
Berg, CD
AF de Gonzalez, Amy Berrington
Kim, Kwang Pyo
Knudsen, Amy B.
Lansdorp-Vogelaar, Iris
Rutter, Carolyn M.
Smith-Bindman, Rebecca
Yee, Judy
Kuntz, Karen M.
van Ballegooijen, Marjolein
Zauber, Ann G.
Berg, Christine D.
TI Radiation-Related Cancer Risks From CT Colonography Screening: A
Risk-Benefit Analysis
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE colonography; colorectal cancer; CT; CT colonography radiation risk;
radiation risk; screening
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; EXTRACOLONIC
FINDINGS; IONIZING-RADIATION; TASK-FORCE; POPULATION; COLONOSCOPY;
POLYPS; COST
AB OBJECTIVE. The purpose of this study was to estimate the ratio of cancers prevented to induced (benefit-risk ratio) for CT colonography (CTC) screening every 5 years from the age of 50 to 80 years.
MATERIALS AND METHODS. Radiation-related cancer risk was estimated using risk projection models based on the National Research Council's Biological Effects of Ionizing Radiation (BEIR) VII Committee's report and screening protocols from the American College of Radiology Imaging Network's National CT Colonography Trial. Uncertainty intervals were estimated using Monte Carlo simulation methods. Comparative modeling with three colorectal cancer microsimulation models was used to estimate the potential reduction in colorectal cancer cases and deaths.
RESULTS. The estimated mean effective dose per CTC screening study was 8 mSv for women and 7 mSv for men. The estimated number of radiation-related cancers resulting from CTC screening every 5 years from the age of 50 to 80 years was 150 cases/100,000 individuals screened (95% uncertainty interval, 80-280) for men and women. The estimated number of colorectal cancers prevented by CTC every 5 years from age 50 to 80 ranged across the three microsimulation models from 3580 to 5190 cases/100,000 individuals screened, yielding a benefit-risk ratio that varied from 24: 1 (95% uncertainty interval, 13: 1-45: 1) to 35: 1 (19:1-65:1). The benefit-risk ratio for cancer deaths was even higher than the ratio for cancer cases. Inclusion of radiation-related cancer risks from CT examinations performed to follow up extracolonic findings did not materially alter the results.
CONCLUSION. Concerns have been raised about recommending CTC as a routine screening tool because of potential harms including the radiation risks. Based on these models, the benefits from CTC screening every 5 years from the age of 50 to 80 years clearly outweigh the radiation risks.
C1 [de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Yongin, Gyeonggi Do, South Korea.
[Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein] Univ Med Ctr Rotterdam, Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
[Rutter, Carolyn M.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA.
[Smith-Bindman, Rebecca] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Yee, Judy] Vet Affairs Med Ctr, Dept Radiol, San Francisco, CA 94121 USA.
[Kuntz, Karen M.] Univ Minnesota, Div Hlth Policy & Management, Minneapolis, MN USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Berg, Christine D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP de Gonzalez, AB (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
RI Berg , Christine/K-1047-2014
FU GE Healthcare; NCI [U01 CA-97427, U01-CA-088204, U01-CA-097426,
U01-CA-115953]
FX J. Yee received a research grant from GE Healthcare.; This research was
funded by the NCI Intramural Research Program and by NCI grants (U01
CA-97427, U01-CA-088204, U01-CA-097426, and U01-CA-115953).
NR 33
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U1 2
U2 7
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 2011
VL 196
IS 4
BP 816
EP 823
DI 10.2214/AJR.10.4907
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 738OP
UT WOS:000288650600038
PM 21427330
ER
PT J
AU Goehler, A
Ollendorf, DA
Jaeger, M
Ladapo, J
Neumann, T
Gazelle, GS
Pearson, SD
AF Goehler, Alexander
Ollendorf, Daniel A.
Jaeger, Marie
Ladapo, Joseph
Neumann, Till
Gazelle, G. Scott
Pearson, Steven D.
TI A Simulation Model of Clinical and Economic Outcomes of Cardiac CT
Triage of Patients With Acute Chest Pain in the Emergency Department
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE acute chest pain; coronary CT angiography; cost effectiveness; decision
analysis; myocardial infarction
ID CORONARY-ARTERY-DISEASE; ELEVATION MYOCARDIAL-INFARCTION; 64-SLICE
COMPUTED-TOMOGRAPHY; COST-EFFECTIVENESS; MISSED DIAGNOSES; ANGIOGRAPHY;
GUIDELINES; ACCURACY; ISCHEMIA; PREVALENCE
AB OBJECTIVE. Uncertainty exists as to whether coronary CT angiography (CTA) compared with standard of care (SOC) is more effective and efficient in the triage of low-risk emergency department (ED) patients with acute chest pain. Our objective was to construct a simulation model to estimate clinical and economic outcomes.
MATERIALS AND METHODS. We constructed a microsimulation model comparing SOC to coronary CTA-based triage of 1000 55-year-old patients (50% men) with acute chest pain, nonsignificant ECG changes, and initial negative cardiac markers. In SOC, patients were reevaluated with serial cardiac markers after 6-8 hours, followed by either nuclear stress imaging (SPECT) or stress echocardiography. In coronary CTA-based triage, patients were imaged immediately and, depending on the results, discharged, held for SPECT or stress echocardiography, or referred directly to invasive coronary angiography.
RESULTS. Compared with SOC, coronary CTA-based triage reduced the number of patients referred for invasive coronary angiography from 406 (SPECT) or 370 (stress echocardiography) to 255 per 1000 and resulted in fewer "missed" cases of acute coronary syndrome overall (5 vs 18). Coronary CTA-based triage also resulted in fewer deaths (4 vs 6). Coronary CTA led to immediate discharge of 706 patients and produced average cost-savings in the ED of $851 (SPECT) or $462 (stress echocardiography) per patient. At 30 days after initial ED triage, coronary CTA-based management produced average savings of $283 (SPECT) and average costs of $292 (stress echocardiography) per patient triaged.
CONCLUSION. Our model suggests that coronary CTA-based triage of low-risk patients with acute chest pain in the ED might reduce invasive catheterizations, could improve survival, and may save money.
C1 [Goehler, Alexander; Jaeger, Marie; Ladapo, Joseph; Gazelle, G. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA.
[Goehler, Alexander] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & Hlth Technol As, Hall In Tirol, Austria.
[Goehler, Alexander] Univ Duisburg Essen, Alfried Krupp von Bohlen & Halbach Fdn Chair Hlth, Essen, Germany.
[Ollendorf, Daniel A.; Pearson, Steven D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Clin & Econ Review, Boston, MA 02114 USA.
[Neumann, Till] Univ Essen Gesamthsch, W German Heart Inst, Essen, Germany.
[Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA.
RP Goehler, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, 101 Merrimac St,10th Fl, Boston, MA 02114 USA.
EM alex@mgh-ita.org
NR 32
TC 6
Z9 6
U1 0
U2 3
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 2011
VL 196
IS 4
BP 853
EP 861
DI 10.2214/AJR.10.4962
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 738OP
UT WOS:000288650600043
PM 21427336
ER
PT J
AU Cronin, CG
Sharma, A
Digumarthy, SR
Gilman, MD
McLoud, T
Muse, VV
Shepard, JO
AF Cronin, Carmel G.
Sharma, Amita
Digumarthy, Subba R.
Gilman, Mathew D.
McLoud, Theresa
Muse, Victorine V.
Shepard, JoAnne O.
TI Percutaneous Lung Biopsy After Pneumonectomy: Factors for Improving
Success in the Care of Patients at High Risk
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE lung biopsy; lung cancer; pneumonectomy
ID NEEDLE ASPIRATION BIOPSY; CHEST TUBE PLACEMENT; COMPUTED-TOMOGRAPHY;
PNEUMOTHORAX RATE; AIR-EMBOLISM; PULMONARY; CANCER; PREVENTION;
SURVIVAL; LESIONS
AB OBJECTIVE. The purpose of this study was to assess the risks and complications of CT-guided needle biopsy of lung nodules in patients with a single lung after pneumonectomy.
MATERIALS AND METHODS. A database search for the records of patients who had undergone lung biopsy over a 9-year period revealed that 1771 patients had done so. Fourteen (0.7%) of these patients (11 men, three women; mean age, 63 years; range, 42.4-79.6 years) had undergone pneumonectomy and been referred for biopsy of the contralateral lung. The images and medical records of these patients were reviewed in detail.
RESULTS. Lung biopsy was technically successful in 86% (12/14) of cases. All procedures were fine-needle aspiration, and a core biopsy specimen also was obtained in one case. Fifty percent (6/12) of the procedures were performed with local anesthesia alone and 50% with a combination of local anesthesia and conscious sedation. The pneumothorax rate was 25% (3/12). All pneumothoraces were small and asymptomatic, and none required a chest drain. There were no cases of hemoptysis. No other immediate or delayed complications were encountered. Malignancy was found in 83% (10/12) of cases. In one of the other two cases (8%) the result was false-negative, and in the other, the nodules resolved without chemotherapy and were presumed to be inflammatory.
CONCLUSION. Percutaneous lung biopsy performed on the single lung in patients who have undergone pneumonectomy is feasible and successful. Lung biopsy in these circumstances should be performed by an experienced radiologist with thoracic surgical backup.
C1 [Cronin, Carmel G.; Sharma, Amita; Digumarthy, Subba R.; Gilman, Mathew D.; McLoud, Theresa; Muse, Victorine V.; Shepard, JoAnne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Cronin, CG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders 202,55 Fruit St, Boston, MA 02114 USA.
NR 30
TC 1
Z9 1
U1 0
U2 3
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 2011
VL 196
IS 4
BP 929
EP 934
DI 10.2214/AJR.10.4920
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 738OP
UT WOS:000288650600054
PM 21427347
ER
PT J
AU Atalay, MK
Prince, EA
Pearson, CA
Chang, KJ
AF Atalay, Michael K.
Prince, Ethan A.
Pearson, Catherine A.
Chang, Kevin J.
TI The Prevalence and Clinical Significance of Noncardiac Findings on
Cardiac MRI
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE cardiac imaging; incidental findings; MRI
ID COMPUTED-TOMOGRAPHY; INCIDENTAL FINDINGS; EXTRACARDIAC FINDINGS; CT;
ANGIOGRAPHY; PATHOLOGY
AB OBJECTIVE. This study aims to evaluate the prevalence, nature, and clinical significance of noncardiac findings (NCFs) at cardiac MRI.
MATERIALS AND METHODS. We retrospectively reviewed 240 consecutive, clinically indicated cardiac MRI examinations conducted over a 21-month period. All noncardiac findings (NCFs) were recorded. Those findings that were included in the report impressions were regarded as clinically important (INCF). Electronic medical records and related imaging studies were then reviewed for all patients having INCFs to determine their actual clinical significance. A finding was significant (SNCF) if it was associated with a new diagnosis, treatment, or intervention. The prevalences of findings in the neck, chest, and abdomen were determined.
RESULTS. We found 162 NCFs in 104 studies (43%), of which 94 (58%) were INCFs, and 16 (10%) were SNCFs. There was at least one INCF in 65 studies (27%)-67% of which were new-and at least one SNCF in 13 studies (5%). Compared with younger patients, patients 60 years and older were much more likely to have INCFs (43% vs 17%) and SNCFs (12% vs 1%). Overall, 29% of NCFs were in the abdomen, 70% in the chest, and 1% in the neck. The most common INCFs were pleural effusion (n = 26), air-space disease or atelectasis (n = 13), and adenopathy (n = 9). Five new cases of cancer were diagnosed, including lung (n = 2), lymphoma (n = 2), and thyroid (n = 1).
CONCLUSION. NCFs are commonly encountered on cardiac MRI studies, many of which are clinically relevant. Proper recognition of NCFs is critical to the comprehensive management of patients referred for cardiac MRI.
C1 [Atalay, Michael K.; Prince, Ethan A.; Chang, Kevin J.] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Dept Diagnost Imaging, Providence, RI 02903 USA.
[Pearson, Catherine A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Atalay, MK (reprint author), Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Dept Diagnost Imaging, 593 Eddy St, Providence, RI 02903 USA.
EM atalay_99@yahoo.com
OI Chang, Kevin/0000-0001-9441-2740
NR 23
TC 20
Z9 20
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 2011
VL 196
IS 4
BP W387
EP W393
DI 10.2214/AJR.09.3302
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 738OP
UT WOS:000288650600005
PM 21427301
ER
PT J
AU Krishnaraj, A
AF Krishnaraj, Arun
TI Impact of a Voice Recognition System on Radiology Report Turnaround
Time: Experience From a Non-English-Speaking South Asian Country Reply
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Letter
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
RP Krishnaraj, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
NR 2
TC 0
Z9 0
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 2011
VL 196
IS 4
BP W486
EP W486
DI 10.2214/AJR.10.5557
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 738OP
UT WOS:000288650600022
ER
PT J
AU Yuki, K
Soriano, SG
Shimaoka, M
AF Yuki, Koichi
Soriano, Sulpicio G.
Shimaoka, Motomu
TI Sedative Drug Modulates T-Cell and Lymphocyte Function-Associated
Antigen-1 Function
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID HUMAN NEUTROPHIL FUNCTIONS; CONFORMATIONAL REGULATION; CYTOKINE
PRODUCTION; INTEGRIN LFA-1; SMALL-MOLECULE; I-DOMAIN; COSTIMULATORY
SIGNAL; PROPOFOL; ACTIVATION; INTERLEUKIN-2
AB BACKGROUND: Sedative drugs modify immune cell functions via several mechanisms. However, the effects of sedatives on immune function have been primarily investigated in neutrophils and macrophages, and to the lesser extent lymphocytes. Lymphocyte function-associated antigen-1 (LFA-1) is an adhesion molecule that has a central role in regulating immune function of lymphocytes including interleukin-2 (IL-2) production and lymphocyte proliferation. Previous clinical studies reported that propofol and isoflurane reduced IL-2 level in patients, but midazolam did not. We previously demonstrated that isoflurane inhibited LFA-1 binding to its counter ligand, intercellular adhesion molecule-1 (ICAM-1), which might contribute to the reduction of IL-2 levels. In the current study, we examined the effect of propofol, midazolam, and dexmedetomidine on LFA-1/ICAM-1 binding, and the subsequent biological effects.
METHODS: The effect of sedative drugs on T-cell proliferation and IL-2 production was measured by calorimetric assays on human peripheral blood mononuclear cells. Because LFA-1/ICAM-1 binding has an important role in T-cell proliferation and IL-2 production, we measured the effect of sedative drugs on ICAM-1 binding to LFA-1 protein (cell-free assay). This analysis was followed by flow cytometric analysis of LFA-1 expressing T-cell binding to ICAM-1 (cell-based assay). To determine whether the drug/LFA-1 interaction is caused by competitive or allosteric inhibition, we analyzed the sedative drug effect on wild-type and high-affinity LFA-1 and a panel of monoclonal antibodies that bind to different regions of LFA-1.
RESULTS: Propofol at 10 to 100 mu M inhibited ICAM-1 binding to LFA-1 in cell-free assays and cell-based assays (P < 0.05). However, dexmedetomidine and midazolam did not affect LFA-1/ICAM-1 binding. Propofol directly inhibits LFA-1 binding to ICAM-1 by binding near the ICAM-1 contact area in a competitive manner. At clinically relevant concentrations, propofol, but not dexmedetomidine or midazolam, inhibited IL-2 production (P < 0.05). Additionally, propofol inhibited lymphocyte proliferation (P < 0.05).
CONCLUSIONS: Our study suggests that propofol competitively inhibits LFA-1 binding to ICAM-1 on T-cells and suppresses T-cell proliferation and IL-2 production, whereas dexmedetomidine and midazolam do not significantly influence these immunological assays. (Anesth Analg 2011;112:830-38)
C1 [Yuki, Koichi; Soriano, Sulpicio G.; Shimaoka, Motomu] Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Shimaoka, Motomu] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Yuki, Koichi; Soriano, Sulpicio G.; Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Shimaoka, Motomu] Immune Dis Inst, Boston, MA USA.
RP Yuki, K (reprint author), Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, 300 Longwood Ave, Boston, MA 02115 USA.
EM koichi.yuki@childrens.harvard.edu
FU National Institutes of Health [HL048675, CA139444]; Children's Hospital
Endowed Chair in Pediatric Neuroanesthesia; CHMC Anesthesia Foundation
FX Supported by National Institutes of Health grants HL048675 and CA139444
(MS), Children's Hospital Endowed Chair in Pediatric Neuroanesthesia
(SGS), and CHMC Anesthesia Foundation (KY and SGS).
NR 53
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U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD APR
PY 2011
VL 112
IS 4
BP 830
EP 838
DI 10.1213/ANE.0b013e31820dcabb
PG 9
WC Anesthesiology
SC Anesthesiology
GA 739ET
UT WOS:000288697000013
PM 21385989
ER
PT J
AU Glance, LG
Neuman, M
Martinez, EA
Pauker, KY
Dutton, RP
AF Glance, Laurent G.
Neuman, Mark
Martinez, Elizabeth A.
Pauker, Kenneth Y.
Dutton, Richard P.
TI Performance Measurement at a "Tipping Point"
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID QUALITY IMPROVEMENT PROGRAM; BYPASS GRAFT-SURGERY; NEW-YORK-STATE;
CLINICAL-PRACTICE GUIDELINES; SURGICAL CARE IMPROVEMENT; EVIDENCE-BASED
MEDICINE; HOSPITAL QUALITY; HEALTH-CARE; OPERATIVE MORTALITY;
ADMINISTRATIVE DATA
C1 [Glance, Laurent G.] Univ Rochester, Med Ctr, Dept Anesthesiol, Sch Med, Rochester, NY 14642 USA.
[Neuman, Mark] Univ Penn, Dept Anesthesiol, Philadelphia, PA 19104 USA.
[Martinez, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA.
[Pauker, Kenneth Y.] Saddleback Mem Med Ctr, Anesthesia Serv Sub Sect, Dept Surg, Laguna Hills, CA USA.
[Dutton, Richard P.] Univ Maryland, Dept Anesthesiol, Baltimore, MD 21201 USA.
RP Glance, LG (reprint author), Univ Rochester, Med Ctr, Dept Anesthesiol, Sch Med, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA.
EM Laurent_Glance@urmc.rochester.edu
FU Agency for Healthcare and Quality Research [RO1 HS 16737, K08 HS
013904]; Department of Anesthesiology at the University of Rochester
School of Medicine and Dentistry
FX Supported in part by grants from the Agency for Healthcare and Quality
Research (RO1 HS 16737 to Dr. Glance, and K08 HS 013904 to Dr.
Martinez), and by the Department of Anesthesiology at the University of
Rochester School of Medicine and Dentistry.
NR 86
TC 11
Z9 11
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD APR
PY 2011
VL 112
IS 4
BP 958
EP 966
DI 10.1213/ANE.0b013e31820e778d
PG 9
WC Anesthesiology
SC Anesthesiology
GA 739ET
UT WOS:000288697000031
PM 21385976
ER
PT J
AU Zapol, WM
AF Zapol, Warren M.
TI Life at the Frontier The Third Annual John W. Severinghaus Lecture on
Translational Science
SO ANESTHESIOLOGY
LA English
DT Article
ID INHALED NITRIC-OXIDE; ACUTE RESPIRATORY-FAILURE; PERSISTENT
PULMONARY-HYPERTENSION; DIVING WEDDELL SEALS; DISTRESS-SYNDROME;
GAS-EXCHANGE; NEWBORN; SUPPORT; DISEASE; LAMBS
C1 [Zapol, Warren M.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
[Zapol, Warren M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Zapol, WM (reprint author), Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, 55 Fruit St,Thier 503, Boston, MA 02114 USA.
EM wzapol@partners.org
FU National Institutes of Health (Bethesda, Maryland)
FX Received from Harvard Medical School, Cambridge, Massachusetts.
Submitted for publication August 27, 2010. Accepted for publication
November 5, 2010. The author and his laboratory receive a portion of
royalties on patents licensed by Massachusetts General Hospital (Boston)
to Linde AG (Munich, Germany) and Ikaria, Inc. (Clinton, New Jersey), on
inhaled nitric oxide. Support is also provided from institutional and/or
departmental sources as well as National Institutes of Health (Bethesda,
Maryland).
NR 59
TC 1
Z9 1
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD APR
PY 2011
VL 114
IS 4
BP 771
EP 781
DI 10.1097/ALN.0b013e31820708d7
PG 11
WC Anesthesiology
SC Anesthesiology
GA 739DT
UT WOS:000288694400008
PM 21358318
ER
PT J
AU Kaur, T
Singh, J
Huffman, MA
Petrzelkova, KJ
Taylor, NS
Xu, SL
Dewhirst, FE
Paster, BJ
Debruyne, L
Vandamme, P
Fox, JG
AF Kaur, Taranjit
Singh, Jatinder
Huffman, Michael A.
Petrzelkova, Klara J.
Taylor, Nancy S.
Xu, Shilu
Dewhirst, Floyd E.
Paster, Bruce J.
Debruyne, Lies
Vandamme, Peter
Fox, James G.
TI Campylobacter troglodytis sp. nov., Isolated from Feces of
Human-Habituated Wild Chimpanzees (Pan troglodytes schweinfurthii) in
Tanzania
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID MAHALE MOUNTAINS; INTESTINAL PARASITES; GENETIC RELATEDNESS;
MACACA-NEMESTRINA; NATIONAL-PARK; GREAT APES; IDENTIFICATION; JEJUNI;
HELICOBACTER; UPSALIENSIS
AB The transmission of simian immunodeficiency and Ebola viruses to humans in recent years has heightened awareness of the public health significance of zoonotic diseases of primate origin, particularly from chimpanzees. In this study, we analyzed 71 fecal samples collected from 2 different wild chimpanzee (Pan troglodytes) populations with different histories in relation to their proximity to humans. Campylobacter spp. were detected by culture in 19/56 (34%) group 1 (human habituated for research and tourism purposes at Mahale Mountains National Park) and 0/15 (0%) group 2 (not human habituated but propagated from an introduced population released from captivity over 30 years ago at Rubondo Island National Park) chimpanzees, respectively. Using 16S rRNA gene sequencing, all isolates were virtually identical (at most a single base difference), and the chimpanzee isolates were most closely related to Campylobacter helveticus and Campylobacter upsaliensis (94.7% and 95.9% similarity, respectively). Whole-cell protein profiling, amplified fragment length polymorphism analysis of genomic DNA, hsp60 sequence analysis, and determination of the mol% G+C content revealed two subgroups among the chimpanzee isolates. DNA-DNA hybridization experiments confirmed that both subgroups represented distinct genomic species. In the absence of differential biochemical characteristics and morphology and identical 16S rRNA gene sequences, we propose to classify all isolates into a single novel nomenspecies, Campylobacter troglodytis, with strain MIT 05-9149 as the type strain; strain MIT 05-9157 is suggested as the reference strain for the second C. troglodytis genomovar. Further studies are required to determine whether the organism is pathogenic to chimpanzees and whether this novel Campylobacter colonizes humans and causes enteric disease.
C1 [Taylor, Nancy S.; Xu, Shilu; Fox, James G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA.
[Kaur, Taranjit; Singh, Jatinder] Virginia Tech, Virginia Maryland Reg Coll Vet Med, Blacksburg, VA 24061 USA.
[Huffman, Michael A.] Kyoto Univ, Primate Res Inst, Aichi, Japan.
[Petrzelkova, Klara J.] Acad Sci Czech Republic, Inst Vertebrate Biol, CS-60365 Brno, Czech Republic.
[Petrzelkova, Klara J.] Liberec Zoo, Liberec 46001, Czech Republic.
[Dewhirst, Floyd E.; Paster, Bruce J.] Forsyth Inst, Boston, MA 02115 USA.
[Debruyne, Lies; Vandamme, Peter] Univ Ghent, Dept Biochem & Microbiol, Fac Sci, B-9000 Ghent, Belgium.
RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16-825, Cambridge, MA 02139 USA.
EM jgfox@mit.edu
RI Vandamme, Peter/B-7967-2009; Petrzelkova, Klara/G-7111-2014;
OI Vandamme, Peter/0000-0002-5581-7937
FU [NSF 0238069]; [NIH R01CA067529]
FX This work was supported by grants NSF 0238069 (T.J.S.) and NIH
R01CA067529 (J.G.F.).
NR 59
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Z9 10
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0099-2240
J9 APPL ENVIRON MICROB
JI Appl. Environ. Microbiol.
PD APR
PY 2011
VL 77
IS 7
BP 2366
EP 2373
DI 10.1128/AEM.01840-09
PG 8
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 741HT
UT WOS:000288855500022
PM 21278267
ER
PT J
AU Nahrendorf, M
Keliher, E
Marinelli, B
Leuschner, F
Robbins, CS
Gerszten, RE
Pittet, MJ
Swirski, FK
Weissleder, R
AF Nahrendorf, Matthias
Keliher, Edmund
Marinelli, Brett
Leuschner, Florian
Robbins, Clinton S.
Gerszten, Robert E.
Pittet, Mikael J.
Swirski, Filip K.
Weissleder, Ralph
TI Detection of Macrophages in Aortic Aneurysms by Nanoparticle Positron
Emission Tomography-Computed Tomography
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE aneurysms; imaging agents; macrophages; positron emission tomography;
nanoparticle
ID FOR-VASCULAR-SURGERY; MYOCARDIAL-INFARCTION; PRACTICE GUIDELINES;
SPLENIC RESERVOIR; INFLAMMATION; MONOCYTES; SOCIETY; MICE; WALL;
MANAGEMENT
AB Objective-Current management of aortic aneurysms (AAs) relies primarily on size criteria to determine whether invasive repair is indicated to preempt rupture. We hypothesized that emerging molecular imaging tools could be used to more sensitively gauge local inflammation. Because macrophages are key effector cells that destabilize the extracellular matrix in the arterial wall, it seemed likely that they would represent suitable imaging targets. We here aimed to develop and validate macrophage-targeted nanoparticles labeled with fluorine-18 ((18)F) for positron emission tomography-computed tomography (PET-CT) detection of inflammation in AAs.
Methods and Results-Aneurysms were induced in apolipoprotein E(-/-) mice via systemic administration of angiotensin II. Mice were imaged using PET-CT and a monocyte/ macrophage-targeted nanoparticle. AAs were detected by contrast-enhanced micro-CT and had a mean diameter of 1.85 +/- 0.08 mm, whereas normal aortas measured 1.07 +/- 0.03 (P < 0.05). The in vivo PET signal was significantly higher in aneurysms (standard uptake value, 2.46 +/- 0.48) compared with wild-type aorta (0.82 +/- 0.05, P < 0.05). Validation with scintillation counting, autoradiography, fluorescence, and immunoreactive histology and flow cytometry demonstrated that nanoparticles localized predominantly to monocytes and macrophages within the aneurysmatic wall.
Conclusion-PET-CT imaging with (18)F-labeled nanoparticles allows quantitation of macrophage content in a mouse model of AA. (Arterioscler Thromb Vasc Biol. 2011;31:750-757.)
C1 [Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.
EM mnahrendorf@mgh.harvard.edu; rweissleder@mgh.harvard.edu
FU NIH [UO1-HL080731/HHSN268201000044C, R24-CA92782, R01-HL095629,
R01-HL096576, R01-HL095612]; American Heart Association Established
Investigator Award; Deutsche Herzstiftung e.V
FX This work was funded in parts by grants from the NIH Translational
Program of Excellence in Nanotechnology Grants
UO1-HL080731/HHSN268201000044C, R24-CA92782 (to R.W.), R01-HL095629 and
R01-HL096576 (to M.N.), and R01-HL095612 (to F.K.S.); an American Heart
Association Established Investigator Award (to R.E.G.); and Deutsche
Herzstiftung e.V. (to F.L.).
NR 28
TC 72
Z9 72
U1 2
U2 14
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 2011
VL 31
IS 4
BP 750
EP U67
DI 10.1161/ATVBAHA.110.221499
PG 11
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 735SP
UT WOS:000288437800009
PM 21252070
ER
PT J
AU Sher, L
AF Sher, Leo
TI Is it possible to predict suicide?
SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY
LA English
DT Letter
C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA.
[Sher, Leo] Mt Sinai Sch Med, New York, NY USA.
RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, New York, NY USA.
NR 7
TC 0
Z9 0
U1 1
U2 3
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 0004-8674
J9 AUST NZ J PSYCHIAT
JI Aust. N. Z. J. Psych.
PD APR
PY 2011
VL 45
IS 4
PG 1
WC Psychiatry
SC Psychiatry
GA 736OK
UT WOS:000288503800012
ER
PT J
AU Lacount, LT
Barbieri, R
Park, K
Kim, J
Brown, EN
Kuo, B
Napadow, V
AF Lacount, Lauren T.
Barbieri, Riccardo
Park, Kyungmo
Kim, Jieun
Brown, Emery N.
Kuo, Braden
Napadow, Vitaly
TI Static and Dynamic Autonomic Response with Increasing Nausea Perception
SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE
LA English
DT Article
DE motion sickness; heart rate variability; skin conductance response;
galvanic skin response; vestibular
ID HEART-RATE-VARIABILITY; MOTION SICKNESS STIMULATION; SUSCEPTIBILITY;
COMPONENTS; CHEMOTHERAPY; DISCOMFORT; MODEL
AB LACOUNT LT, BARBIERI R, PARK K, KIM J, BROWN EN, KUO B, NAPADOW V. Static and dynamic autonomic response with increasing nausea perception. Aviat Space Environ Med 2011; 82:424-33.
Background: Nausea is a commonly occurring symptom typified by epigastric discomfort with urge to vomit. The relationship between autonomic nervous system (ANS) outflow and increasing nausea perception is not fully understood. Methods: Our study employed a nauseogenic visual stimulus (horizontally translating stripes) while 17 female subjects freely rated transitions in nausea level and autonomic outflow was measured (heart rate, HR; heart rate variability, HRV; skin conductance response, SCR; respiratory rate). We also adopted a recent approach to continuous high-frequency (HF) HRV estimation to evaluate dynamic cardiovagal modulation. Results: HR increased from baseline for all increasing nausea transitions, especially transition to strong nausea (15.0 +/- 11.4 bpm), but decreased (-6.6 +/- 4.6 bpm) once the visual stimulus ceased. SCR also increased for all increasing nausea transitions, especially transition to strong nausea (1.76 +/- 1.68 mu S), but continued to increase (0.52 +/- 0.65 mu S) once visual stimulation ceased. LF/HF HRV increased following transition to moderate (1.54 +/- 2.11 a.u.) and strong (2.57 +/- 3.49 a.u.) nausea, suggesting a sympathetic shift in sympathovagal balance. However, dynamic HF HRV suggested that bursts of cardiovagal modulation precede transitions to higher nausea, perhaps influencing subjects to rate higher levels of nausea. No significant change in respiration rate was found. Conclusions: Our results suggest that increasing nausea perception is associated with both increased sympathetic and decreased parasympathetic ANS modulation. These findings corroborate past ANS studies of nausea, applying perception-linked analyses and dynamic estimation of cardiovagal modulation in response to nausea.
C1 [Lacount, Lauren T.; Kim, Jieun; Napadow, Vitaly] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Barbieri, Riccardo; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA.
[Park, Kyungmo] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea.
[Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA.
RP Napadow, V (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, 149 13th St,2301, Charlestown, MA 02129 USA.
EM vitaly@nmr.mgh.harvard.edu
OI Barbieri, Riccardo/0000-0001-9381-3833
FU NIH [R01-HL084502, R01-DA015644, DP1-OD003646, K01-AT002166,
P01-AT002048, R01-AT004714, F05-AT003770, K23-DK069614]; NCRR
[P41RR14075, 1 UL1 RR025758-01]; Mental Illness and Neuroscience
Discovery (MIND) Institute; International Foundation of Functional GI
Disorders; Institute of Information Technology Advancement, Korea
[IITA-2008-(C1090-0801-0002)]
FX We would like to thank NIH for funding support (RB: R01-HL084502; EB:
R01-DA015644 and DP1-OD003646; VN: K01-AT002166, P01-AT002048,
R01-AT004714; KP: F05-AT003770; BK: K23-DK069614), the NCRR (P41RR14075;
CRC 1 UL1 RR025758-01), the Mental Illness and Neuroscience Discovery
(MIND) Institute, and the International Foundation of Functional GI
Disorders. Dr. Park was also supported by the Institute of Information
Technology Advancement, Korea IITA-2008-(C1090-0801-0002). We would also
like to thank Dr. Mark Vangel for technical assistance on statistical
analyses of the data.
NR 38
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U1 2
U2 11
PU AEROSPACE MEDICAL ASSOC
PI ALEXANDRIA
PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA
SN 0095-6562
EI 1943-4448
J9 AVIAT SPACE ENVIR MD
JI Aviat. Space Environ. Med.
PD APR
PY 2011
VL 82
IS 4
BP 424
EP 433
DI 10.3357/ASEM.2932.2011
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Sport Sciences
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Sport Sciences
GA 740YC
UT WOS:000288829300003
PM 21485400
ER
PT J
AU Taylor, L
Zhou, XH
AF Taylor, Leslie
Zhou, Xiao-Hua
TI Methods for clustered encouragement design studies with noncompliance
and missing data
SO BIOSTATISTICS
LA English
DT Article
DE Causal inference; Clustered encouragement design; Complier average
causal effect; Missing data; Multiple imputation; Noncompliance;
Nonresponse; Principal stratification
ID PRINCIPAL STRATIFICATION APPROACH; BROKEN RANDOMIZED EXPERIMENTS;
CHRONIC HEART-FAILURE; TO-TREAT ANALYSIS; CLINICAL-TRIALS;
BAYESIAN-INFERENCE; CAUSAL INFERENCE; POTENTIAL OUTCOMES; IGNORABILITY;
NONRESPONSE
AB Encouragement design studies are particularly useful for estimating the effect of an intervention that cannot itself be randomly administered to some and not to others. They require a randomly selected group receive extra encouragement to undertake the treatment of interest, where the encouragement typically takes the form of additional information or incentives. We consider a "clustered encouragement design" (CED), where the randomization is at the level of the clusters (e.g. physicians), but the compliance with assignment is at the level of the units (e.g. patients) within clusters. Noncompliance and missing data are particular problems in encouragement design studies, where encouragement to take the treatment, rather than the treatment itself, is randomized. The motivating study looks at whether computer-based care suggestions can improve patient outcomes in veterans with chronic heart failure. Since physician adherence has been inadequate, the original study focused on methods to improve physician adherence, although an equally important question is whether physician adherence improves patient outcomes. Here, we reanalyze the data to determine the effect of physician adherence on patient outcomes. We propose causal inference methodology for the effect of a treatment versus a control in a randomized CED study with all-or-none compliance at the unit level. These methods extend the current approaches to account for nonignorable missing data and use an alternative approach to inference using multiple imputation methods, which have been successfully applied to a wide variety of missing data problems and have recently been applied to the potential outcomes framework of causal inference (Taylor and Zhou, 2009b).
C1 [Taylor, Leslie; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Taylor, Leslie; Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, Biostat Unit, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA.
RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
EM taylorl@u.washington.edu; azhou@u.washington.edu
FU VA Puget Sound Health Care System; Dr. Zhou's VA Research Career
Scientist Award [RCD 05-196]
FX The VA Puget Sound Health Care System and Dr. Zhou's VA Research Career
Scientist Award (RCD 05-196).
NR 37
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U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD APR
PY 2011
VL 12
IS 2
BP 313
EP 326
DI 10.1093/biostatistics/kxq065
PG 14
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 740ND
UT WOS:000288800600010
PM 20974677
ER
PT J
AU Baba, Y
Nosho, K
Shima, K
Hayashi, M
Meyerhardt, JA
Chan, AT
Giovannucci, E
Fuchs, CS
Ogino, S
AF Baba, Yoshifumi
Nosho, Katsuhiko
Shima, Kaori
Hayashi, Marika
Meyerhardt, Jeffrey A.
Chan, Andrew T.
Giovannucci, Edward
Fuchs, Charles S.
Ogino, Shuji
TI Phosphorylated AKT Expression Is Associated With PIK3CA Mutation, Low
Stage, and Favorable Outcome in 717 Colorectal Cancers
SO CANCER
LA English
DT Article
DE pAKT; PI3K; clinical outcome; personalized medicine; colorectal
carcinoma
ID ISLAND METHYLATOR PHENOTYPE; FATTY-ACID SYNTHASE; CELL LUNG-CANCER;
MICROSATELLITE INSTABILITY; BREAST-CANCER; ACTIVATED AKT; COLON-CANCER;
PROGNOSTIC-SIGNIFICANCE; BRAF MUTATION; SURVIVAL
AB BACKGROUND: AKT (AKT1, AKT2, and AKT3) was a downstream effector of phosphatidylinositide-3-kinase (PI3K) and played crucial roles in protein synthesis, cellular metabolism, survival, and proliferation. The PI3K/AKT pathway was commonly activated in human cancers and was recognized as a potential target for anticancer therapy. Nonetheless, clinical, molecular, or prognostic features of AKT-activated colon cancer remained uncertain. METHODS: Using a database of 717 colon and rectal cancers in the Nurses' Health Study and the Health Professionals Follow-up Study, Ser473 phosphorylated AKT (p-AKT) expression was detected in 448 (62%) tumors by immunohistochemistry. Cox proportional hazards model was used to compute mortality hazards ratio (HR), adjusting for clinical and tumoral features, including PIK3CA, KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), LINE-1 methylation, TP53 (p53), and FASN (fatty acid synthase). RESULTS: Tumor p-AKT expression was associated with PIK3CA mutation (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.12-2.80; P = .015). p-AKT expression was significantly associated with longer colorectal cancer-specific survival in Kaplan-Meier analysis (log-rank P = .0005), univariate Cox regression (HR, 0.62; 95% CI, 0.47-0.82; P = .0006) and multivariate analysis (adjusted HR, 0.75; 95% CI, 0.56-0.99; P = .048) adjusting for clinical and molecular variables including PIK3CA, MSI, CIMP and LINE-1 hypomethylation. p-AKT expression was inversely associated with high stage (III-IV) (adjusted OR, 0.63; 95% CI, 0.45-0.88, P = .0071). CONCLUSIONS: p-AKT expression in colorectal cancer is associated with low stage and good prognosis. p-AKT may serve as a tissue biomarker to identify patients with superior prognosis and a possible therapeutic target (analogous to estrogen receptor ESR1 in breast cancer). Cancer 2011; 117: 1399-408. (C) 2010 American Cancer Society.
C1 [Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Hayashi, Marika; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA.
[Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Hayashi, Marika; Meyerhardt, Jeffrey A.; Giovannucci, Edward; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
FU U.S. National Institute of Health (NIH) [P01 CA87969, P01 CA55075, P50
CA127003, K07 CA122826, R01 CA151993]; Bennett Family Fund;
Entertainment Industry Foundation through National Colorectal Cancer
Research Alliance; Uehara Memorial Foundation
FX Funding: U.S. National Institute of Health (NIH) grants P01 CA87969 (to
S. Hankinson), P01 CA55075 (to W. Willett), P50 CA127003 (to C. S. F.),
K07 CA122826 (to S.O.), and R01 CA151993 (to S.O.); the Bennett Family
Fund; and the Entertainment Industry Foundation through National
Colorectal Cancer Research Alliance. Y.B. was supported by a fellowship
grant from the Uehara Memorial Foundation. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of NCI or NIH. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 50
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U1 0
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD APR 1
PY 2011
VL 117
IS 7
BP 1399
EP 1408
DI 10.1002/cncr.25630
PG 10
WC Oncology
SC Oncology
GA 737IE
UT WOS:000288561700009
PM 21425139
ER
PT J
AU Friese, CR
Earle, CC
Magazu, LS
Brown, JR
Neville, BA
Hevelone, ND
Richardson, LC
Abel, GA
AF Friese, Christopher R.
Earle, Craig C.
Magazu, Lysa S.
Brown, Jennifer R.
Neville, Bridget A.
Hevelone, Nathanael D.
Richardson, Lisa C.
Abel, Gregory A.
TI Timeliness and Quality of Diagnostic Care for Medicare Recipients With
Chronic Lymphocytic Leukemia
SO CANCER
LA English
DT Article
DE chronic lymphocytic leukemia; diagnosis; outcomes; flow cytometry;
SEER-Medicare
ID FAMILY PHYSICIANS KNOWLEDGE; ACUTE MYOCARDIAL-INFARCTION; BREAST-CANCER;
DELAY; MANAGEMENT; SURVIVAL; OLDER; TIME; SEX
AB BACKGROUND: Little is known about the patterns of care relating to the diagnosis of chronic lymphocytic leukemia (CLL), including the use of modern diagnostic techniques such as flow cytometry. METHODS: The authors used the SEER-Medicare database to identify subjects diagnosed with CLL from 1992 to 2002 and defined diagnostic delay as present when the number of days between the first claim for a CLL-associated sign or symptom and SEER diagnosis date met or exceeded the median for the sample. The authors then used logistic regression to estimate the likelihood of delay and Cox regression to examine survival. RESULTS: For the 5086 patients analyzed, the median time between sign or symptom and CLL diagnosis was 63 days (interquartile range [IQR] = 0-251). Predictors of delay included age >= 75 (OR 1.45 [1.27-1.65]), female gender (OR 1.22 [1.07-1.39]), urban residence (OR 1.46 [1.19 to 1.79]), >= 1 comorbidities (OR 2.83 [2.45-3.28]) and care in a teaching hospital (OR 1.20 [1.05-1.38]). Delayed diagnosis was not associated with survival (HR 1.11 [0.99-1.25]), but receipt of flow cytometry within thirty days before or after diagnosis was (HR 0.84 [0.76-0.91]). CONCLUSIONS: Sociodemographic characteristics affect diagnostic delay for CLL, although delay does not seem to impact mortality. In contrast, receipt of flow cytometry near the time of diagnosis is associated with improved survival. Cancer 2011; 117: 1470-7. (C) 2010 American Cancer Society.
C1 [Abel, Gregory A.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA.
[Hevelone, Nathanael D.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Richardson, Lisa C.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
[Friese, Christopher R.] Univ Michigan, Sch Nursing, Div Nursing Business & Hlth Syst, Ann Arbor, MI 48109 USA.
[Earle, Craig C.] Univ Toronto, Toronto, ON, Canada.
[Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Magazu, Lysa S.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
RP Abel, GA (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Hematol Malignancies, 44 Binney St,Smith 271, Boston, MA 02115 USA.
EM gregory_abel@dfci.harvard.edu
RI Friese, Christopher/D-2097-2013;
OI Friese, Christopher/0000-0002-2281-2056; Hevelone,
Nathanael/0000-0003-4740-2085
FU National Cancer Institute [R25 CA 057711-12]; Division of Cancer
Prevention and Control of the Centers for Disease Control and Prevention
(CDC) in Atlanta GA [200-2002-00, 575]; National Institute of Health
[R00 NR01570]
FX This project was supported by grants from the National Cancer Institute
(R25 CA 057711-12, Glorian Sorensen), and the Division of Cancer
Prevention and Control of the Centers for Disease Control and Prevention
(CDC) in Atlanta GA (Grant #200-2002-00,575, Task Order 21, Gregory A.
Abel, principal investigator). In addition, Dr. Friese was supported by
a grant from the National Institute of Health (R00 NR01570). The
findings and conclusions in this report do not necessarily represent the
CDC's views.
NR 32
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U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD APR 1
PY 2011
VL 117
IS 7
BP 1470
EP 1477
DI 10.1002/cncr.25655
PG 8
WC Oncology
SC Oncology
GA 737IE
UT WOS:000288561700018
PM 21425148
ER
PT J
AU Tolcher, AW
Appleman, LJ
Shapiro, GI
Mita, AC
Cihon, F
Mazzu, A
Sundaresan, PR
AF Tolcher, Anthony W.
Appleman, Leonard J.
Shapiro, Geoffrey I.
Mita, Alain C.
Cihon, Frank
Mazzu, Arthur
Sundaresan, Pavur R.
TI A phase I open-label study evaluating the cardiovascular safety of
sorafenib in patients with advanced cancer
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Cardiovascular adverse event (CAE); Left ventricular ejection fraction
(LVEF); Hypertension; QT/QTc interval; Sorafenib; Cardiovascular profile
ID RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; ENDOTHELIAL
GROWTH-FACTOR; REFRACTORY SOLID TUMORS; SUNITINIB MALATE;
ANTITUMOR-ACTIVITY; CARDIAC TOXICITY; QT PROLONGATION; HEART-FAILURE;
HYPERTENSION
AB To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer.
Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib. QT/QTc interval on the electrocardiograph (ECG) was measured in triplicate with a Holter 12-lead ECG at baseline and after 1 cycle of sorafenib. Heart rate (HR) and blood pressure (BP) were obtained in duplicate at baseline and after 1 and 4 cycles of sorafenib. Plasma pharmacokinetic data were obtained for sorafenib and its 3 main metabolites after 1 and 4 cycles of sorafenib.
LVEF (SD) mean change from baseline was -0.8 (+/- 8.6) LVEF(%) after 2 cycles (n = 31) and -1.2 (+/- 7.8) LVEF(%) after 4 cycles of sorafenib (n = 24). The QT/QTc mean changes from baseline observed at maximum sorafenib concentrations (t (max)) after 1 cycle (n = 31) were small (QTcB: 4.2 ms; QTcF: 9.0 ms). Mean changes observed after 1 cycle in BP (n = 31) and HR (n = 30) at maximum sorafenib concentrations (t (max)) were moderate (up to 11.7 mm Hg and -6.6 bpm, respectively). No correlation was found between the AUC and C (max) of sorafenib and its main metabolites and any cardiovascular parameters.
The effects of sorafenib on changes in QT/QTc interval on the ECG, LVEF, BP, and HR were modest and unlikely to be of clinical significance in the setting of advanced cancer treatment.
C1 [Tolcher, Anthony W.] START S Texas Accelerated Res Therapeut, San Antonio, TX 78229 USA.
[Appleman, Leonard J.] Univ Pittsburgh, Inst Canc, UPMC Canc Pavil, Pittsburgh, PA 15232 USA.
[Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, Boston, MA 02115 USA.
[Shapiro, Geoffrey I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Mita, Alain C.] Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA.
[Cihon, Frank] Bayer Healthcare Pharmaceut Inc, Clin Stat, Montville, NJ 07045 USA.
[Mazzu, Arthur; Sundaresan, Pavur R.] Bayer Healthcare Pharmaceut Inc, Pharmacodynam, Montville, NJ 07045 USA.
RP Tolcher, AW (reprint author), START S Texas Accelerated Res Therapeut, 4319 Med Dr,Suite 205, San Antonio, TX 78229 USA.
EM atolcher@start.stoh.com
OI Appleman, Leonard/0000-0003-4951-7388
FU Bayer HealthCare Pharmaceuticals-Onyx Pharmaceuticals
FX This study was supported by Bayer HealthCare Pharmaceuticals-Onyx
Pharmaceuticals. We thank the study participants and their families;
study center staff; the clinical data management team at Bayer
HealthCare Pharmaceuticals Inc; and Aurora O'Brate, PhD, from Ogilvy
Healthworld, who was supported by Bayer HealthCare Pharmaceuticals Inc,
to provide editorial support for the preparation of this manuscript.
NR 45
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Z9 29
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
EI 1432-0843
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD APR
PY 2011
VL 67
IS 4
BP 751
EP 764
DI 10.1007/s00280-010-1372-3
PG 14
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 740MF
UT WOS:000288798100003
PM 20521052
ER
PT J
AU Shimizu, Y
Hamazaki, Y
Hattori, M
Doi, K
Terada, N
Kobayashi, T
Toda, Y
Yamasaki, T
Inoue, T
Kajita, Y
Maeno, A
Kamba, T
Mikami, Y
Kamoto, T
Yamada, T
Kanno, T
Yoshikawa, K
Ogawa, O
Minato, N
Nakamura, E
AF Shimizu, Yosuke
Hamazaki, Yoko
Hattori, Masakazu
Doi, Keiko
Terada, Naoki
Kobayashi, Takashi
Toda, Yoshinobu
Yamasaki, Toshinari
Inoue, Takahiro
Kajita, Yoichiro
Maeno, Atsushi
Kamba, Tomomi
Mikami, Yoshiki
Kamoto, Toshiyuki
Yamada, Tomomi
Kanno, Toru
Yoshikawa, Kiyotsugu
Ogawa, Osamu
Minato, Nagahiro
Nakamura, Eijiro
TI SPA-1 controls the invasion and metastasis of human prostate cancer
SO CANCER SCIENCE
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; BREAST-CANCER; CELL-ADHESION; RAP1
ACTIVATION; MIGRATION; SURVIVAL; SIGNAL; MECHANISMS; PATHWAY; KINASE
AB Recent studies suggest that SIPA1 encoding a Rap GTPase-activating protein SPA-1 is a candidate metastasis efficiency-modifying gene in human breast cancer. In this study, we investigated the expression and function of SPA-1 in human prostate cancer (CaP). Immunohistochemical studies of tumor specimens from CaP patients revealed a positive correlation of SPA-1 expression with disease progression and metastasis. The correlation was recapitulated in human CaP cell lines; LNCaP that rarely showed metastasis in SCID mice expressed an undetectable level of SPA-1, whereas highly metastatic PC3 showed abundant SPA-1 expression. Moreover, SIPA1 transduction in LNCaP caused prominent abdominal lymph node metastasis without affecting primary tumor size, whereas shRNA-mediated SIPA1 knockdown or expression of a dominant-active Rap1 mutant (Rap1V12) in PC3 suppressed metastasis. LNCaP transduced with SPA-1 (LNCaP/SPA-1) showed attenuated adhesion to the precoated extracellular matrices (ECM) including collagens and fibronectin, due to defective ECM-medicated Rap1 activation. In addition, LNCaP/SPA-1 showed a diminished level of nuclear Brd4, which is known to bind SPA-1, resulting in reduced expression of a series of ECM-related genes. These results suggest that SPA-1 plays an important role in controlling metastasis efficiency of human CaP by regulating the expression of and interaction with ECM in the primary sites. (Cancer Sci 2011; 102: 828-836)
C1 [Yoshikawa, Kiyotsugu; Nakamura, Eijiro] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Yoshikawa, Kiyotsugu; Nakamura, Eijiro] Harvard Univ, Sch Med, Boston, MA USA.
[Shimizu, Yosuke; Terada, Naoki; Kobayashi, Takashi; Yamasaki, Toshinari; Inoue, Takahiro; Kajita, Yoichiro; Maeno, Atsushi; Kamba, Tomomi; Kamoto, Toshiyuki; Kanno, Toru; Ogawa, Osamu] Kyoto Univ, Grad Sch Med, Dept Urol, Kyoto, Japan.
[Hamazaki, Yoko; Hattori, Masakazu; Doi, Keiko; Minato, Nagahiro] Kyoto Univ, Grad Sch Med, Dept Immunol & Cell Biol, Kyoto, Japan.
[Toda, Yoshinobu] Kyoto Univ, Grad Sch Med, Anat Ctr, Kyoto, Japan.
[Mikami, Yoshiki] Kyoto Univ, Grad Sch Med, Anat Pathol Lab, Kyoto, Japan.
[Yamada, Tomomi] Mie Univ, Grad Sch Med, Tsu, Mie 514, Japan.
RP Nakamura, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM nakamura_eijiro@dfci.harvard.edu
FU Ministry of Education, Culture, Sports, Science and Technology, Japan;
Yamaguchi Endocrine Research Association; Organon Urology Academia;
Takeda Science Foundation; Japanese Foundation for Prostate Research
FX This work was supported by Grant-in-Aid from Ministry of Education,
Culture, Sports, Science and Technology, Japan, Yamaguchi Endocrine
Research Association, Organon Urology Academia, Takeda Science
Foundation and the Japanese Foundation for Prostate Research.
NR 35
TC 17
Z9 19
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1347-9032
EI 1349-7006
J9 CANCER SCI
JI Cancer Sci.
PD APR
PY 2011
VL 102
IS 4
BP 828
EP 836
DI 10.1111/j.1349-7006.2011.01876.x
PG 9
WC Oncology
SC Oncology
GA 737DY
UT WOS:000288550300023
PM 21251160
ER
PT J
AU Kalva, SP
Marentis, TC
Yeddula, K
Somarouthu, B
Wicky, S
Stecker, MS
AF Kalva, Sanjeeva P.
Marentis, Theodore C.
Yeddula, Kalpana
Somarouthu, Bhanusupriya
Wicky, Stephan
Stecker, Michael S.
TI Long-Term Safety and Effectiveness of the "OptEase" Vena Cava Filter
SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID CLINICAL-EXPERIENCE; RETRIEVAL; MULTICENTER; RISK
AB To assess the long-term safety and effectiveness of the OptEase inferior vena cava (IVC) filter.
In this Institutional Review Board-approved, retrospective study, we reviewed data of 71 patients who received an OptEase filter at our institution from 2002 to 2007. Thirty-nine (55%) patients had symptoms of venous thromboembolism before filter placement. The indications for filter included contraindication to anticoagulation in 31 (44%) patients, prophylaxis against pulmonary embolism (PE) in 29 (41%) patients, and failure of anticoagulation in 11 (15%) patients. Procedure-related complications, such as symptomatic post-filter PE, deep venous thrombosis (DVT), IVC occlusion, and incidental imaging-evident filter-related complications, were recorded. Safety was assessed by the occurrence of filter-related complications during placement and follow-up. Effectiveness was assessed by the occurrence of post-filter PE.
Sixty-five (92%) filters were placed under fluoroscopy, and 6 (8%) were placed using intravascular ultrasound guidance. Seventy (99%) filters were placed successfully. Seven (10%) filters were placed in the suprarenal cava. Retrieval was attempted in 14 (20%) patients, and 12 filters were successfully retrieved. Clinical follow-up was available for 20 +/- A 21 months. Symptoms of postfilter PE and DVT occurred in 15% (n = 11) and 10% (n = 7) patients, respectively. None of these patients had computed tomography (CT)-proven PE, and only one had ultrasound-proven new DVT. One patient had symptomatic IVC occlusion. Follow-up abdominal CT in 20 patients showed thrombus in the filter in two of them. There were no instances of filter migration, filter tilt, or caval wall penetration.
The OptEase filter appears to have an acceptable long-term safety profile. The filter was effective against PE.
C1 [Kalva, Sanjeeva P.; Yeddula, Kalpana; Somarouthu, Bhanusupriya; Wicky, Stephan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Stecker, Michael S.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Kalva, Sanjeeva P.; Marentis, Theodore C.; Yeddula, Kalpana; Somarouthu, Bhanusupriya; Wicky, Stephan; Stecker, Michael S.] Harvard Univ, Med Sch Boston, Dept Radiol, Boston, MA 02115 USA.
RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 290,55 Fruit St, Boston, MA 02114 USA.
EM skalva@partners.org
FU Angiodynamics; Cook Medical; Cordis Endovascular; Rex Medical
FX Sanjeeva P. Kalva declares receiving a research grant from Angiodynamics
and Cook Medical, consulting fees and honoraria from Cordis
Endovascular, and royalties from Amirsys and Elsevier. Stephan Wicky
reports receiving a research grant from Angiodynamics and Cook Medical
as well as consulting fees and honoraria from Cordis Endovascular.
Michael S. Stecker reports receiving a research grant from Rex Medical.
Theodore C. Marentis, Kalpana Yeddula, and Bhanusupriya Somarouthu
report no conflict of interest.
NR 38
TC 14
Z9 16
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0174-1551
J9 CARDIOVASC INTER RAD
JI Cardiovasc. Interv. Radiol.
PD APR
PY 2011
VL 34
IS 2
BP 331
EP 337
DI 10.1007/s00270-010-9969-9
PG 7
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 735VY
UT WOS:000288449900015
PM 20820780
ER
PT J
AU Ballal, SA
Gallini, CA
Segata, N
Huttenhower, C
Garrett, WS
AF Ballal, Sonia A.
Gallini, Carey Ann
Segata, Nicola
Huttenhower, Curtis
Garrett, Wendy S.
TI Host and gut microbiota symbiotic factors: lessons from inflammatory
bowel disease and successful symbionts
SO CELLULAR MICROBIOLOGY
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; INTESTINAL INFLAMMATION;
HELICOBACTER-HEPATICUS; IN-VIVO; SUSCEPTIBILITY LOCI; BACTERIAL
SYMBIONT; IMMUNE-SYSTEM; GENE ATG16L1; KEY ROLE
AB P>Humans are colonized by a diverse collection of microbes, the largest numbers of which reside in the distal gut. The vast majority of humans coexist in a beneficial equilibrium with these microbes. However, disruption of this mutualistic relationship can manifest itself in human diseases such as inflammatory bowel disease. Thus the study of inflammatory bowel disease and its genetics can provide insight into host pathways that mediate host-microbiota symbiosis. Bacteria of the human intestinal ecosystem face numerous challenges imposed by human dietary intake, the mucosal immune system, competition from fellow members of the gut microbiota, transient ingested microbes and invading pathogens. Considering features of human resident gut bacteria provides the opportunity to understand how microbes have achieved their symbiont status. While model symbionts have provided perspective into host-microbial homeostasis, high-throughput approaches are becoming increasingly practical for functionally characterizing the gut microbiota as a community.
C1 [Ballal, Sonia A.; Gallini, Carey Ann; Segata, Nicola; Huttenhower, Curtis; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Ballal, Sonia A.] Childrens Hosp Boston, Boston, MA USA.
[Garrett, Wendy S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Garrett, Wendy S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Garrett, WS (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM wgarrett@hsph.harvard.edu
OI Huttenhower, Curtis/0000-0002-1110-0096; Segata,
Nicola/0000-0002-1583-5794
FU NCI NIH HHS [R01 CA154426]; NHGRI NIH HHS [R01 HG005969]; NIAID NIH HHS
[K08 AI078942]
NR 85
TC 12
Z9 13
U1 0
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD APR
PY 2011
VL 13
IS 4
BP 508
EP 517
DI 10.1111/j.1462-5822.2011.01572.x
PG 10
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 736SM
UT WOS:000288514400002
PM 21314883
ER
PT J
AU Fried, KM
Nolan, PE
Anthony, M
Woosley, RL
Freeman, MP
AF Fried, Karen M.
Nolan, Paul E., Jr.
Anthony, Marietta
Woosley, Raymond L.
Freeman, Marlene P.
TI LC-MS Analysis of Sertraline and Its Active Metabolite in Human Serum
Using a Silica Column with a Non-Aqueous Polar Mobile Phase
SO CHROMATOGRAPHIA
LA English
DT Article
DE Column liquid chromatography-mass spectrometry; NA-HILIC; Serum;
Sertraline; Norsertraline
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HYDROPHILIC INTERACTION
CHROMATOGRAPHY; SEROTONIN REUPTAKE INHIBITORS; TANDEM MASS-SPECTROMETRY;
HUMAN PLASMA; GAS-CHROMATOGRAPHY; N-DESMETHYLSERTRALINE;
ANTIDEPRESSANTS; DRUG; PHARMACOKINETICS
AB A sensitive liquid chromatography-mass spectrometry method for the simultaneous determination of sertraline (SER) and its major metabolite norsertraline (NOR) from serum was developed and validated in the context of a pharmacokinetic study in pregnant women. The separations were achieved on a silica column with a non-aqueous polar mobile phase consisting of acetonitrile, methanol and ammonium acetate at a flow rate of 0.5 mL min(-1). The concentrations were measured using a single quadruple mass spectroscopic detector supplied with atmospheric pressure ionization electrospray. Sample preparation consisted of a simple liquid-liquid procedure. The detector was set in selective ion mode for each compound of interest, 306 m/z for SER and 275 m/z for NOR. Calibration curves were generated by least square linear regression for concentration of 5-160 ng mL(-1) for SER and from 10 to 320 ng mL(-1) for NOR. The curves for both compounds of interest were linear, with correlation coefficients r (2) a parts per thousand yen 0.999.
C1 [Freeman, Marlene P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Fried, Karen M.] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.
[Nolan, Paul E., Jr.] Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA.
[Anthony, Marietta; Woosley, Raymond L.] Crit Path Inst, Tucson, AZ USA.
RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
EM mfreeman@partners.org
FU FDA Office of Women's Health; NIMH
FX The authors would like to thank Pfizer Pharmaceutical for its generosity
in supplying primary standards for both SER and its metabolite NOR. We
are also grateful to the staff at the University of Arizona GCRC,
Tucson, AZ for drawing the timed samples and processing all the blood.
In addition, we would like to thank Drs. Anne-Francoise Aubry and David
K. Lloyd for their invaluable help in editing this manuscript. Foremost,
we are indebted to both the FDA Office of Women's Health and NIMH for
providing the funding for this project. Finally, we thank Dr. David
Bishop for proofreading the manuscript and preparing the final version
of the figures.
NR 23
TC 5
Z9 5
U1 5
U2 14
PU VIEWEG
PI WIESBADEN
PA ABRAHAM-LINCOLN-STRABE 46, POSTFACH 15 47, D-65005 WIESBADEN, GERMANY
SN 0009-5893
J9 CHROMATOGRAPHIA
JI Chromatographia
PD APR
PY 2011
VL 73
IS 7-8
BP 749
EP 754
DI 10.1007/s10337-011-1919-4
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 740MO
UT WOS:000288799100016
ER
PT J
AU Braun, A
Chang, D
Mahadevappa, K
Gibbons, FK
Liu, Y
Giovannucci, E
Christopher, KB
AF Braun, Andrea
Chang, Domingo
Mahadevappa, Karthik
Gibbons, Fiona K.
Liu, Yan
Giovannucci, Edward
Christopher, Kenneth B.
TI Association of low serum 25-hydroxyvitamin D levels and mortality in the
critically ill
SO CRITICAL CARE MEDICINE
LA English
DT Article
ID VITAMIN-D DEFICIENCY; PROLONGED CRITICAL ILLNESS; MYOCARDIAL-INFARCTION;
UNITED-STATES; ADMINISTRATIVE DATABASES; CARDIOVASCULAR-DISEASE;
COMORBIDITY INDEX; OUTCOMES RESEARCH; CLINICAL-DATA; CO-MORBIDITY
AB Objective: We hypothesized that deficiency in 25-hydroxyvitamin D before hospital admission would be associated with all-cause mortality in the critically ill.
Design: Multicenter observational study of patients treated in medical and surgical intensive care units.
Setting: A total of 209 medical and surgical intensive care beds in two teaching hospitals in Boston, MA.
Patients: A total of 2399 patients, age >= 18 yrs, in whom 25-hydroxyvitamin D was measured before hospitalization between 1998 and 2009.
Interventions: None.
Measurements and Main Results: Preadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (<= 15 ng/mL), insufficiency (16-29 ng/mL), and sufficiency (>= 30 ng/mL). Logistic regression examined death by days 30, 90, and 365 post-intensive care unit admission, in-hospital mortality, and blood culture positivity. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for short-term and long-term mortality. At 30 days following intensive care unit admission, patients with 25-hydroxyvitamin D deficiency have an odds ratio for mortality of 1.69 (95% confidence interval of 1.28-2.23, p <. 0001) relative to patients with 25-hydroxyvitamin D sufficiency. 25-Hydroxyvitamin D deficiency remains a significant predictor of mortality at 30 days following intensive care unit admission following multivariable adjustment (adjusted odds ratio of 1.69, 95% confidence interval of 1.26-2.26, p < .0001). At 30 days following intensive care unit admission, patients with 25-hydroxyvitamin D insufficiency have an odds ratio of 1.32 (95% confidence interval of 1.02-1.72, p = .036) and an adjusted odds ratio of 1.36 (95% confidence interval of 1.03-1.79, p = .029) relative to patients with 25-hydroxyvitamin D sufficiency. Results were similar at 90 and 365 days following intensive care unit admission and for in-hospital mortality. In a subgroup analysis of patients who had blood cultures drawn (n = 1160), 25-hydroxyvitamin D deficiency was associated with increased risk of blood culture positivity. Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for blood culture positivity of 1.64 (95% confidence interval of 1.05-2.55, p = .03) relative to patients with 25-hydroxyvitamin D sufficiency, which remains significant following multivariable adjustment (odds ratio of 1.58, 95% confidence interval of 1.01-2.49, p = .048).
Conclusion: Deficiency of 25-hydroxyvitamin D before hospital admission is a significant predictor of short-and long-term all-cause patient mortality and blood culture positivity in a critically ill patient population. (Crit Care Med 2011; 39:671-677)
C1 [Braun, Andrea; Chang, Domingo; Mahadevappa, Karthik; Christopher, Kenneth B.] Harvard Univ, Sch Publ Hlth, Div Renal, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Gibbons, Fiona K.] Harvard Univ, Sch Publ Hlth, Div Pulm, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Liu, Yan; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Christopher, KB (reprint author), Harvard Univ, Sch Publ Hlth, Div Renal, Brigham & Womens Hosp, 665 Huntington Ave, Boston, MA 02115 USA.
EM kbchristopher@partners.org
FU National Institutes of Health, Bethesda, MD [5K08AI060881]
FX Dr. Christopher is supported, in part, by grant 5K08AI060881 from the
National Institutes of Health, Bethesda, MD. The remaining authors have
not disclosed any potential conflicts of interest.
NR 54
TC 103
Z9 116
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD APR
PY 2011
VL 39
IS 4
BP 671
EP 677
DI 10.1097/CCM.0b013e318206ccdf
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA 736ZD
UT WOS:000288533000009
PM 21242800
ER
PT J
AU Calfee, CS
Ware, LB
Glidden, DV
Eisner, MD
Parsons, PE
Thompson, T
Matthay, MA
AF Calfee, Carolyn S.
Ware, Lorraine B.
Glidden, David V.
Eisner, Mark D.
Parsons, Polly E.
Thompson, Taylor
Matthay, Michael A.
CA Natl Heart Blood & Lung Inst Acute
TI Use of risk reclassification with multiple biomarkers improves mortality
prediction in acute lung injury
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE acute respiratory distress syndrome; biological marker; pulmonary edema;
risk prediction; risk reclassification
ID RESPIRATORY-DISTRESS-SYNDROME; CLINICAL-OUTCOMES; HOSPITAL MORTALITY;
VENTILATION; MARKER; CURVE; DEATH; ICU
AB Objective: Multiple single biomarkers have been associated with poor outcomes in acute lung injury; however, no single biomarker has sufficient discriminating power to clearly indicate prognosis. Using both derivation and replication cohorts, we tested novel risk reclassification methods to determine whether measurement of multiple plasma biomarkers at the time of acute lung injury diagnosis would improve mortality prediction in acute lung injury.
Design: Analysis of plasma biomarker levels and prospectively collected clinical data from patients enrolled in two randomized controlled trials of ventilator therapy for acute lung injury.
Setting: Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network.
Patients: Subjects enrolled in a trial of lower tidal volume ventilation (derivation cohort) and subjects enrolled in a trial of higher vs. lower positive end-expiratory pressure (replication cohort).
Interventions: None.
Measurements and Main Results: The plasma biomarkers were intercellular adhesion molecule-1, von Willebrand factor, interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D. In the derivation cohort (n = 547), adding data on these biomarkers to clinical predictors (Acute Physiology and Chronic Health Evaluation III score) at the time of study enrollment improved the accuracy of risk prediction, as reflected by a net reclassification improvement of 22% (95% confidence interval 13% to 32%; p < .001). In the replication cohort (n = 500), the net reclassification improvement was 17% (95% confidence interval 7% to 26%; p < .001). A reduced set of three biomarkers (interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D) had nearly equivalent prognostic value in both cohorts.
Conclusions: When combined with clinical data, plasma biomarkers measured at the onset of acute lung injury can improve the accuracy of risk prediction. Combining three or more biomarkers may be useful for selecting a high-risk acute lung injury population for enrollment in clinical trials of novel therapies. (Crit Care Med 2011; 39:711-717)
C1 [Calfee, Carolyn S.; Eisner, Mark D.; Matthay, Michael A.] Univ Calif San Francisco, Pulm & Crit Care Div, Dept Med, San Francisco, CA 94143 USA.
[Calfee, Carolyn S.; Eisner, Mark D.; Matthay, Michael A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA.
[Glidden, David V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Calfee, Carolyn S.; Eisner, Mark D.; Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
[Ware, Lorraine B.] Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care, Nashville, TN USA.
[Parsons, Polly E.] Univ Vermont, Dept Med, Div Pulm & Crit Care Med, Burlington, VT USA.
[Thompson, Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Med Unit, Boston, MA 02114 USA.
[Thompson, Taylor] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA.
RP Calfee, CS (reprint author), Univ Calif San Francisco, Pulm & Crit Care Div, Dept Med, 505 Parnassus Ave,Box 0111, San Francisco, CA 94143 USA.
EM carolyn.calfee@ucsf.edu
OI Murray, Susan/0000-0003-4387-7673
FU National Heart, Lung, and Blood Institute [N01-HR 46054, 46055, 46056,
46057, 46058, 46059, 46060, 46061, 46062, 46063, 46064, HL 51856,
HL081332]; National Heart, Lung, and Blood Institute, Bethesda, MD;
Flight Attendant Medical Research Institute, Miami, FL [HL090833];
National Center for Research Resources, a component of the National
Institutes of Health, Bethesda, MD [KL2RR024130]
FX Supported, in part, by contracts National Heart, Lung, and Blood
Institute grant N01-HR 46054, 46055, 46056, 46057, 46058, 46059, 46060,
46061, 46062, 46063, and 46064 with the National Heart, Lung, and Blood
Institute, Bethesda, MD. Dr. Calfee was supported by grant HL090833, by
the Flight Attendant Medical Research Institute, Miami, FL, and by grant
KL2RR024130 from the National Center for Research Resources, a component
of the National Institutes of Health, Bethesda, MD. Dr. Matthay was
supported by National Heart, Lung, and Blood Institute grant HL 51856.
Dr. Ware was supported by grant HL081332.
NR 35
TC 48
Z9 53
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD APR
PY 2011
VL 39
IS 4
BP 711
EP 717
DI 10.1097/CCM.0b013e318207ec3c
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA 736ZD
UT WOS:000288533000015
PM 21283009
ER
PT J
AU Kacmarek, RM
Villar, J
AF Kacmarek, Robert M.
Villar, Jesus
TI When it comes to ventilation, noisy is better than quiet and variability
is healthier than constant!
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID PROPORTIONAL ASSIST VENTILATION; MECHANICAL VENTILATION; PRESSURE
SUPPORT; LUNG INJURY; BENEFITS; MODEL
C1 [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Kacmarek, Robert M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Villar, Jesus] Univ Hosp, Inst Salud Carlos III, CIBER Enfermedades Resp, Las Palmas Gran Canaria, Spain.
[Villar, Jesus] Univ Hosp, Res Unit, Las Palmas Gran Canaria, Spain.
RP Kacmarek, RM (reprint author), Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
NR 15
TC 4
Z9 4
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD APR
PY 2011
VL 39
IS 4
BP 898
EP 899
DI 10.1097/CCM.0b013e31820e6a31
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 736ZD
UT WOS:000288533000052
PM 21613844
ER
PT J
AU Laghi, F
AF Laghi, Franco
TI Ventilator-induced diaphragmatic dysfunction: Is there a dim light at
the end of the tunnel?
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID ANTIOXIDANT SUPPLEMENTATION; FAILURE; HUMANS; DISUSE; MUSCLE; TRIAL
C1 [Laghi, Franco] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA.
[Laghi, Franco] Loyola Univ, Maywood, IL 60153 USA.
RP Laghi, F (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA.
NR 16
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD APR
PY 2011
VL 39
IS 4
BP 903
EP 905
DI 10.1097/CCM.0b013e31820a5135
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA 736ZD
UT WOS:000288533000055
PM 21613847
ER
PT J
AU Denton, J
Newton, AW
Vandeven, AM
AF Denton, Jennifer
Newton, Alice W.
Vandeven, Andrea M.
TI Update on child maltreatment: toward refining the evidence base
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 SEXUALLY-TRANSMITTED INFECTIONS; ABUSIVE HEAD TRAUMA;
MUNCHAUSEN-SYNDROME; RISK-FACTORS; HEALTH; VIOLENCE; VICTIMIZATION;
DISCIPLINE; PREVENTION; PROTECTION
AB Purpose of review
This review is designed to aid general pediatricians as they assess cases of possible child maltreatment. The authors have selected salient articles that inform the daily practice of any professional involved in assessing child abuse.
Recent findings
The incidence of child abuse continues to decline in the United States, although a large number of children still suffer from abuse and neglect, and many are subject to more than one type of maltreatment. Clinicians are encouraged to be vigilant about the subtle indicators of physical abuse, with many authors adding to our understanding about how children present after inflicted abdominal or skeletal trauma. Clinicians are also cautioned to watch for signs of Munchausen syndrome by proxy, which may be elusive and difficult to discern.
Summary
The field of child abuse pediatrics is still young, with the first board certification in 2009. The volume of research in the field is exploding and there is a greater level of awareness and data collection occurring throughout the world. Pediatric clinicians are encouraged to play a role in preventing abuse and neglect, as well as addressing intimate partner violence, and to maintain vigilance about child maltreatment and its subtle clinical presentations.
C1 [Denton, Jennifer; Newton, Alice W.] Childrens Hosp Boston, Child Protect Program, Boston, MA 02115 USA.
[Denton, Jennifer; Newton, Alice W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Newton, Alice W.] Massachusetts Gen Hosp, Child Protect Consultat Program, Boston, MA 02114 USA.
[Vandeven, Andrea M.] Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA.
[Vandeven, Andrea M.] Childrens Mercy Hosp, SCAN Program, Kansas City, MO 64108 USA.
RP Newton, AW (reprint author), Childrens Hosp Boston, Child Protect Program, 300 Longwood Ave, Boston, MA 02115 USA.
EM alice.newton@childrens.harvard.edu
NR 51
TC 2
Z9 2
U1 2
U2 14
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 2011
VL 23
IS 2
BP 240
EP 248
DI 10.1097/MOP.0b013e3283446010
PG 9
WC Pediatrics
SC Pediatrics
GA 736LJ
UT WOS:000288495900018
PM 21293272
ER
PT J
AU Liu, Z
Segawa, H
Aydin, C
Reyes, M
Erben, RG
Weinstein, LS
Chen, M
Marshansky, V
Frohlich, LF
Bastepe, M
AF Liu, Zun
Segawa, Hiroko
Aydin, Cumhur
Reyes, Monica
Erben, Reinhold G.
Weinstein, Lee S.
Chen, Min
Marshansky, Vladimir
Froehlich, Leopold F.
Bastepe, Murat
TI Transgenic Overexpression of the Extra-Large Gs alpha Variant XL alpha s
Enhances Gs alpha-Mediated Responses in the Mouse Renal Proximal Tubule
in Vivo
SO ENDOCRINOLOGY
LA English
DT Article
ID PSEUDOHYPOPARATHYROIDISM-TYPE-IB; ALBRIGHT HEREDITARY OSTEODYSTROPHY;
G(S)ALPHA KNOCKOUT MICE; G-PROTEIN; PARATHYROID-HORMONE; CONTROL REGION;
TARGETED DISRUPTION; GNAS LOCUS; SUBUNIT; GENE
AB XL alpha s, a variant of the stimulatory G protein alpha-subunit (Gs alpha), can mediate receptor-activated cAMP generation and, thus, mimic the actions of Gs alpha in transfected cells. However, it remains unknown whether XL alpha s can act in a similar manner in vivo. We have now generated mice with ectopic transgenic expression of rat XL alpha s in the renal proximal tubule (rptXL alpha s mice), where Gs alpha mediates most actions of PTH. Western blots and quantitative RT-PCR showed that, while Gs alpha and type-1 PTH receptor levels were unaltered, protein kinase A activity and 25-hydroxyvitamin D 1-alpha-hydroxylase (Cyp27b1) mRNAlevels were significantly higher in renal proximal tubules of rptXL alpha s mice than wild-type littermates. Immunohistochemical analysis of kidney sections showed that the sodium- phosphate cotransporter type 2a was modestly reduced in brush border membranes of male rptXL alpha s mice compared to gender-matched controls. Serum calcium, phosphorus, and 1,25 dihydroxyvitamin D were within the normal range, but serum PTH was similar to 30% lower in rptXL alpha s mice than in controls (152 +/- 16 vs. 222 +/- 41 pg/ml; P < 0.05). After crossing the rptXL alpha s mice to mice with ablation of maternal Gnas exon 1 (E1m(-/+)), male offspring carrying both the XL alpha s transgene and maternal Gnas exon 1 ablation (rptXL alpha s/E1m(-/+)) were significantly less hypocalcemic than gender-matched E1m(-/+) littermates. Both E1m(-/+) and rptXL alpha s/E1m(-/+) offspring had higher serum PTH than wild-type littermates, but the degree of secondary hyperparathyroidism tended to be lower in rptXL alpha s/E1m(-/+) mice. Hence, transgenic XL alpha s expression in the proximal tubule enhanced Gs alpha-mediated responses, indicating that XL alpha s can mimic Gs alpha in vivo. (Endocrinology 152: 1222-1233, 2011)
C1 [Liu, Zun; Segawa, Hiroko; Aydin, Cumhur; Reyes, Monica; Froehlich, Leopold F.; Bastepe, Murat] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA.
[Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA.
[Marshansky, Vladimir] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Segawa, Hiroko] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Mol Nutr, Tokushima 7708503, Japan.
[Aydin, Cumhur] Gulhane Mil Med Acad, Ctr Dent Sci, Dept Endodont, TR-06018 Ankara, Turkey.
[Erben, Reinhold G.] Univ Vet Med, Dept Biomed Sci, A-1210 Vienna, Austria.
[Weinstein, Lee S.; Chen, Min] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Froehlich, Leopold F.] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria.
RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, 50 Blossom St,Thier 10, Boston, MA 02114 USA.
EM bastepe@helix.mgh.harvard.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), National Institutes of Health (NIH) [R01DK073911]; NIH
[DK038452]; Boston Area Diabetes Endocrinology Research Center (BADERC)
[DK057521-08]; Gulhane Military Medical Academy, Ankara, Turkey
FX This work was supported in part by a research grant from the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
National Institutes of Health (NIH) (R01DK073911 to M. B). Part of this
study was also supported by a NIH Grant DK038452 and by Boston Area
Diabetes Endocrinology Research Center (BADERC) Grant DK057521-08 (to V.
M.). This work was also partially supported by the Intramural Research
Program of NIDDK, NIH. C. A. received a research fellowship award from
Gulhane Military Medical Academy, Turkish General Staff, Ankara, Turkey.
NR 47
TC 15
Z9 17
U1 0
U2 12
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD APR
PY 2011
VL 152
IS 4
BP 1222
EP 1233
DI 10.1210/en.2010-1034
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 739EM
UT WOS:000288696300005
PM 21303955
ER
PT J
AU Barkhoudarian, MT
Schwarzschild, MA
AF Barkhoudarian, Melita T.
Schwarzschild, Michael A.
TI Preclinical jockeying on the translational track of adenosine A(2A)
receptors
SO EXPERIMENTAL NEUROLOGY
LA English
DT Editorial Material
ID MPTP-TREATED MONKEYS; PARKINSONS-DISEASE; ANTAGONIST ISTRADEFYLLINE;
MOTOR FLUCTUATIONS; VENTRAL STRIATUM; L-DOPA; CAFFEINE; BRAIN;
DYSKINESIA; KW-6002
C1 [Barkhoudarian, Melita T.; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Schwarzschild, MA (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Room 3002,114 16th St, Boston, MA 02129 USA.
EM michaels@helix.mgh.harvard.edu
FU NINDS NIH HHS [K24 NS060991, NS054978, R01 NS054978, K24 NS060991-03,
R01 NS054978-04S1, NS060991, R01 NS054978-05]
NR 47
TC 6
Z9 6
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
J9 EXP NEUROL
JI Exp. Neurol.
PD APR
PY 2011
VL 228
IS 2
BP 160
EP 164
DI 10.1016/j.expneurol.2010.12.022
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 740YI
UT WOS:000288829900002
PM 21211537
ER
PT J
AU Dionne, KR
Leser, JS
Lorenzen, KA
Beckham, JD
Tyler, KL
AF Dionne, Kalen R.
Leser, J. Smith
Lorenzen, Kristi A.
Beckham, J. David
Tyler, Kenneth L.
TI A brain slice culture model of viral encephalitis reveals an innate CNS
cytokine response profile and the therapeutic potential of caspase
inhibition
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Reovirus; Virus; Viral; Apoptosis; Caspase; Encephalitis; Neuron; Ex
vivo; Organotypic; Brain slice; Cytokine; IL6; KC; IL8; CXCL10; RANTES;
Q-VD-OPh
ID CENTRAL-NERVOUS-SYSTEM; HERPES-SIMPLEX-VIRUS; ORGANOTYPIC HIPPOCAMPAL
CULTURES; N-TERMINAL KINASE; JAPANESE ENCEPHALITIS; REOVIRUS INFECTION;
CELL-DEATH; IN-VITRO; CEREBROSPINAL-FLUID; PARKINSONS-DISEASE
AB Viral encephalitis is a significant cause of human morbidity and mortality in large part due to suboptimal diagnosis and treatment. Murine reovirus infection serves as a classic experimental model of viral encephalitis. Infection of neonatal mice with T3 reoviruses results in lethal encephalitis associated with neuronal infection, apoptosis, and CNS tissue injury. We have developed an ex vivo brain slice culture (BSC) system that recapitulates the basic pathological features and kinetics of viral replication seen in vivo. We utilize the BSC model to identify an innate, brain-tissue specific inflammatory cytokine response to reoviral infection, which is characterized by the release of IL6, CXCL10, RANTES, and murine IL8 analog (KC). Additionally, we demonstrate the potential utility of this system as a pharmaceutical screening platform by inhibiting reovirus-induced apoptosis and CNS tissue injury with the pan-caspase inhibitor, Q-VD-OPh. Cultured brain slices not only serve to model events occurring during viral encephalitis, but can also be utilized to investigate aspects of pathogenesis and therapy that are not experimentally accessible in vivo. Published by Elsevier Inc.
C1 [Leser, J. Smith; Beckham, J. David; Tyler, Kenneth L.] Univ Colorado Denver, Dept Neurol, Aurora, CO 80045 USA.
[Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado Denver, Med Scientist Training Program, Aurora, CO 80045 USA.
[Dionne, Kalen R.; Tyler, Kenneth L.] Univ Colorado Denver, Neurosci Program, Aurora, CO 80045 USA.
[Lorenzen, Kristi A.; Beckham, J. David; Tyler, Kenneth L.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
[Beckham, J. David; Tyler, Kenneth L.] Univ Colorado Denver, Dept Microbiol, Aurora, CO 80045 USA.
[Tyler, Kenneth L.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.
RP Tyler, KL (reprint author), Univ Colorado Denver, Dept Neurol, Res Complex 2,12700 E 19th Ave,B182, Aurora, CO 80045 USA.
EM Ken.Tyler@UCDenver.edu
OI Tyler, Kenneth/0000-0003-3294-5888
FU VA; Mentored Clinical Science Development award [5K08AI076518,
5K08AI076518-02S1, 5K08AI076518-03S1]; MST Program [T32 GM008497];
National Research Service [F30 NS071630]; [RO1NS050138]; [RO1NS051403]
FX This work was supported by RO1NS050138 (K.L.T), RO1NS051403 (K.L.T), and
a VA Merit Grant (K.L.T).; J.D.B. was supported by a Mentored Clinical
Science Development award (5K08AI076518, 5K08AI076518-02S1, and
5K08AI076518-03S1).; K.R.D. was supported by an institutional MST
Program training grant (T32 GM008497) and a National Research Service
Award for Predoctoral MD/PhD Fellows (F30 NS071630).
NR 60
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Z9 14
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
J9 EXP NEUROL
JI Exp. Neurol.
PD APR
PY 2011
VL 228
IS 2
BP 222
EP 231
DI 10.1016/j.expneurol.2011.01.006
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 740YI
UT WOS:000288829900010
PM 21241693
ER
PT J
AU Kanwal, F
Hoang, T
Kramer, JR
Asch, SM
Goetz, MB
Zeringue, A
Richardson, P
El-Serag, HB
AF Kanwal, Fasiha
Tuyen Hoang
Kramer, Jennifer R.
Asch, Steven M.
Goetz, Matthew Bidwell
Zeringue, Angelique
Richardson, Peter
El-Serag, Hashem B.
TI Increasing Prevalence of HCC and Cirrhosis in Patients With Chronic
Hepatitis C Virus Infection
SO GASTROENTEROLOGY
LA English
DT Article
DE Liver Cancer; Epidemiology; Virology
ID CHRONIC LIVER-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-B-HEPATITIS;
UNITED-STATES; HEPATOCELLULAR-CARCINOMA; NATURAL-HISTORY; NON-A;
VETERANS; FIBROSIS; PROGRESSION
AB BACKGROUND & AIMS: Patients with hepatitis C virus (HCV) infection are at risk for developing costly and morbid complications, although the actual prevalence of these complications is unknown. We examined time trends in the prevalence of cirrhosis and its related complications, such as hepatic decompensation and hepatocellular carcinoma (HCC). METHODS: We calculated the annual prevalence of cirrhosis, decompensated cirrhosis, and HCC in a national sample of veterans diagnosed with HCV between 1996 and 2006. Patients with HCV who had at least one physician visit in a given calendar year were included in the analysis of prevalence for that year. We used direct standardization to adjust the prevalence of cirrhosis and related complications for increasing age of the cohort as well as sex and changes in clinical characteristics. RESULTS: In this cohort, the number of individuals with HCV increased from 17,261 in 1996 to 106,242 in 2006. The prevalence of cirrhosis increased from 9% in 1996 to 18.5% in 2006. The prevalence of patients with decompensated cirrhosis doubled, from 5% in 1996 to 11% in 2006, whereas the prevalence of HCC increased approximately 20-fold (0.07% in 1996 to 1.3% in 2006). After adjustment, the time trend in the prevalence of cirrhosis (and its complications) was lower than the crude trend, although it still increased significantly. CONCLUSIONS: The prevalence of cirrhosis and HCC in HCV-infected patients has increased significantly over the past 10 years. An aging cohort of patients with HCV could partly explain our findings. Clinicians and health care systems should develop strategies to provide timely and effective care to this high-risk population of patients.
C1 [Kanwal, Fasiha; Zeringue, Angelique] John Cochran VA Med Ctr, Dept Gastroenterol & Hepatol, St Louis, MO USA.
[Kanwal, Fasiha] St Louis Univ, Sch Med, St Louis, MO USA.
[Tuyen Hoang; Asch, Steven M.; Goetz, Matthew Bidwell] Greater Los Angeles VA Healthcare Syst, Dept Med & Hlth Serv Res, Los Angeles, CA USA.
[Kramer, Jennifer R.; Richardson, Peter; El-Serag, Hashem B.] Michael E DeBakey VA Med Ctr, Houston VA HSR&D Ctr Excellence, Hlth Serv Res & Dev Serv, Houston, TX USA.
[Kramer, Jennifer R.; Richardson, Peter; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Asch, Steven M.; Richardson, Peter; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA.
[Asch, Steven M.; Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
RP Kanwal, F (reprint author), St Louis VA Med Ctr, 915 N Grand,111-JC-GI, St Louis, MO 63141 USA.
EM fasiha.kanwal@va.gov
RI Zeringue, Angelique/I-1755-2012;
OI Goetz, Matthew/0000-0003-4542-992X
FU Health Services Research and Development Service, Office of Research and
Development, Department of Veterans Affairs [IIR-07-111, K24DK078154-03,
R01CA125487-03]
FX Supported in part by Health Services Research and Development Service,
Office of Research and Development, Department of Veterans Affairs,
grant IIR-07-111 (to F. K.) and K24DK078154-03 and R01CA125487-03 (to
H.B.E.).
NR 35
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U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2011
VL 140
IS 4
BP 1182
EP +
DI 10.1053/j.gastro.2010.12.032
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 740JV
UT WOS:000288789900025
PM 21184757
ER
PT J
AU Nichols, AC
Kneuertz, PJ
Deschler, DG
Lin, DT
Emerick, KS
Clark, JR
Busse, PW
Rocco, JW
AF Nichols, Anthony C.
Kneuertz, Peter J.
Deschler, Daniel G.
Lin, Derrick T.
Emerick, Kevin S.
Clark, John R.
Busse, Paul W.
Rocco, James W.
TI SURGICAL SALVAGE OF THE OROPHARYNX AFTER FAILURE OF ORGAN-SPARING
THERAPY
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Article
DE surgical salvage; oropharyngeal cancer; radiation; chemoradiation
ID SQUAMOUS-CELL CARCINOMA; TRANSORAL ROBOTIC SURGERY; ADVANCED
LARYNGEAL-CANCER; RADIATION-THERAPY; ONCOLOGY-GROUP; NECK-CANCER;
STAGE-III; HEAD; CHEMORADIATION; PRESERVATION
AB Background. The purpose of this study was to evaluate the efficacy of salvage surgery for local recurrences of oropharyngeal squamous cell carcinoma (OPSCC) and identify predictors of survival.
Methods. The authors reviewed 264 patients with OPSCC treated with radiation or chemoradiation identified retrospectively. Of the 77 patients that experienced recurrences, 37 had local or local and regional recurrences and were considered for salvage surgery.
Results. Of the 37 patients with local or local and regional recurrence, 5 had unresectable disease whereas 3 refused surgery. The remainder underwent salvage surgery with 2-year and 5-year survival rates of 64.5% and 43.4%, respectively. A history of alcohol abuse and positive surgical margins were the only predictors of poorer overall survival (p < .05) after salvage surgery.
Conclusion. Surgical salvage of locoregional recurrences can be effective if wide resections are performed so that negative margins can be achieved. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 516-524, 2011
C1 [Nichols, Anthony C.; Kneuertz, Peter J.; Deschler, Daniel G.; Lin, Derrick T.; Emerick, Kevin S.; Rocco, James W.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Nichols, Anthony C.] Univ Western Ontario, Dept Otolaryngol Head & Neck Surg, London, ON, Canada.
[Clark, John R.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA.
[Busse, Paul W.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Rocco, James W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Rocco, JW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA.
EM jrocco@partners.org
NR 20
TC 17
Z9 17
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1043-3074
J9 HEAD NECK-J SCI SPEC
JI Head Neck-J. Sci. Spec. Head Neck
PD APR
PY 2011
VL 33
IS 4
BP 516
EP 524
DI 10.1002/hed.21480
PG 9
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 737YT
UT WOS:000288607200010
PM 20652974
ER
PT J
AU Schmittdiel, J
Selby, JV
Swain, B
Daugherty, SL
Leong, TK
Ho, M
Margolis, KL
O'Connor, P
Magid, DJ
Bibbins-Domingo, K
AF Schmittdiel, Julie
Selby, Joe V.
Swain, Bix
Daugherty, Stacie L.
Leong, Thomas K.
Ho, Michael
Margolis, Karen L.
O'Connor, Patrick
Magid, David J.
Bibbins-Domingo, Kirsten
TI Missed Opportunities in Cardiovascular Disease Prevention? Low Rates of
Hypertension Recognition for Women at Medicine and Obstetrics-Gynecology
Clinics
SO HYPERTENSION
LA English
DT Article
DE hypertension; sex; CVD prevention; primary care; OBGYN
ID ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; HIGH
BLOOD-PRESSURE; PRIMARY-CARE; HEALTH-CARE; RACIAL-DIFFERENCES; PRACTICE
PATTERNS; SEX-DIFFERENCES; SERVICES; GUIDELINES
AB Younger women use both internal medicine and obstetrics-gynecology (OBGYN) clinics as primary sources of health care. However, the role of OBGYN clinics in cardiovascular disease prevention is largely unexplored. The objective of this study was to examine rates of hypertension recognition in women <50 years of age who presented with elevated blood pressures in family practice and internal medicine (medicine) OBGYN clinics and to compare these rates across clinic type. The study's population consisted of 34 627 nonpregnant women ages 18 to 49 years with new-onset hypertension (defined as 2 consecutive visits with elevated blood pressures of systolic blood pressure >140 mm Hg or diastolic blood pressure >= 90 mm Hg with no previous hypertension history) from 2002 to 2006. Multivariate logistic regressions predicting the clinical recognition of hypertension (a recorded diagnosis of hypertension and/or an antihypertensive prescription by any provider within 1 year of the second elevated blood pressure) assessed the association between hypertension recognition and the clinic where the second elevated blood pressure was recorded. Analysis showed that hypertension was recognized in <33% of women with new-onset hypertension. Women whose second consecutive elevated blood pressure was recorded in OBGYN clinics were less likely to be recognized as having hypertension within 12 months by any provider compared with women whose second consecutive elevated blood pressure was recorded in a medicine clinic (odds ratio: 0.51 [95% CI: 0.48 to 0.54]). This study suggests that further attention be paid to identifying and treating cardiovascular disease risk factors in women <50 years of age presenting in both medicine and OBGYN clinics and that improved coordination across care settings has the potential to improve cardiovascular disease prevention in young women. (Hypertension. 2011;57:717-722.)
C1 [Schmittdiel, Julie; Selby, Joe V.; Swain, Bix; Leong, Thomas K.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA.
[Daugherty, Stacie L.; Ho, Michael] Univ Colorado, Aurora, CO USA.
[Margolis, Karen L.; O'Connor, Patrick] HealthPartners, Minneapolis, MN USA.
[Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA 94143 USA.
[Ho, Michael] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
RP Schmittdiel, J (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA.
EM Julie.A.Schmittdiel@kp.org
FU National Heart, Lung, and Blood Institute [U19 HL91179-01, K08HL103776];
Office of Research in Women's Health Building Interdisciplinary Careers
in Women's Health [K12HD052163]; Veterans Affairs Health Services
Research and Development Service [05-026-1]
FX This study was funded by the National Heart, Lung, and Blood Institute
(U19 HL91179-01). The work by J.S. on this study was supported by the
Office of Research in Women's Health Building Interdisciplinary Careers
in Women's Health K12 Career Development Award (K12HD052163). M. H. is
supported by a Veterans Affairs Health Services Research and Development
Service Career Development Award (05-026-1). S. L. D. is supported by
Award No. K08HL103776 from the National Heart, Lung, and Blood
Institute.
NR 41
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U1 1
U2 5
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 2011
VL 57
IS 4
BP 717
EP 722
DI 10.1161/HYPERTENSIONAHA.110.168195
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 735RL
UT WOS:000288434600017
PM 21339475
ER
PT J
AU Xiao, L
Crabb, DM
Duffy, LB
Paralanov, V
Glass, JI
Hamilos, DL
Waites, KB
AF Xiao, Li
Crabb, Donna M.
Duffy, Lynn B.
Paralanov, Vanya
Glass, John I.
Hamilos, Daniel L.
Waites, Ken B.
TI Mutations in ribosomal proteins and ribosomal RNA confer macrolide
resistance in human Ureaplasma spp.
SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
LA English
DT Article
DE Ureaplasma; Macrolide; Resistance; Ribosomal proteins; Ribosomal RNA;
Antibiotic
ID STREPTOCOCCUS-PNEUMONIAE; CLINICAL STRAINS; ERYTHROMYCIN; GENES;
TETRACYCLINE; UREALYTICUM; MECHANISMS; VITRO; TIME
AB Genetic mechanisms of macrolide resistance were investigated in six isolates of Ureaplasma spp. with erythromycin minimum inhibitory concentrations (MICs)>= 8 mu g/mL that were derived from 370 cultures obtained over a several year period. Point mutations in domain V of 23S rRNA and/or mutations in ribosomal protein L4 genes are likely to be responsible for this drug resistance. Overall, macrolide resistance was uncommon, in contrast to tetracycline resistance that was documented in 121 unique isolates (33%). (c) 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
C1 [Xiao, Li; Crabb, Donna M.; Duffy, Lynn B.; Waites, Ken B.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
[Paralanov, Vanya; Glass, John I.] J Craig Venter Inst, Rockville, MD USA.
[Hamilos, Daniel L.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
RP Waites, KB (reprint author), Univ Alabama, 619 19th St S,WP 230, Birmingham, AL 35249 USA.
EM waiteskb@uab.edu
RI Glass, John/A-6572-2015
OI Glass, John/0000-0002-3784-5301
FU National Institute of Allergy and Infectious Diseases (Bethesda, MD)
[RO1A1072577, N01-A1-30071]
FX This work was supported in part by federal funds under grants
RO1A1072577 and contract N01-A1-30071 from the National Institute of
Allergy and Infectious Diseases (Bethesda, MD).
NR 17
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U1 3
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-8579
J9 INT J ANTIMICROB AG
JI Int. J. Antimicrob. Agents
PD APR
PY 2011
VL 37
IS 4
BP 377
EP 379
DI 10.1016/j.ijantimicag.2010.12.012
PG 3
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA 736IU
UT WOS:000288487700017
PM 21353494
ER
PT J
AU Chaudhry, S
Arena, R
Wasserman, K
Hansen, JE
Lewis, GD
Myers, J
Belardinelli, R
LaBudde, B
Menasco, N
Boden, WE
AF Chaudhry, Sundeep
Arena, Ross
Wasserman, Karlman
Hansen, James E.
Lewis, Gregory D.
Myers, Jonathan
Belardinelli, Romualdo
LaBudde, Brian
Menasco, Nicholas
Boden, William E.
TI The utility of cardiopulmonary exercise testing in the assessment of
suspected microvascular ischemia
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Letter
ID MYOCARDIAL-ISCHEMIA
AB Evidence demonstrating the potential value of cardiopulmonary exercise testing (CPET) to accurately detect myocardial ischemia secondary to macro-vascular disease is beginning to emerge. Despite distinct mechanisms mediating ischemia in micro-vascular and macrovascular coronary artery disease (CAD), the net physiologic effect of exercise-induced left ventricular (LV) dysfunction is common to both. The abnormal physiologic response to CPET may, therefore, be similar in patients with macro-and micro-vascular ischemia. The following case report describes the CPET abnormalities in a patient with suspected microvascular CAD and the subsequent improvement in LV function following three weeks of medical therapy with the anti-ischemic drug ranolazine. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Chaudhry, Sundeep; LaBudde, Brian; Menasco, Nicholas] Met Test Inc, Dept Res & Dev, Atlanta, GA USA.
[Arena, Ross] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA.
[Arena, Ross] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA USA.
[Wasserman, Karlman; Hansen, James E.] Univ Calif Los Angeles, Med Ctr, Div Resp & Crit Care Physiol & Med, Los Angeles Biomed Res Inst Harbor, Torrance, CA 90509 USA.
[Lewis, Gregory D.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Myers, Jonathan] Stanford Univ, Div Cardiol, VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
[Belardinelli, Romualdo] Lancisi Heart Inst, Ancona, Italy.
[Boden, William E.] SUNY Buffalo, Sch Med, Div Cardiovasc Med, Buffalo, NY 14260 USA.
[Boden, William E.] SUNY Buffalo, Sch Publ Hlth Buffalo, Div Cardiovasc Med, Buffalo, NY 14260 USA.
RP Chaudhry, S (reprint author), 1117 Perimeter Ctr W,Suite W-211, Atlanta, GA 30338 USA.
EM schaudhry@mettest.net
RI Arena, Ross/A-3141-2008
OI Arena, Ross/0000-0002-6675-1996
FU NHLBI NIH HHS [K23 HL091106-01A1, K23 HL091106]
NR 7
TC 9
Z9 10
U1 0
U2 1
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 APR
PY 2011
VL 148
IS 1
BP E7
EP E9
DI 10.1016/j.ijcard.2009.01.055
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 736JE
UT WOS:000288489300003
PM 19233492
ER
PT J
AU Astrakas, L
Blekas, KD
Constantinou, C
Andronesi, OC
Mindrinos, MN
Likas, AC
Rahme, LG
Black, PM
Marcus, KJ
Tzika, AA
AF Astrakas, Loukas
Blekas, Konstantinos D.
Constantinou, Caterina
Andronesi, Ovidiu C.
Mindrinos, Michael N.
Likas, Aristidis C.
Rahme, Laurence G.
Black, Peter M.
Marcus, Karen J.
Tzika, A. Aria
TI Combining magnetic resonance spectroscopy and molecular genomics offers
better accuracy in brain tumor typing and prediction of survival than
either methodology alone
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE brain/central nervous system cancers; tumor biomarkers; ex vivo
high-resolution magic angle spinning magnetic resonance spectroscopy;
support vector machines; genomics
ID GENE-EXPRESSION DATA; SUPPORT VECTOR MACHINES; NERVOUS-SYSTEM CANCERS;
RENAL-CELL CARCINOMA; SHORT ECHO TIME; H-1 MR SPECTRA; IN-VIVO;
BINDING-PROTEIN; BIOCHEMICAL-CHARACTERIZATION; MYOCARDIAL-INFARCTION
AB Recent advents in magnetic resonance spectroscopy (MRS) techniques permit subsequent microarray analysis over the entire human transcriptome in the same tissue biopsies. However, extracting information from such immense quantities of data is limited by difficulties in recognizing and evaluating the relevant patterns of apparent gene expression in the context of the existing knowledge of phenotypes by histopathology. Using a quantitative approach derived from a knowledge base of pathology findings, we present a novel methodology used to process genome-wide transcription and MRS data. This methodology was tested to examine metabolite and genome-wide profiles in MRS and RNA in 55 biopsies from human subjects with brain tumors with similar to 100% certainty. With the guidance of histopathology and clinical outcome, 15 genes with the assistance of 15 MRS metabolites were able to be distinguished by tumor categories and the prediction of survival was better than when either method was used alone. This new method, combining MRS, genomics, statistics and biological content, improves the typing and understanding of the complexity of human brain tumors, and assists in the search for novel tumor biomarkers. It is an important step for novel drug development, it generates testable hypotheses regarding neoplasia and promises to guide human brain tumor therapy provided improved in vivo methods for monitoring response to therapy are developed.
C1 [Astrakas, Loukas; Constantinou, Caterina; Andronesi, Ovidiu C.; Tzika, A. Aria] Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, Boston, MA 02114 USA.
[Astrakas, Loukas; Constantinou, Caterina; Andronesi, Ovidiu C.; Rahme, Laurence G.; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA.
[Astrakas, Loukas] Univ Ioannina, Dept Med Phys, GR-45110 Ioannina, Greece.
[Blekas, Konstantinos D.; Likas, Aristidis C.] Univ Ioannina, Dept Comp Sci, GR-45110 Ioannina, Greece.
[Constantinou, Caterina; Rahme, Laurence G.] Massachusetts Gen Hosp, Dept Surg, Mol Surg Lab, Boston, MA 02114 USA.
[Mindrinos, Michael N.] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA.
[Andronesi, Ovidiu C.; Tzika, A. Aria] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA.
[Black, Peter M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Marcus, Karen J.] Harvard Univ, Sch Med, Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
RP Tzika, AA (reprint author), Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, 51 Blossom St, Boston, MA 02114 USA.
EM kmarcus@lroc.harvard.edu; atzika@hms.harvard.edu
RI Astrakas, Loukas/F-5918-2011;
OI Constantinou, Caterina/0000-0003-3589-0739
FU Departments of Surgery and Radiology at Massachusetts General Hospital;
Neurosurgery and Pathology at Brigham; Women's Hospital Boston
FX The study was supported in part by discretional funds to A. Aria Tzika.
The authors thank the Departments of Surgery and Radiology at
Massachusetts General Hospital, as well as Neurosurgery and Pathology at
Brigham and Women's Hospital Boston for supporting this study. We thank
John Passanese, first year medical student at Harvard Medical for
assistance with references cited in Tables. We also thank Drs Ann Power
Smith and Kathryn Edmondson of Write Science Right for editorial
assistance.
NR 147
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PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD APR
PY 2011
VL 38
IS 4
BP 1113
EP 1127
DI 10.3892/ijo.2011.928
PG 15
WC Oncology
SC Oncology
GA 737PQ
UT WOS:000288581100024
PM 21274507
ER
PT J
AU Kostis, WJ
Moreyra, AE
Cheng, JQ
Dobrzynski, JM
Kostis, JB
AF Kostis, William J.
Moreyra, Abel E.
Cheng, Jerry Q.
Dobrzynski, Jeanne M.
Kostis, John B.
TI Continuation of mortality reduction after the end of randomized therapy
in clinical trials of lipid-lowering therapy
SO JOURNAL OF CLINICAL LIPIDOLOGY
LA English
DT Article
DE Clinical trials; Legacy effect; Lipid-lowering therapy; Mortality;
Niacin; Statins
ID CORONARY-HEART-DISEASE; AVERAGE CHOLESTEROL CONCENTRATIONS; SCANDINAVIAN
SIMVASTATIN SURVIVAL; RENAL-TRANSPLANT RECIPIENTS; PRIMARY-PREVENTION
TRIAL; FOLLOW-UP; CARDIAC OUTCOMES; LONG; METAANALYSIS; STATINS
AB BACKGROUND: Long-term follow-up of clinical trials with lipid-lowering medications has suggested a continuation of event reduction after study completion.
OBJECTIVE: To evaluate the persistence of the benefit of lipid-lowering therapy in decreasing mortality after the end of clinical trials, when all patients were advised to take the same open-label lipid-lowering therapy.
METHODS: Through searches of MEDLINE, the Cochrane Library, the Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov until June 2010 we identified randomized clinical trials of lipid-lowering agents with a second report describing results after the end of the trial.
RESULTS: Among the 459 trials reviewed, only 8 including 44,255 patients and 8144 deaths qualified for the meta-anlaysis. All-cause and cardiovascular mortality were lower in the active intervention group during the first phase (0.84, 95% confidence interval [Cl] 0.76-0.93; P = .0006 and 0.72, 95% Cl 0.63-0.82, P < .0001, respectively) when 71 +/- 23% of the patients randomized to receive active therapy actually received it compared with 13 +/- 5% of patients who received active therapy although they were randomized to placebo (P = .0001). The lower mortality among those initially randomized to active therapy persisted during the second phase (odds ratio 0.90, 95% Cl 0.84-0.97, P = .0035, and 0.82 95% CI 0.73-0.93, P =.0014), when patients in both randomized groups received active therapy in the same proportions (5 +/- 2% for both groups). Numerous sensitivity analyses support the conclusions of the paper.
CONCLUSION: The decrease in mortality with lipid-lowering therapy in clinical trials persists after discontinuation of randomized therapy when patients in the treatment and placebo groups receive active therapy. (C) 2011 National Lipid Association. All rights reserved.
C1 [Kostis, William J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Moreyra, Abel E.; Dobrzynski, Jeanne M.; Kostis, John B.] UMDNJ Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ USA.
[Cheng, Jerry Q.] Columbia Univ, Dept Stat, New York, NY USA.
RP Kostis, WJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB-800, Boston, MA 02114 USA.
EM wkostis@partners.org
NR 33
TC 9
Z9 9
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-2874
J9 J CLIN LIPIDOL
JI J. Clin. Lipidol.
PD APR
PY 2011
VL 5
IS 2
BP 97
EP 104
DI 10.1016/j.jacl.2011.01.006
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 740ZA
UT WOS:000288831700006
PM 21392723
ER
PT J
AU Trombetta-ESilva, J
Yu, H
Arias, DN
Rossa, C
Kirkwood, KL
Bradshaw, AD
AF Trombetta-eSilva, J.
Yu, H.
Arias, D. N.
Rossa, C., Jr.
Kirkwood, K. L.
Bradshaw, A. D.
TI LPS Induces Greater Bone and PDL Loss in SPARC-null Mice
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE SPARC; periodontal ligament; collagen; BM-40; osteonectin; extracellular
matrix; matricellular; periodontal diseases; alveolar bone resorption
ID PERIODONTAL-LIGAMENT; EXTRACELLULAR-MATRIX; CYSTEINE SPARC; COLLAGEN;
PROTEIN; REGENERATION; FIBROBLASTS; TISSUES; MODEL; RICH
AB Individuals with periodontal disease have increased risk of tooth loss, particularly in cases with associated loss of alveolar bone and periodontal ligament (PDL). Current treatments do not predictably regenerate damaged PDL. Collagen I is the primary component of bone and PDL extracellular matrix. SPARC/Osteonectin (SP/ON) is implicated in the regulation of collagen content in healthy PDL. In this study, periodontal disease was induced by injections of lipopolysaccharide (LPS) from Aggregatibacter actinomycetemcomitans in wild-type (WT) and SP/ON-null C57/B16 mice. A 20-mu g quantity of LPS was injected between the first and second molars 3 times a week for 4 weeks, whereas PBS control was injected into the contralateral maxilla. LPS injection resulted in a significant decrease in bone volume fraction in both genotypes; however, significantly greater bone loss was detected in SP/ON-null maxilla. SP/ON-null PDL exhibited more extensive degradation of connective tissue in the gingival tissues. Although total cell numbers in the PDL of SP/ON-null were not different from those in WT, the inflammatory infiltrate was reduced in SP/ON-null PDL. Histology of collagen fibers revealed marked reductions in collagen volume fraction and in thick collagen volume fraction in the PDL of SP/ON-null mice. SP/ON protects collagen content in PDL and in alveolar bone in experimental periodontal disease.
C1 [Trombetta-eSilva, J.; Yu, H.; Rossa, C., Jr.; Kirkwood, K. L.; Bradshaw, A. D.] Med Univ S Carolina, Ctr Oral Hlth Res, Charleston, SC 29425 USA.
[Bradshaw, A. D.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Craniofacial Biol, Charleston, SC 29425 USA.
[Trombetta-eSilva, J.; Bradshaw, A. D.] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA.
[Arias, D. N.] Erskine Coll, Due West, SC USA.
[Bradshaw, A. D.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA.
[Rossa, C., Jr.] Univ Estadual Paulista UNESP, Dept Diag & Surg, Fac Odontol Araraquara, Araraquara, SP, Brazil.
RP Bradshaw, AD (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Craniofacial Biol, 114 Doughty St,Rm 223, Charleston, SC 29425 USA.
EM bradshad@musc.edu
RI Rossa Jr, Carlos/D-8328-2012
OI Rossa Jr, Carlos/0000-0003-1705-5481
FU National Institutes of Health [T32DE017551, R25 HL092611, 2P20RR017696,
HL094517, R01DE018290]; Veteran's Administration
FX We thank Kylie Martin, Yuhua Zhang, Lauren Card, and Robert Zinna for
technical support. This work was supported by the National Institutes of
Health [T32DE017551, R25 HL092611, 2P20RR017696, HL094517, R01DE018290]
and by a Veteran's Administration Merit Award.
NR 31
TC 7
Z9 7
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD APR
PY 2011
VL 90
IS 4
BP 477
EP 482
DI 10.1177/0022034510391800
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 740MK
UT WOS:000288798600013
PM 21191126
ER
PT J
AU Tye, CE
Antone, JV
Bartlett, JD
AF Tye, C. E.
Antone, J. V.
Bartlett, J. D.
TI Fluoride Does Not Inhibit Enamel Protease Activity
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE enamel; fluoride; proteases/proteinases
ID HYPOMATURATION AMELOGENESIS-IMPERFECTA; MAXILLARY CENTRAL INCISORS;
IN-VITRO; CRITICAL PERIOD; EXPRESSION; MUTATION; MATRIX; TOOTH;
FLUOROSIS; LOCALIZATION
AB Fluorosed enamel can be porous, mottled, discolored, hypomineralized, and protein-rich if the enamel matrix is not completely removed. Proteolytic processing by matrix metalloproteinase-20 (MMP20) and kallikrein-4 (KLK4) is critical for enamel formation, and homozygous mutation of either protease results in hypomineralized, protein-rich enamel. Herein, we demonstrate that the lysosomal proteinase cathepsin K is expressed in the enamel organ in a developmentally defined manner that suggests a role for cathepsin K in degrading re-absorbed enamel matrix proteins. We therefore asked if fluoride directly inhibits the activity of MMP20, KLK4, dipeptidyl peptidase I (DPPI) (an in vitro activator of KLK4), or cathepsin K. Enzyme kinetics were studied with quenched fluorescent peptides with purified enzyme in the presence of 0-10 mM NaF, and data were fit to Michaelis-Menten curves. Increasing concentrations of known inhibitors showed decreases in enzyme activity. However, concentrations of up to 10 mM NaF had no effect on KLK4, MMP20, DPPI, or cathepsin K activity. Our results show that fluoride does not directly inhibit enamel proteolytic activity.
C1 [Bartlett, J. D.] Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
RP Bartlett, JD (reprint author), Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, 188 Longwood Ave, Boston, MA 02115 USA.
EM jbartlett@forsyth.org
FU NIDCR [DE016276, DE016276-04S1, DE018106]
FX This investigation was supported by NIDCR grants DE016276,
DE016276-04S1, and DE018106 to JDB.
NR 34
TC 2
Z9 3
U1 1
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD APR
PY 2011
VL 90
IS 4
BP 489
EP 494
DI 10.1177/0022034510390043
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 740MK
UT WOS:000288798600015
PM 21118795
ER
PT J
AU Powell, WF
Barry, KJ
Tulum, I
Kobayashi, T
Harris, SE
Bringhurst, FR
Pajevic, PD
AF Powell, William F., Jr.
Barry, Kevin J.
Tulum, Irena
Kobayashi, Tatsuya
Harris, Stephen E.
Bringhurst, F. Richard
Pajevic, Paola Divieti
TI Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone
structure and homeostatic calcemic responses
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID CARBOXYL-TERMINAL REGION; HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE;
TRANSGENIC MICE; BMP ANTAGONIST; IN-VIVO; EXPRESSION; PROTEIN; ALPHA;
CELLS
AB Parathyroid hormone (PTH) is a major physiologic regulator of calcium, phosphorous, and skeletal homeostasis. Cells of the osteoblastic lineage are key targets of PTH action in bone, and recent evidence suggests that osteocytes might be important in the anabolic effects of PTH. To understand the role of PTH signaling through the PTH/PTHrP receptors (PPR) in osteocytes and to determine the role(s) of these cells in mediating the effects of the hormone, we have generated mice in which PPR expression is specifically ablated in osteocytes. Transgenic mice in which the 10 kb-Dmp1 promoter drives a tamoxifen-inducible Cre-recombinase were mated with animals in which exon 1 of PPR is flanked by lox-P sites. In these animals, osteocyte-selective PPR knockout (Ocy-PPR(cKO) mice) could be induced by administration of tamoxifen. Histological analysis revealed a reduction in trabecular bone and mild osteopenia in Ocy-PPR(cKO) mice. Reduction of trabeculae number and thickness was also detected by micro-computed tomography analysis whereas bone volume fraction (BV/TV%) was unchanged. These findings were associated with an increase in Sost and sclerostin expression. When Ocy-PPR(cKO) mice were subjected to a low-calcium diet to induce secondary hyperparathyroidism, their blood calcium levels were significantly lower than littermate controls. Moreover, PTH was unable to suppress Sost and sclerostin expression in the Ocy-PPR(cKO) animals, suggesting an important role of PTH signaling in osteocytes for proper bone remodeling and calcium homeostasis. Journal of Endocrinology (2011) 209, 21-32
C1 [Powell, William F., Jr.; Barry, Kevin J.; Tulum, Irena; Kobayashi, Tatsuya; Bringhurst, F. Richard; Pajevic, Paola Divieti] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Powell, William F., Jr.; Barry, Kevin J.; Tulum, Irena; Kobayashi, Tatsuya; Bringhurst, F. Richard; Pajevic, Paola Divieti] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Harris, Stephen E.] Univ Texas Hlth Sci Ctr San Antonio, Sch Dent, Dept Periodont, San Antonio, TX 78229 USA.
RP Pajevic, PD (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1101,50 Blossom St, Boston, MA 02114 USA.
EM divieti@helix.mgh.harvard.edu
FU National Institutes of Health [DK079161, P01AR46798]; MGH-ECOR Interim
grant
FX This work was supported by the National Institutes of Health grants
DK079161 (P D P), P01AR46798 (S E H), and by an MGH-ECOR Interim grant
(P D P).
NR 40
TC 71
Z9 71
U1 1
U2 6
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0022-0795
J9 J ENDOCRINOL
JI J. Endocrinol.
PD APR
PY 2011
VL 209
IS 1
BP 21
EP 32
DI 10.1530/JOE-10-0308
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 737AG
UT WOS:000288537500003
PM 21220409
ER
PT J
AU Jang, JY
Shao, RX
Lin, WY
Weinberg, E
Chung, WJ
Tsai, WL
Zhao, H
Goto, K
Zhang, LL
Mendez-Navarro, J
Jilg, N
Peng, LF
Brockman, MA
Chung, RT
AF Jang, Jae Young
Shao, Run-Xuan
Lin, Wenyu
Weinberg, Ethan
Chung, Woo Jin
Tsai, Wei Lun
Zhao, Hong
Goto, Kaku
Zhang, Leiliang
Mendez-Navarro, Jorge
Jilg, Nikolaus
Peng, Lee F.
Brockman, Mark A.
Chung, Raymond T.
TI HIV infection increases HCV-induced hepatocyte apoptosis
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE HCV-HIV coinfection; Apoptosis; TRAIL receptor
ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER FIBROSIS
PROGRESSION; TRAIL-INDUCED APOPTOSIS; CELL APOPTOSIS; LIGAND TRAIL;
DISEASE; INJURY; IDENTIFICATION; HEPATOTOXICITY
AB Background 82 Aims: HCV related liver disease is one of the most important complications in persons with HIV, with accelerated fibrosis progression in coinfected persons compared to those with HCV alone. We hypothesized that HCV-HIV coinfection increases HCV related hepatocyte apoptosis and that HCV and HIV influence TRAIL signaling in hepatocytes.
Methods: We analyzed the effect of HIV in JFH1-infected Huh7.5.1 cells. Apoptosis was measured by Caspase-Glo 3/7 assay and Western blotting for cleaved PARP. TRAIL, TRAIL receptor 1 (DR4), and 2 (DR5) mRNA and protein levels were assessed by real-time PCR and Western blot, respectively. We also investigated activation of caspase pathways using caspase inhibitors and assessed expression of Bid and cytochrome C.
Results: We found increased caspase 3/7 activity and cleaved PARP in JFH1 HCV-infected Huh7.5.1 cells in the presence of heat-inactivated HIV, compared to Huh7.5.1 cells infected with JFH1 or exposed to heat-inactivated HIV alone. Both DR4 and DR5 mRNA and protein expression were increased in JFH1-infected cells in the presence of inactivated HIV compared to Huh7.5.1 cells infected with JFH1 or exposed to heat-inactivated HIV alone. Pancaspase, caspase-8, and caspase-9 inhibition blocked apoptosis induced by HCV, inactivated HIV, and HCV plus inactivated HIV. A caspase-9 inhibitor blocked apoptosis induced by HCV, HIV, and HCV-HIV comparably to pancaspase and caspase-8 inhibitors. HCV induced the activation of Bid cleavage and cytochrome C release. The addition of HIV substantially augmented this induction.
Conclusions: Our findings indicate that hepatocyte apoptosis is increased in the presence of HCV and HIV compared to HCV or HIV alone, and that this increase is mediated by DR4 and DR5 up-regulation. These results provide an additional mechanism for the accelerated liver disease progression observed in HCV-HIV co-infection. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 [Jang, Jae Young; Shao, Run-Xuan; Lin, Wenyu; Weinberg, Ethan; Chung, Woo Jin; Tsai, Wei Lun; Zhao, Hong; Goto, Kaku; Zhang, Leiliang; Mendez-Navarro, Jorge; Jilg, Nikolaus; Peng, Lee F.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
[Jang, Jae Young] Soonchunhyang Univ, Inst Digest Res, Ctr Digest Dis, Dept Internal Med,Coll Med, Seoul, South Korea.
[Brockman, Mark A.] Harvard Univ, Div Aids, Cambridge, MA 02138 USA.
[Brockman, Mark A.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Warren 1007, Boston, MA 02114 USA.
EM rtchung@partners.org
OI Brockman, Mark/0000-0001-6432-1426
FU NIH [AI069939, AI082630, R01 AI069939, U19 AI082630]
FX This work was supported in part by NIH grants AI069939 and AI082630
(RTC).; We gratefully acknowledge: Dr. Ralf Bartenschlager, University,
Heidelberg, Germany; and Dr. Takaji Wakita, Second Department of
Virology, National Institute of Infectious Diseases, Tokyo, Japan
(infectious HCV virus JFH1 DNA construct); and Dr. Francis Chisari,
Scripps Institute, CA (Huh7.5.1 cells). This work was support by NIH
Grants R01 AI069939 and U19 AI082630 (to R.T.C.).
NR 44
TC 23
Z9 24
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2011
VL 54
IS 4
BP 612
EP 620
DI 10.1016/j.jhep.2010.07.042
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 740YX
UT WOS:000288831400005
PM 21146890
ER
PT J
AU Duraiswamy, J
Ibegbu, CC
Masopust, D
Miller, JD
Araki, K
Doho, GH
Tata, P
Gupta, S
Zilliox, MJ
Nakaya, HI
Pulendran, B
Haining, WN
Freeman, GJ
Ahmed, R
AF Duraiswamy, Jaikumar
Ibegbu, Chris C.
Masopust, David
Miller, Joseph D.
Araki, Koichi
Doho, Gregory H.
Tata, Pramila
Gupta, Satish
Zilliox, Michael J.
Nakaya, Helder I.
Pulendran, Bali
Haining, W. Nicholas
Freeman, Gordon J.
Ahmed, Rafi
TI Phenotype, Function, and Gene Expression Profiles of Programmed
Death-1(hi) CD8 T Cells in Healthy Human Adults
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; INTERLEUKIN-7 RECEPTOR-ALPHA; C
VIRUS-INFECTION; HUMAN EFFECTOR; UP-REGULATION; PROLIFERATIVE CAPACITY;
INHIBITORY RECEPTORS; DISEASE PROGRESSION; HIV-INFECTION; PD-1 PATHWAY
AB T cell dysfunction is an important feature of many chronic viral infections. In particular, it was shown that programmed death-1 (PD-1) regulates T cell dysfunction during chronic lymphocytic choriomeningitis virus infection in mice, and PD-1(hi) cells exhibit an intense exhausted gene signature. These findings were extended to human chronic infections such as HIV, hepatitis C virus, and hepatitis B virus. However, it is not known if PD-1(hi) cells of healthy humans have the traits of exhausted cells. In this study, we provide a comprehensive description of phenotype, function, and gene expression profiles of PD-1(hi) versus PD-1(lo) CD8 T cells in the peripheral blood of healthy human adults as follows: 1) the percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans, and PD-1 was expressed by the memory CD8 T cells; 2) PD-1(hi) CD8 T cells in healthy humans did not significantly correlate with the PD-1(hi) exhausted gene signature of HIV-specific human CD8 T cells or chronic lymphocytic choriomeningitis virus-specific CD8 T cells from mice; 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults; 4) PD-1 was expressed by the effector memory compared with terminally differentiated effector CD8 T cells; and 5) finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed. In conclusion, our study shows that most PD-1(hi) CD8 T cells in healthy adult humans are effector memory cells rather than exhausted cells. The Journal of Immunology, 2011, 186: 4200-4212.
C1 [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Rollins Res Ctr, Atlanta, GA 30322 USA.
[Duraiswamy, Jaikumar; Ibegbu, Chris C.; Masopust, David; Miller, Joseph D.; Araki, Koichi; Zilliox, Michael J.; Ahmed, Rafi] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Doho, Gregory H.] Emory Univ, Emory Biomarker Serv Ctr, Atlanta, GA 30322 USA.
[Tata, Pramila; Gupta, Satish] Strand Life Sci, Bangalore 560024, Karnataka, India.
[Nakaya, Helder I.; Pulendran, Bali] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA.
[Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Rollins Res Ctr, 1510 Clifton Rd,G211, Atlanta, GA 30322 USA.
EM rahmed@emory.edu
RI Nakaya, Helder/A-1397-2010
OI Nakaya, Helder/0000-0001-5297-9108
FU National Institutes of Health [P01 AI080192-01]; Grand Challenges in
Global Health Initiative [05GCGH0]
FX This work was supported by National Institutes of Health Grant P01
AI080192-01 (to R.A.) and Grand Challenges in Global Health Initiative
Grant 05GCGH0 (to R.A.).
NR 64
TC 68
Z9 69
U1 1
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD APR 1
PY 2011
VL 186
IS 7
BP 4200
EP 4212
DI 10.4049/jimmunol.1001783
PG 13
WC Immunology
SC Immunology
GA 739WH
UT WOS:000288751200045
PM 21383243
ER
PT J
AU Tai, A
Salloum, S
Chung, RT
AF Tai, A.
Salloum, S.
Chung, R. T.
TI AN ESSENTIAL ROLE FOR A PHOSPHATIDYLINOSITOL 4-KINASE IN HEPATITIS C
VIRUS REPLICATION COMPLEX ASSEMBLY
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Combined Annual Meeting on Midwestern Regional Program
CY APR 14-15, 2011
CL Chicago, IL
C1 [Tai, A.; Salloum, S.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Chung, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD APR
PY 2011
VL 59
IS 4
BP 723
EP 723
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 738QE
UT WOS:000288656200111
ER
PT J
AU Wilson, RS
Krueger, KR
Boyle, PA
Bennett, DA
AF Wilson, Robert S.
Krueger, Kristin R.
Boyle, Patricia A.
Bennett, David A.
TI Loss of basic lexical knowledge in old age
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID ADULT READING TEST; ALZHEIMERS-DISEASE; PREMORBID INTELLIGENCE;
COGNITIVE FUNCTION; DEMENTIA; DECLINE; NEUROPATHOLOGY; IMPAIRMENT;
VALIDATION; ABILITY
AB Background Basic lexical skills are hypothesised to be relatively preserved in mild dementia, but clinical studies have reported inconsistent results.
Methods More than 400 older Catholic nuns, priests and brothers recruited from groups across the USA completed annual evaluations for up to 15 years, died and underwent brain autopsy. Each clinical evaluation included administration of a 20-item word reading test and a 15-item vocabulary test, which were combined to form a composite measure of word knowledge. In a uniform neuropathological examination, Alzheimer's disease pathology was quantified with a composite index of plaques and tangles, and the presence of gross and microscopic cerebral infarctions and Lewy bodies was recorded.
Results The post-mortem level of Alzheimer's disease neuropathology was linearly related to rate of decline in word knowledge. Decline was nearly fourfold faster at a relatively high level of pathology (75th percentile) compared with a relatively low level (25th percentile). Neocortical (but not nigral or limbic) Lewy bodies and gross (but not microscopic) cerebral infarction were also associated with a more rapid decline in word knowledge. Effects for word reading and vocabulary were similar, except that gross cerebral infarction was associated with accelerated decline in vocabulary, but not in word reading.
Conclusion Common neuropathological changes associated with late-life dementia impair word knowledge in old age, calling into question the use of word knowledge tests to estimate premorbid cognitive ability.
C1 [Wilson, Robert S.; Boyle, Patricia A.; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Wilson, Robert S.; Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Wilson, Robert S.; Boyle, Patricia A.] Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA.
[Krueger, Kristin R.] S Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX USA.
RP Wilson, RS (reprint author), Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, 600 S Paulina Ave,Suite 1038, Chicago, IL 60612 USA.
EM rwilson@rush.edu
FU National Institute on Aging [P30AG10161, R01AG15819]
FX Support for this project was provided by federal grants from the
National Institute on Aging: P30AG10161 and R01AG15819.
NR 29
TC 7
Z9 7
U1 0
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD APR
PY 2011
VL 82
IS 4
BP 369
EP 372
DI 10.1136/jnnp.2010.212589
PG 4
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 734ZY
UT WOS:000288384100006
PM 20802026
ER
PT J
AU Duhaine, AC
Schwartz, D
AF Duhaine, Ann-Christine
Schwartz, Daniel
TI Monitoring in young patients
SO JOURNAL OF NEUROSURGERY-PEDIATRICS
LA English
DT Editorial Material
C1 [Duhaine, Ann-Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Schwartz, Daniel] Surg Monitoring Associates, Springfield, PA USA.
RP Duhaine, AC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1933-0707
J9 J NEUROSURG-PEDIATR
JI J. Neurosurg.-Pediatr.
PD APR
PY 2011
VL 7
IS 4
BP 329
EP 329
DI 10.3171/2010.11.PEDS10459
PG 1
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA 739NX
UT WOS:000288726000001
PM 21456901
ER
PT J
AU Reidling, JC
Rubin, SA
AF Reidling, Jack C.
Rubin, Stanley A.
TI Promoter analysis of the human ascorbic acid transporters SVCT1 and 2:
mechanisms of adaptive regulation in liver epithelial cells
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Ascorbic acid; Nutrient transport; Promoter regulation; SVCT
ID VITAMIN-C UPTAKE; THIAMIN UPTAKE; WILD-TYPE; ANTIOXIDANT; EXPRESSION;
SLC23A2; HSVCT1
AB Ascorbic acid, the active form of vitamin C, is a vital antioxidant in the human liver, yet the molecular mechanisms involved in the regulation of ascorbic acid transporters [human sodium-dependent vitamin C transporters (hSVCT) 1 and 2] in liver cells are poorly understood. Therefore, we characterized the minimal promoter regions of hSVCT1 and 2 in cultured human liver epithelial cells (HepG2) and examined the effects of ascorbic acid deprivation and supplementation on activity and regulation of the transport systems. Identified minimal promoters required for basal activity were found to include multiple cis regulatory elements, whereas mutational analysis demonstrated that HNF-1 sites in the hSVCT1 promoter and KLF/Sp1 sites in the hSVCT2 promoter were essential for activities. When cultured in ascorbic acid deficient or supplemented media, HepG2 cells demonstrated significant (P<.01) and specific reciprocal changes in [(14)C]-Ascorbic acid uptake, and in hSVCT1 mRNA and protein levels as well as hSVCT1 promoter activity. However, no significant changes in hSVCT2 expression or promoter activity were observed during ascorbic acid deficient or supplemented conditions. We mapped the ascorbic acid responsive region in the hSVCT1 promoter and determined that HNF-1 sites are important for the adaptive regulation response. The results of these studies further characterize the hSVCT1 and 2 promoters establish that ascorbic acid uptake by human liver epithelial cells is adaptively regulated and show that transcriptional mechanisms via HNF-1 in the hSVCT1 promoter may, in part, be involved in this regulation. Published by Elsevier Inc.
C1 [Reidling, Jack C.] VA Med Ctr, Long Beach, CA 90822 USA.
[Reidling, Jack C.] Univ Calif Irvine, Coll Med, Irvine, CA 92697 USA.
[Rubin, Stanley A.] UCLA Sch Med, VA Greater Los Angeles Med Ctr, Dept Med, Los Angeles, CA 90073 USA.
RP Reidling, JC (reprint author), VA Med Ctr, Long Beach, CA 90822 USA.
EM jreidlin@uci.edu
FU National Institutes of Health [DK73032]; Department of Veterans Affairs
FX The work was supported by grants from the National Institutes of Health
DK73032 and the Department of Veterans Affairs.
NR 26
TC 8
Z9 8
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD APR
PY 2011
VL 22
IS 4
BP 344
EP 350
DI 10.1016/j.jnutbio.2010.03.001
PG 7
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 740DT
UT WOS:000288772500006
PM 20471816
ER
PT J
AU Gravaghi, C
La Perle, KMD
Ogrodwski, P
Kang, JX
Quimby, F
Lipkin, M
Lamprecht, SA
AF Gravaghi, Claudia
La Perle, Krista M. D.
Ogrodwski, Paul
Kang, Jing X.
Quimby, Fred
Lipkin, Martin
Lamprecht, Sergio A.
TI Cox-2 expression, PGE(2) and cytokines production are inhibited by
endogenously synthesized n-3 PUFAs in inflamed colon of fat-1 mice
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Cox-2; Fat-1 mice; Colitis; Inflammation
ID POLYUNSATURATED FATTY-ACIDS; TRANSGENIC MICE; COLITIS; INFLAMMATION;
CANCER; CELLS; PROLIFERATION; PREVENTION; RECEPTORS; APOPTOSIS
AB There is great interest in the role of polyunsaturated fatty acids (PUFAs) in promoting (n-6 class) or inhibiting (n-3 class) inflammation. Mammalian cells are devoid of desaturase that converts n-6 to n-3 PUFAs. Consequently, essential n-3 fatty acids must be supplied with the diet. We have studied the effect of endogenously produced n-3 PUFAs on colitis development in fat-1 transgenic mice carrying the Caenorhabditis elegans fat-1 gene encoding n-3 desaturase. Colonic cell lipid profile was measured by capillary gas chromatography in fat-1 and wild-type (WT) littermates fed standard diet supplemented with 10% (w/w) safflower oil rich (76%) in n-6 polyunsaturated linoleic acid (LA). Experimental colitis was induced by administrating 3% dextran sodium sulphate (DSS). Colitis was scored by histopatological analysis. Cyclooxygenase-2 (Cox-2) expression was evaluated by real time polymerase chain reaction. Prostaglandin E-2 (PGE(2)) levels and cytokine production were determined by enzyme and microsphere-based immunoassays, respectively. The n-6/n-3 PUFA ratios in colonic cells of fat-1 mice were markedly lower (9.83 +/- 2.62) compared to WT (54.5 +/- 9.24, P<.001). Results also showed an attenuation of colonic acute and chronic inflammation in fat-1 mice with significant decreases in PGE2 production (P<.01) and Cox-2 expression (P<.01). High levels of colitis-induced proinflammatory cytokines, interleukin (IL)-18, IL-1 alpha, IL-1 beta, IL-6 monocytes chemotactic proteins 1, 2 and 3 (MCP 1,2,3), matrix metalloproteinase 9 and tumor necrosis factor alpha (TNF-alpha) were down-regulated in DSS acutely and chronically treated fat-1 mice. The expression of fat-1 gene in the colon was associated with endogenous n-3 PUFAs production, decreased Cox-2 expression, increased PGE(2) and cytokine production. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Gravaghi, Claudia; Ogrodwski, Paul; Lipkin, Martin; Lamprecht, Sergio A.] Cornell Univ, Weill Med Coll, Dept Med, Div Gastroenterol & Hepatol, New York, NY 10065 USA.
[La Perle, Krista M. D.] Mem Sloan Kettering Canc Ctr, Lab Comparat Pathol, New York, NY 10021 USA.
[Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA.
[Quimby, Fred] Rockefeller Univ, Lab Anim Res Ctr, New York, NY 10021 USA.
RP Gravaghi, C (reprint author), Cornell Univ, Weill Med Coll, Dept Med, Div Gastroenterol & Hepatol, New York, NY 10065 USA.
EM cgravaghi@strang.org
RI La Perle, Krista/B-3099-2015
FU AICR [04B036]; NIH
FX We thank Dr. Andrew J. Dannenberg and Dr. Kotha Subbaramaiah for careful
reading and discussing the manuscript. The work was supported by AICR
Grant #04B036 to S.A.L and NIH R25 Postdoctoral Fellowship to C.G.
NR 35
TC 39
Z9 40
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD APR
PY 2011
VL 22
IS 4
BP 360
EP 365
DI 10.1016/j.jnutbio.2010.03.003
PG 6
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 740DT
UT WOS:000288772500008
PM 20655721
ER
PT J
AU Oshrine, B
Lehmann, LE
Duncan, CN
AF Oshrine, Benjamin
Lehmann, Leslie E.
Duncan, Christine N.
TI Safety and Utility of Liver Biopsy After Pediatric Hematopoietic Stem
Cell Transplantation
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE hematopoietic stem cell transplantation; liver biopsy; liver disease;
hepatic disease; liver dysfunction
ID DYSFUNCTION; CHILDREN
AB Liver dysfunction is common after pediatric hematopoietic stem cell transplantation (HSCT) and liver biopsy may be necessary to diagnosis the cause of liver dysfunction and institute therapy. We report our liver biopsy experience in 356 consecutive patients. During the study period, 16 (4.5%) patients underwent 18 biopsies, all after allogeneic HSCT. The median time from HSCT to biopsy was 205.5 days. All patients had transaminase elevation and 67% had hyperbilirubinemia. The most commonly used method of biopsy was the imaging-guided percutaneous approach, performed in 12 of 18 cases. Five biopsies were done transjugularly and 1 was performed during laparotomy. In all the cases a histopathologic diagnosis was made. The most common diagnosis was graft-versus-host disease (GVHD) followed by iron overload. In 12 cases, management was modified based on biopsy results. Complications occurred after 5 biopsies, 4 of which were performed transjugularly. The most common complication was hemorrhage. Two patients required transfer to the intensive care unit for related complications. No complications were observed after percutaneous biopsies. In 2 cases a second procedure was required to manage the complication. We conclude that while liver biopsy yields a high-rate of diagnoses, it is accompanied by high rates of complications, particularly when the transjugular approach is used.
C1 [Oshrine, Benjamin] Childrens Hosp, Boston, MA 02115 USA.
[Lehmann, Leslie E.; Duncan, Christine N.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Oshrine, B (reprint author), 300 Longwood Ave, Boston, MA 02115 USA.
EM benjamin.oshrine@childrens.harvard.edu
NR 9
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD APR
PY 2011
VL 33
IS 3
BP E92
EP E97
DI 10.1097/MPH.0b013e3182025236
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 739DW
UT WOS:000288694700002
PM 21317809
ER
PT J
AU Mankin, H
Trahan, C
Hornicek, F
AF Mankin, Henry
Trahan, Carol
Hornicek, Francis
TI Pigmented Villonodular Synovitis of Joints
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
DE PVNS; joints; benign
ID GIANT-CELL TUMOR; LOCALIZED NODULAR SYNOVITIS; TENDON SHEATH;
ARTHROSCOPIC TREATMENT; KNEE; HIP; TENOSYNOVITIS; DIAGNOSIS; XANTHOMA;
ANKLE
AB Objectives: The objective of this study is to present two series of cases of pigmented villonodular disease of joints (PVNS) treated at different periods. The 215 cases from our hospital are current (1972-2009) and those 62 from the Jaffe collection from 1920 to 1968.
Methods: By use of our computerized tumor data system we were able to define age, gender, site, treatment, complications, and outcome. Examination of the material from the Jaffe collection included all of the above primary data but none on treatment and outcome.
Results: The data for the two systems studied were remarkably similar. The average ages were in mid years and the disorder was more frequent in females. The largest numbers of cases for both series were in the knee and foot and less commonly in hip, shoulder, and hand. The treatments were mostly surgical excision with the exception of the hip which required total hip replacement. The results show only a small number of recurrences, no metastatic disease and no deaths.
Conclusion: Pigmented villonodular disease of joints is a rare entity, mostly occurring in the knee and foot. The principal treatment is surgical excision which is most often successful in these sites but leads to problems at other locations, especially the hip. J. Surg. Oncol. 2011; 103: 386-389. (C) 2010 Wiley-Liss, Inc.
C1 [Mankin, Henry; Hornicek, Francis] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA.
[Mankin, Henry; Trahan, Carol; Hornicek, Francis] Massachusetts Gen Hosp, Dept Res Orthopaed, Boston, MA 02114 USA.
RP Mankin, H (reprint author), 1122A Jackson Bldg, Boston, MA 02114 USA.
EM hmankin@partners.org
NR 43
TC 25
Z9 28
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-4790
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD APR
PY 2011
VL 103
IS 5
BP 386
EP 389
DI 10.1002/jso.21835
PG 4
WC Oncology; Surgery
SC Oncology; Surgery
GA 737FP
UT WOS:000288554800004
PM 21400520
ER
PT J
AU Johri, AM
Witzke, C
Solis, J
Palacios, IF
Inglessis, I
Picard, MH
Passeri, JJ
AF Johri, Amer M.
Witzke, Christian
Solis, Jorge
Palacios, Igor F.
Inglessis, Ignacio
Picard, Michael H.
Passeri, Jonathan J.
TI Real-Time Three-Dimensional Transesophageal Echocardiography in Patients
with Secundum Atrial Septal Defects: Outcomes following Transcatheter
Closure
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Three-dimensional transesophageal echocardiography; Atrial septal defect
ID FEASIBILITY; GUIDANCE; DEVICE; FOSSA
AB Background: Successful transcatheter closure of atrial septal defects (ASDs) requires the accurate assessment of defect size and morphology. Assessment of ASD anatomy may be difficult by two-dimensional (2D) echocardiography. The aim of this study was to test the hypothesis that real-time three-dimensional (3D) transesophageal echocardiography (TEE) may provide more accurate morphologic assessment of ASDs than multiplane 2D TEE.
Methods: Twenty-four patients with ASDs were imaged using 2D and real-time 3D TEE. ASD shape and size were assessed using 3D TEE retrospectively. Maximal ASD dimensions obtained by 3D TEE were compared with unstretched and balloon-stretched dimensions on 2D TEE. Planimetered defect area by 3D TEE was compared with area calculated using the ellipse formula from 2D imaging. Twenty of the 24 patients underwent transcatheter ASD closure. Closure device size was based on findings on 2D TEE. Follow-up was conducted by 2D transthoracic echocardiography.
Results: Of the 24 ASDs, 6 (25%) were circular, 10 (42%) were oval, and 8 (33%) were complex in shape. The mean maximal dimension was larger by 3D TEE compared with 2D TEE (1.8 +/- 0.8 vs 1.5 +/- 0.6 cm; P < .05). There was no difference in the mean area measured by either modality, but for complex-shaped defects, area measured by 3D TEE was larger than that by 2D TEE (2.8 +/- 1.3 vs 1.7 +/- 1.4 cm(2); P < .05). Follow-up transthoracic echocardiography was available for 19 of the 20 patients undergoing transcatheter closure. Nine patients had residual right-to-left shunting 1 to 6 months after ASD closure, and the majority of these were complex in shape. In patients with residual shunting, ASD area by 3D TEE was 27% larger than by 2D TEE, whereas in patients without residual shunting, there was significantly less discrepancy between 3D and 2D areas (19%; P = .0027).
Conclusions: Three-dimensional TEE can identify ASD shape. Maximal dimensions on 3D TEE were well correlated with balloon-stretched 2D dimensions. Two-dimensional TEE can underestimate the area of complex-shaped ASDs, which may result in residual right-to-left shunting. (J Am Soc Echocardiogr 2011;24:431-7.)
C1 [Johri, Amer M.; Witzke, Christian; Solis, Jorge; Palacios, Igor F.; Inglessis, Ignacio; Picard, Michael H.; Passeri, Jonathan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
RP Passeri, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA.
EM jpasseri@partners.org
OI Picard, Michael/0000-0002-9264-3243
NR 8
TC 18
Z9 24
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD APR
PY 2011
VL 24
IS 4
BP 431
EP 437
DI 10.1016/j.echo.2010.12.011
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 740HG
UT WOS:000288781700012
PM 21262563
ER
PT J
AU Tournoux, F
Petersen, B
Thibault, H
Zou, L
Raher, MJ
Kurtz, B
Halpern, EF
Chaput, M
Chao, W
Picard, MH
Scherrer-Crosbie, M
AF Tournoux, Francois
Petersen, Bodil
Thibault, Helene
Zou, Lin
Raher, Michael J.
Kurtz, Baptiste
Halpern, Elkan F.
Chaput, Miguel
Chao, Wei
Picard, Michael H.
Scherrer-Crosbie, Marielle
TI Validation of Noninvasive Measurements of Cardiac Output in Mice Using
Echocardiography
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Cardiac output; Doppler echocardiography; Flow probe; Mice; Sepsis
ID IN-VIVO; CONDUCTANCE CATHETER; VOLUME; PULMONARY; PERFUSION; MOUSE; RATS
AB Background: Although multiple echocardiographic methods exist to calculate cardiac output (CO), they have not been validated in mice using a reference method.
Methods: Echocardiographic and flow probe measurements of CO were obtained in mice before and after albumin infusion and inferior vena cava occlusions. Echocardiography was also performed before and after endotoxin injection. Cardiac output was calculated using left ventricular volumes obtained from an M-mode or a two-dimensional view, left ventricular stroke volume calculated using the pulmonary flow, or estimated by the measurement of pulmonary velocity time integral (VTI).
Results: Close correlations were demonstrated between flow probe-measured CO and all echocardiographic measurements of CO. All echocardiographic-derived CO overestimated the flow probe-measured CO. Two-dimensional image-derived CO was associated with the smallest overestimation of CO. Interobserver variability was lowest for pulmonary VTI-derived CO.
Conclusion: In mice, CO calculated from two-dimensional parasternal long-axis images is most accurate when compared with flow probe measurements; however, pulmonary VTI-derived CO is subject to less variability. (J Am Soc Echocardiogr 2011;24:465-70.)
C1 [Tournoux, Francois; Thibault, Helene; Kurtz, Baptiste; Chaput, Miguel; Picard, Michael H.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
[Petersen, Bodil; Zou, Lin; Raher, Michael J.; Chao, Wei] Massachusetts Gen Hosp, Anesthesia Res Lab, Boston, MA 02114 USA.
[Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Tournoux, Francois] Univ Paris 07, INSERM, Hop Lariboisiere, APHP,Dept Cardiol,U942, Paris, France.
RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 254,55 Fruit St, Boston, MA 02114 USA.
EM marielle@crosbie.com
OI Picard, Michael/0000-0002-9264-3243
FU National Institutes of Health/National Heart, Lung, and Blood Institute
[1S10RR0225860-1A1]; Claflin; Federation Francaise de Cardiologie
FX Funding: This study was supported by a Shared Equipment Grant (National
Institutes of Health/National Heart, Lung, and Blood Institute
1S10RR0225860-1A1, to M. S. C.), the Claflin Award (to M. S. C.), and
fellowship grants from the Federation Francaise de Cardiologie (to F.T.,
H.T., and B.K.).
NR 22
TC 24
Z9 24
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD APR
PY 2011
VL 24
IS 4
BP 465
EP 470
DI 10.1016/j.echo.2010.12.019
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 740HG
UT WOS:000288781700016
PM 21315557
ER
PT J
AU Teles, FRF
Teles, RP
Siegelin, Y
Paster, B
Haffajee, AD
Socransky, SS
AF Teles, F. R. F.
Teles, R. P.
Siegelin, Y.
Paster, B.
Haffajee, A. D.
Socransky, S. S.
TI RNA-oligonucleotide quantification technique (ROQT) for the enumeration
of uncultivated bacterial species in subgingival biofilms
SO MOLECULAR ORAL MICROBIOLOGY
LA English
DT Article
DE bacteria; biofilms; oligonucleotide; oral; periodontal; quantification;
uncultivated
ID POLYMERASE-CHAIN-REACTION; DNA-DNA HYBRIDIZATION;
PORPHYROMONAS-GINGIVALIS; TANNERELLA-FORSYTHENSIS; PERIODONTITIS;
MICROBIOTA; HEALTHY; PLAQUE; DIVERSITY; MICROORGANISMS
AB Approximately 35% of the species present in subgingival biofilms are as yet uncultivated, so their role in periodontal pathogenesis is unknown. The aim of the present study was to develop a high throughput method to quantify a wide range of cultivated and uncultivated taxa in subgingival biofilm samples associated with periodontal disease or health. Oligonucleotides targeting the 16S ribosomal DNA gene were designed, synthesized and labeled with digoxigenin. These probes were hybridized with the total nucleic acids of pure cultures or subgingival biofilm samples. Target species included cultivated taxa associated with periodontal health and disease, as well as uncultivated species, such as TM7 sp. OT 346, Mitsuokella sp. OT 131 and Desulfobulbus sp. OT 041. Sensitivity and specificity of the probes were determined. A Universal probe was used to assess total bacterial load. Sequences complementary to the probes were used as standards for quantification. Chemiluminescent signals were visualized after film exposure or using a CCD camera. In a pilot clinical study, 266 subgingival plaque samples from eight periodontally healthy people and 11 patients with periodontitis were examined. Probes were specific and sensitivity reached 104 cells. Fusobacterium nucleatum ss. polymorphum and Actinomyces gerencseriae were the most abundant cultivated taxa in clinical samples. Among uncultivated/unrecognized species, Mitsuokella sp. OT 131 and Prevotella sp. OT 306 were the most numerous. Porphyromonas gingivalis and Desulfobulbus sp. OT 041 were only detected in patients with periodontitis. Direct hybridization of total nucleic acids using oligonucleotide probes permitted the quantification of multiple cultivated and uncultivated taxa in mixed species biofilm samples.
C1 [Teles, F. R. F.; Teles, R. P.; Siegelin, Y.; Haffajee, A. D.; Socransky, S. S.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA.
[Teles, F. R. F.; Teles, R. P.; Paster, B.; Haffajee, A. D.; Socransky, S. S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Paster, B.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA.
RP Teles, FRF (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St, Cambridge, MA 02142 USA.
EM fteles@forsyth.org
FU National Institutes of Dental and Craniofacial Research [T32-DE-07327,
DE-12108, DE-14242]; Forsyth Institute/Harvard Medical School
FX This work was supported in part by grants T32-DE-07327, DE-12108 and
DE-14242 from the National Institutes of Dental and Craniofacial
Research. This work was also supported in part by the Eleanor and Miles
Shore 50th Anniversary Fellowship Program for Scholars in Medicine (The
Forsyth Institute/Harvard Medical School).
NR 37
TC 14
Z9 17
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2041-1006
J9 MOL ORAL MICROBIOL
JI Mol. Oral Microbiol.
PD APR
PY 2011
VL 26
IS 2
BP 127
EP 139
DI 10.1111/j.2041-1014.2010.00603.x
PG 13
WC Dentistry, Oral Surgery & Medicine; Microbiology
SC Dentistry, Oral Surgery & Medicine; Microbiology
GA 741DP
UT WOS:000288843600004
PM 21375703
ER
PT J
AU Poelmans, G
Buitelaar, JK
Pauls, DL
Franke, B
AF Poelmans, G.
Buitelaar, J. K.
Pauls, D. L.
Franke, B.
TI A theoretical molecular network for dyslexia: integrating available
genetic findings
SO MOLECULAR PSYCHIATRY
LA English
DT Review
DE dyslexia; genetics; neurodevelopment; molecular network; bioinformatics
ID QUANTITATIVE-TRAIT LOCUS; END-PRODUCTS RAGE; PROTEIN-ASSOCIATED PROTEIN;
FAMILY-BASED ASSOCIATION; LONG-TERM POTENTIATION; FRAGILE-X-SYNDROME;
DEVELOPMENTAL DYSLEXIA; READING-DISABILITY; SUSCEPTIBILITY LOCUS;
NEURONAL MIGRATION
AB Developmental dyslexia is a common specific childhood learning disorder with a strong heritable component. Previous studies using different genetic approaches have identified several genetic loci and candidate genes for dyslexia. In this article, we have integrated the current knowledge on 14 dyslexia candidate genes suggested by cytogenetic findings, linkage and association studies. We found that 10 of the 14 dyslexia candidate genes (ROBO1, KIAA0319, KIAA0319L, S100B, DOCK4, FMR1, DIP2A, GTF2I, DYX1C1 and DCDC2) fit into a theoretical molecular network involved in neuronal migration and neurite outgrowth. Based on this, we also propose three novel dyslexia candidate genes (SLIT2, HMGB1 and VAPA) from known linkage regions, and we discuss the possible involvement of genes emerging from the two reported genome-wide association studies for reading impairment-related phenotypes in the identified network. Molecular Psychiatry (2011) 16, 365-382; doi:10.1038/mp.2010.105; published online 19 October 2010
C1 [Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
[Poelmans, G.; Buitelaar, J. K.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6500 HB Nijmegen, Netherlands.
[Pauls, D. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA USA.
[Franke, B.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands.
RP Franke, B (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, 855,POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM b.franke@antrg.umcn.nl
RI Franke, Barbara/D-4836-2009; Buitelaar, Jan/E-4584-2012
OI Franke, Barbara/0000-0003-4375-6572; Buitelaar, Jan/0000-0001-8288-7757
FU 'Hersenstichting Nederland' (Brain Foundation of The Netherlands)
FX We gratefully acknowledge the families who have made all these studies
possible. We are also indebted to the many investigators whose work
drives the dyslexia genetics field forward. This work was supported by a
research grant from the 'Hersenstichting Nederland' (Brain Foundation of
The Netherlands).
NR 154
TC 49
Z9 50
U1 5
U2 24
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 2011
VL 16
IS 4
BP 365
EP 382
DI 10.1038/mp.2010.105
PG 18
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 739TK
UT WOS:000288740700006
PM 20956978
ER
PT J
AU Kim, DH
Lu, NS
Ghaffari, R
Kim, YS
Lee, SP
Xu, LZ
Wu, JA
Kim, RH
Song, JZ
Liu, ZJ
Viventi, J
de Graff, B
Elolampi, B
Mansour, M
Slepian, MJ
Hwang, S
Moss, JD
Won, SM
Huang, YG
Litt, B
Rogers, JA
AF Kim, Dae-Hyeong
Lu, Nanshu
Ghaffari, Roozbeh
Kim, Yun-Soung
Lee, Stephen P.
Xu, Lizhi
Wu, Jian
Kim, Rak-Hwan
Song, Jizhou
Liu, Zhuangjian
Viventi, Jonathan
de Graff, Bassel
Elolampi, Brian
Mansour, Moussa
Slepian, Marvin J.
Hwang, Sukwon
Moss, Joshua D.
Won, Sang-Min
Huang, Younggang
Litt, Brian
Rogers, John A.
TI Materials for multifunctional balloon catheters with capabilities in
cardiac electrophysiological mapping and ablation therapy
SO NATURE MATERIALS
LA English
DT Article
ID PULMONARY VEIN ISOLATION; PAROXYSMAL ATRIAL-FIBRILLATION; OF-THE-ART;
RADIOFREQUENCY ABLATION; INTEGRATED-CIRCUITS; ARTIFICIAL SKIN; TACTILE
SENSOR; BIOCOMPATIBILITY; HYPERTENSION; SEPTOSTOMY
AB Developing advanced surgical tools for minimally invasive procedures represents an activity of central importance to improving human health. A key challenge is in establishing biocompatible interfaces between the classes of semiconductor device and sensor technologies that might be most useful in this context and the soft, curvilinear surfaces of the body. This paper describes a solution based on materials that integrate directly with the thin elastic membranes of otherwise conventional balloon catheters, to provide diverse, multimodal functionality suitable for clinical use. As examples, we present sensors for measuring temperature, flow, tactile, optical and electrophysiological data, together with radiofrequency electrodes for controlled, local ablation of tissue. Use of such 'instrumented' balloon catheters in live animal models illustrates their operation, as well as their specific utility in cardiac ablation therapy. The same concepts can be applied to other substrates of interest, such as surgical gloves.
C1 [Kim, Dae-Hyeong; Lu, Nanshu; Kim, Yun-Soung; Xu, Lizhi; Kim, Rak-Hwan; Hwang, Sukwon; Won, Sang-Min; Rogers, John A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Mat Sci & Engn, Urbana, IL 61801 USA.
[Kim, Dae-Hyeong; Lu, Nanshu; Kim, Yun-Soung; Xu, Lizhi; Kim, Rak-Hwan; Hwang, Sukwon; Won, Sang-Min; Rogers, John A.] Univ Illinois, Frederick Seitz Mat Res Lab, Urbana, IL 61801 USA.
[Ghaffari, Roozbeh; Lee, Stephen P.; de Graff, Bassel; Elolampi, Brian] MC10 Inc, Cambridge, MA 02140 USA.
[Wu, Jian; Huang, Younggang] Northwestern Univ, Dept Mech Engn, Evanston, IL 60208 USA.
[Wu, Jian; Huang, Younggang] Northwestern Univ, Dept Civil & Environm Engn, Evanston, IL 60208 USA.
[Song, Jizhou] Univ Miami, Dept Mech & Aerosp Engn, Coral Gables, FL 33146 USA.
[Liu, Zhuangjian] Inst High Performance Comp, Singapore 138632, Singapore.
[Viventi, Jonathan; Litt, Brian] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
[Mansour, Moussa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Slepian, Marvin J.] Univ Arizona, Sarver Heart Ctr, Tucson, AZ 85724 USA.
[Moss, Joshua D.] Hosp Univ Penn, Dept Cardiol, Philadelphia, PA 19104 USA.
[Litt, Brian] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
RP Rogers, JA (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Mat Sci & Engn, Urbana, IL 61801 USA.
EM jrogers@uiuc.edu
RI Song, Jizhou/B-1935-2008; Kim, Rak-Hwan/A-6155-2012; Rogers, John
/L-2798-2016; Wu, Jian/I-3466-2012; Lu, Nanshu/B-1611-2008; Huang,
Yonggang/B-6998-2009; Xu, Lizhi/D-8143-2016
OI Lee, Stephen/0000-0002-8521-8652; Xu, Lizhi/0000-0001-6888-0524
FU National Science Foundation [DMI-0328162]; US Department of Energy,
Division of Materials Sciences at the University of Illinois at
Urbana-Champaign [DE-FG02-07ER46471, DE-FG02-07ER46453]; Beckman
Institute; National Security Science and Engineering Faculty
FX We thank K. Dowling for help in high-resolution imaging and analysis of
devices. We thank B. Dehdashti and members of the Sarver Heart Center
for help in preparing the animals for in vivo studies. We thank S.
Laferriere and the Massachusetts General Hospital Electrophysiology
Laboratory for help with X-ray imaging in animals. This material is
based on work supported by the National Science Foundation under grant
DMI-0328162 and the US Department of Energy, Division of Materials
Sciences, under award DE-FG02-07ER46471, through the Materials Research
Laboratory and Center for Microanalysis of Materials (DE-FG02-07ER46453)
at the University of Illinois at Urbana-Champaign. N.L. acknowledges
support from a Beckman Institute postdoctoral fellowship. J.A.R.
acknowledges a National Security Science and Engineering Faculty
Fellowship.
NR 39
TC 227
Z9 232
U1 17
U2 121
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1476-1122
J9 NAT MATER
JI Nat. Mater.
PD APR
PY 2011
VL 10
IS 4
BP 316
EP 323
DI 10.1038/NMAT2971
PG 8
WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics,
Applied; Physics, Condensed Matter
SC Chemistry; Materials Science; Physics
GA 739UU
UT WOS:000288744700023
PM 21378969
ER
PT J
AU Stengel, A
Goebel, M
Tache, Y
AF Stengel, A.
Goebel, M.
Tache, Y.
TI Nesfatin-1: a novel inhibitory regulator of food intake and body weight
SO OBESITY REVIEWS
LA English
DT Article
DE Food intake; hypothalamus; nesfatin-1; NUCB2; X; A-like cells
ID CORTICOTROPIN-RELEASING-FACTOR; MELANOCYTE-STIMULATING HORMONE; SATIETY
MOLECULE NESFATIN-1; EDINGER-WESTPHAL NUCLEUS; BLOOD-BRAIN-BARRIER;
BINDING-PROTEIN; INSULIN-SECRETION; ARCUATE NUCLEUS; PARAVENTRICULAR
NUCLEUS; TRANSCRIPT PEPTIDE
AB P>The protein nucleobindin 2 (NUCB2) or NEFA (DNA binding/EF-hand/acidic amino acid rich region) was identified over a decade ago and implicated in intracellular processes. New developments came with the report that post-translational processing of hypothalamic NUCB2 may result in nesfatin-1, nesfatin-2 and nesfatin-3 and convergent studies showing that nesfatin-1 and full length NUCB2 injected in the brain potently inhibit the dark phase food intake in rodents including leptin receptor deficient Zucker rats. Nesfatin-1 also reduces body weight gain, suggesting a role as a new anorexigenic factor and modulator of energy balance. In light of the obesity epidemic and its associated diseases, underlying new mechanisms regulating food intake may be promising targets in the drug treatment of obese patients particularly as the vast majority of them display reduced leptin sensitivity or leptin resistance while nesfatin-1's mechanism of action is leptin independent. Although much progress on the localization of NUCB2/nesfatin-1 in the brain and periphery as well as on the understanding of nesfatin-1's anorexic effect have been achieved during the past three years, several important mechanisms have yet to be unraveled such as the identification of the nesfatin-1 receptor and the regulation of NUCB2 processing and nesfatin-1 release.
C1 [Tache, Y.] Univ Calif Los Angeles, Ctr Neurobiol Stress, VA GLA Healthcare Syst, Div Digest Dis, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA.
VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Tache, Y (reprint author), Univ Calif Los Angeles, Ctr Neurobiol Stress, VA GLA Healthcare Syst, Div Digest Dis, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM ytache@mednet.ucla.edu
FU German Research Foundation [STE 1765/1-1, GO 1718/1-1]; NIHDK [33061];
[DK-41301]
FX Supported by: German Research Foundation Grants STE 1765/1-1 (A.S.), GO
1718/1-1 (M.G.), VA Research Career Scientist Award, NIHDK 33061, Center
Grant DK-41301 (Animal Core) (Y.T.).
NR 61
TC 29
Z9 35
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1467-7881
J9 OBES REV
JI Obes. Rev.
PD APR
PY 2011
VL 12
IS 4
BP 261
EP 271
DI 10.1111/j.1467-789X.2010.00770.x
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 738ZA
UT WOS:000288679900004
PM 20546141
ER
PT J
AU Jena, AB
Goldman, DP
Joyce, G
AF Jena, Anupam B.
Goldman, Dana P.
Joyce, Geoffrey
TI Association Between the Birth of Twins and Parental Divorce
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID NATURAL EXPERIMENT; MULTIPLE BIRTHS; FERTILITY; CHILDREN; WEIGHT; RATES
AB OBJECTIVE: Mothers of multiple births face higher rates of postpartum depression, yet evidence on the marital consequences of multiple births is limited. We examined the association between twin births and parental divorce.
METHODS: We used the 1980 U.S. Census to identify a large sample of mothers with and without twin births. The goal was to estimate multivariate logistic models of the association between birth of twins and divorce adjusting for race, age at marriage and first birth, and college education. We examined whether the association was affected by maternal education, age and sex composition of twins, and family size.
RESULTS: Twins at first birth were associated with greater parental divorce compared with singletons (odds ratio, 1.08; 95% confidence interval, 1.01-1.16; absolute risk 13.7% with twins compared with 12.7%; P=.02). The association was statistically greater among mothers not attending college (14.9% with twins compared with 13.3%; P=.01) compared with those with some college (10.4% with twins compared with 10.5%; P=.34); those with children older than 8 years (15.6% with twins compared with 13.5%; P <.01) compared with younger children (10.6% with twins compared with 10.8%; P=.42); and those with at least one twin girl (13.8% with twins compared with 12.6%; P=.03) compared with twin boys (12.1% with twins compared with 12.5%, P=.38). Mothers with four or more children had a larger association between birth of twins and divorce (15.4% for mothers with twins at fourth birth compared with 11.3% for all other mothers with four or more children; P <.01) compared with mothers with twins at first birth (13.7% for twins at first birth compared with 12.7%; P=.02).
CONCLUSION: Health consequences of twin births for children and mothers are well known. Twin births may be associated with longer-term parental divorce. Specific groups, namely mothers not completing college and mothers who already have more children, may be at higher risk. (Obstet Gynecol 2011;117:892-7) DOI: 10.1097/AOG.0b013e3182102adf
C1 [Jena, Anupam B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wang Ambulatory Care Ctr,Dept Med, Boston, MA 02114 USA.
Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA.
RP Jena, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wang Ambulatory Care Ctr,Dept Med, 15 Parkman St, Boston, MA 02114 USA.
EM jena.anupam@mgh.harvard.edu
FU National Institutes of Health [5 T32 GM07281]; Agency of Healthcare
Research and Quality [T32 HS 000046]
FX Funding provided by the National Institutes of Health Medical Scientist
National Research Award Grant 5 T32 GM07281 and Agency of Healthcare
Research and Quality Training Grant T32 HS 000046 (A.B.J.).
NR 16
TC 6
Z9 6
U1 0
U2 5
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 2011
VL 117
IS 4
BP 892
EP 897
DI 10.1097/AOG.0b013e3182102adf
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 738NW
UT WOS:000288647500020
PM 21422862
ER
PT J
AU Shimosegawa, T
Chari, ST
Frulloni, L
Kamisawa, T
Kawa, S
Mino-Kenudson, M
Kim, MH
Kloppel, G
Lerch, MM
Lohr, M
Notohara, K
Okazaki, K
Schneider, A
Zhang, LZ
AF Shimosegawa, Tooru
Chari, Suresh T.
Frulloni, Luca
Kamisawa, Terumi
Kawa, Shigeyuki
Mino-Kenudson, Mari
Kim, Myung-Hwan
Kloeppel, Guenter
Lerch, Markus M.
Lohr, Matthias
Notohara, Kenji
Okazaki, Kazuichi
Schneider, Alexander
Zhang, Lizhi
TI International Consensus Diagnostic Criteria for Autoimmune Pancreatitis
Guidelines of the International Association of Pancreatology
SO PANCREAS
LA English
DT Article
DE autoimmune pancreatitis; international consensus diagnostic criteria;
type 1 AIP; type 2 AIP
ID FEATURES; SUBTYPES; BIOPSY
AB Objectives: To achieve the goal of developing international consensus diagnostic criteria (ICDC) for autoimmune pancreatitis (AIP).
Methods: An international panel of experts met during the 14th Congress of the International Association of Pancreatology held in Fukuoka, Japan, from July 11 through 13, 2010. The proposed criteria represent a consensus opinion of the working group.
Results: Autoimmune pancreatitis was classified into types 1 and 2. The ICDC used 5 cardinal features of AIP, namely, imaging of pancreatic parenchyma and duct, serology, other organ involvement, pancreatic histology, and an optional criterion of response to steroid therapy. Each feature was categorized as level 1 and 2 findings depending on the diagnostic reliability. The diagnosis of type 1 and type 2 AIP can be definitive or probable, and in some cases, the distinction between the subtypes may not be possible (AIP-not otherwise specified).
Conclusions: The ICDC for AIP were developed based on the agreement of an international panel of experts in the hope that they will promote worldwide recognition of AIP. The categorization of AIP into types 1 and 2 should be helpful for further clarification of the clinical features, pathogenesis, and natural history of these diseases.
C1 [Shimosegawa, Tooru] Tohoku Univ, Div Gastroenterol, Grad Sch Med, Aoba Ku, Sendai, Miyagi 9808574, Japan.
[Chari, Suresh T.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Frulloni, Luca] Univ Verona, Dept Med, I-37100 Verona, Italy.
[Kamisawa, Terumi] Tokyo Metropolitan Komagome Hosp, Dept Internal Med, Tokyo, Japan.
[Kawa, Shigeyuki] Shinshu Univ, Ctr Hlth Safety & Environm Management, Nagano, Japan.
[Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Kim, Myung-Hwan] Univ Ulsan, Dept Gastroenterol, Coll Med, Asan Med Ctr, Seoul, South Korea.
[Kloeppel, Guenter] Tech Univ Munich, Dept Pathol, Munich, Germany.
[Lerch, Markus M.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med A, Greifswald, Germany.
[Lohr, Matthias] Karolinska Inst, Dept Surg Gastroenterol, Stockholm, Sweden.
[Notohara, Kenji] Kurashiki Cent Hosp, Dept Pathol, Kurashiki, Okayama, Japan.
[Okazaki, Kazuichi] Kansai Med Univ, Div Gastroenterol & Hepatol, Osaka, Japan.
[Schneider, Alexander] Univ Heidelberg, Dept Med Gastroenterol Hepatol Infect Dis 2, D-6800 Mannheim, Germany.
[Zhang, Lizhi] Mayo Clin, Div Anat Pathol, Rochester, MN USA.
RP Shimosegawa, T (reprint author), Tohoku Univ, Div Gastroenterol, Grad Sch Med, Aoba Ku, 1-1 Seiryomachi, Sendai, Miyagi 9808574, Japan.
RI Lohr, Johannes-Matthias/A-3692-2012; Lerch, Markus M./E-2206-2016;
OI Lerch, Markus M./0000-0002-9643-8263; Kloppel,
Gunter/0000-0002-6688-086X; Lohr, Matthias/0000-0002-7647-198X;
Frulloni, Luca/0000-0001-7417-2655
NR 18
TC 366
Z9 404
U1 4
U2 22
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 2011
VL 40
IS 3
BP 352
EP 358
DI 10.1097/MPA.0b013e3182142fd2
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 736NL
UT WOS:000288501300003
PM 21412117
ER
PT J
AU Chiu, CH
Michelow, IC
Cronin, J
Ringer, SA
Ferris, TG
Puopolo, KM
AF Chiu, Chia-Hua
Michelow, Ian C.
Cronin, Jonathan
Ringer, Steven A.
Ferris, Timothy G.
Puopolo, Karen M.
TI Effectiveness of a Guideline to Reduce Vancomycin Use in the Neonatal
Intensive Care Unit
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Pediatric-Academic-Societies
CY MAY 02-05, 2009
CL Baltimore, MD
SP Pediat Acad Soc
DE newborn; neonatal intensive care unit; vancomycin restriction;
antibiotic stewardship; infection control
ID RESISTANT STAPHYLOCOCCUS-AUREUS; LATE-ONSET SEPSIS; EPIDEMIOLOGY;
STEWARDSHIP; ENTEROCOCCI; EXPERIENCE; INFECTION; THERAPY; PROGRAM
AB Background: The Centers for Disease Control and Prevention recommend hospitals develop guidelines for the appropriate use of vancomycin as part of comprehensive antimicrobial stewardship. The objective of this study was to evaluate the effectiveness and safety of a guideline to restrict vancomycin use in the neonatal intensive care unit (NICU).
Methods: A vancomycin use guideline was introduced in 2 tertiary care NICUs with low incidences of methicillin-resistant Staphylococcus aureus infections. We compared all infants >72 hours of age who were evaluated for late-onset infection before and after implementation of this guideline.
Results: Vancomycin start rates were reduced from 6.9 to 4.5 per 1000 patient-days (35% reduction; P = 0.01) at Brigham and Women's Hospital, and from 17 to 6.4 per 1000 patient-days (62% reduction; P < 0.0001) at Massachusetts General Hospital. The number of infants exposed to vancomycin decreased from 5.2 to 3.1 per 1000 patient-days (40% reduction; P = 0.008) at Brigham and Women's Hospital, and 10.8 to 5.5 per 1000 patient-days (49% reduction; P = 0.009) at Massachusetts General Hospital. Causes of infection, duration of bacteremia, and incidence of complications or deaths attributable to late-onset infection did not change significantly at either institution.
Conclusions: Implementation of a NICU vancomycin use guideline significantly reduced exposure of newborns to vancomycin without adversely affecting short-term patient safety. Further studies are required to evaluate the long-term effect of vancomycin restriction on NICU patient safety and microbial ecology, particularly among institutions with higher rates of methicillin-resistant Staphylococcus aureus infections.
C1 [Ringer, Steven A.; Puopolo, Karen M.] Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA.
[Chiu, Chia-Hua] Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA.
[Michelow, Ian C.] Massachusetts Gen Hosp, Div Pediat Infect Dis, Boston, MA 02114 USA.
[Michelow, Ian C.; Cronin, Jonathan; Ringer, Steven A.; Ferris, Timothy G.; Puopolo, Karen M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Cronin, Jonathan] Massachusetts Gen Hosp, Neonatol & Newborn Med Unit, Boston, MA 02114 USA.
[Ferris, Timothy G.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Puopolo, KM (reprint author), Brigham & Womens Hosp, Dept Newborn Med, 75 Francis St, Boston, MA 02115 USA.
EM kpuopolo@partners.org
NR 24
TC 23
Z9 26
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD APR
PY 2011
VL 30
IS 4
BP 273
EP 278
DI 10.1097/INF.0b013e3182011d12
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 735SU
UT WOS:000288438700004
PM 21085051
ER
PT J
AU Marshall-Berenz, EC
Vujanovic, AA
MacPherson, L
AF Marshall-Berenz, Erin C.
Vujanovic, Anka A.
MacPherson, Laura
TI Impulsivity and alcohol use coping motives in a trauma-exposed sample:
The mediating role of distress tolerance
SO PERSONALITY AND INDIVIDUAL DIFFERENCES
LA English
DT Article
DE Impulsivity; Alcohol; Coping; Distress tolerance; PTSD
ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOMETRIC PROPERTIES; SCALE; MODELS;
VALIDATION; DRINKING; URGENCY
AB The present investigation examined the mediating role of distress tolerance in the association between impulsivity and alcohol use coping motives among trauma-exposed individuals. Participants were 86 adults (64.3% women; M(age) = 23.4, SD = 9.3) who met the DSM-IV-TR posttraumatic stress disorder (PTSD) Criterion A for at least one traumatic life event and endorsed alcohol use in the past month. Distress tolerance at least partially mediated the association between impulsivity and alcohol use coping motives, after controlling for the variance explained by PTSD symptom severity and alcohol use problems. Clinical implications and future directions related to this line of inquiry are presented and discussed. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Marshall-Berenz, Erin C.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA.
[Vujanovic, Anka A.] VA Boston Hlth Care Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA.
[Vujanovic, Anka A.] Boston Univ, Sch Med, Boston, MA 02130 USA.
[MacPherson, Laura] Univ Maryland, College Pk, MD 20742 USA.
RP Marshall-Berenz, EC (reprint author), Univ Vermont, Dept Psychol, 2 Colchester Ave,John Dewey Hall, Burlington, VT 05405 USA.
EM Erin.Marshall@uvm.edu
FU NIMH NIH HHS [F31 MH080453, F31 MH080453-01A1]
NR 31
TC 22
Z9 22
U1 3
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0191-8869
J9 PERS INDIV DIFFER
JI Pers. Individ. Differ.
PD APR
PY 2011
VL 50
IS 5
BP 588
EP 592
DI 10.1016/j.paid.2010.11.033
PG 5
WC Psychology, Social
SC Psychology
GA 728RM
UT WOS:000287892200010
PM 21483650
ER
PT J
AU Yuferov, V
Nielsen, DA
Levran, O
Randesi, M
Hamon, S
Ho, A
Morgello, S
Kreek, MJ
AF Yuferov, Vadim
Nielsen, David A.
Levran, Orna
Randesi, Matthew
Hamon, Sara
Ho, Ann
Morgello, Susan
Kreek, Mary Jeanne
TI Tissue-specific DNA methylation of the human prodynorphin gene in
post-mortem brain tissues and PBMCs
SO PHARMACOGENETICS AND GENOMICS
LA English
DT Article
DE anterior cingulate cortex; bisulfite sequencing; caudate; CpG island;
DNA methylation; dynorphin; human post-mortem brain; prodynorphin gene
expression
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MESSENGER-RNA EXPRESSION; CPG ISLANDS;
EPIGENETIC REGULATION; DIFFERENT REGIONS; PDYN EXPRESSION; BINDING
FACTOR; BINGE COCAINE; TRANSCRIPTION; DYNORPHIN
AB Objective Dynorphins, the endogenous ligands for the kappa opioid receptor, are implicated in neuropsychiatric disorders through modulation of basal and stimuli-induced dopaminergic, glutamatergic, and serotonergic tones. Expression of the prodynorphin gene (PDYN) is critical for rewarding properties of drugs of abuse and stress-induced responses. Epigenetic factors, such as DNA methylation, play an important role in modulation of gene expression.
Methods We analyzed DNA methylation patterns of three CpG-rich regions of PDYN, a CpG island, and cluster A in the proximal promoter, and cluster B in coding exon 4, by bisulfite sequencing of DNA from the caudate and anterior cingulate cortex from post-mortem brain of 35 individuals (22 HIV seropositive), and in peripheral blood mononuclear cells from 21 of these individuals.
Results We found remarkably similar patterns of methylation across CpG sites in these tissues. However, there were tissue-specific differences in methylation levels (P=0.000001) of the CpG island: higher levels in peripheral blood mononuclear cells (82%) than in the brain tissues, the caudate (62%), and the anterior cingulate cortex (44%). But there was higher PDYN expression in the caudate than in the anterior cingulate cortex. In contrast, cluster A near the transcription start site is hypomethylated.
Conclusion This DNA methylation profile of the PDYN gene is typical for primary responsive genes with regulatory elements for both basal and tissue-specific transcription. Our findings provide a rationale for further studies of the role of other epigenetic factors in the regulation of PDYN expression in individuals with psychiatric and neurological disorders. Pharmacogenetics and Genomics 21: 185-196 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Yuferov, Vadim; Nielsen, David A.; Levran, Orna; Randesi, Matthew; Hamon, Sara; Ho, Ann; Kreek, Mary Jeanne] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10065 USA.
[Morgello, Susan] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Nielsen, David A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Nielsen, David A.] Michael E DeBakey Med Ctr, Houston, TX USA.
RP Yuferov, V (reprint author), Rockefeller Univ, Lab Biol Addict Dis, Box 171,1230 York Ave, New York, NY 10065 USA.
EM yuferov@rockefeller.edu
RI Nielsen, David/B-4655-2009
FU NIH-NIDA [P60-DA05130]; NIH-NIMH [R01-MH79880, R24-MH59724,
U01MH-083501]
FX This study was supported by the NIH-NIDA P60-DA05130 (M.J.K.), the
NIH-NIMH R01-MH79880 (M.J.K.), the NIH-NIMH R24-MH59724 and U01MH-083501
(S.M.).
NR 60
TC 24
Z9 24
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1744-6872
EI 1744-6880
J9 PHARMACOGENET GENOM
JI Pharmacogenet. Genomics
PD APR
PY 2011
VL 21
IS 4
BP 185
EP 196
DI 10.1097/FPC.0b013e32833eecbc
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
GA 735UH
UT WOS:000288444500004
PM 20808262
ER
PT J
AU Gordon, CR
Avery, RK
Abouhassan, W
Siemionow, M
AF Gordon, Chad R.
Avery, Robin K.
Abouhassan, William
Siemionow, Maria
TI Cytomegalovirus and Other Infectious Issues Related to Face
Transplantation: Specific Considerations, Lessons Learned, and Future
Recommendations
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID SOLID-ORGAN TRANSPLANTATION; COMPOSITE TISSUE ALLOTRANSPLANTATION;
FACIAL TRANSPLANTATION; CMV INFECTION; VALGANCICLOVIR PROPHYLAXIS; HAND
TRANSPLANTATION; PREEMPTIVE THERAPY; RECIPIENTS; DISEASE; ALLOGRAFT
AB Background: Composite tissue allotransplantation is fraught with complexities similar to those of solid organ transplantation, including donor-related cytomegalovirus transmission. With this in mind, the authors' objective was to (1) report their team's experience with infections and donor-related cytomegalovirus transmission in relation to face transplantation and (2) review the facial composite tissue allotransplantation literature as it pertains to cytomegalovirus and other various infections.
Methods: A MEDLINE literature search and article review was performed in July of 2010 on all published articles specific to face transplantation, cytomegalovirus disease, and all related infections and/or complications. In addition, the authors retrospectively reviewed their own institution's experience with face transplantation.
Results: Two of the world's first four face transplant recipients acquired cytomegalovirus viral infection by means of their donated facial organs. Also, the French experience, and our own, has been challenged by cytomegalovints reactivation and graft rejection, therefore necessitating a critical evaluation. The authors have also learned, from their own experience, that facial composite tissue allografts containing mucosa and paranasal sinuses present a distinct challenge with regard to their accompanying flora.
Condusions: Although the risk of donor-derived cytomegalovirus is acceptable in life-saving solid organ transplantation, for face transplantation patients, the scenario is different When the authors' team performed the first nearly total face/maxilla transplantation (December of 2008), there was little known regarding the consequences of cytomegalovints-related donor transmission in face transplantation. Therefore, the authors now recommend that all candidates be fully informed as to the risks of cytomegalovirus/infectious transmission and that aggressive viral, bacterial, and fungal prophylaxis be instituted. (Plast. Reconstr. Surg. 127: 1515, 2011.)
C1 [Gordon, Chad R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg,Dept Surg, Boston, MA 02114 USA.
Cleveland Clin, Dept Plast Surg, Inst Dermatol & Plast Surg, Cleveland, OH 44106 USA.
Cleveland Clin, Dept Infect Dis, Inst Med, Cleveland, OH 44106 USA.
RP Gordon, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg,Dept Surg, 15 Parkman St,WACC Suite 435, Boston, MA 02114 USA.
EM cgordon5@partners.org
NR 59
TC 26
Z9 26
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
EI 1529-4242
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD APR
PY 2011
VL 127
IS 4
BP 1515
EP 1523
DI 10.1097/PRS.0b013e318208d03c
PG 9
WC Surgery
SC Surgery
GA 741CH
UT WOS:000288840200015
PM 21460660
ER
PT J
AU Abbott, MM
Alkire, BC
Meara, JG
AF Abbott, Megan M.
Alkire, Blake C.
Meara, John G.
TI The Value Proposition: Using a Cost Improvement Map to Improve Value for
Patients with Nonsyndromic, Isolated Cleft Palate
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID OROFACIAL CLEFTS; CHILDREN
AB Background: As health care costs rise exponentially in the United States, increasing emphasis is being placed on measuring value, which incorporates both quality and costs. Although the concept of continuous quality improvement has taken a firm foothold in health care, techniques for measuring and continuously improving costs at the patient or system level are lacking.
Methods: A retrospective, microcosting analysis mapped detailed medical costs over 18 months for 25 patients with nonsyndromic, isolated cleft palate to illustrate the concept of a continuous cost improvement map in a complex, multidisciplinary condition.
Results: Care for patients with nonsyndromic, isolated cleft palate was mapped to three timelines based on diagnostic subtype. Patients with Robin sequence requiring early surgical intervention for airway or feeding management (n = 4) had median costs that were triple those of Robin patients managed conservatively (n = 5) ($87,841 versus $27,864, respectively) as compared with patients without Robin sequence (n = 16) ($15,698). Inpatient services accounted for 85 to 95 percent of all costs, which were driven by the operating room, intensive care unit, and inpatient ward. More detailed analysis of each cost driver is reported.
Conclusions: The cost improvement map provides a counterpart to the quality improvement map to illustrate how costs may be incorporated into value improvement efforts for complex, multidisciplinary conditions. The transparency and level of detail provided by this methodology are critical for internal improvement efforts and offer valuable insight for health care managers and policy makers, whose decisions should be based on accurate, patient-centered data. (Plast. Reconstr. Surg. 127: 1650, 2011.)
C1 [Meara, John G.] Childrens Hosp Boston, Dept Plast & Oral Surg, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
RP Meara, JG (reprint author), Childrens Hosp Boston, Dept Plast & Oral Surg, 300 Longwood Ave,Enders 1, Boston, MA 02115 USA.
EM john.meara@childrens.harvard.edu
NR 21
TC 4
Z9 4
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD APR
PY 2011
VL 127
IS 4
BP 1650
EP 1658
DI 10.1097/PRS.0b013e318208d25e
PG 9
WC Surgery
SC Surgery
GA 741CH
UT WOS:000288840200031
PM 21460672
ER
PT J
AU Scibelli, AC
McKinnon, CS
Reed, C
Burkhart-Kasch, S
Li, N
Baba, H
Wheeler, JM
Phillips, TJ
AF Scibelli, Angela C.
McKinnon, Carrie S.
Reed, Cheryl
Burkhart-Kasch, Sue
Li, Na
Baba, Harue
Wheeler, Jeanna M.
Phillips, Tamara J.
TI Selective breeding for magnitude of methamphetamine-induced
sensitization alters methamphetamine consumption
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Reward; Addiction; Stimulation; Locomotor activity; Drinking; Saccharin;
Quinine; Potassium chloride; Heritability; Clearance
ID RECOMBINANT INBRED MICE; BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS;
EXTRACELLULAR DOPAMINE; LOCOMOTOR RESPONSES; ETHANOL-CONSUMPTION;
STIMULANT-DRUGS; ALCOHOL INTAKE; D-AMPHETAMINE; TIME-COURSE
AB Genetically determined differences in susceptibility to drug-induced sensitization could be related to risk for drug consumption.
Studies were performed to determine whether selective breeding could be used to create lines of mice with different magnitudes of locomotor sensitization to methamphetamine (MA). MA sensitization (MASENS) lines were also examined for genetically correlated responses to MA.
Beginning with the F2 cross of C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization. Five selected offspring generations were tested. All generations were also tested for MA consumption, and some were tested for dose-dependent locomotor-stimulant responses to MA, consumption of saccharin, quinine, and potassium chloride as a measure of taste sensitivity, and MA clearance after acute and repeated MA.
Selective breeding resulted in creation of two lines [MA high sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in magnitude of MA-induced sensitization. Initially, greater MA consumption in MAHSENS mice reversed over the course of selection so that MALSENS mice consumed more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant effects of MA, but there were no significant differences between the lines in MA clearance from blood.
Genetic factors influence magnitude of MA-induced locomotor sensitization and some of the genes involved in magnitude of this response also influence MA sensitivity and consumption. Genetic factors leading to greater MA-induced sensitization may serve a protective role against high levels of MA consumption.
C1 [Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR 97239 USA.
[Scibelli, Angela C.; McKinnon, Carrie S.; Reed, Cheryl; Burkhart-Kasch, Sue; Li, Na; Baba, Harue; Wheeler, Jeanna M.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci & Methamphetamine, Abuse Res Ctr, Portland, OR 97201 USA.
[Scibelli, Angela C.; McKinnon, Carrie S.; Reed, Cheryl; Burkhart-Kasch, Sue; Li, Na; Baba, Harue; Wheeler, Jeanna M.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA.
RP Phillips, TJ (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D 32, Portland, OR 97239 USA.
EM phillipt@ohsu.edu
FU NIDA [P50 DA018165, T32 DA07262]; Department of Veterans Affairs
FX This work was supported by grants from NIDA (P50 DA018165 and T32
DA07262) and by the Department of Veterans Affairs. We are grateful to
John Belknap for providing statistical software for performance of
heritability calculations. All experiments were conducted in compliance
with current laws in the United States of America.
NR 63
TC 15
Z9 17
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD APR
PY 2011
VL 214
IS 4
BP 791
EP 804
DI 10.1007/s00213-010-2086-2
PG 14
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 739XQ
UT WOS:000288755500002
PM 21088960
ER
PT J
AU Gerstner, ER
Sorensen, AG
AF Gerstner, Elizabeth R.
Sorensen, A. Gregory
TI Diffusion and Diffusion Tensor Imaging in Brain Cancer
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID MAGNETIC-RESONANCE-SPECTROSCOPY; RADIATION-INDUCED CHANGES;
SQUAMOUS-CELL CARCINOMA; HIGH-GRADE GLIOMA; WHITE-MATTER;
PROSTATE-CANCER; TUMOR RESPONSE; WEIGHTED MRI; CERVICAL-CANCER; THERAPY
C1 [Gerstner, Elizabeth R.] Massachusetts Gen Hosp, Ctr Canc, Dept Neurol, Boston, MA 02114 USA.
[Sorensen, A. Gregory] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Cambridge, MA USA.
[Sorensen, A. Gregory] Massachusetts Gen Hosp, Div Hlth Sci & Technol, Cambridge, MA USA.
[Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA USA.
[Sorensen, A. Gregory] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Sorensen, A. Gregory] MIT, Cambridge, MA 02139 USA.
RP Gerstner, ER (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Neurol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA.
EM egerstner@partners.org
NR 37
TC 18
Z9 18
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 2011
VL 21
IS 2
BP 141
EP 146
DI 10.1016/j.semradonc.2010.10.005
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 736GY
UT WOS:000288480200007
PM 21356481
ER
PT J
AU Schroeder, T
Melo, MFV
Venegas, JG
AF Schroeder, Tobias
Melo, Marcos F. Vidal
Venegas, Jose G.
TI Analysis of 2-[Fluorine-18]-Fluoro-2-deoxy-D-glucose Uptake Kinetics in
PET Studies of Pulmonary Inflammation
SO ACADEMIC RADIOLOGY
LA English
DT Article; Proceedings Paper
CT 4th International Workshop for Pulmonary Functional Imaging
CY SEP, 2009
CL Boston, MA
DE Radionuclide imaging; positron emission tomography; FDG; lung
inflammation; acute respiratory distress syndrome; cystic fibrosis;
chronic obstructive pulmonary disease; compartmental modeling
ID POSITRON-EMISSION-TOMOGRAPHY; ACUTE LUNG INJURY; CEREBRAL
GLUCOSE-UTILIZATION; METABOLIC-ACTIVITY; F-18-FDG UPTAKE; DEOXYGLUCOSE
UPTAKE; CYSTIC-FIBROSIS; INPUT FUNCTION; FDG-PET; DISSOCIATION
AB Dynamic positron emission tomography (PET) imaging of the lung using the radiotracer 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18)F-FDG) is an emerging method to assess noninvasively the metabolic activity of pulmonary inflammatory cells. Nevertheless, because of the distinct functional and structural characteristics of inflamed lung tissue standard methods of (18)F-FDG analysis can be substantially limited and there is no consensus about the best method for quantification of the (18)F-FDG signal for acute or chronic inflammatory lung diseases. This article gives an overview on recent advances in quantitative analysis of (18)F-FDG uptake kinetics in non-neoplastic inflamed lung tissue.
C1 [Schroeder, Tobias; Melo, Marcos F. Vidal; Venegas, Jose G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM mvidalmelo@partners.org
OI Schroeder, Tobias/0000-0002-4439-8060
FU NHLBI NIH HHS [4R01-HL086827-01, R01 HL086827-04, R01 HL068011, R01
HL086827-05, R01 HL086827, 5R01HL-068011-08]
NR 40
TC 10
Z9 10
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD APR
PY 2011
VL 18
IS 4
BP 418
EP 423
DI 10.1016/j.acra.2010.11.019
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 737MF
UT WOS:000288572200003
PM 21292507
ER
PT J
AU Nishino, M
Jackman, DM
Hatabu, H
Janne, PA
Johnson, BE
Van den Abbeele, AD
AF Nishino, Mizuki
Jackman, David M.
Hatabu, Hiroto
Jaenne, Pasi A.
Johnson, Bruce E.
Van den Abbeele, Annick D.
TI Imaging of Lung Cancer in the Era of Molecular Medicine
SO ACADEMIC RADIOLOGY
LA English
DT Article; Proceedings Paper
CT 4th International Workshop for Pulmonary Functional Imaging
CY SEP, 2009
CL Boston, MA
DE Lung cancer; targeted therapy; computed tomography;
dynamic-contrast-enhanced magnetic resonance imaging; positron emission
tomography
ID GROWTH-FACTOR-RECEPTOR; SOLITARY PULMONARY NODULES; CONTRAST-ENHANCED
MRI; POSITRON-EMISSION-TOMOGRAPHY; PREVIOUSLY TREATED PATIENTS; TYROSINE
KINASE INHIBITORS; SQUAMOUS-CELL CARCINOMAS; PHASE-II TRIAL; TUMOR
RESPONSE; ACQUIRED-RESISTANCE
AB Recent discoveries characterizing the molecular basis of lung cancer brought fundamental changes in lung cancer treatment. The authors review the molecular pathogenesis of lung cancer, including genomic abnormalities, targeted therapies, and resistance mechanisms, and discuss lung cancer imaging with novel techniques. Knowledge of the molecular basis of lung cancer is essential for radiologists to properly interpret imaging and assess response to therapy. Quantitative and functional imaging helps assessing the biologic behavior of lung cancer.
C1 [Nishino, Mizuki; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA.
[Jackman, David M.; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Nishino, Mizuki; Hatabu, Hiroto; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA.
EM mizuki_nishino@dfci.harvard.edu
FU NCI NIH HHS [5R21 CA11627-02, P50 CA090578, R01 CA114465, P20 CA090578,
1R01CA114465-01, 2P50CA090578-06]
NR 96
TC 18
Z9 18
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD APR
PY 2011
VL 18
IS 4
BP 424
EP 436
DI 10.1016/j.acra.2010.10.020
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 737MF
UT WOS:000288572200004
PM 21277232
ER
PT J
AU Lee, J
Kosaras, B
Del Signore, SJ
Cormier, K
Mckee, A
Ratan, RR
Kowall, NW
Ryu, H
AF Lee, Junghee
Kosaras, Bela
Del Signore, Steve J.
Cormier, Kerry
McKee, Ann
Ratan, Rajiv R.
Kowall, Neil W.
Ryu, Hoon
TI Modulation of lipid peroxidation and mitochondrial function improves
neuropathology in Huntington's disease mice
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
DE Huntington's disease; Mitochondria; Lipid peroxidation;
4-Hydroxy-2-nonenal (4-HNE); Neuronal survival
ID FIBRILS IN-VITRO; OXIDATIVE STRESS; NORDIHYDROGUAIARETIC ACID;
NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; CORTICAL-NEURONS;
TRANSGENIC MICE; MOUSE MODELS; CELL-DEATH; REPEAT
AB Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Oxidative damage has been associated with pathological neuronal loss in HD. The therapeutic modulation of oxidative stress and mitochondrial function using low molecular weight compounds may be an important strategy for delaying the onset and slowing the progression of HD. In the present study, we found a marked increase of 4-hydroxy-2-nonenal (4-HNE) adducts, a lipid peroxidation marker, in the caudate and putamen of HD brains and in the striatum of HD mice. Notably, 4-HNE immunoreactivity was colocalized with mutant huntingtin inclusions in the striatal neurons of R6/2 HD mice. Administration of nordihydroguaiaretic acid (NDGA), an antioxidant that functions by inhibiting lipid peroxidation, markedly reduced 4-HNE adduct formation in the nuclear inclusions of R6/2 striatal neurons. NDGA also protected cultured neurons against oxidative stress-induced cell death by improving ATP generation and mitochondrial morphology and function. In addition, NDGA restored mitochondrial membrane potential, mitochondrial structure, and synapse structure in the striatum of R6/2 mice and increased their lifespan. The present findings suggest that further therapeutic studies using NDGA are warranted in HD and other neurodegenerative diseases characterized by increased oxidative stress and altered mitochondrial function.
C1 [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Lee, Junghee; Del Signore, Steve J.; Cormier, Kerry; McKee, Ann; Kowall, Neil W.; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol & Pathol, Boston, MA 02118 USA.
[Kosaras, Bela] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA.
[Kosaras, Bela] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Del Signore, Steve J.; Cormier, Kerry; McKee, Ann] Bedford VA Med Ctr, Bedford, MA 01730 USA.
[Ratan, Rajiv R.] Cornell Univ, Dept Neurol, Weill Med Coll, Burke Cornell Med Res Inst, White Plains, NY 10605 USA.
RP Ryu, H (reprint author), VA Boston Healthcare Syst, Bldg 1A,Rm 109, Boston, MA 02130 USA.
EM hoonryu@bu.edu
RI Kowall, Neil/G-6364-2012
OI Kowall, Neil/0000-0002-6624-0213
FU NIH [NS52724]
FX We thank to Katharine Karr and Yu Jin Hwang for the preparation of
manuscript. This study was supported by NIH NS52724 (H.R.).
NR 47
TC 37
Z9 37
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
EI 1432-0533
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD APR
PY 2011
VL 121
IS 4
BP 487
EP 498
DI 10.1007/s00401-010-0788-5
PG 12
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 735US
UT WOS:000288446100005
PM 21161248
ER
PT J
AU Mohapatra, G
Engler, DA
Starbuck, KD
Kim, JC
Bernay, DC
Scangas, GA
Rousseau, A
Batchelor, TT
Betensky, RA
Louis, DN
AF Mohapatra, Gayatry
Engler, David A.
Starbuck, Kristen D.
Kim, James C.
Bernay, Derek C.
Scangas, George A.
Rousseau, Audrey
Batchelor, Tracy T.
Betensky, Rebecca A.
Louis, David N.
TI Genome-wide comparison of paired fresh frozen and formalin-fixed
paraffin-embedded gliomas by custom BAC and oligonucleotide array
comparative genomic hybridization: facilitating analysis of archival
gliomas
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
DE Array CGH; BAC aCGH; Glioma
ID DNA COPY-NUMBER; HIGH-RESOLUTION ANALYSIS; IN-SITU HYBRIDIZATION;
CELL-LINES; GLIOBLASTOMA-MULTIFORME; FFPE SAMPLES; TUMORS;
OLIGOASTROCYTOMAS; SUBTYPES; OLIGODENDROGLIOMAS
AB Array comparative genomic hybridization (aCGH) is a powerful tool for detecting DNA copy number alterations (CNA). Because diffuse malignant gliomas are often sampled by small biopsies, formalin-fixed paraffin-embedded (FFPE) blocks are often the only tissue available for genetic analysis; FFPE tissues are also needed to study the intratumoral heterogeneity that characterizes these neoplasms. In this paper, we present a combination of evaluations and technical advances that provide strong support for the ready use of oligonucleotide aCGH on FFPE diffuse gliomas. We first compared aCGH using bacterial artificial chromosome (BAC) arrays in 45 paired frozen and FFPE gliomas, and demonstrate a high concordance rate between FFPE and frozen DNA in an individual clone-level analysis of sensitivity and specificity, assuring that under certain array conditions, frozen and FFPE DNA can perform nearly identically. However, because oligonucleotide arrays offer advantages to BAC arrays in genomic coverage and practical availability, we next developed a method of labeling DNA from FFPE tissue that allows efficient hybridization to oligonucleotide arrays. To demonstrate utility in FFPE tissues, we applied this approach to biphasic anaplastic oligoastrocytomas and demonstrate CNA differences between DNA obtained from the two components. Therefore, BAC and oligonucleotide aCGH can be sensitive and specific tools for detecting CNAs in FFPE DNA, and novel labeling techniques enable the routine use of oligonucleotide arrays for FFPE DNA. In combination, these advances should facilitate genome-wide analysis of rare, small and/or histologically heterogeneous gliomas from FFPE tissues.
C1 [Mohapatra, Gayatry; Starbuck, Kristen D.; Kim, James C.; Bernay, Derek C.; Scangas, George A.; Rousseau, Audrey; Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Mohapatra, Gayatry; Starbuck, Kristen D.; Kim, James C.; Bernay, Derek C.; Scangas, George A.; Rousseau, Audrey; Louis, David N.] Harvard Univ, Sch Med, Boston, MA USA.
[Engler, David A.] Brigham Young Univ, Dept Stat, Provo, UT 84602 USA.
[Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Batchelor, Tracy T.; Louis, David N.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
RP Mohapatra, G (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM gmohapatra@partners.org; dlouis@partners.org
RI Rousseau, Audrey/L-3193-2015
FU NIH [R21/R33 CA106695]
FX This work was supported by NIH R21/R33 CA106695.
NR 44
TC 8
Z9 8
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
EI 1432-0533
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD APR
PY 2011
VL 121
IS 4
BP 529
EP 543
DI 10.1007/s00401-010-0773-z
PG 15
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 735US
UT WOS:000288446100009
PM 21080181
ER
PT J
AU Lee, JE
Willett, WC
Fuchs, CS
Smith-Warner, SA
Wu, K
Ma, J
Giovannucci, E
AF Lee, Jung Eun
Willett, Walter C.
Fuchs, Charles S.
Smith-Warner, Stephanie A.
Wu, Kana
Ma, Jing
Giovannucci, Edward
TI Folate intake and risk of colorectal cancer and adenoma: modification by
time
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOLIC-ACID FORTIFICATION; COLON-CANCER; MULTIVITAMIN USE;
DIETARY-FOLATE; CARCINOMA SEQUENCE; ALCOHOL; METAANALYSIS; PREVENTION;
METHIONINE; DISEASE
AB Background: Experimental and observational studies have suggested that folate may play dual roles in colorectal cancer risk depending on the timing and dose.
Objective: We examined the latency between folate intake and the incidence of colorectal cancer.
Design: We prospectively examined associations between folate intake assessed every 2 to 4 y by using validated food-frequency questionnaires and risk of colorectal cancer and adenoma in the Nurses' Health Study and Health Professionals Follow-Up Study, which included 2299 incident colorectal cancers and 5655 colorectal adenomas from 1980 to 2004.
Results: There was an association between total folate intake 12-16 y before diagnosis and lower risk of colorectal cancer (relative risk: 0.69; 95% CI: 0.51, 0.94; >= 800 compared with <250 mu g folate/d), but there was no association between intake in the recent past and colorectal cancer risk. Long-and short-term intakes of total folate were associated with a lower risk of colorectal adenoma, with a strong association with intake 4-8 y before diagnosis (odds ratio: 0.68; 95% CI: 0.60, 0.78; >= 800 compared with <250 mu g folate/d). The current use of multivitamins for >15 y, but not a shorter duration of use, was associated with lower risk of colorectal cancer; and a shorter duration of use was related to lower risk of adenoma. We did not observe an adverse effect of total folate or synthetic folic acid on risk of colorectal cancer or adenoma even during the folic acid fortification era.
Conclusion: Folate intake is inversely associated with risk of colorectal cancer only during early preadenoma stages. Am J Clin Nutr 2011; 93: 817-25.
C1 [Willett, Walter C.; Fuchs, Charles S.; Ma, Jing; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea.
[Willett, Walter C.; Fuchs, Charles S.; Ma, Jing; Giovannucci, Edward] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Willett, Walter C.; Smith-Warner, Stephanie A.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Giovannucci, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 667 Huntington Ave, Boston, MA 02115 USA.
EM egiovann@hsph.harvard.edu
OI Lee, Jung Eun/0000-0003-1141-878X
FU National Institutes of Health/National Cancer Institute [CA87969,
CA55075]; Conquer Cancer Coalition of Massachusetts; Prevent Cancer
Foundation
FX Supported by the National Institutes of Health/National Cancer Institute
(grants CA87969 and CA55075), the Conquer Cancer Coalition of
Massachusetts (EG), and the Prevent Cancer Foundation fellowship grant
(JEL).
NR 38
TC 58
Z9 64
U1 1
U2 15
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD APR
PY 2011
VL 93
IS 4
BP 817
EP 825
DI 10.3945/ajcn.110.007781
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 736YS
UT WOS:000288531600020
PM 21270374
ER
PT J
AU Mahon, PB
Pirooznia, M
Goes, FS
Seifuddin, F
Steele, J
Lee, PH
Huang, J
Hamshere, ML
DePaulo, JR
Kelsoe, JR
Rietschel, M
Nothen, M
Cichon, S
Gurling, H
Purcell, S
Smoller, JW
Craddock, N
Schulze, TG
McMahon, FJ
Potash, JB
Zandi, PP
AF Mahon, Pamela Belmonte
Pirooznia, Mehdi
Goes, Fernando S.
Seifuddin, Fayaz
Steele, Jo
Lee, Phil Hyoun
Huang, Jie
Hamshere, Marian L.
DePaulo, J. Raymond, Jr.
Kelsoe, John R.
Rietschel, Marcella
Noethen, Markus
Cichon, Sven
Gurling, Hugh
Purcell, Shaun
Smoller, Jordan W.
Craddock, Nick
Schulze, Thomas G.
McMahon, Francis J.
Potash, James B.
Zandi, Peter P.
CA Bipolar Genome Study BiGS Consort
TI Genome-Wide Association Analysis of Age at Onset and Psychotic Symptoms
in Bipolar Disorder
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
ID I AFFECTIVE-DISORDER; FAMILIAL AGGREGATION; DIAGNOSTIC INTERVIEW;
EUROPEAN ANCESTRY; LINKAGE ANALYSES; METAANALYSIS; PEDIGREES;
SCHIZOPHRENIA; LOCUS; GENE
AB Genome-wide association studies (GWAS) have identified several susceptibility loci for bipolar disorder (BP), most notably ANK3. However, most of the inherited risk for BP remains unexplained. One reason for the limited success may be the genetic heterogeneity of BP. Clinical sub-phenotypes of BP may identify more etiologically homogeneous subsets of patients, which can be studied with increased power to detect genetic variation. Here, we report on a mega-analysis of two widely studied sub-phenotypes of BP, age at onset and psychotic symptoms, which are familial and clinically significant. We combined data from three GWAS: NIMH Bipolar Disorder Genetic Association Information Network (GAIN-BP), NIMH Bipolar Disorder Genome Study (BiGS), and a German sample. The combined sample consisted of 2,836 BP cases with information on sub-phenotypes and 2,744 controls. Imputation was performed, resulting in 2.3 million SNPs available for analysis. No SNP reached genome-wide significance for either sub-phenotype. In addition, no SNP reached genome-wide significance in a meta-analysis with an independent replication sample. We had 80% power to detect associations with a common SNP at an OR of 1.6 for psychotic symptoms and a mean difference of 1.8 years in age at onset. Age at onset and psychotic symptoms in BP may be influenced by many genes of smaller effect sizes or other variants not measured well by SNP arrays, such as rare alleles. (C) 2011 Wiley-Liss, Inc.
C1 [Zandi, Peter P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA.
[Mahon, Pamela Belmonte; Pirooznia, Mehdi; Goes, Fernando S.; Seifuddin, Fayaz; DePaulo, J. Raymond, Jr.; Potash, James B.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Steele, Jo; Schulze, Thomas G.; McMahon, Francis J.] NIMH, US Dept HHS, NIH, Intramural Res Program, Bethesda, MD 20892 USA.
[Lee, Phil Hyoun; Huang, Jie; Purcell, Shaun; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Hamshere, Marian L.; Craddock, Nick] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales.
[Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Rietschel, Marcella] Univ Gottingen, Univ Med Ctr, Dept Psychiat & Psychotherapy, Gottingen, Germany.
[Rietschel, Marcella] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.
[Noethen, Markus] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Noethen, Markus; Cichon, Sven] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany.
[Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany.
[Gurling, Hugh] UCL, Dept Mental Hlth Sci, London, England.
RP Zandi, PP (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Hampton House,Room 857,624 N Broadway, Baltimore, MD 21205 USA.
EM pzandi@jhsph.edu
RI Liu, Chunyu/G-7561-2012; Schulze, Thomas/H-2157-2013; Gurling,
Hugh/A-5029-2010; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014;
OI Liu, Chunyu/0000-0002-5986-4415; Cichon, Sven/0000-0002-9475-086X;
Cichon, Sven/0000-0002-9475-086X; Pirooznia, Mehdi/0000-0002-4210-6458;
McMahon, Francis/0000-0002-9469-305X; Nothen, Markus/0000-0002-8770-2464
FU [R01 MH079799]
FX The authors express their profound appreciation to the families who
participated in this project, and to the many clinicians who facilitated
the referral of participants to the study. Data and biomaterials for the
NIMH samples were collected as part of 10 projects that participated in
the NIMH Bipolar Disorder Genetics Initiative. From 1991 to 1998, the
Principal Investigators and Co-Investigators were: Indiana University,
Indianapolis, IN, U01 MH46282-John Nurnberger, M. D., Ph. D., Marvin
Miller, M. D. and Elizabeth Bowman, M. D.; Washington University, St
Louis, MO, U01 MH46280-Theodore Reich, M. D., Allison Goate, Ph. D. and
John Rice, Ph. D.; Johns Hopkins University, Baltimore, MD U01 MH46274-J
Raymond DePaulo Jr, M. D. Sylvia Simpson, M. D., MPH and Colin Stine,
Ph. D.; NIMH Intramural Research Program, Clinical Neurogenetics Branch,
Bethesda, M. D.-Elliot Gershon, M. D., Diane Kazuba, BA and Elizabeth
Maxwell, M. S. W. From 1999 to 2003, the Principal Investigators and
Co-Investigatorswere: Indiana University, Indianapolis, IN, R01
MH59545-John Nurn-berger, M. D., Ph. D., Marvin J. Miller, M. D.,
Elizabeth S. Bowman, M. D., N. Leela Rau, M. D., P. Ryan Moe, M. D.,
Nalini Samavedy, M. D., Rif El-Mallakh, M. D. (at University of
Louisville), Husseini Manji, M. D. (at Wayne State University), Debra A.
Glitz, M. D. (at Wayne State University), Eric T. Meyer, MS, Carrie
Smiley, RN, Tatiana Foroud, Ph. D., Leah Flury, MS, Danielle M. Dick,
Ph. D. and Howard Edenberg, Ph. D.; Washington University, St Louis, MO,
R01 MH059534, John Rice, Ph. D., Theodore Reich, M. D., Allison Goate,
Ph. D. and Laura Bierut, M. D.; Johns Hopkins University, Baltimore, MD,
R01 MH59533-Melvin McInnis, M. D., J. Raymond DePaulo Jr, M. D., Dean F.
MacKinnon, M. D., Francis M. Mondimore, M. D., James B. Potash, M. D.,
Peter P. Zandi, Ph. D., Dimitrios Avramopoulos and Jennifer Payne;
University of Pennsylvania, PA, R01 MH59553-Wade Berrettini, M. D., Ph.
D.; University of California at Irvine, CA, R01 MH60068-William Byerley,
M. D. and Mark Vawter, M. D.; University of Iowa, IA, R01
MH059548-William Coryell, M. D. and Raymond Crowe, M. D.; University of
Chicago, Chicago, IL, R01 MH59535-Elliot Gershon, M. D., Judith Badner,
Ph. D., Francis McMahon, M. D., Chunyu Liu, Ph. D., Alan Sanders, M. D.,
Maria Caserta, Steven Dinwiddie, M. D., Tu Nguyen, Donna Harakal;
University of California at San Diego, CA, R01 MH59567-John Kelsoe, M.
D., Rebecca McKinney, B. A.; Rush University, IL, R01 MH059556-William
Scheftner, M. D., Howard M. Kravitz, DO, MPH, Diana Marta, B. A.,
Annette Vaughn-Brown, MSN, RN and Laurie Bederow, MA; NIMH Intramural
Research Program, Bethesda, M. D., 1Z01MH002810-01, Francis J. McMahon,
M. D., Layla Kassem, PsyD, Sevilla Detera-Wadleigh, Ph. D., Lisa Austin,
Ph. D., Dennis L. Murphy, M. D. From 2003 to 2007, the Principal
Investigators and Co-Investigators were: Indiana University,
Indianapolis, IN, R01 MH59545, John Nurnberger, M. D., Ph. D., Marvin J.
Miller, M. D., Elizabeth S. Bowman, M. D., N. Leela Rau, M. D., P. Ryan
Moe, M. D., Nalini Samavedy, M. D., Rif El-Mallakh, M. D. (at University
of Louisville), Husseini Manji, M. D. (at Johnson and Johnson), Debra A.
Glitz, M. D. (at Wayne State University), Eric T. Meyer, Ph. D., M. S.
(at Oxford University, UK), Carrie Smiley, R. N., Tatiana Foroud, Ph.
D., Leah Flury, M. S., Danielle M. Dick, Ph. D (at Virginia Commonwealth
University), Howard Edenberg, Ph. D.; Washington University, St. Louis,
MO, R01 MH059534, John Rice, Ph. D, Theodore Reich, M. D., Allison
Goate, Ph. D.; , Laura Bierut M. D. K02 DA21237; Johns Hopkins
University, Baltimore, MD, R01 MH59533, Melvin McInnis, M. D., J.
Raymond DePaulo, Jr., M. D., Dean F. MacKinnon, M. D., Francis M.
Mondimore, M. D., James B. Potash, M. D., Peter P. Zandi, Ph. D,
Dimitrios Avramopoulos, and Jennifer Payne; University of Pennsylvania,
PA, R01 MH59553, Wade Berrettini, M. D., Ph. D.; University of
California at San Francisco, CA, R01 MH60068, William Byerley, M. D.,
and Sophia Vinogradov, M. D.; University of Iowa, IA, R01MH059548,
WilliamCoryell, M. D., and Raymond Crowe, M. D.; University of Chicago,
IL, R01 MH59535, Elliot Gershon, M. D., Judith Badner, Ph. D., Francis
McMahon, M. D., Chunyu Liu, Ph. D., Alan Sanders, M. D., Maria Caserta,
Steven Dinwiddie, M. D., Tu Nguyen, Donna Harakal; University of
California at San Diego, CA, R01 MH59567, John Kelsoe, M. D., Rebecca
McKinney, B. A.; Rush University, IL, R01 MH059556, William Scheftner,
M. D., Howard M. Kravitz, D. O., M. P. H., Diana Marta, B. S., Annette
Vaughn-Brown, M. S. N., R. N., and Laurie Bederow, M. A.; NIMH
Intramural Research Program, Bethesda, M. D., 1Z01MH002810-01, Francis
J. McMahon, M. D., Layla Kassem, Psy. D., Sevilla Detera-Wadleigh, Ph.
D, Lisa Austin, Ph. D, Dennis L. Murphy, M. D.; Howard University,
William B. Lawson, M. D., Ph. D., Evarista Nwulia, M. D., and Maria
Hipolito, M. D. Control subjects from the National Institute of Mental
Health Schizophrenia Genetics Initiative (NIMH-GI), data and
biomaterials are being collected by the `` Molecular Genetics of
Schizophrenia II'' (MGS-2) collaboration. The investigators and
coinvestigators are: ENH/ Northwestern University, Evanston, IL,
MH059571, Pablo V. Gejman, M. D. (Collaboration Coordinator; PI), Alan
R. Sanders, M. D.; Emory University School of Medicine, Atlanta, GA,
MH59587, Farooq Amin, M. D. (PI); Louisiana State University Health
Sciences Center; New Orleans, Louisiana, MH067257, Nancy Buccola APRN,
BC, MSN (PI); University of California-Irvine, Irvine, CA, MH60870,
William Byerley, M. D. (PI); Washington University, St. Louis, MO, U01,
MH060879, C. Robert Cloninger, M. D. (PI); University of Iowa, Iowa, IA,
MH59566, Raymond Crowe, M. D. (PI), Donald Black, M. D.; University of
Colorado, Denver, CO, MH059565, Robert Freedman, M. D. (PI); University
of Pennsylvania, Philadelphia, PA, MH061675, Douglas Levinson M. D.
(PI); University of Queensland, Queensland, Australia, MH059588, Bryan
Mowry, M. D. (PI); Mt. Sinai School of Medicine, New York, NY, MH59586,
Jeremy Silverman, Ph. D. (PI). Genome-wideSNPgenotyping of theNIMH
samples was performed through the Genetic Association Information
Network under the direction of the Bipolar Genetics Studies
Collaboration. The Principal Investigators and Co-Investigators were:
University of California San Diego, La Jolla, CA, John R. Kelsoe, M. D.
(PI), Tiffany A. Greenwood, Ph. D., Paul D. Shilling, Ph. D., Caroline
Nievergelt, Ph. D.; Scripps Research Institute, La Jolla, CA: Nicholas
Schork, Ph. D. (PI), Erin N. Smith, Ph. D., Cinnamon Bloss, Ph. D.;
Indiana University, Bloomington, IN, John Nurnberger, M. D. (PI), Howard
J. Edenberg, Ph. D., Tatiana Foroud, Ph. D.; University of Chicago,
Chicago, IL, Elliot Gershon, M. D. (PI), Chunyu Liu, Ph. D., Judith A.
Badner, Ph. D.; Rush University Medical Center, Chicago, IL, William A.
Scheftner, M. D.; Howard University, Washington, DC, William B. Lawson,
M. D. (PI), Evaristus A. Nwulia, M. D., Maria Hipolito, M. D.;
University of Iowa, Iowa City, IA, William Coryell, M. D. (PI);
Washington University, St.; Louis, MO, John Rice, Ph D. (PI); University
of California San Francisco, San Francisco, CA, William Byerley, M. D.
(PI); National Institute of Mental Health, Bethesda, M. D., Francis
McMahon, M. D. (PI), Thomas G. Schulze, M. D.; University of
Pennsylvania, Philadelphia, PA, Wade Berrettini, M. D., Ph. D. (PI);
JohnsHopkins University, Baltimore, MD, James B. Potash, M. D. (PI),
Peter P. Zandi, Ph. D., Pamela Belmonte Mahon, Ph. D.; University of
Michigan, Ann Arbor, MI, Melvin G. McInnis, M. D. (PI), Sebastian
Zollner, Ph. D.; Translation Genomic Research Institute, Phoenix, AZ,
David Craig, Ph. D. (PI), Szabolics Szelinger. Data and biomaterials for
the subjects in the Wellcome Trust Case-Control Consortium were
collected by: University of Aberdeen, Foresterhill, Aberdeen, UK, Gerome
Breen, David St Clair; Birmingham University, Birmingham, UK, Sian
Caesar, Katherine Gordon-Smith, Lisa Jones; Cardiff University, Cardiff,
UK, Christine Fraser, Elaine K. Green, Detelina Grozeva, Marian L.
Hamshere, Peter A. Holmans, Ian R. Jones, George Kirov, Valentina
Moskvina, Ivan Nikolov, Michael C. O'Donovan, Michael J. Owen, Nick
Craddock; The Institute of Psychiatry, King's College, London, UK, David
A. Collier, Amanda Elkin, Anne Farmer, Richard Williamson, Peter
McGuffin; Royal Victoria Infirmary, Newcastle upon Tyne, UK, Allan H.
Young, I. Nicol Ferrier; Supported in part by R01 MH079799 (Smoller).
NR 42
TC 23
Z9 23
U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD APR
PY 2011
VL 156B
IS 3
BP 370
EP 378
DI 10.1002/ajmg.b.31172
PG 9
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 734KI
UT WOS:000288332600015
ER
PT J
AU Al-Agha, OM
Huwait, HF
Chow, C
Yang, W
Senz, J
Kalloger, SE
Huntsman, DG
Young, RH
Gilks, CB
AF Al-Agha, Osama M.
Huwait, Hassan F.
Chow, Christine
Yang, Winnie
Senz, Janine
Kalloger, Steve E.
Huntsman, David G.
Young, Robert H.
Gilks, C. Blake
TI FOXL2 Is a Sensitive and Specific Marker for Sex Cord-Stromal Tumors of
the Ovary
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE FOXL2; alpha-inhibin; calretinin; sex cord-stromal tumors;
immunohistochemistry
ID GRANULOSA-CELL TUMOR; INHIBIN; CALRETININ; EXPRESSION; NEOPLASMS
AB Sex cord-stromal tumors (SCSTs) of the ovary are relatively uncommon tumors. Diagnosis of SCST rests primarily on the histomorphology of these tumors, and tumors with an atypical or unconventional appearance can pose diagnostic challenges. Previously, we had identified FOXL2 (402C -> G) mutation as being characteristic of adult granulosa cell tumors (aGCTs). However, molecular screening for this mutation is not always possible and adds time and cost to the diagnostic process. In this study, we investigated the potential diagnostic use of immunostaining for FOXL2 on formalin-fixed paraffin-embedded tissue sections. Using a commercially available polyclonal antiserum against FOXL2 protein, immunoexpression of FOXL2 was tested in 501 ovarian tumor samples, including 119 SCSTs, using whole tissue sections and tissue microarrays. Staining was correlated with FOXL2 mutation status. In addition, we compared FOXL2 immunoexpression with that of alpha-inhibin and calretinin, the 2 traditional immunomarkers of SCST, in a subset of 89 SCSTs. FOXL2 immunostaining was present in 95 of 119 (80%) SCSTs, including > 95% of aGCTs, juvenile granulosa cell tumors, fibromas, and sclerosing stromal tumors. Only 50% of Sertoli-Leydig cell tumors (N = 40) expressed FOXL2. One of 11 steroid cell tumors and 3 of 3 female adnexal tumors of probable Wolffian origin showed FOXL2 immunoreactivity, whereas all other non-SCSTs tested (N = 368) were negative for FOXL2 expression. Thus, the sensitivity and specificity of FOXL2 immunoreactivity for SCST are 80% and 99%, respectively. The FOXL2 (402C -> G) mutation was confirmed to be both a sensitive and relatively specific indicator of aGCT. Forty-five of 119 SCSTs were mutation positive. These cases were 39 of 42 (93%) aGCTs, 3 of 40 Sertoli-Leydig cell tumors, 2 of 5 thecomas, and 1 of 4 (25%) SCSTs of unclassified type. SCSTs harboring a FOXL2 mutation consistently immunoexpressed FOXL2 (44 of 45, 98%), but FOXL2 immunostaining was also seen in many SCSTs that lacked a mutation (49 of 73, 67%). FOXL2 immunostaining showed higher sensitivity for the diagnosis of SCST, compared with alpha-inhibin and calretinin, and FOXL2 staining was typically more intense in positive cases compared with either alpha-inhibin or calretinin. In the SCSTs that were negative for FOXL2 expression, alpha-inhibin and/or calretinin immunostaining yielded positive results. In conclusion, FOXL2 is a relatively sensitive and highly specific marker for SCST. FOXL2 staining is present in almost all SCSTs with a FOXL2 mutation, and also in a majority of SCSTs without a mutation. FOXL2, together with alpha-inhibin and calretinin, forms an immunomarker panel that will result in positive staining with 1 or more markers in essentially all cases of SCST.
C1 [Al-Agha, Osama M.; Yang, Winnie; Senz, Janine; Kalloger, Steve E.; Huntsman, David G.; Gilks, C. Blake] Vancouver Gen Hosp, Ctr Translat & Appl Genom, Vancouver, BC, Canada.
[Al-Agha, Osama M.; Chow, Christine; Kalloger, Steve E.; Huntsman, David G.; Gilks, C. Blake] Vancouver Gen Hosp, Genet Pathol Evaluat Ctr, Vancouver, BC, Canada.
[Huwait, Hassan F.; Gilks, C. Blake] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC, Canada.
[Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Huntsman, DG (reprint author), British Columbia Canc Agcy, CTAG, 3427-600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada.
EM dhuntsma@bccancer.bc.ca
FU CIHR [200281, 102198]; sanofiaventis
FX Supported by grants from CIHR (#200281 and 102198) and an unrestricted
educational grant from sanofiaventis.
NR 24
TC 68
Z9 75
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD APR
PY 2011
VL 35
IS 4
BP 484
EP 494
DI 10.1097/PAS.0b013e31820a406c
PG 11
WC Pathology; Surgery
SC Pathology; Surgery
GA 736JT
UT WOS:000288491600003
PM 21378549
ER
PT J
AU Rege, TA
Wagner, AJ
Corless, CL
Heinrich, MC
Hornick, JL
AF Rege, Tanya A.
Wagner, Andrew J.
Corless, Christopher L.
Heinrich, Michael C.
Hornick, Jason L.
TI "Pediatric-type" Gastrointestinal Stromal Tumors in Adults: Distinctive
Histology Predicts Genotype and Clinical Behavior
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE gastrointestinal stromal tumor; KIT; PDGFRA; tyrosine kinase inhibitor;
sarcoma; soft tissue tumor
ID OF-THE-LITERATURE; TERM-FOLLOW-UP; CARNEY TRIAD; GERMLINE MUTATIONS;
PDGFRA MUTATIONS; GASTRIC TUMORS; YOUNG-ADULTS; IMATINIB; PATHOLOGY;
PARAGANGLIOMA
AB Gastrointestinal stromal tumors (GISTs) rarely affect children, mainly girls. Pediatric GISTs typically arise in the stomach as multifocal tumors with a multinodular growth pattern, epithelioid morphology, lymph node metastases, an absence of KIT and PDGFRA gene mutations, and indolent behavior. Occasional GISTs in adults show similar features. Such tumors are not widely recognized. GISTs with a multinodular growth pattern in patients over the age of 18 years were retrieved from surgical and consultation files. Hematoxylin and eosin-stained slides were reviewed, immunohistochemistry was performed, and KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12, 14, and 18) genes were screened for mutations. Clinical follow-up was obtained. Sixteen cases were identified, affecting 13 women and 3 men (median age, 31.5 y; range, 19 to 56 y), all in the stomach. The mean tumor size was 5.4 cm (range, 1.8 to 11 cm); 4 were multifocal. All tumors showed a multinodular or plexiform architecture and epithelioid (N = 3) or mixed epithelioid and spindle cell (N = 13) morphology. Five tumors had vascular invasion; 6 had focal necrosis. Mitotic activity ranged from 3 to 156/50 high-power fields (8 tumors had <= 5/50 high-power fields). Using Armed Forces Institute of Pathology risk stratification, categories for primary tumors were: none (N = 2), very low risk (N = 3), low risk (N = 3), moderate risk (N = 3), and high risk (N = 5). By immunohistochemistry, all tumors were positive for KIT, 82% DOG1, 72% CD34, 18% caldesmon, 9% S-100, 8% smooth muscle actin, and 0% desmin. All tumors were wild type for KIT and PDGFRA in the exons that were screened. At primary resection, 9 patients (56%) had lymph node metastases and 3 patients had liver metastases. Follow-up ranged from 16 months to 16 years (median, 5 y). Two tumors recurred locally in the stomach and 7 patients developed subsequent metastases to the lymph nodes N = 5), liver (N = 3), and peritoneum/omentum (N = 3). Primary tumors from 7 patients with metastases were Armed Forces Institute of Pathology low risk, very low risk, or no risk of recurrence. None of the metastatic tumors responded to treatment with imatinib mesylate. One patient died of disseminated liver and intra-abdominal metastases and the remaining patients were alive at last follow-up. Gastric GISTs in adults with a multinodular or plexiform growth pattern and epithelioid or mixed morphology are similar to pediatric GISTs. Unlike conventional adult GISTs, this distinctive subset predominantly affects women, often metastasizes to lymph nodes, and lacks mutations in KIT and PDGFRA. Current risk assessment criteria do not reliably predict behavior for this group. Although metastases are common and most tumors are imatinib resistant, they pursue a relatively indolent clinical course. Recognition of "pediatric-type" GISTs in adults is critical for prognosis, appropriate therapy, and follow-up.
C1 [Rege, Tanya A.; Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Rege, Tanya A.; Hornick, Jason L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Wagner, Andrew J.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
[Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA.
[Heinrich, Michael C.] Portland VA Med Ctr, Div Hematol & Oncol, Portland, OR USA.
[Corless, Christopher L.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
RP Hornick, JL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM jhornick@partners.org
FU Department of Veterans Affairs; Life Raft Group; GIST
FX Supported in part from a grant from the Merit Review Grant from the
Department of Veterans Affairs (MCH) and funding from the Life Raft
Group and GIST Cancer Research Fund (CLC and MCH).
NR 24
TC 58
Z9 62
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD APR
PY 2011
VL 35
IS 4
BP 495
EP 504
DI 10.1097/PAS.0b013e31820e5f7d
PG 10
WC Pathology; Surgery
SC Pathology; Surgery
GA 736JT
UT WOS:000288491600004
PM 21358303
ER
PT J
AU Chaux, A
Pfannl, R
Rodriguez, IM
Barreto, JE
Velazquez, EF
Lezcano, C
Piris, A
Netto, GJ
Cubilla, AL
AF Chaux, Alcides
Pfannl, Rolf
Rodriguez, Ingrid M.
Barreto, Jose E.
Velazquez, Elsa F.
Lezcano, Cecilia
Piris, Adriano
Netto, George J.
Cubilla, Antonio L.
TI Distinctive Immunohistochemical Profile of Penile Intraepithelial
Lesions: A Study of 74 Cases
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE penile intraepithelial neoplasia; carcinoma in situ; squamous
hyperplasia; differentiated penile intraepithelial neoplasia;
warty/basaloid penile intraepithelial neoplasia
ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS; CANCER; NEOPLASIA; VULVA;
ASSOCIATION; PREVENTION; P16(INK4A); VARIANTS; PATHWAYS
AB Several classification schemes for penile precancerous lesions have been proposed, but none of them seems to correlate with the current understanding of penile cancer pathogenesis. Recently, a system, which takes into account morphologic features and purported etiopathogenesis, was proposed, separating penile intraepithelial neoplasia (PeIN) in differentiated and warty/basaloid subtypes. This study was designed to seek an immunohistochemical profile that can be helpful in the classification and differential diagnosis of penile epithelial abnormalities and precancerous lesions using the aforementioned system. The immunohistochemical panel included stains for p16(INK4a), p53, and Ki-67. For p16(INK4a) immunostaining, only full-thickness positivity in all epithelial cells was considered as positive; for p53 and Ki-67 immunostaining, patchy or diffuse nuclear positivity above the basal layer was considered as positive. Seventy-four lesions in 59 patients were selected and classified as follows: differentiated PeIN, 34 cases; squamous hyperplasia (SH), 21 cases; basaloid PeIN, 15 cases; and warty PeIN, 4 cases. The mean age of patients was 64 years. Forty-two lesions (56.8%) were located in the glans and 32 (43.2%) in the foreskin. Overexpression of p16(INK4a) was useful for distinguishing SH from warty/basaloid PeINs (0% vs. 94.7%, P < 0.0001) but not SH from differentiated PeINs (0% vs. 5.9%, P = 0.519). In addition, p16(INK4a) allowed the distinction of differentiated and warty/basaloid PeINs (5.9% vs. 94.7%, P < 0.0001). Immunohistochemistry results for p53 allowed the separation of SH and differentiated PeIN (9.5% vs. 44.1%, P = 0.0078) and SH and warty/basaloid PeIN (9.5% vs. 55.6%, P = 0.0042). Ki-67 immunostain was useful for distinguishing SH from differentiated PeIN (52.6% vs. 89.7%, P = 0.0062) and SH from PeIN with warty and/or basaloid features (52.6% vs. 100%, P = 0.0011). There seems to be a distinctive immunohistochemical profile for associated and precursor epithelial lesions of the penis. SH was p16(INK4a) and p53 negative, with variable Ki-67 positivity. Differentiated PeIN was p16(INK4a) negative and Ki-67 positive, with variable p53 positivity. Basaloid and warty PeINs were consistently p16(INK4a) and Ki-67 positive, with variable p53 positivity. The use of a triple p16(INK4a)/p53/Ki-67 immunohistochemical panel was found to be helpful in the classification, differential diagnosis, and morphologic standardization of penile intraepithelial lesions.
C1 [Chaux, Alcides; Rodriguez, Ingrid M.; Barreto, Jose E.; Lezcano, Cecilia; Cubilla, Antonio L.] Inst Patol & Invest, Asuncion, Paraguay.
[Chaux, Alcides; Netto, George J.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Pfannl, Rolf] Tufts Med Ctr, Boston, MA USA.
[Lezcano, Cecilia; Piris, Adriano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Velazquez, Elsa F.] Caris Life Sci, Caris Dx Div, Newton, MA USA.
RP Cubilla, AL (reprint author), Inst Patol & Invest, Martin Brizuela 325, Asuncion, Paraguay.
EM acubilla@institutodepatologia.com.py
OI Chaux, Alcides/0000-0002-5824-9867
FU Johns Hopkins Medicine Patana Fund for Research
FX Supported in part by The Johns Hopkins Medicine Patana Fund for
Research.
NR 26
TC 20
Z9 20
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD APR
PY 2011
VL 35
IS 4
BP 553
EP 562
DI 10.1097/PAS.0b013e3182113402
PG 10
WC Pathology; Surgery
SC Pathology; Surgery
GA 736JT
UT WOS:000288491600011
PM 21399489
ER
PT J
AU Wang, JH
Wu, Q
Yang, P
Li, H
Li, J
Mountz, JD
Hsu, HC
AF Wang, John H.
Wu, Qi
Yang, PingAr
Li, Hao
Li, Jun
Mountz, John D.
Hsu, Hui-Chen
TI Type I Interferon-Dependent CD86(high) Marginal Zone Precursor B Cells
Are Potent T Cell Costimulators in Mice
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLASMACYTOID DENDRITIC CELLS; PATHOGENIC
AUTOANTIBODIES; DISEASE-ACTIVITY; LYMPH-NODES; BXD2 MICE; BLOOD;
ACTIVATION; EXPRESSION; RECEPTOR
AB Objective. To investigate the role of CD86(high) marginal zone (MZ) precursor B cells in type I interferon (IFN)-induced T cell-dependent responses in autoimmune BXD2 mice.
Methods. Confocal microscopic imaging was used to determine the location of plasmacytoid dendritic cells (DCs), MZ precursor B cells, and CD4 T cells in the spleens of BXD2 and BXD2-Ifnar(-/-) mice. Immunohistochemical staining was used to determine IgG(bright) cells in the spleens of BXD2 and BXD2-Ifnar(-/-) mice. Enzyme-linked immunosorbent assay was used to determine serum levels of IFN alpha and autoantibodies, and 4-hydroxy-3-nitrophenylacetyl hapten (NP)-chicken gamma-globulin (CGG) (NP-CGG)-or NP-Ficoll-induced anti-NP2 antibody titers. Real-time quantitative polymerase chain reaction was used to determine the levels of type I IFN transcripts. T cell proliferation was measured using H-3-thymidine. The expression of CD86 and CD80 was determined by fluorescence-activated cell sorting analysis.
Results. The deletion of type I IFN receptor abrogated the development of IgGbright cells and sup-pressed a T cell-dependent antibody response. Type I IFN signaling was associated with the expression of CD86, but not CD80, on follicular, MZ, and MZ precursor B cells. However, MZ precursor B cells demonstrated the highest expression of CD86 and the highest capacity for T cell costimulation with intact type I IFN receptor. This effect was blocked by an antibody that neutralizes CD86. In IFN receptor-intact BXD2 mouse spleens, MZ precursor B cells clustered at the T cell-B cell border. CD86 deletion suppressed germinal center formation, autoantibody production, and development of autoimmune diseases in BXD2 mice.
Conclusion. Type I IFN can promote autoimmune responses in BXD2 mice through up-regulation of CD86(high) expression on MZ precursor B cells and trafficking of MZ precursor B cells to the T cell-B cell border to provide costimulation of CD4 T cells.
C1 [Hsu, Hui-Chen] Univ Alabama, Div Clin Immunol & Rheumatol, Dept Med, Birmingham, AL 35294 USA.
[Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA.
RP Hsu, HC (reprint author), Univ Alabama, Div Clin Immunol & Rheumatol, Dept Med, 1825 Univ Blvd,SHELB 311, Birmingham, AL 35294 USA.
EM rheu078@uab.edu
RI Li, Hao/N-7406-2015
OI Li, Hao/0000-0002-2171-8826
FU American College of Rheumatology Research and Education Foundation;
Alliance for Lupus Research; Department of Veterans Affairs
[1I01BX000600-01]; Daiichi-Sankyo Co., Ltd; NIH [1-AI-071110-01A1,
ARRA-3-R01-AI-71110-02S1, P30-AR-48311]; Lupus Research Institute;
Arthritis Foundation
FX Supported by grants to Dr. Mountz from the American College of
Rheumatology Research and Education Foundation (Within Our Reach
research grant), the Alliance for Lupus Research (Target Identification
in Lupus program grant), the Department of Veterans Affairs (Merit
Review grant 1I01BX000600-01), Daiichi-Sankyo Co., Ltd, and the NIH
(grants 1-AI-071110-01A1, ARRA-3-R01-AI-71110-02S1, and P30-AR-48311)
and by grants to Dr. Hsu from the Lupus Research Institute (Novel
Research project grant) and the Arthritis Foundation (Arthritis
Investigator Award).
NR 32
TC 10
Z9 10
U1 1
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD APR
PY 2011
VL 63
IS 4
BP 1054
EP 1064
DI 10.1002/art.30231
PG 11
WC Rheumatology
SC Rheumatology
GA 748VO
UT WOS:000289421100024
PM 21225691
ER
PT J
AU Boserup, MW
Lichota, J
Haile, D
Moos, T
AF Boserup, Michael W.
Lichota, Jacek
Haile, David
Moos, Torben
TI Heterogenous distribution of ferroportin-containing neurons in mouse
brain
SO BIOMETALS
LA English
DT Article
DE Blood-brain barrier; Iron; Neurodegeneration; Oxidative stress; qPCR;
Transferrin
ID DIVALENT METAL TRANSPORTER-1; CENTRAL-NERVOUS-SYSTEM; TRANSFERRIN
RECEPTOR; IRON-METABOLISM; RAT; EXPRESSION; CELLS; CERULOPLASMIN;
PROTEINS; FERRITIN
AB Iron is crucial for a variety of cellular functions in neuronal cells. Neuronal iron uptake is reflected in a robust and consistent expression of transferrin receptors and divalent metal transporter 1 (DMT 1). Conversely, the mechanisms by which neurons neutralize and possibly excrete iron are less clear. Studies indicate that neurons express ferroportin which could reflect a mechanism for iron export. We mapped the distribution of ferroportin in the adult mouse brain using an antibody prepared from a peptide representing amino acid sequences 223-303 of mouse ferroportin. The antibody specifically detected ferroportin in brain homogenates, whereas homogenates of cultured endothelial cells were devoid of immunoreactivity. In brain sections, ferroportin was confined to neuronal cell bodies and peripheral processes of cerebral cortex, hippocampus, thalamus, brain stem, and cerebellum. In brain stem ferroportin-labeling was particularly high in neurons of cranial nerve nuclei and reticular formation. Ferroportin was hardly detectable in striatum, pallidum, or hypothalamus. Among non-neuronal cells, ferroportin was detected in oligodendrocytes and choroid plexus epithelial cells. A comparison with previous studies on the distribution of transferrin receptors in neurons shows that many neuronal pools coincide with those expressing ferroportin. The data therefore indicate that neuronal iron homeostasis consists of a delicate balance between transferrin receptor-mediated uptake of iron-transferrin and ferroportin-related iron excretion. The findings also suggest a particular high turnover of iron in neuronal regions, such as habenula, hippocampus, reticular formation and cerebellum, as several neurons in these regions exhibit a prominent co-expression of transferrin receptors and ferroportin.
C1 [Boserup, Michael W.; Lichota, Jacek; Moos, Torben] Univ Aalborg, Dept Hlth Sci & Technol, Neurobiol Sect, DK-9220 Aalborg, Denmark.
[Haile, David] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Moos, T (reprint author), Univ Aalborg, Dept Hlth Sci & Technol, Neurobiol Sect, Fr Bajers Vej 3B,1-216, DK-9220 Aalborg, Denmark.
EM tmoos@hst.aau.dk
OI Moos, Torben/0000-0001-9989-0207
FU Lundbeck Fund; Danish Parkinson's Disease Fund; Carlsberg Foundation;
Spar Nord Fund; Obelske Familiefond
FX We would like to thank Susan Peters at University of Copenhagen, Denmark
and Merete Fredsgaard, Aalborg University, Denmark for excellent
technical assistance. Murine brain endothelioma cells, bEnd3, were
kindly obtained from Dr. Sara Gosk, University of Bonn, Germany. This
work was supported by grants from the Lundbeck Fund, the Danish
Parkinson's Disease Fund, the Carlsberg Foundation, the Spar Nord Fund,
and the Obelske Familiefond.
NR 42
TC 13
Z9 15
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0966-0844
J9 BIOMETALS
JI Biometals
PD APR
PY 2011
VL 24
IS 2
BP 357
EP 375
DI 10.1007/s10534-010-9405-2
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 735BF
UT WOS:000288387700015
PM 21213119
ER
PT J
AU Lauenstein, HD
Quarcoo, D
Plappert, L
Schleh, C
Nassimi, M
Pilzner, C
Rochlitzer, S
Brabet, P
Welte, T
Hoymann, HG
Krug, N
Muller, M
Lerner, EA
Braun, A
Groneberg, DA
AF Lauenstein, H. D.
Quarcoo, D.
Plappert, L.
Schleh, C.
Nassimi, M.
Pilzner, C.
Rochlitzer, S.
Brabet, P.
Welte, T.
Hoymann, H. G.
Krug, N.
Mueller, M.
Lerner, E. A.
Braun, A.
Groneberg, D. A.
TI Pituitary adenylate cyclase-activating peptide receptor 1 mediates
anti-inflammatory effects in allergic airway inflammation in mice
SO CLINICAL AND EXPERIMENTAL ALLERGY
LA English
DT Article
DE airway inflammation; allergy; asthma; mouse model; neuropeptides; PACAP;
VIP
ID VASOACTIVE-INTESTINAL-PEPTIDE; DENDRITIC CELL EXPRESSION; LATE ASTHMATIC
RESPONSE; LUTZOMYIA-LONGIPALPIS; RESPIRATORY-TRACT; POLYPEPTIDE PACAP;
FERRET TRACHEA; SEPTIC SHOCK; MURINE MODEL; T-CELLS
AB P>Background
Bronchial asthma is characterized by airway inflammation and reversible obstruction. Since the gold standard of therapy, a combination of anti-inflammatory corticosteroids and bronchodilatory beta(2) agonists, has recently been discussed to be related to an increased mortality, there is a need for novel therapeutic pathways.
Objective
A new experimental concept that encompasses the vasoactive intestinal peptide/pituitary adenylate cyclase activating peptide (PACAP) family of receptors by demonstrating the anti-inflammatory effects of the PACAP receptor 1 (PAC1R) in a murine model of allergic asthma is described.
Methods
PAC1R expression was investigated in lung tissue and isolated dendritic cells (DCs) via real-time PCR. Ovalbumin (OVA)-induced asthma models were used in PAC1R-deficient mice and BALB/c mice treated with PAC1R agonist maxadilan (MAX). Bronchoalveolar lavages have been performed and investigated at the cellular and cytokine levels. Fluorescence staining of a frozen lung section has been performed to detect eosinophil granulocytes in lung tissue. Plasma IgE levels have been quantified via the ELISA technique. Lung function was determined using head-out body plethysmography or whole-body plethysmography.
Results
Increased PAC1R mRNA expression in lung tissue was present under inflammatory conditions. PAC1R expression was detected on DCs. In OVA-induced asthma models, which were applied to PAC1R-deficient mice (PAC1R-/-) and to BALB/c mice treated with the specific PAC1R agonist MAX, PAC1R deficiency resulted in inflammatory effects, while agonistic stimulation resulted in anti-inflammatory effects. No effects on lung function were detected both in the gene-depletion and in the pharmacologic studies. In summary, here, we demonstrate that anti-inflammatory effects can be achieved via PAC1R.
Conclusion
PAC1R agonists may represent a promising target for an anti-inflammatory therapy in airway diseases such as bronchial asthma.
C1 [Lauenstein, H. D.; Plappert, L.; Schleh, C.; Nassimi, M.; Pilzner, C.; Rochlitzer, S.; Hoymann, H. G.; Krug, N.; Mueller, M.; Braun, A.] Fraunhofer Inst Toxicol & Expt Med, Dept Immunol Allergol & Immuntoxikol, D-30625 Hannover, Germany.
[Lauenstein, H. D.; Plappert, L.; Pilzner, C.; Welte, T.; Groneberg, D. A.] Hannover Med Sch, Clin Pneumol, D-3000 Hannover, Germany.
[Quarcoo, D.; Groneberg, D. A.] Free Univ Berlin, Inst Occupat Med, Charite Univ Med Berlin, D-1000 Berlin, Germany.
[Quarcoo, D.; Groneberg, D. A.] Humboldt Univ, Berlin, Germany.
[Brabet, P.] INSERM, Inst Neurosci Montpellier, Montpellier, France.
[Lerner, E. A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA.
RP Braun, A (reprint author), Fraunhofer Inst Toxicol & Expt Med, Dept Immunol Allergol & Immuntoxikol, Nikolai Fuchs Str 1, D-30625 Hannover, Germany.
EM armin.braun@item.fraunhofer.de
RI Braun, Armin /B-8750-2009;
OI Braun, Armin /0000-0002-1142-1463; Groneberg, David/0000-0001-8551-6556
FU Deutsche Forschungsgemeinschaft [DFG Br 2126/2-2, SFB 587, B4, B13]
FX Funded by Deutsche Forschungsgemeinschaft (DFG Br 2126/2-2, SFB 587
'Immune reactions of the lung in infection and allergy', projects B4 and
B13).
NR 57
TC 11
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0954-7894
J9 CLIN EXP ALLERGY
JI Clin. Exp. Allergy
PD APR
PY 2011
VL 41
IS 4
BP 592
EP 601
DI 10.1111/j.1365-2222.2010.03636.x
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA 735BA
UT WOS:000288387200018
PM 21059121
ER
PT J
AU Colwell, AS
Craft, RO
AF Colwell, Amy S.
Craft, Randall O.
TI Near-Infrared Spectroscopy in Autologous Breast Reconstruction
SO CLINICS IN PLASTIC SURGERY
LA English
DT Article
DE Near-infrared spectroscopy; Autologous reconstruction; Breast cancer;
Free flap monitoring
ID FREE FLAPS; OXYGEN-SATURATION; PERFUSION; CANCER; RESUSCITATION;
TRANSFERS; HEAD
AB Autologous breast reconstruction is commonly performed after mastectomy and provides a natural replacement that mimics the native breast. Although current free flap success rates exceed 95%, total flap loss can be devastating for patients. As a result, new technologies have emerged to provide an objective means for flap monitoring, with the hope that vaso-occlusive events can be detected before the clinical manifestation of a microvascular complication and the no-reflow phenomenon. This article focuses on the available data for one new technology, near-infrared spectroscopy, and its current use in clinical practice.
C1 [Colwell, Amy S.] Harvard Univ, Div Plast Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Colwell, AS (reprint author), Harvard Univ, Div Plast Surg, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC 435, Boston, MA 02114 USA.
EM acolwell@partners.org
NR 26
TC 3
Z9 4
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0094-1298
J9 CLIN PLAST SURG
JI Clin. Plast. Surg.
PD APR
PY 2011
VL 38
IS 2
BP 301
EP +
DI 10.1016/j.cps.2011.03.014
PG 8
WC Surgery
SC Surgery
GA 780YI
UT WOS:000291896900013
PM 21620154
ER
PT J
AU Mattingly, G
Surman, CB
Mao, AR
Eagan, CA
Onofrey, M
Lerner, M
AF Mattingly, Greg
Surman, Craig B.
Mao, Alice R.
Eagan, Corey A.
Onofrey, Meaghan
Lerner, Marc
TI Improving Communication in ADHD Care: Results from In-office Linguistic
Research
SO CNS SPECTRUMS
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CLINICAL-PRACTICE GUIDELINE;
CHILD; DIAGNOSIS; DOCTORS; TEAM
AB Introduction: An in-office linguistic study was conducted to help improve understanding of how to better evaluate and treat attention-deficit/hyperactivity disorder (ADHD).
Methods: Naturally occurring interactions were recorded among 7 psychiatrists and 23 patients and 8 pediatricians along with 22 patients and their parents. Participants were interviewed separately post-visit. Transcripts of interactions and interviews were analyzed using sociolinguistic techniques.
Results: Visits were variable in length and lacked concrete treatment plans. In the pediatricsetting, children were typically excluded from dialogues, accounting for only 8% of words spoken. School was the primary metric used to evaluate symptoms. Pediatricians allayed parents' concerns about stimulant therapy by promising to prescribe the lowest possible dose, rather than discussing titrating to an optimal dose. Adults were evaluated idiosyncratically without the use of scales or tools. Stimulants were positioned as short-term "trials" without strong physician recommendations.
Discussion: Conversations about stimulant therapy lacked goal- and expectation-setting. Also missing from conversations was a definitive treatment plan based on the core symptoms of ADHD. Incorporating open-ended questions and tools or rating scales may result in a more effective and efficient in-office dialogue.
Conclusion: Further research is warranted to assess the efficacy of communication strategies to enhance in-office discussions of ADHD and stimulant therapy.
C1 [Eagan, Corey A.; Onofrey, Meaghan] Ogilvy CommonHlth Insights & Analyt, Parsippany, NJ 07054 USA.
[Mattingly, Greg] St Charles Psychiat Associates, St Charles, MO USA.
[Surman, Craig B.] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & Adul, Adult ADHD Res Program, Boston, MA 02114 USA.
[Surman, Craig B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Mao, Alice R.] Baylor Coll Med, Houston, TX 77030 USA.
[Lerner, Marc] Univ Calif Irvine, Sch Med, Dept Pediat, Irvine, CA 92717 USA.
RP Eagan, CA (reprint author), Ogilvy CommonHlth Insights & Analyt, 440 Interpace Pkwy, Parsippany, NJ 07054 USA.
EM corey.eagan@ogilvy.com
FU AstraZeneca; Dainnpon-Sumitomo; Eli Lilly; Forest Laboratories;
GlaxoSmithKline; Janssen; Johnson Johnson; Lundbeck; McNeil; Merck; New
River; Novartis; Organon; Pfizer; sanofi-aventis; Schwabe/Ingenix;
Sepracor; Shire; Solvay; Takeda; Vanda; Wyeth; Janssen-Ortho; Abbott;
Alza; Cephalon; Hilda and Preston Davis Foundation; National Institutes
of Health; Addrenex; NIMH; Next Wave; Psychgenics; Quintile; Shionogi;
McNeil Pediatrics
FX Dr. Mattingly has been a consultant for Eli Lilly, Forest Laboratories,
McNeil, Pfizer, Shire, and Vanda; has been on speakers' bureaus for
Abbott, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen,
McNeil, and Shire; and receives research support from AstraZeneca,
Dainnpon-Sumitomo, Eli Lilly, Forest Laboratories, GlaxoSmithKline,
Janssen, Johnson & Johnson, Lundbeck, McNeil, Merck, New River,
Novartis, Organon, Pfizer, sanofi-aventis, Schwabe/Ingenix, Sepracor,
Shire, Solvay, Takeda, Vanda, and Wyeth. Dr. Surman has been a
consultant/advisor to McNeil, Shire, and Takeda; has received support
for speaking and other educational activities from Janssen-Ortho,
McNeil, Novartis, and Shire; has received research support from Abbott,
Alza, Cephalon, Eli Lilly, the Hilda and Preston Davis Foundation,
McNeil, Merck, New River, the National Institutes of Health, Organon,
Pfizer, Shire, and Takeda; and has received honoraria from Reed Medical
Education (a logistics collaborator for the MGH Psychiatry Academy). Dr.
Mao has received honoraria for being on the speaker bureaus for
Bristol-Myers Squibb, Eli Lilly, Novartis, Pfizer, and Shire. Dr. Lerner
is a consultant to McNeil and Shire; is on the speakers' bureaus for Eli
Lilly, McNeil, and Shire; and receives research support from Addrenex,
Eli Lilly, McNeil, the NIMH, Next Wave, Psychgenics, Quintile, Shionogi,
and Shire. Ms. Onofrey has received research support from McNeil
Pediatrics. Ms. Eagan reports no affiliations with or financial interest
in any organization that may pose a conflict of interest.
NR 31
TC 1
Z9 1
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1092-8529
J9 CNS SPECTRUMS
JI CNS Spectr.
PD APR
PY 2011
VL 16
IS 4
BP 85
EP 94
DI 10.1017/S1092852912000235
PG 10
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 951KD
UT WOS:000304718500001
PM 24725370
ER
PT J
AU Chen, KT
Malo, MS
Beasley-Topliffe, LK
Poelstra, K
Millan, JL
Mostafa, G
Alam, SN
Ramasamy, S
Warren, HS
Hohmann, EL
Hodin, RA
AF Chen, Kathryn T.
Malo, Madhu S.
Beasley-Topliffe, Laura Kline
Poelstra, Klaas
Millan, Jose Luis
Mostafa, Golam
Alam, Sayeda N.
Ramasamy, Sundaram
Warren, H. Shaw
Hohmann, Elizabeth L.
Hodin, Richard A.
TI A Role for Intestinal Alkaline Phosphatase in the Maintenance of Local
Gut Immunity
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Mucosal gut defense factor; Lipopolysaccharide; Tolerance; TLR4
ID SALMONELLA-TYPHIMURIUM LIPOPOLYSACCHARIDES; MAJOR HISTOCOMPATIBILITY
COMPLEX; MONOPHOSPHORYL LIPID-A; ALCOHOLIC LIVER-INJURY; ENDOTOXIN
TOLERANCE; KUPFFER CELLS; INTRAPERITONEAL INJECTION; ESCHERICHIA-COLI;
T-CELLS; CLASS-I
AB Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor known to dephosphorylate lipopolysaccharide (LPS); however, the role of IAP in the gut response to luminal bacteria remains poorly defined. We investigated immune responses of wild-type (WT) and IAP-knockout (IAP-KO) mice to LPS and Salmonella typhimurium challenges.
Cryostat sectioning and standard indirect immunohistochemical staining for major histocompatibility complex (MHC) class II molecules were performed on liver tissue from WT and IAP-KO mice. WT and IAP-KO mice were orally gavaged with S. typhimurium; bacterial translocation to mesenteric nodes, liver, and spleen was determined by tissue homogenization and plating. In other experiments, WT and IAP-KO mice received intraperitoneal injections of LPS, with subsequent quantification of complete blood counts and serum interleukin (IL)-6 by enzyme-linked immunosorbent assay (ELISA). WT and IAP-KO whole blood were plated and stimulated with LPS and Pam-3-Cys, followed by cytokine assays.
Immunohistologic liver examinations showed increased expression of MHC class II molecules in IAP-KO mice. Following S. typhimurium challenge, WT mice appeared moribund compared with IAP-KO mice, with increased bacterial translocation. WT mice had > 50% decrease (P < .005) in platelets and 1.8-fold (P < .05) increased serum IL-6 compared with IAP-KO mice in response to LPS injections. IAP-KO whole-blood stimulation with LPS and Pam-3-Cys resulted in increased IL-6 and tumor necrosis factor (TNF)-alpha secretion compared with WT.
IAP-KO mice exhibit characteristics consistent with local LPS tolerance. Whole-blood response of IAP-KO mice did not reflect systemic tolerance. These data suggest that IAP is a local immunomodulating factor, perhaps regulating LPS-toll-like receptor 4 (TLR4) interaction between commensal microflora and intestinal epithelium.
C1 [Chen, Kathryn T.; Malo, Madhu S.; Mostafa, Golam; Ramasamy, Sundaram; Hodin, Richard A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Chen, Kathryn T.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA.
[Poelstra, Klaas] Univ Groningen, Dept Pharmacokinet Toxicol & Targeting, Groningen, Netherlands.
[Millan, Jose Luis] Burnham Inst Med Res, Sanford Childrens Hlth Res Ctr, La Jolla, CA 92037 USA.
[Beasley-Topliffe, Laura Kline; Warren, H. Shaw; Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Hodin, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
EM kathryn.chen@gmail.com; mmalo@partners.org; lbeasleytopliffe@gmail.com;
k.poelstra@rug.nl; millan@burnham.org; gmostafa@partners.org;
snalam@partners.org; ramasamy.sundaram@mgh.harvard.edu;
warren@helix.mgh.harvard.edu; ehohmann@partners.org; rhodin@partners.org
FU National Institutes of Health [R01DK050623, R01DK047186, T32DK007754]
FX Grant support: (1) National Institutes of Health Grant R01DK050623; (2)
National Institutes of Health Grant R01DK047186; (3) National Institutes
of Health Grant T32DK007754.
NR 44
TC 40
Z9 43
U1 1
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD APR
PY 2011
VL 56
IS 4
BP 1020
EP 1027
DI 10.1007/s10620-010-1396-x
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 736RR
UT WOS:000288512300012
PM 20844955
ER
PT J
AU Sonnenberg, A
AF Sonnenberg, Amnon
TI Time Trends of Mortality from Gastric Cancer in Europe
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Birth-cohorts; Duodenal ulcer; Epidemiology; Gastric cancer; Gastric
ulcer; Helicobacter pylori; Mortality; Time trends
ID PEPTIC-ULCER; HELICOBACTER-PYLORI; CENTURIES; DISEASE
AB The time trends of gastric and duodenal ulcer disease are shaped by a birth-cohort phenomenon.
The aim of this study was to assess the extent by which a birth-cohort phenomenon also affected the long-term time trends of gastric cancer among different European countries.
Mortality data from France, Germany, Netherlands, Scotland, Spain, and Sweden of the past 56-85 years were analyzed. The age-specific death rates were plotted against the period of death as period-age contours and against the period of birth as cohort-age contours.
The long-term time trends of gastric cancer mortality were found to have risen among generations born during the 18th century until the mid-19th century and then to have declined in all subsequent generations. The rise and fall of gastric cancer preceded similar birth-cohort patterns of gastric and duodenal ulcer by about 10-30 years. With the exception of gastric cancer in Germany, similar birth-cohort phenomena were found in all countries, as well as in men and women.
The time trends of mortality from gastric cancer and peptic are shaped by birth-cohort patterns that have affected all countries of Europe. It remains an enigma why mortality associated with gastric cancer and peptic ulcer suddenly started to rise within a short time period during the 19th century.
C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM sonnenbe@ohsu.edu
NR 21
TC 12
Z9 13
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD APR
PY 2011
VL 56
IS 4
BP 1112
EP 1118
DI 10.1007/s10620-010-1553-2
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 736RR
UT WOS:000288512300023
PM 21234687
ER
PT J
AU Yasuhara, SE
AF Yasuhara, S. E.
TI EXPLORING THE ROLE OF PHOSPHODIESTERASE PDE5 INHIBITION IN THE TREATMENT
OF MUSCULAR DYSTROPHY
SO DRUGS OF THE FUTURE
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; VASCULAR SMOOTH-MUSCLE; PROTEIN-KINASE-G;
SARCOGLYCAN-SARCOSPAN COMPLEX; DEFICIENT SKELETAL-MUSCLE; MDX MOUSE;
PULMONARY-HYPERTENSION; CHRONIC HEPATITIS; CREATINE-KINASE; CYCLIC-GMP
AB Duchenne muscular dystrophy (DMD) is caused by a mutation of a single gene, dystrophin, and is characterized by a slow progression and the increased turnover of myofiber degeneration and regeneration. Despite the long history of scientific research, the full mechanisms of muscle damage still need to be clarified and the therapeutic choices are limited. Recent studies on blood flow regulation have led to the discovery of a novel pharmacological treatment for muscular dystrophies. Phosphodiesterase PDE5 inhibitors were originally designed to improve blood circulation by inducing vasodilation in target organs and are widely used to treat male erectile dysfunction. Recently, the range of potential clinical applications for PDE5 inhibitors has widened, with increasing reports of their efficacy against various conditions, including pulmonary hypertension. The potential efficacy against DMD was reported in animal studies using the murine equivalent model. In this review, I discuss the recent understanding of the role of blood flow regulation in the pathogenesis of muscular dystrophy. Therapeutic approaches with PDE5 inhibitors will be discussed and include citations from the recent publications with animal studies. Future considerations of PDE5 inhibitor therapies will be examined, including the evaluation of drug efficacy and potential side effects.
C1 Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Shriners Hosp,Sch Med, Boston, MA 02114 USA.
RP Yasuhara, SE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Shriners Hosp,Sch Med, 51 Blossom St, Boston, MA 02114 USA.
EM Shingo_yasuhara@yahoo.com
RI Perez , Claudio Alejandro/F-8310-2010
OI Perez , Claudio Alejandro/0000-0001-9688-184X
NR 170
TC 2
Z9 2
U1 0
U2 1
PU PROUS SCIENCE, SA-THOMSON REUTERS
PI BARCELONA
PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN
SN 0377-8282
J9 DRUG FUTURE
JI Drug Future
PD APR
PY 2011
VL 36
IS 4
BP 321
EP 339
DI 10.1358/dof.2011.36.4.1579114
PG 19
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 782OT
UT WOS:000292019700006
ER
PT J
AU LaPlante, JM
Falardeau, JL
Brown, EM
Slaugenhaupt, SA
Vassilev, PM
AF LaPlante, Janice M.
Falardeau, John L.
Brown, Edward M.
Slaugenhaupt, Susan A.
Vassilev, Peter M.
TI The cation channel mucolipin-1 is a bifunctional protein that
facilitates membrane remodeling via its serine lipase domain
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Membrane remodeling; Phospholipase; TRPML1; Mucolipin; Mucolipidosis IV;
Tubulo-vesicular
ID IV CULTURED FIBROBLASTS; PHOSPHOLIPASE A(2); CA2+-INDEPENDENT FUSION;
LYSOPHOSPHATIDIC ACID; LYSOSOMAL EXOCYTOSIS; GIANT LIPOSOMES; ENDOSOME
FUSION; IN-VITRO; CELLS; IDENTIFICATION
AB Phospholipase modulators have been shown to affect the topology of lipid bilayers and the formation of tubulo-vesicular structures, but the specific endogenous phospholipases involved have yet to be identified. Here we show that TRPML1 (MLN1), a Ca2+-permeable channel, contributes to membrane remodeling through a serine lipase consensus domain, and thus represents a novel type of bifunctional protein. Remarkably, this serine lipase active site determines the ability of MLN1 to generate tubulo-vesicular extensions in mucolipin-1-expressing oocytes, human fibroblasts and model membrane vesicles. Our demonstration that MLN1 is involved in membrane remodeling and the formation of extensions suggests that it may play a role in the formation of cellular processes linked to the late endosome/lysosome (LE/L) pathway. MLN1 is absent or mutated in patients with mucolipidosis IV (MLIV), a lysosomal disorder with devastating neurological and other consequences. This study provides potential insight into the pathophysiology of MLIV. (C) 2011 Elsevier Inc. All rights reserved.
C1 [LaPlante, Janice M.; Brown, Edward M.; Vassilev, Peter M.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[LaPlante, Janice M.; Brown, Edward M.; Vassilev, Peter M.] Brigham & Womens Hosp, Membrane Biol Program, Dept Med, Boston, MA 02115 USA.
[LaPlante, Janice M.; Falardeau, John L.; Brown, Edward M.; Slaugenhaupt, Susan A.; Vassilev, Peter M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Falardeau, John L.; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02115 USA.
RP LaPlante, JM (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 75 Francis St, Boston, MA 02115 USA.
EM jlaplante@rics.bwh.harvard.edu
FU ML4 Foundation; National Institute of Neurological Disorders and Stroke
[NS39995]; NIH; PKDF; Genzyme; NARSAD; Stanley Foundation
FX The authors wish to kindly thank Dr. James Gusella for his helpful
discussions during the preparation of this manuscript. This study was
supported by the ML4 Foundation (J.M.L.), the National Institute of
Neurological Disorders and Stroke NS39995 (S.A.S.), NIH, PKDF, Genzyme,
NARSAD and Stanley Foundation (P.M.V.).
NR 56
TC 8
Z9 8
U1 1
U2 5
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD APR 1
PY 2011
VL 317
IS 6
BP 691
EP 705
DI 10.1016/j.yexcr.2011.01.008
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 736VE
UT WOS:000288522300001
PM 21256127
ER
PT J
AU Arena, R
Guazzi, M
Myers, J
Grinnen, D
Forman, DE
Lavie, CJ
AF Arena, Ross
Guazzi, Marco
Myers, Jonathan
Grinnen, Daniel
Forman, Daniel E.
Lavie, Carl J.
TI Cardiopulmonary exercise testing in the assessment of pulmonary
hypertension
SO EXPERT REVIEW OF RESPIRATORY MEDICINE
LA English
DT Review
DE aerobic capacity; carbon dioxide production; diagnosis; minute
ventilation; prognosis; pulmonary vasculopathy; ventilatory efficiency
ID CHRONIC HEART-FAILURE; TIDAL CARBON-DIOXIDE; 6-MINUTE WALK TEST;
ARTERIAL-HYPERTENSION; VENTILATORY EFFICIENCY; GAS-EXCHANGE;
HYPERTROPHIC CARDIOMYOPATHY; SCIENTIFIC STATEMENT; SYSTEMIC-SCLEROSIS;
VASCULAR-DISEASE
AB The assessment of patients with suspected or confirmed pulmonary arterial hypertension (PAH) and secondary pulmonary hypertension (PH) continues to evolve and, in recent years, evidence demonstrating that cardiopulmonary exercise testing (CPX) provides valuable information has grown at an impressive rate. The key premise supporting the use of CPX is that certain variables obtained provide insight into the degree of ventilation/perfusion mismatching secondary to altered pulmonary hemodynamics. In this article, we discuss the pathophysiology of PAH and secondary PH and its impact on cardiac function, review the clinical presentation of patients with elevated pulmonary pressures and outline a case for the use of CPX as an integral assessment technique, discuss CPX technology and testing procedures, and review the current state of available evidence and provide clinical recommendations for CPX in the setting of known or suspected PAH and secondary PH.
C1 [Arena, Ross; Grinnen, Daniel] Virginia Commonwealth Univ, Richmond, VA 23220 USA.
[Guazzi, Marco] Univ Milan, San Paolo Hosp, Cardiopulm Lab, Div Cardiol, Milan, Italy.
[Myers, Jonathan; Forman, Daniel E.] VA Palo Alto Hlth Care Syst, Div Cardiovasc, Palo Alto, CA USA.
[Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Forman, Daniel E.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Lavie, Carl J.] Univ Queensland, Sch Med, Ochsner Clin Sch, John Ochsner Heart & Vasc Inst,Dept Cardiovasc Di, New Orleans, LA USA.
RP Arena, R (reprint author), Virginia Commonwealth Univ, Richmond, VA 23220 USA.
EM rarena70@gmail.com
RI Arena, Ross/A-3141-2008; Lavie, Carl/A-6014-2011; Guazzi,
Marco/J-3165-2016
OI Arena, Ross/0000-0002-6675-1996; Guazzi, Marco/0000-0002-8456-609X
NR 88
TC 19
Z9 19
U1 0
U2 5
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1747-6348
EI 1747-6356
J9 EXPERT REV RESP MED
JI Expert Rev. Respir. Med.
PD APR
PY 2011
VL 5
IS 2
BP 281
EP 293
DI 10.1586/ERS.11.4
PG 13
WC Respiratory System
SC Respiratory System
GA 056RE
UT WOS:000312508000021
PM 21510737
ER
PT J
AU Aronis, KN
Fiorenza, CG
Chamberland, JP
Mantzoros, CS
AF Aronis, Konstantinos N.
Fiorenza, Christina G.
Chamberland, John P.
Mantzoros, Christos S.
TI Leptin administered in physiologic or pharmacologic doses does not
regulate circulating angiogenesis factors in humans
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Aronis, Konstantinos N.; Fiorenza, Christina G.; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Mantzoros, Christos S.] Boston VA Healthcare Syst, Sect Endocrinol, Boston, MA USA.
RI Aronis, Konstantinos/F-3586-2012; Aronis, Konstantinos/J-6582-2014
OI Aronis, Konstantinos/0000-0001-7189-8434;
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708401216
ER
PT J
AU Beard, RS
Henry, JN
Price, TO
Ercal, N
Banks, WA
Bearden, SE
AF Beard, Richard Scott
Henry, Jamie N.
Price, Tulin Otamis
Ercal, Nuran
Banks, William A.
Bearden, Shawn E.
TI Homocysteine disrupts NO metabolism in brain microvascular endothelial
cells by an mGluR5-dependent mechanism
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Beard, Richard Scott; Henry, Jamie N.; Bearden, Shawn E.] Idaho State Univ, Pocatello, ID 83209 USA.
[Price, Tulin Otamis] St Louis Univ, St Louis, MO 63103 USA.
[Ercal, Nuran] Missouri Univ Sci & Technol, Rolla, MO USA.
[Banks, William A.] VA Puget Sound, Seattle, WA USA.
[Banks, William A.] Univ Washington, Seattle, WA 98195 USA.
RI Beard Jr., Richard/E-2051-2013
OI Beard Jr., Richard/0000-0001-8545-3014
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708405604
ER
PT J
AU Bellani, MA
Muniandy, P
Paramasivam, M
Smogorzewska, A
Wang, WD
de Winter, J
Seidman, MM
AF Bellani, Marina Andrea
Muniandy, Parames
Paramasivam, Manikandian
Smogorzewska, Agata
Wang, Weidong
de Winter, Johan
Seidman, Michael M.
TI Dissecting cellular inter-strand crosslink repair pathways through the
recruitment kinetics of Fanconi Anemia (FA) proteins to localized ICLs
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Bellani, Marina Andrea; Paramasivam, Manikandian; Seidman, Michael M.] LMG, Baltimore, MD USA.
[Wang, Weidong] NIA, LG, NIH, Baltimore, MD 21224 USA.
[Muniandy, Parames] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Smogorzewska, Agata] Rockefeller Univ, New York, NY 10021 USA.
[de Winter, Johan] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708402580
ER
PT J
AU Chen, YX
Gelfond, JA
McManus, LM
Shireman, PK
AF Chen, Yongxin
Gelfond, Jonathan A.
McManus, Linda M.
Shireman, Paula K.
TI MiR-682 Antisense Inhibits Skeletal Muscle Regeneration
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Chen, Yongxin; McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708402405
ER
PT J
AU Clayton, CC
Neve, KA
AF Clayton, Cecilea C.
Neve, Kim A.
TI Analysis of dopamine D2 receptor mutants deficient in arrestin binding
using bioluminescence resonance energy transfer
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Portland VA Med Ctr, Portland, OR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708403585
ER
PT J
AU Cypess, AM
AF Cypess, Aaron M.
TI New Discoveries in Human Brown Adipose Tissue
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Cypess, Aaron M.] Joslin Diabet Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708404514
ER
PT J
AU Farrell, S
Brecha, N
Barnes, S
AF Farrell, Spring
Brecha, Nicholas
Barnes, Steven
TI Somatostatin receptor subtype 4 modulation of L-type Ca2+ channels in
rat retinal ganglion cells
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Farrell, Spring; Barnes, Steven] Dalhousie Univ, Halifax, NS, Canada.
[Brecha, Nicholas; Barnes, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Brecha, Nicholas] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708401102
ER
PT J
AU Feinstein, TN
Vilardaga, JP
AF Feinstein, Timothy N.
Vilardaga, Jean-Pierre
TI Retromer terminates the generation of cAMP by internalized G
protein-coupled PTH receptors
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Feinstein, Timothy N.; Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Vilardaga, Jean-Pierre] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708403577
ER
PT J
AU Gohil, VM
Sheth, SA
Nilsson, R
Lee, JH
Wojtovich, A
Perocchi, F
Chen, W
Clish, C
Ayata, C
Brookes, P
Mootha, V
AF Gohil, Vishal M.
Sheth, Sunil A.
Nilsson, Roland
Lee, Jeong-Hyun
Wojtovich, Andrew
Perocchi, Fabiana
Chen, William
Clish, Clary
Ayata, Cenk
Brookes, Paul
Mootha, Vamsi
TI Nutrient-sensitized screening for drugs that shift energy metabolism
from mitochondrial respiration to glycolysis
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Gohil, Vishal M.; Sheth, Sunil A.; Nilsson, Roland; Perocchi, Fabiana; Chen, William; Mootha, Vamsi] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Lee, Jeong-Hyun; Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
[Wojtovich, Andrew; Brookes, Paul] Univ Rochester, Med Ctr, Dept Pharmacol & Physiol, Rochester, NY 14642 USA.
[Clish, Clary; Mootha, Vamsi] Broad Inst MIT & Harvard, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708402712
ER
PT J
AU Harston, RK
McKillop, JC
Moschella, PC
Van Laer, A
Quinones, LS
Baicu, CF
Balasubramanian, S
Zile, MR
Kuppuswamy, D
AF Harston, Rebecca Kate
McKillop, John C.
Moschella, Phillip C.
Van Laer, An
Quinones, Lakeya S.
Baicu, Catalin F.
Balasubramanian, Sundaravadivel
Zile, Michael R.
Kuppuswamy, Dhandapani
TI Acute rapamycin treatment augments both protein ubiquitination and Akt
activation in pressure-overloaded rat myocardium
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Harston, Rebecca Kate] ABL Inc, Prod Dev, Kensington, MD USA.
[McKillop, John C.; Moschella, Phillip C.; Van Laer, An; Quinones, Lakeya S.; Baicu, Catalin F.; Balasubramanian, Sundaravadivel; Zile, Michael R.; Kuppuswamy, Dhandapani] Med Univ S Carolina, Charleston, SC 29425 USA.
[Zile, Michael R.; Kuppuswamy, Dhandapani] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708404524
ER
PT J
AU Hernandez-Corbacho, M
Mather, AR
Jenkins, R
Clarke, C
Hannun, Y
Obeid, L
Snider, A
Siskind, L
AF Hernandez-Corbacho, Maria
Mather, Andrew R.
Jenkins, Rusell
Clarke, Christopher
Hannun, Yusuf
Obeid, Lina
Snider, Ashley
Siskind, Leah
TI Long-Chain Glycosphingolipids Mediate Renal Aging
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Hernandez-Corbacho, Maria; Mather, Andrew R.; Jenkins, Rusell; Clarke, Christopher; Hannun, Yusuf; Obeid, Lina; Snider, Ashley; Siskind, Leah] Med Univ S Carolina, Charleston, SC 29425 USA.
[Obeid, Lina; Snider, Ashley; Siskind, Leah] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708402724
ER
PT J
AU Hsiao, PYL
Mitchell, DC
Hartman, TJ
Jensen, GL
Coffman, DL
Still, CD
Allman, RM
Sawyer, P
AF Hsiao, Pao Ying Lin
Mitchell, Diane C.
Hartman, Terryl J.
Jensen, Gordon L.
Coffman, Donna L.
Still, Christopher D.
Allman, Richard M.
Sawyer, Patricia
TI Characterizing dietary patterns in older adults using a novel approach
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Hsiao, Pao Ying Lin; Mitchell, Diane C.; Hartman, Terryl J.; Jensen, Gordon L.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Coffman, Donna L.] Penn State Univ, Methodol Ctr, University Pk, PA 16802 USA.
[Still, Christopher D.] Geisinger Med Ctr, Danville, PA 17822 USA.
[Allman, Richard M.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Allman, Richard M.; Sawyer, Patricia] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA.
RI Coffman, Donna/C-3038-2013
OI Coffman, Donna/0000-0001-6305-6579
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708405192
ER
PT J
AU Jain, A
Munn, LL
AF Jain, Abhishek
Munn, Lance L.
TI Rare Blood Cell Separation on a Microfluidic Platform: A Case Study of
Circulating Tumor Cells
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Jain, Abhishek] Boston Univ, Boston, MA 02215 USA.
[Jain, Abhishek; Munn, Lance L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA.
RI Munn, Lance/L-3950-2016
OI Munn, Lance/0000-0003-0698-7232
NR 0
TC 0
Z9 0
U1 1
U2 11
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708405516
ER
PT J
AU Korkmaz, B
Jegot, G
Derache, C
Remold-O'Donnell, E
Kellenberger, C
Gauthier, F
AF Korkmaz, Brice
Jegot, Gwenhael
Derache, Chrystelle
Remold-O'Donnell, Eileen
Kellenberger, Christine
Gauthier, Francis
TI A substrate-based approach to convert serpinB1 into a specific inhibitor
of proteinase 3, the Wegener granulomatosis autoantigen
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Korkmaz, Brice; Jegot, Gwenhael; Gauthier, Francis] INSERM, Proteases & Vectorisat Pulm U618, Tours, France.
[Derache, Chrystelle] CNRS, Ctr Biophys Mol, Orleans, France.
[Remold-O'Donnell, Eileen] Immune Dis Inst, Boston, MA USA.
[Kellenberger, Christine] CNRS, Marseille, France.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708403544
ER
PT J
AU Li, Y
Si, R
Feng, Y
Zou, L
Wang, E
Chao, W
AF Li, Yan
Si, Rui
Feng, Yan
Zou, Lin
Wang, E.
Chao, Wei
TI Myocardial ischemia induces a rapid activation of innate immune
signaling via cardiac heat-shock protein-60 and Toll-like receptor 4
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Li, Yan; Si, Rui; Feng, Yan; Zou, Lin; Wang, E.; Chao, Wei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
[Li, Yan] Tongji Hosp, HUST, Wuhan, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708402288
ER
PT J
AU Moore, C
Rosenblum, JL
Kaplan, LM
AF Moore, Carolyn
Rosenblum, Jennifer L.
Kaplan, Lee M.
TI Calcium and vitamin D supplementation is associated with decreased
intra-abdominal fat mass
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Moore, Carolyn] Texas Womans Univ, Houston, TX USA.
[Rosenblum, Jennifer L.; Kaplan, Lee M.] MGH Weight Ctr, Boston, MA USA.
[Rosenblum, Jennifer L.; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708401851
ER
PT J
AU Munn, L
Kunert, C
Kamoun, W
Tyrrell, JA
AF Munn, Lance
Kunert, Christian
Kamoun, Walid
Tyrrell, James Alex
TI Simulating vascular remodeling and transport in tumors
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Munn, Lance; Kunert, Christian; Kamoun, Walid] Massachusetts Gen Hosp, Charlestown, MA USA.
[Tyrrell, James Alex] Thomson Reuters, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708403694
ER
PT J
AU Munn, L
Liao, S
Wong, A
Lacorre, D
Jain, RK
Fukumura, D
Cheng, G
AF Munn, Lance
Liao, Shan
Wong, Andus
Lacorre, Delphine
Jain, Rakesh K.
Fukumura, Dai
Cheng, Gang
TI Wrapping-and-tapping anastomosis connects implanted endothelial networks
to host vasculature
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Munn, Lance; Liao, Shan; Wong, Andus; Lacorre, Delphine; Jain, Rakesh K.; Fukumura, Dai; Cheng, Gang] Massachusetts Gen Hosp, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708402313
ER
PT J
AU Naar, AM
Walker, AK
Yang, FJ
Najafi-Shoushtari, SH
Rottiers, V
Kristo, F
Li, YX
Shioda, T
Cohen, DE
Gerszten, RE
AF Naeaer, Anders M.
Walker, Amy K.
Yang, Fajun
Najafi-Shoushtari, S. Hani
Rottiers, Veerle
Kristo, Fjoralba
Li, Yingxia
Shioda, Toshi
Cohen, David E.
Gerszten, Robert E.
TI Conserved Gene Regulatory Mechanisms Controlling Cholesterol and Fat
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Naeaer, Anders M.; Walker, Amy K.; Yang, Fajun; Najafi-Shoushtari, S. Hani; Rottiers, Veerle; Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA.
[Naeaer, Anders M.; Walker, Amy K.; Yang, Fajun; Najafi-Shoushtari, S. Hani; Rottiers, Veerle] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Kristo, Fjoralba; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA.
[Li, Yingxia; Cohen, David E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708401739
ER
PT J
AU Nansel, TR
Liu, AY
Lipsky, LM
Haynie, DL
Mehta, SN
Laffel, LMB
AF Nansel, Tonja R.
Liu, Aiyi
Lipsky, Leah M.
Haynie, Denise L.
Mehta, Sanjeev N.
Laffel, Lori M. B.
TI Differences in diet quality between weekdays and weekends: utility of a
random effects model
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Nansel, Tonja R.; Liu, Aiyi; Lipsky, Leah M.; Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Mehta, Sanjeev N.; Laffel, Lori M. B.] Joslin Diabet Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708403308
ER
PT J
AU Perez, KY
Hyun-Park, J
Tanwar, PS
Teixeira, J
AF Perez, Kayla Y.
Hyun-Park, Joo
Tanwar, Pradeep S.
Teixeira, Jose
TI The Expression of Pluripotent Genes in Normal Human Endometrium
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Perez, Kayla Y.] Interamer Univ Puerto Rico San German, Mayaguez, PR USA.
[Hyun-Park, Joo; Tanwar, Pradeep S.; Teixeira, Jose] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708402864
ER
PT J
AU Ruan, YC
Da Silva, N
Belleannee, C
Shum, WWC
Breton, S
AF Ruan, Ye Chun
Da Silva, Nicolas
Belleannee, Clemence
Shum, Winnie W. C.
Breton, Sylvie
TI Involvement of CFTR in ATP and HCO3-secretion in epididymal principal
cells
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 Massachusetts Gen Hosp, Div Nephrol, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708400501
ER
PT J
AU Sas, KM
Amria, MY
Bell, PD
AF Sas, Kelli Margot
Amria, May Y.
Bell, P. Darwin
TI Diabetes accelerates cystogenesis in the adult conditional ift88
knockout mouse
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Sas, Kelli Margot; Amria, May Y.; Bell, P. Darwin] Med Univ S Carolina, Charleston, SC 29425 USA.
[Bell, P. Darwin] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708404141
ER
PT J
AU Segal, RA
AF Segal, Rosalind A.
TI Retrograde Response Genes and Neuronal Survival
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Segal, Rosalind A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708401768
ER
PT J
AU Sengupta, A
Molkentin, JD
Paik, JH
DePinho, RA
Yutzey, KE
AF Sengupta, Arunima
Molkentin, Jeffery D.
Paik, Ji-Hye
DePinho, Ronald A.
Yutzey, Katherine E.
TI FOXO transcription factors promote cardiomyocyte survival upon induction
of oxidative stress
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Sengupta, Arunima; Molkentin, Jeffery D.; Yutzey, Katherine E.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708404380
ER
PT J
AU Song, JW
Munn, LL
AF Song, Jonathan W.
Munn, Lance L.
TI Biomechanical Determinants of Endothelial Cell Sprouting in a
Microfluidic Device
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 Massachusetts Gen Hosp, EL Steele Lab Tumor Biol Radiat Oncol, Charlestown, MA USA.
Harvard Univ, Sch Med, Charlestown, MA USA.
RI Munn, Lance/L-3950-2016; Song, Jonathan/C-1922-2013
OI Munn, Lance/0000-0003-0698-7232; Song, Jonathan/0000-0002-6991-5298
NR 0
TC 0
Z9 0
U1 0
U2 4
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708401218
ER
PT J
AU Soto-Pina, AE
Kadapakkam, S
Mehring, C
Hinojosa-Laborde, C
Strong, R
AF Soto-Pina, Alexandra Estela
Kadapakkam, Sheela
Mehring, Cinthya
Hinojosa-Laborde, Carmen
Strong, Randy
TI Inhibition of tyrosine hydroxylase reduces dexamethasone-induced
hypertension
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Soto-Pina, Alexandra Estela; Kadapakkam, Sheela; Mehring, Cinthya; Hinojosa-Laborde, Carmen; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Soto-Pina, Alexandra Estela; Kadapakkam, Sheela; Strong, Randy] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708405701
ER
PT J
AU Soydan, G
Waeber, C
AF Soydan, Guray
Waeber, Christian
TI Sphingosine-1-phosphate-induced vasoconstriction is increased in basilar
but not in peripheral arteries in type 2 diabetic mice
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Soydan, Guray; Waeber, Christian] Massachusetts Gen Hosp, Charlestown, MA USA.
[Soydan, Guray] Hacettepe Univ, Sch Med, Ankara, Turkey.
RI Waeber, Christian/A-8333-2009
OI Waeber, Christian/0000-0001-6078-0027
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708405414
ER
PT J
AU Soydan, G
Waeber, C
AF Soydan, Guray
Waeber, Christian
TI Sphingosine-1-phosphate mediate vasoconstriction in femoral and
mesenteric arteries of mice via S1P3 receptors
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Soydan, Guray; Waeber, Christian] Massachusetts Gen Hosp, Charlestown, MA USA.
[Soydan, Guray] Hacettepe Univ, Sch Med, Ankara, Turkey.
RI Waeber, Christian/A-8333-2009
OI Waeber, Christian/0000-0001-6078-0027
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708400221
ER
PT J
AU Soydan, G
Ferrari, MD
van den Maagdenberg, AMJM
Ayata, C
AF Soydan, Guray
Ferrari, Michel D.
van den Maagdenberg, Arn M. J. M.
Ayata, Cenk
TI Functional changes of vascular responses in familial hemiplegic migraine
type 1
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Soydan, Guray; Ayata, Cenk] Massachusetts Gen Hosp, Charlestown, MA USA.
[Soydan, Guray] Hacettepe Univ, Ankara, Turkey.
[Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Leiden, Netherlands.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708400213
ER
PT J
AU Soydan, G
Xu, J
Sims, JR
AF Soydan, Guray
Xu, Jian
Sims, John Randall
TI Dantrolene and nimodipine inhibits vasoconstriction of basilar artery in
a rat subarachnoid hemorrhage model
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Soydan, Guray; Xu, Jian; Sims, John Randall] Massachusetts Gen Hosp, Charlestown, MA USA.
[Soydan, Guray] Hacettepe Univ, Sch Med, Ankara, Turkey.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708400211
ER
PT J
AU Soydan, G
Xu, J
Sims, JR
Waeber, C
AF Soydan, Guray
Xu, Jian
Sims, John Randall
Waeber, Christian
TI S1P-induced vasoconstriction increased in basilar artery of a
subarachnoid hemorrhage model in rats
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Soydan, Guray; Xu, Jian; Sims, John Randall; Waeber, Christian] Massachusetts Gen Hosp, Charlestown, MA USA.
[Soydan, Guray] Hacettepe Univ, Sch Med, Ankara, Turkey.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708400212
ER
PT J
AU Spassieva, SD
Rahmaniyan, M
Bielawski, J
Kraveka, JM
Obeid, LM
AF Spassieva, Stefka D.
Rahmaniyan, Mehrdad
Bielawski, Jacek
Kraveka, Jacqueline M.
Obeid, Lina M.
TI Cell Density Dependent Inhibition of Dihydroceramide Desaturase
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Spassieva, Stefka D.; Rahmaniyan, Mehrdad; Bielawski, Jacek; Kraveka, Jacqueline M.; Obeid, Lina M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Obeid, Lina M.] Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708404667
ER
PT J
AU Trager, RE
Wills, L
Lindsey, C
Beeson, G
Beeson, C
Schnellmann, R
Peterson, Y
AF Trager, Richard Edwin
Wills, Lauren
Lindsey, Christopher
Beeson, Gyda
Beeson, Craig
Schnellmann, Rick
Peterson, Yuri
TI High throughput identification of mitochondrial toxicophores
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Trager, Richard Edwin; Wills, Lauren; Lindsey, Christopher; Beeson, Gyda; Beeson, Craig; Schnellmann, Rick; Peterson, Yuri] Med Univ S Carolina, Charleston, SC 29425 USA.
[Schnellmann, Rick] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708403539
ER
PT J
AU Wang, HZ
Porter, L
Sarwar, ZU
Wells, JT
McManus, LM
Shireman, PK
AF Wang, Hanzhou
Porter, Laurel
Sarwar, Zaheer U.
Wells, Jason T.
McManus, Linda M.
Shireman, Paula K.
TI Macrophage Ablation in CD11b-diphtheria Toxin Receptor (DTR) Transgenic
Mice Impairs Skeletal Muscle Regeneration
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Wang, Hanzhou; Porter, Laurel; Sarwar, Zaheer U.; Wells, Jason T.; McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708403413
ER
PT J
AU Wang, W
Zhu, JQ
Springer, TA
Luo, BH
AF Wang, Wei
Zhu, Jieqing
Springer, Timothy A.
Luo, Binghao
TI TESTS OF INTEGRIN TRANSMEMBRANE DOMAIN HOMO-OLIGOMERIZATION DURING
INTEGRIN LIGAND BINDING AND SIGNALING
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Wang, Wei; Luo, Binghao] Louisiana State Univ, Baton Rouge, LA 70803 USA.
[Zhu, Jieqing; Springer, Timothy A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA.
[Zhu, Jieqing; Springer, Timothy A.] Childrens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708406731
ER
PT J
AU Wick, MJ
Loomis, ZL
Buesing, EJ
Wehling, CA
Cool, CD
Hersh, LB
Voelkel, NF
Dempsey, EC
AF Wick, Marilee J.
Loomis, Zoe L.
Buesing, Erica J.
Wehling, Carol A.
Cool, Carlyne D.
Hersh, Louis B.
Voelkel, Norbert F.
Dempsey, Edward C.
TI Decreased lung neprilysin gene expression in humans with COPD and
pulmonary vascular remodeling
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Wick, Marilee J.; Loomis, Zoe L.; Buesing, Erica J.; Cool, Carlyne D.; Voelkel, Norbert F.; Dempsey, Edward C.] Univ Colorado Denver, CVP Res Lab, Aurora, CO USA.
[Wick, Marilee J.; Loomis, Zoe L.; Buesing, Erica J.; Cool, Carlyne D.; Voelkel, Norbert F.; Dempsey, Edward C.] Univ Colorado Denver, Div Pulm, Aurora, CO USA.
[Wick, Marilee J.; Loomis, Zoe L.; Wehling, Carol A.; Dempsey, Edward C.] Denver VAMC, Denver, CO USA.
[Hersh, Louis B.] Univ Kentucky, Lexington, KY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708400449
ER
PT J
AU Zhong, Z
Liu, QL
Rehman, H
He, SQ
Shi, YJ
Krishnasamy, Y
Schnellmann, RG
AF Zhong, Zhi
Liu, Qinlong
Rehman, Hasibur
He, Songqing
Shi, Yanjun
Krishnasamy, Yasodha
Schnellmann, Rick G.
TI Supplementation of amphiregulin improves fatty liver regeneration after
partial hepatectomy (PHX): the role of c-Jun N-terminal kinase (JNK) and
extracellular signal-regulated kinases (ERK)
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting 2011
CY APR 09-13, 2011
CL Washington, DC
SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET)
C1 [Schnellmann, Rick G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Zhong, Zhi; Liu, Qinlong; Rehman, Hasibur; He, Songqing; Shi, Yanjun; Krishnasamy, Yasodha; Schnellmann, Rick G.] Med Univ S Carolina, Charleston, SC 29425 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2011
VL 25
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IE
UT WOS:000310708407181
ER
PT J
AU Cacoub, PP
Zeymer, U
Limbourg, T
Baumgartner, I
Poldermans, D
Rother, J
Bhatt, DL
Steg, PG
AF Cacoub, Patrice P.
Zeymer, Uwe
Limbourg, Tobias
Baumgartner, Iris
Poldermans, Don
Roether, Joachim
Bhatt, Deepak L.
Steg, Philippe Gabriel
CA REACH Registry Investigators
TI Effects of adherence to guidelines for the control of major
cardiovascular risk factors on outcomes in the REduction of
Atherothrombosis for Continued Health (REACH) Registry Europe
SO HEART
LA English
DT Article
ID PERIPHERAL-ARTERIAL-DISEASE; ASSOCIATION/AMERICAN-STROKE-ASSOCIATION;
TRANSIENT ISCHEMIC ATTACK; CARE PROFESSIONALS; VASCULAR-DISEASE; EVENT
RATES; CORONARY; STATEMENT; CHOLESTEROL; OUTPATIENTS
AB Objectives To examine the impact of cardiovascular risk factor control on 3-year cardiovascular event rates in patients with stable symptomatic atherothrombotic disease in Europe.
Methods The REduction of Atherothrombosis for Continued Health (REACH) Registry recruited patients aged >= 45 years with established atherothrombotic disease or three or more risk factors, of whom 20 588 symptomatic patients from 18 European countries were analysed in this study at baseline and 12, 24 and 36 months. 'Good control' of cardiovascular risk factors was defined as three to five risk factors at target values of international guideline recommendations (systolic blood pressure < 140 mm Hg, diastolic blood pressure < 90 mm Hg, fasting glycaemia < 110 mg/dl, total cholesterol < 200 mg/dl, non-smoking). Independent predictors of 'good control' of major risk factors were assessed by multivariate analysis.
Results Among symptomatic patients in the REACH Registry Europe (mean age 67 years, 70.6% male), 59.4% had good control of risk factors at baseline. Good risk factor control was associated with lower cardiovascular death/non-fatal stroke/non-fatal myocardial infarction (OR 0.76; 95% CI 0.69 to 0.83) and mortality (OR 0.89; 95% CI 0.79 to 0.99) at 36 months, compared with poor control. Independent predictors of good control of risk factors included residence in western versus eastern Europe (OR 1.29), high level of education (OR 1.16), established coronary artery disease (OR 1.18), treatment with one or more antithrombotic (OR 1.59) and one or more lipid-lowering agent (OR 1.16).
Conclusions In REACH, less than 60% of patients with stable atherothrombotic disease had good control of the five major cardiovascular risk factors. Improved risk factor control is associated with a positive impact on 3-year cardiovascular event rates and mortality.
C1 [Cacoub, Patrice P.] Univ Paris 06, INSERM, U959, UMR Pierre & Marie Curie 7211, Paris, France.
[Cacoub, Patrice P.] Hosp La Pitie Salpetriere, AP HP, Paris, France.
[Zeymer, Uwe; Limbourg, Tobias] Heidelberg Univ, Inst Herzinfarktforsch Ludwigshafen, Ludwigshafen, Germany.
[Baumgartner, Iris] Univ Hosp Bern, Inselspital, Div Clin & Intervent Angiol, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland.
[Poldermans, Don] Erasmus MC, Dept Vasc Surg, Rotterdam, Netherlands.
[Roether, Joachim] Hannover Med Sch, Johannes Wesling Klinikum Minden, D-3000 Hannover, 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, Philippe Gabriel] Univ Paris 07, INSERM, U698, Paris, France.
RP Cacoub, PP (reprint author), Grp Hosp La Pitie Salpetriere, AP HP, Serv Med Interne, 47-83 Blvd Hop, F-75013 Paris, France.
EM patrice.cacoub@psl.aphp.fr
OI ELISAF, MOSES/0000-0003-0505-078X
FU Sanofi-Aventis (Paris, France); Bristol-Myers Squibb (Princeton, New
Jersey, USA); Waksman Foundation (Tokyo, Japan); Sanofi-Aventis;
Schering Plough; Servier and Roche; Bristol-Myers-Squibb; Lundbeck and
Boehringer Ingelheim; Eisai; Ethicon; Heartscape; Medicines Company
FX The REACH Registry is sponsored by Sanofi-Aventis (Paris, France),
Bristol-Myers Squibb (Princeton, New Jersey, USA) and the Waksman
Foundation (Tokyo, Japan). The sponsors provide logistical support. All
manuscripts in the REACH Registry are led by independent authors who are
not governed by the funding sponsors and are reviewed by an academic
publication committee before submission. The funding sponsors have the
opportunity to review manuscript submissions but do not have authority
to change any aspect of a manuscript.; PPC has received research grants
from Sanofi-Aventis, Schering Plough, Servier and Roche; honoraria from
Sanofi-Aventis, Schering Plough, Servier, Roche, AstraZeneca and
Bristol-Myers Squibb. UZ has received research grants and speaker
honoraria from Bristol-Myers-Squibb and Sanofi Aventis. JR has received
honoraria and consulting fees from Sanofi-Aventis, Bristol-Myers Squibb,
Lundbeck and Boehringer Ingelheim. DLB has received research grants (to
the institution) from: AstraZeneca, Bristol-Myers Squibb, Eisai,
Ethicon, Heartscape, Sanofi-Aventis and The Medicines Company; has
served as a consultant (honoraria waived or donated for past three
years) for Arena, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb,
Cardax, Centocor, Cogentus, Daiichi-Sankyo, Eisai, Eli Lilly,
GlaxoSmithKline, Johnson & Johnson, McNeil, Medtronic, Millennium,
Molecular Insights, Otsuka, Paringenix, PDL, Philips, Portola,
Sanofi-Aventis, Schering Plough, Scios, Takeda, The Medicines Company
and Vertex. PGS has received a research grant from Sanofi-Aventis (1999
to 2008); is on the speaker's bureau for Boehringer-Ingelheim,
Bristol-Myers Squibb, GlaxoSmithKline, Menarini, Medtronic, Nycomed,
Pierre Fabre, Sanofi-Aventis, Servier and The Medicines Company; is on
the consulting/advisory boards for Astellas, AstraZeneca, Bayer,
Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Endotis,
GlaxoSmithKline, Medtronic, MSD, Nycomed, Sanofi-Aventis, Servier and
The Medicines Company and is a stockholder for Aterovax. TL, IB and DP:
No interests declared.
NR 28
TC 34
Z9 37
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD APR
PY 2011
VL 97
IS 8
BP 660
EP 667
DI 10.1136/hrt.2010.213710
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 737CA
UT WOS:000288544700011
PM 21357372
ER
PT J
AU Oral, E
Ghali, BW
Muratoglu, OK
AF Oral, Ebru
Ghali, Bassem W.
Muratoglu, Orhun K.
TI The elimination of free radicals in irradiated UHMWPEs with and without
vitamin E stabilization by annealing under pressure
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
LA English
DT Article
DE arthroplasty; bearing surfaces; crystallinity; polyethylene (UHMWPE);
radiation
ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; ELECTRON-BEAM
RADIATION; ALPHA-TOCOPHEROL; MECHANICAL-PROPERTIES; CROSS-LINKING;
ACETABULAR COMPONENTS; ORTHOPEDIC UHMWPE; PHASE-TRANSITION; MEDICAL
IMPLANTS
AB Radiation crosslinking of ultrahigh molecular weight polyethylene (UHMWPE) has been used to decrease the wear of joint implant bearing surfaces. While radiation crosslinking has been successful in decreasing femoral head penetration into UHMWPE acetabular liners in vivo, postirradiation thermal treatment of the polymer is required to ensure the oxidative stability of joint implants in the long term. Two types of thermal treatment have been used: (i) annealing below the melting point preserves the mechanical properties but the residual free radicals trapped in the crystalline regions are not completely eliminated, leading to oxidation in the long-term and (ii) annealing above the melting point (melting) eliminates the free radicals but leads to a decrease in mechanical properties through loss of crystallinity during the melting process. In this study, we hypothe-sized that free radicals could be reduced by annealing below the melting point under pressure effectively without melting due to the elevation of the melting point. By avoiding the complete melting of UHMWPE, mechanical properties would be preserved. Our hypothesis tested positive in that we found the radiation-induced free radicals to be markedly reduced (below the detection limit of state-of-the-art electron spin resonance) by thermal annealing under pressure in radiation crosslinked virgin UHMWPE and UHMWPE/vitamin-E blends without loss of mechanical properties. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 97B: 167-174, 2011.
C1 [Oral, Ebru; Ghali, Bassem W.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA.
RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
EM omuratoglu@partners.org
FU NIH [AR051142]; Zimmer, Inc.
FX Contract grant sponsor: NIH; contract grant number: AR051142; Contract
grant sponsor: Zimmer, Inc. and laboratory funds
NR 51
TC 10
Z9 12
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4973
EI 1552-4981
J9 J BIOMED MATER RES B
JI J. Biomed. Mater. Res. Part B
PD APR
PY 2011
VL 97B
IS 1
BP 167
EP 174
DI 10.1002/jbm.b.31799
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 735KT
UT WOS:000288413900019
PM 21381192
ER
PT J
AU Guyatt, GH
Oxman, AD
Kunz, R
Atkins, D
Brozek, J
Vist, G
Alderson, P
Glasziou, P
Falck-Ytter, Y
Schunemann, HJ
AF Guyatt, Gordon H.
Oxman, Andrew D.
Kunz, Regina
Atkins, David
Brozek, Jan
Vist, Gunn
Alderson, Philip
Glasziou, Paul
Falck-Ytter, Yngve
Schuenemann, Holger J.
TI GRADE guidelines: 2. Framing the question and deciding on important
outcomes
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE GRADE; PICO; Patient-important outcomes; Surrogate; Guideline
development; Quality of evidence; Indirectness
ID PATIENT-IMPORTANT OUTCOMES; ATRIAL-FIBRILLATION; CONTROLLED-TRIALS;
CLINICAL-TRIALS; METAANALYSIS; THERAPY
AB GRADE requires a clear specification of the relevant setting, population, intervention, and comparator. It also requires specification of all important outcomes whether evidence from research studies is, or is not, available. For a particular management question, the population, intervention, and outcome should be sufficiently similar across studies that a similar magnitude of effect is plausible. Guideline developers should specify the relative importance of the outcomes before gathering the evidence and again when evidence summaries are complete. In considering the importance of a surrogate outcome, authors should rate the importance of the patient-important outcome for which the surrogate is a substitute and subsequently rate down the quality of evidence for indirectness of outcome. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Guyatt, Gordon H.; Brozek, Jan; Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
[Oxman, Andrew D.; Vist, Gunn] Norwegian Knowledge Ctr Hlth Serv, Oslo, Norway.
[Kunz, Regina] Univ Basel Hosp, Acad Swiss Insurance Med, CH-4031 Basel, Switzerland.
[Atkins, David] US Dept Vet Affairs, Off Res & Dev, Washington, DC USA.
[Alderson, Philip] Natl Inst Hlth & Clin Excellence, Ctr Clin Practice, Manchester, Lancs, England.
[Glasziou, Paul] Bond Univ, Gold Coast, Qld, Australia.
[Falck-Ytter, Yngve] Case Western Reserve Univ, Div Gastroenterol, Case & VA Med Ctr, Cleveland, OH 44106 USA.
RP Guyatt, GH (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, CLARITY Res Grp, Room 2C12,1200 Main St, W Hamilton, ON L8N 3Z5, Canada.
EM guyatt@mcmaster.ca
RI Glasziou, Paul/A-7832-2008
OI Glasziou, Paul/0000-0001-7564-073X
NR 16
TC 298
Z9 311
U1 1
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0895-4356
EI 1878-5921
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD APR
PY 2011
VL 64
IS 4
BP 395
EP 400
DI 10.1016/j.jclinepi.2010.09.012
PG 6
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 734UF
UT WOS:000288364300008
PM 21194891
ER
PT J
AU Balshem, H
Helfand, M
Schunemann, HJ
Oxman, AD
Kunz, R
Brozek, J
Vist, GE
Falck-Ytter, Y
Meerpohl, J
Norris, S
Guyatt, GH
AF Balshem, Howard
Helfand, Mark
Schuenemann, Holger J.
Oxman, Andrew D.
Kunz, Regina
Brozek, Jan
Vist, Gunn E.
Falck-Ytter, Yngve
Meerpohl, Joerg
Norris, Susan
Guyatt, Gordon H.
TI GRADE guidelines: 3. Rating the quality of evidence
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Quality assessment; Body of evidence; Imprecision; Indirectness;
Inconsistency; Publication bias
ID REYES-SYNDROME; VENOUS THROMBOEMBOLISM; 1ST EPISODE; RISK-FACTOR;
ANTICOAGULATION
AB This article introduces the approach of GRADE to rating quality of evidence. GRADE specifies four categories high, moderate, low, and very low that are applied to a body of evidence, not to individual studies. In the context of a systematic review, quality reflects our confidence that the estimates of the effect are correct. In the context of recommendations, quality reflects our confidence that the effect estimates are adequate to support a particular recommendation. Randomized trials begin as high-quality evidence, observational studies as low quality. "Quality" as used in GRADE means more than risk of bias and so may also be compromised by imprecision, inconsistency, indirectness of study results, and publication bias. In addition, several factors can increase our confidence in an estimate of effect. GRADE provides a systematic approach for considering and reporting each of these factors. GRADE separates the process of assessing quality of evidence from the process of making recommendations. Judgments about the strength of a recommendation depend on more than just the quality of evidence. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Balshem, Howard] Oregon Hlth & Sci Univ, BICC, Oregon Evidence Based Practice Ctr, Portland, OR 97239 USA.
[Helfand, Mark] Portland VA Med Ctr, Portland, OR USA.
[Schuenemann, Holger J.; Brozek, Jan; Guyatt, Gordon H.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8N 3Z5, Canada.
[Oxman, Andrew D.; Vist, Gunn E.] Norwegian Knowledge Ctr Hlth Serv, N-0130 Oslo, Norway.
[Kunz, Regina] Univ Basel Hosp, Basel Inst Clin Epidemiol, CH-4031 Basel, Switzerland.
[Falck-Ytter, Yngve] Case Western Reserve Univ, Div Gastroenterol, Case Med Ctr & VA, Cleveland, OH 44106 USA.
[Meerpohl, Joerg] Univ Med Ctr Freiburg, German Cochrane Ctr, Inst Med Biometry & Med Informat, D-79104 Freiburg, Germany.
[Meerpohl, Joerg] Univ Med Ctr Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, D-79106 Freiburg, Germany.
[Norris, Susan] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA.
RP Balshem, H (reprint author), Oregon Hlth & Sci Univ, BICC, Oregon Evidence Based Practice Ctr, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM balshemh@ohsu.edu
RI Meerpohl, Joerg/J-4224-2013
OI Meerpohl, Joerg/0000-0002-1333-5403
NR 13
TC 963
Z9 991
U1 9
U2 48
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD APR
PY 2011
VL 64
IS 4
BP 401
EP 406
DI 10.1016/j.jclinepi.2010.07.015
PG 6
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 734UF
UT WOS:000288364300009
PM 21208779
ER
PT J
AU Guyatt, GH
Oxman, AD
Vist, G
Kunz, R
Brozek, J
Alonso-Coello, P
Montori, V
Akl, EA
Djulbegovic, D
Falck-Ytter, Y
Norris, SL
Williams, JW
Atkins, D
Meerpohl, J
Schunemann, HJ
AF Guyatt, Gordon H.
Oxman, Andrew D.
Vist, Gunn
Kunz, Regina
Brozek, Jan
Alonso-Coello, Pablo
Montori, Victor
Akl, Elie A.
Djulbegovic, Ben
Falck-Ytter, Yngve
Norris, Susan L.
Williams, John W., Jr.
Atkins, David
Meerpohl, Joerg
Schuenemann, Holger J.
TI GRADE guidelines: 4. Rating the quality of evidence-study limitations
(risk of bias)
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE GRADE; quality of evidence; risk of bias; confidence in estimates;
blinding; concealment
ID RANDOMIZED CONTROLLED-TRIALS; OUTCOME REPORTING BIAS;
SPINAL-CORD-INJURY; EMPIRICAL-EVIDENCE; VENOUS THROMBOEMBOLISM;
CLINICAL-TRIALS; HEART-FAILURE; METAANALYSIS; THERAPY; BENEFIT
AB In the GRADE approach, randomized trials start as high-quality evidence and observational studies as low-quality evidence, but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias. Well-established limitations of randomized trials include failure to conceal allocation, failure to blind, loss to follow-up, and failure to appropriately consider the intention-to-treat principle. More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results. Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance. Risk of bias may vary across outcomes (e.g., loss to follow-up may be far less for all-cause mortality than for quality of life), a consideration that many systematic reviews ignore. In deciding whether to rate down for risk of bias whether for randomized trials or observational studies-authors should not take an approach that averages across studies. Rather, for any individual outcome, when there are some studies with a high risk, and some with a low risk of bias, they should consider including only the studies with a lower risk of bias. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Guyatt, Gordon H.; Brozek, Jan; Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8N 3Z5, Canada.
[Oxman, Andrew D.; Vist, Gunn] Norwegian Knowledge Ctr Hlth Serv, N-0130 Oslo, Norway.
[Kunz, Regina] Univ Basel Hosp, Acad Swiss Insurance Med, CH-4031 Basel, Switzerland.
[Kunz, Regina] Univ Basel Hosp, Basel Inst Clin Epidemiol & Biostat, CH-4031 Basel, Switzerland.
[Alonso-Coello, Pablo] Univ Autonoma Barcelona, Iberoamer Cochrane Ctr, Serv Epidemiol Clin & Salud Publ, Hosp St Pau, Barcelona 08041, Spain.
[Alonso-Coello, Pablo] Univ Autonoma Barcelona, CIBERESP, Hosp St Pau, Barcelona 08041, Spain.
[Montori, Victor] Mayo Clin, Knowledge & Encounter Res Unit, Rochester, MN USA.
[Akl, Elie A.] SUNY Buffalo, Dept Med, Buffalo, NY 14260 USA.
[Djulbegovic, Ben] Univ S Florida, Ctr Evidence Based Med & Hlth Outcomes Res, Tampa, FL 33612 USA.
[Djulbegovic, Ben] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol, Tampa, FL 33612 USA.
[Djulbegovic, Ben] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hlth Outcomes & Behav, Tampa, FL 33612 USA.
[Falck-Ytter, Yngve] Case Western Reserve Univ, Div Gastroenterol, Case & VA Med Ctr, Cleveland, OH 44106 USA.
[Norris, Susan L.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA.
[Williams, John W., Jr.] Duke Univ, Med Ctr, Durham, NC 27705 USA.
[Williams, John W., Jr.] Durham Vet Affairs Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA.
[Atkins, David] US Dept Vet Affairs, QUERI Program, Off Res & Dev, Washington, DC USA.
[Meerpohl, Joerg] Univ Med Ctr Freiburg, German Cochrane Ctr, Inst Med Biometry & Med Informat, D-79104 Freiburg, Germany.
[Meerpohl, Joerg] Univ Med Ctr Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, D-79106 Freiburg, Germany.
RP Guyatt, GH (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, CLARITY Res Grp, Room 2C12,1200 Main St, W Hamilton, ON L8N 3Z5, Canada.
EM guyatt@mcmaster.ea
RI Djulbegovic, Benjamin/I-3661-2012; Meerpohl, Joerg/J-4224-2013;
OI Djulbegovic, Benjamin/0000-0003-0671-1447; Meerpohl,
Joerg/0000-0002-1333-5403; Montori, Victor/0000-0003-0595-2898
NR 37
TC 501
Z9 514
U1 6
U2 27
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD APR
PY 2011
VL 64
IS 4
BP 407
EP 415
DI 10.1016/j.jclinepi.2010.07.017
PG 9
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 734UF
UT WOS:000288364300010
PM 21247734
ER
PT J
AU Dalrymple, LS
Katz, R
Kestenbaum, B
Shlipak, MG
Sarnak, MJ
Stehman-Breen, C
Seliger, S
Siscovick, D
Newman, AB
Fried, L
AF Dalrymple, Lorien S.
Katz, Ronit
Kestenbaum, Bryan
Shlipak, Michael G.
Sarnak, Mark J.
Stehman-Breen, Catherine
Seliger, Stephen
Siscovick, David
Newman, Anne B.
Fried, Linda
TI Chronic Kidney Disease and the Risk of End-Stage Renal Disease versus
Death
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE renal disease; cardiovascular disease; clinical epidemiology
ID CARDIOVASCULAR HEALTH; COMPETING RISK; UNITED-STATES; OLDER-ADULTS;
MORTALITY; OUTCOMES; EVENTS; POPULATION
AB Among older adults with chronic kidney disease (CKD), the comparative event rates of end-stage renal disease (ESRD) and cause-specific death are unknown.
To compare the rates of ESRD, cardiovascular and non-cardiovascular death and examine risk factors for ESRD and all-cause mortality in Cardiovascular Health Study (CHS) participants.
The CHS is a longitudinal cohort study of community-dwelling adults aged 65 years and older.
1,268 participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m(2) were followed until the time of first event (ESRD, cardiovascular or non-cardiovascular death) or until March 31, 2003.
The outcomes were ESRD, cardiovascular- and non-cardiovascular death. Rates of each event were calculated, and a Cox Proportional Hazards Model with a competing risk framework was used to examine risk factors for ESRD as compared with death. Predictors included age, gender, race, BMI, hypertension, diabetes, cardiovascular disease, heart failure, tobacco use, eGFR, and total cholesterol.
During 9.7 years of follow-up, 5% of the cohort progressed to ESRD, and 61% of the cohort died. The rate (per 100 person-years) was 0.5 for ESRD and 6.8 for all-cause mortality (3.0 for cardiovascular and 3.8 for non-cardiovascular mortality). In the competing risk framework, lower eGFR, male gender, African-American race, and higher BMI were associated with an increased risk of ESRD.
Older adults with CKD are 13-fold more likely to die from any cause than progress to ESRD and are 6-fold more likely to die from cardiovascular causes than develop ESRD.
C1 [Dalrymple, Lorien S.] Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA.
[Katz, Ronit] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Kestenbaum, Bryan] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Shlipak, Michael G.] Vet Affairs Med Ctr, Med Serv, Gen Internal Med Sect, San Francisco, CA 94121 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Boston, MA USA.
[Stehman-Breen, Catherine] Amgen Inc, Thousand Oaks, CA 91320 USA.
[Seliger, Stephen] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Newman, Anne B.; Fried, Linda] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Newman, Anne B.; Fried, Linda] Univ Pittsburgh, Sch Med, Dept Epidemiol, Pittsburgh, PA USA.
[Fried, Linda] VA Pittsburgh Hlth Care Syst, Renal Sect, Pittsburgh, PA USA.
RP Dalrymple, LS (reprint author), Univ Calif Davis, Dept Med, 4150V St,3500 PSSB, Sacramento, CA 95817 USA.
EM lorien.dalrymple@ucdmc.ucdavis.edu
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU Amgen Inc.; Tap Pharmaceuticals; Merck
FX Drs. Dalrymple, Katz, Shlipak, Seliger, Siscovick, and Newman report no
conflicts of interest. Dr. Kestenbaum has received honoraria from Shire,
Abbott, and Genzyme Inc., and has received grant funding from Amgen Inc.
Dr. Sarnak has received funding from Tap Pharmaceuticals. Dr.
Stehman-Breen is an employee of Amgen. Dr. Fried has provided expert
testimony for Bayer and received a grant from Merck.
NR 25
TC 61
Z9 65
U1 0
U2 6
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 2011
VL 26
IS 4
BP 379
EP 385
DI 10.1007/s11606-010-1511-x
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 733KD
UT WOS:000288260700007
PM 20853156
ER
PT J
AU Walz, SE
Smith, M
Cox, E
Sattin, J
Kind, AJH
AF Walz, Stacy E.
Smith, Maureen
Cox, Elizabeth
Sattin, Justin
Kind, Amy J. H.
TI Pending Laboratory Tests and the Hospital Discharge Summary in Patients
Discharged To Sub-Acute Care
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE laboratory tests; hospital discharge; sub-acute care
ID MEDICAL REHABILITATION REPORT; UNIFORM DATA SYSTEM; BLOOD CULTURES;
TIME; COMMUNICATION; PREVALENCE; BACTEREMIA; PHYSICIANS; ATTITUDES;
PROGRAMS
AB Previous studies have noted a high (41%) prevalence and poor discharge summary communication of pending laboratory (lab) tests at the time of hospital discharge for general medical patients. However, the prevalence and communication of pending labs within a high-risk population, specifically those patients discharged to sub-acute care (i.e., skilled nursing, rehabilitation, long-term care), remains unknown.
To determine the prevalence and nature of lab tests pending at hospital discharge and their inclusion within hospital discharge summaries, for common sub-acute care populations.
Retrospective cohort study.
Stroke, hip fracture, and cancer patients discharged from a single large academic medical center to sub-acute care, 2003-2005 (N = 564)
Pending lab tests were abstracted from the laboratory information system (LIS) and from each patient's discharge summary, then grouped into 14 categories and compared. Microbiology tests were sub-divided by culture type and number of days pending prior to discharge.
Of sub-acute care patients, 32% (181/564) were discharged with pending lab tests per the LIS; however, only 11% (20/181) of discharge summaries documented these. Patients most often left the hospital with pending microbiology tests (83% [150/181]), particularly blood and urine cultures, and reference lab tests (17% [30/181]). However, 82% (61/74) of patients' pending urine cultures did not have 24-hour preliminary results, and 19% (13/70) of patients' pending blood cultures did not have 48-hour preliminary results available at the time of hospital discharge.
Approximately one-third of the sub-acute care patients in this study had labs pending at discharge, but few were documented within hospital discharge summaries. Even after considering the availability of preliminary microbiology results, these omissions remain common. Future studies should focus on improving the communication of pending lab tests at discharge and evaluating the impact that this improved communication has on patient outcomes.
C1 [Walz, Stacy E.; Smith, Maureen; Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53706 USA.
[Smith, Maureen] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA.
[Smith, Maureen] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA.
[Cox, Elizabeth] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA.
[Sattin, Justin] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI USA.
[Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Div Geriatr, Dept Med, Madison, WI USA.
[Kind, Amy J. H.] William S Middleton Mem Vet Adm Med Ctr, GRECC, US Dept Vet Affairs, Madison, WI USA.
RP Walz, SE (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53706 USA.
EM sewalz@wisc.edu
FU University of Wisconsin (UW) Hartford Center of Excellence in
Geriatrics; UW; NIH [1KL2RR025012-01]; National Center for Research
Resources, National Institute of Health [1UL1RR025011]; University of
Wisconsin Institute for Clinical and Translational Research (UW ICTR);
National Center for Research Resources, National Institutes of Health
[1UL1RR025011]; National Institute on Aging [K23AG034551]
FX Funding for this project was provided by the University of Wisconsin
(UW) Hartford Center of Excellence in Geriatrics and the UW Health
Innovation Program. Dr. Kind is supported by a K-L2 through the NIH
grant 1KL2RR025012-01 [Institutional Clinical and Translational Science
Award (UW-Madison) 1UL1RR025011 (KL2) program of the National Center for
Research Resources, National Institute of Health]. Additional support
was provided by the Health Innovation Program and the Community-Academic
Partnerships core of the University of Wisconsin Institute for Clinical
and Translational Research (UW ICTR), grant 1UL1RR025011 from the
Clinical and Translational Science Award (CTSA) program of the National
Center for Research Resources, National Institutes of Health. The
project described was supported by Award Number K23AG034551 from the
National Institute on Aging. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institute on Aging or the National Institutes of Health.
NR 29
TC 14
Z9 14
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 2011
VL 26
IS 4
BP 393
EP 398
DI 10.1007/s11606-010-1583-7
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 733KD
UT WOS:000288260700009
PM 21116868
ER
PT J
AU Press, MJ
Silber, JH
Rosen, AK
Romano, PS
Itani, KMF
Zhu, JS
Wang, YL
Even-Shoshan, O
Halenar, MJ
Volpp, KG
AF Press, Matthew J.
Silber, Jeffrey H.
Rosen, Amy K.
Romano, Patrick S.
Itani, Kamal M. F.
Zhu, Jingsan
Wang, Yanli
Even-Shoshan, Orit
Halenar, Michael J.
Volpp, Kevin G.
TI The Impact of Resident Duty Hour Reform on Hospital Readmission Rates
Among Medicare Beneficiaries
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE education; medical; graduate; hospital; readmission
ID QUALITY-OF-CARE; ADMINISTRATIVE DATA; ACCREDITATION COUNCIL; COMORBIDITY
MEASURES; PATIENT PREDICTORS; STATISTICAL-MODELS; REGULATIONS;
INFORMATION; MORTALITY; TRANSITIONS
AB A key goal of resident duty hour reform by the Accreditation Council for Graduate Medical Education (ACGME) in 2003 was to improve patient outcomes.
To assess whether the reform led to a change in readmission rates.
Observational study using multiple time series analysis with hospital discharge data from July 1, 2000 to June 30, 2005. Fixed effects logistic regression was used to examine the change in the odds of readmission in more versus less teaching-intensive hospitals before and after duty hour reform.
All unique Medicare patients (n = 8,282,802) admitted to acute-care nonfederal hospitals with principal diagnoses of acute myocardial infarction, congestive heart failure, gastrointestinal bleeding, or stroke (combined medical group), or a DRG classification of general, orthopedic, or vascular surgery (combined surgical group).
Primary outcome was 30-day all-cause readmission. Secondary outcomes were (1) readmission or death within 30 days of discharge, and (2) readmission, death during the index admission, or death within 30 days of discharge.
For the combined medical group, there was no evidence of a change in readmission rates in more versus less teaching-intensive hospitals [OR = 0.99 (95% CI 0.94, 1.03) in post-reform year 1 and OR = 0.99 (95% CI 0.95, 1.04) in post-reform year 2]. There was also no evidence of relative changes in readmission rates for the combined surgical group: OR = 1.03 (95% CI 0.98, 1.08) for post-reform year 1 and OR = 1.02 (95% CI 0.98, 1.07) for post-reform year 2. Findings for the secondary outcomes combining readmission and death were similar.
Among Medicare beneficiaries, there were no changes in hospital readmission rates associated with resident duty hour reform.
C1 [Press, Matthew J.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA.
[Press, Matthew J.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Halenar, Michael J.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Silber, Jeffrey H.; Zhu, Jingsan; Halenar, Michael J.; Volpp, Kevin G.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.; Even-Shoshan, Orit; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.; Wang, Yanli; Even-Shoshan, Orit] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA.
[Rosen, Amy K.; Itani, Kamal M. F.] VA Boston Hlth Care Syst, Boston, MA USA.
[Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA.
[Romano, Patrick S.] UC Davis Sch Med, Div Gen Med, Sacramento, CA USA.
[Romano, Patrick S.] UC Davis Sch Med, Ctr Healthcare Policy & Res, Sacramento, CA USA.
[Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA.
[Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Res, Boston, MA 02215 USA.
RP Press, MJ (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, 402 E 67th St, New York, NY 10065 USA.
EM map9069@med.cornell.edu
RI Romano, Patrick/N-4225-2014
OI Romano, Patrick/0000-0001-6749-3979
FU National Heart, Lung, and Blood Institute
FX Dr. Press was in the Robert Wood Johnson Foundation Clinical Scholars
Program at the University of Pennsylvania and the Philadelphia VA
Medical Center at the time this work was conducted. Funding for this
work was provided by a grant from the National Heart, Lung, and Blood
Institute. We presented an earlier version of the manuscript as an oral
presentation at the 2010 SGIM Annual Meeting in Minneapolis.
NR 47
TC 15
Z9 15
U1 0
U2 3
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 2011
VL 26
IS 4
BP 405
EP 411
DI 10.1007/s11606-010-1539-y
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 733KD
UT WOS:000288260700011
PM 21057883
ER
PT J
AU Barnett, L
Goenka, R
Silver, J
O'Neill, P
Hunter, C
Cancro, M
Laufer, T
AF Barnett, Lisa
Goenka, Radhika
Silver, Jonathan
O'Neill, Patrick
Hunter, Christopher
Cancro, Michael
Laufer, Terri
TI T follicular helper cells require cognate B cell interactions for
acquisition of full effector function
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Barnett, Lisa; Goenka, Radhika; O'Neill, Patrick; Cancro, Michael; Laufer, Terri] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Silver, Jonathan; Hunter, Christopher] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
[Laufer, Terri] Philadelphia VA Med Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 63.4
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751702037
ER
PT J
AU Basher, F
Harrell, M
Richard, E
Nowling, T
AF Basher, Fahmin
Harrell, Maria
Richard, Erin
Nowling, Tamara
TI Effects of Fli1 on T cell function in systemic lupus erythematosus
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Basher, Fahmin; Harrell, Maria; Richard, Erin; Nowling, Tamara] Med Univ S Carolina, Med Rheumatol, Charleston, SC 29425 USA.
[Nowling, Tamara] Ralph H Johnson VA Med, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 44.44
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751700006
ER
PT J
AU Bodhankar, S
Wang, CH
Vandenbark, A
Offner, H
AF Bodhankar, Sheetal
Wang, Chunhe
Vandenbark, Arthur
Offner, Haling
TI Indispensable role of B cells in mediating protective effects of
estrogen against EAE
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Bodhankar, Sheetal; Wang, Chunhe; Vandenbark, Arthur; Offner, Haling] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Bodhankar, Sheetal; Vandenbark, Arthur; Offner, Haling] Portland VA Med Ctr, Portland, OR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 167.20
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751708025
ER
PT J
AU Bu, X
DeKruyff, R
Umetsu, D
Freeman, G
AF Bu, Xia
DeKruyff, Rosemarie
Umetsu, Dale
Freeman, Gordon
TI TIM-3-and TIM-4-mediated phagocytosis of apoptotic cells induces
cytokine production in peritoneal macrophages
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Bu, Xia; Freeman, Gordon] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA.
[DeKruyff, Rosemarie; Umetsu, Dale] Childrens Hosp Boston, Boston, MA USA.
[Bu, Xia; DeKruyff, Rosemarie; Umetsu, Dale; Freeman, Gordon] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 100.55
PG 2
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751703080
ER
PT J
AU De Costala, AM
Walker, D
Schuyler, C
Young, R
AF De Costala, Anna-Maria
Walker, David
Schuyler, Corinne
Young, Rita
TI Administration of a vaccine composed of dendritic cells pulsed with
premalignant oral lesion lysate stimulates Th1 and Th17 immunity in mice
bearing carcinogen-induced premalignant oral lesions
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [De Costala, Anna-Maria; Young, Rita] Med Univ South Carolina, Microbiol & Immunol, Charleston, SC USA.
[De Costala, Anna-Maria; Walker, David; Schuyler, Corinne; Young, Rita] Ralph H Johnson VA Med Ctr, Med Res Serv, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 165.13
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751708014
ER
PT J
AU Dileepan, T
Linehan, J
Moon, J
Pepper, M
Jenkins, M
Cleary, P
AF Dileepan, Thamotharampillai
Linehan, Jonathan
Moon, James
Pepper, Marion
Jenkins, Marc
Cleary, Patrick
TI Epitope-specific CD4(+) T cell response to Group A Streptococcal
infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Dileepan, Thamotharampillai; Linehan, Jonathan; Pepper, Marion; Jenkins, Marc; Cleary, Patrick] Univ Minnesota, Microbiol, Minneapolis, MN USA.
[Moon, James] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 99.27
PG 2
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751703001
ER
PT J
AU Dileepan, T
Kim, H
Moon, J
Linehan, J
Jenkins, M
Cleary, P
Skinner, P
AF Dileepan, Thamotharampillai
Kim, Hyeon
Moon, James
Linehan, Jonathan
Jenkins, Marc
Cleary, Patrick
Skinner, Pamela
TI In situ peptide-MHC-II tetramer staining of antigen-specific CD4(+) T
cells in tissues
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Dileepan, Thamotharampillai; Kim, Hyeon; Linehan, Jonathan; Jenkins, Marc; Cleary, Patrick; Skinner, Pamela] Univ Minnesota, Microbiol, Minneapolis, MN USA.
[Moon, James] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 65.37
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751702121
ER
PT J
AU Ding, YN
Hsu, HC
Wu, Q
Yang, P
Mountz, J
AF Ding, Yanna
Hsu, Hui-Chen
Wu, Qi
Yang, Pingar
Mountz, John
TI Sequential effects of IL-21 and IL-17 to regulate spleen CXCR5(+)
follicular T helper cells in autoimmune BXD2 mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Ding, Yanna; Hsu, Hui-Chen; Wu, Qi; Yang, Pingar; Mountz, John] Univ Alabama Birmingham, Birmingham, AL USA.
[Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 101.44
PG 2
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751703111
ER
PT J
AU Farley, K
Stolley, J
Cooley, J
Remold-O'Donnelll, E
AF Farley, Kalamo
Stolley, James
Cooley, Jessica
Remold-O'Donnelll, Eileen
TI SerpinB1 functions in generating neutrophil extracellular traps
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Farley, Kalamo; Stolley, James; Cooley, Jessica; Remold-O'Donnelll, Eileen] Harvard Univ, Childrens Hosp, Sch Med, Immune Dis Inst Program Cellular & Mol Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 111.11
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751704176
ER
PT J
AU Jiang, XD
Wagers, A
Clark, R
Liu, LZ
Fuhlbrigge, R
Kupper, T
AF Jiang, Xiaodong
Wagers, Amy
Clark, Rachael
Liu, Luzheng
Fuhlbrigge, Robert
Kupper, Thomas
TI CD8 T cells are rapidly recruited to both immunized and unimmunized skin
after vaccinica virus skin scarification persist long-term as
nonmigratory resident memory T cells (Trm), and provide rapid,
effective, and specific local immunity
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Jiang, Xiaodong; Clark, Rachael; Liu, Luzheng; Fuhlbrigge, Robert; Kupper, Thomas] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wagers, Amy] Harvard Univ, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Harvard Stem Cell Inst,Joslin Diabet Ctr, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 102.25
PG 2
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751703150
ER
PT J
AU Kalsy, A
Bhuiyan, M
Charles, R
Arifuzzaman, M
Clemens, JD
Larocque, RC
Harris, JB
Calderwood, SB
Czerkinsky, C
Qadri, F
Ryan, E
AF Kalsy, Anuj
Bhuiyan, Md
Charles, Richelle
Arifuzzaman, Mohammad
Clemens, John D.
Larocque, Regina C.
Harris, Jason B.
Calderwood, Stephen B.
Czerkinsky, Cecil
Qadri, Firdausi
Ryan, Edward
TI Induction of memory responses following transcutaneous immunization
requires presence of immunoadjuvantative cholera holotoxin
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Bhuiyan, Md; Qadri, Firdausi] Int Ctr Diarrheal Dis Res, Dhaka, Bangladesh.
[Kalsy, Anuj; Charles, Richelle; Arifuzzaman, Mohammad; Larocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward] Harvard Univ, Massachusetts Gen Hosp, Med, Boston, MA USA.
[Kalsy, Anuj; Charles, Richelle; Larocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward] Harvard Univ, Sch Med, Boston, MA USA.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Med Genet, Boston, MA USA.
[Ryan, Edward] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Clemens, John D.; Czerkinsky, Cecil] Int Vaccine Inst, Seoul, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 53.4
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751701044
ER
PT J
AU Li, H
Wu, Q
Yang, PA
Cua, D
Hsu, HC
Mountz, J
AF Li, Hao
Wu, Qi
Yang, PingAr
Cua, Daniel
Hsu, Hui-Chen
Mountz, John
TI IL-23 induces apoptosis of self-reactive thymocytes in thymic negative
selection by an Rorc dependent mechanism
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Li, Hao] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Li, Hao; Wu, Qi; Yang, PingAr; Hsu, Hui-Chen; Mountz, John] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Cua, Daniel] Merck Res Labs, Palo Alto, CA USA.
[Mountz, John] Birmingham VA Med Ctr, Birmingham, AL USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 64.19
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751702078
ER
PT J
AU Li, J
Hsu, HC
Yang, PA
Wu, Q
Li, H
Mountz, J
AF Li, Jun
Hsu, Hui-Chen
Yang, PingAr
Wu, Qi
Li, Hao
Mountz, John
TI Anti-DR5 antibody eliminates inflammatory macrophages rebalancing
IL-23/Th17 axis and regulatory T cells in arthritis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Li, Hao; Mountz, John] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA.
[Mountz, John] Birmingham VA Med Ctr, Birmigham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 147.26
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751705167
ER
PT J
AU Lukacs-Kornek, V
Malhotra, D
Fletcher, A
Pinner, S
Tayalia, P
Turley, S
AF Lukacs-Kornek, Veronika
Malhotra, Deepali
Fletcher, Anne
Pinner, Sophie
Tayalia, Prakriti
Turley, Shannon
TI Regulated release of nitric oxide by fibroblastic reticular cells
controls the frequency and pathogenicity of autoreactive T cells in a
model of intestinal tolerance
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Lukacs-Kornek, Veronika; Malhotra, Deepali; Fletcher, Anne; Pinner, Sophie; Turley, Shannon] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Turley, Shannon] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Tayalia, Prakriti] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 44.37
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751700022
ER
PT J
AU Nowling, T
Richard, EM
Harrell, M
Basher, F
Zhang, J
AF Nowling, Tamara
Richard, Erin Morris
Harrell, Maria
Basher, Fahmin
Zhang, John
TI Specific effects of Fli1 levels on T cells in the MRL/Ipr lupus prone
model
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Nowling, Tamara; Richard, Erin Morris; Harrell, Maria; Basher, Fahmin; Zhang, John] Med Univ S Carolina, Med Rheumatol, Charleston, SC 29425 USA.
[Nowling, Tamara; Zhang, John] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 44.30
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751700025
ER
PT J
AU Paintlia, A
Paintlia, M
Singh, A
Singh, I
AF Paintlia, Ajaib
Paintlia, Manjeet
Singh, Avtar
Singh, Inderjit
TI Lovastatin exhibits synergy with Vitamin D hormone to confer protection
from experimental autoimmune encephalomylitis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Paintlia, Ajaib; Paintlia, Manjeet; Singh, Inderjit] Med Univ S Carolina, Charleston, SC 29425 USA.
[Singh, Avtar] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 148.5
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751705190
ER
PT J
AU Paintlia, M
Paintlia, A
Singh, A
Singh, I
AF Paintlia, Manjeet
Paintlia, Ajaib
Singh, Avtar
Singh, Inderjit
TI Interleukin-17 exacerbates tumor necrosis Factor-alpha induced apoptotic
cell death of oligodendrocytes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Paintlia, Manjeet; Paintlia, Ajaib; Singh, Inderjit] MUSC, Charleston, SC USA.
[Singh, Avtar] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 148.8
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751705192
ER
PT J
AU Penaloza-MacMaster, P
Araki, K
Kamphorst, A
Iyer, S
West, E
Konieczny, B
Freeman, G
Rudenski, A
Ahmed, R
AF Penaloza-MacMaster, Pablo
Araki, Koichi
Kamphorst, Alice
Iyer, Smita
West, Erin
Konieczny, Bogna
Freeman, Gordon
Rudenski, Alexander
Ahmed, Rafi
TI FoxP3+CD4+cells promote CD8 T cell exhaustion during chronic infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Penaloza-MacMaster, Pablo; Araki, Koichi; Kamphorst, Alice; Iyer, Smita; West, Erin; Konieczny, Bogna; Ahmed, Rafi] Emory Univ, Atlanta, GA 30322 USA.
[Rudenski, Alexander] Sloan Kettering Inst, New York, NY USA.
[Freeman, Gordon] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 105.5
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751704002
ER
PT J
AU Pinner, S
Turley, S
AF Pinner, Sophie
Turley, Shannon
TI Podoplanin-rich stromal networks induce dendritic cell motility via
activation of CLEC-2
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Pinner, Sophie; Turley, Shannon] Dana Farber Canc Inst, Canc Immunol & AIDS, Boston, MA 02115 USA.
[Pinner, Sophie] UCL, London, England.
[Turley, Shannon] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 102.21
PG 2
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751703148
ER
PT J
AU Suzuki, E
Williams, S
Karam, E
Zhang, X
AF Suzuki, Eiji
Williams, Sarah
Karam, Eva
Zhang, Xian
TI Transcription factor Fli-1 is involved in regulation of dendritic cell
and monocyte development
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Suzuki, Eiji; Karam, Eva; Zhang, Xian] Med Univ S Carolina, Charleston, SC 29425 USA.
[Williams, Sarah; Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 153.33
PG 2
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751706107
ER
PT J
AU Taniguchi, R
Devoss, J
Moon, J
Jenkins, M
Anderson, M
AF Taniguchi, Ruth
Devoss, Jason
Moon, James
Jenkins, Marc
Anderson, Mark
TI Aire mediates peptide epitope-specific thymic deletion of self reactive
T cells to prevent autoimmune uveitis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Taniguchi, Ruth; Devoss, Jason; Anderson, Mark] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Moon, James] Univ Minnesota, Minneapolis, MN USA.
[Moon, James; Jenkins, Marc] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 148.3
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751705182
ER
PT J
AU Walker, D
Reeves, T
De Costa, AM
Schuyler, C
Young, MR
AF Walker, David
Reeves, Travis
De Costa, Anna-Maria
Schuyler, Corinne
Young, M. Rita
TI The effects of 1,25-dihydroxy vitamin D3 on tumor-associated
immunosuppression in squamous cell carcinoma of the head and neck.
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Walker, David; Reeves, Travis; Young, M. Rita] Med Univ S Carolina, Otolaryngol, Charleston, SC 29425 USA.
[Schuyler, Corinne; Young, M. Rita] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[De Costa, Anna-Maria] Med Univ S Carolina, Microbiol & Immunol, Charleston, SC 29425 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 165.29
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751707188
ER
PT J
AU Wang, S
Villablanca, E
Gomes, D
Nguyen, D
Mizoguchi, E
Kagan, J
Reinecker, HC
Hacohen, N
Nagler, C
Xavier, R
Rossi-Bergmann, B
Chen, YB
Blomhoff, R
Snapper, S
Mora, R
AF Wang, Sen
Villablanca, Eduardo
Gomes, Daniel
Nguyen, Deanna
Mizoguchi, Emiko
Kagan, Jonathan
Reinecker, Hans-Christian
Hacohen, Nir
Nagler, Cathryn
Xavier, Ramnik
Rossi-Bergmann, Bartira
Chen, Yi-Bin
Blomhoff, Rune
Snapper, Scott
Mora, Rodrigo
TI MyD88-dependent TLR signals are necessary and sufficient to confer
dendritic cells with gut-specific imprinting properties.
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Wang, Sen; Villablanca, Eduardo; Nguyen, Deanna; Mizoguchi, Emiko; Reinecker, Hans-Christian; Xavier, Ramnik; Snapper, Scott; Mora, Rodrigo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA.
[Gomes, Daniel; Rossi-Bergmann, Bartira] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio De Janeiro, Brazil.
[Kagan, Jonathan] Childrens Hosp, Gastrointestinal Unit, Boston, MA 02115 USA.
[Hacohen, Nir] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA.
[Nagler, Cathryn] Univ Chicago, Dept Pathol, Comm Immunol, BSD, Chicago, IL 60637 USA.
[Chen, Yi-Bin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat, Boston, MA USA.
[Blomhoff, Rune] Univ Oslo, Inst Basic Med Sci, Bostonoslo, Norway.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 161.2
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751707088
ER
PT J
AU Zhang, X
Williams, S
Suzuki, E
Karam, E
Gikeson, G
AF Zhang, Xian
Williams, Sarah
Suzuki, Eiji
Karam, Eva
Gilkeson, Gary
TI Fli-1 transcription factor affects inflammatory cell infiltration in the
lupus nephritis development by regulating expression of inflammatory
chemokines
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Zhang, Xian; Suzuki, Eiji; Karam, Eva; Gilkeson, Gary] Med Univ S Carolina, Med, Charleston, SC 29425 USA.
[Zhang, Xian; Williams, Sarah; Gilkeson, Gary] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD APR
PY 2011
VL 186
SU 1
MA 44.12
PG 1
WC Immunology
SC Immunology
GA V44LY
UT WOS:000209751700040
ER
PT J
AU Hatano, H
Hayes, TL
Dahl, V
Sinclair, E
Lee, TH
Hoh, R
Lampiris, H
Hunt, PW
Palmer, S
McCune, JM
Martin, JN
Busch, MP
Shacklett, BL
Deeks, SG
AF Hatano, Hiroyu
Hayes, Timothy L.
Dahl, Viktor
Sinclair, Elizabeth
Lee, Tzong-Hae
Hoh, Rebecca
Lampiris, Harry
Hunt, Peter W.
Palmer, Sarah
McCune, Joseph M.
Martin, Jeffrey N.
Busch, Michael P.
Shacklett, Barbara L.
Deeks, Steven G.
TI A Randomized, Controlled Trial of Raltegravir Intensification in
Antiretroviral-treated, HIV-infected Patients with a Suboptimal CD4(+) T
Cell Response
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; LOW-LEVEL VIREMIA;
POLYMERASE-CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS; IMMUNE
RECONSTITUTION; TYPE-1 INFECTION; THERAPY; ACTIVATION; SUPPRESSION;
INDIVIDUALS
AB Background. Some human immunodeficiency virus (HIV)-infected individuals are not able to achieve a normal CD4(+) T cell count despite prolonged, treatment-mediated viral suppression. We conducted an intensification study to assess whether residual viral replication contributes to replenishment of the latent reservoir and whether mucosal HIV-specific T cell responses limit the reservoir size.
Methods. Thirty treated subjects with CD4(+) T cell counts of <350 cells/mm(3) despite viral suppression for >= 1 year were randomized to add raltegravir (400 mg twice daily) or matching placebo for 24 weeks. The primary end points were the proportion of subjects with undetectable plasma viremia (determined using an ultrasensitive assay with a lower limit of detection of <.3 copy/mL) and a change in the percentage of CD38(+)HLA-DR(+)CD8(+) T cells in peripheral blood mononuclear cells (PBMCs).
Results. The proportion of subjects with undetectable plasma viremia did not differ between the 2 groups (P = .42). Raltegravir intensification did not have a significant effect on immune activation or HIV-specific responses in PBMCs or gut-associated lymphoid tissue.
Conclusions. Low-level viremia is not likely to be a significant cause of suboptimal CD4(+) T cell gains during HIV treatment.
C1 [Hatano, Hiroyu; Sinclair, Elizabeth; Hoh, Rebecca; Lampiris, Harry; Hunt, Peter W.; McCune, Joseph M.; Martin, Jeffrey N.; Busch, Michael P.; Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hayes, Timothy L.; Shacklett, Barbara L.] Univ Calif Davis, Davis, CA 95616 USA.
[Dahl, Viktor; Palmer, Sarah] Karolinska Inst, Solna, Sweden.
[Dahl, Viktor; Palmer, Sarah] Swedish Inst Infect Dis Control, Solna, Sweden.
[Lee, Tzong-Hae; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Lampiris, Harry] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Hatano, H (reprint author), San Francisco Gen Hosp, Bldg 80,Ward 84,995 Potrero Ave, San Francisco, CA 94110 USA.
EM hhatano@php.ucsf.edu
RI Shacklett, Barbara/A-7288-2009;
OI Shacklett, Barbara/0000-0002-7067-732X; Dahl, Viktor/0000-0001-9921-5172
FU National Institute of Allergy and Infectious Diseases [K23AI075985,
K24AI069994, AI052745, AI055273, RR16482, R01 AI087145, R01 AI057020];
American Foundation for AIDS Research [106710-40-RGRL, 107170-44-RGRL];
Universitywide AIDS Research Program [CC99-SF-001]; UCSF/Gladstone
Institute of Virology and Immunology Center for AIDS Research [P30
AI027763]; UCSF Clinical and Translational Research Institute Clinical
Research Center [UL1 RR024131]; Center for AIDS Prevention Studies [P30
MH62246]; Center for HIV/AIDS Vaccine Immunology [U01-AI067854]; NCRR
[C06 RR - 12088]; Swedish Research Council; National Institutes of
Health (NIH) [DPI OD00329]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (grant numbers K23AI075985, K24AI069994, AI052745,
AI055273, RR16482, R01 AI087145, R01 AI057020), the American Foundation
for AIDS Research (grant number 106710-40-RGRL), the Universitywide AIDS
Research Program (grant number CC99-SF-001), the UCSF/Gladstone
Institute of Virology and Immunology Center for AIDS Research (grant
number P30 AI027763), the Clinical Research Center at San Francisco
General Hospital, supported by the UCSF Clinical and Translational
Research Institute Clinical Research Center (grant number UL1 RR024131),
the Center for AIDS Prevention Studies (P30 MH62246), and the Center for
HIV/AIDS Vaccine Immunology (grant number U01-AI067854). Mucosal samples
were analyzed in a facility constructed with support from NCRR (grant
number C06 RR - 12088). S. P. was funded, in part, by the Swedish
Research Council and by the American Foundation for AIDS Research (grant
number 107170-44-RGRL). J.M.M. is a recipient of the National Institutes
of Health (NIH) Director's Pioneer Award Program, part of the NIH
Roadmap for Medical Research (grant number DPI OD00329).
NR 46
TC 116
Z9 116
U1 0
U2 0
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 APR 1
PY 2011
VL 203
IS 7
BP 960
EP 968
DI 10.1093/infdis/jiq138
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 737FF
UT WOS:000288553800011
PM 21402547
ER
PT J
AU Li, JZ
Brumme, ZL
Brumme, CJ
Wang, HY
Spritzler, J
Robertson, MN
Lederman, MM
Carrington, M
Walker, BD
Schooley, RT
Kuritzkes, DR
AF Li, Jonathan Z.
Brumme, Zabrina L.
Brumme, Chanson J.
Wang, Hongying
Spritzler, John
Robertson, Michael N.
Lederman, Michael M.
Carrington, Mary
Walker, Bruce D.
Schooley, Robert T.
Kuritzkes, Daniel R.
CA AIDS Clinical Trials Grp A5197
TI Factors Associated With Viral Rebound in HIV-1-Infected Individuals
Enrolled in a Therapeutic HIV-1 gag Vaccine Trial
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; CLASS-I; DISEASE
PROGRESSION; ESCAPE MUTATIONS; IMMUNE-RESPONSES; INFECTION; HLA; LOAD;
VIREMIA
AB Background. Human immunodeficiency virus type 1 (HIV-1) vaccines directed to the cell-mediated immune system could have a role in lowering the plasma HIV-1 RNA set point, which may reduce infectivity and delay disease progression.
Methods. Randomized, placebo-controlled trial involving HIV-1-infected participants who received a recombinant adenovirus serotype 5 (rAd5) HIV-1 gag vaccine or placebo. Sequence-based HLA typing was performed for all 110 participants who initiated analytic treatment interruption (ATI) to assess the role of HLA types previously associated with HIV prognosis. Plasma HIV-1 gag and pol RNA sequences were obtained during the ATI. Virologic endpoints and HLA groups were compared between treatment arms using the 2-sample rank sum test. A linear regression model was fitted to derive independent correlates of ATI week 16 plasma viral load (w16 PVL).
Results. Vaccinated participants with neutral HLA alleles had lower median w16 PVLs than did vaccinated participants with protective HLA alleles (P = .01) or placebo participants with neutral HLA alleles (P = .02). Factors independently associated with lower w16 PVL included lower pre-antiretroviral therapy PVL, greater Gag sequence divergence from the vaccine sequence, decreased proportion of HLA-associated polymorphisms in Gag, and randomization to the vaccine arm.
Conclusions. Therapeutic vaccination with a rAd5-HIV gag vaccine was associated with lower ATI week 16 PVL even after controlling for viral and host genetic factors.
C1 [Li, Jonathan Z.; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Cambridge, MA 02139 USA.
[Li, Jonathan Z.; Walker, Bruce D.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA.
[Brumme, Zabrina L.; Brumme, Chanson J.; Carrington, Mary; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA.
[Brumme, Zabrina L.; Brumme, Chanson J.; Carrington, Mary; Walker, Bruce D.] Harvard Univ, Cambridge, MA 02138 USA.
[Brumme, Zabrina L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
[Wang, Hongying; Spritzler, John] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Robertson, Michael N.] Merck Res Labs, N Wales, PA USA.
[Lederman, Michael M.] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA.
[Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Schooley, Robert T.] Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA.
RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Therapeut, 65 Landsdowne St,Rm 449, Cambridge, MA 02139 USA.
EM dkuritzkes@partners.org
OI Brumme, Chanson/0000-0003-2722-5288
FU Canadian Institutes of Health Research; Intramural NIH HHS; NCRR NIH HHS
[K24 RR016482]; NIAID NIH HHS [P30 AI60354, U01 AI068636, P30 AI060354,
T32 AI007387, T32 AI07387, U01 AI068634]; PHS HHS [HHSN261200800001E]
NR 43
TC 15
Z9 16
U1 1
U2 1
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 APR 1
PY 2011
VL 203
IS 7
BP 976
EP 983
DI 10.1093/infdis/jiq143
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 737FF
UT WOS:000288553800013
PM 21402549
ER
PT J
AU Branowicki, P
Driscoll, M
Hickey, P
Renaud, K
Sporing, E
AF Branowicki, Patricia
Driscoll, Margaret
Hickey, Patricia
Renaud, Kristen
Sporing, Eileen
TI Exemplary Professional Practice Through Nurse Peer Review
SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES
LA English
DT Review
DE Exemplary professional practice; Peer review; Nursing practice
ID QUALITY; CARE
AB The development and execution of a nurse peer review program to evaluate nursing practice associated with significant adverse events has resulted in systemic changes. Descriptive analyses were conducted for 23 peer-reviewed cases involving 41 RNs and 2 advanced practice nurses from 14 specialties over a 4-year period. Thematic analysis revealed four common event categories: assessment and monitoring, team communication, skin integrity, and vascular access. This approach demonstrates the impact of professional nurse accountability for improving the quality of care and may serve as an exemplar for professional practice. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Branowicki, Patricia; Hickey, Patricia; Renaud, Kristen; Sporing, Eileen] Childrens Hosp Boston, Dana Farber Canc Inst, Dept Nursing Patient Serv, Nursing Patient Care Serv, Boston, MA 02115 USA.
[Driscoll, Margaret] Childrens Hosp Boston, Program Patient Safety & Qual, Boston, MA USA.
RP Branowicki, P (reprint author), Childrens Hosp Boston, Dana Farber Canc Inst, Dept Nursing Patient Serv, Nursing Patient Care Serv, Boston, MA 02115 USA.
EM patricia.branowicki@childrens.harvard.edu
NR 24
TC 3
Z9 4
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0882-5963
J9 J PEDIATR NURS
JI J. Pediatr. Nurs.
PD APR
PY 2011
VL 26
IS 2
SI SI
BP 128
EP 136
DI 10.1016/j.pedn.2010.12.009
PG 9
WC Nursing; Pediatrics
SC Nursing; Pediatrics
GA 045OA
UT WOS:000311704900005
PM 21419972
ER
PT J
AU Patti, JA
AF Patti, John A.
TI Clouds on Radiology's Research Horizon
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA.
EM jpatti@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD APR
PY 2011
VL 8
IS 4
BP 215
EP 215
DI 10.1016/j.jacr.2011.03.005
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 961FI
UT WOS:000305449100001
PM 21458753
ER
PT J
AU Cuaron, JJ
Hirsch, AE
Medich, DC
Hirsch, JA
Rosenstein, BS
AF Cuaron, John J.
Hirsch, Ariel E.
Medich, David C.
Hirsch, Joshua A.
Rosenstein, Barry S.
TI Introduction to Radiation Safety and Monitoring
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Radiation safety; monitoring; radiology; precaution
AB Ionizing radiation is used in diagnostic imaging, external-beam radiation therapy, brachytherapy, and nuclear medicine to diagnose and treat a number of common conditions. To ensure the safety of patients, providers, and surrounding staff members, it is important that the health care community become familiar with the terminology, common equipment, and standard practices used in radiation safety and monitoring. The authors aim to provide an introduction to radiation safety and monitoring so that health care providers and support personnel who may have contact with patients, equipment, and facilities that use radioactive material may be more aware of the policies and precautions that are in place to ensure their safety.
C1 [Hirsch, Ariel E.] Boston Univ, Med Ctr, Dept Radiat Oncol, Sch Med, Boston, MA 02118 USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Neuroradiol, Boston, MA 02114 USA.
[Medich, David C.] Univ Massachusetts Lowell, Radiat Lab, Lowell, MA USA.
[Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Radiat Oncol, New York, NY USA.
[Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA.
[Rosenstein, Barry S.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA.
[Rosenstein, Barry S.] NYU, Sch Med, New York, NY USA.
RP Hirsch, JA (reprint author), Boston Univ, Med Ctr, Dept Radiat Oncol, Sch Med, 830 Harrison Ave,Moakley Bldg LL, Boston, MA 02118 USA.
EM ariel.hirsch@bmc.org
RI Medich, David/B-6006-2013
NR 6
TC 3
Z9 3
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD APR
PY 2011
VL 8
IS 4
BP 259
EP 264
DI 10.1016/j.jacr.2010.08.020
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 961FI
UT WOS:000305449100012
PM 21458764
ER
PT J
AU Friedlander, AH
AF Friedlander, Arthur H.
TI OSTEONECROSIS OF THE JAW
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Letter
C1 VA Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA.
RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA 90073 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER DENTAL ASSOC
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA
SN 0002-8177
EI 1943-4723
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD APR
PY 2011
VL 142
IS 4
BP 370
EP 371
PG 2
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 749EU
UT WOS:000289447200006
PM 21454841
ER
PT J
AU Seliverstov, I
AF Seliverstov, Irina
TI Practical management approaches to anticoagulation non-compliance,
health literacy, and limited English proficiency in the outpatient
clinic setting
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Article; Proceedings Paper
CT 11th National Conference on Anticoagulant Therapy
CY MAY 05-07, 2011
CL Boston, MA
SP Anticoagulat Forum
DE Warfarin; Non-compliance; Health literacy
ID WARFARIN; ADHERENCE; QUALITY
AB Warfarin is a widely used oral anticoagulant. It is highly efficacious for the treatment and prevention of thromboembolic disorders despite its narrow therapeutic window. Poor compliance with warfarin is common and a major contributor to poor anticoagulation control. A number of psychosocial issues (e.g. depressive symptoms, attitudinal and behavioral factors, cognitive function, lack of social support, limited English proficiency, health illiteracy) have been associated with warfarin non-compliance among patients in anticoagulation clinics. Patient-specific features, such as these, are important to identify in order to develop appropriate and practical interventions. Health literacy and limited English proficiency are the extension of issues related to culture, language, and ethnicity. A better understanding of patients' functioning level and health utilization factors may help to develop and target interventions for high risk patients and reduce complications from suboptimal therapy and poor warfarin management due to non-compliance. Four patient case scenarios will be used to illustrate these issues and identify potential interventions to optimize warfarin therapy.
C1 Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA.
RP Seliverstov, I (reprint author), Massachusetts Gen Hosp, Anticoagulat Management Serv, 275 Cambridge St,Suite 101, Boston, MA 02114 USA.
EM iseliverstov@partners.org
NR 7
TC 6
Z9 7
U1 1
U2 6
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 2011
VL 31
IS 3
SI SI
BP 321
EP 325
DI 10.1007/s11239-011-0560-2
PG 5
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 733KZ
UT WOS:000288262900012
PM 21337118
ER
PT J
AU Sullivan, K
Sherman, O
Eng, C
Ribner, H
Liao, S
AF Sullivan, K.
Sherman, O.
Eng, C.
Ribner, H.
Liao, S.
TI Management recommendations for subtherapeutic international normalized
ratio (INR) and consecutive subtherapeutic INR in an anticoagulation
clinic
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Meeting Abstract
C1 [Sullivan, K.; Sherman, O.; Eng, C.; Ribner, H.; Liao, S.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
NR 0
TC 0
Z9 0
U1 1
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 2011
VL 31
IS 3
SI SI
BP 379
EP 379
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 733KZ
UT WOS:000288262900043
ER
PT J
AU Oertel, LB
O'Neil, JA
AF Oertel, L. B.
O'Neil, J. A.
TI Impact of patient self testing on time in therapeutic range
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Meeting Abstract
C1 [Oertel, L. B.; O'Neil, J. A.] Massachusetts Gen Hosp, Anticoagulat Management Serv, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2011
VL 31
IS 3
SI SI
BP 380
EP 381
PG 2
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 733KZ
UT WOS:000288262900047
ER
PT J
AU Banerjee, I
Sharma, N
Yarmush, M
AF Banerjee, Ipsita
Sharma, Nripen
Yarmush, Martin
TI Impact of co-culture on pancreatic differentiation of embryonic stem
cells
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Article
DE embryonic stem cell; differentiation; pancreatic islet; co-culture;
diabetes; endothelial cell
ID INSULIN-PRODUCING CELLS; IN-VITRO DIFFERENTIATION; TRANS-RETINOIC ACID;
BETA-CELLS; GENE-EXPRESSION; SECRETING CELLS; ENDOCRINE-CELLS; ISLETS;
PRECURSORS; INDUCTION
AB Promise of cellular therapy for type 1 diabetes has inspired the search for transplantable cell sources, and embryonic stem cells (ESCs) have emerged as strong candidates. We have developed a directed differentiation protocol to obtain insulin-producing cells from ESCs. The ESCs are first induced towards a homogeneous monolayer of definitive endoderm-like cells by co-culture with primary hepatocytes. Pancreatic commitment is induced by plating the ESC-derived endoderms on Matrigel, along with Sonic hedgehog inhibition and retinoid induction. More than 70% of differentiated cells positively upregulated Pdx-1, along with pro-endocrine transcription factors Ngn3, beta 2/neroD1, Nkx2.2 and Nkx6.1. Final maturation to islet-specific cells is achieved by co-culturing the ESC-derived pancreatic endocrine cells with endothelial cells, which resulted in Insulin 1 upregulation in 60% of the cell population, along with high levels of IAPP and Glut2. The differentiated cell population also secreted high levels of insulin. Our findings illustrate the significant effect of co-culture in different stages of differentiation and maturation of ESCs in vitro. Such a high yield of pancreatic islet cells has not yet been reported. Our findings establish a robust protocol for islet differentiation. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Banerjee, Ipsita; Sharma, Nripen; Yarmush, Martin] Harvard Univ, Sch Med, Ctr Engn Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Banerjee, Ipsita] Univ Pittsburgh, Dept Chem Engn, Pittsburgh, PA 15261 USA.
[Yarmush, Martin] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA.
RP Banerjee, I (reprint author), Harvard Univ, Sch Med, Ctr Engn Med, Massachusetts Gen Hosp, 55 Blossom St, Boston, MA 02114 USA.
EM ipb1@pitt.edu
NR 43
TC 15
Z9 16
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1932-6254
J9 J TISSUE ENG REGEN M
JI J. Tissue Eng. Regen. Med.
PD APR
PY 2011
VL 5
IS 4
BP 313
EP 323
DI 10.1002/term.317
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Engineering, Biomedical
SC Cell Biology; Biotechnology & Applied Microbiology; Engineering
GA 737HD
UT WOS:000288558800013
PM 20717889
ER
PT J
AU Budde, ML
Lhost, JJ
Burwitz, BJ
Becker, EA
Burns, CM
O'Connor, SL
Karl, JA
Wiseman, RW
Bimber, BN
Zhang, GL
Hildebrand, W
Brusic, V
O'Connor, DH
AF Budde, Melisa L.
Lhost, Jennifer J.
Burwitz, Benjamin J.
Becker, Ericka A.
Burns, Charles M.
O'Connor, Shelby L.
Karl, Julie A.
Wiseman, Roger W.
Bimber, Benjamin N.
Zhang, Guang Lan
Hildebrand, William
Brusic, Vladimir
O'Connor, David H.
TI Transcriptionally Abundant Major Histocompatibility Complex Class I
Alleles Are Fundamental to Nonhuman Primate Simian Immunodeficiency
Virus-Specific CD8(+) T Cell Responses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INFECTED RHESUS-MONKEYS; PEPTIDE-BINDING SPECIFICITY; CYNOMOLGUS
MACAQUES; LYMPHOCYTE RESPONSES; MAMU-B-ASTERISK-08-POSITIVE MACAQUES;
SIVMAC239 REPLICATION; DISEASE PROGRESSION; VIRAL PROTEIN; CTL EPITOPE;
MOLECULE
AB Simian immunodeficiency virus (SIV)-infected macaques are the preferred animal model for human immunodeficiency virus (HIV) vaccines that elicit CD8(+) T cell responses. Unlike humans, whose CD8(+) T cell responses are restricted by a maximum of six HLA class I alleles, macaques express up to 20 distinct major histocompatibility complex class I (MHC-I) sequences. Interestingly, only a subset of macaque MHC-I sequences are transcriptionally abundant in peripheral blood lymphocytes. We hypothesized that highly transcribed MHC-I sequences are principally responsible for restricting SIV-specific CD8(+) T cell responses. To examine this hypothesis, we measured SIV-specific CD8(+) T cell responses in MHC-I homozygous Mauritian cynomolgus macaques. Each of eight CD8(+) T cell responses defined by full-proteome gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay were restricted by four of the five transcripts that are transcriptionally abundant (>1% of total MHC-I transcripts in peripheral blood lymphocytes). The five transcriptionally rare transcripts shared by these animals did not restrict any detectable CD8(+) T cell responses. Further, seven CD8(+) T cell responses were defined by identifying peptide binding motifs of the three most frequent MHC-I transcripts on the M3 haplotype. Combined, these results suggest that transcriptionally abundant MHC-I transcripts are principally responsible for restricting SIV-specific CD8(+) T cell responses. Thus, only a subset of the thousands of known MHC-I alleles in macaques should be prioritized for CD8(+) T cell epitope characterization.
C1 [Budde, Melisa L.; Lhost, Jennifer J.; Burwitz, Benjamin J.; Burns, Charles M.; O'Connor, Shelby L.; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
[Becker, Ericka A.; Karl, Julie A.; Wiseman, Roger W.; Bimber, Benjamin N.; O'Connor, David H.] Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA.
[Hildebrand, William] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA.
[Zhang, Guang Lan; Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
RP O'Connor, DH (reprint author), 555 Sci Dr, Madison, WI 53711 USA.
EM doconnor@primate.wisc.edu
OI o'connor, david/0000-0003-2139-470X
FU National Institutes of Health [R01 AI077376-01, R21 AI082880-01];
National Institute of Allergy and Infectious Diseases [R01
5R01A1084787-02]; Research Facilities Improvement Program [RR15459-01,
RR020141-01]; National Center for Research Resources, a component of the
National Institutes of Health [P51 RR000167]
FX This research was supported by National Institutes of Health grants R01
AI077376-01 and R21 AI082880-01 and grant R01 5R01A1084787-02 from the
National Institute of Allergy and Infectious Diseases. Work for this
manuscript was conducted in a facility constructed with support from
Research Facilities Improvement Program grants RR15459-01 and
RR020141-01.; We thank David Watkins and his lab members Shari
Piaskowski, Matthew Reynolds, and Nancy Wilson. Additionally, we thank
David Price and Emma Gostick for their aid in generating tetramers and
Ann Detmer for her help with viral sequencing. We thank the staff at the
Wisconsin National Primate Research Center, a facility supported by
grant P51 RR000167 from the National Center for Research Resources, a
component of the National Institutes of Health.
NR 56
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U2 2
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 2011
VL 85
IS 7
BP 3250
EP 3261
DI 10.1128/JVI.02355-10
PG 12
WC Virology
SC Virology
GA 734WT
UT WOS:000288373000020
PM 21270169
ER
PT J
AU Shtanko, O
Watanabe, S
Jasenosky, LD
Watanabe, T
Kawaoka, Y
AF Shtanko, Olena
Watanabe, Shinji
Jasenosky, Luke D.
Watanabe, Tokiko
Kawaoka, Yoshihiro
TI ALIX/AIP1 Is Required for NP Incorporation into Mopeia Virus Z-Induced
Virus-Like Particles
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; ZINC-BINDING PROTEIN; FINGER
Z-PROTEIN; MULTIVESICULAR BODY; LATE DOMAINS; ASSEMBLY DOMAIN;
C-PROTEIN; ESCRT-III; ALIX; HIV-1
AB During virus particle assembly, the arenavirus nucleoprotein (NP) associates with the viral genome to form nucleocapsids, which ultimately become incorporated into new virions at the cell membrane. Virion release is facilitated by the viral matrix Z protein through its interaction with the cellular endosomal sorting complex required for transport (ESCRT) machinery. However, the mechanism of nucleocapsid incorporation into virions is not well understood. Here, we demonstrate that ALIX/AIP1, an ESCRT-associated host protein, is required for the incorporation of the NP of Mopeia virus, a close relative of Lassa virus, into Z-induced virus-like particles (VLPs). Furthermore, we show that the Bro1 domain of ALIX/AIP1 interacts with the NP and Z proteins simultaneously, facilitating their interaction, and we identify residues 342 to 399 of NP as being necessary for its interaction with ALIX/AIP1. Our observations suggest a potential role for ALIX/AIP1 in linking Mopeia virus NP to Z and the budding apparatus, thereby promoting NP incorporation into virions.
C1 [Shtanko, Olena; Watanabe, Shinji; Watanabe, Tokiko; Kawaoka, Yoshihiro] Univ Wisconsin, Dept Pathobiol Sci, Sch Vet Med, Madison, WI 53711 USA.
[Watanabe, Shinji; Watanabe, Tokiko; Kawaoka, Yoshihiro] Japan Sci & Technol Agcy, ERATO Infect Induced Host Responses Project, Kawaguchi, Saitama 3320012, Japan.
[Jasenosky, Luke D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Kawaoka, Yoshihiro] Univ Tokyo, Div Virol, Dept Microbiol & Immunol, Tokyo 1088639, Japan.
[Kawaoka, Yoshihiro] Univ Tokyo, Int Res Ctr Infect Dis, Inst Med Sci, Tokyo 1088639, Japan.
RP Watanabe, T (reprint author), Univ Wisconsin, Dept Pathobiol Sci, Sch Vet Med, 575 Sci Dr, Madison, WI 53711 USA.
EM twatanabe@svm.vetmed.wisc.edu; kawaokay@svm.vetmed.wisc.edu
FU U.S. National Institutes of Health; National Institute of Allergy and
Infectious Diseases Public Health Service
FX This work was supported by a U.S. National Institutes of Health and
National Institute of Allergy and Infectious Diseases Public Health
Service grant.
NR 50
TC 19
Z9 19
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2011
VL 85
IS 7
BP 3631
EP 3641
DI 10.1128/JVI.01984-10
PG 11
WC Virology
SC Virology
GA 734WT
UT WOS:000288373000054
PM 21248028
ER
PT J
AU Koh, Y
Matreyek, KA
Engelman, A
AF Koh, Yasuhiro
Matreyek, Kenneth A.
Engelman, Alan
TI Differential Sensitivities of Retroviruses to Integrase Strand Transfer
Inhibitors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS INTEGRASE; HIV-1 INTEGRASE; CRYSTAL-STRUCTURE;
FOAMY VIRUS; IN-VITRO; RALTEGRAVIR; RESISTANCE; REPLICATION; INFECTION;
EVOLUTION
AB Integrase inhibitors are emerging anti-human immunodeficiency virus (HIV) drugs, and multiple retroviruses and transposable elements were evaluated here for susceptibilities to raltegravir (RAL) and elvitegravir (EVG). All viruses, including primate and nonprimate lentiviruses, a Betaretrovirus, a Gammaretrovirus, and the Alpharetrovirus Rous sarcoma virus (RSV), were susceptible to inhibition by RAL. EVG potently inhibited all lentiviruses and intermediately inhibited Betaretrovirus and Gammaretrovirus infections yet was basically ineffective against RSV. Substitutions based on HIV type 1 (HIV-1) resistance changes revealed that integrase residue Ser150 contributed significantly to the resistance of RSV. The drugs intermediately inhibited intracisternal A-particle retrotransposition but were inactive against Sleeping Beauty transposition and long interspersed nucleotide element 1 (LINE-1) retrotransposition.
C1 [Engelman, Alan] Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Engelman, A (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, 44 Binney St,CLS-1010, Boston, MA 02115 USA.
EM alan_engelman@dfci.harvard.edu
OI Matreyek, Kenneth/0000-0001-9149-551X
FU U.S. NIH [AI039394]; Mitsubishi Pharma Foundation; Japanese Association
for Infectious Diseases; Japanese Society of Chemotherapy; Harvard
University Center for AIDS Research; NIH [P30AI060354]; NIAID; NCI;
NIMH; NIDA; NICHD; NHLBI; NCCAM
FX This work was supported by U.S. NIH grant AI039394 (A.E.), the
Mitsubishi Pharma Foundation (Y.K.), the Japanese Association for
Infectious Diseases (Y.K.), the Japanese Society of Chemotherapy (Y.K.),
and the Harvard University Center for AIDS Research, an NIH-funded
program (P30AI060354) that is supported by the following NIH institutes
and centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, and NCCAM.
NR 54
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U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2011
VL 85
IS 7
BP 3677
EP 3682
DI 10.1128/JVI.02541-10
PG 6
WC Virology
SC Virology
GA 734WT
UT WOS:000288373000058
PM 21270168
ER
PT J
AU Popov, S
Strack, B
Sanchez-Merino, V
Popova, E
Rosin, H
Gottlinger, HG
AF Popov, Sergei
Strack, Bettina
Sanchez-Merino, Victor
Popova, Elena
Rosin, Heike
Goettlinger, Heinrich G.
TI Human Immunodeficiency Virus Type 1 and Related Primate Lentiviruses
Engage Clathrin through Gag-Pol or Gag
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CATALYTIC DOMAIN; HIV-1 GAG; REVERSE-TRANSCRIPTASE; PARTICLE-PRODUCTION;
INTEGRASE MUTANTS; ADAPTER COMPLEX; BINDING; PROTEIN; ALIX; REPLICATION
AB The Gag-Pol polyprotein of human immunodeficiency virus type 1 (HIV-1) is not required for efficient viral particle production. However, premature termination codons in pol, particularly in the integrase (IN)-coding region, can markedly impair HIV-1 particle formation, apparently due to the premature activation of the viral protease (PR). We now report that the IN domain of Gag-Pol is required for the incorporation of clathrin into HIV-1 virions. Significantly, PR-dependent effects of point mutations in IN on particle production correlated strictly with their effects on clathrin incorporation. A possible interpretation of these findings is that certain IN mutations impair particle production in a PR-dependent manner by promoting Gag-Pol dimerization, which also occludes a binding site for clathrin. Consistently with this model, the reverse transcriptase (RT) inhibitor efavirenz, which is thought to promote Gag-Pol dimerization, inhibited the incorporation of clathrin into HIV-1 virions. Clathrin-depleted cells produced normal amounts of HIV-1 virions; however, their infectivity was reduced. We also observed that HIV-2 and the simian immunodeficiency virus SIVmac interact with clathrin through one or two copies of a peptide motif in the p6 domain of Gag that resembles the clathrin box of cellular adaptor proteins. Furthermore, the substitution of the hydrophobic residues in the single clathrin box motif of SIVmac caused a replication defect in primary cells. Taken together, our results indicate that primate lentiviruses from two different subgroups functionally interact with clathrin during assembly.
C1 [Popov, Sergei; Popova, Elena; Goettlinger, Heinrich G.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Program Mol Med, Worcester, MA 01605 USA.
[Strack, Bettina; Sanchez-Merino, Victor; Rosin, Heike; Goettlinger, Heinrich G.] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Gottlinger, HG (reprint author), UMass Med Sch, LRB 526,364 Plantat St, Worcester, MA 01605 USA.
EM heinrich.gottlinger@umassmed.edu
FU National Institute of Allergy and Infectious Diseases [R37AI029873]
FX This work was supported by grant number R37AI029873 from the National
Institute of Allergy and Infectious Diseases.
NR 49
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U1 0
U2 2
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 2011
VL 85
IS 8
BP 3792
EP 3801
DI 10.1128/JVI.02329-10
PG 10
WC Virology
SC Virology
GA 736ZV
UT WOS:000288536100009
PM 21289110
ER
PT J
AU Wright, JK
Novitsky, V
Brockman, MA
Brumme, ZL
Brumme, CJ
Carlson, JM
Heckerman, D
Wang, BX
Losina, E
Leshwedi, M
van der Stok, M
Maphumulo, L
Mkhwanazi, N
Chonco, F
Goulder, PJR
Essex, M
Walker, BD
Ndung'u, T
AF Wright, Jaclyn K.
Novitsky, Vladimir
Brockman, Mark A.
Brumme, Zabrina L.
Brumme, Chanson J.
Carlson, Jonathan M.
Heckerman, David
Wang, Bingxia
Losina, Elena
Leshwedi, Mopo
van der Stok, Mary
Maphumulo, Lungile
Mkhwanazi, Nompumelelo
Chonco, Fundisiwe
Goulder, Philip J. R.
Essex, Max
Walker, Bruce D.
Ndung'u, Thumbi
TI Influence of Gag-Protease-Mediated Replication Capacity on Disease
Progression in Individuals Recently Infected with HIV-1 Subtype C
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ESCAPE MUTATIONS; CLASS-I; VIRAL LOAD;
HLA; FITNESS; EPITOPE; PLASMA; AIDS; TRANSMISSION
AB HLA class I-mediated selection of immune escape mutations in functionally important Gag epitopes may partly explain slower disease progression in HIV-1-infected individuals with protective HLA alleles. To investigate the impact of Gag function on disease progression, the replication capacities of viruses encoding Gag-protease from 60 individuals in early HIV-1 subtype C infection were assayed in an HIV-1-inducible green fluorescent protein reporter cell line and were correlated with subsequent disease progression. Replication capacities did not correlate with viral load set points (P = 0.37) but were significantly lower in individuals with below-median viral load set points (P = 0.03), and there was a trend of correlation between lower replication capacities and lower rates of CD4 decline (P = 0.09). Overall, the proportion of host HLA-specific Gag polymorphisms in or adjacent to epitopes was negatively associated with replication capacities (P = 0.04), but host HLA-B-specific polymorphisms were associated with higher viral load set points (P = 0.01). Further, polymorphisms associated with host-specific protective HLA alleles were linked with higher viral load set points (P = 0.03). These data suggest that transmission or early HLA-driven selection of Gag polymorphisms results in reduced early cytotoxic T-lymphocyte (CTL) responses and higher viral load set points. In support of the former, 46% of individuals with nonprotective alleles harbored a Gag polymorphism exclusively associated with a protective HLA allele, indicating a high rate of their transmission in sub-Saharan Africa. Overall, HIV disease progression is likely to be affected by the ability to mount effective Gag CTL responses as well as the replication capacity of the transmitted virus.
C1 [Wright, Jaclyn K.; Leshwedi, Mopo; van der Stok, Mary; Maphumulo, Lungile; Mkhwanazi, Nompumelelo; Chonco, Fundisiwe; Walker, Bruce D.; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa.
[Novitsky, Vladimir; Essex, Max] Botswana Harvard Sch Publ Hlth, AIDS Initiat Partnership HIV Res & Educ, Gaborone, Botswana.
[Novitsky, Vladimir; Essex, Max] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Brockman, Mark A.; Brumme, Zabrina L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
[Brockman, Mark A.; Brumme, Zabrina L.; Brumme, Chanson J.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
[Carlson, Jonathan M.; Heckerman, David] Microsoft Res, ESci Grp, Redmond, WA USA.
[Wang, Bingxia; Losina, Elena] Massachusetts Gen Hosp, Program HIV Outcomes Res, Boston, MA 02114 USA.
[Goulder, Philip J. R.] Univ Oxford, Nuffield Dept Med, Dept Paediat, Oxford, England.
[Goulder, Philip J. R.; Walker, Bruce D.; Ndung'u, Thumbi] MIT, Ragon Inst, Massachusetts Gen Hosp, Boston, MA USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Ndung'u, T (reprint author), Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, 719 Umbilo Rd, ZA-4013 Durban, South Africa.
EM ndungu@ukzn.ac.za
OI Ndung'u, Thumbi/0000-0003-2962-3992; Brumme,
Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426
FU NIH [RO1-AI067073, RO1-AI057027]; Bill and Melinda Gates Foundation;
South African AIDS Vaccine Initiative; South African Department of
Science and Technology through the National Research Foundation; Ragon
Institute Fund for Innovation; New International Initiatives; National
Research Foundation; Ragon Institute of Massachusetts General Hospital,
Massachusetts Institute of Technology, and Harvard University; Canadian
Institutes for Health Research (CIHR)
FX This research was funded by NIH (RO1-AI067073 and RO1-AI057027), the
Bill and Melinda Gates Foundation, the South African AIDS Vaccine
Initiative, the South African Department of Science and Technology
through the National Research Foundation, and the Ragon Institute Fund
for Innovation and New International Initiatives. J.K.W. is funded by
the National Research Foundation and the Ragon Institute of
Massachusetts General Hospital, Massachusetts Institute of Technology,
and Harvard University. Z.L.B. is supported by a New Investigator Award
from the Canadian Institutes for Health Research (CIHR). T.N. holds the
South African Department of Science and Technology/National Research
Foundation Research Chair in Systems Biology of HIV/AIDS. Additional
support was provided by the Mark and Lisa Schwartz Foundation.
NR 49
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U1 2
U2 4
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 2011
VL 85
IS 8
BP 3996
EP 4006
DI 10.1128/JVI.02520-10
PG 11
WC Virology
SC Virology
GA 736ZV
UT WOS:000288536100028
PM 21289112
ER
PT J
AU Baddley, JW
AF Baddley, John W.
TI Clinical risk factors for invasive aspergillosis
SO MEDICAL MYCOLOGY
LA English
DT Article; Proceedings Paper
CT 4th Advances Against Aspergillosis (AAA) Conference
CY FEB 04-06, 2010
CL Rome, ITALY
DE Aspergillus; clinical risk factors; invasive aspergillosis
ID CRITICALLY-ILL PATIENTS; CELL TRANSPLANT RECIPIENTS; OBSTRUCTIVE
PULMONARY-DISEASE; SOLID-ORGAN TRANSPLANTATION; INTENSIVE-CARE-UNIT;
FUNGAL-INFECTIONS; RESPIRATORY-TRACT; IMMUNOCOMPROMISED PATIENTS; MOLD
INFECTIONS; EPIDEMIOLOGY
AB Despite improvements in the antifungal armamentarium and diagnostic modalities, invasive aspergillosis (IA) remains an important cause of morbidity and mortality in immunocompromised patients. There is an emergence of non-traditional groups at risk for IA, including intensive care unit (ICU) patients, post-operative patients, those with chronic pulmonary diseases, patients with AIDS and patients on immunomodulating drugs (TNF-alpha inhibitors). Identification of clinical risk factors for IA may help in determining which patients require risk modification and other prevention measures.
C1 [Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
[Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA.
EM jbaddley@uab.edu
NR 57
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Z9 28
U1 1
U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1369-3786
J9 MED MYCOL
JI Med. Mycol.
PD APR
PY 2011
VL 49
SU 1
BP S7
EP S12
DI 10.3109/13693786.2010.505204
PG 6
WC Infectious Diseases; Mycology; Veterinary Sciences
SC Infectious Diseases; Mycology; Veterinary Sciences
GA 734IE
UT WOS:000288327000002
PM 20718606
ER
PT J
AU Williams, HJ
Norton, N
Dwyer, S
Moskvina, V
Nikolov, I
Carroll, L
Georgieva, L
Williams, NM
Morris, DW
Quinn, EM
Giegling, I
Ikeda, M
Wood, J
Lencz, T
Hultman, C
Lichtenstein, P
Thiselton, D
Maher, BS
Malhotra, AK
Riley, B
Kendler, KS
Gill, M
Sullivan, P
Sklar, P
Purcell, S
Nimgaonkar, VL
Kirov, G
Holmans, P
Corvin, A
Rujescu, D
Craddock, N
Owen, MJ
O'Donovan, MC
AF Williams, H. J.
Norton, N.
Dwyer, S.
Moskvina, V.
Nikolov, I.
Carroll, L.
Georgieva, L.
Williams, N. M.
Morris, D. W.
Quinn, E. M.
Giegling, I.
Ikeda, M.
Wood, J.
Lencz, T.
Hultman, C.
Lichtenstein, P.
Thiselton, D.
Maher, B. S.
Malhotra, A. K.
Riley, B.
Kendler, K. S.
Gill, M.
Sullivan, P.
Sklar, P.
Purcell, S.
Nimgaonkar, V. L.
Kirov, G.
Holmans, P.
Corvin, A.
Rujescu, D.
Craddock, N.
Owen, M. J.
O'Donovan, M. C.
CA Mol Genetics Schizophrenia
ISC
SGENE-Plus
GROUP
TI Fine mapping of ZNF804A and genome-wide significant evidence for its
involvement in schizophrenia and bipolar disorder
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE ZNF804A; association; schizophrenia; bipolar disorder; meta-analysis
ID GENE-EXPRESSION; COMMON VARIANTS; ASSOCIATION; RISK; PSYCHOSIS;
INSIGHTS; LOCUS; TWIN
AB A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P = 1.61 x 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P = 9.96 x 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N = 18 945, schizophrenia plus bipolar disorder N = 21 274 and controls N = 38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P = 2.5 x 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P = 4.1 x 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder. Molecular Psychiatry (2011) 16, 429-441; doi:10.1038/mp.2010.36; published online 6 April 2010
C1 [Williams, H. J.; Norton, N.; Dwyer, S.; Moskvina, V.; Nikolov, I.; Carroll, L.; Georgieva, L.; Williams, N. M.; Ikeda, M.; Kirov, G.; Holmans, P.; Craddock, N.; Owen, M. J.; O'Donovan, M. C.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Cardiff CF14 4XN, S Glam, Wales.
[Morris, D. W.; Quinn, E. M.; Gill, M.; Corvin, A.] Trinity Coll Dublin, Sch Med, Neuropsychiat Genet Res Grp, Dublin, Ireland.
[Giegling, I.; Rujescu, D.] Univ Munich, Div Mol & Clin Neurobiol, Munich, Germany.
[Ikeda, M.] Fujita Hlth Univ, Sch Med, Dept Psychiat, Aichi, Japan.
[Wood, J.; Nimgaonkar, V. L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Wood, J.; Nimgaonkar, V. L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Lencz, T.; Malhotra, A. K.] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Translat Psychiat, Manhasset, NY USA.
[Lencz, T.; Malhotra, A. K.] Zucker Hillside Hosp, Div Res, Glen Oaks, NY USA.
[Lencz, T.; Malhotra, A. K.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA.
[Hultman, C.; Lichtenstein, P.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Thiselton, D.; Maher, B. S.; Riley, B.; Kendler, K. S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA.
[Thiselton, D.; Maher, B. S.; Riley, B.; Kendler, K. S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Maher, B. S.; Riley, B.; Kendler, K. S.] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA.
[Sullivan, P.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sklar, P.; Purcell, S.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Sklar, P.; Purcell, S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Sklar, P.; Purcell, S.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA.
RP O'Donovan, MC (reprint author), Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol, Henry Wellcome Bldg, Cardiff CF14 4XN, S Glam, Wales.
EM owenmj@Cardiff.ac.uk; odonovanmc@Cardiff.ac.uk
RI Maher, Brion/F-9185-2010; Holmans, Peter/F-4518-2015; Lencz,
Todd/J-3418-2014;
OI Holmans, Peter/0000-0003-0870-9412; Lencz, Todd/0000-0001-8586-338X;
Corvin, Aiden/0000-0001-6717-4089; O'Donovan,
Michael/0000-0001-7073-2379; Morris, Derek/0000-0002-3413-570X; Gill,
Michael/0000-0003-0206-5337; lichtenstein, paul/0000-0003-3037-5287;
Escott-Price, Valentina/0000-0003-1784-5483
FU Wellcome Trust [076113]; MRC; NIMH (USA) [CONTE: 2 P50 MH066392-05A1]
FX We thank all the families who contributed to the sample collections we
used. We also thank The MRC London Neurodegenerative Diseases Brain
Bank, UK; The Stanley Medical Research Institute Brain Bank, USA; and
The Karolinska Institute, Sweden, that supplied the post-mortem brain
tissue. This study makes use of control 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
www.wtccc.org.uk. Funding for the project was provided by the Wellcome
Trust under award 076113. The UK research was supported by grants from
the MRC, the Wellcome Trust and by a NIMH (USA) CONTE: 2 P50
MH066392-05A1.
NR 31
TC 43
Z9 49
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD APR
PY 2011
VL 16
IS 4
BP 429
EP 441
DI 10.1038/mp.2010.36
PG 13
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 739TK
UT WOS:000288740700010
PM 20368704
ER
PT J
AU Deng, XM
Dzamko, N
Prescott, A
Davies, P
Liu, QS
Yang, QK
Lee, JD
Patricelli, MP
Nomanbhoy, TK
Alessi, DR
Gray, NS
AF Deng, Xianming
Dzamko, Nicolas
Prescott, Alan
Davies, Paul
Liu, Qingsong
Yang, Qingkai
Lee, Jiing-Dwan
Patricelli, Matthew P.
Nomanbhoy, Tyzoon K.
Alessi, Dario R.
Gray, Nathanael S.
TI Characterization of a selective inhibitor of the Parkinson's disease
kinase LRRK2
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID CYTOPLASMIC LOCALIZATION; 14-3-3 BINDING; MUTATIONS; MAP
AB Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson's disease. We employed a new, parallel, compound-centric approach to identify a potent and selective LRRK2 inhibitor, LRRK2-IN-1, and demonstrated that inhibition of LRRK2 induces dephosphorylation of Ser910 and Ser935 and accumulation of LRRK2 within aggregate structures. LRRK2-IN-1 will serve as a versatile tool to pharmacologically interrogate LRRK2 biology and study its role in Parkinson's disease.
C1 [Deng, Xianming; Liu, Qingsong; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Deng, Xianming; Liu, Qingsong; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Dzamko, Nicolas; Davies, Paul; Alessi, Dario R.] Univ Dundee, MRC Prot Phosphorylat Unit, Coll Life Sci, Dundee, Scotland.
[Prescott, Alan] Univ Dundee, Div Cell Biol & Immunol, Coll Life Sci, Dundee, Scotland.
[Yang, Qingkai; Lee, Jiing-Dwan] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Patricelli, Matthew P.; Nomanbhoy, Tyzoon K.] ActivX Biosci, La Jolla, CA USA.
RP Deng, XM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM r.alessi@dundee.ac.uk; nathanael_gray@dfci.harvard.edu
OI Alessi, Dario/0000-0002-2140-9185; Yang, Qingkai/0000-0001-6628-5393;
Prescott, Alan/0000-0002-0747-7317; liu, qing song/0000-0002-7829-2547;
Dzamko, Nicolas/0000-0002-9121-0294
FU US National Institutes of Health [P41 GM079575-03, CA079871, CA114059];
Medical Research Council; National Health and Medical Research Council;
Michael J. Fox Foundation for Parkinson's Disease Research; University
of California [19XT-0084]
FX We wish to thank staff at the National Centre for Protein Kinase
Profiling (http://www.kinase-screen.mrc.ac.uk) for undertaking Dundee
kinase specificity screening, F. Hentati (Institut National de
Neurologie, Tunisia) and A. Reith (GlaxoSmithKline Pharmaceuticals
Research and Development) for providing EBV immortalized human
lymphoblastoid cells, P. Bamborough (GlaxoSmithKline Pharmaceuticals
Research and Development) for providing LRRK2 homology model and the
antibody purification teams (Division of Signal Transduction Therapy
(DSTT), University of Dundee) coordinated by H. McLauchlan and J. Hastie
for generation of antibodies. This work was supported by US National
Institutes of Health grant P41 GM079575-03 (N.S.G.), the Medical
Research Council Technology Industry Collaboration Award and a National
Health and Medical Research Council postdoctoral fellowship (N.D.), the
Medical Research Council (D. R. A.), the Michael J. Fox Foundation for
Parkinson's Disease Research (D. R. A.), the pharmaceutical companies
supporting the DSTT (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline,
Merck KgaA and Pfizer) (D. R. A.), the US National Institutes of Health
grants CA079871 and CA114059 (J.-D.L.) and funds from the
Tobacco-Related Disease Research Program of the University of
California, 19XT-0084, (J.-D.L.).
NR 22
TC 175
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U1 2
U2 39
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 2011
VL 7
IS 4
BP 203
EP 205
DI 10.1038/NCHEMBIO.538
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 737CC
UT WOS:000288545000007
PM 21378983
ER
PT J
AU Zhu, H
Lensch, MW
Cahan, P
Daley, GQ
AF Zhu, Hao
Lensch, M. William
Cahan, Patrick
Daley, George Q.
TI Investigating monogenic and complex diseases with pluripotent stem cells
SO NATURE REVIEWS GENETICS
LA English
DT Review
ID QT INTERVAL DURATION; HUMAN SOMATIC-CELLS; MOTOR-NEURONS; MOUSE EMBRYOS;
COMMON VARIANTS; DEFINED FACTORS; DOWNS-SYNDROME; ALS; CULTURE; MODELS
AB Human genetic studies have revealed the molecular basis of countless monogenic diseases but have been less successful in associating phenotype to genotype in complex multigenic conditions. Pluripotent stem cells (PSCs), which can differentiate into any cell type, offer promise for defining the functional effects of genetic variation. Here, we recount the advantages and practical limitations of coupling PSCs to genome-wide analyses to probe complex genetics and discuss the ability to investigate epigenetic contributions to disease states. We also describe new ways of using mice and mouse embryonic stem cells (ESCs) in tandem with human stem cells to further define genotype-phenotype relationships.
C1 [Zhu, Hao; Lensch, M. William; Cahan, Patrick; Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Harvard Stem Cell Inst, Stem Cell Transplantat Program,Div Pediat Haemata, Boston, MA 02115 USA.
[Zhu, Hao] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Harvard Stem Cell Inst, Stem Cell Transplantat Program,Div Pediat Haemata, 300 Longwood Ave, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
OI Zhu, Hao/0000-0002-8417-9698; Cahan, Patrick/0000-0003-3652-2540
FU US National Institutes of Health [RO1-DK70055, RO1-DK59279,
UO1-HL100001]; American Recovery and Reinvestment Act (ARRA)
[RC2-HL102815]; Roche Foundation for Anaemia Research; Alex's Lemonade
Stand Foundation; Harvard Stem Cell Institute
FX G. Q. D. is an investigator of the Howard Hughes Medical Institute and
the Manton Center for Orphan Disease Research. G. Q. D. is supported by
grants from the US National Institutes of Health (RO1-DK70055,
RO1-DK59279 and UO1-HL100001, and special funds from the American
Recovery and Reinvestment Act (ARRA) stimulus package (RC2-HL102815)),
the Roche Foundation for Anaemia Research, Alex's Lemonade Stand
Foundation and the Harvard Stem Cell Institute.
NR 73
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U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0056
EI 1471-0064
J9 NAT REV GENET
JI Nat. Rev. Genet.
PD APR
PY 2011
VL 12
IS 4
BP 266
EP 275
DI 10.1038/nrg2951
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 736YT
UT WOS:000288531700010
PM 21386866
ER
PT J
AU Hazlett, EA
Goldstein, KE
Tajima-Pozo, K
Speidel, ER
Zelmanova, Y
Entis, JJ
Silverman, JM
New, AS
Koenigsberg, HW
Haznedar, MM
Byne, W
Siever, LJ
AF Hazlett, Erin A.
Goldstein, Kim E.
Tajima-Pozo, Kazuhiro
Speidel, Elizabeth R.
Zelmanova, Yuliya
Entis, Jonathan J.
Silverman, Jeremy M.
New, Antonia S.
Koenigsberg, Harold W.
Haznedar, M. Mehmet
Byne, William
Siever, Larry J.
TI Cingulate and temporal lobe fractional anisotropy in schizotypal
personality disorder
SO NEUROIMAGE
LA English
DT Article
DE Diffusion tensor imaging; Schizotypal personality disorder; Dorsolateral
prefrontal cortex; Temporal lobe; Cingulum; Fractional anisotropy
ID WHITE-MATTER INTEGRITY; THALAMIC MEDIODORSAL NUCLEUS; DIFFUSION TENSOR
ANISOTROPY; EARLY-ONSET SCHIZOPHRENIA; ANTERIOR CINGULATE; GYRUS VOLUME;
GRAY-MATTER; ABNORMALITIES; MRI; SPECTRUM
AB Background: Consistent with the clinical picture of milder symptomatology in schizotypal personality disorder (SPD) than schizophrenia, morphological studies indicate SPD abnormalities in temporal lobe regions but to a much lesser extent in prefrontal regions implicated in schizophrenia. Lower fractional anisotropy (FA), a measure of white-matter integrity within prefrontal, temporal, and cingulate regions has been reported in schizophrenia but has been little studied in SPD.
Aims: The study aim was to examine temporal and prefrontal white matter FA in 30 neuroleptic-naive SPD patients and 35 matched healthy controls (HCs). We hypothesized that compared with HCs, SPD patients would exhibit lower FA in temporal lobe and anterior cingulum regions but relative sparing in prefrontal regions.
Method: We acquired diffusion tensor imaging (DTI) in all participants and examined FA in the white matter underlying Brodmann areas (BAs) in dorsolateral prefrontal (BAs 44, 45, and 46), temporal lobe (BAs 22, 21, and 20), and cingulum (BAs 25, 24, 31, 23, and 29) regions with a series of analyses using multivariate analysis of variance.
Results: Compared with HCs, the SPD group had significantly lower FA in the left temporal lobe but not prefrontal regions. In the cingulum. FA was lower in the SPD group in the posterior regions (BAs 31 and 23), higher in the anterior (BA 25) regions and lower overall in the right but not the left cingulum. Among the SPD group, lower FA in the cingulum was associated with more severe negative symptoms (e.g., odd speech).
Conclusions: Similar to schizophrenia, our results indicate cingulum-temporal lobe FA abnormalities in SPD and suggest that cingulum abnormalities are associated with negative symptoms. Published by Elsevier Inc.
C1 [Hazlett, Erin A.; Goldstein, Kim E.; Tajima-Pozo, Kazuhiro; Speidel, Elizabeth R.; Zelmanova, Yuliya; Entis, Jonathan J.; Silverman, Jeremy M.; New, Antonia S.; Koenigsberg, Harold W.; Haznedar, M. Mehmet; Byne, William; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Hazlett, Erin A.; Silverman, Jeremy M.; New, Antonia S.; Koenigsberg, Harold W.; Haznedar, M. Mehmet; Byne, William; Siever, Larry J.] James J Peters Dept Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN3, Bronx, NY 10468 USA.
RP Hazlett, EA (reprint author), James J Peters Dept Vet Adm Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC VISN3, 130 W Kingsbridge Rd,Room 6A-45, Bronx, NY 10468 USA.
EM erin.hazlett@mssm.edu
FU VA MERIT [7609-28]; NIMH [R01MH073911]; National Center for Research
Resources (NCRR), NIH [M01-Patient Care RR-00071]; Mental Illness,
Research, Education, and Clinical Center, VISN 3 Veterans Health
Administration
FX This study was supported by VA MERIT 7609-28 to Dr. Siever and NIMH
grant R01MH073911 to Dr. Hazlett. Other support came from a grant
(M01-Patient Care RR-00071) from the National Center for Research
Resources (NCRR), a component of the NIH and the Mental Illness,
Research, Education, and Clinical Center, VISN 3 Veterans Health
Administration.
NR 73
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U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD APR 1
PY 2011
VL 55
IS 3
BP 900
EP 908
DI 10.1016/j.neuroimage.2010.12.082
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 734DQ
UT WOS:000288313800006
PM 21223999
ER
PT J
AU Cohen-Adad, J
El Mendili, MM
Lehericy, S
Pradat, PF
Blancho, S
Rossignol, S
Benali, H
AF Cohen-Adad, J.
El Mendili, M-M.
Lehericy, S.
Pradat, P-F.
Blancho, S.
Rossignol, S.
Benali, H.
TI Demyelination and degeneration in the injured human spinal cord detected
with diffusion and magnetization transfer MRI
SO NEUROIMAGE
LA English
DT Article
DE Spinal cord injury; Diffusion-weighted MRI; Magnetization transfer;
Atrophy; ASIA
ID MULTIPLE-SCLEROSIS BRAIN; INDUCED B-0 FLUCTUATIONS; WHITE-MATTER
PATHOLOGY; ANGULAR RESOLUTION; AXONAL INJURY; WALLERIAN DEGENERATION;
MULTIEXPONENTIAL T-2; TENSOR TRACTOGRAPHY; FIBER ORIENTATIONS;
CORPUS-CALLOSUM
AB Characterizing demyelination/degeneration of spinal pathways in traumatic spinal cord injured (SCI) patients is crucial for assessing the prognosis of functional rehabilitation. Novel techniques based on diffusion-weighted (DW) magnetic resonance imaging (MRI) and magnetization transfer (MT) imaging provide sensitive and specific markers of white matter pathology. In this paper we combined for the first time high angular resolution diffusion-weighted imaging (HARDI), MT imaging and atrophy measurements to evaluate the cervical spinal cord of fourteen SCI patients and age-matched controls. We used high in-plane resolution to delineate dorsal and ventrolateral pathways. Significant differences were detected between patients and controls in the normal-appearing white matter for fractional anisotropy (FA, p < 0.0001), axial diffusivity (p < 0.05), radial diffusivity (p < 0.05), generalized fractional anisotropy (GFA, p < 0.0001), magnetization transfer ratio (MTR, p < 0.0001) and cord area (p < 0.05). No significant difference was detected in mean diffusivity (p = 0.41), T1-weighted (p = 0.76) and 12-weighted (p = 0.09) signals. MRI metrics were remarkably well correlated with clinical disability (Pearson's correlations, FA: p < 0.01, GFA: p < 0.01, radial diffusivity: p = 0.01, MTR: p = 0.04 and atrophy: p < 0.01). Stepwise linear regressions showed that measures of MTR in the dorsal spinal cord predicted the sensory disability whereas measures of MTR in the ventrolateral spinal cord predicted the motor disability (ASIA score). However, diffusion metrics were not specific to the sensorimotor scores. Due to the specificity of axial and radial diffusivity and MT measurements, results suggest the detection of demyelination and degeneration in SCI patients. Combining HARDI with MT imaging is a promising approach to gain specificity in characterizing spinal cord pathways in traumatic injury. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Cohen-Adad, J.] Harvard Univ, AA Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Cohen-Adad, J.; El Mendili, M-M.; Benali, H.] Hop La Pitie Salpetriere, UMR 678, INSERM UPMC, Paris, France.
[Lehericy, S.] Grp Hosp Pitie Salpetriere, Ctr Neuroimaging Res CENIR, Inst Cerveau & Moelle Epiniere,Ctr Rech, UPMC,UMR 5975,INSERM U975,CNRS UMR 7225, F-75634 Paris, France.
[Pradat, P-F.] Hop La Pitie Salpetriere, AP HP, Paris, France.
[Blancho, S.] Inst Rech Moelle Epiniere & Encephale, Paris, France.
[Rossignol, S.] Univ Montreal, Fac Med, GRSNC, Montreal, PQ H3C 3J7, Canada.
RP Cohen-Adad, J (reprint author), Harvard Univ, AA Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp, 149 13 St, Charlestown, MA 02129 USA.
EM jcohen@nmr.mgh.harvard.edu
FU Association Francaise contre les Myopathies (AFM); Institut pour la
Recherche sur la Moelle epiniere et l'Encephale (IRME)
FX We thank Dr. Maxime Descoteaux for providing the code to compute the
Q-Ball ODF and Dr. Henrik Lundell for providing the code to measure the
cord area. We also thank Drs. Stephane Ouary, Olivier Freund, Kevin
Nigaud, Alexandre Vignaud and Eric Bardinet for helping with the
project. We thank Drs. Thierry Albert, Bertrand Baussart, Caroline
Hugeron, Hugues Pascal Moussellard, Frederic Petit and Marc-Antoine
Rousseau for helping with patient recruitment and we thank all subjects.
We also thank the reviewers for their helpful comments that greatly
improved the quality of the manuscript. This study was supported by the
Association Francaise contre les Myopathies (AFM) and by the Institut
pour la Recherche sur la Moelle epiniere et l'Encephale (IRME). S.R.
received a special fellowship from the IRME to participate in these
studies during a sabbatical leave in Paris.
NR 96
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U1 0
U2 15
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 2011
VL 55
IS 3
BP 1024
EP 1033
DI 10.1016/j.neuroimage.2010.11.089
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 734DQ
UT WOS:000288313800017
PM 21232610
ER
PT J
AU Harvey, PO
Lee, J
Cohen, MS
Engel, SA
Glahn, DC
Nuechterlein, KH
Wynn, JK
Green, MF
AF Harvey, Philippe-Olivier
Lee, Junghee
Cohen, Mark S.
Engel, Stephen A.
Glahn, David C.
Nuechterlein, Keith H.
Wynn, Jonathan K.
Green, Michael F.
TI Altered dynamic coupling of lateral occipital complex during visual
perception in schizophrenia
SO NEUROIMAGE
LA English
DT Article
DE Functional connectivity/ Dynamic coupling; Lateral occipital complex;
Backward visual masking; Schizophrenia; fMRI
ID BACKWARD-MASKING DEFICITS; MULTIPLE TRIAL TYPES; EVENT-RELATED FMRI;
FUNCTIONAL CONNECTIVITY; OBJECT RECOGNITION; CORTEX; MECHANISMS;
PATTERNS; ENTROPY; HUMANS
AB Introduction: There is mounting evidence that visual perception abnormalities in schizophrenia are partly explained by a dysfunction of the lateral occipital complex (LO). We previously demonstrated that schizophrenia patients had broader topography and reduced magnitude of activity of LO. However, the functional connectivity of LO with other brain regions during visual perception has not been directly investigated in schizophrenia.
Materials and methods: Eighteen patients with schizophrenia and eighteen matched controls performed a backward masking task during functional magnetic resonance imaging (fMRI). Stimulus onset asynchronies were manipulated to change the level of target visibility. To examine connectivity with LO function we conducted psychophysiological interactions (PPI) analyses using: 1) a region of interest (ROI) approach and 2) a whole brain analysis. ROIs were defined based on a contrast of trials on which a target was presented versus null trials in which no stimuli were presented.
Results: Eleven ROIs were identified. Both groups showed similar strength of coupling between LO and the 11 ROIs when visibility was not taken into account. Healthy controls showed clear changes in coupling between LO and prefrontal and parietal regions as a function of target visibility (higher coupling with more visible targets). In comparison, patients showed reduced dynamic coupling with LO in the right superior frontal gyrus (significant after correcting for multiple comparisons) and a trend for reduced coupling in the left precuneus and left inferior frontal regions. Whole brain analysis identified additional regions that showed dynamic coupling with LO in healthy controls, but not in patients.
Discussion: The increased coupling between LO and higher-level parietal and prefrontal regions during visual awareness in healthy controls likely reflects visual reentrant processing. The lack of modulation of coupling between LO and key prefrontal and parietal regions found in schizophrenia may partly reflect abnormalities in LO tuning. The altered LO coupling may contribute to visual perception abnormalities in schizophrenia. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Harvey, Philippe-Olivier; Lee, Junghee; Cohen, Mark S.; Nuechterlein, Keith H.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90073 USA.
[Harvey, Philippe-Olivier; Lee, Junghee; Wynn, Jonathan K.; Green, Michael F.] VA Greater Los Angeles, Healthcare Ctr Syst, Los Angeles, CA USA.
[Engel, Stephen A.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Glahn, David C.] Olin Neuropsychiat Res Ctr, New Haven, CT USA.
[Glahn, David C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
RP Harvey, PO (reprint author), Univ Calif Los Angeles, Semel Inst, W LA VA Healthcare Ctr, 11301 Wilshire Blvd,210A,Room 131, Los Angeles, CA 90073 USA.
EM poharvey@ucla.edu
RI Cohen, Mark/C-6610-2011; Lee, Junghee/C-5226-2014; Wynn,
Jonathan/H-3749-2014
OI Cohen, Mark/0000-0001-6731-4053; Lee, Junghee/0000-0001-9567-8700; Wynn,
Jonathan/0000-0002-1763-8540
FU Canadian Institutes of Health Research; William M. and Linda R Dietel
Philanthropic Fund at the Northern Piedmont Community Foundation;
Northstar Fund; [MH043292]
FX This work was supported by grant MH043292 to Dr. Green. Poorang Non and
Alisa Malin assisted in data collection. Dr. Harvey is supported by a
postdoctoral fellowship from the Canadian Institutes of Health Research.
For generous support of the UCLA Brain Mapping Center, we also thank the
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,
Capital Group Companies Charitable Foundation, Robson Family, and
Northstar Fund.
NR 51
TC 16
Z9 17
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD APR 1
PY 2011
VL 55
IS 3
BP 1219
EP 1226
DI 10.1016/j.neuroimage.2010.12.045
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 734DQ
UT WOS:000288313800035
PM 21194569
ER
PT J
AU Golfinopoulos, E
Tourville, JA
Bohland, JW
Ghosh, SS
Nieto-Castanon, A
Guenther, FH
AF Golfinopoulos, Elisa
Tourville, Jason A.
Bohland, Jason W.
Ghosh, Satrajit S.
Nieto-Castanon, Alfonso
Guenther, Frank H.
TI fMRI investigation of unexpected somatosensory feedback perturbation
during speech
SO NEUROIMAGE
LA English
DT Article
DE Functional magnetic resonance imaging; Structural equation modeling;
Speech motor control; Right hemisphere; Somatosensory feedback
ID PHASE BIMANUAL MOVEMENTS; FUNCTIONAL IMAGING DATA; WORKING-MEMORY
NETWORK; SURFACE-BASED ANALYSIS; FALSE DISCOVERY RATE; EVENT-RELATED
FMRI; STRUCTURAL EQUATION; EFFECTIVE CONNECTIVITY; AUDITORY-FEEDBACK;
MOTOR CONTROL
AB Somatosensory feedback plays a critical role in the coordination of articulator movements for speech production. In response to unexpected resistance to lip or jaw movements during speech, fluent speakers can use the difference between the somatosensory expectations of a speech sound and the actual somatosensory feedback to adjust the trajectories of functionally relevant but unimpeded articulators. In an effort to investigate the neural substrates underlying the somatosensory feedback control of speech, we used an event-related sparse sampling functional magnetic resonance imaging paradigm and a novel pneumatic device that unpredictably blocked subjects' jaw movements. In comparison to speech, perturbed speech, in which jaw perturbation prompted the generation of compensatory speech motor commands, demonstrated increased effects in bilateral ventral motor cortex, right-lateralized anterior supramarginal gyrus, inferior frontal gyrus pars triangularis and ventral premotor cortex, and bilateral inferior posterior cerebellum (lobule VIII). Structural equation modeling revealed a significant increased influence from left anterior supramarginal gyrus to right anterior supramarginal gyrus and from left anterior supramarginal gyrus to right ventral premotor cortex as well as a significant increased reciprocal influence between right ventral premotor cortex and right ventral motor cortex and right anterior supramarginal gyrus and right inferior frontal gyrus pars triangularis for perturbed speech relative to speech. These results suggest that bilateral anterior supramarginal gyrus, right inferior frontal gyrus pars triangularis, right ventral premotor and motor cortices are functionally coupled and influence speech motor output when somatosensory feedback is unexpectedly perturbed during speech production. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Golfinopoulos, Elisa; Tourville, Jason A.; Bohland, Jason W.; Ghosh, Satrajit S.; Guenther, Frank H.] Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA.
[Bohland, Jason W.] Boston Univ, Dept Hlth Sci, Boston, MA 02215 USA.
[Ghosh, Satrajit S.; Guenther, Frank H.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
[Nieto-Castanon, Alfonso] StatsANC LLC, Buenos Aires, DF, Argentina.
[Guenther, Frank H.] Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA.
[Guenther, Frank H.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Guenther, Frank H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Golfinopoulos, E (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA.
EM egolfino@cns.bu.edu
RI Bohland, Jason/L-4807-2016;
OI Bohland, Jason/0000-0002-6305-5848; Ghosh, Satrajit/0000-0002-5312-6729
FU National Institute on Deafness and other Communication Disorders [R01
DC02852]; CELEST, an NSF Science of Learning Center [NSF SMA-0835976];
National Center for Research Resources [P41RR14075]; MIND Institute
FX This research was supported by the National Institute on Deafness and
other Communication Disorders (R01 DC02852, F. Guenther PI) and by
CELEST, an NSF Science of Learning Center (NSF SMA-0835976). Imaging was
made possible with support from the National Center for Research
Resources grant P41RR14075 and the MIND Institute. The authors would
like to thank Joseph Perkell, Mark Tiede, Kevin Reilly, Oren Civier,
Bruce Fischl, Julie Goodman, Lawrence Wald and the anonymous reviewers
for their time and consideration.
NR 100
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U2 14
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 2011
VL 55
IS 3
BP 1324
EP 1338
DI 10.1016/j.neuroimage.2010.12.065
PG 15
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 734DQ
UT WOS:000288313800045
PM 21195191
ER
PT J
AU Wozniak, J
AF Wozniak, Janet
TI Challenges remain in the diagnosis and treatment of childhood-onset
bipolar disorder
SO NEUROPSYCHIATRY
LA English
DT Editorial Material
C1 [Wozniak, Janet] Massachusetts Gen Hosp, Pediat Bipolar Disorder Clin & Res Program, Boston, MA 02114 USA.
[Wozniak, Janet] Harvard Univ, Sch Med, Boston, MA USA.
RP Wozniak, J (reprint author), Massachusetts Gen Hosp, Pediat Bipolar Disorder Clin & Res Program, Boston, MA 02114 USA.
EM jwozniak@partners.org
NR 10
TC 0
Z9 0
U1 1
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-2008
J9 NEUROPSYCHIATRY-LOND
JI Neuropsychiatry
PD APR
PY 2011
VL 1
IS 2
BP 93
EP 95
DI 10.2217/NPY.11.14
PG 3
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 961DD
UT WOS:000305443200001
ER
PT J
AU Wilens, TE
AF Wilens, Timothy Edwin
TI Current controversies in ADHD: diagnosis, treatment and comorbid
substance abuse
SO NEUROPSYCHIATRY
LA English
DT Editorial Material
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ADULTS; SYMPTOMS; EFFICACY;
SUBTYPES; ABT-089; THERAPY
C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA.
RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, YAW6A,55 Fruit St, Boston, MA 02114 USA.
EM twilens@partners.org
NR 10
TC 0
Z9 0
U1 1
U2 7
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-2008
J9 NEUROPSYCHIATRY-LOND
JI Neuropsychiatry
PD APR
PY 2011
VL 1
IS 2
BP 115
EP 121
DI 10.2217/NPY.11.15
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 961DD
UT WOS:000305443200009
ER
PT J
AU Garzon-Serrano, J
Ryan, C
Waak, K
Hirschberg, R
Tully, S
Bittner, EA
Chipman, DW
Schmidt, U
Kasotakis, G
Benjamin, J
Zafonte, R
Eikermann, M
AF Garzon-Serrano, Jaime
Ryan, Cheryl
Waak, Karen
Hirschberg, Ronald
Tully, Susan
Bittner, Edward A.
Chipman, Daniel W.
Schmidt, Ulrich
Kasotakis, Georgios
Benjamin, John
Zafonte, Ross
Eikermann, Matthias
TI Early Mobilization in Critically Ill Patients: Patients' Mobilization
Level Depends on Health Care Provider's Profession
SO PM&R
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; ACUTE RESPIRATORY-FAILURE; INTENSIVE-CARE;
UNIT MOBILITY; OLDER-ADULTS; REHABILITATION; EXERCISE; THERAPY;
PHYSIOTHERAPY; MEDICINE
AB Objective: To evaluate whether the level of mobilization achieved and the barriers for progressing to the next mobilization level differ between nurses and physical therapists.
Design: Prospective, observational study.
Setting: Twenty-bed surgical intensive care unit (SICU) of the Massachusetts General Hospital.
Participants: Sixty-three critically ill patients.
Methods: Physical therapists and nurses performed 179 mobilization therapies with 63 patients.
Outcome Measurement: Mobilization was defined as the process of enhancing mobility in the SICU, including bed mobility, edge of bed activities, transfers out of bed to a chair, and gait training; the mobilization level was measured on the SICU optimal mobilization scale, a 5-point (0-4) numerical rating scale.
Results: Patients' level of mobilization achieved by physical therapists was significantly higher compared with that achieved by nurses (2.3 +/- 1.2 mean +/- SD versus 1.2 +/- 1.2, respectively P < .0001). Different barriers for mobilization were identified by physical therapists and nurses: hemodynamic instability (26% versus 12%, P = .03) and renal replacement therapy (12% versus 1%, P = .03) were barriers rated higher by nurses, whereas neurologic impairment was rated higher by physical therapists providers (18% versus 38%, P = .002). No mobilization-associated adverse events were observed in this study.
Conclusions: This study showed that physical therapists mobilize their critically ill patients to higher levels compared with nurses. Nurse and physical therapists identify different barriers for mobilization. Routine involvement of physical therapists in directing mobilization treatment may promote early mobilization of critically ill patients. PM R 2011;3:307-313
C1 [Garzon-Serrano, Jaime; Ryan, Cheryl; Tully, Susan; Bittner, Edward A.; Schmidt, Ulrich; Benjamin, John; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA.
[Garzon-Serrano, Jaime; Ryan, Cheryl; Hirschberg, Ronald; Tully, Susan; Bittner, Edward A.; Schmidt, Ulrich; Benjamin, John; Zafonte, Ross; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA.
[Chipman, Daniel W.; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Ryan, Cheryl; Tully, Susan] Massachusetts Gen Hosp, Dept Clin Nursing Serv, Boston, MA 02114 USA.
[Waak, Karen] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA.
[Hirschberg, Ronald; Zafonte, Ross] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA.
[Kasotakis, Georgios] Massachusetts Gen Hosp, Div Trauma & Surg Crit Care, Boston, MA 02114 USA.
RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA.
EM meikermann@partners.org
FU Massachusetts General Hospital Department of Anesthesia, Critical Care
and Pain Medicine, Boston, MA
FX This work was supported by funds from the Massachusetts General Hospital
Department of Anesthesia, Critical Care and Pain Medicine, Boston, MA.
NR 33
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U1 4
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
EI 1934-1563
J9 PM&R
JI PM&R
PD APR
PY 2011
VL 3
IS 4
BP 307
EP 313
PG 7
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 961AY
UT WOS:000305437500005
PM 21497316
ER
PT J
AU Jackson, GL
Lee, SYD
Edelman, D
Weinberger, M
Yano, EM
AF Jackson, George L.
Lee, Shoou-Yih Daniel
Edelman, David
Weinberger, Morris
Yano, Elizabeth M.
TI Employment of mid-level providers in primary care and control of
diabetes
SO PRIMARY CARE DIABETES
LA English
DT Article
DE Diabetes; Mid-level providers; United States Department of Veterans
Affairs
ID NURSE-PRACTITIONERS; NONPHYSICIAN CLINICIAN; PHYSICIAN ASSISTANTS;
CONTROLLED-TRIAL; CASE-MANAGEMENT; UNITED-STATES; VETERANS; OUTCOMES;
QUALITY; ORGANIZATION
AB Aims: Examine potential associations between inclusion of mid-level providers in United States Veterans Affairs (VA) primary care programs and diabetes control.
Methods: We established a cohort of diabetes patients (alive October 1, 1999) using the VA Diabetes Registry and VA corporate databases. 1999 VA Survey of Primary Care Practices data were combined with individual-patient information. We used a two-level hierarchical model to determine the relationship between staffing characteristics and hemoglobin A1c (HbAlc), among 88,682 patients from 198 clinics.
Results: Inclusion of nurse practitioners (NPs) at relatively limited levels (% of all providers who are NPs) in the primary care program was significantly associated with HbA1c lower by 0.31 percentage points (95% CI, -0.50% to -0.12%) compared to programs that did not include NPs. Having some level of NP staffing vs. no NP staffing was associated HbA1c lower by 0.25%. Inclusion of physician assistants (PAs) in primary care programs was generally not associated with a statistically significant difference in HbA1c. The exception is that moderate levels of PA staffing were associated with slightly higher HbA1c [0.18%, 95% CI, 0.02-0.34)].
Conclusions: Diabetes control among primary care patients appeared to benefit from inclusion of NPs, while an analogous association was not found for PAs. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe.
C1 [Jackson, George L.; Edelman, David; Weinberger, Morris] Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[Jackson, George L.; Edelman, David] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA.
[Lee, Shoou-Yih Daniel] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA.
[Weinberger, Morris] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA.
[Yano, Elizabeth M.] VA Greater Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Sepulveda, CA USA.
[Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA.
RP Jackson, GL (reprint author), Durham VA Med Ctr, HSR&D Serv 152, 508 Fulton St, Durham, NC 27705 USA.
EM george.l.jackson@duke.edu
OI Edelman, David/0000-0001-7112-6151
FU VA grant [MRP 05-312]; VA HSRD Service [MPC 97-012]; [2T32HS000079-06]
FX Support: During part of this work, Dr. Jackson was a National Research
Service Award-Agency for Healthcare Research and Quality Postdoctoral
Fellow (institutional training grant 2T32HS000079-06) and a Veterans
Affairs Health Services Research & Development (HSR&D) Merit Review
Entry Program awardee (VA grant MRP 05-312). Dr. Weinberger is a VA
HSR&D Senior Career Scientist awardee. Dr. Yano is a VA HSR&D Research
Career Scientist awardee (RCS 05-195). Survey data collection was funded
by the VA HSR&D Service (Project MPC 97-012).
NR 39
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U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1751-9918
J9 PRIM CARE DIABETES
JI Prim. Care Diabetes
PD APR
PY 2011
VL 5
IS 1
BP 25
EP 31
DI 10.1016/j.pcd.2010.09.005
PG 7
WC Endocrinology & Metabolism; Primary Health Care
SC Endocrinology & Metabolism; General & Internal Medicine
GA 943MR
UT WOS:000304128200004
PM 20980212
ER
PT J
AU Porkka-Heiskanen, T
Kalinchuk, AV
AF Porkka-Heiskanen, Tarja
Kalinchuk, Anna V.
TI Adenosine, energy metabolism and sleep homeostasis
SO SLEEP MEDICINE REVIEWS
LA English
DT Review
DE Adenosine; Caffeine; Energy metabolism; Glia; NF-kB; Sleep; SD; Recovery
sleep
ID BASAL FOREBRAIN NEURONS; ACTIVITY-DEPENDENT RELEASE; ACTIVATED
PROTEIN-KINASE; EQUILIBRATIVE NUCLEOSIDE TRANSPORTERS; VENTROLATERAL
PREOPTIC NEURONS; PONTINE RETICULAR-FORMATION; CENTRAL-NERVOUS-SYSTEM;
MOUSE CEREBRAL-CORTEX; EYE-MOVEMENT SLEEP; NITRIC-OXIDE
AB Adenosine is directly linked to the energy metabolism of cells. In the central nervous system (CNS) an increase in neuronal activity enhances energy consumption as well as extracellular adenosine concentrations. In most brain areas high extracellular adenosine concentrations, through A1 adenosine receptors, decrease neuronal activity and thus the need for energy. Adenosine may be a final common pathway for various sleep factors.
We have identified a relatively specific area, the basal forebrain (BF), which appears to be central in the regulation/execution of recovery sleep after sleep deprivation (SD), or prolonged wakefulness. Adenosine concentration increases in this area during SD, and this increase induces sleep while prevention of the increase during SD abolishes recovery sleep. The increase in adenosine is associated with local changes in energy metabolism as indicated by increases in levels of pyruvate and lactate and increased phosphorylation of AMP-activated protein kinase. The increases in adenosine and sleep are associated with intact cholinergic system since specific lesion of the BF cholinergic cells abolishes both. Whether adenosine during SD is produced by the cholinergic neurons or astrocytes associated with them remains to be explored.
An interesting, but so far unexplored question regards the relationship between the local, cortical regulation of sleep homeostasis and the global regulation of the state of sleep as executed by lower brain mechanisms, including the BF. The increase in adenosine concentration during SD also in cortical areas suggests that adenosine may have a role in the local regulation of sleep homeostasis. The core of sleep need is probably related to primitive functions of life, like energy metabolism. It can be noted that this assumption in no way excludes the possibility that later in evolution additional functions may have developed, e.g., related to complex neuronal network functions like memory and learning. (C) 2010 Published by Elsevier Ltd.
C1 [Porkka-Heiskanen, Tarja] Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland.
[Kalinchuk, Anna V.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02132 USA.
RP Porkka-Heiskanen, T (reprint author), Univ Helsinki, Inst Biomed, POB 63, FIN-00014 Helsinki, Finland.
EM porkka@cc.helsinki.fi; anna_kalinchuk@hms.haivard.edu
OI Stenberg, Tarja/0000-0003-1843-7625
FU Academy of Finland
FX This work was supported by a grant from the Academy of Finland.
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PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1087-0792
EI 1532-2955
J9 SLEEP MED REV
JI Sleep Med. Rev.
PD APR
PY 2011
VL 15
IS 2
BP 123
EP 135
DI 10.1016/j.smrv.2010.06.005
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 737LV
UT WOS:000288571200007
PM 20970361
ER
PT J
AU Agler, AH
Kurth, T
Gaziano, JM
Buring, JE
Cassano, PA
AF Agler, Anne H.
Kurth, Tobias
Gaziano, J. Michael
Buring, Julie E.
Cassano, Patricia A.
TI Randomised vitamin E supplementation and risk of chronic lung disease in
the Women's Health Study
SO THORAX
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; NUTRITION EXAMINATION SURVEY; 3RD
NATIONAL-HEALTH; ANTIOXIDANT STATUS; ALPHA-TOCOPHEROL; CONTROLLED-TRIAL;
COPD; MORTALITY; BURDEN; ASTHMA
AB Background The oxidant/antioxidant balance in lung tissue is hypothesised to contribute to the risk of chronic obstructive pulmonary disease (COPD). Observational studies consistently report higher antioxidant status associated with lower COPD risk, but few randomised studies have been reported.
Methods A post hoc analysis of 38 597 women without chronic lung disease at baseline was conducted in the Women's Health Study (WHS) to test the effect of vitamin E on the risk of incident chronic lung disease. The WHS is a randomised double-blind placebo-controlled factorial trial of vitamin E (600 IU every other day) and aspirin (100 mg every other day) in female health professionals aged >= 45 years. Using Cox proportional hazards models, the effect of randomised vitamin E assignment on self-reported physician-diagnosed chronic lung disease was evaluated.
Results During 10 years of follow-up (376 710 person-years), 760 first occurrences of chronic lung disease were reported in the vitamin E arm compared with 846 in the placebo arm (HR 0.90; 95% CI 0.81 to 0.99; p=0.029). This 10% reduction in the risk of incident chronic lung disease was not modified by cigarette smoking, age, randomised aspirin assignment, multivitamin use or dietary vitamin E intake (minimum p for interaction=0.19). Current cigarette smoking was a strong predictor of chronic lung disease risk (HR 4.17; 95% CI 3.70 to 4.70; vs. never smokers).
Conclusions In this large randomised trial, assignment to 600 IU vitamin E led to a 10% reduction in the risk of chronic lung disease in women.
C1 [Agler, Anne H.; Cassano, Patricia A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Kurth, Tobias; Gaziano, J. Michael; Buring, Julie E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Kurth, Tobias] INSERM, Unit Neuroepidemiol 708, Paris, France.
[Kurth, Tobias] Univ Paris 06, Paris, France.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, GRECC, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA.
RP Cassano, PA (reprint author), Cornell Univ, Div Nutr Sci, 209 Savage Hall, Ithaca, NY 14853 USA.
EM pac6@cornell.edu
RI Kurth, Tobias/A-9243-2012
OI Kurth, Tobias/0000-0001-7169-2620
FU National Institutes for Health, USA [NIH HL071022, NIH HL043851,
CA47988]
FX This study was funded by grants from the National Institutes for Health,
USA, grants NIH HL071022 (PAC); NIH HL043851 and CA47988 (Women's Health
Study).
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PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
EI 1468-3296
J9 THORAX
JI Thorax
PD APR
PY 2011
VL 66
IS 4
BP 320
EP 325
DI 10.1136/thx.2010.155028
PG 6
WC Respiratory System
SC Respiratory System
GA 737WA
UT WOS:000288598900012
PM 21257986
ER
PT J
AU Johnson, AS
O'Sullivan, E
D'Aoust, LN
Omer, A
Bonner-Weir, S
Fisher, RJ
Weir, GC
Colton, CK
AF Johnson, Amy S.
O'Sullivan, Esther
D'Aoust, Laura N.
Omer, Abdulkadir
Bonner-Weir, Susan
Fisher, Robert J.
Weir, Gordon C.
Colton, Clark K.
TI Quantitative Assessment of Islets of Langerhans Encapsulated in Alginate
SO TISSUE ENGINEERING PART C-METHODS
LA English
DT Article
ID STIMULATED INSULIN-SECRETION; ISOLATED PANCREATIC-ISLETS;
SILICONE-RUBBER MEMBRANES; INTRACELLULAR ATP CONTENT; OXYGEN-CONSUMPTION
RATE; BETA-CELL APOPTOSIS; ISOLATED RAT ISLETS; NUDE-MICE; DIFFERENT
DONORS; ADP/ATP RATIO
AB Improved methods have recently been developed for assessing islet viability and quantity in human islet preparations for transplantation, and these measurements have proven useful for predicting transplantation outcome. The objectives of this study were to adapt these methods for use with microencapsulated islets, to verify that they provide meaningful quantitative measurements, and to test them with two model systems: (1) barium alginate and (2) barium alginate containing a 70% (w/v) perfluorocarbon (PFC) emulsion, which presents challenges to use of these assays and is of interest in its own right as a means for reducing oxygen supply limitations to encapsulated tissue. Mitochondrial function was assessed by oxygen consumption rate measurements, and the analysis of data was modified to account for the increased solubility of oxygen in the PFC-alginate capsules. Capsules were dissolved and tissue recovered for nuclei counting to measure the number of cells. Capsule volume was determined from alginate or PFC content and used to normalize measurements. After low oxygen culture for 2 days, islets in normal alginate lost substantial viable tissue and displayed necrotic cores, whereas most of the original oxygen consumption rate was recovered with PFC alginate, and little necrosis was observed. All nuclei were recovered with normal alginate, but some nuclei from nonrespiring cells were lost with PFC alginate. Biocompatibility tests revealed toxicity at the islet periphery associated with the lipid emulsion used to provide surfactants during the emulsification process. We conclude that these new assay methods can be applied to islets encapsulated in materials as complex as PFC-alginate. Measurements made with these materials revealed that enhancement of oxygen permeability of the encapsulating material with a concentrated PFC emulsion improves survival of encapsulated islets under hypoxic conditions, but reformulation of the PFC emulsion is needed to reduce toxicity.
C1 [Johnson, Amy S.; D'Aoust, Laura N.; Fisher, Robert J.; Colton, Clark K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[O'Sullivan, Esther; Omer, Abdulkadir; Bonner-Weir, Susan; Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Colton, CK (reprint author), MIT, Dept Chem Engn, Room 66-452,77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM ckcolton@mit.edu
OI Bonner-Weir, Susan/0000-0003-4682-0656
FU NIH [R01DK50657, R01-DK063108-01A1, NCRR ICR U42 16606]; JDRF Center
FX This work was supported by grants from the NIH (R01DK50657,
R01-DK063108-01A1, and NCRR ICR U42 16606) and JDRF Center for Islet
Transplantation at Harvard Medical School. Rat islet isolations were
performed with the assistance of Jennifer Hollister-Lock, Vaja
Tchipasvilli, and Vassileios Kostaras from Joslin Diabetes Center. Human
islets used for DNA measurements were obtained from various Islet Cell
Resource centers administered by the Administrative and Bioinformatics
Coordinating Center at the City of Hope National Medical Center and
supported by NCRR, NIDDK, and JDRF. Histology sections were prepared by
Chris Cahill (Joslin DERC, NIH DK 36836). Bio-spherix provided the Xvivo
System for use in these experiments.
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U2 9
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3384
J9 TISSUE ENG PART C-ME
JI Tissue Eng. Part C-Methods
PD APR
PY 2011
VL 17
IS 4
BP 435
EP 449
DI 10.1089/ten.tec.2009.0510
PG 15
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 744FD
UT WOS:000289079400007
PM 21067465
ER
PT J
AU Cady, B
Michaelson, JS
Chung, MA
AF Cady, Blake
Michaelson, James S.
Chung, Maureen A.
TI The "Tipping Point" for Breast Cancer Mortality Decline Has Resulted
from Size Reductions Due to Mammographic Screening
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Editorial Material
ID US
C1 [Cady, Blake] Cambridge Hosp, Cambridge Breast Ctr, Dept Surg, Cambridge, MA 02139 USA.
[Michaelson, James S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA USA.
[Chung, Maureen A.] Brown Univ, Rhode Isl Hosp, Dept Surg, Sch Med, Providence, RI 02903 USA.
RP Cady, B (reprint author), Cambridge Hosp, Cambridge Breast Ctr, Dept Surg, Cambridge, MA 02139 USA.
EM bcady123@comcast.net
NR 17
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U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD APR
PY 2011
VL 18
IS 4
BP 903
EP 906
DI 10.1245/s10434-011-1557-y
PG 4
WC Oncology; Surgery
SC Oncology; Surgery
GA 732TW
UT WOS:000288213600001
PM 21267787
ER
PT J
AU Oklu, R
Hesketh, R
Wicky, S
Metcalfe, JC
AF Oeklue, Rahmi
Hesketh, Robin
Wicky, Stephan
Metcalfe, James C.
TI Expression of mRNA Isoforms of Latent Transforming Growth Factor-beta
Binding Protein-1 in Coronary Atherosclerosis and Human Tissues
SO BIOCHEMICAL GENETICS
LA English
DT Article
DE Latent transforming growth factor-beta binding protein; Q-RT-PCR;
Alternative splicing; Genetic variation
ID SMOOTH-MUSCLE-CELLS; AMERICAN-HEART-ASSOCIATION; TGF-BETA;
VASCULAR-LESIONS; RECEPTOR; TGF-BETA-1; GROWTH-FACTOR-BETA-1;
ARTERIOSCLEROSIS; IDENTIFICATION; DEFINITION
AB Latent transforming growth factor-beta binding protein-1 (LTBP1) has been implicated in the control of secretion, localization, and activation of TGF beta (transforming growth factor-beta). We developed a quantitative reverse-transcriptase polymerase chain reaction (Q-RT-PCR) assay using an RNA internal standard to examine the expression of three alternatively spliced isoforms of LTBP1 (LTBP1 Delta 41, LTBP1 Delta 53, and LTBP1 Delta 55) in a variety of human tissues. The assays were also used to determine the expression of LTBP1L and LTBP1S isoforms and total LTBP1. The Q-RT-PCR assays were highly reproducible and showed that in most tissues LTBP1 Delta 55 and LTBP1L were minor components of LTBP1. The proportion of LTBP1 Delta 41 ranged from 2% of total LTBP1 mRNA in early coronary atherosclerotic lesions to 54% in advanced lesions.
C1 [Oeklue, Rahmi; Wicky, Stephan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02155 USA.
[Hesketh, Robin; Metcalfe, James C.] Univ Cambridge, Dept Biochem, Sect Cardiovasc Biol, Cambridge CB2 1QW, England.
RP Oklu, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02155 USA.
EM roklu@partners.org
FU British Heart Foundation; Ali Y. Koc, Koc Holding, Istanbul, Turkey
FX This work was supported by a British Heart Foundation program grant to
JCM. RO is the recipient of a Koc scholarship from Ali Y. Koc, Koc
Holding, Istanbul, Turkey. We are grateful to Drs. Chris Byrne and
Junlong Zhang for helpful discussion of their Q-RT-PCR method.
NR 25
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U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0006-2928
J9 BIOCHEM GENET
JI Biochem. Genet.
PD APR
PY 2011
VL 49
IS 3-4
BP 213
EP 225
DI 10.1007/s10528-010-9400-x
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 732EV
UT WOS:000288168700007
PM 21161366
ER
PT J
AU Cigler, T
Richardson, H
Yaffe, MJ
Fabian, CJ
Johnston, D
Ingle, JN
Nassif, E
Brunner, RL
Wood, ME
Pater, JL
Hu, H
Qi, S
Tu, D
Goss, PE
AF Cigler, T.
Richardson, H.
Yaffe, M. J.
Fabian, C. J.
Johnston, D.
Ingle, J. N.
Nassif, E.
Brunner, R. L.
Wood, M. E.
Pater, J. L.
Hu, H.
Qi, S.
Tu, D.
Goss, P. E.
TI A randomized, placebo-controlled trial (NCIC CTG MAP.2) examining the
effects of exemestane on mammographic breast density, bone density,
markers of bone metabolism and serum lipid levels in postmenopausal
women
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Chemoprevention; Aromatase inhibitors; Breast density; Bone density
ID HORMONE REPLACEMENT THERAPY; CANCER RISK; PARENCHYMAL PATTERNS; ADJUVANT
TAMOXIFEN; MINERAL DENSITY; COMPLETING 5; LETROZOLE; CLASSIFICATION;
PROLIFERATION; POLYMORPHISMS
AB We hypothesized that exemestane (EXE) would reduce mammographic breast density and have unique effects on biomarkers of bone and lipid metabolism. Healthy postmenopausal women were randomized to EXE (25 mg daily) or placebo (PLAC) for 12 months and followed for a total of 24 months. The primary endpoint was change in percent breast density (PD) between the baseline and 12-month mammograms and secondary endpoints were changes in serum lipid levels, bone biomarkers, and bone mineral density (BMD). Ninety-eight women were randomized (49 to EXE; 49 to PLAC) and 65 had PD data at baseline and 12 months. Among women treated with EXE, PD was not significantly changed from baseline at 6, 12, or 24 months and was not different from PLAC. EXE was associated with significant percentage increase from baseline in N-telopeptide at 12 months compared with PLAC. No differences in percent change from baseline in BMD (lumbar spine and femoral neck) were observed between EXE and PLAC at either 12 or 24 months. Patients on EXE had a significantly larger percent decrease in total cholesterol than in the PLAC arm at 6 months and in HDL cholesterol at 3, 6, and 12 months. No significant differences in percent change in LDL or triglycerides were noted at any time point between the two treatment arms. EXE administered for 1 year to healthy postmenopausal women did not result in significant changes in mammographic density. A reversible increase in the bone resorption marker N-telopeptide without significant change in bone specific alkaline phosphatase or BMD during the 12 months treatment period and 1 year later was noted. Changes in lipid parameters on this trial were modest and reversible.
C1 [Hu, H.; Qi, S.; Goss, P. E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Cigler, T.] Weill Cornell Med Coll, New York, NY USA.
[Richardson, H.; Johnston, D.; Pater, J. L.; Tu, D.] NCIC Clin Trials Grp, Kingston, ON, Canada.
[Yaffe, M. J.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Fabian, C. J.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Ingle, J. N.] Mayo Clin, Rochester, MN USA.
[Nassif, E.] Univ Montreal, Notre Dame Hosp, Montreal, PQ H3C 3J7, Canada.
[Brunner, R. L.] Univ Nevada, Sch Med, Reno, NV 89557 USA.
[Wood, M. E.] Fletcher Allen Hlth Care, Burlington, VT USA.
RP Goss, PE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA.
EM pgoss@partners.org
FU The Avon Foundation, New York; Pfizer Inc; Canadian Cancer Society
FX Paul Goss is supported in part by The Avon Foundation, New York. This
project was supported by Pfizer Inc and the Canadian Cancer Society. We
are also indebted to the hard-working investigators and staff at the
participating MAP.2 centres and to all the women who generously agreed
to participate in this trial.
NR 42
TC 21
Z9 21
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD APR
PY 2011
VL 126
IS 2
BP 453
EP 461
DI 10.1007/s10549-010-1322-0
PG 9
WC Oncology
SC Oncology
GA 733GK
UT WOS:000288251000017
PM 21221773
ER
PT J
AU Choi, HR
von Knoch, F
Zurakowski, D
Nelson, SB
Malchau, H
AF Choi, Ho-Rim
von Knoch, Fabian
Zurakowski, David
Nelson, Sandra B.
Malchau, Henrik
TI Can Implant Retention be Recommended for Treatment of Infected TKA?
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID TOTAL-KNEE-ARTHROPLASTY; PROSTHETIC JOINT INFECTION; TOTAL HIP; 2-STAGE
REVISION; DEBRIDEMENT; COMPONENTS; SALVAGE; MANAGEMENT; SPACER;
IRRIGATION
AB Retention treatment is reportedly associated with lower infection control rates than two-stage revision. However, the studies on which this presumption are based depend on comparisons of historical rather than concurrent controls.
We (1) asked whether the infection control rates, number of additional procedures, length of hospital stay, and treatment duration differed between implant retention and two-stage revision treatment; and (2) identified risk factors that can contribute to failure of infection control.
We reviewed the records of 60 patients treated for 64 infected TKA from 2002 to 2007. Twenty-eight patients (32 knees) underwent d,bridement with retention of component, and 32 patients (32 knees) were treated with component removal and two-stage revision surgery. We determined patients' demographics, type of infection, causative organisms, and outcome of treatment. Mean followup was 36 months (range, 12-84 months).
Infection control rate was 31% in retention and 59% in the removal group after initial surgical treatment, and 81% and 91% at latest followup, respectively. Treatment duration was shorter in the retention group and there was no difference in number of additional surgeries and length of hospital stay. Type of treatment (retention versus removal) was the only factor associated with infection control; subgroup analysis in the retention group showed Staphylococcus aureus infection and polyethylene nonexchange as contributing factors for failure of infection control.
Although initial infection control rate was substantially lower in the retention group than the removal group, final results were comparable at latest followup. We believe retention treatment can be selectively considered for non-S. aureus infection, and when applied in selected patients, polyethylene exchange should be performed.
Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
C1 [Choi, Ho-Rim; von Knoch, Fabian; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthoped Lab, Dept Orthoped Surg, Boston, MA 02114 USA.
[Choi, Ho-Rim] SoonChunHyang Univ Hosp, Dept Orthoped Surg, Cheonan, South Korea.
[Zurakowski, David] Harvard Univ, Dept Anesthesiol, Sch Med, Childrens Hosp Boston, Boston, MA USA.
[Zurakowski, David] Harvard Univ, Dept Surg, Sch Med, Childrens Hosp Boston, Boston, MA USA.
[Nelson, Sandra B.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA.
RP Malchau, H (reprint author), Massachusetts Gen Hosp, Harris Orthoped Lab, Dept Orthoped Surg, 55 Fruit St,GRJ-1126, Boston, MA 02114 USA.
EM hmalchau@partners.org
NR 37
TC 28
Z9 30
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD APR
PY 2011
VL 469
IS 4
BP 961
EP 969
DI 10.1007/s11999-010-1679-8
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 730HA
UT WOS:000288023200006
PM 21080127
ER
PT J
AU Wuerz, TH
Regenbogen, SE
Ehrenfeld, JM
Malchau, H
Rubash, HE
Gawande, AA
Kent, DM
AF Wuerz, Thomas H.
Regenbogen, Scott E.
Ehrenfeld, Jesse M.
Malchau, Henrik
Rubash, Harry E.
Gawande, Atul A.
Kent, David M.
TI The Surgical Apgar Score in Hip and Knee Arthroplasty
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID ADVERSE EVENTS; BLOOD-PRESSURE; ERRORS; HANDWRITTEN; HOSPITALS; RECORDS;
RISK
AB A 10-point Surgical Apgar Score, based on patients' estimated blood loss, lowest heart rate, and lowest mean arterial pressure during surgery, was developed to rate patients' outcomes in general and vascular surgery but has not been tested for patients having orthopaedic surgery.
For patients undergoing hip and knee arthroplasties, we asked (1) whether the score provides accurate risk stratification for major postoperative complications, and (2) whether it captures intraoperative variables contributing to postoperative risk based on the three parameters independent of preoperative risk.
We retrospectively reviewed the electronic records for all 3511 patients who underwent a hip or knee arthroplasty from March 2003 to August 2006 and extracted data to calculate a Surgical Apgar Score. We evaluated the relationship between scores and likelihood of major postoperative in-hospital complications and assessed its discrimination and calibration.
Complication rates increased monotonically as the score decreased. Even after controlling for preoperative risk, each 1-point decrease in the score was associated with a 34.0% increase (95% confidence interval, 0.66-0.84) in the odds of a complication. The overall discriminatory performance of the score was a c-statistic of 0.61. Seventy-six percent of all major complications occurred in patients classified as low risk with scores of 7 or greater.
For patients undergoing hip and knee arthroplasties, the score captures important intraoperative information regarding risk of complications and contributes additional information to preoperative risk, but on its own is insufficient to provide comprehensive postoperative risk stratification for arthroplasties.
Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
C1 [Wuerz, Thomas H.; Kent, David M.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Predict Med Res, Boston, MA 02111 USA.
[Wuerz, Thomas H.] Tufts Univ, Sackler Sch Grad Biomed Sci, Clin Res Program, Boston, MA 02111 USA.
[Wuerz, Thomas H.; Malchau, Henrik; Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Regenbogen, Scott E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Regenbogen, Scott E.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Ehrenfeld, Jesse M.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
RP Wuerz, TH (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Ctr Predict Med Res, 35 Kneeland St, Boston, MA 02111 USA.
EM twuerz@partners.org
OI Ehrenfeld, Jesse/0000-0003-3427-0140; Gawande, Atul/0000-0002-1824-9176
FU National Institutes of Health [T32 HS00060]
FX One of the authors (THW) has received funding from the National
Institutes of Health under Ruth L. Kirschstein National Research Service
Award (Agency for Healthcare Research and Quality Grant Number T32
HS00060).
NR 22
TC 22
Z9 22
U1 1
U2 3
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 2011
VL 469
IS 4
BP 1119
EP 1126
DI 10.1007/s11999-010-1721-x
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 730HA
UT WOS:000288023200028
PM 21132410
ER
PT J
AU Clements, JL
Bouchard, CS
Lee, WB
Dunn, SP
Mannis, MJ
Reidy, JJ
John, T
Hannush, SB
Goins, KM
Wagoner, MD
Adi, MA
Rubenstein, JB
Udell, IJ
Babiuch, AS
AF Clements, John L.
Bouchard, Charles S.
Lee, W. Barry
Dunn, Steven P.
Mannis, Mark J.
Reidy, James J.
John, Thomas
Hannush, Sadeer B.
Goins, Kenneth M.
Wagoner, Michael D.
Adi, Marwa A.
Rubenstein, Jonathan B.
Udell, Ira J.
Babiuch, Amy S.
TI Retrospective Review of Graft Dislocation Rate Associated With Descemet
Stripping Automated Endothelial Keratoplasty After Primary Failed
Penetrating Keratoplasty
SO CORNEA
LA English
DT Review
DE cornea transplant; Descemet stripping endothelial keratoplasty;
penetrating keratoplasty; endothelial keratoplasty
ID CELL LOSS; UNITED-STATES; EYES; OUTCOMES; TRENDS
AB Purpose: To report the rate of graft dislocation in patients who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) after a previous penetrating keratoplasty (PKP).
Methods: Institutional review board-approved, multicenter, retrospective chart review. Inclusion criteria included: prior failed PKP and subsequent DSAEK. The primary outcomes measured in this study were the presence of a graft dislocation, rate of rebubble, and graft attachment. Additional variables included: presence of a prior glaucoma drainage device, graft-to-host size disparity, number of sutures remaining in PKP, and stripping of the Descemet membrane at the time of DSAEK surgery.
Results: Ninety patients (97 eyes) were included in the study. In 31% (30 of 97), the endothelial graft dislocated after surgery. All 30 cases required a rebubble except 1, which reattached spontaneously. Ninety-eight percent (95 of 97) of all grafts remained attached for the duration of the follow-up period. Only 2 eyes (2.2%) required repeat graft. Endothelial grafts dislocated in 67% of patients with glaucoma draining devices. The dislocation rate for grafts larger than the host was 12 of 49 (24%), equal to the host was 3 of 17 (18%), and smaller than the host was 8 of 19 (42%). Dislocations occurred in 5 of 21 (24%) of grafts with sutures remaining and 22 of 76 (29%) of those with all sutures out. Five of 12 (42%) cases of grafts performed without stripping the Descemet had dislocations.
Conclusions: The graft dislocation rate in DSAEK procedures after PKP is comparable to that after primary DSAEK cases. Donor grafts that are smaller than the host PKP and the presence of prior glaucoma drainage devices are risk factors for higher rates of graft dislocation.
C1 [Clements, John L.; Bouchard, Charles S.; John, Thomas] Loyola Univ, Dept Ophthalmol, Med Ctr, Maywood, IL 60153 USA.
[Clements, John L.; Bouchard, Charles S.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Ophthalmol, Hines, IL 60141 USA.
[Lee, W. Barry] Eye Consultants Atlanta Piedmont Hosp, Dept Ophthalmol, Atlanta, GA USA.
[Dunn, Steven P.] William Beaumont Hosp, Dept Ophthalmol, Royal Oak, MI 48072 USA.
[Mannis, Mark J.] Univ Calif Davis, Dept Ophthalmol & Vis Sci, Sacramento, CA 95817 USA.
[Reidy, James J.] SUNY Buffalo, Dept Ophthalmol, Buffalo, NY 14260 USA.
[Hannush, Sadeer B.] Wills Eye Inst, Dept Ophthalmol, Philadelphia, PA USA.
[Goins, Kenneth M.; Wagoner, Michael D.] Univ Iowa Hosp & Clin, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
[Adi, Marwa A.] Georgetown Univ, Med Ctr, Dept Ophthalmol, Washington, DC 20007 USA.
[Rubenstein, Jonathan B.; Babiuch, Amy S.] Rush Univ, Dept Ophthalmol, Med Ctr, Chicago, IL 60612 USA.
[Udell, Ira J.] Albert Einstein Coll Med, Northshore Long Isl Jewish Hlth Syst, Dept Ophthalmol, Bronx, NY 10467 USA.
RP Bouchard, CS (reprint author), Loyola Univ, Dept Ophthalmol, Med Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA.
EM cboucha@lumc.edu
FU Richard A. Perritt Charitable Foundation
FX Supported in part by the Richard A. Perritt Charitable Foundation.
NR 21
TC 28
Z9 30
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 2011
VL 30
IS 4
BP 414
EP 418
DI 10.1097/ICO.0b013e3181f7f163
PG 5
WC Ophthalmology
SC Ophthalmology
GA 732OJ
UT WOS:000288196200009
PM 21099405
ER
PT J
AU Wessel, MM
Sarkar, JS
Jakobiec, FA
Dang, NT
Bhat, P
Michaud, N
Starr, CE
AF Wessel, Matthew M.
Sarkar, Jayati S.
Jakobiec, Frederick A.
Dang, Natasha
Bhat, Pooja
Michaud, Norman
Starr, Christopher E.
TI Treatment of Lisch Corneal Dystrophy With Photorefractive Keratectomy
and Mitomycin C
SO CORNEA
LA English
DT Article
DE Lisch corneal dystrophy; photorefractive keratectomy; mitomycin C;
electron microscopy
ID WHORLED MICROCYSTIC DYSTROPHY; KERATOCYTES; EPITHELIUM
AB Purpose: To describe a case of Lisch dystrophy; review the clinical, histopathologic, and electron microscopic features of this entity; and discuss a novel treatment approach using photorefractive keratectomy (PRK) and mitomycin C (MMC).
Methods: A 45-year-old man with a feathery, comet-shaped, right-sided, corneal lesion was treated with excimer laser PRK and 20 seconds of MMC. The uninvolved fellow eye underwent traditional PRK without the use of MMC. Epithelial scrapings were sent for histopathologic analysis.
Results: Histopathologic analysis showed vacuolated cells in the epithelial layer. Electron microscopy revealed empty intracytoplasmic vacuoles, electron-dense whorled inclusions, and reduced tonofilaments. Surface ablation and MMC was successful in treating the initial lesion, with only minimal recurrence noted in the affected eye. Surprisingly, a new asymptomatic lesion was noted in the unaffected eye but dissipated over time.
Conclusions: Although the whorled inclusions represent a novel finding, the overall clinical and microscopic analysis was consistent with Lisch dystrophy. Surface ablation with MMC should be considered as a treatment option for this disease.
C1 [Wessel, Matthew M.; Sarkar, Jayati S.; Starr, Christopher E.] Cornell Univ, Weill Cornell Med Coll, New York Presbyterian Hosp, Dept Ophthalmol, New York, NY 10021 USA.
[Jakobiec, Frederick A.; Bhat, Pooja; Michaud, Norman] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, Boston, MA USA.
[Dang, Natasha] Univ Ottawa, Ottawa Hosp, Inst Eye, Dept Ophthalmol, Ottawa, ON, Canada.
RP Starr, CE (reprint author), Cornell Univ, Weill Cornell Med Coll, New York Presbyterian Hosp, Dept Ophthalmol, 1305 York Ave,11th Floor, New York, NY 10021 USA.
EM cestarr@med.cornell.edu
NR 12
TC 6
Z9 6
U1 0
U2 1
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 2011
VL 30
IS 4
BP 481
EP 485
DI 10.1097/ICO.0b013e3181ec8e26
PG 5
WC Ophthalmology
SC Ophthalmology
GA 732OJ
UT WOS:000288196200026
PM 21045666
ER
PT J
AU Mianowska, B
Fendler, W
Szadkowska, A
Baranowska, A
Grzelak-Agaciak, E
Sadon, J
Keenan, H
Mlynarski, W
AF Mianowska, B.
Fendler, W.
Szadkowska, A.
Baranowska, A.
Grzelak-Agaciak, E.
Sadon, J.
Keenan, H.
Mlynarski, W.
TI HbA(1c) levels in schoolchildren with type 1 diabetes are seasonally
variable and dependent on weather conditions
SO DIABETOLOGIA
LA English
DT Article
DE Adolescents; Children; HbA(1c); Seasonal variation; Type 1 diabetes
mellitus
ID PHYSICAL-ACTIVITY; INTENSIVE TREATMENT; VITAMIN-D; MELLITUS; CHILDREN;
INSULIN; MELATONIN; TIME; VALUES; MEN
AB We evaluated seasonal HbA(1c) changes in children with type 1 diabetes and its relation with measures of weather conditions.
HbA(1c) changes over more than 3 years were evaluated in type 1 diabetic patients who were younger than 18 years and had diabetes duration of more than 12 months, and correlated with measures of weather conditions (ambient temperature, hours of sunshine and solar irradiance). After comparison of autocorrelation patterns, patterns of metabolic control and meteorological data were evaluated using Spearman rank correlation.
A total of 3,935 HbA(1c) measurements in 589 school (a parts per thousand yen7 years) and 88 preschool (< 7 years) children were analysed. Mean (+/- SD) HbA(1c) level for the whole study period was 7.65 +/- 1.12%. The lowest HbA(1c) levels were observed in late summer and the highest in winter months, with differences consistently exceeding 0.44%. Autocorrelation analysis of HbA(1c) levels in schoolchildren showed a sine-wave pattern with a cycle length of roughly 12 months, which mirrored changes in ambient temperature. Strong negative correlations of HbA(1c) with ambient temperature (R = -0.56; p = 0.0002), hours of sunshine (R = -0.52; p = 0.0007) and solar irradiance (R = -0.52; p = 0.0006) were present in schoolchildren, but not in preschoolers (p a parts per thousand yenaEuro parts per thousand 0.29 for each correlation).
Seasonal changes of HbA(1c) levels in schoolchildren with type 1 diabetes are a significant phenomenon and should be considered in patient education and diabetes management. They may potentially affect the results of clinical trials using HbA(1c) levels as their primary outcome, as well as HbA(1c)-based diagnosis of diabetes.
C1 [Mianowska, B.; Fendler, W.; Szadkowska, A.; Baranowska, A.; Mlynarski, W.] Med Univ Lodz, Dept Pediat Oncol Hematol & Diabetol, PL-91738 Lodz, Poland.
[Grzelak-Agaciak, E.; Sadon, J.] Inst Meteorol & Water Management, Warsaw, Poland.
[Keenan, H.] Harvard Univ, Sch Med, Dept Med, Clin Res Joslin Diabet Ctr, Boston, MA USA.
RP Mlynarski, W (reprint author), Med Univ Lodz, Dept Pediat Oncol Hematol & Diabetol, 36-50 Sporna St, PL-91738 Lodz, Poland.
EM Wojciech.Mlynarski@umed.lodz.pl
RI Mianowska, Beata/S-9485-2016; Fendler, Wojciech/S-9592-2016
OI Fendler, Wojciech/0000-0002-5083-9168
FU Innovative Economy Operational Program; Foundation for Polish Science;
Polish Ministry of Science and Higher Education [N407 022135, N407
099437]; Foundation for Development of Polish Pharmacy and Medicine
FX The study was funded by TEAM programme 'Polish Registry for Pediatric
and Adolescent Diabetes-nationwide genetic screening for monogenic
diabetes' of the Innovative Economy Operational Program and Foundation
for Polish Science. W. Fendler was supported by a research grant of the
Polish Ministry of Science and Higher Education (N407 022135) and the
Foundation for Development of Polish Pharmacy and Medicine. W. Mlynarski
was supported by a research grant of the Polish Ministry of Science and
Higher Education (N407 099437).
NR 30
TC 22
Z9 22
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD APR
PY 2011
VL 54
IS 4
BP 749
EP 756
DI 10.1007/s00125-010-2013-4
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 732VG
UT WOS:000288217200006
PM 21188352
ER
PT J
AU Xavier, GD
Farhan, H
Kim, H
Caxaria, S
Johnson, P
Hughes, S
Bugliani, M
Marselli, L
Marchetti, P
Birzele, F
Sun, G
Scharfmann, R
Rutter, J
Siniakowicz, K
Weir, G
Parker, H
Reimann, F
Gribble, FM
Rutter, GA
AF Xavier, G. da Silva
Farhan, H.
Kim, H.
Caxaria, S.
Johnson, P.
Hughes, S.
Bugliani, M.
Marselli, L.
Marchetti, P.
Birzele, F.
Sun, G.
Scharfmann, R.
Rutter, J.
Siniakowicz, K.
Weir, G.
Parker, H.
Reimann, F.
Gribble, F. M.
Rutter, G. A.
TI Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in
human islets in type 2 diabetes and regulates glucagon secretion
SO DIABETOLOGIA
LA English
DT Article
DE Alpha cells; Glucagon secretion; Human islets of Langerhans; Knockout
mouse; PASK
ID GAMMA-AMINOBUTYRIC-ACID; PANCREATIC ALPHA-CELLS; SERINE/THREONINE
KINASE; BETA-CELLS; GENE-EXPRESSION; IN-VIVO; INSULIN; GLUCOSE; MOUSE;
SOMATOSTATIN
AB We assessed whether per-arnt-sim (PAS) domain-containing protein kinase (PASK) is involved in the regulation of glucagon secretion.
mRNA levels were measured in islets by quantitative PCR and in pancreatic beta cells obtained by laser capture microdissection. Glucose tolerance, plasma hormone levels and islet hormone secretion were analysed in C57BL/6 Pask homozygote knockout mice (Pask (-/-)) and control littermates. Alpha-TC1-9 cells, human islets or cultured E13.5 rat pancreatic epithelia were transduced with anti-Pask or control small interfering RNAs, or with adenoviruses encoding enhanced green fluorescent protein or PASK.
PASK expression was significantly lower in islets from human type 2 diabetic than control participants. PASK mRNA was present in alpha and beta cells from mouse islets. In Pask (-/-) mice, fasted blood glucose and plasma glucagon levels were 25 +/- 5% and 50 +/- 8% (mean +/- SE) higher, respectively, than in control mice. At inhibitory glucose concentrations (10 mmol/l), islets from Pask (-/-) mice secreted 2.04 +/- 0.2-fold (p < 0.01) more glucagon and 2.63 +/- 0.3-fold (p < 0.01) less insulin than wild-type islets. Glucose failed to inhibit glucagon secretion from PASK-depleted alpha-TC1-9 cells, whereas PASK overexpression inhibited glucagon secretion from these cells and human islets. Extracellular insulin (20 nmol/l) inhibited glucagon secretion from control and PASK-deficient alpha-TC1-9 cells. PASK-depleted alpha-TC1-9 cells and pancreatic embryonic explants displayed increased expression of the preproglucagon (Gcg) and AMP-activated protein kinase (AMPK)-alpha2 (Prkaa2) genes, implying a possible role for AMPK-alpha2 downstream of PASK in the control of glucagon gene expression and release.
PASK is involved in the regulation of glucagon secretion by glucose and may be a useful target for the treatment of type 2 diabetes.
C1 [Xavier, G. da Silva; Farhan, H.; Kim, H.; Caxaria, S.; Sun, G.; Rutter, G. A.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Endocrinol Diabet & Metab, Sect Cell Biol, London SW7 2AZ, England.
[Johnson, P.; Hughes, S.] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England.
[Bugliani, M.; Marselli, L.; Marchetti, P.] Univ Pisa, Dipartimento Endocrinol & Metab, Unita Metab, Pisa, Italy.
[Birzele, F.] Boehringer Ingelheim Pharma GmbH & Co KG, Target Discovery Res, Ingelheim, Germany.
[Scharfmann, R.] Univ Paris 05, INSERM U845, Ctr Rech Croissance & Signalisat, Hop Necker,Fac Med, Paris, France.
[Rutter, J.] Univ Utah, Sch Med, Div Endocrinol, Salt Lake City, UT USA.
[Siniakowicz, K.; Weir, G.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol,Res Div, Boston, MA 02115 USA.
[Siniakowicz, K.; Weir, G.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Parker, H.; Reimann, F.; Gribble, F. M.] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England.
[Parker, H.; Reimann, F.; Gribble, F. M.] Addenbrookes Hosp, Dept Clin Biochem, Cambridge, England.
RP Xavier, GD (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Endocrinol Diabet & Metab, Sect Cell Biol, Exhibit Rd, London SW7 2AZ, England.
EM g.dasilva-xavier@imperial.ac.uk; g.rutter@imperial.ac.uk
RI Marchetti, Piero/J-7439-2013;
OI Marchetti, Piero/0000-0003-4907-0635; da Silva Xavier,
Gabriela/0000-0002-0678-012X
FU Juvenile Diabetes Research Foundation; European Foundation; Wellcome
Trust [081958/2/07/2]; Medical Research Council [G0401641]; Imperial
College London; Diabetes Research and Wellness Foundation
FX The authors thank S. Vakhshouri for technical assistance, and F.
Semplici and M. K. Loder for scientific input during manuscript
preparation. This work was supported by a Juvenile Diabetes Research
Foundation post-doctoral fellowship and an European Foundation for the
Study of Diabetes Albert Renold travelling fellowship to G. da Silva
Xavier, and by grants to G. A. Rutter from the Wellcome Trust
(081958/2/07/2) and the Medical Research Council (G0401641). H. Farhan,
H. Kim and S. Caxaria were supported by Imperial College London BSc and
MSc project funds. The Diabetes Research and Wellness Foundation
supported P. Johnson and S. Hughes.
NR 37
TC 12
Z9 13
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD APR
PY 2011
VL 54
IS 4
BP 819
EP 827
DI 10.1007/s00125-010-2010-7
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 732VG
UT WOS:000288217200016
ER
PT J
AU Dubovsky, SL
Dubovsky, AN
AF Dubovsky, Steven L.
Dubovsky, Amelia N.
TI Ziprasidone for maintenance treatment of bipolar I disorder in adults
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE antipsychotic drug; bipolar; maintenance; mania; prophylaxis
ID RANDOMIZED CONTROLLED-TRIALS; ATYPICAL ANTIPSYCHOTICS; DOUBLE-BLIND;
MOOD STABILIZER; ACUTE MANIA; DE-POINTES; PLACEBO; EFFICACY; MANAGEMENT;
LITHIUM
AB Introduction: Antipsychotic drugs are increasingly used in the maintenance treatment of bipolar disorder. This review addresses the evidence supporting the use of one of these medications for this indication in order to place available data in perspective for the clinician.
Areas covered: The approval of ziprasidone for maintenance treatment of bipolar I disorder was based on two open-label extensions of industry-sponsored 3-week monotherapy trials in mania, involving a total of 189 patients and an industry-sponsored study using sample enrichment of 584 outpatients who had either ziprasidone or a placebo added to lithium or valproate. Patients enrolled in maintenance studies did not have refractory mood disorders or comorbid conditions or risk of dangerousness, and they were able to give sustained consent. Ziprasidone is generally well tolerated, but should be taken with food. Primary interactions of concern are those with other serotonergic medications and other medications that prolong the QT interval.
Expert opinion: Although antipsychotic drugs are used frequently for maintenance treatment, current guidelines recommend that an attempt be made to withdraw them after acute treatment. The use of these medications as part of a maintenance regimen is most appropriate in cases of persistent psychosis or failure to respond to standard mood stabilizer combinations.
C1 [Dubovsky, Steven L.] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14215 USA.
[Dubovsky, Amelia N.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Dubovsky, Steven L.] Univ Colorado, Dept Med, Denver, CO USA.
RP Dubovsky, SL (reprint author), SUNY Buffalo, Dept Psychiat, 462 Grider St, Buffalo, NY 14215 USA.
EM dubovsky@buffalo.edu
FU Pfizer; Biogen; Eli Lilly; Otsuka; Sumitomo
FX SL Dubovsky has received research support from Pfizer, Biogen, Eli
Lilly, Otsuka and Sumitomo.
NR 45
TC 1
Z9 2
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-6566
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD APR
PY 2011
VL 12
IS 5
BP 817
EP 824
DI 10.1517/14656566.2011.563237
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 732VS
UT WOS:000288218400013
PM 21385150
ER
PT J
AU Furukawa, T
Hatori, T
Fujita, I
Yamamoto, M
Kobayashi, M
Ohike, N
Morohoshi, T
Egawa, S
Unno, M
Takao, S
Osako, M
Yonezawa, S
Mino-Kenudson, M
Lauwers, GY
Yamaguchi, H
Ban, S
Shimizu, M
AF Furukawa, Toru
Hatori, Takashi
Fujita, Izumi
Yamamoto, Masakazu
Kobayashi, Makio
Ohike, Nobuyuki
Morohoshi, Toshio
Egawa, Shinichi
Unno, Michiaki
Takao, Sonshin
Osako, Masahiko
Yonezawa, Suguru
Mino-Kenudson, Mari
Lauwers, Gregory Y.
Yamaguchi, Hiroshi
Ban, Shinichi
Shimizu, Michio
TI Prognostic relevance of morphological types of intraductal papillary
mucinous neoplasms of the pancreas
SO GUT
LA English
DT Article
ID CYSTIC NEOPLASMS; EXPRESSION; TUMORS; CLASSIFICATION; MANAGEMENT;
CONSENSUS
AB Objective The clinicopathological significance of four morphological types of intraductal papillary mucinous neoplasms of the pancreas (IPMNs; gastric, intestinal, pancreatobiliary and oncocytic) was assessed.
Design Retrospective multicentre analysis of 283 surgically resected IPMNs.
Results Of the 283 IPMNs, 139 were of the gastric type, 101 were intestinal, 19 were pancreatobiliary and 24 were oncocytic. These types were significantly associated with clinicopathological factors including sex (p=0.0032), age (p=0.00924), ectatic duct size (p=0.0245), detection of mural nodules (p=4.09x10(-6)), histological grade (p < 2.20x10(-16)), macroscopic types with differential involvement of the pancreatic duct system (p=3.91x10(-5)), invasive phenotypes (p=3.34x10(-12)), stage (p < 2.20x10(-16)) and recurrence (p=0.00574). Kaplan-Meier analysis showed significant differences in patient survival by morphological type (p=5.24x10(-6)). Survival rates at 5 and 10 years, respectively, were 0.937 (95% CI 0.892 to 0.984) for patients with gastric-type IPMNs; 0.886 (95% CI 0.813 to 0.965) and 0.685 (95% CI 0.553 to 0.849) for those with intestinal-type IPMNs; 0.839 (95% CI 0.684 to 1.000) and 0.734 (95% CI 0.526 to 1.000) for those with oncocytic-type IPMNs; and 0.520 (95% CI 0.298 to 0.909) and undetermined for those with pancreatobiliary-type IPMNs. Analysis by the Cox proportional hazards model comparing prognostic risks determined by stage and the morphological and macroscopic types indicated that staging was the most significant predictor of survival (p=3.68x10(-8)) followed by the morphological type (p=0.0435). Furthermore, the morphological type remained a significant predictor in a subcohort of invasive cases (p=0.0089).
Conclusion In this multicentre retrospective analysis, the morphological type of IPMN appears to be an independent predictor of patient prognosis.
C1 [Furukawa, Toru] Tokyo Womens Med Univ, Inst Integrated Med Sci, Shinjuku Ku, Tokyo 1628666, Japan.
[Furukawa, Toru; Kobayashi, Makio] Tokyo Womens Med Univ Hosp, Dept Surg Pathol, Tokyo, Japan.
[Hatori, Takashi; Fujita, Izumi; Yamamoto, Masakazu] Tokyo Womens Med Univ, Dept Surg, Inst Gastroenterol, Tokyo 1628666, Japan.
[Kobayashi, Makio] Tokyo Womens Med Univ, Dept Pathol, Tokyo 1628666, Japan.
[Ohike, Nobuyuki; Morohoshi, Toshio] Showa Univ, Sch Med, Dept Pathol 1, Tokyo 142, Japan.
[Egawa, Shinichi; Unno, Michiaki] Tohoku Univ, Div Hepatobiliary Pancreat Surg, Grad Sch Med, Sendai, Miyagi 980, Japan.
[Takao, Sonshin] Kagoshima Univ, Frontier Sci Res Ctr, Kagoshima 890, Japan.
[Osako, Masahiko] Kagoshima Shi Med Assoc Hosp, Dept Surg, Kagoshima, Japan.
[Yonezawa, Suguru] Kagoshima Univ, Dept Human Pathol, Field Oncol, Grad Sch Med & Dent Sci, Kagoshima 890, Japan.
[Mino-Kenudson, Mari; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Yamaguchi, Hiroshi; Ban, Shinichi; Shimizu, Michio] Saitama Med Univ, Int Med Ctr, Dept Pathol, Hidaka, Saitama, Japan.
RP Furukawa, T (reprint author), Tokyo Womens Med Univ, Inst Integrated Med Sci, Shinjuku Ku, 8-1 Kawada Cho, Tokyo 1628666, Japan.
EM toru.furukawa@twmu.ac.jp
RI Unno, Michiaki/A-8633-2010
OI Unno, Michiaki/0000-0002-2145-6416
FU Ministry of Education, Culture, Sports, Science and Technology; Ministry
of Education, Culture, Sports, Science and Technology (Japan)
FX This work was supported in part by a grant-in-aid from the Ministry of
Education, Culture, Sports, Science and Technology and by the Program
for Promoting the Establishment of Strategic Research Centers, Special
Coordination Funds for Promoting Science and Technology, Ministry of
Education, Culture, Sports, Science and Technology (Japan).
NR 20
TC 90
Z9 92
U1 0
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD APR
PY 2011
VL 60
IS 4
BP 509
EP 516
DI 10.1136/gut.2010.210567
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730CZ
UT WOS:000288010600016
PM 21193453
ER
PT J
AU Pett, SL
Carey, C
Lin, E
Wentworth, D
Lazovski, J
Miro, JM
Gordin, F
Angus, B
Rodriguez-Barradas, M
Rubio, R
Tambussi, G
Cooper, DA
Emery, S
AF Pett, S. L.
Carey, C.
Lin, E.
Wentworth, D.
Lazovski, J.
Miro, J. M.
Gordin, F.
Angus, B.
Rodriguez-Barradas, M.
Rubio, R.
Tambussi, G.
Cooper, D. A.
Emery, S.
CA INSIGHT-ESPRIT Study Grp
TI Predictors of bacterial pneumonia in Evaluation of Subcutaneous
Interleukin-2 in a Randomized International Trial (ESPRIT)
SO HIV MEDICINE
LA English
DT Article
DE bacterial pneumonia; combination antiretroviral therapy; ESPRIT; rIL-2
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; INCREASED
APOPTOSIS; THERAPY; RISK; INDIVIDUALS; SMOKING; CYCLES; PLASMA; COHORT
AB Background and Objectives
Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts >= 300 cells/mu L, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections.
Methods
Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected.
Results
IL-2 cycling was most intense in years 1-2. Over approximate to 7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570 cells/mu L (IL-2 arm) and 463 cells/mu L (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P < 0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/mu L higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received < 180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs. >= 180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively.
Conclusions
Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration.
C1 [Pett, S. L.] Univ New S Wales, Fac Med, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2034, Australia.
[Pett, S. L.; Cooper, D. A.] St Vincents Hosp, Ctr Appl Med Res, Sydney, NSW 2010, Australia.
[Wentworth, D.] Univ Minnesota, Dept Biostat, Minneapolis, MN USA.
[Lazovski, J.] Fdn ESPRIT, Buenos Aires, DF, Argentina.
[Miro, J. M.] Univ Barcelona, Hosp Clin IDIBAPS, Barcelona, Spain.
[Gordin, F.] VA Med Ctr, Dept Infect Dis, Washington, DC USA.
[Angus, B.] John Radcliffe Hosp, Wellcome Trust Ctr Clin Trop Med, Oxford OX3 9DU, England.
[Rodriguez-Barradas, M.] VA Med Ctr, Houston, TX USA.
[Rubio, R.] Hosp 12 Octubre, E-28041 Madrid, Spain.
[Tambussi, G.] Univ Milan, Osped San Raffaele, Div Malattie, I-20127 Milan, Italy.
RP Pett, SL (reprint author), Univ New S Wales, Fac Med, Natl Ctr HIV Epidemiol & Clin Res, UNSW Coogee Campus,45 Beach St, Sydney, NSW 2034, Australia.
EM spett@nchecr.unsw.edu.au
RI Yee, Thynn Thynn/H-5862-2012; Beral, Valerie/B-2979-2013; Doerler,
Martin/C-2015-2013; Pulido, Federico/B-8417-2009; Arribas,
Jose/A-1595-2015; Victor, Moreno-Cuerda/G-3851-2016; Bouza,
Emilio/D-8661-2014; Emery, Sean/H-4920-2013
OI Okhuysen, Pablo/0000-0002-1596-3411; Magenta,
Lorenzo/0000-0002-7644-3647; Angus, Brian/0000-0003-3598-7784; Pulido,
Federico/0000-0002-7414-8812; Arribas, Jose/0000-0002-7410-9450; Victor,
Moreno-Cuerda/0000-0003-0262-8216; Bouza, Emilio/0000-0001-6967-9267;
Emery, Sean/0000-0001-6072-8309
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI46957, U01 AI068641]
FX The Writing Group acknowledges the efforts of the many ESPRIT and
SILCAAT investigators who collected these data, and the International
Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
Executive Committee (J. D. Neaton, D. Abrams, A. Babiker, J. Baxter, D.
A. Cooper, C. J. Cohen, D. Cohn, J. H. Darbyshire, W. El-Sadr, S. Emery,
F. Gordin, H. C. Lane, G. Larson, M. H. Losso, J. D. Lundgren, J. Nadler
and A. N. Phillips) for their oversight of the ESPRIT study and valuable
editorial assistance. ESPRIT was supported by grants U01 AI46957 and U01
AI068641 from the National Institute of Allergy and Infectious Diseases
(NIAID). rIL-2 was provided by Chiron and Novartis. This study is
ClinicalTrials.gov number NCT00004978.
NR 25
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-2662
J9 HIV MED
JI HIV Med.
PD APR
PY 2011
VL 12
IS 4
BP 219
EP 227
DI 10.1111/j.1468-1293.2010.00875.x
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 730GB
UT WOS:000288020700005
PM 20812949
ER
PT J
AU Eyler, LT
Prom-Wormley, E
Fennema-Notestine, C
Panizzon, MS
Neale, MC
Jernigan, TL
Fischl, B
Franz, CE
Lyons, MJ
Stevens, A
Pacheco, J
Perry, ME
Schmitt, JE
Spitzer, NC
Seidman, LJ
Thermenos, HW
Tsuang, MT
Dale, AM
Kremen, WS
AF Eyler, Lisa T.
Prom-Wormley, Elizabeth
Fennema-Notestine, Christine
Panizzon, Matthew S.
Neale, Michael C.
Jernigan, Terry L.
Fischl, Bruce
Franz, Carol E.
Lyons, Michael J.
Stevens, Allison
Pacheco, Jennifer
Perry, Michele E.
Schmitt, J. Eric
Spitzer, Nicholas C.
Seidman, Larry J.
Thermenos, Heidi W.
Tsuang, Ming T.
Dale, Anders M.
Kremen, William S.
TI Genetic Patterns of Correlation Among Subcortical Volumes in Humans:
Results From a Magnetic Resonance Imaging Twin Study
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE behavioral genetics; hippocampus; amygdala; striatum; pallidum; caudate;
putamen; thalamus; ventricles
ID FACTOR VAL66MET POLYMORPHISM; VIETNAM ERA TWIN; HUMAN BRAIN;
NEUROTROPHIC FACTOR; CEREBRAL-CORTEX; HIPPOCAMPAL VOLUMES;
HEALTHY-SUBJECTS; OLDER-ADULTS; MORPHOLOGY; MRI
AB Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease. Hum Brain Mapp 32:641-653, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [Eyler, Lisa T.; Fennema-Notestine, Christine; Panizzon, Matthew S.; Jernigan, Terry L.; Franz, Carol E.; Perry, Michele E.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Eyler, Lisa T.] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, San Diego, CA USA.
[Prom-Wormley, Elizabeth; Neale, Michael C.; Schmitt, J. Eric] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA.
[Prom-Wormley, Elizabeth; Neale, Michael C.; Schmitt, J. Eric] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA.
[Prom-Wormley, Elizabeth; Neale, Michael C.; Schmitt, J. Eric] Virginia Commonwealth Univ, Dept Mol Genet, Richmond, VA USA.
[Jernigan, Terry L.; Perry, Michele E.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA.
[Fischl, Bruce; Stevens, Allison; Pacheco, Jennifer] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Fischl, Bruce; Stevens, Allison; Pacheco, Jennifer] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lyons, Michael J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Spitzer, Nicholas C.] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA.
[Seidman, Larry J.; Thermenos, Heidi W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA.
[Tsuang, Ming T.] Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA.
[Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Tsuang, Ming T.; Kremen, William S.] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA.
RP Eyler, LT (reprint author), 9500 Gilman Dr,Mail Code 9151B, La Jolla, CA 92093 USA.
EM lteyler@ucsd.edu
RI Lyons, Michael/B-6119-2011;
OI Prom-Wormley, Elizabeth/0000-0001-9230-9723; Lyons,
Michael/0000-0001-6516-9219; Fennema-Notestine,
Christine/0000-0002-6527-6361
FU National Institute on Aging, National Institutes of Health (NIH) [U24
RR021382, R01 AG18386, R01 AG18384, R01 AG22381, R01 AG 22982]; National
Institute for Mental Health, NIH [R01 MH20030]; National Institute for
Drug Abuse, NIH [R01 DA18673]; VA Desert Pacific Mental Illness Research
Education and Clinical Center
FX Contract grant sponsor: National Institute on Aging, National Institutes
of Health (NIH); Contract grant numbers: U24 RR021382, R01 AG18386, R01
AG18384, R01 AG22381, R01 AG 22982; Contract grant sponsor: National
Institute for Mental Health, NIH; Contract grant number: R01 MH20030;
Contract grant sponsor: National Institute for Drug Abuse, NIH; Contract
grant number: R01 DA18673; Contract grant sponsor: VA Desert Pacific
Mental Illness Research Education and Clinical Center.
NR 45
TC 19
Z9 19
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD APR
PY 2011
VL 32
IS 4
BP 641
EP 653
DI 10.1002/hbm.21054
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 732ID
UT WOS:000288177300012
PM 20572207
ER
PT J
AU Wang, MJ
Tang, ST
Stryhn, A
Justesen, S
Larsen, MV
Dziegiel, MH
Lewinsohn, DM
Buus, S
Lund, O
Claesson, MH
AF Wang, Mingjun
Tang, Sheila T.
Stryhn, Anette
Justesen, Sune
Larsen, Mette V.
Dziegiel, Morten H.
Lewinsohn, David M.
Buus, Soren
Lund, Ole
Claesson, Mogens H.
TI Identification of MHC class II restricted T-cell-mediated reactivity
against MHC class I binding Mycobacterium tuberculosis peptides
SO IMMUNOLOGY
LA English
DT Article
DE cytotoxic T lymphocyte epitope; HLA-I; HLA-II; Mycobacterium
tuberculosis; vaccine
ID CD8-T-CELL MEMORY; IMMUNE-RESPONSES; CD4-T-CELL HELP; ACUTE INFECTION;
CTL EPITOPES; GENOME-WIDE; MICE; VIVO; MACROPHAGES; VACCINATION
AB P>Major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTL) are known to play an important role in the control of Mycobacterium tuberculosis infection so identification of CTL epitopes from M. tuberculosis is of importance for the development of effective peptide-based vaccines. In the present work, bioinformatics technology was employed to predict binding motifs of 9mer peptides derived from M. tuberculosis for the 12 HLA-I supertypes. Subsequently, the predicted peptides were synthesized and assayed for binding to HLA-I molecules in a biochemically based system. The antigenicity of a total of 157 peptides with measured affinity for HLA-I molecules of K(D) <= 500 nm were evaluated using peripheral blood T cells from strongly purified protein derivative reactive healthy donors. Of the 157 peptides, eight peptides (5%) were found to induce T-cell responses. As judged from blocking with HLA class I and II subtype antibodies in the ELISPOT assay culture, none of the eight antigenic peptides induced HLA class I restricted CD8(+) T-cell responses. Instead all responses were blocked by pan-HLA class II and anti-HLA-DR antibodies. In addition, CD4(+) T-cell depletion before the 10 days of expansion, resulted in total loss of reactivity in the ELISPOT culture for most peptide specificities. FACS analyses with intracellular interferon-gamma staining of T cells expanded in the presence of M. tuberculosis peptides confirmed that the responsive cells were indeed CD4(+). In conclusion, T-cell immunity against HLA-I binding 9mer M. tuberculosis-derived peptides might in many cases turn out to be mediated by CD4(+) T cells and restricted by HLA-II molecules. The use of 9mer peptides recognized by both CD8(+) and CD4(+) T cells might be of importance for the development of future M. tuberculosis peptide-based vaccines.
C1 [Claesson, Mogens H.] Univ Copenhagen, Panum Inst, Dept Int Hlth Immunol & Microbiol, Fac Heath Sci, DK-2200 Copenhagen N, Denmark.
[Tang, Sheila T.; Larsen, Mette V.; Lund, Ole] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark.
[Dziegiel, Morten H.] Univ Copenhagen Hosp, HS Blood Bank KI 2034, DK-2100 Copenhagen, Denmark.
[Lewinsohn, David M.] Portland VA Med Ctr, CCM, Portland, OR USA.
RP Claesson, MH (reprint author), Univ Copenhagen, Panum Inst, Dept Int Hlth Immunol & Microbiol, Fac Heath Sci, Bldg 18-3,Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark.
EM claesson@sund.ku.dk
RI Lund, Ole/F-4437-2014; Buus, Soren/F-5446-2010; Lewinsohn,
David/I-4936-2013;
OI Lund, Ole/0000-0003-1108-0491; Lewinsohn, David/0000-0001-9906-9494;
Buus, Soren/0000-0001-8363-1999
FU National Institute of Allergy and Infectious Disease [HHSN266200400083C,
HHSN266200400025C]; EU [503231]; National Institutes of Health
[HHSN266200400081C]
FX We are grateful to Ms Maja Udsen and Ms Trine Devantier for excellent
technical assistance. This work was supported by National Institute of
Allergy and Infectious Disease contracts HHSN266200400083C,
HHSN266200400025C, EU 6FP 503231 and National Institutes of Health
contract HHSN266200400081C (DML).
NR 55
TC 11
Z9 13
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD APR
PY 2011
VL 132
IS 4
BP 482
EP 491
DI 10.1111/j.1365-2567.2010.03383.x
PG 10
WC Immunology
SC Immunology
GA 732UV
UT WOS:000288216100004
PM 21294723
ER
PT J
AU Ananthakrishnan, AN
McGinley, EL
Saeian, K
Binion, DG
AF Ananthakrishnan, Ashwin N.
McGinley, Emily L.
Saeian, Kia
Binion, David G.
TI Temporal Trends in Disease Outcomes Related to Clostridium Difficile
Infection in Patients with Inflammatory Bowel Disease
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE inflammatory bowel disease; Crohn's disease; ulcerative colitis;
Clostridium difficile; colectomy; hospitalization; severity
ID TOXIN; DIARRHEA; IMPACT; HOSPITALIZATION; EPIDEMIOLOGY; OUTBREAK;
COLITIS; STRAIN
AB Background: Clostridium difficile has emerged as an important pathogen in patients with inflammatory bowel disease (IBD) and is associated with increased morbidity and mortality. No studies have examined the temporal change in severity of C. difficile infection (CDI) complicating IBD.
Methods: Using data from the Nationwide Inpatient Sample, we identified all IBD-related hospitalizations during the years 1998, 2004, and 2007 and examined hospitalizations with a coexisting diagnosis of C. difficile. We compared the absolute outcomes of in-hospital mortality and colectomy in the C. difficile-IBD cohort during these timepoints, and also examined these outcomes relative to non-C. difficile IBD controls during each corresponding year.
Results: During 1998, 2004, and 2007, approximately 1.4%, 2.3%, and 2.9% of all IBD hospitalizations nationwide were complicated by CDI (P < 0.001). The absolute mortality in the C. difficile-IBD cohort increased from 5.9%-7.2% (P = 0.052) with a nonsignificant increase in colectomy rate from 3.8%-4.5% between 1998 and 2007. Compared to non-C. difficile IBD controls, there was an increase in the relative mortality risk associated with C. difficile from 1998 (odds ratio [OR] 2.38, 95% confidence interval [CI]: 1.52-3.72) to 2007 (OR 3.38, 95% CI: 2.66-4.29) (P = 0.15) with a significant increase in total colectomy odds from 1998 (OR 1.39, 95% CI: 0.81-2.37) to 2007 (OR 2.51, 95% CI: 1.90-3.34) (P = 0.03).
Conclusion: There has been a temporal increase nationwide in CDI complicating IBD hospitalizations. The excess morbidity associated with C. difficile infection in hospitalized IBD patients has increased between 1998 and 2007.
C1 [Ananthakrishnan, Ashwin N.; Saeian, Kia] Med Coll Wisconsin, Div Gastroenterol & Hepatol, Milwaukee, WI 53226 USA.
[McGinley, Emily L.] Med Coll Wisconsin, Div Epidemiol, Milwaukee, WI 53226 USA.
[Binion, David G.] Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.
EM aananthakrishnan@partners.org
NR 35
TC 58
Z9 58
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1078-0998
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD APR
PY 2011
VL 17
IS 4
BP 976
EP 983
DI 10.1002/ibd.21457
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 732GR
UT WOS:000288173500012
PM 20824818
ER
PT J
AU Meade, CS
Conn, NA
Skalski, LM
Safren, SA
AF Meade, Christina S.
Conn, Nina A.
Skalski, Linda M.
Safren, Steven A.
TI Neurocognitive impairment and medication adherence in HIV patients with
and without cocaine dependence
SO JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; SUBSTANCE-ABUSE TREATMENT; SELF-REPORTED
ADHERENCE; QUALITY-OF-LIFE; COGNITIVE IMPAIRMENT; DRUG-USE;
NEUROPSYCHOLOGICAL PERFORMANCE; INFECTED PERSONS; VIROLOGICAL RESPONSE;
DISEASE PROGRESSION
AB Cocaine abuse among HIV patients is associated with faster disease progression and mortality. This study examined the relationship between neurocognitive functioning and medication adherence in HIV patients with (n = 25) and without (n = 39) current cocaine dependence. Active users had greater neurocognitive impairment (mean T-score = 35.16 vs. 40.97, p < .05) and worse medication adherence (mean z-score = -0.44 vs. 0.27, p < .001). In a multiple regression model, neurocognitive functioning (beta = .33, p < .01) and cocaine dependence (beta = -.36, p < .01) were predictive of poorer adherence. There was a significant indirect effect of cocaine dependence on medication adherence through neurocognitive impairment (estimate = -0.15, p < .05), suggesting that neurocognitive impairment partially mediated the relationship between cocaine dependence and poorer adherence. These results confirm that cocaine users are at high risk for poor HIV outcomes and underscore the importance of treating both neurocognitive impairment and cocaine dependence among HIV patients.
C1 [Meade, Christina S.] Duke Univ, Dept Psychiat & Behav Sci, Sch Med, Durham, NC 27708 USA.
[Meade, Christina S.; Skalski, Linda M.] Duke Global Hlth Inst, Durham, NC USA.
[Meade, Christina S.; Conn, Nina A.] McLean Hosp, Behav Psychopharmacol Res Lab, Belmont, MA 02178 USA.
[Meade, Christina S.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Safren, Steven A.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA.
RP Meade, CS (reprint author), Duke Univ, Dept Psychiat & Behav Sci, Sch Med, Box 90519, Durham, NC 27708 USA.
EM christina.meade@duke.edu
FU NIAID NIH HHS [R21 AI064519, P30 AI060354, P30 AI060354-04, P30
AI060354-05, P30 AI064518, P30 AI064518-04, P30 AI064518-05,
P30-AI064519, P30-AI60354]; NIDA NIH HHS [T32 DA015036, T32 DA015036-06,
T32 DA015036-07, T32-DA01536]
NR 93
TC 23
Z9 23
U1 5
U2 9
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 2011
VL 34
IS 2
BP 128
EP 138
DI 10.1007/s10865-010-9293-5
PG 11
WC Psychology, Clinical
SC Psychology
GA 730HZ
UT WOS:000288025700006
PM 20857187
ER
PT J
AU Teo, KK
Sleight, P
Gao, P
Yusuf, S
Connolly, S
Yusuf, S
Swedberg, K
Pfeffer, MA
Granger, CB
McMurray, JJV
Sjoelie, AK
Massie, BM
Carson, P
Lewis, JB
Wachtell, K
Dahlof, B
Devereux, RB
Kjeldsen, SE
Julius, S
Ibsen, H
Lindholm, LH
Olsen, MH
Okin, PM
Califf, R
Holman, RR
Haffner, SM
Dagenais, G
Probstfield, J
Anderson, C
Diaz, R
Dans, A
Levine, M
Unger, T
Fagard, R
Diener, HC
Sacco, RL
Zanchetti, A
Cohn, JN
Weber, M
AF Teo, Koon K.
Sleight, Peter
Gao, Peggy
Yusuf, Salim
Connolly, Stuart
Yusuf, Salim
Swedberg, Karl
Pfeffer, Marc A.
Granger, Christopher B.
McMurray, John J. V.
Sjoelie, Anne K.
Massie, Barry M.
Carson, Peter
Lewis, Julia B.
Wachtell, Kristian
Dahlof, Bjorn
Devereux, Richard B.
Kjeldsen, Sverre E.
Julius, Stevo
Ibsen, Hans
Lindholm, Lars H.
Olsen, Michael H.
Okin, Peter M.
Califf, Robert
Holman, Rury R.
Haffner, Steven M.
Dagenais, Gilles
Probstfield, Jeffrey
Anderson, Craig
Diaz, Rafael
Dans, Antonio
Levine, Mark
Unger, Thomas
Fagard, Robert
Diener, Hans-Christoph
Sacco, Ralph L.
Zanchetti, Alberto
Cohn, Jay N.
Weber, Michael
CA ARB Trialists Collaboration
TI Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan
on cancers in 15 trials enrolling 138 769 individuals The ARB Trialists
Collaboration
SO JOURNAL OF HYPERTENSION
LA English
DT Review
DE angiotensin receptor blockers; cancer incidence; candesartan; clinical
trials; irbesartan; losartan; meta-analysis; telmisartan; valsartan
ID CONVERTING-ENZYME-INHIBITORS; ANGIOTENSIN-RECEPTOR BLOCKER;
LEFT-VENTRICULAR DYSFUNCTION; CHRONIC HEART-FAILURE; RANDOMIZED
CONTROLLED-TRIALS; HIGH-RISK PATIENTS; CARDIOVASCULAR EVENTS;
PROSTATE-CANCER; ANTIHYPERTENSIVE MEDICATION; MYOCARDIAL-INFARCTION
AB Background Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks.
Objective Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138 769 participants.
Patients and methods Individuals at high CVD risk were randomized to telmisartan (three trials, n=51 878), irbesartan (three trials, n=14 859), valsartan (four trials, n=44 264), candesartan (four trials, n=18 566), and losartan (one trial, n=9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n=42 403), the ARBs were compared to ACEi and in 11 trials (n=63 313) to controls without ACEi. In addition, in seven trials (n=47 020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n=25 712).
Results Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [ 4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment.
Conclusion There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls. J Hypertens 29: 623-635 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Teo, Koon K.; Gao, Peggy; Yusuf, Salim] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Sleight, Peter] Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England.
[Connolly, Stuart; Yusuf, Salim] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Swedberg, Karl] Univ Gothenburg, Dept Emergency, Sahlgrenska Acad, Gothenburg, Sweden.
[Swedberg, Karl] Univ Gothenburg, Dept Cardiovasc Med, Sahlgrenska Acad, Gothenburg, Sweden.
[Pfeffer, Marc A.] Harvard Univ, Sch Med, Boston, MA USA.
[McMurray, John J. V.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Granger, Christopher B.] Duke Univ, Med Ctr, Div Cardiovasc Med, Duke Clin Res Inst, Durham, NC USA.
[McMurray, John J. V.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland.
[Sjoelie, Anne K.] Odense Hosp, Dept Ophthalmol, Odense, Denmark.
[Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Carson, Peter] Washington VAMC Georgetown Univ, Washington, DC USA.
[Lewis, Julia B.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Wachtell, Kristian] Gentofte Univ Hosp, Dept Cardiol, Copenhagen, Denmark.
[Dahlof, Bjorn] Sahlgrens Univ Hosp, Dept Med, Gothenburg, Sweden.
[Okin, Peter M.] Weill Cornell Med Coll, Div Cardiol, Dept Med, New York, NY USA.
[Kjeldsen, Sverre E.] Univ Oslo Hosp, Oslo, Norway.
[Julius, Stevo] Univ Michigan, Ann Arbor, MI 48109 USA.
[Ibsen, Hans] Aarhus Univ, DK-8000 Aarhus C, Denmark.
[Ibsen, Hans] Univ Copenhagen, DK-1168 Copenhagen, Denmark.
[Ibsen, Hans] Hlobaek Hosp, Hlobaek, Denmark.
[Lindholm, Lars H.] Umea Univ, Dept Publ Hlth, S-90187 Umea, Sweden.
[Lindholm, Lars H.] Umea Univ, Dept Clin Med, S-90187 Umea, Sweden.
[Olsen, Michael H.] Glostrup Univ Hosp, Dept Internal Med, Div Cardiol, Glostrup, Denmark.
[Cohn, Jay N.] Duke Univ, Med Ctr, Div Cardiovasc Med, Duke Clin Res Inst, Durham, NC USA.
[Holman, Rury R.] Univ Oxford, OCDEM, Oxford OX1 2JD, England.
[Haffner, Steven M.] Baylor Coll Med, Dept Med, San Antonio, TX USA.
[Dagenais, Gilles] Univ Laval, Laval Hosp, Heart & Lung Inst, Ste Foy, PQ G1V 4G5, Canada.
[Probstfield, Jeffrey] Univ Washington, Dept Med, Seattle, WA USA.
[Anderson, Craig] Royal Prince Alfred Hosp, George Inst Int Hlth, Sydney, NSW, Australia.
[Anderson, Craig] Univ Sydney, Sydney, NSW 2006, Australia.
[Diaz, Rafael] Estudios Clin Latinoamer, Rosario, Santa Fe, Argentina.
[Dans, Antonio] Univ Philippines, Coll Med, Manila, Philippines.
[Levine, Mark] McMaster Univ, Dept Oncol, Hamilton, ON L8V 1C3, Canada.
[Unger, Thomas] Charite, Cardiovasc Res Ctr, D-13353 Berlin, Germany.
[Unger, Thomas] Charite, Inst Pharmacol, D-13353 Berlin, Germany.
[Fagard, Robert] Univ Leuven KU Leuven, Hypertens & Cardiovasc Rehabil Unit, Leuven, Belgium.
[Diener, Hans-Christoph] Univ Hosp Essen, Dept Neurol, Essen, Germany.
[Diener, Hans-Christoph] Univ Hosp Essen, Stroke Ctr, Essen, Germany.
[Sacco, Ralph L.] Univ Miami, Miami, FL USA.
[Zanchetti, Alberto] Univ Milan, Ctr Clin Physiol & Hypertens, Milan, Italy.
[Zanchetti, Alberto] Ist Auxol Italiano, Milan, Italy.
[Cohn, Jay N.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Weber, Michael] Suny Downstate Med Ctr, Coll Med, Brooklyn, NY 11203 USA.
RP Teo, KK (reprint author), Hamilton Gen Hosp, Populat Hlth Res Inst, David Braley Cardiac Vasc Stroke Res Inst, Rm C2-106,237 Barton St E, Hamilton, ON L8L 2X2, Canada.
EM koon.teo@phri.ca
RI Granger, Christopher/D-3458-2014; Olsen, Michael/H-8176-2014
OI Granger, Christopher/0000-0002-0045-3291;
FU Boehringer Ingelheim; Bristol-Myers Squibb; Sanofi-Aventis;
Sanofi-Synthelabo; Novartis; AstraZenica; Takeda; Merck
FX K.K.T. and P.S. received consulting and lecture fees and research grants
from Boehringer Ingelheim; S.Y. received grants and honoraria from
Boehringer Ingelheim, Bristol-Myers Squibb, and Sanofi-Aventis. P.G.
does not have relevant information to disclose.; Boehringer-Ingelheim
was the sponsor of the telmisartan trials. The irbesartan trials were
sponsored by Bristol-Myers Squibb and Sanofi-Synthelabo, the valsartan
trials by Novartis, the candesartan trials by AstraZenica (CHARM and
DIRECT were also sponsored by Takeda) and the losartan trial by Merck.
Data for this meta-analysis were obtained from the investigators and
sponsors and were analyzed at PHRI independent of the sponsors.
NR 44
TC 63
Z9 63
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD APR
PY 2011
VL 29
IS 4
BP 623
EP 635
DI 10.1097/HJH.0b013e328344a7de
PG 13
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 732PH
UT WOS:000288199500001
ER
PT J
AU Liu, PA
Zhang, C
Chen, J
Zhang, RG
Ren, JH
Huang, YH
Zhu, F
Li, ZY
Wu, G
AF Liu, Pian
Zhang, Chen
Chen, Jing
Zhang, Ruiguang
Ren, Jinghua
Huang, Yuhui
Zhu, Fang
Li, Zhenyu
Wu, Gang
TI Combinational Therapy of Interferon-alpha and Chemotherapy Normalizes
Tumor Vasculature by Regulating Pericytes Including the Novel Marker
RGS5 in Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE melanoma; chemoimmunotherapy; interferon-alpha; pericytes; RGS5
ID ANTI-ANGIOGENIC THERAPY; ORTHOTOPIC MOUSE MODEL; CANCER-THERAPY;
GROWTH-FACTOR; PANCREATIC-ADENOCARCINOMA; ANTIANGIOGENIC THERAPY;
METASTATIC MELANOMA; ENDOTHELIAL SPROUTS; DOWN-REGULATION; BLOOD-VESSELS
AB Several large randomized clinical trials show that chemotherapy in combination with interferon-alpha (IFN-alpha) seems superior to single-agent chemotherapy, such as dacarbazine (DTIC) in melanoma, but the molecular mechanism of this better efficacy is unclear. IFN-alpha has antiangiogenic activity and could downregulate expression of regulator of G-protein signalling-5 (RGS5) recognized as a novel pericyte marker and a master gene loss of which results in pericyte maturation, vascular normalization, and consequent marked reductions in tumor hypoxia and vessel leakiness in pancreatic carcinoma. Here, we investigated the molecular mechanism of the effects of this combination therapy on melanoma tumor growth. In B16 tumor-bearing mice, the addition of IFN-alpha to DTIC treatment significantly reduced tumor volume, compared with control or DTIC alone. Consistently, Digital Radiography data showed less chaotic vessel morphology and a decrease in microvessel density and mean vessel diameter in the combinational treatment. Furthermore, the combination therapy showed a remarkable reduction in tumor hypoxia, downregulated RGS5 expression, and increased mature pericyte coverage. Our data suggest that the combination of IFN-alpha and DTIC therapy more efficiently inhibits tumor growth by normalizing tumor vasculature. This study shows a previously unrecognized role of IFN-alpha in melanoma vascular normalization and suggests that pericyte including its novel marker RGS5 is an important target of IFN-alpha.
C1 [Liu, Pian; Chen, Jing; Zhang, Ruiguang; Ren, Jinghua; Zhu, Fang; Li, Zhenyu; Wu, Gang] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Ctr Canc, Wuhan 430022, Peoples R China.
[Zhang, Chen] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Hepatobiliary Surg, Wuhan 430022, Peoples R China.
[Huang, Yuhui] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA.
[Huang, Yuhui] Harvard Univ, Sch Med, Boston, MA USA.
RP Wu, G (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Ctr Canc, 1277 Jiefang Ave, Wuhan 430022, Peoples R China.
EM wugangzr@yahoo.com.cn
FU National Natural Science Fund of China [30973473]
FX Supported by the National Natural Science Fund of China (NO. 30973473).
NR 41
TC 8
Z9 8
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD APR
PY 2011
VL 34
IS 3
BP 320
EP 326
DI 10.1097/CJI.0b013e318213cd12
PG 7
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 733CO
UT WOS:000288238200010
PM 21389866
ER
PT J
AU Ellis, KL
Newton-Cheh, C
Wang, TJ
Frampton, CM
Doughty, RN
Whalley, GA
Ellis, CJ
Skelton, L
Davis, N
Yandle, TG
Troughton, RW
Richards, AM
Cameron, VA
AF Ellis, Katrina L.
Newton-Cheh, Christopher
Wang, Thomas J.
Frampton, Chris M.
Doughty, Rob N.
Whalley, Gillian A.
Ellis, Chris J.
Skelton, Lorraine
Davis, Nick
Yandle, Tim G.
Troughton, Richard W.
Richards, A. Mark
Cameron, Vicky A.
TI Association of genetic variation in the natriuretic peptide system with
cardiovascular outcomes
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Natriuretic peptides; Polymorphisms; Cardiovascular outcomes
ID VENTRICULAR EJECTION FRACTION; ACUTE MYOCARDIAL-INFARCTION;
SYMPATHETIC-NERVE ACTIVITY; RECEPTOR GENE; ESSENTIAL-HYPERTENSION;
BLOOD-PRESSURE; HEART-FAILURE; 5'-FLANKING REGION; HUMAN-PLASMA;
POLYMORPHISM
AB Polymorphisms within individual natriuretic peptide genes have been associated with risk factors for cardiovascular disease, but their association with clinical outcomes was previously unknown. This study aimed to investigate the association between genetic variants in key genes of the natriuretic peptide system with cardiovascular outcomes in patients with coronary artery disease. Coronary disease patients (n = 1810) were genotyped for polymorphisms within NPPA, NPPB, NPPC, NPR1 and NPR2. Clinical history, natriuretic peptide concentrations, echocardiography, all-cause mortality and cardiovascular hospital readmissions were recorded over a median 2.8 years. Minor alleles of NPPA rs5068, rs5065 and rs198358 were associated with less history of hypertension; minor alleles of NPPA rs5068 and rs198358 was also associated with higher circulating natriuretic peptide levels (p = 0.003 to p = 0.04). Minor alleles of NPPB rs198388, rs198389, and rs632793 were associated with higher circulating BNP and NT-proBNP (p = 0.001 to p = 0.03), and reduced E/E-1 (p = 0.011), or LVESVI (p = 0.001) and LVEDVI (p = 0.004). Within NPPC, both rs11079028 and rs479651 were associated with higher NT-proBNP and CNP (p = 0.01 to p = 0.03), and rs479651 was associated with lower LVESVI (p = 0.008) and LVEDVI (p = 0.018). NPR2 rs10758325 was associated with smaller LVMI (p<0.02). A reduced rate of cardiovascular readmission was observed for minor alleles of NPPA rs5065 (p<0.0001), NPPB rs632793 (p<0.0001), rs198388 (p<0.0001), rs198389 (p<0.0001), and NPR2 rs10758325 (p<0.0001). There were no associations with all-cause mortality. In established cardiovascular disease, natriuretic peptide system polymorphisms were associated with natriuretic peptide levels, hypertension, echocardiographic indices and the incidence of hospital readmission for cardiovascular events. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Ellis, Katrina L.; Frampton, Chris M.; Skelton, Lorraine; Davis, Nick; Yandle, Tim G.; Troughton, Richard W.; Richards, A. Mark; Cameron, Vicky A.] Univ Otago, Christchurch Cardioendocrine Res Grp, Dept Med, Christchurch 8140, New Zealand.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Newton-Cheh, Christopher; Wang, Thomas J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA.
[Newton-Cheh, Christopher; Wang, Thomas J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Doughty, Rob N.; Whalley, Gillian A.; Ellis, Chris J.] Univ Auckland, Dept Med, Auckland, New Zealand.
[Whalley, Gillian A.] Unitec Inst Technol, Dept Med Imaging, Auckland, New Zealand.
RP Ellis, KL (reprint author), Univ Otago, Christchurch Cardioendocrine Res Grp, Dept Med, POB 4345, Christchurch 8140, New Zealand.
EM katina.ellis@otago.ac.nz
OI Whalley, Gillian/0000-0002-5713-6967
FU Health Research Council of New Zealand (Auckland, New Zealand); New
Zealand Lotteries Grant Board (Wellington, New Zealand); National Heart
Foundation of New Zealand (Auckland, New Zealand)
FX This work was supported by the Health Research Council of New Zealand
(Auckland, New Zealand); New Zealand Lotteries Grant Board (Wellington,
New Zealand), and National Heart Foundation of New Zealand (Auckland,
New Zealand).
NR 42
TC 34
Z9 34
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD APR
PY 2011
VL 50
IS 4
BP 695
EP 701
DI 10.1016/j.yjmcc.2011.01.010
PG 7
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 734CM
UT WOS:000288310800014
PM 21276798
ER
PT J
AU Guimaraes, AR
Ross, R
Figuereido, JL
Waterman, P
Weissleder, R
AF Guimaraes, Alexander R.
Ross, Robert
Figuereido, Jose L.
Waterman, Peter
Weissleder, Ralph
TI MRI with Magnetic Nanoparticles Monitors Downstream Anti-Angiogenic
Effects of mTOR Inhibition
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE Magnetic resonance imaging; MRI; Magnetic nanoparticle imaging;
Ultrasmall superparamagnetic iron oxide nanoparticle; Renal cell cancer;
mTOR; Angiogenesis
ID RENAL-CELL CARCINOMA; PROGRESSION-FREE SURVIVAL; IN-VIVO ASSESSMENT;
TUMOR ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; RAD001 EVEROLIMUS;
INTERFERON-ALPHA; COLON-CARCINOMA; CONTRAST; MODEL
AB To study the effect of mammalian target of rapamycin (mTOR) inhibition on angiogenesis with magnetic resonance imaging (MRI) using magnetic iron oxide nanoparticles (MNP).
One million CAK-1 renal cell carcinoma cells were subcutaneously implanted into each of 20 nude mice. When tumors reached similar to 750 mu l, four daily treatment arms began and continued for 4 weeks: rapamycin (mTOR inhibitor) 10 mg/kg/day; sorafenib (VEGF inhibitor) high dose (80 mg/kg/day) and low dose (30 mg/kg/day); and saline control. Weekly MRI (4.7 T Bruker Pharmascan) was performed before and after IV MION-48, a prototype MNP similar to MNP in clinical trials. Vascular volume fraction (VVF) was quantified as Delta R2 (from multi-contrast T2 sequences) and normalized to assumed muscle VVF of 3%. Linear regression compared VVF to microvascular density (MVD) as determined by histology.
VVF correlated with MVD (R(2) = 0.95). VVF in all treatment arms differed from control (p < 0.05) and declined weekly with treatment. VVF changes with rapamycin were similar to high-dose sorafenib.
This study demonstrates noninvasive, in vivo anti-angiogenic monitoring using MRI of mTOR inhibition.
C1 [Guimaraes, Alexander R.; Figuereido, Jose L.; Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA.
[Guimaraes, Alexander R.; Figuereido, Jose L.; Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Ross, Robert] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
[Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA 02114 USA.
RP Guimaraes, AR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA.
EM aguimaraes1@partners.org
FU Renal Spore-Dana Farber Cancer Institute; MGH-AstraZeneca Strategic
Alliance
FX Funding provided by the Renal Spore-Dana Farber Cancer Institute &
MGH-AstraZeneca Strategic Alliance
NR 24
TC 9
Z9 9
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD APR
PY 2011
VL 13
IS 2
BP 314
EP 320
DI 10.1007/s11307-010-0357-2
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 732IH
UT WOS:000288177700015
PM 20559742
ER
PT J
AU Sheehan, J
Gaman, A
Vangel, M
Kuo, B
AF Sheehan, J.
Gaman, A.
Vangel, M.
Kuo, B.
TI Pooled analysis of brain activity in irritable bowel syndrome and
controls during rectal balloon distension
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Article
DE brain imaging; colo-rectal stimulation; irritable bowel syndrome; pooled
analysis
ID VISCERAL PAIN; CEREBRAL ACTIVATION; DESCENDING COLON; HEALTHY CONTROLS;
GI DISORDERS; IBS PATIENTS; HYPERSENSITIVITY; RESPONSES; STIMULI; FMRI
AB Background
Brain-imaging literature of irritable bowel syndrome (IBS) suggests an abnormal brain-gut communication. We analyzed the literature to evaluate and compare the aspects of brain activity in individuals with IBS and control subjects experiencing controlled rectal stimulation.
Methods
PubMed was searched until September 2010. Data from 16 articles reporting brain activity during rectal balloon distensions in IBS compared to control groups was analyzed. Prevalence rates and pairwise activations were assessed using binomial distributions for 11 selected regions of interest. The data were aggregated to adjust for center effect.
Key Results
There was considerable variability in the literature regarding regions and their activity patterns in controls and individuals with IBS. There was no significant difference found in the thalamus, anterior cingulate cortex, posterior cingulate cortex, and prefrontal cortex, however, results show limited evidence of consensus for the anterior insula (AI) (P = 0.22). Pairwise activity results suggest that pairs involving the AI tend to have more consistent activity together than pairs which do not involve the AI (posterior insula and AI, P = 0.08; posterior cingulate cortex and AI, P = 0.16), however, no pairwise evaluation reached significance.
Conclusions & Inferences
Our pooled analysis demonstrates that the literature reports are quite heterogeneous but there is some evidence that there may be patterns of higher activity more common in individuals with IBS than in controls. A consensus, though, regarding study designs, analysis approach and reporting could create a clearer understanding of brain involvement in IBS pathophysiology.
C1 [Sheehan, J.; Gaman, A.; Vangel, M.; Kuo, B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,GI Unit,Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
RP Kuo, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,GI Unit,Martinos Ctr Biomed Imaging, 55 Fruit St, Boston, MA 02114 USA.
EM bkuo@partners.org
NR 54
TC 1
Z9 1
U1 3
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD APR
PY 2011
VL 23
IS 4
DI 10.1111/j.1365-2982.2010.01635.x
PG 12
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 733KR
UT WOS:000288262100009
ER
PT J
AU Yang, XL
Cao, WD
Zhou, J
Zhang, W
Zhang, XA
Lin, W
Fei, Z
Lin, H
Wang, B
AF Yang, Xiaoliang
Cao, Weidong
Zhou, Jie
Zhang, Wei
Zhang, Xiang
Lin, Wei
Fei, Zhou
Lin, Hong
Wang, Bo
TI 14-3-3Zeta Positive Expression is Associated With a Poor Prognosis in
Patients With Glioblastoma
SO NEUROSURGERY
LA English
DT Article
DE 14-3-3 zeta; Glioblastoma; Prognostic factor
ID ISOFORM-SPECIFIC EXPRESSION; CANCER-CELL-SURVIVAL; LUNG-CANCER;
BREAST-CANCER; PROMOTER METHYLATION; HUMAN ASTROCYTOMA; APOPTOTIC
SIGNAL; DOWN-REGULATION; UP-REGULATION; 14-3-3-ZETA
AB BACKGROUND: When identifying clinical markers predicting clinical outcome, disease recurrence and resistance to therapies often determine the diagnosis and therapy of some cancer types.
OBJECTIVE: To investigate whether 14-3-3zeta positive expression is an indicator of prognosis in patients with glioblastoma.
METHODS: Forty-seven patients treated with surgery, radiotherapy, and adjuvant chemotherapy between 2005 and 2007 were divided into 2 groups according to 14-3-3zeta expression in an immunohistochemical study: the 14-3-3zeta negative group (n = 12 patients) and the 14-3-3zeta positive group (n = 35 patients). The clinicopathologic features and survival data for patients in the 14-3-3zeta positive group were compared with data from the patients in the 14-3-3zeta negative group. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed to determine the prognostic factors that influenced patient survival.
RESULTS: 14-3-3zeta positive expression was observed in approximately 74.5% of patients with glioblastoma. Patients in the 14-3-3zeta positive group had lower overall survival rates and median survival time than those in the 14-3-3zeta negative group (overall 2-year actuarial survival rates, 8.6% for the 14-3-3zeta positive group vs 16.7% for the 14-3-3zeta negative group; overall 2-year median survival time, 12.9 months for the 14-3-3zeta positive group vs 17.9 months for the 14-3-3zeta negative group, P = .019). 14-3-3zeta positive expression in tumor cells also was correlated with a shorter interval to tumor recurrence (median interval to recurrence, 5.9 months in the 14-3-3zeta positive group vs 8.3 months in the 14-3-3zeta negative group, P = .002). Univariate and multivariate analyses showed that 14-3-3zeta positive expression was an independent prognostic factor.
CONCLUSION: 14-3-3zeta positive expression can be used as a potential molecular risk factor in patients with glioblastoma.
C1 [Yang, Xiaoliang; Cao, Weidong; Zhou, Jie; Zhang, Wei; Zhang, Xiang; Lin, Wei; Fei, Zhou; Lin, Hong] Fourth Mil Med Univ, Xijing Hosp, Inst Neurosurg, Xian 710032, Shaanxi Prov, Peoples R China.
[Zhang, Wei] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg, Mol Neurosurg Lab,Brain Tumor Res Ctr, Boston, MA USA.
[Wang, Bo] Fourth Mil Med Univ, Sch Mil Prevent Med, Dept Epidemiol, Xian 710032, Shaanxi Prov, Peoples R China.
RP Zhang, XA (reprint author), Fourth Mil Med Univ, Xijing Hosp, Inst Neurosurg, Xian 710032, Shaanxi Prov, Peoples R China.
EM zhiyin100@163.com
FU National Natural Science Foundation of China [81072083]; Scientific and
Technological Project of ShaanXi Province [2008K09-09]
FX This work is supported by National Natural Science Foundation of China
(No. 81072083) and Scientific and Technological Project of ShaanXi
Province (No. 2008K09-09). The auithors have no personal financial or
institutional interest in any of the drugs, materials, or devices
described in this article.
NR 38
TC 16
Z9 16
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD APR
PY 2011
VL 68
IS 4
BP 932
EP 937
DI 10.1227/NEU.0b013e3182098c30
PG 6
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 731QA
UT WOS:000288123100044
PM 21242845
ER
PT J
AU Joffe, S
Kodish, E
AF Joffe, Steven
Kodish, Eric
TI Protecting the Rights and Interests of Pediatric Stem Cell
SO PEDIATRIC BLOOD & CANCER
LA English
DT Editorial Material
ID BONE-MARROW; TRANSPLANTATION; SIBLINGS; CHILDREN; DONORS
C1 [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[Kodish, Eric] Cleveland Clin, Ctr Eth Humanities & Spiritual Care, Cleveland, OH 44106 USA.
RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Smith 207 450 Brookline Ave, Boston, MA 02215 USA.
EM steven_joffe@dfci.harvard.edu
OI Joffe, Steven/0000-0002-0667-7384
NR 10
TC 6
Z9 6
U1 2
U2 3
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD APR
PY 2011
VL 56
IS 4
BP 517
EP 519
DI 10.1002/pbc.23028
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 729XD
UT WOS:000287986700004
PM 21298734
ER
PT J
AU Badalian-Very, G
Vergilio, JA
Degar, BA
Calicchio, M
Fleming, MD
Rollins, BJ
AF Badalian-Very, Gayane
Vergilio, Jo-Anne
Degar, Barbara A.
Calicchio, Monica
Fleming, Mark D.
Rollins, Barrett J.
TI TOLL RECEPTORS AND LANGERHANS CELL HISTIOCYTOSIS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
Childrens Hosp, Dept Med, Boston, MA 02115 USA.
Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD APR
PY 2011
VL 56
IS 4
BP 689
EP 690
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 729XD
UT WOS:000287986700041
ER
PT J
AU Campbell, PK
Abraham, A
Jeng, M
Cardenas-Cardos, R
Rodriguez-Galindo, C
AF Campbell, P. K.
Abraham, A.
Jeng, M.
Cardenas-Cardos, R.
Rodriguez-Galindo, C.
TI USE OF CLOFARABINE IN THE TREATMENT OF REFRACTORY AND RECURRENT
MULTISYSTEM LANGERHANS CELL HISTIOCYTOSIS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 St Jude Childrens Hosp, Memphis, TN 38105 USA.
Stanford Univ, Sch Med, Lucile Packard Childrens Hosp, Stanford, CA 94305 USA.
Inst Nacl Pediat, Delegac Coyoacan, Mexico City, DF, Mexico.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD APR
PY 2011
VL 56
IS 4
BP 691
EP 692
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 729XD
UT WOS:000287986700048
ER
PT J
AU Akilov, OE
Wu, MX
Jin, YZ
Zhou, ZY
Geskin, LJ
Falo, LD
Hasan, T
AF Akilov, Oleg E.
Wu, Mei X.
Jin, Yongzhu
Zhou, Zhuoyan
Geskin, Larisa J.
Falo, Louis D.
Hasan, Tayyaba
TI Vaccination with photodynamic therapy-treated macrophages induces highly
suppressive T-regulatory cells
SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE
LA English
DT Article
DE Leishmania; macrophage; tolerance; T regulatory cells; vaccination
ID LEISHMANIA-MAJOR; IMMUNOREGULATORY FUNCTIONS; CUTANEOUS LEISHMANIASIS;
DENDRITIC CELLS; NATURAL MODEL; NITRIC-OXIDE; RESPONSES; IMMUNITY;
TOLERANCE; INFECTION
AB Background/purpose
The present study explores whether photodynamic therapy (PDT)-induced apoptosis can increase the number of tolerogenic regulatory T cells (Treg) and limit collateral tissue damage.
Methods
BALB/c mice were vaccinated subcutaneously three times with PDT-induced apoptotic or thaw-frozen, necrotic non-infected autologous macrophages (M). Two weeks after the last vaccination, mice were infected intradermally with 106 promastigotes of Leishmania major.
Results
Mice that received PDT-induced apoptotic M had fewer parasites and higher numbers of Treg than mice vaccinated with thaw-frozen necrotic M or phosphate-buffered saline (PBS). Interleukin (IL)-4 and IL-6 were significantly suppressed, while IL-10 was increased in mice that received the PDT-induced apoptotic M. The role of Treg in this process was confirmed through Treg transfer from vaccinated to naive mice. Mice receiving CD4+CD25+ cells from mice vaccinated with PDT-induced apoptotic M showed smaller lesions 3 weeks after infection and lower parasitic burdens than mice that received Tregs from mice of thaw-frozen necrotic M or PBS groups. These changes were mediated by the depletion of CD3+CD8+ and NKT cells and increased levels of IL-12p70 and interferon-gamma, IL-10, and TGF-beta in the cutaneous leishmaniasis lesions.
Conclusion
Vaccination with apoptotic M-induced tolerogenic Treg cells that limited collateral tissue damage and diminished parasitic burden.
C1 [Akilov, Oleg E.; Geskin, Larisa J.; Falo, Louis D.] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15213 USA.
[Akilov, Oleg E.; Wu, Mei X.; Jin, Yongzhu; Zhou, Zhuoyan; Hasan, Tayyaba] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Ctr Photomed, Boston, MA 02115 USA.
RP Akilov, OE (reprint author), Univ Pittsburgh, Dept Dermatol, 200 Lothrop St,Presby S Tower,Suit 3880, Pittsburgh, PA 15213 USA.
EM oea2@pitt.edu
FU Department of Defense [FA9550-04-1-0079]; Harvard Skin Disease Research
Center
FX We are grateful to Mary Ann McDowell, PhD (University of Notre Dame,
Notre Dame, IN, USA), for providing us with the L. major V1 strain. We
are appreciative of the assistance of Andrea Johnston, Ezra Mirvish and
Sue McCann with the manuscript preparation. We thank Kasper Hoebe
(Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA) and
Thomas A. Ferguson (Department of Ophthalmology and Visual Sciences,
Washington University School of Medicine, St. Louis, MO, USA) for
critically reading our manuscript. This work was supported by the
Department of Defense Medical Free Electron Laser Program Grant No.
FA9550-04-1-0079 (to T. Hasan), Harvard Skin Disease Research Center
Pilot and Feasibility Grant (to O. Akilov).
NR 43
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0905-4383
J9 PHOTODERMATOL PHOTO
JI Photodermatol. Photoimmunol. Photomed.
PD APR
PY 2011
VL 27
IS 2
BP 97
EP 107
DI 10.1111/j.1600-0781.2011.00578.x
PG 11
WC Dermatology
SC Dermatology
GA 733FT
UT WOS:000288249300007
PM 21392113
ER
PT J
AU Rutemark, C
Alicot, E
Bergman, A
Carroll, MC
Heyman, B
AF Rutemark, Christian
Alicot, Elisabeth
Bergman, Anna
Carroll, Michael C.
Heyman, Birgitta
TI The Requirement for Classical Complement Activation in Antibody
Responses is not Explained by IgM-Mediated Activation
SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT 40th Scandinavian-Society for Immunology Meeting
CY 2011
CL Geilo, NORWAY
SP Scandinavian-Soc Immunol
C1 [Rutemark, Christian; Bergman, Anna; Heyman, Birgitta] Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden.
[Alicot, Elisabeth; Carroll, Michael C.] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0300-9475
J9 SCAND J IMMUNOL
JI Scand. J. Immunol.
PD APR
PY 2011
VL 73
IS 4
MA 25
BP 357
EP 357
PG 1
WC Immunology
SC Immunology
GA 728KA
UT WOS:000287871800037
ER
PT J
AU Delmonico, FL
AF Delmonico, Francis L.
TI Striving to achieve a national self-sufficiency
SO TRANSPLANT INTERNATIONAL
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Delmonico, FL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM francis_delmonico@neob.org
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0934-0874
J9 TRANSPL INT
JI Transpl. Int.
PD APR
PY 2011
VL 24
IS 4
BP 315
EP 316
DI 10.1111/j.1432-2277.2011.01227.x
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 732SU
UT WOS:000288210800004
PM 21276091
ER
PT J
AU Dominguez-Gil, B
Delmonico, FL
Shaheen, FAM
Matesanz, R
O'Connor, K
Minina, M
Muller, E
Young, K
Manyalich, M
Chapman, J
Kirste, G
Al-Mousawi, M
Coene, L
Garcia, VD
Gautier, S
Hasegawa, T
Jha, V
Kwek, TK
Chen, ZK
Loty, B
Costa, AN
Nathan, HM
Ploeg, R
Reznik, O
Rosendale, JD
Tibell, A
Tsoulfas, G
Vathsala, A
Noel, L
AF Dominguez-Gil, Beatriz
Delmonico, Francis L.
Shaheen, Faissal A. M.
Matesanz, Rafael
O'Connor, Kevin
Minina, Marina
Muller, Elmi
Young, Kimberly
Manyalich, Marti
Chapman, Jeremy
Kirste, Guenter
Al-Mousawi, Mustafa
Coene, Leen
Garcia, Valter Duro
Gautier, Serguei
Hasegawa, Tomonori
Jha, Vivekanand
Kwek, Tong Kiat
Chen, Zhonghua Klaus
Loty, Bernard
Costa, Alessandro Nanni
Nathan, Howard M.
Ploeg, Rutger
Reznik, Oleg
Rosendale, John D.
Tibell, Annika
Tsoulfas, George
Vathsala, Anantharaman
Noel, Luc
TI The critical pathway for deceased donation: reportable uniformity in the
approach to deceased donation
SO TRANSPLANT INTERNATIONAL
LA English
DT Review
DE assessment; identification; possible deceased donors; referral
ID DEATH
AB P>The critical pathway of deceased donation provides a systematic approach to the organ donation process, considering both donation after cardiac death than donation after brain death. The pathway provides a tool for assessing the potential of deceased donation and for the prospective identification and referral of possible deceased donors.
C1 [Delmonico, Francis L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dominguez-Gil, Beatriz; Matesanz, Rafael] Org Nacl Trasplantes, Madrid, Spain.
[Shaheen, Faissal A. M.] Saudi Ctr Organ Transplantat SCOT, Minist Hlth, Riyadh, Saudi Arabia.
[O'Connor, Kevin] LifeCtr NW, Bellevue, WA USA.
[Minina, Marina] Moscow Coordinating Ctr Organ Donat, Moscow, Russia.
[Muller, Elmi] Univ Cape Town, Dept Surg, Groote Schuur Hosp, ZA-7925 Cape Town, South Africa.
[Young, Kimberly] Canadian Blood Serv, Ottawa, ON, Canada.
[Manyalich, Marti] Hosp Clin Barcelona, Barcelona, Spain.
[Chapman, Jeremy] Westmead Hosp, Sydney, NSW, Australia.
[Kirste, Guenter] Deutsch Stiftung Organtransplantat, Frankfurt, Germany.
[Al-Mousawi, Mustafa] Organ Transplant Ctr Kuwait, Kuwait, Kuwait.
[Coene, Leen] Fed Serv Publ Hlth, Brussels, Belgium.
[Garcia, Valter Duro] Brazilian Soc Organ Transplantat, Porto Alegre, RS, Brazil.
[Gautier, Serguei] Russian Transplantat Soc, Natl Res Inst Transplantol & Artificial Organs, Moscow, Russia.
[Hasegawa, Tomonori] Toho Univ, Sch Med, Dept Social Med, Tokyo, Japan.
[Jha, Vivekanand] Postgrad Inst Med Educ & Res, Dept Nephrol, Chandigarh 160012, India.
[Jha, Vivekanand] Indian Soc Nephrol, Chandigarh, India.
[Kwek, Tong Kiat] Tan Tock Seng Hosp, Dept Anaesthesiol, Singapore, Singapore.
[Chen, Zhonghua Klaus] Tongji Hosp, Tongji Med Coll, Inst Organ Transplantat, Wuhan, Peoples R China.
[Loty, Bernard] Agence Biomed, La Plaine St Denis, France.
[Costa, Alessandro Nanni] Italian Natl Transplant Ctr, Rome, Italy.
[Nathan, Howard M.] Gift Life Donor Program, Philadelphia, PA USA.
[Ploeg, Rutger] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Reznik, Oleg] Assoc Transplant Coordinators, Dept Transplantat, State Res Inst Emergency, St Petersburg, Russia.
[Tibell, Annika] Karolinska Univ Hosp, Dept Transplantat Surg, Stockholm, Sweden.
[Tsoulfas, George] Aristotele Univ Thessaloniki, Thessaloniki, Greece.
[Vathsala, Anantharaman] Natl Univ Singapore, Dpt Med, Singapore 117548, Singapore.
[Noel, Luc] WHO, Essential Hlth Technol, Clin Procedures, CH-1211 Geneva, Switzerland.
RP Delmonico, FL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM francis_delmonico@neob.org
RI Tsoulfas, Georgios/K-4801-2012; Muller, Elmi/I-3258-2014;
OI Tsoulfas, Georgios/0000-0001-5043-7962; Muller,
Elmi/0000-0003-4891-5296; Reznik, Oleg/0000-0003-2770-1432
NR 15
TC 43
Z9 45
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0934-0874
J9 TRANSPL INT
JI Transpl. Int.
PD APR
PY 2011
VL 24
IS 4
BP 373
EP 378
DI 10.1111/j.1432-2277.2011.01243.x
PG 6
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 732SU
UT WOS:000288210800011
PM 21392129
ER
PT J
AU Quinn, TM
Taylor, JJ
Magarik, JA
Vought, E
Kindy, MS
Ellegala, DB
AF Quinn, T. M.
Taylor, J. J.
Magarik, J. A.
Vought, E.
Kindy, M. S.
Ellegala, D. B.
TI Decompressive craniectomy: technical note
SO ACTA NEUROLOGICA SCANDINAVICA
LA English
DT Review
DE cerebral edema; decompressive craniectomy; intracranial pressure;
patient management; traumatic brain injury
ID TRAUMATIC BRAIN-INJURY; CEREBRAL-ARTERY INFARCTION; INTRACRANIAL
HYPERTENSION; ISCHEMIC-STROKE; MANAGEMENT; MULTICENTER; RECOVERY;
PRESSURE; THERAPY
AB Decompressive craniectomy is a neurosurgical technique in which a portion of the skull is removed to reduce intracranial pressure. The rationale for this procedure is based on the Monro-Kellie Doctrine; expanding the physical space confining edematous brain tissue after traumatic brain injury will reduce intracranial pressure. There is significant debate over the efficacy of decompressive craniectomy despite its sound rationale and historical significance. Considerable variation in the employment of decompressive craniectomy, particularly for secondary brain injury, explains the inconsistent results and mixed opinions of this potentially valuable technique. One way to address these concerns is to establish a consistent methodology for performing decompressive craniectomies. The purpose of this paper is to begin accomplishing this goal and to emphasize the critical points of the hemicraniectomy and bicoronal (Kjellberg type) craniectomy.
C1 [Quinn, T. M.; Taylor, J. J.; Magarik, J. A.; Vought, E.; Ellegala, D. B.] Med Univ S Carolina, Div Neurosurg, Dept Neurosci, Charleston, SC 29425 USA.
[Kindy, M. S.] Med Univ S Carolina, Div Res, Dept Neurosci, Charleston, SC 29425 USA.
[Kindy, M. S.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA.
RP Ellegala, DB (reprint author), Med Univ S Carolina, Div Neurosurg, Dept Neurosci, Room CSB 428,96 Jonathan Lucas St, Charleston, SC 29425 USA.
EM ellegala@musc.edu
FU Veterans Administration
FX The authors do not have any conflicts of interest. This work was
supported in part by grants from the Veterans Administration (MSK).
NR 39
TC 12
Z9 14
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-6314
J9 ACTA NEUROL SCAND
JI Acta Neurol. Scand.
PD APR
PY 2011
VL 123
IS 4
BP 239
EP 244
DI 10.1111/j.1600-0404.2010.01397.x
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 728GR
UT WOS:000287863100002
PM 20637010
ER
PT J
AU Franklin, TR
Wang, Z
Li, Y
Suh, JJ
Goldman, M
Lohoff, FW
Cruz, J
Hazan, R
Jens, W
Detre, JA
Berrettini, W
O'Brien, CP
Childress, AR
AF Franklin, Teresa R.
Wang, Ze
Li, Yin
Suh, Jesse J.
Goldman, Marina
Lohoff, Falk W.
Cruz, Jeffrey
Hazan, Rebecca
Jens, Will
Detre, John A.
Berrettini, Wade
O'Brien, Charles P.
Childress, Anna Rose
TI Dopamine transporter genotype modulation of neural responses to smoking
cues: confirmation in a new cohort
SO ADDICTION BIOLOGY
LA English
DT Article
DE Addiction; dopamine transporter; genetic variability; neuroimaging;
relapse vulnerability; smoking cues
ID FAGERSTROM TOLERANCE QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIAL;
RECEPTOR PARTIAL AGONIST; DRD4 VNTR POLYMORPHISM; FMRI-BOLD RESPONSES;
NICOTINE-DEPENDENCE; CIGARETTE-SMOKING; ORBITOFRONTAL CORTEX; WITHDRAWAL
SYMPTOMS; PREFRONTAL CORTEX
AB Previously we demonstrated profound effects of dopamine transporter (DAT) SLC6A3 genotype on limbic responses to smoking cues (SCs). Probands carrying at least one copy of the 9-repeat allele (9-repeat carriers) had greater neural responses to SCs in the anatomically interconnected rostral ventral striatum/medial orbitofrontal cortex (VS/mOFC), compared with homozygotes for the 10-repeat allele (10/10-repeats). To test the reliability of the initial findings, we examined perfusion functional magnetic resonance images acquired during SC exposure in a new cohort of smokers (N = 26) who were genotyped for the SLC6A3 polymorphism. In smokers overall, activity was enhanced in the VS/mOFC (t = 3.77). Contrasts between allelic groups revealed that 9-repeat carriers had a greater response to SCs in the VS (t = 3.12) and mOFC (t = 3.19). In separate groups, 9-repeat carriers showed increased activity in the VS (t = 5.47) and mOFC (T = 4.96), while no increases were observed in 10-repeats. Subjective reports of craving correlated with increased activity in reward-related structures including the extended amygdala, insula and post-central gyrus, and decreased activity in the dorsolateral prefrontal cortex, and were DAT-genotype dependent (r = 0.63-0.96). In secondary analyses, we found that The Fagerstrom Test for Nicotine Dependence scores correlated with enhanced SC-induced perfusion in 10/10-repeats in the insula, mOFC, medial temporal and superior frontal gyri (r = 0.50-0.82), while correlations were absent in 9-repeat carriers. Despite heterogeneity introduced by a host of factors, including variance in other genes involved in smoking behavior, we confirm that DAT genotype predicts the direction and location of neural responses to SCs.
C1 [Franklin, Teresa R.; Wang, Ze; Li, Yin; Suh, Jesse J.; Goldman, Marina; Lohoff, Falk W.; Cruz, Jeffrey; Hazan, Rebecca; Jens, Will; Berrettini, Wade; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Philadelphia Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Detre, John A.] Univ Penn, Philadelphia Sch Med, Dept Radiol & Neurol, Philadelphia, PA 19104 USA.
[Suh, Jesse J.; O'Brien, Charles P.; Childress, Anna Rose] Philadelphia VA Med Ctr, Philadelphia, PA USA.
RP Franklin, TR (reprint author), Univ Penn, Dept Psychiat, Addict Treatment Res Ctr, Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA.
EM franklin_t@mail.trc.upenn.edu
RI Wang, Ze/A-1043-2007; Lohoff, Falk/M-7951-2016;
OI Jens, William/0000-0001-5201-1412
FU NIH [5-P60-DA-005186-18]; Pfizer Pharmaceuticals; Alexander Foundation
FX Work supported by NIH 5-P60-DA-005186-18, Pfizer Pharmaceuticals (an
Investigator-initiated research grant) and The Alexander Foundation.
NR 82
TC 33
Z9 33
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD APR
PY 2011
VL 16
IS 2
BP 308
EP 322
DI 10.1111/j.1369-1600.2010.00277.x
PG 15
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 730HQ
UT WOS:000288024800012
PM 21299752
ER
PT J
AU Izamis, ML
Sharma, NS
Uygun, B
Bieganski, R
Saeidi, N
Nahmias, Y
Uygun, K
Yarmush, ML
Berthiaume, F
AF Izamis, Maria-Louisa
Sharma, Nripen S.
Uygun, Basak
Bieganski, Robert
Saeidi, Nima
Nahmias, Yaakov
Uygun, Korkut
Yarmush, Martin L.
Berthiaume, Francois
TI In Situ Metabolic Flux Analysis to Quantify the Liver Metabolic Response
to Experimental Burn Injury
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE hypermetabolism; metabolic flux analysis; liver; trauma and burns; rat;
in vivo
ID MASS ISOTOPOMER ANALYSIS; CITRIC-ACID CYCLE; AMINO-ACID; RAT-LIVER;
HYPERMETABOLIC LIVERS; FAILURE MODEL; ENERGY; GLUCONEOGENESIS; CACHEXIA;
SUPPORT
AB Trauma such as burns induces a hypermetabolic response associated with altered central carbon and nitrogen metabolism. The liver plays a key role in these metabolic changes; however, studies to date have evaluated the metabolic state of liver using ex vivo perfusions or isotope labeling techniques targeted to specific pathways. Herein, we developed a unique mass balance approach to characterize the metabolic state of the liver in situ, and used it to quantify the metabolic changes to experimental burn injury in rats. Rats received a sham (control uninjured), 20% or 40% total body surface area (TBSA) scald burn, and were allowed to develop a hypermetabolic response. One day prior to evaluation, all animals were fasted to deplete glycogen stores. Four days post-burn, blood flow rates in major vessels of the liver were measured, and blood samples harvested. We combined measurements of metabolite concentrations and flow rates in the major vessels entering and leaving the liver with a steady-state mass balance model to generate a quantitative picture of the metabolic state of liver. The main findings were: (1) Sham-burned animals exhibited a gluconeogenic pattern, consistent with the fasted state; (2) the 20% TBSA burn inhibited gluconeogenesis and exhibited glycolytic-like features with very few other significant changes; (3) the 40% TBSA burn, by contrast, further enhanced gluconeogenesis and also increased amino acid extraction, urea cycle reactions, and several reactions involved in oxidative phosphorylation. These results suggest that increasing the severity of injury does not lead to a simple dose-dependent metabolic response, but rather leads to qualitatively different responses. Biotechnol. Bioeng. 2011;108: 839-852. (C) 2010 Wiley Periodicals, Inc.
C1 [Izamis, Maria-Louisa; Sharma, Nripen S.; Uygun, Basak; Bieganski, Robert; Saeidi, Nima; Nahmias, Yaakov; Uygun, Korkut; Yarmush, Martin L.; Berthiaume, Francois] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Ctr Engn Med, Boston, MA 02114 USA.
[Sharma, Nripen S.; Yarmush, Martin L.; Berthiaume, Francois] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
RP Berthiaume, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children,Ctr Engn Med, Boston, MA 02114 USA.
EM fberthia@rci.rutgers.edu
RI Nahmias, Yaakov/H-4725-2013; Uygun, Basak/I-1792-2012; Lorkiewicz,
Pawel/A-2126-2011;
OI Uygun, Basak/0000-0002-2600-7900; Lorkiewicz, Pawel/0000-0002-1755-9826;
Nahmias, Yaakov/0000-0002-6051-616X
FU Shriners Hospitals for Children [8640, 8450, 8460, 8490, 8496, 8503];
National Institutes of Health [DK080942]
FX This work was supported by the Shriners Hospitals for Children (8640,
8450, 8460, 8490, 8496, and 8503) and the National Institutes of Health
grant # DK080942.
NR 39
TC 7
Z9 10
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3592
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD APR
PY 2011
VL 108
IS 4
BP 839
EP 852
DI 10.1002/bit.22998
PG 14
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 730LL
UT WOS:000288034700013
PM 21404258
ER
PT J
AU Hamdy, O
AF Hamdy, Osama
TI Nonsurgical Diabetes Weight Management: Be Prepared for Sustainable and
Practical Interventions
SO CURRENT DIABETES REPORTS
LA English
DT Editorial Material
ID LIFE-STYLE INTERVENTION; OUTCOMES
C1 Joslin Diabet Ctr, Boston, MA 02481 USA.
RP Hamdy, O (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02481 USA.
EM Osama.hamdy@joslin.harvard.edu
NR 8
TC 1
Z9 1
U1 0
U2 0
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 2011
VL 11
IS 2
BP 75
EP 76
DI 10.1007/s11892-010-0172-9
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 729CI
UT WOS:000287925200002
PM 21222057
ER
PT J
AU Arathuzik, GG
Goebel-Fabbri, AE
AF Arathuzik, Gillian G.
Goebel-Fabbri, Ann E.
TI Nutrition Therapy and the Management of Obesity and Diabetes: An Update
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Weight management; Obesity; Type 2 diabetes; Diet; Nutrition
ID LOW-FAT DIET; WEIGHT-LOSS; LOW-CARBOHYDRATE; RISK-FACTORS; TYPE-2;
INTERVENTION; PROTEIN; TRIAL; INDIVIDUALS; MELLITUS
AB Diabetes and obesity have each become a national health crisis in recent years. The number of people who have diabetes and prediabetes continues to grow with a predicted number of 336 million people worldwide with type 2 diabetes by 2030. The prevalence of diabetes has risen in parallel with the increased prevalence of obesity. The optimal nutrition therapy for the treatment of both diabetes and obesity remains controversial. Health care practitioners are no longer solely prescribing the conventional low-fat, higher-carbohydrate diet approach that was used for over a decade. Lower-carbohydrate, higher-fat, or higher-protein diets are now being viewed as equally or sometimes more effective treatment plans for diabetes and obesity. In addition, there are other aspects of diet beyond macronutrient composition that are currently being investigated. This article will summarize research conducted over the past 2 years examining medical nutrition therapy for diabetes and obesity. It will also describe the unique challenges that come with treating this patient population.
C1 [Arathuzik, Gillian G.; Goebel-Fabbri, Ann E.] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Arathuzik, GG (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM Gillian.arathuzik@joslin.harvard.edu;
Ann.goebel-fabbri@joslin.harvard.edu
NR 29
TC 9
Z9 9
U1 0
U2 17
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 2011
VL 11
IS 2
BP 106
EP 110
DI 10.1007/s11892-011-0176-0
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 729CI
UT WOS:000287925200007
PM 21240571
ER
PT J
AU Hamdy, O
Horton, ES
AF Hamdy, Osama
Horton, Edward S.
TI Protein Content in Diabetes Nutrition Plan
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Medical nutrition therapy; Diabetes; Protein; Nutrition
ID GLUCOSE APPEARANCE RATE; WEIGHT-LOSS DIET; RENAL-FUNCTION; BARIATRIC
SURGERY; ORAL GLUCOSE; RISK-FACTORS; FOLLOW-UP; TYPE-2; INGESTION;
RESTRICTION
AB Medical nutrition therapy plays a major role in diabetes management. Macronutrient composition has been debated for a long time. However, there is increasing evidence that a modest increase in dietary protein intake above the current recommendation is a valid option toward better diabetes control, weight reduction, and improvement in blood pressure, lipid profile, and markers of inflammation. Increasing the absolute protein intake to 1.5-2 g/kg (or 20-30% of total caloric intake) during weight reduction has been suggested for overweight and obese patients with type 2 diabetes and normal kidney function. Increased protein intake does not increase plasma glucose, but increases the insulin response and results in a significant reduction in hemoglobin A(1c). In addition, a higher dietary protein intake reduces hunger, improves satiety, increases thermogenesis, and limits lean muscle mass loss during weight reduction using a reduced calorie diet and increased physical activity. It is preferable to calculate protein intake for patients with diabetes as grams per kilogram of body weight and not as a fixed percentage of total energy intake to avoid protein malnutrition when a hypocaloric diet is used. The relationship between protein intake as grams per kilogram of body weight and albumin excretion rate is very weak, except in hypertensive patients and particularly in those with uncontrolled diabetes. A protein intake of 0.8-1 g/kg should be recommended only for patients with diabetes and chronic kidney disease. Other patients with diabetes should not reduce protein intake to less than 1 g/kg of body weight. This review discusses the effects of different amounts of protein intake in a diabetes meal plan. It particular, it discusses the effects of protein intake on renal function, the effects of protein content on diabetes control, and the effects of increased dietary protein on body weight.
C1 [Hamdy, Osama; Horton, Edward S.] Harvard Univ, Sch Med, Dept Endocrinol, Joslin Diabet Ctr, Boston, MA 02481 USA.
RP Hamdy, O (reprint author), Harvard Univ, Sch Med, Dept Endocrinol, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02481 USA.
EM Osama.hamdy@joslin.harvard.edu
RI Biguzzi, Felipe/E-4724-2015
NR 36
TC 7
Z9 7
U1 0
U2 6
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 2011
VL 11
IS 2
BP 111
EP 119
DI 10.1007/s11892-010-0171-x
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 729CI
UT WOS:000287925200008
PM 21207203
ER
PT J
AU Lo, J
AF Lo, Janet
TI Dyslipidemia and lipid management in HIV-infected patients
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Article
DE cardiovascular risk factors; HIV; lipids
ID IMMUNODEFICIENCY-VIRUS-INFECTION; COMBINATION ANTIRETROVIRAL THERAPY;
CLINICAL-TRIALS GROUP; TREATMENT PANEL-III; PROTEASE INHIBITORS;
RISK-FACTORS; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; DISEASE;
CHOLESTEROL
AB Purpose of review
Dyslipidemia is highly prevalent among patients living with chronic HIV infection and may confer increased risk of cardiovascular disease in this patient population. This review summarizes recent data investigating lipid abnormalities and its management in HIV-infected patients.
Recent findings
Studies in the last year have evaluated the effects of various lipid-lowering therapies not previously investigated in the HIV patient population. Rosuvastatin is a potent statin that appears to be well tolerated and effective in HIV-infected patients with hypercholesterolemia.
Summary
Dyslipidemia is common in HIV-infected individuals. Medical therapy of lipid disorders needs to take potential drug-drug interactions of lipid-lowering medications and antiretroviral agents into consideration.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Program Nutr Metab, Boston, MA 02114 USA.
RP Lo, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA.
EM jlo@partners.org
FU NHLBI NIH HHS [K23 HL092792-04, K23 HL092792]
NR 29
TC 15
Z9 15
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1752-296X
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD APR
PY 2011
VL 18
IS 2
BP 144
EP 147
DI 10.1097/MED.0b013e328344556e
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 729AV
UT WOS:000287919500008
PM 21297466
ER
PT J
AU Goldstein, JN
Gilson, AJ
AF Goldstein, Joshua N.
Gilson, Aaron J.
TI Critical Care Management of Acute Intracerebral Hemorrhage
SO CURRENT TREATMENT OPTIONS IN NEUROLOGY
LA English
DT Review
ID ASSOCIATION/AMERICAN-STROKE-ASSOCIATION; HYPERTENSIVE
CEREBRAL-HEMORRHAGE; PREDICTS HEMATOMA EXPANSION; CT ANGIOGRAPHY;
CLINICAL-TRIAL; BLOOD-PRESSURE; INTRAVENTRICULAR THROMBOLYSIS;
CONSERVATIVE TREATMENT; AMYLOID ANGIOPATHY; HIGHEST RISK
AB Intracerebral hemorrhage is a medical emergency. It is the most deadly and disabling form of stroke, and no individual therapy has been demonstrated to improve outcome. However, it appears that aggressive medical care in general, and management by neuroscience specialists in particular, offers substantial benefit. Therefore, providing the best supportive care based on currently available evidence may well improve outcomes. Airway management and management of blood pressure aimed at maximizing cerebral perfusion while minimizing ongoing bleeding, as well as rapid reversal of anticoagulation, are likely to be important in the early phase. Additionally, efforts should be undertaken to provide careful glucose management and temperature management and to maximize cerebral perfusion pressure. Selected patients are likely to benefit from external ventricular drainage or even hematoma evacuation. Except in rare circumstances, most patients should be managed in a neuroscience intensive care unit during the acute phase. Some patients appear to have no reasonable likelihood of recovery and can be considered for limitations of care such as Do Not Resuscitate orders or Comfort Measures Only orders. However, it can be difficult to accurately predict long-term outcome in the acute phase; formal prognostic tools should be used to offer information to patients and their families. After the hemorrhage has stabilized, efforts to minimize complications include thromboembolism prophylaxis, physical therapy, and acute rehabilitation.
C1 [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA.
EM jgoldstein@partners.org; aaron.gilson@lmunet.edu
RI Goldstein, Joshua/H-8953-2016
FU CSL Behring
FX Conflicts of Interest: J. Goldstein: Consulting fees and travel expenses
from CSL Behring; A. Gilson: None.
NR 61
TC 7
Z9 9
U1 1
U2 3
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1092-8480
J9 CURR TREAT OPTION NE
JI Curr. Treat. Options Neurol.
PD APR
PY 2011
VL 13
IS 2
BP 204
EP 216
DI 10.1007/s11940-010-0109-2
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 729CV
UT WOS:000287926800007
PM 21222062
ER
PT J
AU Simard, JM
Sahuquillo, J
Sheth, KN
Kahle, KT
Walcott, BP
AF Simard, J. Marc
Sahuquillo, Juan
Sheth, Kevin N.
Kahle, Kristopher T.
Walcott, Brian P.
TI Managing Malignant Cerebral Infarction
SO CURRENT TREATMENT OPTIONS IN NEUROLOGY
LA English
DT Review
ID INTENSIVE-CARE-UNIT; ARTERY INFARCTION; DECOMPRESSIVE CRANIECTOMY;
INTRACRANIAL-PRESSURE; ISCHEMIC-STROKE; HYPERTONIC SALINE; HEMISPHERIC
INFARCTION; RANDOMIZED-TRIAL; HEAD-INJURY; HEMICRANIECTOMY
AB Managing patients with malignant cerebral infarction remains one of the foremost challenges in medicine. These patients are at high risk for progressive neurologic deterioration and death due to malignant cerebral edema, and they are best cared for in the intensive care unit of a comprehensive stroke center. Careful initial assessment of neurologic function and of findings on MRI, coupled with frequent reassessment of clinical and radiologic findings using CT or MRI are mandatory to promote the prompt initiation of treatments that will ensure the best outcome in these patients. Significant deterioration in either neurologic function or radiologic findings or both demand timely treatment using the best medical management, which may include osmotherapy (mannitol or hypertonic saline), endotracheal intubation, and mechanical ventilation. Under appropriate circumstances, decompressive craniectomy may be warranted to improve outcome or to prevent death.
C1 [Simard, J. Marc] Dept Neurosurg, Baltimore, MD 21201 USA.
[Sahuquillo, Juan] Univ Autonoma Barcelona, Dept Neurosurg, Hosp Univ Vall dHebron, Barcelona 08035, Spain.
[Sheth, Kevin N.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, DC 20201 USA.
[Kahle, Kristopher T.; Walcott, Brian P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA.
RP Simard, JM (reprint author), Dept Neurosurg, 22 S Greene St,Suite S12D, Baltimore, MD 21201 USA.
EM msimard@smail.umaryland.edu
RI Sahuquillo, Juan/B-3577-2008
OI Sahuquillo, Juan/0000-0003-0713-5875
FU NHLBI NIH HHS [R01 HL082517]; NINDS NIH HHS [R01 NS061808, R01
NS061808-04]
NR 49
TC 18
Z9 20
U1 0
U2 6
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1092-8480
J9 CURR TREAT OPTION NE
JI Curr. Treat. Options Neurol.
PD APR
PY 2011
VL 13
IS 2
BP 217
EP 229
DI 10.1007/s11940-010-0110-9
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 729CV
UT WOS:000287926800008
PM 21190097
ER
PT J
AU Chung, JH
Kradin, RL
Greene, RE
Shepard, JAO
Digumarthy, SR
AF Chung, Jonathan H.
Kradin, Richard L.
Greene, Reginald E.
Shepard, Jo-Anne O.
Digumarthy, Subba R.
TI CT predictors of mortality in pathology confirmed ARDS
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE Acute respiratory distress syndrome; Diffuse alveolar damage;
Right-sided heart strain; Mortality; CT
ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE INTERSTITIAL PNEUMONIA; ACUTE LUNG
INJURY; PULMONARY VASCULAR OBSTRUCTION; RIGHT-VENTRICULAR DYSFUNCTION;
THIN-SECTION CT; COMPUTED-TOMOGRAPHY; CLINICAL-COURSE; FOLLOW-UP;
EMBOLISM
AB To identify CT findings that predict mortality in acute respiratory distress syndrome (ARDS) and to identify CT findings that differentiate diffuse alveolar damage (DAD) from DAD with prominent histopathological features of organizing pneumonia (DAD-OP).
Twenty-eight patients with ARDS (corroborated by open biopsy) and chest CT within 2 weeks of biopsy were included in our study. Differences in CT findings in patients with survivors versus nonsurvivors as well as for DAD versus DAD-OP were compared using Fisher's exact test.
Lung involvement of greater than 80%, RA/LA ratio > 1, and varicoid traction bronchiectasis were statistically more common in nonsurvivors than in survivors (respective p values of 0.001, 0.008, and 0.038). PA dilation greater than 3 cm and RV/LV ratio greater than 0.9 were also more common in nonsurvivors than in survivors but these factors did not achieve significance. CT findings did not differentiate DAD from DAD-OP.
Our study suggests that > 80% of lung involvement, RA/LA ratio > 1, and varicoid bronchiectasis predict mortality in patients with ARDS/DAD. Signs of right-sided heart failure (PA dilation greater than 3 cm and RV/LV ratio greater than 0.9) approached significance. CT findings did not differentiate DAD from DAD-OP.
C1 [Chung, Jonathan H.; Greene, Reginald E.; Shepard, Jo-Anne O.; Digumarthy, Subba R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol & Pulm Med, Boston, MA 02114 USA.
RP Digumarthy, SR (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA.
EM sdigumarthy@partners.org
NR 35
TC 11
Z9 12
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
J9 EUR RADIOL
JI Eur. Radiol.
PD APR
PY 2011
VL 21
IS 4
BP 730
EP 737
DI 10.1007/s00330-010-1979-0
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 729DI
UT WOS:000287928200008
PM 20927526
ER
PT J
AU Matschke, S
Wentzensen, A
Ring, D
Marent-Huber, M
Audige, L
Jupiter, JB
AF Matschke, S.
Wentzensen, A.
Ring, D.
Marent-Huber, M.
Audige, L.
Jupiter, J. B.
TI Comparison of angle stable plate fixation approaches for distal radius
fractures
SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
LA English
DT Article
DE Distal radius fractures; Dorsal plating; Volar plating; LCP; 2-Year
follow-up
ID INTERNAL-FIXATION; INTRAARTICULAR FRACTURES; UNSTABLE FRACTURES; LOCKING
PLATES; PI PLATE; DORSAL; VOLAR; COMPLICATIONS; MANAGEMENT;
CLASSIFICATION
AB Introduction: The aim of the study was to compare radiological and functional outcomes between volar and dorsal surgical fixation of distal radius fractures using low-profile, fixed-angle implants.
Patients and methods: A total of 305 distal radius fracture patients were treated with Synthes locking compression plate (LCP) 2.4- or 3.5-mm fixation using either a volar (n = 266) or dorsal (n = 39) approach. The patients were examined at 6 months, 1 and 2 years for radiological assessment of fracture healing, alignment, reduction and arthritis, as well as the determination of various functional outcome scores.
Results: Both groups were comparable with respect to baseline and injury characteristics. The complication rate was higher for the volar approach (15%). No significant differences were observed for Disabilities of the Arm, Shoulder and Hand (DASH) and Short Form (36) Health Survey (SF-36) scores, pain, arthritis grade, grip strength and radiological measurements. However, a significantly better functional outcome represented by a low mean Gartland and Werley score was observed for the volar approach after 6 and 12 months. Significantly higher percentages of dorsal extension, palmar flexion, ulnar deviation and supination angle (relative to the mean contralateral healthy wrist) were also reported for volar approach patients at the 6-month follow-up.
Conclusions: Volar internal fixation of distal radius fractures with LCP DR implants can result in earlier and better functional outcome compared with the dorsal approach, yet is associated with a higher incidence of complications. After 2 years, these differences are no longer observed between the two surgical methods. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Matschke, S.; Wentzensen, A.] Univ Heidelberg, Unfallchirurg Klin, Klin Unfallchirurg & Orthopad, Berufsgenossenschaftliche Unfallklin Ludwigshafen, D-67071 Ludwigshafen, Germany.
[Ring, D.; Jupiter, J. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Marent-Huber, M.; Audige, L.] AO Clin Invest & Documentat, Davos, Switzerland.
RP Matschke, S (reprint author), Univ Heidelberg, Unfallchirurg Klin, Klin Unfallchirurg & Orthopad, Berufsgenossenschaftliche Unfallklin Ludwigshafen, Ludwig Guttmann Str 13, D-67071 Ludwigshafen, Germany.
EM matschke@bgu-ludwigshafen.de
RI AOCID, AO Foundation/R-6455-2016
NR 29
TC 16
Z9 24
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0020-1383
J9 INJURY
JI Injury-Int. J. Care Inj.
PD APR
PY 2011
VL 42
IS 4
BP 385
EP 392
DI 10.1016/j.injury.2010.10.010
PG 8
WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery
SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery
GA 730CM
UT WOS:000288008500014
PM 21144514
ER
PT J
AU Baumueller, S
Alkadhi, H
Stolzmann, P
Frauenfelder, T
Goetti, R
Schertler, T
Plass, A
Falk, V
Feuchtner, G
Scheffel, H
Desbiolles, L
Leschka, S
AF Baumueller, Stephan
Alkadhi, Hatem
Stolzmann, Paul
Frauenfelder, Thomas
Goetti, Robert
Schertler, Thomas
Plass, Andre
Falk, Volkmar
Feuchtner, Gudrun
Scheffel, Hans
Desbiolles, Lotus
Leschka, Sebastian
TI Computed Tomography of the Lung in the High-Pitch Mode Is Breath Holding
Still Required?
SO INVESTIGATIVE RADIOLOGY
LA English
DT Article
DE computed tomography scanner; lung; breathing
ID HIGH-RESOLUTION CT; THIN-SECTION CT; ADAPTED EXAMINATION PROTOCOLS;
SPIRAL VOLUMETRIC CT; RADIATION-EXPOSURE; PULMONARY NODULES;
AORTIC-ANEURYSM; IMAGE QUALITY; HELICAL CT; REDUCTION
AB Objectives: To prospectively investigate whether the high-pitch mode (HPM) for computed tomography (CT) enables the diagnostic visualization of the lung parenchyma without suspended respiration.
Materials and Methods: A total of 40 consecutive patients (age, 67 +/- 11 years) underwent 128-slice dual-source CT of the chest including nonenhanced, arterial, and venous phase of contrast. CT was performed in the HPM with a pitch of 3.2 during continuous breathing (group A) and during breath-hold (group B), and at standard pitch of 1 during deep-inspiratory breath-hold (group C). The 3 protocols were scanned in a random order in each patient. Two blinded readers independently assessed the image quality of 5 regions in both the lungs using a semiquantitative 3-point score. Image noise was measured as the standard deviation of attenuation. Presence and size of pulmonary nodules were noted and measured on each CT dataset. Lung volume was measured using dedicated semi-automated segmentation software.
Results: Interobserver agreement for image quality ratings was excellent (kappa = 0.91). There were no significant differences in the number of lung regions having an image quality other than excellent between group A (2.5%) and B (1.5%, P = 0.48), whereas significantly less regions had impaired image quality in group B compared with group C (5.5%, P < 0.01). Image quality impairment in group C was because of breathing in 36% and cardiac pulsation in 64%. Image noise in group C (9 +/- 2 HU) was significantly lower than that in group B (30 +/- 2 HU, P < 0.001) whereas no significant difference was found between group A and B (P = 0.52). There were no significant differences for the depiction (P = 1.0) and size (P = 0.94) of lung nodules among the 3 modes. Average lung volume in group A was 75% +/- 15% of that in deep inspiration (group B/C) being significantly smaller (P < 0.05). Estimated effective radiation doses in group C and group B were 5.8 +/- 0.5 mSv and 1.6 +/- 0.1 mSv, respectively.
Conclusions: CT of the lung can be accomplished using the HPM at a low radiation dose with a diagnostic image quality even without suspended respiration.
C1 [Leschka, Sebastian] Cantonal Hosp St Gallen, Inst Radiol, CH-9007 St Gallen, Switzerland.
[Baumueller, Stephan; Alkadhi, Hatem; Stolzmann, Paul; Frauenfelder, Thomas; Goetti, Robert; Schertler, Thomas; Feuchtner, Gudrun; Scheffel, Hans; Desbiolles, Lotus] Univ Zurich Hosp, Inst Diagnost & Intervent Radiol, CH-8091 Zurich, Switzerland.
[Alkadhi, Hatem; Stolzmann, Paul; Scheffel, Hans] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Alkadhi, Hatem; Stolzmann, Paul; Scheffel, Hans] Harvard Univ, Sch Med, Boston, MA USA.
[Plass, Andre; Falk, Volkmar] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland.
RP Leschka, S (reprint author), Cantonal Hosp St Gallen, Inst Radiol, Rorschacher Str 95, CH-9007 St Gallen, Switzerland.
EM sebastian.leschka@kssg.ch
RI Goetti, Robert/I-8961-2012; Frauenfelder, Thomas/O-1734-2016
OI Frauenfelder, Thomas/0000-0002-3295-6619
NR 37
TC 34
Z9 37
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-9996
J9 INVEST RADIOL
JI Invest. Radiol.
PD APR
PY 2011
VL 46
IS 4
BP 240
EP 245
DI 10.1097/RLI.0b013e3181feee1a
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 729WK
UT WOS:000287984600004
PM 21217528
ER
PT J
AU McCall, AA
Linthicum, FH
O'Malley, JT
Adams, JC
Merchant, SN
Bassim, MK
Gellibolian, R
Fayad, JN
AF McCall, Andrew A.
Linthicum, Fred H., Jr.
O'Malley, Jennifer T.
Adams, Joe C.
Merchant, Saumil N.
Bassim, Marc K.
Gellibolian, Robert
Fayad, Jose N.
TI Extralabyrinthine Manifestations of DFNA9
SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
LA English
DT Article
DE cochlin; COCH; hearing loss; deafness
ID SENSORINEURAL HEARING-LOSS; VESTIBULAR DYSFUNCTION; INNER-EAR;
OTITIS-MEDIA; A DOMAIN; COCHLIN; DEAFNESS; GENE; MUTATIONS
AB DFNA9 is an autosomal dominant cause of non-syndromic adult-onset sensorineural hearing loss with associated variable vestibular dysfunction caused by mutations in the COCH gene. DFNA9 has previously been characterized by the presence of unique histopathologic features limited to the cochlear and vestibular labyrinth. This report describes newly discovered extralabyrinthine findings within the middle ear in DFNA9 and discusses their implications. The histopathologic anatomy of extralabyrinthine structures was reviewed in 12 temporal bones from seven individuals with DFNA9 and compared with age-matched controls. All temporal bones with DFNA9 had abnormal deposits within the tympanic membrane, incudomalleal joint, and incudostapedial joint. Hematoxylin and eosin stain and Movat's pentachrome stain both revealed different staining patterns of the extralabyrinthine deposits compared with the intralabyrinthine deposits suggesting that the composition of the deposits varies with location. The deposits within the tympanic membrane resembled cartilage morphologically and stained positively for aggrecan, an extracellular matrix protein found in cartilage. However, the cellular component of the tympanic membrane deposits did not stain with immunomarkers for chondrocytes (s100 and connective tissue growth factor). These novel findings in DFNA9 have implications for the phenotypic expression of the disorder and the clinical workup of adult-onset sensorineural hearing loss.
C1 [McCall, Andrew A.; O'Malley, Jennifer T.; Adams, Joe C.; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[McCall, Andrew A.; O'Malley, Jennifer T.; Adams, Joe C.; Merchant, Saumil N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Linthicum, Fred H., Jr.; Gellibolian, Robert; Fayad, Jose N.] House Ear Res Inst, Los Angeles, CA 90057 USA.
[Bassim, Marc K.; Fayad, Jose N.] House Ear Clin, Los Angeles, CA 90057 USA.
RP McCall, AA (reprint author), Univ Pittsburgh, Dept Otolaryngol, Inst Eye & Ear, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA.
EM mccallaa@upmc.edu
FU National Institutes of Health [U24 DC 008559, U24 DC 008625]
FX This work was supported by the National Institutes of Health (grants U24
DC 008559 and U24 DC 008625 Human Temporal Bone Consortium for Research
Resource Enhancement of the National Institute on Deafness and Other
Communication Disorders). We acknowledge Diane Jones and Barbara Burgess
from the Massachusetts Eye and Ear Infirmary temporal bone
histopathology laboratory for technical assistance with the project. We
thank Andrew E. Rosenberg, MD bone and soft tissue pathology specialist
from the Department of Pathology at the Massachusetts General Hospital
for providing his expertise and guidance as well as providing the s100
antibody utilized in this project.
NR 26
TC 3
Z9 3
U1 0
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1525-3961
J9 JARO-J ASSOC RES OTO
JI JARO
PD APR
PY 2011
VL 12
IS 2
BP 141
EP 149
DI 10.1007/s10162-010-0245-0
PG 9
WC Neurosciences; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 728FA
UT WOS:000287858600002
PM 21052762
ER
PT J
AU McClintock, SM
Husain, MM
Wisniewski, SR
Nierenberg, AA
Stewart, JW
Trivedi, MH
Cook, I
Morris, D
Warden, D
Rush, AJ
AF McClintock, Shawn M.
Husain, Mustafa M.
Wisniewski, Stephen R.
Nierenberg, Andrew A.
Stewart, Jonathan W.
Trivedi, Madhukar H.
Cook, Ian
Morris, David
Warden, Diane
Rush, Augustus John
TI Residual Symptoms in Depressed Outpatients Who Respond by 50% But Do Not
Remit to Antidepressant Medication
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE depression; STAR*D; residual; symptoms; treatment response
ID STAR-ASTERISK-D; DIAGNOSTIC SCREENING QUESTIONNAIRE; SEQUENCED TREATMENT
ALTERNATIVES; MAJOR DEPRESSION; COGNITIVE THERAPY; PARTIAL REMISSION;
DISORDER; RELAPSE; RISK; SYMPTOMATOLOGY
AB Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD who responded without remitting after up to 12 weeks of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Response was defined as 50% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)) by treatment exit, and remission as a final QIDS-SR16 of less than 6. Residual symptom domains and individual symptoms were based on the QIDS-SR16 and classified as either persisting from baseline or emerging during treatment. Most responders who did not remit endorsed approximately 5 residual symptom domains and 6 to 7 residual depressive symptoms. The most common domains were insomnia (94.6%), sad mood (70.8%), and decreased concentration (69.6%). The most common individual symptoms were midnocturnal insomnia (79.0%), sad mood (70.8%), and decreased concentration/decision making (69.6%). The most common treatment-emergent symptoms were midnocturnal insomnia (51.4%) and decreased general interest (40.0%). The most common persistent symptoms were midnocturnal insomnia (81.6%), sad mood (70.8%), and decreased concentration/decision making (70.6%). Suicidal ideation was the least common treatment-emergent symptom (0.7%) and the least common persistent residual symptom (17.1%). These findings suggest that depressed outpatients who respond by 50% without remitting to citalopram treatment have a broad range of residual symptoms. Individualized treatments are warranted to specifically address each patient's residual depressive symptoms.
C1 [McClintock, Shawn M.; Husain, Mustafa M.; Trivedi, Madhukar H.; Morris, David; Warden, Diane] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[McClintock, Shawn M.] Columbia Univ, Dept Psychiat, Div Brain Stimulat & Therapeut Modulat, New York State Psychiat Inst, New York, NY USA.
[Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA.
[Nierenberg, Andrew A.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Stewart, Jonathan W.] New York State Psychiat Inst & Hosp, Depress Evaluat Serv, Dept Psychiat, New York, NY 10032 USA.
[Cook, Ian] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Depress Res & Clin Program, Los Angeles, CA USA.
[Rush, Augustus John] Duke Natl Univ Singapore, Off Clin Sci, Grad Sch Med, Singapore, Singapore.
RP McClintock, SM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM shawn.mcclintock@utsouthwestern.edu
OI Wisniewski, Stephen/0000-0002-3877-9860; Rush,
Augustus/0000-0003-2004-2382
FU National Institute of Mental Health [N01MH90003]; National Institutes of
Health; National Center for Research Resources; National Alliance for
the Research of Schizophrenia and Depression; Aspect Medical
Systems/Covidien; Cyberonics, Inc.; Eli Lilly Company; Neuronetics;
Novartis; Sepracor; National Institutes of Health, National Institute of
Mental Health; Stanley Medical Research Institute; St. Jude Medical
Center; Brainsway; Pfizer, Inc.; Cephalor, Inc.; Cederroth; Cyberonics;
Forest; Medtronics; National Alliance for Research on Schizophrenia and
Depression; Ortho-McNeil-Janssen; Pamlab; Pfizer; Shire; Stanley
Foundation through the Broad Institute; Bristol-Myers Squibb; Eli Lilly;
GlaxoSmithKline; Janssen; Lictwer Pharma; Wyeth; AstraZeneca; Advanced
Neuromodulation Systems; Best Practice Project Management; Bristol-Myers
Squibb/Otsuka; Gerson Lehrman Group; Jazz Pharmaceuticals; Magellan
Health Services; Merck Co.; Novartis Pharmaceuticals; Ono
Pharmaceuticals; Organon; Otsuka Pharmaceuticals; Transcept
Pharmaceuticals; Urban Institute; Wyeth Ayerst; University of Michigan;
Brain Resource; Forest Pharmaceuticals; Society of Biological
Psychiatry; Agency for Healthcare Research and Quality (AHRQ); Corcept
Therapeutics, Inc.; National Institute on Drug Abuse; Pharmacia Upjohn;
Predix Pharmaceuticals (Epix); Solvay Pharmaceuticals, Inc.; Targacept;
ImaRx Therapeutics, Inc.; Case Western Reserve University; Singapore
Clinical Research Institute; Dey Pharmaceuticals; Venebio; National
Institute of Health, National Institute of Neurological Disorders and
Stroke; National Institute of Health, National Institute of Aging
FX This project was funded by the National Institute of Mental Health under
contract N01MH90003 to the University of Texas Southwestern Medical
Center at Dallas (A. J. Rush and M. H. Trivedi, principal
investigators). The NIMH had no further role in the study design;
collection, analysis, and interpretation of the data; writing of the
report; or in the decision to submit the paper for publication. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government.; Dr McClintock has received research
support from the National Institutes of Health, the National Center for
Research Resources, and the National Alliance for the Research of
Schizophrenia and Depression. Dr Cook has served as an advisor and
consultant for Ascend Media, Bristol-Meyers Squibb, Cyberonics, Inc,
Lilly, and the US Department of Justice. He has served on the speaker's
bureaus for Bristol-Meyers Squibb, Neuronetics, and Wyeth/Pfizer. He has
received research support from Aspect Medical Systems/Covidien,
Cyberonics, Inc., Eli Lilly & Company, Neuronetics, Novartis, Sepracor,
and the National Institutes of Health. His patents on biomedical devices
are assigned to the Regents of the University of California. Dr Husain
has received research support from the National Institutes of Health
(including National Institute of Mental Health, National Institute of
Neurological Disorders and Stroke, and National Institute of Aging), the
Stanley Medical Research Institute, St. Jude Medical Center, Cyberonics,
Inc., Brainsway, Neuronetics, and he has received equipment from
Magstim, Inc. Dr Morris has received consultation fees from Pfizer, Inc.
and Cephalor, Inc. Dr Nierenberg has consulted to or served on the
advisory boards of Abbott, Appliance Computing, Brain Cells,
Bristol-Myers Squibb, Eli Lilly, EpiQ, Forest, GlaxoSmithKline, Janssen,
Jazz, Merck, Novartis, Pamlab, Pfizer, PGx Health, Pharmaceutica,
Schering-Plough, Sepracor, Shire, Somerset, Takeda, and Targacept; has
received research support from Cederroth, Cyberonics, Forest,
Medtronics, the National Alliance for Research on Schizophrenia and
Depression, the National Institute of Mental Health,
Ortho-McNeil-Janssen, Pamlab, Pfizer, Shire, and the Stanley Foundation
through the Broad Institute; has received past support from
Bristol-Myers Squibb, Cederroth, Eli Lilly, Forest, GlaxoSmithKline,
Janssen, Lictwer Pharma, Pfizer, and Wyeth; has received honoraria from
the Massachusetts General Hospital (MGH) Psychiatry Academy (MGHPA
activities are supported through Independent Medical Education grants
from AstraZeneca, Eli Lilly, and Janssen); earns fees for editorial
functions for CNS Spectrums through MBL Communications, and Psychiatric
Annals through Slack; receives honoraria as a CME executive director for
the Journal of Clinical Psychiatry through Physicians Postgraduate
Press; has been on the speaker's bureaus of Bristol-Myers Squibb,
Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, and Wyeth; has received
royalties from Cambridge University Press and Belvoir Publishing; owns
stock options in Appliance Computing; and owns the copyrights to the
Clinical Positive Affect Scale and the MGH Structured Clinical Interview
for the Montgomery Asberg Depression Scale, exclusively licensed to the
MGH Clinical Trials Network and Institute. Dr Rush has received
consultation fees from Advanced Neuromodulation Systems, AstraZeneca,
Best Practice Project Management, Bristol-Myers Squibb/Otsuka, the
Gerson Lehrman Group, Jazz Pharmaceuticals, Magellan Health Services,
Merck & Co., Neuronetics, Novartis Pharmaceuticals, Ono Pharmaceuticals,
Organon, Otsuka Pharmaceuticals, Pamlab, Transcept Pharmaceuticals,
Urban Institute, Wyeth Ayerst, University of Michigan, and Brain
Resource. He has received consulting fee/honoraria from Cyberonics,
Forest Pharmaceuticals, GlaxoSmithKline, and Pfizer. He has received
royalties from Guilford Publications, Healthcare Technology Systems, and
the University of Texas Southwestern Medical Center.; He has received
research support from the National Institute of Mentl Health and the
Stanley Medical Research Institute, and a stipend from the Society of
Biological Psychiatry. Dr Stewart has received consultation fees from
Merck & Co., study funding from Eli Lilly & Company and the National
Institute of Mental Health, and study medication from Forest
Pharmaceuticals. Dr Trivedi has acted as a paid consultant to or served
on speaker's bureaus for Abbott Laboratories, Inc., Abdi Ibrahim, Akzo
(Organon Pharmaceuticals, Inc.), AstraZeneca, Bristol-Meyers Squibb,
Cephalon, Inc., Cyberonics, Inc., Eli Lilly & Company, Evotec, Fabre
Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline,
Janssen Pharmaceuticals Products, LP, Johnson & Johnson PRD, Mead
Johnson, Medtronic, Neuronetics, Otsuka Pharmaceuticals, Parke-Davis
Pharmaceuticals, Inc., Pfizer, Inc., Sepracor, SHIRE Development, Solvay
Pharmaceuticals, VantagePoint, and Wyeth-Ayerst Laboratories. He has
also received research funding from the Agency for Healthcare Research
and Quality (AHRQ), Corcept Therapeutics, Inc., Cyberonics, Inc., Merck,
National Alliance for Research in Schizophrenia and Depression, National
Institute of Mental Health, National Institute on Drug Abuse, Novartis,
Pharmacia & Upjohn, Predix Pharmaceuticals (Epix), Solvay
Pharmaceuticals, Inc., and Targacept. Dr Warden has received research
funding from the National Alliance for the Research of Schizophrenia and
Depression, the National Institutes of Health, and has owned shares of
stock in Pfizer, Inc. Dr Wisniewski has received consulting fees from
Cyberonics, Inc. (2005-2009), ImaRx Therapeutics, Inc. (2006),
Bristol-Myers Squibb (2007-08), Organon (2007), Case Western Reserve
University (2007), Singapore Clinical Research Institute (2009), Dey
Pharmaceuticals (2010), and Venebio (2010).
NR 39
TC 60
Z9 64
U1 0
U2 5
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 2011
VL 31
IS 2
BP 180
EP 186
DI 10.1097/JCP.0b013e31820ebd2c
PG 7
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 729AJ
UT WOS:000287917500008
PM 21346613
ER
PT J
AU Fan, XD
Copeland, PM
Liu, EY
Chiang, EL
Freudenreich, O
Goff, DC
Henderson, DC
AF Fan, Xiaoduo
Copeland, Paul M.
Liu, Emily Y.
Chiang, Elaine
Freudenreich, Oliver
Goff, Donald C.
Henderson, David C.
TI No Effect of Single-Dose Intranasal Insulin Treatment on Verbal Memory
and Sustained Attention in Patients With Schizophrenia
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE intranasal insulin; cognition; attention; schizophrenia
ID RAT HIPPOCAMPUS; DIABETIC-RATS; RECEPTOR; MODULATION; BRAIN;
PERFORMANCE; COGNITION; HUMANS
AB Background: Impairments in verbal memory and attention are among the most severe and disabling cognitive deficits in patients with schizophrenia. Whereas efficacy for cognition has not yet been established for any pharmacologic strategy in schizophrenia, an accumulating body of evidence suggests a possible beneficial role of insulin.
Methods: We conducted a double-blind, placebo-controlled trial to examine the effect of single-dose intranasal insulin treatment on cognition in nondiabetic patients with schizophrenia. After fasting for 12 hours, subjects received either 40 IU regular human insulin or placebo administered by intranasal pump. The Hopkins Verbal Learning Test and the Continuous Performance Test-Identical Pairs were administered before and 30 minutes after intranasal treatment.
Results: Thirty patients were enrolled and completed the study. The 2 treatment groups (insulin vs placebo, n = 15 in each group) did not differ on any demographic or general clinical variable (P > 0.40). There was no significant difference between the 2 treatment groups in change on Hopkins Verbal Learning Test immediate recall total score and delayed recall score, or on CPT d', hits rate, reaction time of hits, or false-alarm rate (P > 0.1).
Conclusions: Results of the present study suggest that single-dose intranasal insulin treatment does not have a large-enough effect on verbal memory or sustained attention to be detected by a sample of this size in patients with schizophrenia but was safe and well tolerated. Longitudinal studies to explore cognitive benefits of repeated dosing of intranasal insulin treatment are needed.
C1 [Fan, Xiaoduo; Freudenreich, Oliver; Goff, Donald C.; Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA.
[Fan, Xiaoduo; Copeland, Paul M.; Freudenreich, Oliver; Goff, Donald C.; Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA.
[Copeland, Paul M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Liu, Emily Y.] Partners Community Healthcare Inc, Haverhill, MA USA.
[Chiang, Elaine] George Washington Univ, Sch Med, Washington, DC USA.
RP Fan, XD (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA.
EM xfan@partners.org
FU Massachusetts General Hospital; Eli Lilly; AstraZeneca; Bristol-Myers
Squibb; Janssen; Pfizer; Cephalon; Organon; Xytis; Wyeth; Forest Labs;
Indevus; Schering Plough; Janssen and Bristol-Myers Squibb; Novartis;
Takeda; Solvay; COVANCE
FX The study was sponsored by an internal fund from the Massachusetts
General Hospital Schizophrenia Program.; Dr Fan has received research
support or honoraria from Eli Lilly, AstraZeneca, Bristol-Myers Squibb,
Janssen, and Pfizer. Dr Copeland has received honoraria from Amylin, Eli
Lilly, Merck, Sanofi-Aventis, and Takeda. Dr Freudenreich has received
research support or honoraria from AstraZeneca, Bristol-Myers Squibb,
Janssen, Eli Lilly, Cephalon, and Pfizer. Dr Goff has received research
support or honoraria from Organon, Xytis, Wyeth, Forest Labs, Eli Lilly,
Pfizer, Indevus, Schering Plough, AstraZeneca, Janssen and Bristol-Myers
Squibb, Novartis, and Cephalon. Dr Henderson has received research
support or honoraria from Takeda, Bristol-Myers Squibb, Pfizer,
AstraZeneca, Eli Lilly, Solvay, Janssen, and COVANCE. Dr Liu and Ms
Chiang report no disclosures.
NR 24
TC 8
Z9 8
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD APR
PY 2011
VL 31
IS 2
BP 231
EP 234
DI 10.1097/JCP.0b013e31820ebd0e
PG 4
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 729AJ
UT WOS:000287917500016
PM 21346605
ER
PT J
AU Siddappa, NB
Hemashettar, G
Wong, YL
Lakhashe, S
Rasmussen, RA
Watkins, JD
Novembre, FJ
Villinger, F
Else, JG
Montefiori, DC
Ruprecht, RM
AF Siddappa, Nagadenahalli B.
Hemashettar, Girish
Wong, Yin Ling
Lakhashe, Samir
Rasmussen, Robert A.
Watkins, Jennifer D.
Novembre, Francis J.
Villinger, Francois
Else, James G.
Montefiori, David C.
Ruprecht, Ruth M.
TI Development of a tier 1 R5 clade C simian-human immunodeficiency virus
as a tool to test neutralizing antibody-based immunoprophylaxis
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article
DE clade C SHIV; neutralization sensitive; R5 SHIV; tier 1; vaccine
development
ID NEIGHBOR-JOINING METHOD; TYPE-1 SUBTYPE-C; CORECEPTOR SWITCH; HIV-1
INFECTION; MACAQUES; ENV; ENVELOPE; ISOLATE; TRANSMISSION; CELLS
AB Background
While some recently transmitted HIV clade C (HIV-C) strains exhibited tier 1 neutralization phenotypes, most were tier 2 strains (J Virol 2010; 84:1439). Because induction of neutralizing antibodies (nAbs) through vaccination against tier 2 viruses has proven difficult, we have generated a tier 1, clade C simian-human immunodeficiency virus (SHIV-C) to permit efficacy testing of candidate AIDS vaccines against tier 1 viruses.
Methods
SHIV-1157ipEL was created by swapping env of a late-stage virus with that of a tier 1, early form.
Results
After adaptation to rhesus macaques (RM), passaged SHIV-1157ipEL-p replicated vigorously in vitro and in vivo while maintaining R5 tropism. The virus was reproducibly transmissible intrarectally. Phylogenetically, SHIV-1157ipEL-p Env clustered with HIV-C sequences. All RM chronically infected with SHIV-1157ipEL-p developed high nAb titers against autologous as well as heterologous tier 1 strains.
Conclusions
SHIV-1157ipEL-p was reproducibly transmitted in RM, induced cross-clade nAbs, and represents a tool to evaluate anti-HIV-C nAb responses in primates.
C1 [Siddappa, Nagadenahalli B.; Hemashettar, Girish; Wong, Yin Ling; Lakhashe, Samir; Rasmussen, Robert A.; Watkins, Jennifer D.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Siddappa, Nagadenahalli B.; Lakhashe, Samir; Rasmussen, Robert A.; Watkins, Jennifer D.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA.
[Novembre, Francis J.; Villinger, Francois; Else, James G.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Novembre, Francis J.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Villinger, Francois; Else, James G.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
RP Siddappa, NB (reprint author), Dana Farber Canc Inst, JFB809,44 Binney St, Boston, MA 02115 USA.
EM nb_siddappa@dfci.harvard.edu; 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, R01 DE016013, R37
AI034266]; [RR-00165]
FX We thank Elizabeth Samit for assistance in the preparation of this
manuscript and Stephanie Ehnert, Chris Souder and Kalpana Patel for
coordinating sample collections. We thank Mahesh Bachu for help with
phylogenetic analysis. This work was supported by National Institutes of
Health grants P01 AI048240, R01 DE016013, and R37 AI034266 to R.M.R.
Base grant RR-00165 provided support to the Yerkes National Primate
Research Center.
NR 26
TC 6
Z9 6
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD APR
PY 2011
VL 40
IS 2
BP 120
EP 128
DI 10.1111/j.1600-0684.2010.00454.x
PG 9
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 729QK
UT WOS:000287965500007
PM 21044092
ER
PT J
AU Liu, XH
Manzano, G
Kim, HT
Feeley, BT
AF Liu, Xuhui
Manzano, Givenchy
Kim, Hubert T.
Feeley, Brian T.
TI A Rat Model of Massive Rotator Cuff Tears
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE rotator cuff tear; muscular atrophy; fat infiltration
ID SKELETAL-MUSCLE ATROPHY; FACTOR-KAPPA-B; FATTY INFILTRATION;
SUPRASPINATUS MUSCLE; FUNCTIONAL OUTCOMES; TENDON DETACHMENT;
SINGLE-ROW; LONG-TERM; REPAIR; DEGENERATION
AB Rotator cuff tears (RCTs) are the most common tendon injury seen in orthopedic patients. Massive RCT does not heal spontaneously and results in poor clinical outcomes. Muscle atrophy and fatty infiltration in rotator cuff muscles are major complications of chronic massive RCT and are thought to be the key factors responsible for the failure of attempted massive RCT repair. However, the pathophysiology of rotator cuff muscle atrophy and fat infiltration remains largely unknown, and no small animal model has been shown to reproduce the histologic and molecular changes seen in massive RCT. In this article, we report a novel rat massive RCT model, in which significant and consistent muscle atrophy and fat infiltration were observed in the rotator cuff muscles after rotator cuff tendon transection and denervation. The supraspinatus and infraspinatus muscle lost 25.4% and 28.9% of their wet weight 2 weeks after complete tendon transection, respectively. Six weeks after surgery, the average wet weight of supraspinatus and infraspinatus muscles decreased 13.2% and 28.3%, respectively. Significant fat infiltration was only observed in infraspinatus 6 weeks after tendon transection. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:588-595, 2011
C1 [Liu, Xuhui; Manzano, Givenchy; Kim, Hubert T.; Feeley, Brian T.] Univ Calif San Francisco Sports Med & Shoulder Su, Dept Orthoped Surg, San Francisco, CA 94153 USA.
[Liu, Xuhui; Manzano, Givenchy; Kim, Hubert T.] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA.
RP Feeley, BT (reprint author), Univ Calif San Francisco Sports Med & Shoulder Su, Dept Orthoped Surg, 1500 Owens Ave, San Francisco, CA 94153 USA.
EM feeleyb@orthosurg.ucsf.edu
FU Orthopaedic Research & Education Foundation
FX This work was supported by the Orthopaedic Research & Education
Foundation. The authors have no personal or financial affiliations that
may have biased the presentation.
NR 42
TC 41
Z9 41
U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0736-0266
J9 J ORTHOP RES
JI J. Orthop. Res.
PD APR
PY 2011
VL 29
IS 4
BP 588
EP 595
DI 10.1002/jor.21266
PG 8
WC Orthopedics
SC Orthopedics
GA 731LV
UT WOS:000288109300018
PM 20949443
ER
PT J
AU Samelson, EJ
Christiansen, BA
Demissie, S
Broe, KE
Zhou, Y
Meng, CA
Yu, W
Cheng, X
O'Donnell, CJ
Hoffmann, U
Genant, HK
Kiel, DP
Bouxsein, ML
AF Samelson, E. J.
Christiansen, B. A.
Demissie, S.
Broe, K. E.
Zhou, Y.
Meng, C. A.
Yu, W.
Cheng, X.
O'Donnell, C. J.
Hoffmann, U.
Genant, H. K.
Kiel, D. P.
Bouxsein, M. L.
TI Reliability of vertebral fracture assessment using multidetector CT
lateral scout views: the Framingham Osteoporosis Study
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Computed tomography; Lateral scout; Reliability; Scoutviews;
Semiquantitative; Vertebral fracture
ID X-RAY ABSORPTIOMETRY; COMPUTED-TOMOGRAPHY; PREVALENCE; WOMEN; HEART;
IDENTIFICATION; RECOGNITION; RADIOGRAPHY; DIAGNOSIS; DEFORMITIES
AB Two radiologists evaluated images of the spine from computed tomography (CT) scans on two occasions to diagnose vertebral fracture in 100 individuals. Agreement was fair to good for mild fractures, and agreement was good to excellent for more severe fractures. CT scout views are useful to assess vertebral fracture.
We investigated inter-reader agreement between two radiologists and intra-reader agreement between duplicate readings for each radiologist, in assessment of vertebral fracture using a semi-quantitative method from lateral scout views obtained by CT.
Participants included 50 women and 50 men (age 50-87 years, mean 70 years) in the Framingham Study. T4-L4 vertebrae were assessed independently by two radiologists on two occasions using a semi-quantitative scale as normal, mild, moderate, or severe fracture.
Vertebra-specific prevalence of grade a parts per thousand yen1 (mild) fracture ranged from 3% to 5%. We found fair (kappa = 56-59%) inter-reader agreement for grade a parts per thousand yen1 vertebral fractures and good (kappa = 68-72%) inter-reader agreement for grade a parts per thousand yen2 fractures. Intra-reader agreement for grade a parts per thousand yen1 vertebral fracture was fair (kappa = 55%) for one reader and excellent for another reader (kappa = 77%), whereas intra-reader agreement for grade a parts per thousand yen2 vertebral fracture was excellent for both readers (kappa = 76% and 98%). Thoracic vertebrae were more difficult to evaluate than the lumbar region, and agreement was lowest (inter-reader kappa = 43%) for fracture at the upper (T4-T9) thoracic levels and highest (inter-reader kappa = 76-78%) for the lumbar spine (L1-L4).
Based on a semi-quantitative method to classify vertebral fractures using CT scout views, agreement within and between readers was fair to good, with the greatest source of variation occurring for fractures of mild severity and for the upper thoracic region. Agreement was good to excellent for fractures of at least moderate severity. Lateral CT scout views can be useful in clinical research settings to assess vertebral fracture.
C1 [Samelson, E. J.; O'Donnell, C. J.; Hoffmann, U.; Kiel, D. P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Samelson, E. J.; Broe, K. E.; Meng, C. A.; Kiel, D. P.] Inst Aging Res Boston, Boston, MA USA.
[Christiansen, B. A.; Bouxsein, M. L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA 02215 USA.
[Christiansen, B. A.; Bouxsein, M. L.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA.
[Christiansen, B. A.] Univ Calif Davis, Dept Orthopaed, Sacramento, CA 95817 USA.
[Demissie, S.; Zhou, Y.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Yu, W.] Beijing Union Med Coll Hosp, Beijing, Peoples R China.
[Cheng, X.] Beijing Ji Shui Tan Hosp, Beijing, Peoples R China.
[O'Donnell, C. J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Hoffmann, U.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Genant, H. K.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
[Genant, H. K.] Synarc Inc, San Francisco, CA USA.
RP Samelson, EJ (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
EM Samelson@hrca.harvard.edu; bchristiansen@ucdavis.edu; demissie@bu.edu;
broe@hrca.harvard.edu; zyanhua@bu.edu; Ching-AnMeng@hrca.harvard.edu;
weiyu5508@yahoo.com; xiao65@263.net; codonnell@nih.gov;
uhoffmann@partners.org; harry.genant@ucsf.edu; kiel@hrca.harvard.edu;
mbouxsei@bidmc.harvard.edu
RI Christiansen, Blaine/F-9021-2010;
OI Kiel, Douglas/0000-0001-8474-0310
FU NIH [R01AR053986, R01AR/AG041398, K01 AR053118, T32 AG023480]; National
Heart, Lung, and Blood Institute (NHLBI) (NIH/NHLBI) [N01-HC-25195]
FX This work was supported by NIH R01AR053986, R01AR/AG041398, K01
AR053118, T32 AG023480, and by the National Heart, Lung, and Blood
Institute (NHLBI) Framingham Heart Study (NIH/NHLBI Contract
N01-HC-25195).
NR 45
TC 17
Z9 20
U1 0
U2 1
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD APR
PY 2011
VL 22
IS 4
BP 1123
EP 1131
DI 10.1007/s00198-010-1290-6
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 728DN
UT WOS:000287854500012
PM 20495902
ER
PT J
AU Landman, AB
Rokos, IC
Burns, K
Van Gelder, CM
Fisher, RM
Dunford, JV
Cone, DC
Bogucki, S
AF Landman, Adam B.
Rokos, Ivan C.
Burns, Kevin
Van Gelder, Carin M.
Fisher, Roger M.
Dunford, James V.
Cone, David C.
Bogucki, Sandy
TI AN OPEN, INTEROPERABLE, AND SCALABLE PREHOSPITAL INFORMATION TECHNOLOGY
NETWORK ARCHITECTURE
SO PREHOSPITAL EMERGENCY CARE
LA English
DT Article
DE emergency medical services communication systems; emergency medical
services; information management; computer communication networks
ID ELEVATION MYOCARDIAL-INFARCTION; TO-BALLOON TIME; HOSPITAL
CARDIAC-ARREST; STANDARDIZED COMMUNICATION; SYNDROMIC SURVEILLANCE;
MEDICINE PROJECT; UTSTEIN STYLE; EMERGENCY; SYSTEMS; INTEGRATION
AB Some of the most intractable challenges in prehospital medicine include response time optimization, inefficiencies at the emergency medical services (EMS)-emergency department (ED) interface, and the ability to correlate field interventions with patient outcomes. Information technology (IT) can address these and other concerns by ensuring that system and patient information is received when and where it is needed, is fully integrated with prior and subsequent patient information, and is securely archived. Some EMS agencies have begun adopting information technologies, such as wireless transmission of 12-lead electrocardiograms, but few agencies have developed a comprehensive plan for management of their prehospital information and integration with other electronic medical records. This perspective article highlights the challenges and limitations of integrating IT elements without a strategic plan, and proposes an open, interoperable, and scalable prehospital information technology (PHIT) architecture. The two core components of this PHIT architecture are 1) routers with broadband network connectivity to share data between ambulance devices and EMS system information services and 2) an electronic patient care report to organize and archive all electronic prehospital data. To successfully implement this comprehensive PHIT architecture, data and technology requirements must be based on best available evidence, and the system must adhere to health data standards as well as privacy and security regulations. Recent federal legislation prioritizing health information technology may position federal agencies to help design and fund PHIT architectures.
C1 [Landman, Adam B.] Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06520 USA.
[Landman, Adam B.; Burns, Kevin; Van Gelder, Carin M.; Cone, David C.; Bogucki, Sandy] Yale Univ, Dept Emergency Med, Sch Med, New Haven, CT 06520 USA.
[Landman, Adam B.] US Dept Vet Affairs, West Haven, CT USA.
[Rokos, Ivan C.] Olive View UCLA Med Ctr, Dept Emergency Med, Sylmar, CA 91342 USA.
[Fisher, Roger M.] San Diego Med Serv, San Diego, CA USA.
[Dunford, James V.] Univ Calif San Diego, Dept Emergency Med, San Diego Med Ctr, La Jolla, CA 92093 USA.
RP Landman, AB (reprint author), Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, 333 Cedar St,IE 61 SHM,POB 208088, New Haven, CT 06520 USA.
EM adam.landman@yahoo.com
OI Cone, David/0000-0002-7437-959X; Landman, Adam/0000-0002-2166-0521
FU US Department of Veterans Affairs; Robert Wood Johnson Foundation
FX Dr. Landman is a Robert Wood Johnson Foundation Clinical Scholar at Yale
University, supported by the US Department of Veterans Affairs and the
Robert Wood Johnson Foundation.
NR 48
TC 8
Z9 8
U1 0
U2 15
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1090-3127
J9 PREHOSP EMERG CARE
JI Prehosp. Emerg. Care
PD APR-JUN
PY 2011
VL 15
IS 2
BP 149
EP 157
DI 10.3109/10903127.2010.534235
PG 9
WC Emergency Medicine; Public, Environmental & Occupational Health
SC Emergency Medicine; Public, Environmental & Occupational Health
GA 729FG
UT WOS:000287933400002
PM 21294627
ER
PT J
AU Coppadoro, A
Berra, L
Bigatello, LM
AF Coppadoro, Andrea
Berra, Lorenzo
Bigatello, Luca M.
TI Modifying endotracheal tubes to prevent ventilator-associated pneumonia
SO CURRENT OPINION IN INFECTIOUS DISEASES
LA English
DT Review
DE aspiration pneumonia; biofilm; endotracheal tube coating; endotracheal
tube cuff; ventilator-associated pneumonia
ID SUBGLOTTIC SECRETION DRAINAGE; REDUCES PULMONARY ASPIRATION; TRACHEAL
TUBE; BACTERIAL-COLONIZATION; FLUID LEAKAGE; MUCUS SHAVER; CUFF;
POLYURETHANE; TRIAL; BIOFILM
AB Purpose of review
The endotracheal tube (ETT) is the main avenue leading to airway contamination and subsequent ventilator-associated pneumonia (VAP) during mechanical ventilation. A number of modifications to the ETT are available, aimed at reducing the incidence of VAP. We review here available systems and devices, and clinical data regarding their efficacy.
Recent findings
Three main modifications of ETTs have been developed: coating with antimicrobials, adding a suction channel for the removal of oro-pharyngeal secretions, and modifying the design of the cuff. Each of these interventions has been shown to limit bacterial colonization of the distal airways and to decrease the incidence of VAP. Data on their ultimate effect on related clinical outcomes are still lacking.
Summary
Modifications of ETTs aimed at decreasing the onset of VAP show promising results. However, the lack of a significant effect on outcomes prompts us to use caution before recommending their widespread use.
C1 [Bigatello, Luca M.] VA Boston Healthcare Syst, Anesthesia & Crit Care Serv, W Roxbury, MA 02132 USA.
[Coppadoro, Andrea; Berra, Lorenzo; Bigatello, Luca M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Coppadoro, Andrea] Univ Milano Bicocca, Dipartimento Med Sperimentale, Milan, Italy.
RP Bigatello, LM (reprint author), VA Boston Healthcare Syst, Anesthesia & Crit Care Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM luca.bigatello@va.gov
FU Covidien
FX A.C. has no conflict of interest to declare. L. B. has no conflict of
interest to declare. L. M. B. has received a consulting fee from
Covidien.
NR 39
TC 7
Z9 8
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7375
J9 CURR OPIN INFECT DIS
JI Curr. Opin. Infect. Dis.
PD APR
PY 2011
VL 24
IS 2
BP 157
EP 162
DI 10.1097/QCO.0b013e328343b733
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 726BO
UT WOS:000287693500013
PM 21252657
ER
PT J
AU Messou, E
Chaix, ML
Gabillard, D
Minga, A
Losina, E
Yapo, V
Kouakou, M
Danel, C
Sloan, C
Rouzioux, C
Freedberg, KA
Anglaret, X
AF Messou, Eugene
Chaix, Marie-Laure
Gabillard, Delphine
Minga, Albert
Losina, Elena
Yapo, Vincent
Kouakou, Martial
Danel, Christine
Sloan, Caroline
Rouzioux, Christine
Freedberg, Kenneth A.
Anglaret, Xavier
TI Association Between Medication Possession Ratio, Virologic Failure and
Drug Resistance in HIV-1-Infected Adults on Antiretroviral Therapy in
Cote d'Ivoire
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
ID HIV-INFECTED ADULTS; SUB-SAHARAN AFRICA; ADHERENCE; ABIDJAN; STRAINS;
OUTCOMES; DETERMINANTS; ASSESSMENTS; PERFORMANCE; PROGRESSION
AB Background: Adherence is a strong determinant of viral suppression with antiretroviral therapy (ART) but measuring it is challenging. Medication delivery can be measured accurately in settings with computerized prescription databases. We studied the association between medication possession ratio (MPR), virologic suppression, and resistance to ART in Cote d'Ivoire.
Methods: We conducted a prospective cohort study of HIV-1-infected adults initiating ART in 3 clinics using computerized monitoring systems. Patients had viral load (VL) tests at month 6 (M6) and month 12 (M12) after ART initiation and genotype tests if VL was detectable (>= 300 copies/mL). MPR was defined as the number of daily doses of antiretroviral drug actually provided divided by the total number of follow-up days since ART initiation.
Results: Overall, 1573 patients started ART with stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M6 and M12, 996 and 942 patients were in active follow-up; 20% (M6) and 25% (M12) of patients had detectable VL, including 7% (M6) and 11% (M12) with >= 1 resistance mutation. Among patients with MPR of >= 95%, 80%-94%, 65%-79%, 50%-64%, and <50% at M12, the proportion with detectable VL [resistance] was 9% [4%], 17% [7%], 45% [24%], 67% [31%], and 85% [37%]. Among patients with >= 1 mutation at M12, 86% were resistant to lamivudine/emtricitabine and/or nevirapine/efavirenz but not to other drugs.
Conclusions: MPR was strongly associated with virologic outcomes. Half of those with detectable VL at M12 had no resistance mutations. MPR should be used at M6 to identify patients who might benefit from early interventions to reinforce adherence.
C1 [Messou, Eugene; Gabillard, Delphine; Minga, Albert; Danel, Christine; Anglaret, Xavier] Univ Bordeaux, INSERM, U897, Bordeaux, France.
[Messou, Eugene; Gabillard, Delphine; Minga, Albert; Yapo, Vincent; Kouakou, Martial; Danel, Christine; Sloan, Caroline; Anglaret, Xavier] Programme PAC CI ANRS, Abidjan, Cote Ivoire.
[Chaix, Marie-Laure; Rouzioux, Christine] Univ Paris 05, EA 3620, Paris, France.
[Chaix, Marie-Laure; Rouzioux, Christine] CHU Necker, AP HP, Virol Lab, Paris, France.
[Losina, Elena; Freedberg, Kenneth A.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA.
[Yapo, Vincent] CHU Treichville, CeDReS, Abidjan, Cote Ivoire.
RP Anglaret, X (reprint author), Univ Bordeaux 2, INSERM, Unite 897, 146 Rue Leo Saignat, F-33076 Bordeaux, France.
EM xavier.anglaret@isped.u-bordeaux2.fr
RI Anglaret, Xavier/F-7333-2013
FU Agence Nationale de Recherches sur le SIDA et les hepatitis virales
[ANRS 12136, ANRS 12212]; National Institute of Allergy and Infectious
Diseases [R01 AI058736, K24 AI062476]; Institute of International
Education
FX Supported by the Agence Nationale de Recherches sur le SIDA et les
hepatitis virales (ANRS 12136, ANRS 12212), the National Institute of
Allergy and Infectious Diseases (R01 AI058736, K24 AI062476), and the
Institute of International Education Fulbright (Fellowship CS).
NR 38
TC 30
Z9 31
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2011
VL 56
IS 4
BP 356
EP 364
DI 10.1097/QAI.0b013e3182084b5a
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 726QH
UT WOS:000287740700019
PM 21191309
ER
PT J
AU Bogoch, II
Andrews, JR
Marty, FM
Hohmann, EL
AF Bogoch, Isaac I.
Andrews, Jason R.
Marty, Francisco M.
Hohmann, Elizabeth L.
TI HIV-1 and 2009 H1N1 Influenza A in Adults
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Letter
C1 [Bogoch, Isaac I.; Andrews, Jason R.; Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Bogoch, Isaac I.; Andrews, Jason R.; Marty, Francisco M.; Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Boston, MA USA.
[Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
RP Bogoch, II (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD APR
PY 2011
VL 56
IS 4
BP E111
EP E113
DI 10.1097/QAI.0b013e31820a9afb
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 726QH
UT WOS:000287740700003
PM 21350357
ER
PT J
AU Hirano, AA
Brandstatter, JH
Morgans, CW
Brecha, NC
AF Hirano, Arlene A.
Brandstaetter, Johann Helmut
Morgans, Catherine W.
Brecha, Nicholas C.
TI SNAP25 Expression in Mammalian Retinal Horizontal Cells
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE SNARE complex; exocytosis; immunocytochemistry; retina; vision
ID SYNAPTOSOMAL-ASSOCIATED PROTEIN; CALCIUM-BINDING PROTEINS;
ACTIVITY-DEPENDENT PHOSPHORYLATION; ACID TRANSPORTER EXPRESSION;
VESICULAR GABA TRANSPORTER; SYNAPTIC CORE COMPLEX; MACAQUE MONKEY
RETINA; T-SNARE SNAP-25; RIBBON SYNAPSES; DIFFERENTIAL EXPRESSION
AB Horizontal cells mediate inhibitory feedforward and feedback lateral interactions in the outer retina at photoreceptor terminals and bipolar cell dendrites; however, the mechanisms that underlie synaptic transmission from mammalian horizontal cells are poorly understood. The localization of a vesicular gamma-aminobutyric acid (GABA) transporter (VGAT) to horizontal cell processes in primate and rodent retinae suggested that mammalian horizontal cells release transmitter in a vesicular manner. Toward determining whether the molecular machinery for vesicular transmitter release is present in horizontal cells, we investigated the expression of SNAP25 (synaptosomal-associated protein of 25 kDa), a key SNARE protein, by immunocytochemistry with cell type-specific markers in the retinae of mouse, rat, rabbit, and monkey. Different commercial antibodies to SNAP25 were tested on vertical sections of retina. We report the robust expression of SNAP25 in both plexiform layers. Double labeling with SNAP25 and calbindin antibodies demonstrated that horizontal cell processes and their endings in photoreceptor triad synapses were strongly labeled for both proteins in mouse, rat, rabbit, and monkey retinae. Double labeling with parvalbumin antibodies in monkey retina verified SNAP25 immunoreactivity in all horizontal cells. Pre-embedding immunoelectron microscopy in rabbit retina confirmed expression of SNAP25 in lateral elements within photoreceptor triad synapses. The SNAP25 immunoreactivity in the plexiform layers and outer nuclear layer fell into at least three patterns depending on the antibody, suggesting a differential distribution of SNAP25 isoforms. The presence of SNAP25a and SNAP25b isoforms in mouse retina was established by reverse transcriptase-polymerase chain reaction. SNAP25 expression in mammalian horizontal cells along with other SNARE proteins is consistent with vesicular exocytosis. J. Comp. Neurol. 519:972-988, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [Hirano, Arlene A.; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA.
[Hirano, Arlene A.; Brecha, Nicholas C.] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA 90073 USA.
[Brandstaetter, Johann Helmut] Univ Erlangen Nurnberg, Dept Biol, D-91508 Erlangen, Germany.
[Morgans, Catherine W.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97239 USA.
RP Hirano, AA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, 10833 Le Conte Ave,Box 951763, Los Angeles, CA 90095 USA.
EM ahirano@mednet.ucla.edu
FU National Institutes of Health [EY15573]; Veterans Administration;
University of California-Los Angeles; German Research Foundation [BR
1643/4-1]
FX Grant sponsor: National Institutes of Health; Grant number: EY15573;
Grant sponsors: Veterans Administration Career Scientist Award;
University of California-Los Angeles Stein-Oppenheimer Award (to
N.C.B.); German Research Foundation; Grant number: BR 1643/4-1 (to
J.H.B.).
NR 113
TC 23
Z9 23
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD APR
PY 2011
VL 519
IS 5
BP 972
EP 988
DI 10.1002/cne.22562
PG 17
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 719MR
UT WOS:000287209400010
PM 21280047
ER
PT J
AU Wang, Q
Wu, PC
Roberson, RS
Luk, BV
Ivanova, I
Chu, E
Wu, DY
AF Wang, Qin
Wu, Peter C.
Roberson, Rachel S.
Luk, Belinda V.
Ivanova, Iana
Chu, Elizabeth
Wu, Daniel Y.
TI Survivin and escaping in therapy-induced cellular senescence
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE survivin; accelerated senescence; Cdc2/Cdk1
ID GERANYLGERANYLTRANSFERASE-I INHIBITOR; TERMINAL PROLIFERATION ARREST;
LUNG-CANCER CELLS; TUMOR-CELLS; MITOTIC CATASTROPHE; CARCINOMA-CELLS;
DNA-DAMAGE; APOPTOSIS; PHOSPHORYLATION; EXPRESSION
AB Therapy-induced accelerated cellular senescence (ACS) is a reversible tumor response to chemotherapy that is likely detrimental to the overall therapeutic efficacy of cancer treatment. To further understand the mechanism by which cancer cells can escape the sustained cell cycle arrest in ACS, we established a tissue culture model, in which the p53-null NCI-H1299 cells can be induced into senescence by an abbreviated exposure to a chemotherapeutic agent. Previously, we have reported that senescent cells overexpress Cdc2/Cdk1 when they bypassed the prolonged arrest and their viability is dependent on Cdc2/Cdk1 kinase activity. In our study, we show that human survivin is the immediate downstream effector of the Cdc2/Cdk1 mediated survival signal. Survivin cooperates with Cdc2/Cdk1 to inhibit apoptosis following chemotherapy and promote senescence escape. Using HIV-1 TAT peptides to disrupt survivin phosphorylation by Cdc2/Cdk1, we also found that phosphorylated survivin is necessary both for the escape of senescent cells and for maintenance of subsequent viability after bypassing senescence. These results further propose survivin as an important determinant of senescence reversibility and as a putative molecular target to enforce cell death in ACS.
C1 [Wang, Qin; Wu, Peter C.; Roberson, Rachel S.; Luk, Belinda V.; 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.
[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 proteinss@hotmail.com
FU National Cancer Institute [R01-CA113892-01]
FX Grant sponsor: National Cancer Institute; Grant number: R01-CA113892-01
NR 41
TC 24
Z9 27
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD APR 1
PY 2011
VL 128
IS 7
BP 1546
EP 1558
DI 10.1002/ijc.25482
PG 13
WC Oncology
SC Oncology
GA 718XI
UT WOS:000287159400005
PM 20503268
ER
PT J
AU Saboo, SS
Krajewski, KM
Jagannathan, JP
O'Regan, KN
Odze, R
Ramaiya, N
Wolpin, BM
AF Saboo, Sachin S.
Krajewski, Katherine M.
Jagannathan, Jyothi P.
O'Regan, Kevin N.
Odze, Robert
Ramaiya, Nikhil
Wolpin, Brian M.
TI Rapid progression of combined hepatocellular carcinoma and
cholangiocarcinoma
SO CANCER IMAGING
LA English
DT Article
DE Combined hepatocellular carcinoma and cholangiocarcinoma; MRI
ID CLINICOPATHOLOGICAL FEATURES; COMPUTED-TOMOGRAPHY; PROGNOSTIC-FACTORS;
GEMCITABINE; CANCER; CT
AB Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is a rare entity comprising 1 - 14.2% of all primary liver carcinomas. In this report, we present a case of rapid progression of cHCC-CC, a rare tumor in a 77-year-old Caucasian male patient with hepatitis B-induced cirrhosis, moderately elevated alpha fetoprotein, and imaging and pathologic features of a mixed liver tumor. There was no evidence of metastatic disease in the chest, abdomen or pelvis by computed tomography (CT) scan at the time of diagnosis. Needle biopsy of the segment 8 lesion revealed two discrete histologic components to the tumor: well-differentiated HCC and poorly differentiated adenocarcinoma, consistent with intrahepatic CC. The patient rapidly developed metastatic disease after initial local therapy with hepatic arterial chemoembolization and percutaneous cryoablation, dying within 5 months of diagnosis. Radiofrequency ablation, cryoablation and radioembolization with yttrium-90 microspheres remain possible treatment strategies for patients with cHCC-CC unable to undergo surgical resection. The diagnosis and treatment of cHCC-CC can be challenging due to clinical, imaging and histological features that overlap with pure HCC and CC.
C1 [Saboo, Sachin S.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; O'Regan, Kevin N.; Ramaiya, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
[Odze, Robert] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Wolpin, Brian M.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Saboo, SS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA.
EM ssaboo@partners.org
NR 25
TC 3
Z9 3
U1 0
U2 1
PU E-MED
PI LONDON
PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND
SN 1470-7330
J9 CANCER IMAGING
JI Cancer Imaging
PD MAR 31
PY 2011
VL 11
IS 1
BP 37
EP 41
DI 10.1102/1470-7330.2011.0009
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 826DA
UT WOS:000295330400001
PM 21507775
ER
PT J
AU Reeves, RK
Evans, TI
Gillis, J
Wong, FE
Connole, M
Carville, A
Johnson, RP
AF Reeves, R. Keith
Evans, Tristan I.
Gillis, Jacqueline
Wong, Fay E.
Connole, Michelle
Carville, Angela
Johnson, R. Paul
TI Quantification of mucosal mononuclear cells in tissues with a
fluorescent bead-based polychromatic flow cytometry assay
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Fluorescent beads; Lymphocyte enumeration; Flow cytometry; Mucosal
lymphocytes
ID SIV INFECTION; LYMPHOCYTE; BLOOD; GUT
AB Since the vast majority of infections occur at mucosal surfaces, accurate characterization of mucosal immune cells is critically important for understanding transmission and control of infectious diseases. Standard flow cytometric analysis of cells obtained from mucosal tissues can provide valuable information on the phenotype of mucosal leukocytes and their relative abundance, but does not provide absolute cell counts of mucosal cell populations. We developed a bead-based flow cytometry assay to determine the absolute numbers of multiple mononuclear cell types in colorectal biopsies of rhesus macaques. Using 10-color flow cytometry panels and pan-fluorescent beads, cells were enumerated in biopsy specimens by adding a constant ratio of beads per mg of tissue and then calculating cell numbers/mg of tissue based on cell-to-bead ratios determined at the time of sample acquisition. Testing in duplicate specimens showed the assay to be highly reproducible (Spearman R=0.9476, P<0.0001). Using this assay, we report enumeration of total CD45(+) leukocytes, CD4(+) and CD8(+) T cells, B cells, NK cells, CD14(+) monocytes, and myeloid and plasmacytoid dendritic cells in colorectal biopsies, with cell numbers in normal rhesus macaques varying from medians of 4486 cells/mg (T cells) to 3 cells/mg (plasmacytoid dendritic cells). This assay represents a significant advancement in rapid, accurate quantification of mononuclear cell populations in mucosal tissues and could be applied to provide absolute counts of a variety of different cell populations in diverse tissues. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Reeves, R. Keith; Evans, Tristan I.; Gillis, Jacqueline; Wong, Fay E.; Connole, Michelle; Johnson, R. Paul] Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA.
[Johnson, R. Paul] Massachusetts Gen Hosp, Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Boston, MA 02115 USA.
[Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA.
RP Johnson, RP (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA.
EM paul_johnson@hms.harvard.edu
FU NIH [AI071306, AI090735, RR00168]; CHAVI/HVTN Early Career Investigator
award [U19 AI 067854-04]
FX The authors thank Elaine Roberts for dedicated animal care and Yi Yu for
quality technical assistance. This work was supported through NIH grants
AI071306, AI090735, and RR00168, and a CHAVI/HVTN Early Career
Investigator award, grant number U19 AI 067854-04, to R.K.R.
NR 10
TC 4
Z9 4
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD MAR 31
PY 2011
VL 367
IS 1-2
BP 95
EP 98
DI 10.1016/j.jim.2011.02.002
PG 4
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 767CV
UT WOS:000290833800012
PM 21315723
ER
PT J
AU Eccles, MP
Weijer, C
Mittman, B
AF Eccles, Martin P.
Weijer, Charles
Mittman, Brian
TI Requirements for ethics committee review for studies submitted to
Implementation Science
SO IMPLEMENTATION SCIENCE
LA English
DT Editorial Material
AB The requirement for ethics review of studies submitted to Implementation Science has been unclear. Therefore, in this editorial, we set out our requirements for ethics committee review of experimental and non-experimental studies. For any study that meets the criteria of human subject research (which includes research on healthcare providers), irrespective of study design, we will require proof of either satisfactory ethics committee review or of the granting of an official exemption or waiver.
C1 [Eccles, Martin P.] Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
[Weijer, Charles] Univ Western Ontario, Rotman Inst Philosophy, London, ON N6A 5B6, Canada.
[Mittman, Brian] VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support, Sepulveda, CA 91343 USA.
RP Eccles, MP (reprint author), Inst Hlth & Soc, Baddiley Clark Bldg, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
EM martin.eccles@ncl.ac.uk
OI Mittman, Brian/0000-0003-3589-9178
NR 3
TC 2
Z9 2
U1 0
U2 5
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 31
PY 2011
VL 6
AR 32
DI 10.1186/1748-5908-6-32
PG 3
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 749NN
UT WOS:000289475200001
PM 21453451
ER
PT J
AU Holodniy, M
Brown, ST
Cameron, DW
Kyriakides, TC
Angus, B
Babiker, A
Singer, J
Owens, DK
Anis, A
Goodall, R
Hudson, F
Piaseczny, M
Russo, J
Schechter, M
Deyton, L
Darbyshire, J
AF Holodniy, Mark
Brown, Sheldon T.
Cameron, D. William
Kyriakides, Tassos C.
Angus, Brian
Babiker, Abdel
Singer, Joel
Owens, Douglas K.
Anis, Aslam
Goodall, Ruth
Hudson, Fleur
Piaseczny, Mirek
Russo, John
Schechter, Martin
Deyton, Lawrence
Darbyshire, Janet
CA OPTIMA Team
TI Results of Antiretroviral Treatment Interruption and Intensification in
Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial
SO PLOS ONE
LA English
DT Article
ID STRUCTURED TREATMENT INTERRUPTION; QUALITY-OF-LIFE; CROSS-RESISTANCE;
CLINICAL PROGRESSION; VIROLOGICAL FAILURE; MEGA-HAART; COHORT; THERAPY;
INHIBITORS; VIRUS
AB Background: Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting.
Methods and Findings: We conducted a 262 factorial randomized open label controlled trial in patients with a CD4 count <= 300 cells/mu l who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (<= 4 ARVs) or intensive (>= 5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/mu l, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options.
Conclusions: We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options.
C1 [Holodniy, Mark; Owens, Douglas K.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
[Holodniy, Mark; Owens, Douglas K.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY USA.
[Brown, Sheldon T.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Cameron, D. William] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
[Cameron, D. William; Singer, Joel; Anis, Aslam; Piaseczny, Mirek; Schechter, Martin] St Pauls Hosp, Canadian HIV Trials Network, Vancouver, BC V6Z 1Y6, Canada.
[Kyriakides, Tassos C.; Russo, John] VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA.
[Angus, Brian] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England.
[Babiker, Abdel; Goodall, Ruth; Hudson, Fleur; Darbyshire, Janet] MRC Clin Trials Unit, London, England.
[Deyton, Lawrence] Off Publ Hlth & Environm Hazards, Dept Vet Affairs, Washington, DC USA.
RP Holodniy, M (reprint author), VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
EM bcameron@ohri.ca
OI Schechter, Martin/0000-0001-6063-2155; Angus, Brian/0000-0003-3598-7784;
Cameron, Bill/0000-0002-0090-3539; Goodall, Ruth/0000-0003-0622-5035
FU Ontario Ministry of Health/Ontario HIV Treatment Network; CIHR Canadian
HIV Trials Network, Canada
FX DWC is supported with a Career Scientist Award of the Ontario Ministry
of Health/Ontario HIV Treatment Network. The study was supported in part
in Canada through the CIHR Canadian HIV Trials Network. The study
funders (MRC-UK, VACSP, CIHR) reviewed and approved the design and
conduct of the trial, with external expert reviewers who were
represented on the Trial Steering Committee. The OPTIMA Writing
Committee and the OPTIMA team had full access to the statistical report
and to the study data by request and the Writing Committee had final
responsibility for the submitted manuscript. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 30
TC 14
Z9 14
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 31
PY 2011
VL 6
IS 3
AR e14764
DI 10.1371/journal.pone.0014764
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YU
UT WOS:000289057200001
PM 21483491
ER
PT J
AU Watkins, JD
Siddappa, NB
Lakhashe, SK
Humbert, M
Sholukh, A
Hemashettar, G
Wong, YL
Yoon, JK
Wang, W
Novembre, FJ
Villinger, F
Ibegbu, C
Patel, K
Corti, D
Agatic, G
Vanzetta, F
Bianchi, S
Heeney, JL
Sallusto, F
Lanzavecchia, A
Ruprecht, RM
AF Watkins, Jennifer D.
Siddappa, Nagadenahalli B.
Lakhashe, Samir K.
Humbert, Michael
Sholukh, Anton
Hemashettar, Girish
Wong, Yin Ling
Yoon, John K.
Wang, Wendy
Novembre, Francis J.
Villinger, Francois
Ibegbu, Chris
Patel, Kalpana
Corti, Davide
Agatic, Gloria
Vanzetta, Fabrizia
Bianchi, Siro
Heeney, Jonathan L.
Sallusto, Federica
Lanzavecchia, Antonio
Ruprecht, Ruth M.
TI An Anti-HIV-1 V3 Loop Antibody Fully Protects Cross-Clade and Elicits
T-Cell Immunity in Macaques Mucosally Challenged with an R5 Clade C SHIV
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES;
MONOCLONAL-ANTIBODIES; CHIMERIC VIRUS; HIV-1 VACCINE; TRANSMISSION;
IMMUNIZATION; INFECTION; GP120; TRIAL
AB Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant form (CRF). HGN194 targets an epitope in the third hypervariable loop (V3) of HIV-1 gp120 and neutralizes a range of relatively neutralization-sensitive and resistant viruses. We evaluated the potential of HGN194 to protect infant rhesus monkeys against a SHIV encoding a primary CCR5-tropic HIV-1 clade C envelope. After high-dose mucosal challenge, all untreated controls became highly viremic while all HGN194-treated animals (50 mg/kg) were completely protected. When HGN194 was given at 1 mg/kg, one out of two monkeys remained aviremic, whereas the other had delayed, lower peak viremia. Interestingly, all protected monkeys given high-dose HGN194 developed Gagspecific proliferative responses of both CD4+ and CD8+ T cells. To test whether generation of the latter involved cryptic infection, we ablated CD8+ cells after HGN194 clearance. No viremia was detected in any protected monkeys, thus ruling out virus reservoirs. Thus, induction of CD8 T-cell immunity may have resulted from transient `` Hit and Run'' infection or cross priming via Ag-Ab-mediated cross-presentation. Together, our data identified the HGN194 epitope as protective and provide proof-of-concept that this anti-V3 loop mAb can prevent infection with sterilizing immunity after challenge with virus of a different clade, implying that V3 is a potential vaccine target.
C1 [Watkins, Jennifer D.; Siddappa, Nagadenahalli B.; Lakhashe, Samir K.; Humbert, Michael; Sholukh, Anton; Hemashettar, Girish; Wong, Yin Ling; Yoon, John K.; Wang, Wendy; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Watkins, Jennifer D.; Siddappa, Nagadenahalli B.; Lakhashe, Samir K.; Humbert, Michael; Sholukh, Anton; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA.
[Novembre, Francis J.; Villinger, Francois; Ibegbu, Chris; Patel, Kalpana] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Novembre, Francis J.] Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Corti, Davide; Agatic, Gloria; Vanzetta, Fabrizia; Bianchi, Siro] Humabs SAGL, Bellinzona, Switzerland.
[Heeney, Jonathan L.] Univ Cambridge, Dept Vet Med, Cambridge, England.
[Sallusto, Federica; Lanzavecchia, Antonio] Inst Res Biomed, Bellinzona, Switzerland.
RP Watkins, JD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM ruth_ruprecht@dfci.harvard.edu
RI Lakhashe, Samir/F-1150-2014;
OI Byrareddy, Siddappa /0000-0002-7423-1763; Heeney,
Jonathan/0000-0003-2702-1621; Bianchi, Siro/0000-0002-5100-8905
FU National Institutes of Health [R37 AI34266, P01 AI48240]; Bill and
Melinda Gates Foundation [38637]; Center For AIDS Research Immunology
Core [P30 A01050409]; [RR-00165]
FX This work was supported in part by National Institutes of Health grant
R37 AI34266 and P01 AI48240 to RMR, by the Bill and Melinda Gates
Foundation Collaboration for AIDS Vaccine Discovery (CAVD) UCL-VDC
(Weiss) grant 38637, and by Center For AIDS Research Immunology Core P30
A01050409. Base grant RR-00165 provided support to the Yerkes National
Primate Research Center. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 26
TC 45
Z9 45
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 31
PY 2011
VL 6
IS 3
AR e18207
DI 10.1371/journal.pone.0018207
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YU
UT WOS:000289057200043
PM 21483815
ER
PT J
AU Abel, GA
AF Abel, Gregory A.
TI The real world: CLL
SO BLOOD
LA English
DT Editorial Material
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SEER-MEDICARE DATA; CANCER-TREATMENT
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Abel, GA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 11
TC 2
Z9 2
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 31
PY 2011
VL 117
IS 13
BP 3481
EP 3482
PG 2
WC Hematology
SC Hematology
GA 743EH
UT WOS:000288999800003
PM 21454464
ER
PT J
AU Morgan, BA
AF Morgan, Bruce A.
TI DEVELOPMENTAL BIOLOGY A hair-raising tale
SO NATURE
LA English
DT Editorial Material
ID FOLLICLE STEM-CELLS; NICHE
C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
EM bruce.morgan@cbrc2.mgh.harvard.edu
FU NIAMS NIH HHS [R01 AR055256]
NR 6
TC 1
Z9 1
U1 1
U2 4
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 31
PY 2011
VL 471
IS 7340
BP 586
EP 587
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 742NN
UT WOS:000288951200029
PM 21455169
ER
PT J
AU Treadway, K
Chatterjee, N
AF Treadway, Katharine
Chatterjee, Neal
TI BECOMING A PHYSICIAN Into the Water - The Clinical Clerkships
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID MEDICAL-EDUCATION
C1 [Treadway, Katharine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Treadway, K (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 5
TC 18
Z9 18
U1 1
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 31
PY 2011
VL 364
IS 13
BP 1190
EP 1193
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 742NO
UT WOS:000288951300003
PM 21449782
ER
PT J
AU Tierney, LM
Thabet, A
Nishino, H
AF Tierney, Lawrence M., Jr.
Thabet, Ashraf
Nishino, Ha
TI A Woman with Fever, Confusion, Liver Failure, Anemia, and
Thrombocytopenia Hemophagocytic lymphohistiocytosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HEPATITIS-C VIRUS; EXTRAHEPATIC MANIFESTATIONS; INFECTION; VETERANS;
DISEASES; THERAPY
C1 [Tierney, Lawrence M., Jr.] Univ Calif San Francisco, Dept Med, Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Thabet, Ashraf] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Nishino, Ha] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Thabet, Ashraf] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Nishino, Ha] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Tierney, LM (reprint author), Univ Calif San Francisco, Dept Med, Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
NR 20
TC 10
Z9 10
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 31
PY 2011
VL 364
IS 13
BP 1259
EP 1270
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 742NO
UT WOS:000288951300013
PM 21449790
ER
PT J
AU Bautista, PA
Yagi, Y
AF Bautista, Pinky A.
Yagi, Yukako
TI Localization of Eosinophilic Esophagitis from H&E stained images using
multispectral imaging
SO DIAGNOSTIC PATHOLOGY
LA English
DT Article; Proceedings Paper
CT 10th European Congress on Telepathology/4th International Congress on
Virtual Microscopy
CY JUL 01-03, 2010
CL Vilnius, LITHUANIA
AB This study is an initial investigation on the capability of multispectral imaging to capture subtle spectral information that would enable the automatic delineation between the eosinophilic esophagitis and other eosin stained tissue components, especially the RBCs. In the method, a principal component analysis (PCA) was performed on the spectral transmittance samples of the different tissue components, excluding however the transmittance samples of the eosinophilic esophagitis. From the average spectral error configuration of the eosinophilic esophagitis transmittance samples, i.e. the difference between the actual transmittance and the estimated transmittance using m PC vectors, we indentified two spectral bands by which we can localize the eosinophils. Initial results show the possibility of automatically localizing the eosinophilic esophagitis by utilizing spectral information.
C1 [Bautista, Pinky A.; Yagi, Yukako] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Bautista, PA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM pbautista@partners.org
NR 9
TC 2
Z9 3
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1746-1596
J9 DIAGN PATHOL
JI Diagn. Pathol.
PD MAR 30
PY 2011
VL 6
SU 1
AR S2
DI 10.1186/1746-1596-6-S1-S2
PG 8
WC Pathology
SC Pathology
GA 759IS
UT WOS:000290234600002
PM 21489190
ER
PT J
AU Yagi, Y
AF Yagi, Yukako
TI Color standardization and optimization in Whole Slide Imaging
SO DIAGNOSTIC PATHOLOGY
LA English
DT Article; Proceedings Paper
CT 10th European Congress on Telepathology/4th International Congress on
Virtual Microscopy
CY JUL 01-03, 2010
CL Vilnius, LITHUANIA
AB Introduction: Standardization and validation of the color displayed by digital slides is an important aspect of digital pathology implementation. While the most common reason for color variation is the variance in the protocols and practices in the histology lab, the color displayed can also be affected by variation in capture parameters (for example, illumination and filters), image processing and display factors in the digital systems themselves.
Method: We have been developing techniques for color validation and optimization along two paths. The first was based on two standard slides that are scanned and displayed by the imaging system in question. In this approach, one slide is embedded with nine filters with colors selected especially for H&E stained slides (looking like tiny Macbeth color chart); the specific color of the nine filters were determined in our previous study and modified for whole slide imaging (WSI). The other slide is an H&E stained mouse embryo. Both of these slides were scanned and the displayed images were compared to a standard. The second approach was based on our previous multispectral imaging research.
Discussion: As a first step, the two slide method (above) was used to identify inaccurate display of color and its cause, and to understand the importance of accurate color in digital pathology. We have also improved the multispectral-based algorithm for more consistent results in stain standardization. In near future, the results of the two slide and multispectral techniques can be combined and will be widely available. We have been conducting a series of researches and developing projects to improve image quality to establish Image Quality Standardization. This paper discusses one of most important aspects of image quality-color.
C1 [Yagi, Yukako] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Yagi, Yukako] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Yagi, Y (reprint author), Massachusetts Gen Hosp, Dept Pathol, 101 Merrimac St,Suite 820, Boston, MA 02114 USA.
EM yyagi@partners.org
NR 4
TC 28
Z9 28
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1746-1596
J9 DIAGN PATHOL
JI Diagn. Pathol.
PD MAR 30
PY 2011
VL 6
SU 1
AR S15
DI 10.1186/1746-1596-6-S1-S15
PG 12
WC Pathology
SC Pathology
GA 759IS
UT WOS:000290234600015
PM 21489185
ER
PT J
AU Mick, E
McGough, JJ
Middleton, FA
Neale, B
Faraone, SV
AF Mick, Eric
McGough, James J.
Middleton, Frank A.
Neale, Benjamin
Faraone, Stephen V.
TI Genome-wide association study of blood pressure response to
methylphenidate treatment of attention-deficit/hyperactivity disorder
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE ADHD; Blood pressure; Genome-wide association study; Methylphenidate;
Pharmacogenomic
ID CORONARY-ARTERY-DISEASE; QT INTERVAL DURATION; COMMON VARIANTS;
CARDIOVASCULAR HEALTH; LINKAGE ANALYSES; GENE VARIANTS; PR INTERVAL;
HEART; IDENTIFICATION; POLYMORPHISMS
AB Objective: We conducted a genome-wide association study of blood pressure in an open-label study of the methylphenidate transdermal system (MTS) for the treatment of attention-deficit/hyperactivity disorder (ADHD).
Method: Genotyping was conducted with the Affymetrix Genome-Wide Human SNP Array 6.0. Multivariate association analyses were conducted using the software package PLINK. After data cleaning and quality control we tested 316,934 SNPs in 140 children with ADHD.
Results: We observed no genome-wide statistically significant findings, but a SNP in a K(+)-dependent Na(+)/Ca(2+) exchanger expressed in vascular smooth muscle (SLC24A3) was included in our top associations at p<1E-04. Genetic enrichment analyses of genes with >= 1 SNP significant at p<0.01, implicated several functional categories (FERM domain, p = 5.0E-07; immunoglobulin domain, p = 8.1E-06; the transmembrane region, p = 4.4E-05; channel activity, p = 2.0E-04; and type-Ill fibronectins, p = 2.7E-05) harboring genes previously associated with related cardiovascular phenotypes.
Conclusions: The hypothesis generating results from this study suggests that polymorphisms in several genes consistently associated with cardiovascular diseases may impact changes in blood pressure observed with methylphenidate pharmacotherapy in children with ADHD. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Mick, Eric] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Mick, Eric] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[McGough, James J.] UCLA Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Middleton, Frank A.; Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
[Middleton, Frank A.; Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA.
[Neale, Benjamin] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Neale, Benjamin] Harvard & MIT, Broad Inst, Cambridge Ctr 7, Cambridge, MA 02142 USA.
RP Mick, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 705, Boston, MA 02114 USA.
EM mick@helix.mgh.harvard.edu
OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982
NR 68
TC 8
Z9 11
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD MAR 30
PY 2011
VL 35
IS 2
SI SI
BP 466
EP 472
DI 10.1016/j.pnpbp.2010.11.037
PG 7
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 753WP
UT WOS:000289811200023
PM 21130132
ER
PT J
AU Abbott, C
Juarez, M
White, T
Gollub, RL
Pearlson, GD
Bustillo, J
Lauriello, J
Ho, B
Bockholt, HJ
Clark, VP
Magnotta, V
Calhoun, VD
AF Abbott, C.
Juarez, M.
White, T.
Gollub, R. L.
Pearlson, G. D.
Bustillo, J.
Lauriello, J.
Ho, B.
Bockholt, H. J.
Clark, V. P.
Magnotta, V.
Calhoun, V. D.
TI Antipsychotic dose and diminished neural modulation: A multi-site fMRI
study
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Antipsychotic; Default mode network; fMRI; Independent component
analysis; Motor cortex
ID INDEPENDENT COMPONENT ANALYSIS; RESONANCE-IMAGING DATA;
SCHIZOPHRENIC-PATIENTS; WORKING-MEMORY; 1ST-EPISODE SCHIZOPHRENIA;
SENSORIMOTOR CORTEX; PARKINSONS-DISEASE; CORTICAL RESPONSE; MOTOR
STIMULATION; HEALTHY-SUBJECTS
AB Background: The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.
Methods: Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.
Results: Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho=-0.32, P=0.0039), motor/caudate (rho= -0.22, P=0.046), posterior default mode (rho=0.26, P=0.020), and anterior default mode networks (rho=0.24, P=0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t(77)=2.01, P=0.048).
Conclusion: The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Abbott, C.; Bustillo, J.; Calhoun, V. D.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA.
[Juarez, M.; Bockholt, H. J.; Clark, V. P.; Calhoun, V. D.] Mind Res Network, Albuquerque, NM 87131 USA.
[Juarez, M.; Calhoun, V. D.] Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA.
[Clark, V. P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
[Gollub, R. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Magnotta, V.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
[Ho, B.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Pearlson, G. D.; Calhoun, V. D.] Yale Univ, Sch Med, Dept Psychiat, Hartford, CT 06106 USA.
[White, T.] Univ Minnesota, Div Child Psychiat, Minneapolis, MN 55454 USA.
[Pearlson, G. D.; Calhoun, V. D.] Olin Neuropsychiat Res Ctr, Hartford, CT 06106 USA.
[White, T.] Erasmus MC, Dept Child Psychiat, Rotterdam, Netherlands.
[Lauriello, J.] Univ Missouri Columbia, Columbia, MO 65212 USA.
RP Abbott, C (reprint author), Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA.
EM cabbott@salud.unm.edu
RI Ho, Beng-Choon/D-6959-2011; Calhoun, Vince/H-7146-2013; bustillo,
juan/J-7067-2013; Clark, Vincent/B-3343-2010;
OI Ho, Beng-Choon/0000-0003-3976-1555; Calhoun, Vince/0000-0001-9058-0747;
Clark, Vincent/0000-0002-9151-2102; Gollub, Randy L./0000-0002-9434-4044
FU Department of Energy [DE-FG02-99ER62764]; NIH NCRR [P41RR14075,
5MO1-RR001066, U24 RR021992]; National Institutes of Health [R01
EB000840, K08 MH068540]
FX The Department of Energy DE-FG02-99ER62764, NIH NCRR P41RR14075,
5MO1-RR001066, and U24 RR021992 funded data collection. National
Institutes of Health grant R01 EB000840 and K08 MH068540 also funded
this study. The authors would like to thank the Mind Research Network
staff for their efforts during the data collection processes and
Guilherme Machado for help with data organization and analysis.
NR 63
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U1 4
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD MAR 30
PY 2011
VL 35
IS 2
SI SI
BP 473
EP 482
DI 10.1016/j.pnpbp.2010.12.001
PG 10
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 753WP
UT WOS:000289811200024
PM 21185903
ER
PT J
AU Bagrow, JP
Wang, DS
Barabasi, AL
AF Bagrow, James P.
Wang, Dashun
Barabasi, Albert-Laszlo
TI Collective Response of Human Populations to Large-Scale Emergencies
SO PLOS ONE
LA English
DT Article
ID MOBILE COMMUNICATION-NETWORKS; PREDICTABILITY; EPIDEMICS; BEHAVIOR; LAWS
AB Despite recent advances in uncovering the quantitative features of stationary human activity patterns, many applications, from pandemic prediction to emergency response, require an understanding of how these patterns change when the population encounters unfamiliar conditions. To explore societal response to external perturbations we identified real-time changes in communication and mobility patterns in the vicinity of eight emergencies, such as bomb attacks and earthquakes, comparing these with eight non-emergencies, like concerts and sporting events. We find that communication spikes accompanying emergencies are both spatially and temporally localized, but information about emergencies spreads globally, resulting in communication avalanches that engage in a significant manner the social network of eyewitnesses. These results offer a quantitative view of behavioral changes in human activity under extreme conditions, with potential long-term impact on emergency detection and response.
C1 [Bagrow, James P.; Wang, Dashun; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA.
[Bagrow, James P.; Wang, Dashun; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Bagrow, JP (reprint author), Northeastern Univ, Dept Phys, Ctr Complex Network Res, Boston, MA 02115 USA.
EM bagrowjp@gmail.com
FU James S. McDonnell Foundation 21st Century Initiative in Studying
Complex Systems; National Science Foundation within the Information
Technology Research [DMR-0426737]; Defense Threat Reduction Agency
[HDTRA1-08-1-0027]; United States Army Research Laboratory
[W911NF-09-2-0053]; United States Office of Naval Research
[N000141010968]; [IIS-0513650]
FX The authors were funded by the James S. McDonnell Foundation 21st
Century Initiative in Studying Complex Systems, National Science
Foundation within the Information Technology Research (DMR-0426737) and
IIS-0513650 programs, the Defense Threat Reduction Agency award
HDTRA1-08-1-0027, the Network Science Collaborative Technology Alliance
sponsored by the United States Army Research Laboratory under agreement
number W911NF-09-2-0053, and the United States Office of Naval Research
Award (N000141010968). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 30
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Z9 61
U1 1
U2 29
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 30
PY 2011
VL 6
IS 3
AR e17680
DI 10.1371/journal.pone.0017680
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YK
UT WOS:000289055700014
PM 21479206
ER
PT J
AU Iwasa, Y
Michor, F
AF Iwasa, Yoh
Michor, Franziska
TI Evolutionary Dynamics of Intratumor Heterogeneity
SO PLOS ONE
LA English
DT Article
ID DNA POLYMORPHISM DATA; TUMOR HETEROGENEITY; DROSOPHILA-MELANOGASTER;
GENETIC-VARIATION; CANCER; MODEL; PROGRESSION; CELLS; CARCINOGENESIS;
POPULATIONS
AB Intraneoplastic diversity in human tumors is a widespread phenomenon of critical importance for tumor progression and the response to therapeutic intervention. Insights into the evolutionary events that control tumor heterogeneity would be a major breakthrough in our comprehension of cancer development and could lead to more effective prevention methods and therapies. In this paper, we design an evolutionary mathematical framework to study the dynamics of heterogeneity over time. We consider specific situations arising during tumorigenesis, such as the emergence of positively selected mutations ("drivers") and the accumulation of neutral variation ("passengers"). We perform exact computer simulations of the emergence of diverse tumor cell clones over time, and derive analytical estimates for the extent of heterogeneity within a population of cancer cells. Our methods contribute to a quantitative understanding of tumor heterogeneity and the impact of heritable alterations on this tumor trait.
C1 [Iwasa, Yoh] Kyushu Univ, Fac Sci, Dept Biol, Fukuoka 812, Japan.
[Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Iwasa, Y (reprint author), Kyushu Univ, Fac Sci, Dept Biol, Fukuoka 812, Japan.
EM michor@jimmy.harvard.edu
RI Iwasa, Yoh/G-5368-2010
OI Iwasa, Yoh/0000-0003-0691-1852
FU National Cancer Institute (NCI) initiative [U54CA143798]
FX This work was supported by the National Cancer Institute (NCI)
initiative to fund Physical Science-Oncology Centers (grant U54CA143798)
(F.M.). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 39
TC 24
Z9 24
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 30
PY 2011
VL 6
IS 3
AR e17866
DI 10.1371/journal.pone.0017866
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YK
UT WOS:000289055700016
PM 21479218
ER
PT J
AU Velez, JM
Miriyala, S
Nithipongvanitch, R
Noel, T
Plabplueng, CD
Oberley, T
Jungsuwadee, P
Van Remmen, H
Vore, M
Clair, DKS
AF Velez, Joyce M.
Miriyala, Sumitra
Nithipongvanitch, Ramaneeya
Noel, Teresa
Plabplueng, Chotiros D.
Oberley, Terry
Jungsuwadee, Paiboon
Van Remmen, Holly
Vore, Mary
Clair, Daret K. St.
TI p53 Regulates Oxidative Stress-Mediated Retrograde Signaling: A Novel
Mechanism for Chemotherapy-Induced Cardiac Injury
SO PLOS ONE
LA English
DT Article
ID MANGANESE SUPEROXIDE-DISMUTASE; GLUTATHIONE TRANSFERASE;
LIPID-PEROXIDATION; NITRIC-OXIDE; CELL-DEATH; ACTIVATION; MICE;
AUTOPHAGY; PROTEINS; HEART
AB The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin (DOX), a potent cancer chemotherapeutic drug. The production of ROS by DOX has been linked to DNA damage, nuclear translocation of p53, and mitochondrial injury; however, the causal relationship and molecular mechanisms underlying these events are unknown. The present study used wild-type (WT) and p53 homozygous knock-out (p53(-/-)) mice to investigate the role of p53 in the crosstalk between mitochondria and nucleus. Injecting mice with DOX (20 mg/kg) causes oxidative stress in cardiac tissue as demonstrated by immunogold analysis of the levels of 4-hydroxy-2'-nonenal (4HNE)-adducted protein, a lipid peroxidation product bound to proteins. 4HNE levels increased in both nuclei and mitochondria of WT DOX-treated mice but only in nuclei of DOX-treated p53((-/-)) mice, implicating a critical role for p53 in causing DOX-induced oxidative stress in mitochondria. The stress-activated protein c-Jun amino-terminal kinase (JNKs) was activated in response to increased 4HNE in WT mice but not p53((-/-)) mice receiving DOX treatment, as determined by co-immunoprecipitation of HNE and pJNK. The activation of JNK in DOX treated WT mice was accompanied by Bcl-2 dissociation from Beclin in mitochondria and induction of type II cell death (autophagic cell death), as evidenced by an increase in LC3-I/LC-3-II ratio and gamma-H2AX, a biomarker for DNA damage. The absence of p53 significantly reduces mitochondrial injury, assessed by quantitative morphology, and decline in cardiac function, assessed by left ventricular ejection fraction and fraction shortening. These results demonstrate that p53 plays a critical role in DOX-induced cardiac toxicity, in part, by the induction of oxidative stress mediated retrograde signaling.
C1 [Velez, Joyce M.; Miriyala, Sumitra; Noel, Teresa; Jungsuwadee, Paiboon; Vore, Mary; Clair, Daret K. St.] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40526 USA.
[Oberley, Terry] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA.
[Oberley, Terry] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Pathol & Lab Med Serv, Madison, WI 53792 USA.
[Nithipongvanitch, Ramaneeya; Plabplueng, Chotiros D.] Mahidol Univ, Fac Med Technol, Bangkok 10700, Thailand.
[Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
RP Velez, JM (reprint author), Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40526 USA.
EM DSTCL00@uky.edu
RI Vore, Mary/E-2177-2012
FU National Institutes of Health [CA 139483, CA 139484, T32 HL072743];
Interdisciplinary Cardiovascular Training Program
FX This work is supported by National Institutes of Health grants CA
139483, CA 139484 and T32 HL072743, Interdisciplinary Cardiovascular
Training Program (Joyce M. Velez). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 37
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U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 30
PY 2011
VL 6
IS 3
AR e18005
DI 10.1371/journal.pone.0018005
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YK
UT WOS:000289055700021
PM 21479164
ER
PT J
AU Vidwans, SJ
Flaherty, KT
Fisher, DE
Tenenbaum, JM
Travers, MD
Shrager, J
AF Vidwans, Smruti J.
Flaherty, Keith T.
Fisher, David E.
Tenenbaum, Jay M.
Travers, Michael D.
Shrager, Jeff
TI A Melanoma Molecular Disease Model
SO PLOS ONE
LA English
DT Article
ID P16 PROTEIN EXPRESSION; METASTATIC MELANOMA; MALIGNANT-MELANOMA;
CUTANEOUS MELANOMA; SIGNALING PATHWAYS; BRAF MUTATIONS; HUMAN CANCER;
CYCLIN D1; COMBINED INHIBITION; SEQUENCE VARIANTS
AB While advanced melanoma remains one of the most challenging cancers, recent developments in our understanding of the molecular drivers of this disease have uncovered exciting opportunities to guide personalized therapeutic decisions. Genetic analyses of melanoma have uncovered several key molecular pathways that are involved in disease onset and progression, as well as prognosis. These advances now make it possible to create a "Molecular Disease Model" (MDM) for melanoma that classifies individual tumors into molecular subtypes (in contrast to traditional histological subtypes), with proposed treatment guidelines for each subtype including specific assays, drugs, and clinical trials. This paper describes such a Melanoma Molecular Disease Model reflecting the latest scientific, clinical, and technological advances.
C1 [Vidwans, Smruti J.; Tenenbaum, Jay M.; Travers, Michael D.; Shrager, Jeff] CollabRx Inc, Palo Alto, CA 94301 USA.
[Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA.
[Fisher, David E.] Massachusetts Gen Hosp, Melanoma Program, Boston, MA 02114 USA.
[Shrager, Jeff] Stanford Univ, Symbol Syst Program Consulting, Stanford, CA 94305 USA.
RP Vidwans, SJ (reprint author), CollabRx Inc, Palo Alto, CA 94301 USA.
EM jshrager@stanford.edu
FU NIAMS NIH HHS [R01 AR043369]
NR 92
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U1 0
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 30
PY 2011
VL 6
IS 3
AR e18257
DI 10.1371/journal.pone.0018257
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YK
UT WOS:000289055700041
PM 21479172
ER
PT J
AU Sheth, SA
Abuelem, T
Gale, JT
Eskandar, EN
AF Sheth, Sameer A.
Abuelem, Tarek
Gale, John T.
Eskandar, Emad N.
TI Basal Ganglia Neurons Dynamically Facilitate Exploration during
Associative Learning
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FOREBRAIN CIRCUIT; STRIATAL NEURONS; CAUDATE; CORTEX; MONKEY; RESPONSES;
DOPAMINE; MOVEMENT; PRIMATE; INPUTS
AB The basal ganglia (BG) appear to play a prominent role in associative learning, the process of pairing external stimuli with rewarding responses. Accumulating evidence suggests that the contributions of various BG components may be described within a reinforcement learning model, in which a broad repertoire of possible responses to environmental stimuli are evaluated before the most profitable one is chosen. The striatum receives diverse cortical inputs, providing a rich source of contextual information about environmental cues. It also receives projections from midbrain dopaminergic neurons, whose phasic activity reflects a reward prediction error signal. These coincident information streams are well suited for evaluating responses and biasing future actions toward the most profitable response. Still lacking in this model is a mechanistic description of how initial response variability is generated. To investigate this question, we recorded the activity of single neurons in the globus pallidus internus (GPi), the primary BG output nucleus, in nonhuman primates ( Macaca mulatta) performing a motor associative learning task. A subset (29%) of GPi neurons showed learning-related effects, decreasing firing during the early stages of learning, then returning to higher baseline rates as associations were mastered. On a trial-by-trial basis, lower firing rates predicted exploratory behavior, whereas higher rates predicted an exploitive response. These results suggest that, during associative learning, BG output is initially permissive, allowing exploration of a variety of responses. Once a profitable response is identified, increased GPi activity suppresses alternative responses, sharpening the response profile and encouraging exploitation of the profitable learned behavior.
C1 [Sheth, Sameer A.; Gale, John T.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA.
[Abuelem, Tarek] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA.
RP Eskandar, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 55 Fruit St,White 502, Boston, MA 02114 USA.
EM eeskandar@partners.org
FU National Institutes of Health [R25 NS065743, R01 EY017658, R01
NS063249]; National Science Foundation [IOB 0645886]; Howard Hughes
Medical Institute
FX This work was supported by National Institutes of Health Grants R25
NS065743 (to S.A.S.) and R01 EY017658 and R01 NS063249 (to E.N.E.),
National Science Foundation Grant IOB 0645886 (to E.N.E.), and Howard
Hughes Medical Institute Early Career Award (to E.N.E.).
NR 31
TC 25
Z9 26
U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 30
PY 2011
VL 31
IS 13
BP 4878
EP 4885
DI 10.1523/JNEUROSCI.3658-10.2011
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 742JM
UT WOS:000288938200014
PM 21451026
ER
PT J
AU Palva, S
Kulashekhar, S
Hamalainen, M
Palva, JM
AF Palva, Satu
Kulashekhar, Shrikanth
Haemaelaeinen, Matti
Palva, J. Matias
TI Localization of Cortical Phase and Amplitude Dynamics during Visual
Working Memory Encoding and Retention
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SHORT-TERM-MEMORY; HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS;
PREFRONTAL CORTEX; OSCILLATORY ACTIVITY; ALPHA OSCILLATIONS;
EVOKED-RESPONSES; INDIVIDUAL-DIFFERENCES; OBJECT RECOGNITION; NEURONAL
SYNCHRONY
AB Several studies show that the amplitudes of human brain oscillations are modulated during the performance of visual working memory (VWM) tasks in a load-dependent manner. Less is known about the dynamics and identities of the cortical regions in which these modulations take place, and hence their functional significance has remained unclear. We used magnetoencephalography and electroencephalography together with minimum norm estimate-based source modeling to study the dynamics of ongoing brain activity during a parametric VWM task. Early stimulus processing and memory encoding were associated with a memory load-dependent spread of neuronal activity from occipital to temporal, parietal, and frontal cortical regions. During the VWM retention period, the amplitudes of oscillations in theta/alpha-(5-9 Hz), high-alpha-(10-14 Hz), beta-(15-30 Hz), gamma-(30-50 Hz), and high-gamma-(50-150 Hz) frequency bands were suppressed below baseline levels, and yet, in frontoparietal regions, load dependently strengthened. However, in occipital and occipitotemporal structures, only beta, gamma, and high-gamma amplitudes were robustly strengthened by memory load. Individual behavioral VWM capacity was predicted by both the magnitude of the N1 evoked response component in early visual regions and by the amplitudes of frontoparietal high-alpha and high-gamma band oscillations. Thus, both early stimulus processing and late retention period activities may influence the behavioral outcome in VWM tasks. These data support the notion that beta-and gamma-band oscillations support the maintenance of object representations in VWM whereas alpha-, beta-, and gamma-band oscillations together contribute to attentional and executive processing.
C1 [Palva, Satu; Kulashekhar, Shrikanth; Palva, J. Matias] Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland.
[Kulashekhar, Shrikanth] HUSLAB, BioMag Lab, Helsinki 00029, Finland.
[Haemaelaeinen, Matti] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Haemaelaeinen, Matti] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Palva, S (reprint author), Univ Helsinki, Ctr Neurosci, POB 56, FIN-00014 Helsinki, Finland.
EM satu.palva@helsinki.fi; matias.palva@helsinki.fi
RI Palva, J. Matias/D-5837-2013; Palva, Satu/D-7400-2013; Hamalainen,
Matti/C-8507-2013;
OI Palva, Satu/0000-0001-9496-7391
FU Academy of Finland; Helsinki University; National Institutes of Health
National Center for Research [P41 RR14075]; National Institute of
Biomedical Imaging and Bioengineering [1R01EB009048, 1R01 EB006385]
FX This study was supported by the Academy of Finland, by the Helsinki
University Research Funds, the National Institutes of Health National
Center for Research Resources Grant P41 RR14075, and National Institute
of Biomedical Imaging and Bioengineering Grants 1R01EB009048 and 1R01
EB006385.
NR 79
TC 54
Z9 58
U1 0
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 30
PY 2011
VL 31
IS 13
BP 5013
EP 5025
DI 10.1523/JNEUROSCI.5592-10.2011
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 742JM
UT WOS:000288938200027
PM 21451039
ER
PT J
AU Biederman, J
Petty, CR
Wozniak, J
Wilens, TE
Fried, R
Doyle, A
Henin, A
Bateman, C
Evans, M
Faraone, SV
AF Biederman, Joseph
Petty, Carter R.
Wozniak, Janet
Wilens, Timothy E.
Fried, Ronna
Doyle, Alysa
Henin, Aude
Bateman, Clancey
Evans, Maggie
Faraone, Stephen V.
TI Impact of executive function deficits in youth with bipolar I disorder:
A controlled study
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Mania; Children; Cognition; Neuropsychology
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HYPERACTIVITY DISORDER;
LEARNING-DISABILITIES; CHILDREN; ASSOCIATION; ADOLESCENTS; PERFORMANCE;
DYSFUNCTION; SYMPTOMS; MANIA
AB Although psychometrically-defined executive function deficits (EFDs) and ecologically valid functional outcomes have been documented among youth with bipolar I (BP-I) disorder, little is known about their association. We hypothesized that EFDs would be associated with significant ecologically valid impairments beyond those predicted by having BP-I disorder. Youth with BP-I disorder were ascertained from psychiatric clinics and community sources. We defined EFDs as having at least two out of eight EF measures impaired from a battery of six tests. Significantly more youth with BP-I disorder had EFDs than controls (45% versus 17%). Comparisons were made between controls without EFDs (N=81), controls with EFDs (N=17), BP-I youth without EFDs (N=76), and BP-I youth with EFDs (N=62). EFDs were associated with an increased risk for placement in a special class and a decrease in academic achievement (WRAT-3 reading and arithmetic). EFDs in BP-I subjects were associated with an increased risk for speech/language disorder (as assessed in the K-SADS-E) relative to BP-I subjects without EFDs. Youth with BP-I disorder and EFDs are at high risk for significant impairments in academic functioning. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA.
[Biederman, Joseph; Wozniak, Janet; Wilens, Timothy E.; Henin, Aude] Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA.
RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Clin & Res Program Pediat Psychopharmacol, Yawkey 6A,Fruit St, Boston, MA 02114 USA.
EM jbiederman@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU NIH [R01MH066237, R01DA12945]; Neal-Kimmerly Fund for the Study of
Cognition; Heinz C. Prechter Bipolar Research Fund; MGH Pediatric
Psychopharmacology Council
FX This work was supported by NIH grants R01MH066237 to Dr. Wozniak and
R01DA12945 to Dr. Wilens. This work was also supported by the
Neal-Kimmerly Fund for the Study of Cognition, a grant from the Heinz C.
Prechter Bipolar Research Fund, and the support of members of the MGH
Pediatric Psychopharmacology Council.
NR 46
TC 14
Z9 14
U1 1
U2 7
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 2011
VL 186
IS 1
BP 58
EP 64
DI 10.1016/j.psychres.2010.08.029
PG 7
WC Psychiatry
SC Psychiatry
GA 739OX
UT WOS:000288728600011
PM 20864180
ER
PT J
AU Schoenfeld, DA
Rajicic, N
Ficociello, LH
Finkelstein, DM
AF Schoenfeld, David A.
Rajicic, Natasa
Ficociello, Linda H.
Finkelstein, Dianne M.
TI A test for the relationship between a time-varying marker and both
recovery and progression with missing data
SO STATISTICS IN MEDICINE
LA English
DT Article
DE interval-censored failure time data; polychotomous logistic regression;
longitudinal marker; random effects model; PRO logistic model
ID LONGITUDINAL DATA; EVENT; MODEL; REGRESSION; COVARIATE
AB For clinical studies of chronic diseases, patients are followed to determine whether treatment results in either improvement or decline in their clinical status. During periodic exams, laboratory specimens are collected that are believed to reflect both the progression and improvement in the disease status. Often patients miss visits and return with a changed disease status, resulting in interval-censored laboratory markers and indicators of disease status. The goal of this paper is to propose a single test that would evaluate the relationship between a longitudinal marker and clinical progression or recovery when missing visits result in interval-censored covariate and outcome data. We apply our test to evaluate the relationship between treatment compliance and progression and remission of renal disease in diabetic patients. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Schoenfeld, David A.; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Schoenfeld, David A.; Finkelstein, Dianne M.] Harvard Univ, Biostat Unit, Boston, MA 02114 USA.
[Rajicic, Natasa] Pfizer Inc, New York, NY 10017 USA.
[Ficociello, Linda H.] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA.
EM dfinkelstein@partners.org
FU NIH [HD05520, CA 74302, CA 75971, DK-41526]
FX We thank Andrej Krolewski for providing the diabetes data. This work was
partially funded by grants from the NIH: HD05520, CA 74302, CA 75971,
and DK-41526.
NR 11
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD MAR 30
PY 2011
VL 30
IS 7
BP 718
EP 724
DI 10.1002/sim.4145
PG 7
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 736RV
UT WOS:000288512700003
PM 21394748
ER
PT J
AU Granziera, C
Hadjikhani, N
Arzy, S
Seeck, M
Meuli, R
Krueger, G
AF Granziera, Cristina
Hadjikhani, Nouchine
Arzy, Shahar
Seeck, Margitta
Meuli, Reto
Krueger, Gunnar
TI In-vivo magnetic resonance imaging of the structural core of the Papez
circuit in humans
SO NEUROREPORT
LA English
DT Article
DE diffusion spectrum imaging; Papez circuit; tractography
ID TEMPORAL-LOBE EPILEPSY; ALZHEIMERS-DISEASE; ABNORMALITIES; MRI
AB Papez circuit is one of the major pathways of the limbic system, and it is involved in the control of memory and emotion. Structural and functional alterations have been reported in psychiatric, neurodegenerative, and epileptic diseases. Despite the clinical interest, however, in-vivo imaging of the entire circuit remains a technological challenge. We used magnetic resonance diffusion spectrum imaging to comprehensively picture the Papez circuit in healthy humans: (i) the hippocampus-mammillary body pathway, (ii) the connections between the lateral subiculum and the cingulate cortex, and (iii) the mammillo-thalamic tract. The diagnostic and therapeutic implications of these results are discussed in the context of recent findings reporting the involvement of the Papez circuit in neurological and psychiatric diseases. NeuroReport 22:227-231 (C) 2011 Wolters KluwerHealth | Lippincott Williams & Wilkins.
C1 [Granziera, Cristina] CHU Vaudois, Dept Neurol, CH-1011 Lausanne, Switzerland.
[Meuli, Reto] CHU Vaudois, Dept Radiol, CH-1011 Lausanne, Switzerland.
Univ Lausanne, Lausanne, Switzerland.
[Granziera, Cristina; Hadjikhani, Nouchine; Arzy, Shahar] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lausanne, Switzerland.
[Arzy, Shahar; Seeck, Margitta] Univ Hosp Geneva, Dept Neurol, Geneva, Switzerland.
[Krueger, Gunnar] Siemens Schweiz AG, Healthcare Sector IM&WS S, Renens, Switzerland.
[Hadjikhani, Nouchine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Granziera, C (reprint author), EPFL SV BMI GRHAD, Batiment AAB 1 32,Stn 15, CH-1015 Lausanne, Switzerland.
EM cristina.granziera@chuv.ch
RI Centre d'imagerie Biomedicale, CIBM/B-5740-2012; Hadjikhani,
Nouchine/C-2018-2008;
OI Hadjikhani, Nouchine/0000-0003-4075-3106; Arzy,
Shahar/0000-0001-6500-8095; Granziera, Cristina/0000-0002-4917-8761
FU Centre d'Imagerie BioMedicale of the University of Lausanne; Swiss
Federal Institute of Technology Lausanne (EPFL); University of Geneva;
Centre Hospitalier Universitaire Vaudois; Hopitaux Universitaires de
Geneve; Leenaards foundation; Jeantet foundation; Stoicescu fellowship;
Swiss National Fund [33CM30-124089, 33CM30-124115, 320030-122073]
FX This work was supported by the Centre d'Imagerie BioMedicale of the
University of Lausanne, the Swiss Federal Institute of Technology
Lausanne (EPFL), the University of Geneva, the Centre Hospitalier
Universitaire Vaudois, the Hopitaux Universitaires de Geneve, the
Leenaards and the Jeantet foundations, the Stoicescu fellowship, and the
Swiss National Fund 33CM30-124089, 33CM30-124115, and 320030-122073.
NR 20
TC 12
Z9 13
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD MAR 30
PY 2011
VL 22
IS 5
BP 227
EP 231
DI 10.1097/WNR.0b013e328344f75f
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 732BC
UT WOS:000288155900007
PM 21346644
ER
PT J
AU Dias-Santagata, D
Lam, Q
Vernovsky, K
Vena, N
Lennerz, JK
Borger, DR
Batchelor, TT
Ligon, KL
Iafrate, AJ
Ligon, AH
Louis, DN
Santagata, S
AF Dias-Santagata, Dora
Lam, Quynh
Vernovsky, Kathy
Vena, Natalie
Lennerz, Jochen K.
Borger, Darrell R.
Batchelor, Tracy T.
Ligon, Keith L.
Iafrate, A. John
Ligon, Azra H.
Louis, David N.
Santagata, Sandro
TI BRAF V600E Mutations Are Common in Pleomorphic Xanthoastrocytoma:
Diagnostic and Therapeutic Implications
SO PLOS ONE
LA English
DT Article
ID GIANT-CELL GLIOBLASTOMAS; LOW-GRADE ASTROCYTOMAS; PILOCYTIC
ASTROCYTOMAS; ANAPLASTIC FEATURES; GENETIC ALTERATIONS; MAPK PATHWAY;
FUSION GENE; EXPRESSION; GLIOMAS; TUMORS
AB Pleomorphic xanthoastrocytoma (PXA) is low-grade glial neoplasm principally affecting children and young adults. Approximately 40% of PXA are reported to recur within 10 years of primary resection. Upon recurrence, patients receive radiation therapy and conventional chemotherapeutics designed for high-grade gliomas. Genetic changes that can be targeted by selective therapeutics have not been extensively evaluated in PXA and ancillary diagnostic tests to help discriminate PXA from other pleomorphic and often more aggressive astrocytic malignancies are limited. In this study, we apply the SNaPshot multiplexed targeted sequencing platform in the analysis of brain tumors to interrogate 60 genetic loci that are frequently mutated in 15 cancer genes. In our analysis we detect BRAF V600E mutations in 12 of 20 (60%) WHO grade II PXA, in 1 of 6 (17%) PXA with anaplasia and in 1 glioblastoma arising in a PXA. Phospho-ERK was detected in all tumors independent of the BRAF mutation status. BRAF duplication was not detected in any of the PXA cases. BRAF V600E mutations were identified in only 2 of 71 (2.8%) glioblastoma (GBM) analyzed, including 1 of 9 (11.1%) giant cell GBM (gcGBM). The finding that BRAF V600E mutations are common in the majority of PXA has important therapeutic implications and may help in differentiating less aggressive PXAs from lethal gcGBMs and GBMs.
C1 [Dias-Santagata, Dora; Lam, Quynh; Lennerz, Jochen K.; Iafrate, A. John; Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Dias-Santagata, Dora; Lam, Quynh; Lennerz, Jochen K.; Iafrate, A. John; Louis, David N.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
[Vernovsky, Kathy; Borger, Darrell R.; Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA.
[Dias-Santagata, Dora; Lam, Quynh; Vernovsky, Kathy; Lennerz, Jochen K.; Borger, Darrell R.; Batchelor, Tracy T.; Ligon, Keith L.; Iafrate, A. John; Ligon, Azra H.; Louis, David N.; Santagata, Sandro] Harvard Univ, Sch Med, Boston, MA USA.
[Vena, Natalie; Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Vena, Natalie; Ligon, Keith L.; Ligon, Azra H.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Ligon, Keith L.; Santagata, Sandro] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ligon, Keith L.; Ligon, Azra H.; Santagata, Sandro] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Dias-Santagata, D (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM ssantagata@partners.org
OI Ligon, Keith/0000-0002-7733-600X
FU Aid for Cancer Research Foundation; PLGA Foundation; National Institutes
of Health (NIH) [CA095616, CA57683, K08NS064168]; Sontag Foundation;
Goldhirsh Foundation; V Foundation for Cancer Research; Brain Science
Foundation
FX This work was supported by the Aid for Cancer Research Foundation and
from an anonymous donor (to MGH) and the PLGA Foundation. KLL is
supported by National Institutes of Health (NIH) grant CA095616, the
Sontag Foundation, and the Goldhirsh Foundation. DNL is supported by NIH
grant CA57683. SS is supported by NIH grant K08NS064168, the V
Foundation for Cancer Research and the Brain Science Foundation. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 56
TC 119
Z9 122
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 29
PY 2011
VL 6
IS 3
AR e17948
DI 10.1371/journal.pone.0017948
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YC
UT WOS:000289054600021
PM 21479234
ER
PT J
AU Gregory, MS
Hackett, CG
Abernathy, EF
Lee, KS
Saff, RR
Hohlbaum, AM
Moody, KSL
Hobson, MW
Jones, A
Kolovou, P
Karray, S
Giani, A
John, SWM
Chen, DF
Marshak-Rothstein, A
Ksander, BR
AF Gregory, Meredith S.
Hackett, Caroline G.
Abernathy, Emma F.
Lee, Karen S.
Saff, Rebecca R.
Hohlbaum, Andreas M.
Moody, Krishna-sulayman L.
Hobson, Maura W.
Jones, Alexander
Kolovou, Paraskevi
Karray, Saoussen
Giani, Andrea
John, Simon W. M.
Chen, Dong Feng
Marshak-Rothstein, Ann
Ksander, Bruce R.
TI Opposing Roles for Membrane Bound and Soluble Fas Ligand in
Glaucoma-Associated Retinal Ganglion Cell Death
SO PLOS ONE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; FIBER LAYER THICKNESS; OCULAR IMMUNE
PRIVILEGE; OPEN-ANGLE GLAUCOMA; INFLAMMATORY RESPONSES; INDUCED
APOPTOSIS; GENE-EXPRESSION; DBA/2J MICE; ALPHA; ACTIVATION
AB Glaucoma, the most frequent optic neuropathy, is a leading cause of blindness worldwide. Death of retinal ganglion cells (RGCs) occurs in all forms of glaucoma and accounts for the loss of vision, however the molecular mechanisms that cause RGC loss remain unclear. The pro-apoptotic molecule, Fas ligand, is a transmembrane protein that can be cleaved from the cell surface by metalloproteinases to release a soluble protein with antagonistic activity. Previous studies documented that constitutive ocular expression of FasL maintained immune privilege and prevented neoangeogenesis. We now show that FasL also plays a major role in retinal neurotoxicity. Importantly, in both TNF alpha triggered RGC death and a spontaneous model of glaucoma, gene-targeted mice that express only full-length FasL exhibit accelerated RGC death. By contrast, FasL-deficiency, or administration of soluble FasL, protected RGCs from cell death. These data identify membrane-bound FasL as a critical effector molecule and potential therapeutic target in glaucoma.
C1 [Gregory, Meredith S.; Hackett, Caroline G.; Abernathy, Emma F.; Hobson, Maura W.; Jones, Alexander; Kolovou, Paraskevi; Chen, Dong Feng; Ksander, Bruce R.] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02163 USA.
[Lee, Karen S.; Hohlbaum, Andreas M.; Moody, Krishna-sulayman L.; Hobson, Maura W.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Saff, Rebecca R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Moody, Krishna-sulayman L.; Marshak-Rothstein, Ann] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Karray, Saoussen] Hop Necker Enfants Malad, INSERM, U580, Paris, France.
[Giani, Andrea] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
[John, Simon W. M.] Jackson Lab, Howard Hughes Med Inst, Bar Harbor, ME 04609 USA.
RP Gregory, MS (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02163 USA.
EM ann.rothstein@umassmed.edu; bruce.ksander@schepens.harvard.edu
FU Lions Research Foundation; American Health Assistance Foundation; NEI
[EY016486, EY016145]; NCI [CA90691]; Glaucoma Foundation; [EY11721]
FX Funding sources: Lions Research Foundation (BRK), American Health
Assistance Foundation (MSG), NEI EY016486 (BRK), NEI EY016145 (MSG), NCI
CA90691 (AMR), EY11721 (SWMJ), the Glaucoma Foundation (BRK) and SWMJ is
an investigator of the Howard Hughes Medical Institute. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 61
TC 37
Z9 38
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 29
PY 2011
VL 6
IS 3
AR e17659
DI 10.1371/journal.pone.0017659
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YC
UT WOS:000289054600014
PM 21479271
ER
PT J
AU Konstantinopoulos, PA
Cannistra, SA
Fountzilas, H
Culhane, A
Pillay, K
Rueda, B
Cramer, D
Seiden, M
Birrer, M
Coukos, G
Zhang, L
Quackenbush, J
Spentzos, D
AF Konstantinopoulos, Panagiotis A.
Cannistra, Stephen A.
Fountzilas, Helen
Culhane, Aedin
Pillay, Kamana
Rueda, Bo
Cramer, Daniel
Seiden, Michael
Birrer, Michael
Coukos, George
Zhang, Lin
Quackenbush, John
Spentzos, Dimitrios
TI Integrated Analysis of Multiple Microarray Datasets Identifies a
Reproducible Survival Predictor in Ovarian Cancer
SO PLOS ONE
LA English
DT Article
ID GYNECOLOGIC-ONCOLOGY-GROUP; GENE-EXPRESSION; GENOMIC SIGNATURES;
STAGE-III; PACLITAXEL; CISPLATIN; PATTERNS; PATHWAY; CELL; CARBOPLATIN
AB Background: Public data integration may help overcome challenges in clinical implementation of microarray profiles. We integrated several ovarian cancer datasets to identify a reproducible predictor of survival.
Methodology/Principal Findings: Four microarray datasets from different institutions comprising 265 advanced stage tumors were uniformly reprocessed into a single training dataset, also adjusting for inter-laboratory variation ("batcheffect"). Supervised principal component survival analysis was employed to identify prognostic models. Models were independently validated in a 61-patient cohort using a custom array genechip and a publicly available 229-array dataset. Molecular correspondence of high-and low-risk outcome groups between training and validation datasets was demonstrated using Subclass Mapping. Previously established molecular phenotypes in the 2(nd) validation set were correlated with high and low-risk outcome groups. Functional representational and pathway analysis was used to explore gene networks associated with high and low risk phenotypes. A 19-gene model showed optimal performance in the training set (median OS 31 and 78 months, p < 0.01), 1(st) validation set (median OS 32 months versus not-yet-reached, p=0.026) and 2(nd) validation set (median OS 43 versus 61 months, p=0.013) maintaining independent prognostic power in multivariate analysis. There was strong molecular correspondence of the respective high-and low-risk tumors between training and 1(st) validation set. Low and high-risk tumors were enriched for favorable and unfavorable molecular subtypes and pathways, previously defined in the public 2(nd) validation set.
Conclusions/Significance: Integration of previously generated cancer microarray datasets may lead to robust and widely applicable survival predictors. These predictors are not simply a compilation of prognostic genes but appear to track true molecular phenotypes of good-and poor-outcome.
C1 [Konstantinopoulos, Panagiotis A.; Cannistra, Stephen A.; Fountzilas, Helen; Pillay, Kamana; Spentzos, Dimitrios] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med,Sch Med, Boston, MA 02215 USA.
[Culhane, Aedin; Quackenbush, John] Harvard Univ, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Dept Biostat,Sch Publ Hlth, Boston, MA 02215 USA.
[Rueda, Bo] Harvard Univ, Dept Obstet Gynecol & Reprod Biol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA.
[Cramer, Daniel] Harvard Univ, Dept Obstet Gynecol & Reprod Biol, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA.
[Seiden, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Birrer, Michael] Harvard Univ, Div Gynecol Med Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA.
[Coukos, George; Zhang, Lin] Univ Penn, Dept Gynecol Oncol, Philadelphia, PA 19104 USA.
[Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Konstantinopoulos, PA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med,Sch Med, Boston, MA 02215 USA.
EM dspentzo@bidmc.harvard.edu
FU NIH/NCI [P50CA105009]; Clinical Investigation Training Program; Beth
Israel Deaconess Medical Center; Harvard-MIT Division of Health Sciences
and Technology, Boston; Bernice Shopkin Weisman Fund; Ovarian Cancer
Research Fund in memory of Amy Sachs Simon; LeAnn's Fund; Sisters
Against Ovarian Cancer
FX This study was supported via the NIH/NCI P50CA105009 Ovarian Cancer
SPORE (Career Development Award to Dimitrios Spentzos, and Project 4 to
Daniel Cramer/Stephen Cannistra), the Clinical Investigation Training
Program, Beth Israel Deaconess Medical Center and Harvard-MIT Division
of Health Sciences and Technology, Boston, to Panagiotis
Konstantinopoulos, the Bernice Shopkin Weisman Fund, the Ovarian Cancer
Research Fund in memory of Amy Sachs Simon, LeAnn's Fund, and the
Sisters Against Ovarian Cancer. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 34
TC 15
Z9 15
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 29
PY 2011
VL 6
IS 3
AR e18202
DI 10.1371/journal.pone.0018202
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743YC
UT WOS:000289054600033
PM 21479231
ER
PT J
AU Budin, I
Szostak, JW
AF Budin, Itay
Szostak, Jack W.
TI Physical effects underlying the transition from primitive to modern cell
membranes
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE origin of life; ribozymes; coevolution
ID LIPID-BILAYERS; VESICLES; RNA; PHOSPHOLIPIDS; AMPHIPHILES; TRANSPORTER;
COMPETITION; KINETICS; EXCHANGE; FLUIDITY
AB To understand the emergence of Darwinian evolution, it is necessary to identify physical mechanisms that enabled primitive cells to compete with one another. Whereas all modern cell membranes are composed primarily of diacyl or dialkyl glycerol phospholipids, the first cell membranes are thought to have self-assembled from simple, single-chain lipids synthesized in the environment. We asked what selective advantage could have driven the transition from primitive to modern membranes, especially during early stages characterized by low levels of membrane phospholipid. Here we demonstrate that surprisingly low levels of phospholipids can drive protocell membrane growth during competition for single-chain lipids. Growth results from the decreasing fatty acid efflux from membranes with increasing phospholipid content. The ability to synthesize phospholipids from single-chain substrates would have therefore been highly advantageous for early cells competing for a limited supply of lipids. We show that the resulting increase in membrane phospholipid content would have led to a cascade of new selective pressures for the evolution of metabolic and transport machinery to overcome the reduced membrane permeability of diacyl lipid membranes. The evolution of phospholipid membranes could thus have been a deterministic outcome of intrinsic physical processes and a key driving force for early cellular evolution.
C1 [Budin, Itay; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Budin, Itay; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Budin, Itay; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU NASA [EXB02-0031-0018]; Howard Hughes Medical Institute
FX We thank R. Bruckner, A. Ricardo, S. Tobe, T. Zhu, and C. Blain for
discussions and S. Tobe for assistance with nucleotide permeability
experiments. This work was supported by a grant from the NASA Exobiology
Program (EXB02-0031-0018 to J.W.S.). J.W.S. is an Investigator of the
Howard Hughes Medical Institute.
NR 36
TC 75
Z9 79
U1 55
U2 125
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 29
PY 2011
VL 108
IS 13
BP 5249
EP 5254
DI 10.1073/pnas.1100498108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 741VY
UT WOS:000288894800026
PM 21402937
ER
PT J
AU Tinoco, AD
Kim, YG
Tagore, DM
Wiwczar, J
Lane, WS
Danial, NN
Saghatelian, A
AF Tinoco, Arthur D.
Kim, Yun-Gon
Tagore, Debarati M.
Wiwczar, Jessica
Lane, William S.
Danial, Nika N.
Saghatelian, Alan
TI A Peptidomics Strategy To Elucidate the Proteolytic Pathways That
Inactivate Peptide Hormones
SO BIOCHEMISTRY
LA English
DT Article
ID ENHANCED INSULIN-SECRETION; IMPROVED GLUCOSE-TOLERANCE; GLUCAGON-LIKE
PEPTIDE-1; INTESTINAL POLYPEPTIDE; SUBSTRATE-SPECIFICITY;
MASS-SPECTROMETRY; IV INHIBITOR; HUMAN PLASMA; IN-VIVO; MICE
AB Proteolysis plays a key role in regulating the levels and activity of peptide hormones. Characterization of the proteolytic pathways that cleave peptide hormones is of basic interest and can, in some cases, spur the development of novel therapeutics. The lack, however, of an efficient approach to identify endogenous fragments of peptide hormones has hindered the elucidation of these proteolytic pathways. Here, we apply a mass spectrometry (MS) based peptidomics approach to characterize the intestinal fragments of peptide histidine isoleucine (PHI), a hormone that promotes glucose-stimulated insulin secretion (GSIS). Our approach reveals a proteolytic pathway in the intestine that truncates PHI at its C-terminus to produce a PHI fragment that is inactive in a GSIS assay, a result that provides a potential mechanism of PHI regulation in vivo. Differences between these in vivo peptidomics studies and in vitro lysate experiments, which showed N- and C-terminal processing of PHI, underscore the effectiveness of this approach to discover physiologically relevant proteolytic pathways. Moreover, integrating this peptidomics approach with bioassays (i.e., GSIS) provides a general strategy to reveal proteolytic pathways that may regulate the activity of peptide hormones.
C1 [Tinoco, Arthur D.; Kim, Yun-Gon; Tagore, Debarati M.; Saghatelian, Alan] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Wiwczar, Jessica; Danial, Nika N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Wiwczar, Jessica; Danial, Nika N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Lane, William S.] Harvard Univ, Ctr Syst Biol, Mass Spectrometry & Prote Resource Lab, Cambridge, MA 02138 USA.
RP Saghatelian, A (reprint author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA.
EM saghatelian@chemistry.harvard.edu
FU Mary Fieser Postdoctoral Fellowship; Searle Scholar Award; Burroughs
Wellcome Fund Career Award in the Biomedical Sciences; National
Institutes of Health [5 R01 DK078081, 1DP2OD002374]
FX This work was supported by the Mary Fieser Postdoctoral Fellowship
(A.D.T.), Searle Scholar Award (A.S.), Burroughs Wellcome Fund Career
Award in the Biomedical Sciences (N.N.D. and A.S.), National Institutes
of Health Grant 5 R01 DK078081 (N.N.D.), and National Institutes of
Health Grant 1DP2OD002374 (A.S.).
NR 37
TC 11
Z9 11
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 29
PY 2011
VL 50
IS 12
BP 2213
EP 2222
DI 10.1021/bi2000033
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 737MS
UT WOS:000288573500024
PM 21299233
ER
PT J
AU Rolland, M
Frahm, N
Nickle, DC
Jojic, N
Deng, WJ
Allen, TM
Brander, C
Heckerman, DE
Mullins, JI
AF Rolland, Morgane
Frahm, Nicole
Nickle, David C.
Jojic, Nebojsa
Deng, Wenjie
Allen, Todd M.
Brander, Christian
Heckerman, David E.
Mullins, James I.
TI Increased Breadth and Depth of Cytotoxic T Lymphocytes Responses against
HIV-1-B Nef by Inclusion of Epitope Variant Sequences
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR IMMUNE-RESPONSES; INFECTION;
LOAD; HIV; RECOGNITION; PROTEINS; VIREMIA; AIDS; CTL
AB Different vaccine approaches cope with HIV-1 diversity, ranging from centralized(1-4) to variability-encompassing(5-7) antigens. For all these strategies, a concern remains: how does HIV-1 diversity impact epitope recognition by the immune system? We studied the relationship between HIV-1 diversity and CD8(+) T Lymphocytes (CTL) targeting of HIV-1 subtype B Nef using 944 peptides (10-mers overlapping by nine amino acids (AA)) that corresponded to consensus peptides and their most common variants in the HIV-1-B virus population. IFN-gamma ELISpot assays were performed using freshly isolated PBMC from 26 HIV-1-infected persons. Three hundred and fifty peptides elicited a response in at least one individual. Individuals targeted a median of 7 discrete regions. Overall, 33% of responses were directed against viral variants but not elicited against consensus-based test peptides. However, there was no significant relationship between the frequency of a 10-mer in the viral population and either its frequency of recognition (Spearman's correlation coefficient rho = 0.24) or the magnitude of the responses (rho = 0.16). We found that peptides with a single mutation compared to the consensus were likely to be recognized (especially if the change was conservative) and to elicit responses of similar magnitude as the consensus peptide. Our results indicate that cross-reactivity between rare and frequent variants is likely to play a role in the expansion of CTL responses, and that maximizing antigenic diversity in a vaccine may increase the breadth and depth of CTL responses. However, since there are few obvious preferred pathways to virologic escape, the diversity that may be required to block all potential escape pathways may be too large for a realistic vaccine to accommodate. Furthermore, since peptides were not recognized based on their frequency in the population, it remains unclear by which mechanisms variability-inclusive antigens (i.e., constructs enriched with frequent variants) expand CTL recognition.
C1 [Rolland, Morgane; Nickle, David C.; Deng, Wenjie; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Frahm, Nicole; Allen, Todd M.; Brander, Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Jojic, Nebojsa; Brander, Christian] Hosp Badalona Germans Trias & Pujol, AIDS Res Inst IrsiCaixa HIVACAT, Barcelona, Spain.
[Brander, Christian] ICREA, Barcelona, Spain.
[Heckerman, David E.] Microsoft Res, Redmond, WA USA.
RP Rolland, M (reprint author), Henry M Jackson Fdn, Mil HIV Res Program, Rockville, MD 20852 USA.
EM mrolland@hivresearch.org
RI Allen, Todd/F-5473-2011;
OI Brander, Christian/0000-0002-0548-5778
FU Microsoft Research; Bill and Melinda Gates Foundation [43437]; amfAR
[107005-43-RFNT]; Computational Biology Core of the University of
Washington Centers for AIDS Research and STD (National Institutes of
Health) [AI27757]; University of Washington Center for AIDS Research
[P30 AI27757]
FX This work was supported by an unrestricted gift from Microsoft Research,
the Bill and Melinda Gates Foundation (43437) and by grants to MR from
amfAR (Mathilde Krim Fellowship - 107005-43-RFNT), the Computational
Biology Core of the University of Washington Centers for AIDS Research
and STD (National Institutes of Health AI27757), and a grant to JIM from
the University of Washington Center for AIDS Research (P30
AI27757)(bioinformatics core). These funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. DEH is an employee of Microsoft Research
and MR is currently employed by the Henry M. Jackson Foundation for the
Advancement of Military Medicine (HJF) (this study was completed prior
to MR's employment at HJF).
NR 24
TC 15
Z9 15
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 28
PY 2011
VL 6
IS 3
AR e17969
DI 10.1371/journal.pone.0017969
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 743XV
UT WOS:000289053800009
PM 21464919
ER
PT J
AU Yamin, CK
Emani, S
Williams, DH
Lipsitz, SR
Karson, AS
Wald, JS
Bates, DW
AF Yamin, Cyrus K.
Emani, Srinivas
Williams, Deborah H.
Lipsitz, Stuart R.
Karson, Andrew S.
Wald, Jonathan S.
Bates, David W.
TI The Digital Divide in Adoption and Use of a Personal Health Record
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
AB Background: Personal health records (PHRs) offer the potential to improve the patient experience and the quality of patient care. However, the "digital divide," the population-level gap in Internet and computer access, may prevent certain groups from accessing the PHR.
Methods: We conducted a cross-sectional analysis of a PHR within a northeastern health system. We compared adopters (ie, those activating a PHR account online) with nonadopters (ie, those who see a physician offering the PHR but do not activate an account). We further categorized adopters by intensity of PHR use, measured by number of log-ins and number of messages sent to physicians' practices.
Results: As of September 30, 2009, among 75 056 patients, 43% had adopted the PHR since 2002. Blacks and Hispanics were less likely to adopt the PHR compared with whites (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.45-0.55; and 0.64; 0.57-0.73, respectively), and those with lower annual income were less likely to adopt the PHR than were those with higher income. Compared with nonadopters, adopters were more likely to have more than 2 comorbidities (OR, 1.27; 95% CI, 1.17-1.30). Use of an aggressive marketing strategy for PHR enrollment increased adoption nearly 3-fold (OR, 2.92; 95% CI, 1.58-5.40). Intensity of use was best predicted by increasing number of comorbidities, followed by race/ethnicity (whites more than blacks and Hispanics) and insurance status. We found no association between income and log-in frequency or secure messages sent.
Conclusions: Despite increasing Internet availability, racial/ethnic minority patients adopted a PHR less frequently than white patients, and patients with the lowest annual income adopted a PHR less often than those with higher incomes. Among adopters, however, income did not have an effect on PHR use.
C1 [Yamin, Cyrus K.; Emani, Srinivas; Williams, Deborah H.; Lipsitz, Stuart R.; Wald, Jonathan S.; Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med, Dept Med, Boston, MA 02120 USA.
[Yamin, Cyrus K.; Emani, Srinivas; Karson, Andrew S.] Harvard Univ, Sch Med, Boston, MA USA.
[Karson, Andrew S.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA.
[Wald, Jonathan S.; Bates, David W.] Partners HealthCare, Partners Informat Syst, Boston, MA USA.
RP Bates, DW (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, Dept Med, 1620 Tremont St, Boston, MA 02120 USA.
EM dbates@partners.org
FU Harvard Medical School
FX Dr Bates reported owning stock in Medicalis, which makes radiology
ordering applications. Mr Yamin reported receiving funding from Harvard
Medical School.
NR 20
TC 97
Z9 97
U1 5
U2 27
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAR 28
PY 2011
VL 171
IS 6
BP 568
EP 574
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 741LB
UT WOS:000288864100014
PM 21444847
ER
PT J
AU Mendelson, TB
Meltzer, M
Campbell, EG
Caplan, AL
Kirkpatrick, JN
AF Mendelson, Todd B.
Meltzer, Michele
Campbell, Eric G.
Caplan, Arthur L.
Kirkpatrick, James N.
TI Conflicts of Interest in Cardiovascular Clinical Practice Guidelines
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID ASSOCIATION STROKE COUNCIL; PHARMACEUTICAL COMPANY PAYMENTS;
INTERDISCIPLINARY-WORKING-GROUP; PERIPHERAL-VASCULAR-DISEASE;
CARDIOLOGY-COUNCIL; HEART-ASSOCIATION; ISCHEMIC-STROKE; HEALTH-POLICY;
TASK-FORCE; MANAGEMENT
AB Background: Clinical practice guidelines (CPGs) serve as standards of care in practice, quality improvement, and reimbursement. The extent of conflicts of interest (COIs) in cardiology guideline production has not been well studied. Herein, we describe the scope of COIs in CPGs.
Methods: We examined the 17 most recent American College of Cardiology/American Heart Association guidelines through 2008. Using disclosure lists, we cataloged COIs for each participant as receiving a research grant, being on a speaker's bureau and/or receiving honoraria, owning stock, or being a consultant or member of an advisory board. We also cataloged the companies and institutions reported in each disclosure. "Episode" describes 1 instance of participation in 1 guideline by 1 person. "Individual" describes 1 person who may be involved in multiple episodes. "Company" describes a commercial or industry affiliation reported by an individual in a single episode. Analysis involved descriptive statistics and correlation analyses (Pearson correlation coefficient, chi(2) and R(2)).
Results: Fifty-six percent of the 498 individuals reported a COI, corresponding to 56% of the 651 episodes. Being a consultant or member of an advisory board was the most common type. The percentage of episodes involving a COI varied between guidelines (range, 13%-87%). The number of episodes per individual was associated with both presence and number of disclosures (P < .001 for both comparisons). Of 478 companies, the number per guideline ranged from 2 to 242 companies (mean, 38 companies). One company was the most frequently reported company in 7 of 17 guidelines.
Conclusion: Conflicts of interest are prevalent in cardiology guidelines, but there seems to be a significant number of experienced experts without COIs.
C1 [Kirkpatrick, James N.] Univ Penn, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Mendelson, Todd B.; Caplan, Arthur L.; Kirkpatrick, James N.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA.
[Mendelson, Todd B.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Meltzer, Michele] Thomas Jefferson Univ, Dept Med, Div Rheumatol, Philadelphia, PA 19107 USA.
[Campbell, Eric G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA.
RP Kirkpatrick, JN (reprint author), Univ Penn, Dept Med, Div Cardiovasc Med, 3400 Spruce St,9021 Gates Pavil, Philadelphia, PA 19104 USA.
EM James.kirkpatrick@uphs.upenn.edu
NR 49
TC 74
Z9 74
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAR 28
PY 2011
VL 171
IS 6
BP 577
EP 584
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 741LB
UT WOS:000288864100016
PM 21444849
ER
PT J
AU Lo, B
Kelch, RP
Grady, D
AF Lo, Bernard
Kelch, Robert P.
Grady, Deborah
TI Illuminating Physicians' Financial Relationships With Industry
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Lo, Bernard] Univ Calif San Francisco, Program Med Eth, San Francisco, CA 94143 USA.
[Lo, Bernard; Grady, Deborah] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Grady, Deborah] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Kelch, Robert P.] Univ Michigan, Off Execut Vice President Med Affairs Emeritus, Ann Arbor, MI 48109 USA.
[Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Lo, B (reprint author), Univ Calif San Francisco, Program Med Eth, 521 Parnassus Ave,Box 0903,Room C-126, San Francisco, CA 94143 USA.
EM bernie@medicine.ucsf.edu
FU NCRR NIH HHS [1UL1RR024131-01]; NIMH NIH HHS [MH062246]
NR 9
TC 5
Z9 5
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAR 28
PY 2011
VL 171
IS 6
BP 587
EP 589
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 741LB
UT WOS:000288864100019
PM 21444852
ER
PT J
AU Pop-Eleches, C
Thirumurthy, H
Habyarimana, JP
Zivin, JG
Goldstein, MP
de Walque, D
MacKeen, L
Haberer, J
Kimaiyo, S
Sidle, J
Ngare, D
Bangsberg, DR
AF Pop-Eleches, Cristian
Thirumurthy, Harsha
Habyarimana, James P.
Zivin, Joshua G.
Goldstein, Markus P.
de Walque, Damien
MacKeen, Leslie
Haberer, Jessica
Kimaiyo, Sylvester
Sidle, John
Ngare, Duncan
Bangsberg, David R.
TI Mobile phone technologies improve adherence to antiretroviral treatment
in a resource-limited setting: a randomized controlled trial of text
message reminders
SO AIDS
LA English
DT Article
DE adherence; antiretroviral therapy; HIV/AIDS; mobile phones; randomized
controlled trial; sub-Saharan Africa; text message reminders
ID SUB-SAHARAN AFRICA; HIV-INFECTED PATIENTS; MEDICATION ADHERENCE; THERAPY
ADHERENCE; BEHAVIOR-CHANGE; INTERVENTIONS; HEALTH; KENYA; CARE;
NONADHERENCE
AB Objective: There is limited evidence on whether growing mobile phone availability in sub-Saharan Africa can be used to promote high adherence to antiretroviral therapy (ART). This study tested the efficacy of short message service (SMS) reminders on adherence to ART among patients attending a rural clinic in Kenya.
Design: A randomized controlled trial of four SMS reminder interventions with 48 weeks of follow-up.
Methods: Four hundred and thirty-one adult patients who had initiated ART within 3 months were enrolled and randomly assigned to a control group or one of the four intervention groups. Participants in the intervention groups received SMS reminders that were either short or long and sent at a daily or weekly frequency. Adherence was measured using the medication event monitoring system. The primary outcome was whether adherence exceeded 90% during each 12-week period of analysis and the 48-week study period. The secondary outcome was whether there were treatment interruptions lasting at least 48 h.
Results: In intention-to-treat analysis, 53% of participants receiving weekly SMS reminders achieved adherence of at least 90% during the 48 weeks of the study, compared with 40% of participants in the control group (P = 0.03). Participants in groups receiving weekly reminders were also significantly less likely to experience treatment interruptions exceeding 48 h during the 48-week follow-up period than participants in the control group (81 vs. 90%, P = 0.03).
Conclusion: These results suggest that SMS reminders may be an important tool to achieve optimal treatment response in resource-limited settings. (c) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Thirumurthy, Harsha; Goldstein, Markus P.; de Walque, Damien] World Bank, Dev Res Grp, Washington, DC 20433 USA.
[Pop-Eleches, Cristian] Columbia Univ, Sch Int & Publ Affairs, New York, NY USA.
[Pop-Eleches, Cristian] Columbia Univ, Dept Econ, New York, NY 10027 USA.
[Thirumurthy, Harsha] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA.
[Habyarimana, James P.] Georgetown Univ, Publ Policy Inst, Washington, DC USA.
[Zivin, Joshua G.] Univ Calif San Diego, Sch Int Relat & Pacific Studies, San Diego, CA 92103 USA.
[MacKeen, Leslie] US Agcy Int Dev, Bur Global Hlth, Washington, DC 20523 USA.
[Haberer, Jessica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kimaiyo, Sylvester] Moi Univ, Sch Med, Eldoret, Kenya.
[Sidle, John] Indiana Univ Sch Med, Div Gen Internal Med, Indianapolis, IN USA.
[Sidle, John] Moi Univ, Fac Hlth Sci, Dept Med, Eldoret, Kenya.
[Ngare, Duncan] Moi Univ, Sch Publ Hlth, Eldoret, Kenya.
[Bangsberg, David R.] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Haberer, Jessica] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda.
RP Thirumurthy, H (reprint author), World Bank, Dev Res Grp, 1818 H St NW, Washington, DC 20433 USA.
EM hthirumurthy@worldbank.org
RI de Walque, Damien/K-7049-2012; Emchi, Karma/Q-1952-2016;
OI de Walque, Damien/0000-0003-1592-7602; Graff Zivin,
Joshua/0000-0002-0820-4900
FU Bank Netherlands Partnership Program (BNPP) [71 44 565, 7 142 349];
United States Agency for International Development; National Institute
of Mental Health [87228, 87227]
FX The World Bank Research Group provided financial support for this study
under contracts 7 142 349 and 71 44 565 funded by the Bank Netherlands
Partnership Program (BNPP). This research was also supported in part by
a grant to the USAID-AMPATH Partnership from the United States Agency
for International Development as part of the President's Emergency Plan
for AIDS Relief (PEPFAR). J.H. and D. R. B. received support from the
National Institute of Mental Health (87228 and 87227, respectively).
NR 43
TC 315
Z9 320
U1 1
U2 54
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 27
PY 2011
VL 25
IS 6
BP 825
EP 834
DI 10.1097/QAD.0b013e32834380c1
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 736IR
UT WOS:000288487400013
PM 21252632
ER
PT J
AU Eggert, US
AF Eggert, Ulrike S.
TI Chemical approach to understanding cell division
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 241st National Meeting and Exposition of the American-Chemical-Society
(ACS)
CY MAR 27-31, 2011
CL Anaheim, CA
SP Amer Chem Soc
C1 [Eggert, Ulrike S.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 27
PY 2011
VL 241
MA 33-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 782BO
UT WOS:000291982801533
ER
PT J
AU Karajanagi, SS
Lopez-Guerra, G
Park, H
Kobler, JB
Galindo, M
Aanestad, J
Mehta, DD
Kumai, Y
Giordano, N
d'Almeida, A
Heaton, JT
Langer, RS
Herrera, VLM
Faquin, W
Hillman, RE
Zeitels, SM
AF Karajanagi, Sandeep S.
Lopez-Guerra, Gerardo
Park, Hyoungshin
Kobler, James B.
Galindo, Marilyn
Aanestad, Jon
Mehta, Daryush D.
Kumai, Yoshihiko
Giordano, Nicholas
d'Almeida, Anthony
Heaton, James T.
Langer, Robert S.
Herrera, Victoria L. M.
Faquin, William
Hillman, Robert E.
Zeitels, Steven M.
TI Assessment of a new biomaterial designed to restore pliability to
scarred vocal folds
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 241st National Meeting and Exposition of the American-Chemical-Society
(ACS)
CY MAR 27-31, 2011
CL Anaheim, CA
SP Amer Chem Soc
C1 Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Dept Surg, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
Boston Univ, Sch Engn, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 27
PY 2011
VL 241
MA 10-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 782BO
UT WOS:000291982801857
ER
PT J
AU Shur, O
Szilvay, GR
Blenner, MA
Cropek, DM
Banta, SA
AF Shur, Oren
Szilvay, Geza R.
Blenner, Mark A.
Cropek, Donald M.
Banta, Scott A.
TI Beta roll motifs as a novel scaffold for engineering biomolecular
recognition
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 241st National Meeting and Exposition of the American-Chemical-Society
(ACS)
CY MAR 27-31, 2011
CL Anaheim, CA
SP Amer Chem Soc
C1 Columbia Univ, New York, NY USA.
Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA.
Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
USA, Construct Engn Res Lab, Engineer Res & Dev Ctr, Champaign, IL 61824 USA.
VTT Tech Res Ctr, Espoo, Finland.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 27
PY 2011
VL 241
MA 511-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 782BO
UT WOS:000291982801961
ER
PT J
AU Tena, A
Vallabhajosyula, P
Hawley, RJ
Griesemer, A
Yamada, K
Sachs, DH
AF Tena, Aseda
Vallabhajosyula, Prashanth
Hawley, Robert J.
Griesemer, Adam
Yamada, Kazuhiko
Sachs, David H.
TI Quantification of Baboon Thymopoiesis in Porcine Thymokidney Xenografts
by the Signal-Joining T-Cell Receptor Excision Circle Assay
SO TRANSPLANTATION
LA English
DT Article
DE Thymokidney; Thymopoiesis; Signal joint TCR excision circles (sjTREC);
Xenograft
ID THYMIC LOBE TRANSPLANTATION; SKIN-GRAFT TOLERANCE; MINIATURE SWINE;
INDUCTION; BARRIER; TISSUE; MODEL; MICE
AB Background. Transplantation of vascularized donor thymic tissue along with a kidney transplant has markedly improved graft survival across the discordant pig-to-baboon xenogeneic barrier. To quantify the production of baboon T cells by the porcine thymic tissue, we recently developed an assay to measure the excised DNA products of baboon T-cell receptor (TCR) gene rearrangement (signal-joining TCR excision circles, sjTREC).
Methods. Initial polymerase chain reaction (PCR) analysis documented that TCR delta REC-psi J alpha rearrangement occurs in baboons. Primers, specific to baboon sjTREC sequence were designed and used to quantify sjTREC molecules in peripheral blood mononuclear cells and thymic tissue using a quantitative PCR assay.
Results. sjTREC levels were higher in phenotypically naive (CD3(+) CD45RA(+) (+)) T cells (650 copies/100,000 cells) than in phenotypically memory (CD3(+)CD45RA(low)) T cells, with sjTREC below the limit of detection (40 copies/100,000 cells). Surgical removal of the native thymus in two baboons led to a significant decrease of sjTREC in peripheral blood (from 1104 and 920 copies to 184 and 190 copies/100,000 cells, respectively), confirming the role of the thymus in maintaining the peripheral T-cell pool. In two thymectomized baboons that received porcine thymokidney xenografts, sjTREC levels remained low in the peripheral blood (< 40 copies/100,000 cells), but increased to 52 and 192 copies/100,000 cells in thymic biopsies, implying that baboon thymopoiesis had begun to occur in the porcine thymic xenografts.
Conclusions. Baboon sjTREC can be quantified by quantitative PCR using primers specific to baboon sequence. Initial results suggest that baboon thymopoiesis occurs in vascularized porcine thymus xenografts.
C1 [Tena, Aseda; Vallabhajosyula, Prashanth; Hawley, Robert J.; Griesemer, Adam; Yamada, Kazuhiko; Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA.
RP Sachs, DH (reprint author), Massachusetts Gen Hosp E, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA.
EM david.sachs@tbrc.mgh.harvard.edu
FU NIH/NIAID [5PO1A145897-09]; NIH/NIAID/NIDDK [1U01DK080653-02]
FX This work was supported in part by grants from NIH/NIAID 5PO1A145897-09
and NIH/NIAID/NIDDK 1U01DK080653-02.
NR 17
TC 8
Z9 10
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD MAR 27
PY 2011
VL 91
IS 6
BP 639
EP 644
DI 10.1097/TP.0b013e31820b6b52
PG 6
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 731NM
UT WOS:000288115800017
PM 21285918
ER
PT J
AU Spitzer, TR
Sykes, M
Tolkoff-Rubin, N
Kawai, T
McAfee, SL
Dey, BR
Ballen, K
Delmonico, F
Saidman, S
Sachs, DH
Cosimi, AB
AF Spitzer, Thomas R.
Sykes, Megan
Tolkoff-Rubin, Nina
Kawai, Tatsuo
McAfee, Steven L.
Dey, Bimalangshu R.
Ballen, Karen
Delmonico, Francis
Saidman, Susan
Sachs, David H.
Cosimi, A. Benedict
TI Long-Term Follow-Up of Recipients of Combined Human Leukocyte
Antigen-Matched Bone Marrow and Kidney Transplantation for Multiple
Myeloma With End-Stage Renal Disease
SO TRANSPLANTATION
LA English
DT Article
DE Bone marrow; Kidney transplant; Multiple myeloma
ID MIXED LYMPHOHEMATOPOIETIC CHIMERISM; HEMATOPOIETIC-CELL TRANSPLANTATION;
ANTITUMOR RESPONSES; CONDITIONING REGIMEN; DONOR CHIMERISM; IFN-GAMMA;
TOLERANCE; INFUSIONS; THERAPY; HOST
AB Background. Specific tolerance after combined kidney and bone marrow transplantation for multiple myeloma with end-stage renal disease through mixed lymphohematopoietic chimerism has been achieved, as evidenced by prolonged normal renal function without ongoing immunosuppression.
Methods. To achieve potent antimyeloma responses and induce tolerance for the renal allograft, seven patients (median age: 48 years [range: 34-55 years]) with multiple myeloma and end-stage renal disease underwent a combined human leukocyte antigen-matched kidney and bone marrow transplant with lead follow-up time of more than 12 years. Preparative therapy for the transplant consisted of high-dose cyclophosphamide, equine antithymocyte globulin and pretransplant thymic irradiation. Cyclosporine as the sole posttransplant immunosuppressive therapy was tapered and discontinued as early as day 73 posttransplant.
Results. All seven patients achieved mixed chimerism. One patient developed acute graft-versus-host disease and two chronic graft-versus-host disease. Five of seven patients are alive, four with no evidence of myeloma from 4 to 12.1 years posttransplant. Three patients have normal or near-normal renal function without needing systemic immunosuppression. Two patients with normal renal function off immunosuppression were returned to immunosuppressive therapy without evidence of rejection because of the occurrence of chronic graft-versus-host disease.
Conclusions. These long-term follow-up data show that sustained renal allograft tolerance and prolonged antimyeloma responses are achievable after human leukocyte antigen-matched kidney and bone marrow transplantation and the induction of mixed lymphohematopoietic chimerism.
C1 [Spitzer, Thomas R.] Massachusetts Gen Hosp, Bone Marrow Transplant Program, Bone Marrow Transplant Unit, Dept Med, Boston, MA 02114 USA.
[Sykes, Megan; Sachs, David H.] Massachusetts Gen Hosp, Transplant Biol Res Ctr, Dept Surg, Boston, MA 02114 USA.
[Tolkoff-Rubin, Nina] Massachusetts Gen Hosp, Renal Unit, Dept Med, Boston, MA 02114 USA.
[Kawai, Tatsuo; Delmonico, Francis; Cosimi, A. Benedict] Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA.
[Saidman, Susan] Massachusetts Gen Hosp, Dept Pathol, Histocompatibil Lab, Boston, MA 02114 USA.
RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, Bone Marrow Transplant Unit, Dept Med, 0 Emerson Pl,Suite 118, Boston, MA 02114 USA.
EM tspitzer@partners.org
FU Immune Tolerance Network (NIH) [N01 AI15416]; National Institute of
Allergy and Infectious Diseases; Juvenile Diabetes Research Foundation
FX This research was performed with the support of the Immune Tolerance
Network (NIH Contract #N01 AI15416), an international clinical research
consortium headquartered at the University of California San Francisco
and supported by the National Institute of Allergy and Infectious
Diseases and the Juvenile Diabetes Research Foundation (M.S.).
NR 21
TC 63
Z9 67
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD MAR 27
PY 2011
VL 91
IS 6
BP 672
EP 676
DI 10.1097/TP.0b013e31820a3068
PG 5
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 731NM
UT WOS:000288115800022
PM 21217460
ER
PT J
AU Ascierto, PA
De Maio, E
Bertuzzi, S
Palmieri, G
Halaban, R
Hendrix, M
Kashani-Sabet, M
Ferrone, S
Wang, E
Cochran, A
Rivoltini, L
Lee, PP
Fox, BA
Kirkwood, JM
Ullmann, CD
Lehmann, FF
Sznol, M
Schwartzentruber, DJ
Maio, M
Flaherty, K
Galon, J
Ribas, A
Yang, J
Stroncek, DF
Mozzillo, N
Marincola, FM
AF Ascierto, Paolo A.
De Maio, Eleonora
Bertuzzi, Stefano
Palmieri, Giuseppe
Halaban, Ruth
Hendrix, Mary
Kashani-Sabet, Mohamed
Ferrone, Soldano
Wang, Ena
Cochran, Alistair
Rivoltini, Licia
Lee, Peter P.
Fox, Bernard A.
Kirkwood, John M.
Ullmann, Claudio Dansky
Lehmann, Frederic F.
Sznol, Mario
Schwartzentruber, Douglas J.
Maio, Michele
Flaherty, Keith
Galon, Jerome
Ribas, Antoni
Yang, James
Stroncek, David F.
Mozzillo, Nicola
Marincola, Franco M.
TI Future perspectives in melanoma research. Meeting report from the
"Melanoma Research: a bridge Naples-USA. Naples, December 6(th)-7(th)
2010"
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Review
ID PRIMARY CUTANEOUS MELANOMA; PROGNOSTIC-SIGNIFICANCE; COLORECTAL-CANCER;
CELLS; PROTEIN; TUMORS
AB Progress in understanding the molecular basis of melanoma has made possible the identification of molecular targets with important implications in clinical practice. In fact, new therapeutic approaches are emerging from basic science and it will be important to implement their rapid translation into clinical practice by active clinical investigation.
The first meeting of Melanoma Research: a bridge Naples-USA, organized by Paolo A. Ascierto (INT, Naples, Italy) and Francesco Marincola (NIH, Bethesda, USA) took place in Naples, on 6-7 December 2010.
This international congress gathered more than 30 international and Italian faculty members and was focused on recent advances in melanoma molecular biology, immunology and therapy, and created an interactive discussion across Institutions belonging to Government, Academy and Pharmaceutical Industry, in order to stimulate new approaches in basic, translational and clinical research. Four topics of discussion were identified: New pathways in Melanoma, Biomarkers, Clinical Trials and New Molecules and Strategies.
C1 [Ascierto, Paolo A.; De Maio, Eleonora; Mozzillo, Nicola] Fdn Pascale, Ist Nazl Tumori, Dept Melanoma Sarcoma & Head & Neck Dis, Naples, Italy.
[Bertuzzi, Stefano] NIH, Off Director, Off Sci Policy Anal, Off Sci Policy, Bethesda, MD 20892 USA.
[Palmieri, Giuseppe] CNR, Inst Biomol Chem, Unit Canc Genet, Sassari, Italy.
[Halaban, Ruth] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
[Hendrix, Mary] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kashani-Sabet, Mohamed] Calif Pacific Med Ctr, Res Inst, Ctr Melanoma Res & Treatment, San Francisco, CA USA.
[Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Wang, Ena; Stroncek, David F.; Marincola, Franco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Wang, Ena; Stroncek, David F.; Marincola, Franco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA.
[Cochran, Alistair] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Rivoltini, Licia] IRCCS Fdn, Ist Nazl Tumori, Unit Immunotherapy Human Tumors, Milan, Italy.
[Lee, Peter P.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Fox, Bernard A.] Providence Portland Med Ctr, Lab Mol & Tumor Immunol, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Portland, OR USA.
[Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
[Kirkwood, John M.] Univ Pittsburgh, Dept Med, Div Hematol Oncol, Inst Canc, Pittsburgh, PA USA.
[Kirkwood, John M.] Pittsburgh Canc Inst, Melanoma Program, Pittsburgh, PA 15213 USA.
[Ullmann, Claudio Dansky] NCI, Clin Invest Branch, Canc Therapy Evaluat Program DCTD, Bethesda, MD 20892 USA.
[Lehmann, Frederic F.] GlaxoSmithKline Biol, Canc Immunotherapeut Business Unit, Rixensart, Belgium.
[Sznol, Mario] Yale Canc Ctr, New Haven, CT USA.
[Schwartzentruber, Douglas J.] Indiana Univ, Hlth Goshen Ctr Canc Care, Goshen, IN USA.
[Maio, Michele] Univ Siena, Hosp Siena, Ist Toscano Tumori, I-53100 Siena, Italy.
[Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Galon, Jerome] INSERM, U872, Cordeliers Res Ctr, Inserm Grp Leader,Team 15, Paris, France.
[Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Los Angeles, CA 90024 USA.
[Yang, James] NIH, Bethesda, MA USA.
RP Ascierto, PA (reprint author), Fdn Pascale, Ist Nazl Tumori, Dept Melanoma Sarcoma & Head & Neck Dis, Naples, Italy.
EM paolo.ascierto@gmail.com
RI altomonte, maresa/G-7734-2011
FU Italian Ministry of Health [M2/11]; Fondazione Melanoma Onlus; Bristol
Myers Squibb
FX This work was supported by the Italian Ministry of Health "Progetto
Ricerca Corrente Istituto Nazionale Tumori Pascale M2/11 Approccio
multidisciplinare dalla ricerca alla cura del melanoma" and by
Fondazione Melanoma Onlus. Authors would like to thank authors who have
provided Tables originally published in Cancer Vaccines, Second Edition
(2011) edited by Adrian Bot, Mihail Obrocea, and Franco Marincola;
available from Informa Healthcare http://informahealthcare.com/.; PAA
participated in advisory board for Bristol Myers Squibb,
Merck/Schering-Plough, GlaxoSmithKline and Roche. MKS has served on the
Merck/Schering-Plough Advisory Board and Speakers' Bureau, and owns
stock in Melanoma Diagnostics. Myriad Genetics has licensed intellectual
property developed by MKS. JMK is consultant to GSKbio and Morphotek.
FFL is employee of GlaxoSmithKline Biologicals. MS received consulting
fees from Bristol Myers Squibb. KF is consultant to Roche/Genentech and
GlaxoSmithKline. AR participated in advisory board for Roche-Genentech
and Bristol Myers Squibb.
NR 28
TC 8
Z9 8
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD MAR 26
PY 2011
VL 9
AR 32
DI 10.1186/1479-5876-9-32
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 750RE
UT WOS:000289564900001
PM 21439082
ER
PT J
AU Huynh, H
Zheng, JK
Umikawa, M
Silvany, R
Xie, XJ
Wu, CJ
Holzenberger, M
Wang, QM
Zhang, CC
AF Huynh, HoangDinh
Zheng, Junke
Umikawa, Masato
Silvany, Robert
Xie, Xian-Jin
Wu, Catherine J.
Holzenberger, Martin
Wang, Qianming
Zhang, Cheng Cheng
TI Components of the Hematopoietic Compartments in Tumor Stroma and
Tumor-Bearing Mice
SO PLOS ONE
LA English
DT Article
ID EX-VIVO EXPANSION; STEM-CELLS; GROWTH-FACTOR; PROGENITOR CELLS; NICHE;
POPULATION; CANCER; LIVER; IGF-1
AB Solid tumors are composed of cancerous cells and non-cancerous stroma. A better understanding of the tumor stroma could lead to new therapeutic applications. However, the exact compositions and functions of the tumor stroma are still largely unknown. Here, using a Lewis lung carcinoma implantation mouse model, we examined the hematopoietic compartments in tumor stroma and tumor-bearing mice. Different lineages of differentiated hematopoietic cells existed in tumor stroma with the percentage of myeloid cells increasing and the percentage of lymphoid and erythroid cells decreasing over time. Using bone marrow reconstitution analysis, we showed that the tumor stroma also contained functional hematopoietic stem cells. All hematopoietic cells in the tumor stroma originated from bone marrow. In the bone marrow and peripheral blood of tumor-bearing mice, myeloid populations increased and lymphoid and erythroid populations decreased and numbers of hematopoietic stem cells markedly increased with time. To investigate the function of hematopoietic cells in tumor stroma, we co-implanted various types of hematopoietic cells with cancer cells. We found that total hematopoietic cells in the tumor stroma promoted tumor development. Furthermore, the growth of the primary implanted Lewis lung carcinomas and their metastasis were significantly decreased in mice reconstituted with IGF type I receptor-deficient hematopoietic stem cells, indicating that IGF signaling in the hematopoietic tumor stroma supports tumor outgrowth. These results reveal that hematopoietic cells in the tumor stroma regulate tumor development and that tumor progression significantly alters the host hematopoietic compartment.
C1 [Huynh, HoangDinh; Zheng, Junke; Umikawa, Masato; Silvany, Robert; Zhang, Cheng Cheng] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
[Huynh, HoangDinh; Zheng, Junke; Umikawa, Masato; Silvany, Robert; Zhang, Cheng Cheng] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA.
[Xie, Xian-Jin] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
[Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Holzenberger, Martin] Hop St Antoine, INSERM, U515, F-75571 Paris, France.
[Wang, Qianming] S China Normal Univ, Sch Chem & Environm, Guangzhou, Guangdong, Peoples R China.
RP Huynh, H (reprint author), Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
EM Alec.Zhang@UTSouthwestern.edu
FU American Cancer Society [ACS-IRG-02-196]; NIH [K01CA120099]; Welch
Foundation [I-1701]; March of Dimes Foundation; DOD [PR093256]; Cancer
Prevention and Research Institute of Texas [RP100402]
FX American Cancer Society grant ACS-IRG-02-196 (http://www.cancer.org/),
NIH grant K01CA120099
(http://grants1.nih.gov/grants/funding/funding.htm), Welch Foundation
I-1701 ( http://www.welch1.org/), Basil O'Connor Award from the March of
Dimes Foundation (http://www.marchofdimes.com/research/research.html),
DOD Peer Reviewed Medical Research Program PR093256
(https://cdmrp.org/), and Cancer Prevention and Research Institute of
Texas RP100402 (http://www.cprit.state.tx.us/funding-opportunities/)
supported this work. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 21
TC 5
Z9 5
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 25
PY 2011
VL 6
IS 3
AR e18054
DI 10.1371/journal.pone.0018054
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 740SE
UT WOS:000288813900030
PM 21464968
ER
PT J
AU Levis, M
Ravandi, F
Wang, ES
Baer, MR
Perl, A
Coutre, S
Erba, H
Stuart, RK
Baccarani, M
Cripe, LD
Tallman, MS
Meloni, G
Godley, LA
Langston, AA
Amadori, S
Lewis, ID
Nagler, A
Stone, R
Yee, K
Advani, A
Douer, D
Wiktor-Jedrzejczak, W
Juliusson, G
Litzow, MR
Petersdorf, S
Sanz, M
Kantarjian, HM
Sato, T
Tremmel, L
Bensen-Kennedy, DM
Small, D
Smith, BD
AF Levis, Mark
Ravandi, Farhad
Wang, Eunice S.
Baer, Maria R.
Perl, Alexander
Coutre, Steven
Erba, Harry
Stuart, Robert K.
Baccarani, Michele
Cripe, Larry D.
Tallman, Martin S.
Meloni, Giovanna
Godley, Lucy A.
Langston, Amelia A.
Amadori, Sergio
Lewis, Ian D.
Nagler, Arnon
Stone, Richard
Yee, Karen
Advani, Anjali
Douer, Dan
Wiktor-Jedrzejczak, W.
Juliusson, Gunnar
Litzow, Mark R.
Petersdorf, Stephen
Sanz, Miguel
Kantarjian, Hagop M.
Sato, Takashi
Tremmel, Lothar
Bensen-Kennedy, Debra M.
Small, Donald
Smith, B. Douglas
TI Results from a randomized trial of salvage chemotherapy followed by
lestaurtinib for patients with FLT3 mutant AML in first relapse
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE
INHIBITOR; ACUTE MYELOGENOUS LEUKEMIA; IN-VITRO; MUTATIONS; SORAFENIB;
CEP-701; PKC412; COMBINATIONS
AB In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20 mu M. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482. (Blood. 2011;117(12): 3294-3301)
C1 [Levis, Mark; Sato, Takashi; Smith, B. Douglas] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
[Ravandi, Farhad; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Wang, Eunice S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Baer, Maria R.] Univ Maryland, Baltimore, MD 21201 USA.
[Perl, Alexander] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Coutre, Steven] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Erba, Harry] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Stuart, Robert K.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Baccarani, Michele] Univ Bologna, Seragnoli Inst Hematol & Med Oncol, Bologna, Italy.
[Cripe, Larry D.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Tallman, Martin S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Meloni, Giovanna] Univ Roma La Sapienza, Rome, Italy.
[Godley, Lucy A.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Langston, Amelia A.] Emory Univ, Sch Med, Atlanta, GA USA.
[Amadori, Sergio] Univ Roma Tor Vergata, Dept Hematol, Rome, Italy.
[Lewis, Ian D.] Inst Med & Vet Sci, Div Haematol, Adelaide, SA 5000, Australia.
[Nagler, Arnon] Chaim Sheba Med Ctr, Div Hematol & Bone Marrow Transplantat, IL-52621 Tel Hashomer, Israel.
[Stone, Richard] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Yee, Karen] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Advani, Anjali] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA.
[Douer, Dan] Univ So Calif, Keck Sch Med, Norris Canc Ctr, Los Angeles, CA 90033 USA.
[Wiktor-Jedrzejczak, W.] Med Univ Warsaw, Dept Hematol Oncol, Warsaw, Poland.
[Wiktor-Jedrzejczak, W.] Med Univ Warsaw, Dept Internal Dis, Warsaw, Poland.
[Juliusson, Gunnar] Lund Stem Cell Ctr, Dept Hematol, Lund, Sweden.
[Litzow, Mark R.] Mayo Clin, Rochester, MN USA.
[Petersdorf, Stephen] Seattle Canc Care Alliance, Seattle, WA USA.
[Sanz, Miguel] Hosp Univ La Fe, Valencia, Spain.
[Tremmel, Lothar; Bensen-Kennedy, Debra M.] Cephalon Inc, Frazer, PA USA.
RP Levis, M (reprint author), Kimmel Canc Ctr Johns Hopkins, 1650 Orleans St,Rm 243, Baltimore, MD 21231 USA.
EM levisma@jhmi.edu
OI Stuart, Robert/0000-0001-7549-8008; Amadori, Sergio/0000-0002-2356-8681
FU National Cancer Institute (NCI) [P50 CA100632-06, R01 CA128864];
American Society of Clinical Oncology
FX This work was supported the National Cancer Institute (NCI; Leukemia
SPORE P50 CA100632-06, R01 CA128864) and the American Society of
Clinical Oncology (M.L.). M.L. is a Clinical Scholar of the Leukemia &
Lymphoma Society.
NR 31
TC 156
Z9 160
U1 2
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 24
PY 2011
VL 117
IS 12
BP 3294
EP 3301
DI 10.1182/blood-2010-08-301796
PG 8
WC Hematology
SC Hematology
GA 741FJ
UT WOS:000288848500012
PM 21270442
ER
PT J
AU Weisenburger, DD
Savage, KJ
Harris, NL
Gascoyne, RD
Jaffe, ES
MacLennan, KA
Rudiger, T
Pileri, S
Nakamura, S
Nathwani, B
Campo, E
Berger, F
Coiffier, B
Kim, WS
Holte, H
Federico, M
Au, WY
Tobinai, K
Armitage, JO
Vose, JM
AF Weisenburger, Dennis D.
Savage, Kerry J.
Harris, Nancy Lee
Gascoyne, Randy D.
Jaffe, Elaine S.
MacLennan, Kenneth A.
Ruediger, Thomas
Pileri, Stefano
Nakamura, Shigeo
Nathwani, Bharat
Campo, Elias
Berger, Francoise
Coiffier, Bertrand
Kim, Won-Seog
Holte, Harald
Federico, Massimo
Au, Wing Y.
Tobinai, Kensei
Armitage, James O.
Vose, Julie M.
CA Int Peripheral T-Cell Lymphoma Pro
TI Peripheral T-cell lymphoma, not otherwise specified: a report of 340
cases from the International Peripheral T-cell Lymphoma Project
SO BLOOD
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; PROGNOSTIC-FACTORS; CLINICAL-FEATURES;
CLINICOPATHOLOGICAL FEATURES; REAL CLASSIFICATION; JAPANESE PATIENTS;
UNITED-STATES; SINGLE-CENTER; EXPRESSION; OUTCOMES
AB The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (>= 10 cm), thrombocytopenia (< 150 x 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies. (Blood. 2011;117(12):3402-3408)
C1 [Savage, Kerry J.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada.
[Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Harris, Nancy Lee] Harvard Univ, Sch Med, Boston, MA USA.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada.
[Jaffe, Elaine S.] NCI, Dept Hematopathol, Bethesda, MD 20892 USA.
[MacLennan, Kenneth A.] St James Univ Hosp, Sect Pathol, Leeds LS9 7TF, W Yorkshire, England.
[MacLennan, Kenneth A.] St James Univ Hosp, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England.
[Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, Karlsruhe, Germany.
[Pileri, Stefano] Univ Bologna Hosp, Dept Pathol, Bologna, Italy.
[Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
[Nakamura, Shigeo] Nagoya Univ Hosp, Dept Pathol & Lab Med, Nagoya, Aichi, Japan.
[Nathwani, Bharat] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA.
[Nathwani, Bharat] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Campo, Elias] Univ Barcelona, Hosp Clin, Dept Pathol, Barcelona, Spain.
[Berger, Francoise] Ctr Hosp Lyon Sud, Dept Pathol, Lyon, France.
[Coiffier, Bertrand] Ctr Hosp Lyon Sud, Dept Med, Lyon, France.
[Kim, Won-Seog] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol, Seoul, South Korea.
[Holte, Harald] Norwegian Radium Hosp, Dept Oncol, Oslo, Norway.
[Holte, Harald] Oslo Univ Hosp, Oslo, Norway.
[Federico, Massimo] Modena Hosp, Dept Med, Modena, Italy.
[Au, Wing Y.] Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Tobinai, Kensei] Natl Canc Ctr, Hematol & Stem Cell Transplantat Div, Tokyo, Japan.
[Armitage, James O.; Vose, Julie M.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA.
RP Weisenburger, DD (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM dweisenb@unmc.edu
RI Federico, Massimo/A-6801-2012; Nakamura, Shigeo/I-1571-2012; Federico,
Massimo/J-5984-2014; Cuadros, Marta/K-1576-2014; Zinzani, Pier
Luigi/J-9182-2016;
OI Federico, Massimo/0000-0002-9889-3796; Federico,
Massimo/0000-0002-5074-3262; Cuadros, Marta/0000-0002-8329-4854;
Zinzani, Pier Luigi/0000-0002-2112-2651; Jaffe,
Elaine/0000-0003-4632-0301; Campo, elias/0000-0001-9850-9793
NR 39
TC 121
Z9 129
U1 0
U2 10
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 24
PY 2011
VL 117
IS 12
BP 3402
EP 3408
DI 10.1182/blood-2010-09-310342
PG 7
WC Hematology
SC Hematology
GA 741FJ
UT WOS:000288848500023
PM 21270441
ER
PT J
AU Nelson, EA
Walker, SR
Weisberg, E
Bar-Natan, M
Barrett, R
Gashin, LB
Terrell, S
Klitgaard, JL
Santo, L
Addorio, MR
Ebert, BL
Griffin, JD
Frank, DA
AF Nelson, Erik A.
Walker, Sarah R.
Weisberg, Ellen
Bar-Natan, Michal
Barrett, Rosemary
Gashin, Laurie B.
Terrell, Shariya
Klitgaard, Josephine L.
Santo, Loredana
Addorio, Martha R.
Ebert, Benjamin L.
Griffin, James D.
Frank, David A.
TI The STAT5 inhibitor pimozide decreases survival of chronic myelogenous
leukemia cells resistant to kinase inhibitors
SO BLOOD
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; DNA-BINDING ACTIVITY; BCR-ABL; CONSTITUTIVE
ACTIVATION; STEM-CELLS; CONFER RESISTANCE; CANCER-THERAPY; BCR/ABL;
IMATINIB; PHOSPHORYLATION
AB The transcription factor STAT5 is an essential mediator of the pathogenesis of chronic myelogenous leukemia (CML). In CML, the BCR/ABL fusion kinase causes the constitutive activation of STAT5, thereby driving the expression of genes promoting survival. BCR/ABL kinase inhibitors have become the mainstay of therapy for CML, although CML cells can develop resistance through mutations in BCR/ABL. To overcome this problem, we used a cell-based screen to identify drugs that inhibit STAT-dependent gene expression. Using this approach, we identified the psychotropic drug pimozide as a STAT5 inhibitor. Pimozide decreases STAT5 tyrosine phosphorylation, although it does not inhibit BCR/ABL or other tyrosine kinases. Furthermore, pimozide decreases the expression of STAT5 target genes and induces cell cycle arrest and apoptosis in CML cell lines. Pimozide also selectively inhibits colony formation of CD34(+) bone marrow cells from CML patients. Importantly, pimozide induces similar effects in the presence of the T315I BCR/ABL mutation that renders the kinase resistant to presently available inhibitors. Simultaneously inhibiting STAT5 with pimozide and the kinase inhibitors imatinib or nilotinib shows enhanced effects in inhibiting STAT5 phosphorylation and in inducing apoptosis. Thus, targeting STAT5 may be an effective strategy for the treatment of CML and other myeloproliferative diseases. (Blood. 2011;117(12):3421-3429)
C1 [Nelson, Erik A.; Walker, Sarah R.; Weisberg, Ellen; Bar-Natan, Michal; Barrett, Rosemary; Gashin, Laurie B.; Terrell, Shariya; Klitgaard, Josephine L.; Santo, Loredana; Addorio, Martha R.; Ebert, Benjamin L.; Griffin, James D.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Nelson, Erik A.; Walker, Sarah R.; Weisberg, Ellen; Bar-Natan, Michal; Ebert, Benjamin L.; Griffin, James D.; Frank, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Klitgaard, Josephine L.] Symphogen AS, Lyngby, Denmark.
[Klitgaard, Josephine L.] Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark.
RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 522B,44 Binney St, Boston, MA 02115 USA.
EM david_frank@dfci.harvard.edu
OI Grossberg, Laurie/0000-0003-3676-868X
FU National Cancer Institute; Initiative for Chemical Genetics (Bethesda,
MD); Multiple Myeloma Research Foundation (Norwalk, CT); Kittredge
Foundation (Dana-Farber Cancer Institute); Dana-Farber Cancer Institute;
Gabrielle's Angel Foundation (NewYork, NY)
FX This work was supported by the National Cancer Institute and the
Initiative for Chemical Genetics (Bethesda, MD) and was assisted by the
Chemical Biology Platform of the Broad Institute of Harvard and MIT
(Boston, MA). Tissue samples were obtained from the Ted and Eileen
Pasquarello Tissue Bank for Hematologic Malignancies (Dana-Farber Cancer
Institute). This work was also supported by the Multiple Myeloma
Research Foundation (Norwalk, CT), the Kittredge Foundation (Dana-Farber
Cancer Institute), the Brent Leahey Fund (Dana-Farber Cancer Institute),
Gabrielle's Angel Foundation (NewYork, NY), and the Claudia Adams Barr
Program in Innovative Basic Cancer Research (Dana-Farber Cancer
Institute).
NR 34
TC 104
Z9 108
U1 1
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 24
PY 2011
VL 117
IS 12
BP 3421
EP 3429
DI 10.1182/blood-2009-11-255232
PG 9
WC Hematology
SC Hematology
GA 741FJ
UT WOS:000288848500025
PM 21233313
ER
PT J
AU Chapman, MA
Lawrence, MS
Keats, JJ
Cibulskis, K
Sougnez, C
Schinzel, AC
Harview, CL
Brunet, JP
Ahmann, GJ
Adli, M
Anderson, KC
Ardlie, KG
Auclair, D
Baker, A
Bergsagel, PL
Bernstein, BE
Drier, Y
Fonseca, R
Gabriel, SB
Hofmeister, CC
Jagannath, S
Jakubowiak, AJ
Krishnan, A
Levy, J
Liefeld, T
Lonial, S
Mahan, S
Mfuko, B
Monti, S
Perkins, LM
Onofrio, R
Pugh, TJ
Rajkumar, SV
Ramos, AH
Siegel, DS
Sivachenko, A
Stewart, AK
Trudel, S
Vij, R
Voet, D
Winckler, W
Zimmerman, T
Carpten, J
Trent, J
Hahn, WC
Garraway, LA
Meyerson, M
Lander, ES
Getz, G
Golub, TR
AF Chapman, Michael A.
Lawrence, Michael S.
Keats, Jonathan J.
Cibulskis, Kristian
Sougnez, Carrie
Schinzel, Anna C.
Harview, Christina L.
Brunet, Jean-Philippe
Ahmann, Gregory J.
Adli, Mazhar
Anderson, Kenneth C.
Ardlie, Kristin G.
Auclair, Daniel
Baker, Angela
Bergsagel, P. Leif
Bernstein, Bradley E.
Drier, Yotam
Fonseca, Rafael
Gabriel, Stacey B.
Hofmeister, Craig C.
Jagannath, Sundar
Jakubowiak, Andrzej J.
Krishnan, Amrita
Levy, Joan
Liefeld, Ted
Lonial, Sagar
Mahan, Scott
Mfuko, Bunmi
Monti, Stefano
Perkins, Louise M.
Onofrio, Robb
Pugh, Trevor J.
Rajkumar, S. Vincent
Ramos, Alex H.
Siegel, David S.
Sivachenko, Andrey
Stewart, A. Keith
Trudel, Suzanne
Vij, Ravi
Voet, Douglas
Winckler, Wendy
Zimmerman, Todd
Carpten, John
Trent, Jeff
Hahn, William C.
Garraway, Levi A.
Meyerson, Matthew
Lander, Eric S.
Getz, Gad
Golub, Todd R.
TI Initial genome sequencing and analysis of multiple myeloma
SO NATURE
LA English
DT Article
ID B-CELL LYMPHOMA; HUMAN CANCER; SOMATIC MUTATIONS; STRESS-RESPONSE; GENE;
PATHOGENESIS; BLIMP-1; EXOSOME; DIFFERENTIATION; CLASSIFICATION
AB Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-kappa B signalling was indicated by mutations in 11 members of the NF-kappa B pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.
C1 [Chapman, Michael A.; Lawrence, Michael S.; Cibulskis, Kristian; Sougnez, Carrie; Harview, Christina L.; Brunet, Jean-Philippe; Adli, Mazhar; Ardlie, Kristin G.; Bernstein, Bradley E.; Drier, Yotam; Gabriel, Stacey B.; Liefeld, Ted; Mahan, Scott; Monti, Stefano; Onofrio, Robb; Pugh, Trevor J.; Ramos, Alex H.; Sivachenko, Andrey; Voet, Douglas; Winckler, Wendy; Hahn, William C.; Garraway, Levi A.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Golub, Todd R.] Eli & Edythe L Broad Inst, Cambridge Ctr 7, Cambridge, MA 02412 USA.
[Keats, Jonathan J.; Ahmann, Gregory J.; Bergsagel, P. Leif; Fonseca, Rafael; Stewart, A. Keith] Mayo Clin Arizona, Scottsdale, AZ 85259 USA.
[Keats, Jonathan J.; Ahmann, Gregory J.; Anderson, Kenneth C.; Auclair, Daniel; Bergsagel, P. Leif; Fonseca, Rafael; Hofmeister, Craig C.; Jagannath, Sundar; Jakubowiak, Andrzej J.; Krishnan, Amrita; Levy, Joan; Lonial, Sagar; Mfuko, Bunmi; Perkins, Louise M.; Rajkumar, S. Vincent; Siegel, David S.; Stewart, A. Keith; Trudel, Suzanne; Vij, Ravi; Zimmerman, Todd] Multiple Myeloma Res Consortium, Norwalk, CT 06581 USA.
[Schinzel, Anna C.; Anderson, Kenneth C.; Hahn, William C.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Auclair, Daniel; Levy, Joan; Mfuko, Bunmi; Perkins, Louise M.] Multiple Myeloma Res Fdn, Norwalk, CT 06581 USA.
[Baker, Angela; Carpten, John; Trent, Jeff] Translat Genom Res Inst, Phoenix, AZ 85004 USA.
[Bernstein, Bradley E.; Hahn, William C.; Meyerson, Matthew; Lander, Eric S.; Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Bernstein, Bradley E.; Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
[Hofmeister, Craig C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
[Jagannath, Sundar] St Vincents Comprehens Canc Ctr, New York, NY 11001 USA.
[Jakubowiak, Andrzej J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Krishnan, Amrita] City Hope Comprehens Canc Ctr, Duarte, CA 91010 USA.
[Lonial, Sagar] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Rajkumar, S. Vincent] Mayo Clin Rochester, Rochester, MN 55905 USA.
[Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ 07601 USA.
[Trudel, Suzanne] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada.
[Vij, Ravi] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Zimmerman, Todd] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Lander, Eric S.] MIT, Cambridge, MA 02142 USA.
RP Golub, TR (reprint author), Eli & Edythe L Broad Inst, Cambridge Ctr 7, Cambridge, MA 02412 USA.
EM gadgetz@broadinstitute.org; golub@broadinstitute.org
RI Bergsagel, Peter/A-7842-2011; Meyerson, Matthew/E-7123-2012; Hofmeister,
Craig/E-3256-2011; Drier, Yotam/K-5208-2012;
OI Bergsagel, Peter/0000-0003-1523-7388; Hofmeister,
Craig/0000-0003-4816-1607; Drier, Yotam/0000-0003-1725-2995; Monti,
Stefano/0000-0002-9376-0660; Fonseca, Rafael/0000-0002-5938-3769;
Rajkumar, S. Vincent/0000-0002-5862-1833
FU Multiple Myeloma Research Foundation; Leukaemia and Lymphoma Research
(UK)
FX This project was funded by a grant from the Multiple Myeloma Research
Foundation. M.A.C. was supported by a Clinician Scientist Fellowship
from Leukaemia and Lymphoma Research (UK). We are grateful to all
members of the Broad Institute's Biological Samples Platform, Genetic
Analysis Platform, and Genome Sequencing Platform, without whom this
work would not have been possible.
NR 47
TC 649
Z9 661
U1 18
U2 101
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 24
PY 2011
VL 471
IS 7339
BP 467
EP 472
DI 10.1038/nature09837
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200053
PM 21430775
ER
PT J
AU Ceol, CJ
Houvras, Y
Jane-Valbuena, J
Bilodeau, S
Orlando, DA
Battisti, V
Fritsch, L
Lin, WM
Hollmann, TJ
Ferre, F
Bourque, C
Burke, CJ
Turner, L
Uong, A
Johnson, LA
Beroukhim, R
Mermel, CH
Loda, M
Ait-Si-Ali, S
Garraway, LA
Young, RA
Zon, LI
AF Ceol, Craig J.
Houvras, Yariv
Jane-Valbuena, Judit
Bilodeau, Steve
Orlando, David A.
Battisti, Valentine
Fritsch, Lauriane
Lin, William M.
Hollmann, Travis J.
Ferre, Fabrizio
Bourque, Caitlin
Burke, Christopher J.
Turner, Laura
Uong, Audrey
Johnson, Laura A.
Beroukhim, Rameen
Mermel, Craig H.
Loda, Massimo
Ait-Si-Ali, Slimane
Garraway, Levi A.
Young, Richard A.
Zon, Leonard I.
TI The histone methyltransferase SETDB1 is recurrently amplified in
melanoma and accelerates its onset
SO NATURE
LA English
DT Article
ID MALIGNANT-MELANOMA; BRAF MUTATIONS; HUMAN CANCER; GENES; NEVI;
SENESCENCE; EXPRESSION; REPRESSION; LYSINE-9; CELLS
AB The most common mutation in human melanoma, BRAF(V600E), activates the serine/threonine kinase BRAF and causes excessive activity in the mitogen-activated protein kinase pathway(1,2). BRAF(V600E) mutations are also present in benign melanocytic naevi(3), highlighting the importance of additional genetic alterations in the genesis of malignant tumours. Such changes include recurrent copy number variations that result in the amplification of oncogenes(4,5). For certain amplifications, the large number of genes in the interval has precluded an understanding of the cooperating oncogenic events. Here we have used a zebrafish melanoma model to test genes in a recurrently amplified region of chromosome 1 for the ability to cooperate with BRAF(V600E) and accelerate melanoma. SETDB1, an enzyme that methylates histone H3 on lysine 9 (H3K9), was found to accelerate melanoma formation significantly in zebrafish. Chromatin immunoprecipitation coupled with massively parallel DNA sequencing and gene expression analyses uncovered genes, including HOX genes, that are transcriptionally dysregulated in response to increased levels of SETDB1. Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumorigenesis.
C1 [Ceol, Craig J.; Houvras, Yariv; Bourque, Caitlin; Burke, Christopher J.; Turner, Laura; Uong, Audrey; Zon, Leonard I.] Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Houvras, Yariv] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Jane-Valbuena, Judit; Lin, William M.; Johnson, Laura A.; Beroukhim, Rameen; Mermel, Craig H.; Garraway, Levi A.] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
[Jane-Valbuena, Judit; Lin, William M.; Johnson, Laura A.; Beroukhim, Rameen; Mermel, Craig H.; Garraway, Levi A.] Harvard Univ, Ctr Canc Genome Discovery, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
[Jane-Valbuena, Judit; Lin, William M.; Johnson, Laura A.; Beroukhim, Rameen; Mermel, Craig H.; Garraway, Levi A.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA.
[Bilodeau, Steve; Orlando, David A.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Battisti, Valentine; Fritsch, Lauriane; Ait-Si-Ali, Slimane] Univ Paris Diderot, Epigenet & Destin Cellulaire UMR7216, CNRS, F-75013 Paris, France.
[Hollmann, Travis J.; Loda, Massimo] Harvard Univ, Ctr Mol Oncol Pathol, Brigham & Womens Hosp, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA.
[Ferre, Fabrizio] Univ Roma La Sapienza, A Rossi Fanelli Biochem Sci Dept, I-00185 Rome, Italy.
RP Zon, LI (reprint author), Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
RI Young, Richard/F-6495-2012;
OI Young, Richard/0000-0001-8855-8647; FERRE', FABRIZIO/0000-0003-2768-5305
FU Damon Runyon Cancer Research Foundation [DRG-1855-05]; Charles A. King
Trust Foundation; American Society of Clinical Oncology; Canadian
Institutes of Health Research; National Institutes of Health
[K99AR056899-02, K08DK075432-04, CA146455, HG002668, CA103846, DK055381]
FX We thank D. Harrington, R. White and Y. Zhou for discussions; C.
Lawrence, I. Adatto and L.-K. Zhang for expert fish care; G. Frampton
for bioinformatics assistance; and K. Kwan, C.-B. Chien, and J. Boehm
for reagents. This work was supported by grants from the Damon Runyon
Cancer Research Foundation (C.J.C., DRG-1855-05), the Charles A. King
Trust Foundation (C.J.C.), a Young Investigator Award from the American
Society of Clinical Oncology (Y.H.), the Canadian Institutes of Health
Research (S.B.) and the National Institutes of Health (C.J.C.,
K99AR056899-02; Y.H., K08DK075432-04; R.A.Y., CA146455, HG002668; and
L.I.Z., CA103846 and DK055381).
NR 23
TC 184
Z9 187
U1 2
U2 35
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 24
PY 2011
VL 471
IS 7339
BP 513
EP +
DI 10.1038/nature09806
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200062
PM 21430779
ER
PT J
AU White, RM
Cech, J
Ratanasirintrawoot, S
Lin, CY
Rahl, PB
Burke, CJ
Langdon, E
Tomlinson, ML
Mosher, J
Kaufman, C
Chen, F
Long, HK
Kramer, M
Datta, S
Neuberg, D
Granter, S
Young, RA
Morrison, S
Wheeler, GN
Zon, LI
AF White, Richard Mark
Cech, Jennifer
Ratanasirintrawoot, Sutheera
Lin, Charles Y.
Rahl, Peter B.
Burke, Christopher J.
Langdon, Erin
Tomlinson, Matthew L.
Mosher, Jack
Kaufman, Charles
Chen, Frank
Long, Hannah K.
Kramer, Martin
Datta, Sumon
Neuberg, Donna
Granter, Scott
Young, Richard A.
Morrison, Sean
Wheeler, Grant N.
Zon, Leonard I.
TI DHODH modulates transcriptional elongation in the neural crest and
melanoma
SO NATURE
LA English
DT Article
ID CARBAMOYL-PHOSPHATE SYNTHETASE; ZEBRAFISH; LEFLUNOMIDE; EXPRESSION;
INHIBITOR; DISCOVERY; KINASE; CELLS; GENE
AB Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma(1). We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation.
C1 [White, Richard Mark; Cech, Jennifer; Ratanasirintrawoot, Sutheera; Burke, Christopher J.; Langdon, Erin; Kaufman, Charles; Datta, Sumon; Zon, Leonard I.] Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
[White, Richard Mark; Kaufman, Charles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lin, Charles Y.; Rahl, Peter B.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Lin, Charles Y.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Tomlinson, Matthew L.; Wheeler, Grant N.] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England.
[Mosher, Jack; Morrison, Sean] Univ Michigan, Howard Hughes Med Inst, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA.
[Chen, Frank] Harvard Univ, Cambridge, MA 02138 USA.
[Long, Hannah K.] Univ Cambridge, Cambridge CB2 1TN, England.
[Kramer, Martin] Genzyme Corp, Cambridge, MA 02142 USA.
[Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Granter, Scott] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Zon, LI (reprint author), Harvard Univ, Stem Cell Program & Hematol Oncol, Childrens Hosp Boston,Med Sch, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
RI Wheeler, Grant/D-3023-2009; Young, Richard/F-6495-2012; Long,
Hannah/A-6301-2013
OI Young, Richard/0000-0001-8855-8647;
FU Howard Hughes Medical Institute; National Cancer Institute (National
Institutes of Health); American Society for Clinical Oncology; National
Institute of Arthritis and Musculoskeletal and SkinDiseases (National
Institutes of Health); Biotechnology and Biological Sciences Research
Council/Pfizer
FX We thank G. Bollag and P. Lin for supplying PLX4720. The melanoma
xenografts were performed with the assistance of T. Venezia-Bowman. In
situ hybridization probes for crestin were supplied by P. Henion. We
thank S. Lacadie, C. Ceol, Y. Houvras, T. Bowman, X. Bai and R. Field
for discussions and/or comments on the manuscript. This work was
supported by the Howard Hughes Medical Institute and the National Cancer
Institute (National Institutes of Health) (L.I.Z.), Aid for Cancer
Research, the American Society for Clinical Oncology and the National
Institute of Arthritis and Musculoskeletal and SkinDiseases (National
Institutes of Health) (R.M.W.). M.L.T. was a Biotechnology and
Biological Sciences Research Council/Pfizer Industrial CASE award
recipient.
NR 26
TC 154
Z9 157
U1 2
U2 21
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 24
PY 2011
VL 471
IS 7339
BP 518
EP 522
DI 10.1038/nature09882
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200063
PM 21430780
ER
PT J
AU Negre, N
Brown, CD
Ma, LJ
Bristow, CA
Miller, SW
Wagner, U
Kheradpour, P
Eaton, ML
Loriaux, P
Sealfon, R
Li, ZR
Ishii, H
Spokony, RF
Chen, J
Hwang, L
Cheng, C
Auburn, RP
Davis, MB
Domanus, M
Shah, PK
Morrison, CA
Zieba, J
Suchy, S
Senderowicz, L
Victorsen, A
Bild, NA
Grundstad, AJ
Hanley, D
MacAlpine, DM
Mannervik, M
Venken, K
Bellen, H
White, R
Gerstein, M
Russell, S
Grossman, RL
Ren, B
Posakony, JW
Kellis, M
White, KP
AF Negre, Nicolas
Brown, Christopher D.
Ma, Lijia
Bristow, Christopher Aaron
Miller, Steven W.
Wagner, Ulrich
Kheradpour, Pouya
Eaton, Matthew L.
Loriaux, Paul
Sealfon, Rachel
Li, Zirong
Ishii, Haruhiko
Spokony, Rebecca F.
Chen, Jia
Hwang, Lindsay
Cheng, Chao
Auburn, Richard P.
Davis, Melissa B.
Domanus, Marc
Shah, Parantu K.
Morrison, Carolyn A.
Zieba, Jennifer
Suchy, Sarah
Senderowicz, Lionel
Victorsen, Alec
Bild, Nicholas A.
Grundstad, A. Jason
Hanley, David
MacAlpine, David M.
Mannervik, Mattias
Venken, Koen
Bellen, Hugo
White, Robert
Gerstein, Mark
Russell, Steven
Grossman, Robert L.
Ren, Bing
Posakony, James W.
Kellis, Manolis
White, Kevin P.
TI A cis-regulatory map of the Drosophila genome
SO NATURE
LA English
DT Article
ID TRANSCRIPTION FACTOR; ENHANCERS; MELANOGASTER; EXPRESSION; BLASTODERM;
PROTEINS
AB Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide(1,2) has successfully identified specific subtypes of regulatory elements(3). In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements(4), chromatin states(5), transcription factor binding sites(6-9), RNA polymerase II regulation(8) and insulator elements(10); however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships.
C1 [Negre, Nicolas; Brown, Christopher D.; Ma, Lijia; Spokony, Rebecca F.; Davis, Melissa B.; Domanus, Marc; Morrison, Carolyn A.; Zieba, Jennifer; Suchy, Sarah; Senderowicz, Lionel; Victorsen, Alec; Bild, Nicholas A.; Grundstad, A. Jason; Grossman, Robert L.; White, Kevin P.] Univ Chicago, Inst Genom & Syst Biol, Dept Human Genet, Chicago, IL 60637 USA.
[Bristow, Christopher Aaron; Kheradpour, Pouya; Sealfon, Rachel; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Broad Inst MIT & Harvard, Cambridge, MA 02139 USA.
[Miller, Steven W.; Ishii, Haruhiko; Posakony, James W.] Univ Calif San Diego, Div Biol Sci CDB, La Jolla, CA 92093 USA.
[Wagner, Ulrich; Li, Zirong; Hwang, Lindsay; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
[Eaton, Matthew L.] Duke Univ, Dept Pharmacol & Canc Biol, Med Ctr, Durham, NC 27710 USA.
[Loriaux, Paul] Univ Calif San Diego, Signaling Syst Lab, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Chen, Jia; Hanley, David; Grossman, Robert L.] Univ Illinois, Natl Ctr Data Min, Chicago, IL 60607 USA.
[Cheng, Chao; Gerstein, Mark] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
[Cheng, Chao; Gerstein, Mark] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Cheng, Chao] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
[Auburn, Richard P.; Russell, Steven] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
[Auburn, Richard P.; Russell, Steven] Univ Cambridge, Cambridge Syst Biol Ctr, Cambridge CB2 3EH, England.
[Shah, Parantu K.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Mannervik, Mattias] Stockholm Univ, Dept Dev Biol, Wenner Gren Inst, Arrhenius Labs E3, S-10691 Stockholm, Sweden.
[Venken, Koen; Bellen, Hugo] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[White, Robert] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England.
[Grossman, Robert L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Ren, Bing] Inst Genom Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[Ren, Bing] Moores Canc Ctr, La Jolla, CA 92093 USA.
RP White, KP (reprint author), Univ Chicago, Inst Genom & Syst Biol, Dept Human Genet, 900 E 57th St, Chicago, IL 60637 USA.
EM kpwhite@uchicago.edu
RI Eaton, Matthew/C-4408-2011; White, Rob/G-4835-2012; Russell,
Steve/A-4072-2011; Venken, Koen/B-9909-2013;
OI Russell, Steve/0000-0003-0546-3031; Venken, Koen/0000-0003-0741-4698;
Mannervik, Mattias/0000-0003-4999-9655; Grossman,
Robert/0000-0003-3741-5739; Bellen, Hugo/0000-0001-5992-5989; Negre,
Nicolas/0000-0001-9727-3416; Brown, Christopher/0000-0002-3785-5008
FU National Human Genome Research Institute [U01HG004264]; Chicago
Biomedical Consortium; Chicago Community Trust; Lilly-Life Sciences
Research Foundation; NIH NRSA; Isaac Newton Trust; Department of Energy;
NHGRI [U01 HG004279]
FX This work was supported by U01HG004264 from the National Human Genome
Research Institute to K.P.W. and also funded by the Chicago Biomedical
Consortium with support from the Searle Funds at the Chicago Community
Trust. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Human
Genome Research Institute (NHGRI) or the National Institutes of Health
(NIH). C.D.B. is supported by a Lilly-Life Sciences Research Foundation
fellowship. C.A.B. is supported by a NIH NRSA postdoctoral fellowship.
R.P.A. is in part supported by an Isaac Newton Trust award to R.W.P.L.
was supported by a grant from the Department of Energy Computational
Sciences Graduate Fellowship (DOE CSGF). M.E.L. and D.M.M. work was
supported by NHGRI grant U01 HG004279. We thank the Functional Genomics
Facility at the University of Chicago and the High-Throughput Genome
Analysis Core at Argonne National Laboratory for processing of
microarrays and of Illumina sequence. We thank T.-R. Li, J.D. Lambert,
S. Rifkin, T. Herreman, C. Mason, L. Sun and Z. Gauhar for producing the
developmental expression microarray data. We also thank the many members
of the Drosophila community who contributed to this work by providing
reagents. A complete list of community participants is included in the
Supplementary Methods.
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PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 24
PY 2011
VL 471
IS 7339
BP 527
EP 531
DI 10.1038/nature09990
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200065
PM 21430782
ER
PT J
AU Flynn, RL
Centore, RC
O'Sullivan, RJ
Rai, R
Tse, A
Zhou, SY
Chang, S
Karlseder, J
Zou, L
AF Flynn, Rachel Litman
Centore, Richard C.
O'Sullivan, Roderick J.
Rai, Rekha
Tse, Alice
Zhou Songyang
Chang, Sandy
Karlseder, Jan
Zou, Lee
TI TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric
single-stranded DNA
SO NATURE
LA English
DT Article
ID REPLICATION PROTEIN-A; REPEAT-CONTAINING RNA; FISSION YEAST; CHROMOSOME
ENDS; BINDING PROTEIN; ATR; DAMAGE; POT1; RPA; ELONGATION
AB Maintenance of telomeres requires both DNA replication and telomere 'capping' by shelterin. These two processes use two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomeres 1 (POT1). Although RPA and POT1 each have a critical role at telomeres, how they function in concert is not clear. POT1 ablation leads to activation of the ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase at telomeres(1,2), suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. Unexpectedly, we found that purified POT1 and its functional partner TPP1 are unable to prevent RPA binding to telomeric ssDNA efficiently. In cell extracts, we identified a novel activity that specifically displaces RPA, but not POT1, from telomeric ssDNA. Using purified protein, here we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) recapitulates the RPA displacing activity. The RPA displacing activity is inhibited by the telomeric repeat-containing RNA (TERRA) in early S phase, but is then unleashed in late S phase when TERRA levels decline at telomeres(3). Interestingly, TERRA also promotes POT1 binding to telomeric ssDNA by removing hnRNPA1, suggesting that the reaccumulation of TERRA after S phase helps to complete the RPA-to-POT1 switch on telomeric ssDNA. Together, our data suggest that hnRNPA1, TERRA and POT1 act in concert to displace RPA from telomeric ssDNA after DNA replication, and promote telomere capping to preserve genomic integrity.
C1 [Flynn, Rachel Litman; Centore, Richard C.; Tse, Alice; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
[Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[O'Sullivan, Roderick J.; Karlseder, Jan] Salk Inst Biol Studies, Mol & Cellular Lab, La Jolla, CA 92037 USA.
[Rai, Rekha; Chang, Sandy] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA.
[Zhou Songyang] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
EM zou.lee@mgh.harvard.edu
RI rai, rekha/A-3680-2012
FU National Institutes of Health (NIH) [5T32CA009216-28, F32-GM089150,
CA133249, CA129037, GM06525, AG025837, GM076388]; American Cancer
Society [0902501]; George E. Hewitt Foundation for Medical Research;
Welch Foundation [Q-1673]; ACS [RSG-08-297]
FX We thank T. de Lange, A. Krainer, B. Chabot and M. Wold for reagents,
and members of the Zou laboratory for discussion. L.Z. is an Ellison New
Scholar on Aging. R.L.F. is supported by National Institutes of Health
(NIH) fellowship 5T32CA009216-28 and American Cancer Society fellowship
0902501. R.C.C. is supported by NIH fellowship F32-GM089150. R.J.O. is
supported by the George E. Hewitt Foundation for Medical Research. This
work is supported by a Welch Foundation grant (Q-1673) to Z.S., an ACS
grant (RSG-08-297) to L.Z., and NIH grants CA133249 to Z.S., CA129037 to
S.C., GM06525 and AG025837 to J.K. and GM076388 to L.Z.
NR 30
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U1 2
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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 24
PY 2011
VL 471
IS 7339
BP 532
EP +
DI 10.1038/nature09772
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 739GJ
UT WOS:000288702200066
PM 21399625
ER
PT J
AU Chabner, BA
AF Chabner, Bruce A.
TI Early Accelerated Approval for Highly Targeted Cancer Drugs
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CELL LUNG-CANCER; INHIBITION
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
NR 7
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U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 24
PY 2011
VL 364
IS 12
BP 1087
EP 1089
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 739FY
UT WOS:000288701100002
PM 21428763
ER
PT J
AU McCormack, M
Alfirevic, A
Bourgeois, S
Farrell, JJ
Kasperaviciute, D
Carrington, M
Sills, GJ
Marson, T
Jia, XM
de Bakker, PIW
Chinthapalli, K
Molokhia, M
Johnson, MR
O'Connor, GD
Chaila, E
Alhusaini, S
Shianna, KV
Radtke, RA
Heinzen, EL
Walley, N
Pandolfo, M
Pichler, W
Park, BK
Depondt, C
Sisodiya, SM
Goldstein, DB
Deloukas, P
Delanty, N
Cavalleri, GL
Pirmohamed, M
AF McCormack, Mark
Alfirevic, Ana
Bourgeois, Stephane
Farrell, John J.
Kasperaviciute, Dalia
Carrington, Mary
Sills, Graeme J.
Marson, Tony
Jia, Xiaoming
de Bakker, Paul I. W.
Chinthapalli, Krishna
Molokhia, Mariam
Johnson, Michael R.
O'Connor, Gerard D.
Chaila, Elijah
Alhusaini, Saud
Shianna, Kevin V.
Radtke, Rodney A.
Heinzen, Erin L.
Walley, Nicole
Pandolfo, Massimo
Pichler, Werner
Park, B. Kevin
Depondt, Chantal
Sisodiya, Sanjay M.
Goldstein, David B.
Deloukas, Panos
Delanty, Norman
Cavalleri, Gianpiero L.
Pirmohamed, Munir
TI HLA-A*3101 and Carbamazepine-Induced Hypersensitivity Reactions in
Europeans
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID STEVENS-JOHNSON-SYNDROME; TOXIC EPIDERMAL NECROLYSIS; ADVERSE
DRUG-REACTIONS; HUMAN-LEUKOCYTE ANTIGEN-B-ASTERISK-5701; GENERALIZED
EXANTHEMATOUS PUSTULOSIS; INDUCED LIVER-INJURY; HLA-B; ABACAVIR
HYPERSENSITIVITY; COST-EFFECTIVENESS; DRESS SYNDROME
AB BACKGROUND
Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.
METHODS
We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions.
RESULTS
The HLA-A*3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P = 3.5x10(-8)). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLAA*3101 allele (P = 1.1x10(-6)). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS-TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18).
CONCLUSIONS
The presence of the HLA-A* 3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%.
C1 [Alfirevic, Ana] Univ Liverpool, Wolfson Ctr Personalised Med, Dept Mol & Clin Pharmacol, Inst Translat Med, Liverpool L69 3GL, Merseyside, England.
[McCormack, Mark; Alhusaini, Saud; Delanty, Norman; Cavalleri, Gianpiero L.] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[O'Connor, Gerard D.; Chaila, Elijah; Delanty, Norman] Beaumont Hosp, Div Neurol, Dublin 9, Ireland.
[Marson, Tony] Walton Ctr Neurol, Liverpool, Merseyside, England.
[Bourgeois, Stephane; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England.
[Chinthapalli, Krishna; Sisodiya, Sanjay M.] Natl Soc Epilepsy, Gerrards Cross, Bucks, England.
[Farrell, John J.] Boston Univ, Dept Med, Boston, MA 02215 USA.
[Carrington, Mary] Harvard Univ, Massachusetts Gen Hosp, MIT, Sch Med,Ragon Inst, Boston, MA USA.
[Jia, Xiaoming] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA.
[de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Div Genet, Dept Med,Med Sch, Boston, MA 02115 USA.
[Kasperaviciute, Dalia; Chinthapalli, Krishna; Sisodiya, Sanjay M.] UCL, Dept Clin & Expt Epilepsy, Inst Neurol, London, England.
[Molokhia, Mariam] Kings Coll London, Dept Primary Care & Publ Hlth Sci, Div Hlth & Social Care Res, London WC2R 2LS, England.
[Johnson, Michael R.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Ctr Neurosci, London, England.
[Carrington, Mary] NCI, Canc & Inflammat Program, Lab Expt Immunol, SAIC Frederick, Frederick, MD 21701 USA.
[de Bakker, Paul I. W.] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[de Bakker, Paul I. W.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr, Dept Med Genet, Div Biomed Genet, Utrecht, Netherlands.
[Shianna, Kevin V.; Heinzen, Erin L.; Walley, Nicole; Goldstein, David B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC USA.
[Radtke, Rodney A.] Duke Univ, Sch Med, Dept Med Neurol, Durham, NC USA.
[Pandolfo, Massimo; Depondt, Chantal] Univ Libre Bruxelles, Dept Neurol, Hop Erasme, Brussels, Belgium.
[Pichler, Werner] Univ Bern, Dept Rheumatol Clin Immunol & Allergol, Bern, Switzerland.
RP Alfirevic, A (reprint author), Univ Liverpool, Wolfson Ctr Personalised Med, Dept Mol & Clin Pharmacol, Inst Translat Med, Block A,Waterhouse Bldgs,1-5 Brownlow St, Liverpool L69 3GL, Merseyside, England.
EM ana.alfirevic@liv.ac.uk
RI Cavalleri, Gianpiero/A-6632-2010; Pirmohamed, Munir/H-6004-2011;
Deloukas, Panos/B-2922-2013; de Bakker, Paul/B-8730-2009; McCormack,
Mark/A-5482-2010;
OI Pirmohamed, Munir/0000-0002-7534-7266; Deloukas,
Panos/0000-0001-9251-070X; de Bakker, Paul/0000-0001-7735-7858;
McCormack, Mark/0000-0002-8213-6141; Delaney,
Norman/0000-0002-3953-9842; Cavalleri, Gianpiero/0000-0002-9802-0506
FU U.K. Department of Health; Department of Health; National Health Service
Chair of Pharmacogenetics; Medical Research Council Centre for Drug
Safety Science; Wolfson Foundation; Wellcome Trust Sanger Institute;
National Institute for Health Research; Medical Research Council
[G0400126]; Wellcome Trust [084730]; University College London Hospitals
Charity; Clinical Research and Development Committee [F136]; National
Institute for Health Research [08-08-SCC]; Brainwave-the Irish Epilepsy
Association [2009/001]; Medical Research Charities Group of Ireland;
Health Research Board; National Society for Epilepsy; Fonds National de
la Recherche Scientifique; Fonds Erasme pour la Recherche Medicale;
Universite Libre de Bruxelles (Belgium); Health Research Board of
Ireland; Department of Health National Institute for Health Research
Biomedical Research Centres; National Cancer Institute
[HHS-N261200800001E]; National Cancer Institute, National Institutes of
Health
FX Funded by the U.K. Department of Health and others.; Supported by grants
to the Liverpool collaborators from the Department of Health, the
National Health Service Chair of Pharmacogenetics, the Medical Research
Council Centre for Drug Safety Science, the Wolfson Foundation, the
Wellcome Trust Sanger Institute, and the National Institute for Health
Research (to Dr. Pirmohamed); by grants to the EPIGEN consortium from
the Medical Research Council (G0400126), the Wellcome Trust (084730),
University College London Hospitals Charity, Clinical Research and
Development Committee (F136), and the National Institute for Health
Research (08-08-SCC); by an award (2009/001) from Brainwave-the Irish
Epilepsy Association; by the Medical Research Charities Group of
Ireland, the Health Research Board, the National Society for Epilepsy,
Fonds National de la Recherche Scientifique, and Fonds Erasme pour la
Recherche Medicale, Universite Libre de Bruxelles (Belgium); by a
Translational Research Scholars award from the Health Research Board of
Ireland (to Mr. McCormack); by the Department of Health National
Institute for Health Research Biomedical Research Centres; and by a
contract from the National Cancer Institute (HHS-N261200800001E) and the
Intramural Research Program at the National Cancer Institute, National
Institutes of Health.
NR 40
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U1 6
U2 32
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 24
PY 2011
VL 364
IS 12
BP 1134
EP 1143
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 739FY
UT WOS:000288701100008
PM 21428769
ER
PT J
AU Murali, MR
Castells, MC
Song, JY
Dudzinski, DM
Hasserjian, RP
AF Murali, Mandakolathur R.
Castells, Mariana C.
Song, James Y.
Dudzinski, David M.
Hasserjian, Robert P.
TI A Man with Flushing and Hypotension Indolent systemic mastocytosis.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID KOUNIS-SYNDROME; SM-AHNMD; TRYPTASE; ANAPHYLAXIS; DISEASE
C1 [Murali, Mandakolathur R.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
[Dudzinski, David M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Song, James Y.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Castells, Mariana C.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Murali, Mandakolathur R.; Castells, Mariana C.; Dudzinski, David M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Song, James Y.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Hasserjian, Robert P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Murali, MR (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
NR 26
TC 4
Z9 4
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 24
PY 2011
VL 364
IS 12
BP 1155
EP 1165
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 739FY
UT WOS:000288701100012
PM 21428772
ER
PT J
AU Sequist, LV
Waltman, BA
Dias-Santagata, D
Digumarthy, S
Turke, AB
Fidias, P
Bergethon, K
Shaw, AT
Gettinger, S
Cosper, AK
Akhavanfard, S
Heist, RS
Temel, J
Christensen, JG
Wain, JC
Lynch, TJ
Vernovsky, K
Mark, EJ
Lanuti, M
Iafrate, AJ
Mino-Kenudson, M
Engelman, JA
AF Sequist, Lecia V.
Waltman, Belinda A.
Dias-Santagata, Dora
Digumarthy, Subba
Turke, Alexa B.
Fidias, Panos
Bergethon, Kristin
Shaw, Alice T.
Gettinger, Scott
Cosper, Arjola K.
Akhavanfard, Sara
Heist, Rebecca S.
Temel, Jennifer
Christensen, James G.
Wain, John C.
Lynch, Thomas J.
Vernovsky, Kathy
Mark, Eugene J.
Lanuti, Michael
Iafrate, A. John
Mino-Kenudson, Mari
Engelman, Jeffrey A.
TI Genotypic and Histological Evolution of Lung Cancers Acquiring
Resistance to EGFR Inhibitors
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITORS; NONSMALL CELL;
MESENCHYMAL TRANSITION; GEFITINIB RESISTANCE; MET AMPLIFICATION;
NEUROENDOCRINE TUMORS; ACTIVATING MUTATIONS; T790M MUTATIONS; GENE
MUTATION
AB Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitors, but drug resistance invariably emerges. To elucidate mechanisms of acquired drug resistance, we performed systematic genetic and histological analyses of tumor biopsies from 37 patients with drug-resistant non-small cell lung cancers (NSCLCs) carrying EGFR mutations. All drug-resistant tumors retained their original activating EGFR mutations, and some acquired known mechanisms of resistance including the EGFR T790M mutation or MET gene amplification. Some resistant cancers showed unexpected genetic changes including EGFR amplification and mutations in the PIK3CA gene, whereas others underwent a pronounced epithelial-to-mesenchymal transition. Surprisingly, five resistant tumors (14%) transformed from NSCLC into small cell lung cancer (SCLC) and were sensitive to standard SCLC treatments. In three patients, serial biopsies revealed that genetic mechanisms of resistance were lost in the absence of the continued selective pressure of EGFR inhibitor treatment, and such cancers were sensitive to a second round of treatment with EGFR inhibitors. Collectively, these results deepen our understanding of resistance to EGFR inhibitors and underscore the importance of repeatedly assessing cancers throughout the course of the disease.
C1 [Sequist, Lecia V.; Turke, Alexa B.; Fidias, Panos; Shaw, Alice T.; Cosper, Arjola K.; Heist, Rebecca S.; Temel, Jennifer; Wain, John C.; Vernovsky, Kathy; Lanuti, Michael; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Sequist, Lecia V.; Waltman, Belinda A.; Dias-Santagata, Dora; Digumarthy, Subba; Turke, Alexa B.; Fidias, Panos; Shaw, Alice T.; Akhavanfard, Sara; Heist, Rebecca S.; Temel, Jennifer; Wain, John C.; Mark, Eugene J.; Lanuti, Michael; Iafrate, A. John; Mino-Kenudson, Mari; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Dias-Santagata, Dora; Bergethon, Kristin; Akhavanfard, Sara; Mark, Eugene J.; Iafrate, A. John; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Gettinger, Scott; Lynch, Thomas J.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Gettinger, Scott; Lynch, Thomas J.] Yale Canc Ctr, New Haven, CT 06520 USA.
[Christensen, James G.] Pfizer Oncol, Translat Pharmacol, La Jolla, CA 92121 USA.
[Wain, John C.; Lanuti, Michael] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM lvsequist@partners.org; jengelman@partners.org
FU Uniting Against Lung Cancer; UALC: New England; Marjorie E. Korff Fund;
NIH [P50 CA127003, CA120060-01, R01CA137008-01, R01CA140594,
1U01CA141457-01]; National Cancer Institute [P50CA090578];
Dana-Farber/Harvard Cancer Center; American Association for Cancer
Research; V Foundation; American Cancer Society [RSG-06-102-01-CCE];
Ellison Foundation; Doris Duke Charitable Foundation; Daniel Crane
Foundation
FX This study is supported by grants from Uniting Against Lung Cancer,
sponsored by UALC: New England and the Marjorie E. Korff Fund (L. V.
S.), the NIH Gastrointestinal Cancer SPORE P50 CA127003 (J.A.E. and
M.M.-K.), K08 grant CA120060-01 (J.A.E.), R01CA137008-01 (J.A.E.),
R01CA140594 (J.A.E.), 1U01CA141457-01 (J.A.E.), National Cancer
Institute Lung SPORE P50CA090578 (J.A.E.), Dana-Farber/Harvard Cancer
Center, the American Association for Cancer Research (J.A.E.), the V
Foundation (J.A.E.), American Cancer Society RSG-06-102-01-CCE (J.A.E.),
the Ellison Foundation Scholar (J.A.E.), and the Doris Duke Charitable
Foundation (B. A. W.). This work was supported by a gift from the Daniel
Crane Foundation.
NR 64
TC 832
Z9 875
U1 18
U2 80
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 23
PY 2011
VL 3
IS 75
AR 75ra26
DI 10.1126/scitranslmed.3002003
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795LD
UT WOS:000292974800004
PM 21430269
ER
PT J
AU Jackevicius, CA
Tu, JV
Ross, JS
Ko, DT
Carreon, D
Krumholz, HM
AF Jackevicius, Cynthia A.
Tu, Jack V.
Ross, Joseph S.
Ko, Dennis T.
Carreon, Daniel
Krumholz, Harlan M.
TI Use of Fibrates in the United States and Canada
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID TYPE-2 DIABETES-MELLITUS; CORONARY-HEART-DISEASE; TREATMENT PANEL-III;
RHABDOMYOLYSIS; GEMFIBROZIL; CHOLESTEROL; TRIAL; PREVENTION; THERAPY;
EVENTS
AB Context Interest in the role of fibrates intensified after the publication of the negative results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which assessed therapy with fenofibrate plus statins. The evidence for clinical benefit in outcomes with the use of fibrates is heavily weighted on the use of the older fibrates such as gemfibrozil and clofibrate.
Objectives To examine trends in the current use of fibrates and to examine the relationship between differences in the availability and use of brand-name vs generic formulations of fenofibrate and the economic implications in the United States compared with Canada.
Design, Setting, and Patients Population-level, observational cohort study using IMS Health data from the United States and Canada of patients prescribed fibrates between January 2002 and December 2009.
Main Outcome Measures Fibrate prescriptions dispensed and expenditures.
Results In the United States, fibrate prescriptions dispensed increased from 336 prescriptions/100 000 population in January 2002 to 730 prescriptions/100 000 population in December 2009, an increase of 117.1% (95% confidence interval [CI], 116.0%-117.9%), whereas in Canada, fibrate prescriptions increased from 402 prescriptions/100 000 population in January 2002 to 474 prescriptions/100 000 population in December 2009, an increase of 18.1% (95% CI, 17.9%-18.3%) (P<.001). In the United States, fenofibrate prescriptions dispensed increased from 150 prescriptions/100 000 population in January 2002 to 440 prescriptions/100 000 population in December 2009, an increase of 159.3% (95% CI, 157.7%-161.0%), comprising 47.9% of total fibrate prescriptions in 2002 and 65.2% in 2009. In Canada, fenofibrate prescriptions increased from 321 prescriptions/100 000 population in January 2002 to 429 prescriptions/100 000 population in December 2009. The annual ratio of generic to brand-name fenofibrate use in the United States ranged from 0:1 to 0.09:1 between 2002 and 2008, while the ratio in Canada steadily increased from 0.51:1 to 1.89:1 between 2005 and 2008. In the United States, crude fenofibrate expenditures increased from $11 535/100 000 population/month in 2002 to $44 975/100 000 population/month in 2009, while the rates in Canada declined from $17 695/100 000 population/month in 2002 to $16 112/100 000 population/month in 2009. Fibrate expenditures per 100 000 population were 3-fold higher in 2009 in the United States compared with Canada.
Conclusion During the past decade, prescriptions for fibrates (particularly fenofibrate) increased in the United States, while prescriptions for fibrates in Canada remained stable. JAMA. 2011; 305(12): 1217-1224
C1 [Jackevicius, Cynthia A.; Carreon, Daniel] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA 91766 USA.
[Jackevicius, Cynthia A.; Tu, Jack V.; Ko, Dennis T.] Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Jackevicius, Cynthia A.; Tu, Jack V.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada.
[Tu, Jack V.; Ko, Dennis T.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Div Cardiol, Toronto, ON, Canada.
[Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada.
[Ross, Joseph S.] Yale Univ, Sch Med, Dept Med,Sect Gen Internal Med, Ctr Outcomes Res & Evaluat,Yale New Haven Hosp, New Haven, CT 06510 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth,Sect Hlth Policy & Adm, Ctr Outcomes Res & Evaluat,Yale New Haven Hosp, New Haven, CT 06510 USA.
[Ross, Joseph S.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, Ctr Outcomes Res & Evaluat,Yale New Haven Hosp, New Haven, CT USA.
[Krumholz, Harlan M.] Robert Wood Johnson Clin Scholars Program, New Haven, CT USA.
RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, 309 E 2nd St, Pomona, CA 91766 USA.
EM cjackevicius@westernu.edu
OI Ko, Dennis/0000-0001-6840-8051; Tu, Jack/0000-0003-0111-722X
FU College of Pharmacy of Western University of Health Sciences, Pomona,
California; Canadian Institutes of Health Research; Canada Research
Chair in Health Services Research; Heart and Stroke Foundation of
Ontario, Toronto; National Institute on Aging [K08 AG032886]; American
Federation of Aging Research; National Heart, Lung, and Blood Institute
[U01-HL105270]; Ontario Ministry of Health and Long-Term Care, Toronto
FX This study was funded in part by the College of Pharmacy of Western
University of Health Sciences, Pomona, California, and in part by a
Canadian Institutes of Health Research team grant in cardiovascular
outcomes research awarded to the Canadian Cardiovascular Outcomes
Research Team. Dr Tu is supported by a Canada Research Chair in Health
Services Research and by a Career Investigator award of the Heart and
Stroke Foundation of Ontario, Toronto. Dr Ross is currently supported by
the National Institute on Aging grant K08 AG032886 and by the American
Federation of Aging Research through the Paul B. Beeson Career
Development Award Program. Dr Ko is supported by a new investigator
award from the Canadian Institutes of Health Research. Dr Krumholz is
supported by grant U01-HL105270 (awarded to the Center for
Cardiovascular Outcomes Research at Yale University) from the National
Heart, Lung, and Blood Institute. The Institute for Clinical Evaluative
Sciences is supported by an operating grant from the Ontario Ministry of
Health and Long-Term Care, Toronto.
NR 35
TC 46
Z9 46
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 23
PY 2011
VL 305
IS 12
BP 1217
EP 1224
DI 10.1001/jama.2011.353
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 738PA
UT WOS:000288652100017
PM 21427374
ER
PT J
AU Resnik, DB
Koski, G
AF Resnik, David B.
Koski, Greg
TI A National Registry for Healthy Volunteers in Phase 1 Clinical Trials
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Koski, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Mongan Inst Hlth Policy, Boston, MA USA.
[Koski, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
RP Resnik, DB (reprint author), NIEHS, NIH, POB 12233,Mail Drop CU03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102646-01, ZIA ES102646-02]
NR 9
TC 17
Z9 17
U1 1
U2 3
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 23
PY 2011
VL 305
IS 12
BP 1236
EP 1237
DI 10.1001/jama.2011.354
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 738PA
UT WOS:000288652100020
PM 21406636
ER
PT J
AU Duncan, DT
Wolin, KY
Scharoun-Lee, M
Ding, EL
Warner, ET
Bennett, GG
AF Duncan, Dustin T.
Wolin, Kathleen Y.
Scharoun-Lee, Melissa
Ding, Eric L.
Warner, Erica T.
Bennett, Gary G.
TI Does perception equal reality? Weight misperception in relation to
weight-related attitudes and behaviors among overweight and obese US
adults
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
ID PREVALENCE ODDS RATIO; BODY-MASS INDEX; SELF-PERCEPTION;
PHYSICAL-ACTIVITY; UNITED-STATES; LOSE WEIGHT; UNIVERSITY-STUDENTS;
GENDER-DIFFERENCES; RACIAL-DIFFERENCES; IDEAL WEIGHT
AB Background: Weight misperception might preclude the adoption of healthful weight-related attitudes and behaviors among overweight and obese individuals, yet limited research exists in this area. We examined associations between weight misperception and several weight-related attitudes and behaviors among a nationally representative sample of overweight and obese US adults.
Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used. Analyses included non-pregnant, overweight and obese (measured body mass index >= 25) adults aged 20 and older. Weight misperception was identified among those who reported themselves as "underweight" or "about the right weight". Outcome variables and sample sizes were: weight-loss attitudes/behaviors (wanting to weigh less and having tried to lose weight; n = 4,784); dietary intake (total energy intake; n = 4,894); and physical activity (meets 2008 US physical activity recommendations, insufficiently active, and sedentary; n = 5,401). Multivariable regression models were stratified by gender and race/ethnicity. Analyses were conducted in 2009-2010.
Results: These overweight/obese men and women who misperceived their weight were 71% (RR 0.29, 95% CI 0.25-0.34) and 65% (RR 0.35, 95% CI 0.29-0.42) less likely to report that they want to lose weight and 60% (RR 0.40, 95% CI 0.30-0.52) and 56% (RR 0.44, 95% CI 0.32-0.59) less likely to have tried to lose weight within the past year, respectively, compared to those who accurately perceived themselves as overweight. Blacks were particularly less likely to have tried to lose weight. Weight misperception was not a significant predictor of total energy intake among most subgroups, but was associated with lower total energy intake among Hispanic women (change -252.72, 95% CI -433.25, -72.18). Men who misperceived their weight were less likely (RR 0.68, 95% CI 0.52-0.89) to be insufficiently active (the strongest results were among Black men) and women who misperceived their weight were less likely (RR 0.74, 95% CI 0.54, 1.00, p = 0.047) to meet activity recommendations compared to being sedentary.
Conclusion: Overall, weight misperception among overweight and obese adults was associated with less likelihood of interest in or attempts at weight loss and less physical activity. These associations varied by gender and race/ethnicity. This study highlights the importance of focusing on inaccurate weight perceptions in targeted weight loss efforts.
C1 [Duncan, Dustin T.; Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Duncan, Dustin T.] Harvard Univ, Sch Publ Hlth, Harvard Prevent Res Ctr Nutr & Phys Act, Boston, MA 02115 USA.
[Wolin, Kathleen Y.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Wolin, Kathleen Y.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
[Scharoun-Lee, Melissa; Bennett, Gary G.] Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
[Ding, Eric L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ding, Eric L.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Ding, Eric L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Warner, Erica T.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Warner, Erica T.; Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
RP Bennett, GG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM gary.bennett@duke.edu
RI Wolin, Kathleen/I-2154-2014
OI Ding, Eric/0000-0002-5881-8097; Wolin, Kathleen/0000-0001-7950-9042
FU Association of Schools of Public Health/Centers for Disease Control and
Prevention/Prevention Research Center Minority Health; National Cancer
Institute [CA091842, 5K22CA126992-04]; American Diabetes Association;
National Institute of Diabetes and Digestive and Kidney Diseases
[5R01DK078798-03]
FX DTD was supported in part by an Association of Schools of Public
Health/Centers for Disease Control and Prevention/Prevention Research
Center Minority Health Fellowship. KYW was supported in part by grant
CA091842 from the National Cancer Institute. ELD was supported in part
by an American Diabetes Association Postoctoral Fellowship. GGB was
supported by grants 5K22CA126992-04 from the National Cancer Institute
and 5R01DK078798-03 from the National Institute of Diabetes and
Digestive and Kidney Diseases. We are especially gratefully to two
anonymous reviewers who offered very helpful comments.
NR 75
TC 79
Z9 79
U1 6
U2 18
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD MAR 22
PY 2011
VL 8
AR 20
DI 10.1186/1479-5868-8-20
PG 9
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 747XU
UT WOS:000289355400001
PM 21426567
ER
PT J
AU Singh, JP
Klein, HU
Huang, DT
Reek, S
Kuniss, M
Quesada, A
Barsheshet, A
Cannom, D
Goldenberg, I
McNitt, S
Daubert, JP
Zareba, W
Moss, AJ
AF Singh, Jagmeet P.
Klein, Helmut U.
Huang, David T.
Reek, Sven
Kuniss, Malte
Quesada, Aurelio
Barsheshet, Alon
Cannom, David
Goldenberg, Ilan
McNitt, Scott
Daubert, James P.
Zareba, Wojciech
Moss, Arthur J.
TI Left Ventricular Lead Position and Clinical Outcome in the Multicenter
Automatic Defibrillator Implantation Trial-Cardiac Resynchronization
Therapy (MADIT-CRT) Trial
SO CIRCULATION
LA English
DT Article
DE biventricular pacing; cardiac resynchronization therapy; congestive
heart failure; heart failure; resynchronization
ID HEART-FAILURE PATIENTS; BUNDLE-BRANCH BLOCK; DELAY; SITE; HEMODYNAMICS;
ACTIVATION; CONDUCTION
AB Background-An important determinant of successful cardiac resynchronization therapy for heart failure is the position of the left ventricular (LV) pacing lead. The aim of this study was to analyze the impact of the LV lead position on outcome in patients randomized to cardiac resynchronization-defibrillation in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT) study.
Methods and Results--The location of the LV lead was assessed by means of coronary venograms and chest x-rays recorded at the time of device implantation. The LV lead location was classified along the short axis into an anterior, lateral, or posterior position and along the long axis into a basal, midventricular, or apical region. The primary end point of MADIT-CRT was heart failure (HF) hospitalization or death, whichever came first. The LV lead position was assessed in 799 patients, (55% patients >= 65 years of age, 26% female, 10% LV ejection fraction <= 25%, 55% ischemic cardiomyopathy, and 71% left bundle-branch block) with a follow-up of 29 +/- 11 months. The extent of cardiac resynchronization therapy benefit was similar for leads in the anterior, lateral, or posterior position (P=0.652). The apical lead location compared with leads located in the nonapical position (basal or midventricular region) was associated with a significantly increased risk for heart failure/death (hazard ratio=1.72; 95% confidence interval, 1.09 to 2.71; P=0.019) after adjustment for the clinical covariates. The apical lead position was also associated with an increased risk for death (hazard ratio=2.91; 95% confidence interval, 1.42 to 5.97; P=0.004).
Conclusion-LV leads positioned in the apical region were associated with an unfavorable outcome, suggesting that this lead location should be avoided in cardiac resynchronization therapy.
C1 [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA.
[Klein, Helmut U.; Huang, David T.; Barsheshet, Alon; McNitt, Scott; Zareba, Wojciech; Moss, Arthur J.] Univ Rochester, Med Ctr, Dept Med, Cardiol Unit, Rochester, NY 14627 USA.
[Kuniss, Malte] Max Planck Inst Physiol & Clin Res, Kerckhoff Klin, D-6350 Bad Nauheim, Germany.
[Reek, Sven] Univ Hosp, Magdeburg, Germany.
[Quesada, Aurelio] Hosp Gen Valencia, Valencia, Spain.
[Cannom, David] Good Samaritan Hosp, Los Angeles, CA USA.
[Daubert, James P.] Duke Univ, Durham, NC USA.
RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, GRB 109,55 Fruit St, Boston, MA 02114 USA.
EM jsingh@partners.org
FU Boston Scientific; University of Rochester; St. Jude Medical; Medtronic
Inc.; Boston Scientific Corp; Biotronik; Guidant Corp; Sorin Group;
Medtronic; CV Therapeutics; Biosense Webster; St. Jude
FX This study was supported by a research grant from Boston Scientific to
the University of Rochester, with funds distributed to the coordination
and data center, enrolling centers, core laboratories, committees, and
boards under subcontracts from the University of Rochester. Dr Singh
reports receiving research grants from St. Jude Medical, Medtronic Inc.,
Boston Scientific Corp, and Biotronik; serving on advisory boards or as
a consultant for Boston Scientific Corp, Medtronic Inc., Sorin Group,
and St. Jude Medical; and receiving lecture fees from Medtronic Inc.,
Biotronik, Guidant Corp, St. Jude Medical, and Sorin Group. Dr Klein has
received grant support and lecture fees from Boston Scientific. Dr Huang
has received research grants and lecture fees from Boston Scientific. Dr
Reek reports receiving consulting fees from St. Jude Medical. Dr Kuniss
has received lecture fees from Boston Scientific. Dr Quesada has
received consulting fees from Medtronic and Boston Scientific. Dr Cannom
reports receiving consulting and lecture fees from Medtronic and lecture
fees from Boston Scientific. Dr Goldenberg has received research grants
from Boston Scientific. Dr Daubert has received lecture fees from Boston
Scientific; consulting fees from Medtronic, CV Therapeutics, and
Biosense Webster; and institutional fellowship support from Boston
Scientific, Medtronic, St. Jude, Biosense Webster, and Biotronik. Dr
Zareba has received lecture fees from Boston Scientific and grant
support from Medtronic. Dr Moss reports receiving grant support from
Boston Scientific and lecture fees from Boston Scientific, Medtronic,
and St. Jude Medical. The other authors report no conflicts.
NR 25
TC 209
Z9 224
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAR 22
PY 2011
VL 123
IS 11
BP 1159
EP 1166
DI 10.1161/CIRCULATIONAHA.110.000646
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 741GM
UT WOS:000288852200009
PM 21382893
ER
PT J
AU Lau, KS
Juchheim, AM
Cavaliere, KR
Philips, SR
Lauffenburger, DA
Haigis, KM
AF Lau, Ken S.
Juchheim, Alwin M.
Cavaliere, Kimberly R.
Philips, Sarah R.
Lauffenburger, Douglas A.
Haigis, Kevin M.
TI In Vivo Systems Analysis Identifies Spatial and Temporal Aspects of the
Modulation of TNF-alpha-Induced Apoptosis and Proliferation by MAPKs
SO SCIENCE SIGNALING
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; KINASE INHIBITORS; EPITHELIAL-CELLS;
ACTIVATE ERK; CROSS-TALK; RECEPTORS; INDUCTION; COLITIS; SIGNALS
AB Cellular responses to external stimuli depend on dynamic features of multipathway network signaling; thus, cell behavior is influenced in a complex manner by the environment and by intrinsic properties. Methods of multivariate systems analysis have provided an understanding of these convoluted effects, but only for relatively simplified examples in vitro. To determine whether such approaches could be successfully used in vivo, we analyzed the signaling network that determines the response of intestinal epithelial cells to tumor necrosis factor-alpha (TNF-alpha). We built data-driven, partial least-squares discriminant analysis (PLSDA) models based on signaling, apoptotic, and proliferative responses in the mouse small intestinal epithelium after systemic exposure to TNF-alpha. The extracellular signal-regulated kinase (ERK) signaling axis was a critical modulator of the temporal variation in apoptosis at different doses of TNF-alpha and of the spatial variation in proliferation in distinct intestinal regions. Inhibition of MEK, a mitogen-activated protein kinase kinase upstream of ERK, altered the signaling network and changed the temporal and spatial phenotypes consistent with model predictions. Our results demonstrate the dynamic, adaptive nature of in vivo signaling networks and identify natural, tissue-level variation in responses that can be deconvoluted only with quantitative, multivariate computational modeling. This study lays a foundation for the use of systems-based approaches to understand how dysregulation of the cellular network state underlies complex diseases.
C1 [Lau, Ken S.; Juchheim, Alwin M.; Cavaliere, Kimberly R.; Philips, Sarah R.; Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA.
[Lau, Ken S.; Juchheim, Alwin M.; Cavaliere, Kimberly R.; Philips, Sarah R.; Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA.
[Lau, Ken S.; Juchheim, Alwin M.; Haigis, Kevin M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Lau, Ken S.; Lauffenburger, Douglas A.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Lau, Ken S.; Lauffenburger, Douglas A.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
RP Haigis, KM (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA.
EM khaigis@partners.org
OI Lau, Ken/0000-0001-8438-0319
FU National Institute of General Medical Sciences [R01-GM088827]; National
Cancer Institute [U54-CA112967]
FX We thank J. Pritchard, L. Kleiman, D. Clarke, and B. Cosgrove for
comments on the manuscript. Funding: This work was supported by grants
from the National Institute of General Medical Sciences (R01-GM088827 to
K. M. H. and D. A. L.) and the National Cancer Institute (U54-CA112967
to D. A. L.). K. S. L. is a Robert Black Fellow of the Damon Runyon
Cancer Research Foundation. Author contributions: K. S. L., D. A. L.,
and K. M. H. designed the experiments; K. S. L., A. M. J., K. R. C., and
S. R. P. conducted the experiments; K. S. L. performed computational
analyses; K. S. L., D. A. L., and K. M. H. wrote the manuscript; all of
the authors discussed the results and edited the manuscript; and K. M.
H. coordinated all aspects of the project. Competing interests: The
authors declare that they have no competing financial interests.
NR 36
TC 46
Z9 46
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD MAR 22
PY 2011
VL 4
IS 165
AR ra16
DI 10.1126/scisignal.2001338
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 738OR
UT WOS:000288651000002
PM 21427409
ER
PT J
AU Albers, J
Schulze, J
Beil, FT
Gebauer, M
Baranowsky, A
Keller, J
Marshall, RP
Wintges, K
Friedrich, FW
Priemel, M
Schilling, AF
Rueger, JM
Cornils, K
Fehse, B
Streichert, T
Sauter, G
Jakob, F
Insogna, KL
Pober, B
Knobeloch, KP
Francke, U
Amling, M
Schinke, T
AF Albers, Joachim
Schulze, Jochen
Beil, F. Timo
Gebauer, Matthias
Baranowsky, Anke
Keller, Johannes
Marshall, Robert P.
Wintges, Kristofer
Friedrich, Felix W.
Priemel, Matthias
Schilling, Arndt F.
Rueger, Johannes M.
Cornils, Kerstin
Fehse, Boris
Streichert, Thomas
Sauter, Guido
Jakob, Franz
Insogna, Karl L.
Pober, Barbara
Knobeloch, Klaus-Peter
Francke, Uta
Amling, Michael
Schinke, Thorsten
TI Control of bone formation by the serpentine receptor Frizzled-9
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID WILLIAMS-SYNDROME DELETION; PROTEIN-COUPLED RECEPTORS; NEGATIVE
REGULATOR; ISG15 MODIFICATION; SIGNALING PATHWAY; OSTEOBLAST
DIFFERENTIATION; BETA-CATENIN; MICE; GENE; MASS
AB Although Wnt signaling in osteoblasts is of critical importance for the regulation of bone remodeling, it is not yet known which specific Wnt receptors of the Frizzled family are functionally relevant in this process. In this paper, we show that Fzd9 is induced upon osteoblast differentiation and that Fzd9(-/-) mice display low bone mass caused by impaired bone formation. Our analysis of Fzd9(-/-) primary osteoblasts demonstrated defects in matrix mineralization in spite of normal expression of established differentiation markers. In contrast, we observed a reduced expression of chemokines and interferon-regulated genes in Fzd9(-/-) osteoblasts. We also identified the ubiquitin-like modifier Isg15 as one potential downstream mediator of Fzd9 in these cells. Importantly, our molecular analysis further revealed that canonical Wnt signaling is not impaired in the absence of Fzd9, thus explaining the absence of a bone resorption phenotype. Collectively, our results reveal a previously unknown function of Fzd9 in osteoblasts, a finding that may have therapeutic implications for bone loss disorders.
C1 [Albers, Joachim; Schulze, Jochen; Beil, F. Timo; Baranowsky, Anke; Keller, Johannes; Marshall, Robert P.; Wintges, Kristofer; Friedrich, Felix W.; Schilling, Arndt F.; Amling, Michael; Schinke, Thorsten] Univ Med Ctr Hamburg Eppendorf, Dept Osteol & Biomech, D-20246 Hamburg, Germany.
[Gebauer, Matthias; Priemel, Matthias; Rueger, Johannes M.] Univ Med Ctr Hamburg Eppendorf, Dept Trauma Hand & Reconstruct Surg, D-20246 Hamburg, Germany.
[Cornils, Kerstin; Fehse, Boris] Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, D-20246 Hamburg, Germany.
[Streichert, Thomas] Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem, D-20246 Hamburg, Germany.
[Sauter, Guido] Univ Med Ctr Hamburg Eppendorf, Dept Pathol, D-20246 Hamburg, Germany.
[Jakob, Franz] Univ Wurzburg, Dept Orthoped, D-97074 Wurzburg, Germany.
[Insogna, Karl L.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06519 USA.
[Pober, Barbara] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Knobeloch, Klaus-Peter] Univ Clin Freiburg, Dept Neurol, D-79106 Freiburg, Germany.
[Francke, Uta] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
RP Schinke, T (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Osteol & Biomech, D-20246 Hamburg, Germany.
EM schinke@uke.uni-hamburg.de
RI Fehse, Boris/A-8721-2012; Jakob, Franz/D-8526-2015; Jakob, Prof. Dr.
Franz/F-9894-2015;
OI Fehse, Boris/0000-0001-9780-7211
FU Deutsche Forschungsgemeinschaft within the transregional research group
Mechanisms of Fracture Healing and Bone Regeneration in Osteoporosis
[SCHI 504/5-1, SCHI 504/5-2]
FX This work was supported by grants from the Deutsche
Forschungsgemeinschaft (SCHI 504/5-1 and SCHI 504/5-2) within the
transregional research group Mechanisms of Fracture Healing and Bone
Regeneration in Osteoporosis.
NR 68
TC 41
Z9 42
U1 0
U2 12
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD MAR 21
PY 2011
VL 192
IS 6
BP 1057
EP 1072
DI 10.1083/jcb.201008012
PG 16
WC Cell Biology
SC Cell Biology
GA 743AD
UT WOS:000288986200015
PM 21402791
ER
PT J
AU Nanthakumar, N
Meng, D
Goldstein, AM
Zhu, WS
Lu, L
Uauy, R
Llanos, A
Claud, EC
Walker, WA
AF Nanthakumar, Nanda
Meng, Di
Goldstein, Allan M.
Zhu, Weishu
Lu, Lei
Uauy, Ricardo
Llanos, Adolfo
Claud, Erika C.
Walker, W. Allan
TI The Mechanism of Excessive Intestinal Inflammation in Necrotizing
Enterocolitis: An Immature Innate Immune Response
SO PLOS ONE
LA English
DT Article
ID EPITHELIAL-CELLS; ENDOTOXIN TOLERANCE; BACTERIAL LIGANDS; UP-REGULATION;
CORTICOSTEROIDS; ENTEROCYTES; EXPRESSION
AB Necrotizing enterocolitis (NEC) is a devastating neonatal intestinal inflammatory disease, occurring primarily in premature infants, causing significant morbidity and mortality. The pathogenesis of NEC is associated with an excessive inflammatory IL-8 response. In this study, we hypothesized that this excessive inflammatory response is related to an immature expression of innate immune response genes. To address this hypothesis, intestinal RNA expression analysis of innate immune response genes was performed after laser capture microdissection of resected ileal epithelium from fetuses, NEC patients and children and confirmed in ex vivo human intestinal xenografts. Changes in mRNA levels of toll-like receptors (TLR)-2 and -4, their signaling molecules and transcription factors (MyD88, TRAF-6 and NF kappa B1) and negative regulators (SIGIRR, IRAK-M, A-20 and TOLLIP) and the effector IL-8 were characterized by qRT-PCR. The expression of TLR2, TLR4, MyD88, TRAF-6, NFkB1 and IL-8 mRNA was increased while SIGIRR, IRAK-M, A-20 and TOLLIP mRNA were decreased in fetal vs. mature human enterocytes and further altered in NEC enterocytes. Similar changes in mRNA expression were observed in immature, but not mature, human intestinal xenografts. Confirmation of gene expression was also validated with selective protein measurements and with suggested evidence that immature TRL4 enterocyte surface expression was internalized in mature enterocytes. Cortisone, an intestinal maturation factor, treatment corrected the mRNA differences only in the immature intestinal xenograft. Using specific siRNA to attenuate expression of primary fetal enterocyte cultures, both TOLLIP and A-20 were confirmed to be important when knocked down by exhibiting the same excessive inflammatory response seen in the NEC intestine. We conclude that the excessive inflammatory response of the immature intestine, a hallmark of NEC, is due to a developmental immaturity in innate immune response genes.
C1 [Nanthakumar, Nanda; Meng, Di; Zhu, Weishu; Lu, Lei; Walker, W. Allan] Harvard Univ, Sch Med, Dev Gastroenterol Lab, Boston, MA 02115 USA.
[Goldstein, Allan M.] Harvard Univ, Sch Med, Pediat Surg Res Lab, MassGen Hosp Children, Boston, MA USA.
[Uauy, Ricardo; Llanos, Adolfo] Univ Chile, Inst Nutr & Food Technol, Santiago, Chile.
[Claud, Erika C.] Univ Chicago, Dept Pediat & Med, Sect Neonatol, Chicago, IL 60637 USA.
RP Nanthakumar, N (reprint author), Harvard Univ, Sch Med, Dev Gastroenterol Lab, Boston, MA 02115 USA.
EM wwalker@partners.org
FU National Institutes of Health (NIH) [R01 HD059126, R01-HD012437, R01
DK070260, P01 DK033506, P30 DK040561, R01 DK080914, R01 HD059123, R21
HD055237, R21 AT004044]; March of Dimes Basil O'Connor Starter Award
FX This work was supported by grants from National Institutes of Health
(NIH): R01 HD059126 (Nanda Nanthakumar); R01-HD012437, R01 DK070260, P01
DK033506 and P30 DK040561 (W. Allan Walker); R01 DK080914 (Allan
Goldstein); R01 HD059123, R21 HD055237, R21 AT004044 and the March of
Dimes Basil O'Connor Starter Award (Erika Claud). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 28
TC 115
Z9 121
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2011
VL 6
IS 3
AR e17776
DI 10.1371/journal.pone.0017776
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 738BC
UT WOS:000288613300015
PM 21445298
ER
PT J
AU Tu, DQ
Li, YQ
Song, HK
Toms, AV
Gould, CJ
Ficarro, SB
Marto, JA
Goode, BL
Eck, MJ
AF Tu, Daqi
Li, Yiqun
Song, Hyun Kyu
Toms, Angela V.
Gould, Christopher J.
Ficarro, Scott B.
Marto, Jarrod A.
Goode, Bruce L.
Eck, Michael J.
TI Crystal Structure of a Coiled-Coil Domain from Human ROCK I
SO PLOS ONE
LA English
DT Article
ID RHO-ASSOCIATED KINASE; MYOSIN LIGHT-CHAIN; SMOOTH-MUSCLE CONTRACTION;
BINDING PROTEIN RHO; FOCAL ADHESIONS; SERINE/THREONINE KINASE; STRESS
FIBERS; PHOSPHORYLATION; ACTIVATION; REORGANIZATION
AB The small GTPase Rho and one of its targets, Rho-associated kinase (ROCK), participate in a variety of actin-based cellular processes including smooth muscle contraction, cell migration, and stress fiber formation. The ROCK protein consists of an N-terminal kinase domain, a central coiled-coil domain containing a Rho binding site, and a C-terminal pleckstrin homology domain. Here we present the crystal structure of a large section of the central coiled-coil domain of human ROCK I (amino acids 535-700). The structure forms a parallel alpha-helical coiled-coil dimer that is structurally similar to tropomyosin, an actin filament binding protein. There is an unusual discontinuity in the coiled-coil; three charged residues (E613, R617 and D620) are positioned at what is normally the hydrophobic core of coiled-coil packing. We speculate that this conserved irregularity could function as a hinge that allows ROCK to adopt its autoinhibited conformation.
C1 [Tu, Daqi; Toms, Angela V.; Ficarro, Scott B.; Marto, Jarrod A.; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Tu, Daqi; Li, Yiqun; Toms, Angela V.; Ficarro, Scott B.; Marto, Jarrod A.; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Song, Hyun Kyu] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea.
[Gould, Christopher J.; Goode, Bruce L.] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA.
[Gould, Christopher J.; Goode, Bruce L.] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA.
RP Tu, DQ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM eck@red.dfci.harvard.edu
RI Song, Hyun Kyu/D-6763-2016
OI Song, Hyun Kyu/0000-0001-5684-4059
FU National Institutes of Health (NIH) [GM071834]; Ministry of Education,
Science and Technology [R33-10108]
FX This research was supported by National Institutes of Health (NIH) grant
GM071834 to M.J.E. and by WCU (World Class University) program through
the National Research Foundation of Korea funded by the Ministry of
Education, Science and Technology (R33-10108) to M.J.E. and H.K.S.
NR 48
TC 17
Z9 20
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2011
VL 6
IS 3
AR e18080
DI 10.1371/journal.pone.0018080
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 738BC
UT WOS:000288613300035
PM 21445309
ER
PT J
AU Roditi, LD
Michor, F
AF Roditi, Laura De Vargas
Michor, Franziska
TI Evolutionary dynamics of BRCA1 alterations in breast tumorigenesis
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE Stochastic modeling; Breast cancer; Moran model
ID TUMOR-SUPPRESSOR GENE; OVARIAN-CANCER; MUTATION; IRRADIATION;
INSTABILITY; HYPOTHESIS; REPAIR; DAMAGE
AB Cancer results from the accumulation of alterations in oncogenes and tumor suppressor genes. Tumor suppressors are classically defined as genes which contribute to tumorigenesis if their function is lost. Genetic or epigenetic alterations inactivating such genes may arise during somatic cell divisions or alternatively may be inherited from a parent. One notable exception to this rule is the BACA] tumor suppressor that predisposes to hereditary breast cancer when lost. Genetic alterations of this gene are hardly ever observed in sporadic breast cancer, while individuals harboring a germline mutation readily accumulate a second alteration inactivating the remaining allele a finding which represents a conundrum in cancer genetics. In this paper, we present a novel mathematical framework of sporadic and hereditary breast tumorigenesis. We study the dynamics of genetic alterations driving breast tumorigenesis and explore those scenarios which can explain the absence of somatic BRCA1 alterations while replicating all other disease statistics. Our results support the existence of a heterozygous phenotype of BRCA1 and suggest that the loss of one BRCA1 allele may suppress the fitness advantage caused by the inactivation of other tumor suppressor genes. This paper contributes to the mathematical investigation of breast tumorigenesis. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Roditi, Laura De Vargas] Mem Sloan Kettering Canc Ctr, Computat Biol Program, New York, NY 10065 USA.
[Roditi, Laura De Vargas] Weill Cornell Med Coll, Tri Inst Training Program Computat Biol & Med, New York, NY 10065 USA.
RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
EM michor@jimmy.harvard.edu
FU NCI [U54CA143798]
FX The authors would like to thank the Michor laboratory for helpful
comments and discussions. This work is supported by NCI Grant
U54CA143798.
NR 34
TC 3
Z9 3
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
EI 1095-8541
J9 J THEOR BIOL
JI J. Theor. Biol.
PD MAR 21
PY 2011
VL 273
IS 1
BP 207
EP 215
DI 10.1016/j.jtbi.2010.12.033
PG 9
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA 725XX
UT WOS:000287681300021
ER
PT J
AU Tamura, Y
Watanabe, K
Kantani, T
Hayashi, J
Ishida, N
Kaneki, M
AF Tamura, Yoshiaki
Watanabe, Keiichi
Kantani, Tomomi
Hayashi, Junichi
Ishida, Nobuhiko
Kaneki, Masao
TI Upregulation of circulating IL-15 by treadmill running in healthy
individuals: Is IL-15 an endocrine mediator of the beneficial effects of
endurance exercise?
SO ENDOCRINE JOURNAL
LA English
DT Article
DE IL-15; Myokine; Endurance exercise; Treadmill
ID HUMAN SKELETAL-MUSCLE; CARBOHYDRATE INGESTION; INSULIN ACTION;
INTERLEUKIN-15; ADIPOCYTES; ASSOCIATION; EXPRESSION; ADIPOSE; OBESITY;
MASS
AB The beneficial effects of endurance exercise include insulin-sensitization and reduction of fat mass. Limited knowledge is available about the mechanisms by which endurance exercise exerts the salutary effects. Myokines, cytokines secreted by skeletal muscle, have been recognized as a potential mediator. Recently, a role of skeletal muscle-derived interleukin-15 (IL-15) in improvement of fat-lean body mass composition and insulin sensitivity has been proposed. Yet, previous studies have reported that endurance training does not increase production or secretion of IL-15 in skeletal muscle. Here, we show that in opposition to previous findings, 30-min treadmill running at 70% of age-predicted maximum heart rate resulted in a significant increase in circulating IL-15 level in untrained healthy young men. These findings suggest that IL-15 might play a role in the systemic anti-obesogenic and insulin-sensitizing effects of endurance exercise, not only as a paracrine and autocrine but also as an endocrine factor.
C1 [Tamura, Yoshiaki; Kaneki, Masao] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Hosp Children,Dept Anesthesia Crit Care, Charlestown, MA 02129 USA.
[Watanabe, Keiichi; Ishida, Nobuhiko] Wafukai Med Corp, Tama Rehabil Acad, Ome 1980004, Japan.
[Kantani, Tomomi] Wafukai Tama Rehabil Hosp, Ome 1980052, Japan.
[Hayashi, Junichi] Kyorin Univ, Sch Med, Dept Gen Med, Mitaka, Tokyo 1818611, Japan.
RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Hosp Children,Dept Anesthesia Crit Care, 149 13th St,Rm 6604, Charlestown, MA 02129 USA.
EM mkaneki@helix.mgh.harvard.edu
FU National Institutes of Health [R01DK05827]; American Diabetes
Association [7-08-RA-77]
FX This work was supported by research grants to M.K. from the National
Institutes of Health (R01DK05827) and American Diabetes Association
(7-08-RA-77).
NR 18
TC 32
Z9 38
U1 1
U2 16
PU JAPAN ENDOCRINE SOC
PI KYOTO
PA 75 YANAGINOBANBA NISHIIRU-MASUYA-CHO, SANJOU-DORI, NAKAGYOU-KU, KYOTO,
604-8111, JAPAN
SN 0918-8959
J9 ENDOCR J
JI Endocr. J.
PD MAR 20
PY 2011
VL 58
IS 3
BP 211
EP 215
DI 10.1507/endocrj.K10E-400
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 764MS
UT WOS:000290634300009
PM 21307608
ER
PT J
AU Finkelstein, DM
Schoenfeld, DA
AF Finkelstein, Dianne M.
Schoenfeld, David A.
TI Correcting for Discretionary Treatment Crossover in an Analysis of
Survival in the Breast International Group BIG 1-98 Trial by Using the
Inverse Probability of Censoring Weighted Method
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID CLINICAL-TRIAL
C1 [Finkelstein, Dianne M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Boston, MA 02115 USA.
RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 4
TC 12
Z9 12
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 20
PY 2011
VL 29
IS 9
BP 1093
EP 1095
DI 10.1200/JCO.2010.33.9374
PG 3
WC Oncology
SC Oncology
GA 736YZ
UT WOS:000288532500018
PM 21321297
ER
PT J
AU Ganz, PA
Land, SR
Geyer, CE
Cecchini, RS
Costantino, JP
Pajon, ER
Fehrenbacher, L
Atkins, JN
Polikoff, JA
Vogel, VG
Erban, JK
Livingston, RB
Perez, EA
Mamounas, EP
Wolmark, N
Swain, SM
AF Ganz, Patricia A.
Land, Stephanie R.
Geyer, Charles E., Jr.
Cecchini, Reena S.
Costantino, Joseph P.
Pajon, Eduardo R.
Fehrenbacher, Louis
Atkins, James N.
Polikoff, Jonathan A.
Vogel, Victor G.
Erban, John K.
Livingston, Robert B.
Perez, Edith A.
Mamounas, Eleftherios P.
Wolmark, Norman
Swain, Sandra M.
TI Menstrual History and Quality-of-Life Outcomes in Women With
Node-Positive Breast Cancer Treated With Adjuvant Therapy on the NSABP
B-30 Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID MUSTARD L-PAM; PREMENOPAUSAL WOMEN; FUNCTIONAL ASSESSMENT; PREVENTION
TRIAL; CHEMOTHERAPY; SYMPTOMS; MANAGEMENT; AMENORRHEA; PRESERVATION;
FERTILITY
AB Purpose
Premenopausal women with breast cancer receiving adjuvant chemotherapy are at risk for amenorrhea. The National Surgical Adjuvant Breast and Bowel Project B-30 trial included menstrual history (MH) and quality-of-life (QOL) studies to compare treatments on these outcomes.
Patients and Methods
Patients were randomly assigned to sequential doxorubicin (A) and cyclophosphamide (C) followed by docetaxel (T; AC -> T), concurrent TAC, or AT, which varied in duration (24, 12, 12 weeks, respectively), and use of C. Endocrine therapy was prescribed for women with hormone receptor-positive tumors. MH and QOL were assessed with standardized questionnaires at baseline; cycle 4, day 1; and every 6 months through 24 months. Prespecified analyses examined rates of amenorrhea by treatment arm, the relationship between amenorrhea and QOL, and QOL by treatment arm.
Results
Amenorrhea 12 months after random assignment was significantly different between treatment groups: 69.8% for AC -> T, 57.7% for TAC, and 37.9% for AT (P < .001). The AT group without tamoxifen had the lowest rate of amenorrhea. QOL was poorer for patients receiving AC -> T at 6 months but similar to others by 12 months. Post-treatment symptoms were increased above baseline for all treatments. Multivariable repeated measures modeling demonstrated that treatment arm, time point, age, and tamoxifen use were significantly associated with symptom severity (all P values < .002).
Conclusion
Amenorrhea rates differed significantly by treatment arm, with the AT arm having the lowest rate. Patients treated with longer duration therapy (AC -> T) had greater symptom severity and poorer QOL at 6 months, but did not differ from shorter duration treatments at 12 months. J Clin Oncol 29: 1110-1116. (C) 2011 by American Society of Clinical Oncology
C1 Univ Pittsburgh, Sch Publ Hlth, NSABP Biostat Ctr, Pittsburgh, PA 15260 USA.
Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
Eastern Cooperat Oncol Grp, Philadelphia, PA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
Kaiser Permanente No Calif, Vallejo, CA USA.
So Calif Kaiser Permanente, San Diego, CA USA.
Colorado Canc Res Program, Denver, CO USA.
SE Canc Control Consortium Community Clin, Goldsboro, NC USA.
Amer Canc Soc, Atlanta, GA 30329 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Univ Arizona, Arizona Canc Ctr, Arizona Hlth Sci Ctr, Tucson, AZ USA.
SW Oncol Grp, Ann Arbor, MI USA.
Mayo Clin, Jacksonville, FL 32224 USA.
N Cent Canc Treatment Grp, Rochester, MN USA.
Aultman Hlth Fdn, Canton, OH USA.
Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
Univ Pittsburgh, Ctr Canc, Pittsburgh, PA 15260 USA.
RP Ganz, PA (reprint author), Univ Calif Los Angeles, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, 650 Charles Young Dr S,Room A2-125 CHS, Los Angeles, CA 90095 USA.
EM pganz@mednet.ucla.edu
OI Cecchini, Reena/0000-0002-9075-9357; Swain, Sandra/0000-0002-1320-3830
FU AstraZeneca
FX Research Funding: Victor G. Vogel, AstraZeneca
NR 24
TC 53
Z9 57
U1 0
U2 5
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 2011
VL 29
IS 9
BP 1110
EP 1116
DI 10.1200/JCO.2010.29.7689
PG 7
WC Oncology
SC Oncology
GA 736YZ
UT WOS:000288532500022
PM 21300930
ER
PT J
AU Colleoni, M
Giobbie-Hurder, A
Regan, MM
Thurlimann, B
Mouridsen, H
Mauriac, L
Forbes, JF
Paridaens, R
Lang, I
Smith, I
Chirgwin, J
Pienkowski, T
Wardley, A
Price, KN
Gelber, RD
Coates, AS
Goldhirsch, A
AF Colleoni, Marco
Giobbie-Hurder, Anita
Regan, Meredith M.
Thuerlimann, Beat
Mouridsen, Henning
Mauriac, Louis
Forbes, John F.
Paridaens, Robert
Lang, Istvan
Smith, Ian
Chirgwin, Jacquie
Pienkowski, Tadeusz
Wardley, Andrew
Price, Karen N.
Gelber, Richard D.
Coates, Alan S.
Goldhirsch, Aron
TI Analyses Adjusting for Selective Crossover Show Improved Overall
Survival With Adjuvant Letrozole Compared With Tamoxifen in the BIG 1-98
Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID EARLY BREAST-CANCER; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; INVERSE
PROBABILITY; THERAPY; TRIAL; ANASTROZOLE; NONCOMPLIANCE; ARNO-95; TESTS
AB Purpose
Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy.
Patients and Methods
Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling.
Results
Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P < .05 for DFS, OS, and TDR). Median follow-up was 74 months.
Conclusion
Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor-positive breast cancer. J Clin Oncol 29: 1117-1124. (C) 2011 by American Society of Clinical Oncology
C1 [Colleoni, Marco] Ist Europeo Oncol, I-20141 Milan, Italy.
Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Frontier Sci & Technol Res Fdn Inc, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
Kantonsspital, Breast Ctr, St Gallen, Switzerland.
Swiss Grp Clin Canc Res, Int Breast Canc Study Grp, Bern, Switzerland.
Oncol Inst So Switzerland, Bellinzona, Switzerland.
Rigshosp, Danish Breast Canc Cooperat Grp, DK-2100 Copenhagen, Denmark.
Inst Bergonie, French Breast Canc Grp, Bordeaux, France.
Univ Newcastle, Calvary Mater Hosp, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia.
Box Hill Hosp, Melbourne, Vic, Australia.
Maroondah Hosp, Melbourne, Vic, Australia.
Univ Sydney, Sydney, NSW 2006, Australia.
Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Louvain, Belgium.
Natl Inst Oncol, Budapest, Hungary.
Royal Marsden Hosp, London, England.
Inst Canc Res, London SW3 6JB, England.
S Manchester Univ Hosp Trust, Christie Hosp Natl Hlth Serv Trust, Manchester, Lancs, England.
Canc Ctr Maria Sklodowska Curie Mem, Inst Oncol, Warsaw, Poland.
RP Colleoni, M (reprint author), Ist Europeo Oncol, Via Ripamonti 435, I-20141 Milan, Italy.
EM marco.colleoni@ieo.it
RI Wardley, ANdrew/N-8135-2015
OI Wardley, ANdrew/0000-0002-9639-0888
FU Novartis; AstraZeneca; Pfizer
FX Research Funding: Jacquie Chirgwin, Novartis, AstraZeneca, Pfizer;
Tadeusz Pienkowski, Novartis; Richard D. Gelber, Novartis
NR 20
TC 74
Z9 77
U1 1
U2 4
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 2011
VL 29
IS 9
BP 1117
EP 1124
DI 10.1200/JCO.2010.31.6455
PG 8
WC Oncology
SC Oncology
GA 736YZ
UT WOS:000288532500023
PM 21321298
ER
PT J
AU O'Connor, OA
Pro, B
Pinter-Brown, L
Bartlett, N
Popplewell, L
Coiffier, B
Lechowicz, MJ
Savage, KJ
Shustov, AR
Gisselbrecht, C
Jacobsen, E
Zinzani, PL
Furman, R
Goy, A
Haioun, C
Crump, M
Zain, JM
Hsi, E
Boyd, A
Horwitz, S
AF O'Connor, Owen A.
Pro, Barbara
Pinter-Brown, Lauren
Bartlett, Nancy
Popplewell, Leslie
Coiffier, Bertrand
Lechowicz, Mary Jo
Savage, Kerry J.
Shustov, Andrei R.
Gisselbrecht, Christian
Jacobsen, Eric
Zinzani, Pier Luigi
Furman, Richard
Goy, Andre
Haioun, Corinne
Crump, Michael
Zain, Jasmine M.
Hsi, Eric
Boyd, Adam
Horwitz, Steven
TI Pralatrexate in Patients With Relapsed or Refractory Peripheral T-Cell
Lymphoma: Results From the Pivotal PROPEL Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; CLASSIFICATION; METHOTREXATE; MALIGNANCIES;
MANAGEMENT; SUPERIOR; WORKSHOP; FEATURES; MODELS; REAL
AB Purpose
Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and tolerability of pralatrexate, a novel antifolate with promising activity.
Patients and Methods
Patients with independently confirmed PTCL who progressed following >= 1 line of prior therapy received pralatrexate intravenously at 30 mg/m(2)/wk for 6 weeks in 7-week cycles. Primary assessment of response was made by independent central review using the International Workshop Criteria. The primary end point was overall response rate. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS).
Results
Of 115 patients enrolled, 111 were treated with pralatrexate. The median number of prior systemic therapies was three (range, 1 to 12). The response rate in 109 evaluable patients was 29% (32 of 109), including 12 complete responses (11%) and 20 partial responses (18%), with a median DoR of 10.1 months. Median PFS and OS were 3.5 and 14.5 months, respectively. The most common grade 3/4 adverse events were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%).
Conclusion
To our knowledge, PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) is the largest prospective study conducted in patients with relapsed or refractory PTCL. Pralatrexate induced durable responses in relapsed or refractory PTCL irrespective of age, histologic subtypes, amount of prior therapy, prior methotrexate, and prior autologous stem-cell transplant. These data formed the basis for the US Food and Drug Administration approval of pralatrexate, the first drug approved for this disease. J Clin Oncol 29:1182-1189. (C) 2011 by American Society of Clinical Oncology
C1 [O'Connor, Owen A.] NYU, Inst Canc, NYU Langone Med Ctr, New York, NY 10003 USA.
New York Weill Cornell Med Ctr, New York, NY USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Washington Univ, Siteman Canc Ctr, St Louis, MO USA.
Ctr Hosp Lyon Sud, F-69310 Pierre Benite, France.
Emory Univ, Atlanta, GA 30322 USA.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Princess Margaret Hosp, Toronto Univ Hlth Network, Toronto, ON M4X 1K9, Canada.
Seattle Canc Care Alliance, Seattle, WA USA.
Hop St Louis, Paris, France.
Hop Henri Mondor, F-94010 Creteil, France.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Bologna, Bologna, Italy.
Hackensack Univ, Med Ctr, Hackensack, NJ USA.
Clin Univ UCL Mt Godinne, Yvoir, Belgium.
Cleveland Clin, Cleveland, OH 44106 USA.
Allos Therapeut Inc, Westminster, CO USA.
RP O'Connor, OA (reprint author), NYU, Inst Canc, NYU Langone Med Ctr, 550 1st Ave,Suite 1121, New York, NY 10003 USA.
EM owen.o'connor@nyumc.org
RI Zinzani, Pier Luigi/J-9182-2016
OI Zinzani, Pier Luigi/0000-0002-2112-2651
FU Allos Therapeutics; Allos Therapeutics, Inc
FX Owen A. O'Connor, Allos Therapeutics; Barbara Pro, Allos Therapeutics,
Inc; Lauren Pinter-Brown, Allos Therapeutics; Nancy Bartlett, Allos
Therapeutics, Inc; Leslie Popplewell, Allos Therapeutics, Inc.; Andrei
R. Shustov, Allos Therapeutics, Inc; Christian Gisselbrecht, Allos
Therapeutics, Inc; Andre Goy, Allos Therapeutics, Inc; Eric Hsi, Allos
Therapeutics; Steven Horwitz, Gloucester Pharmaceuticals, Allos
Therapeutics
NR 21
TC 197
Z9 208
U1 2
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 20
PY 2011
VL 29
IS 9
BP 1182
EP 1189
DI 10.1200/JCO.2010.29.9024
PG 8
WC Oncology
SC Oncology
GA 736YZ
UT WOS:000288532500032
PM 21245435
ER
PT J
AU Wen, PY
Van den Bent, MJ
Macdonald, DR
Vogelbaum, MA
Chang, SM
AF Wen, Patrick Y.
Van den Bent, Martin J.
Macdonald, David R.
Vogelbaum, Michael A.
Chang, Susan M.
TI New Agents and New End Points for Recurrent Gliomas Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Van den Bent, Martin J.] Erasmus Univ Hosp, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands.
[Macdonald, David R.] Univ Western Ontario, London Reg Canc Program, London, ON, Canada.
[Vogelbaum, Michael A.] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA.
[Chang, Susan M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 20
PY 2011
VL 29
IS 9
BP E247
EP E247
DI 10.1200/JCO.2010.33.4383
PG 1
WC Oncology
SC Oncology
GA 736YZ
UT WOS:000288532500013
ER
PT J
AU Drucker, DJ
Goldfine, AB
AF Drucker, Daniel J.
Goldfine, Allison B.
TI Cardiovascular safety and diabetes drug development
SO LANCET
LA English
DT Editorial Material
ID EXENATIDE TWICE; OPEN-LABEL; TYPE-2; LIRAGLUTIDE; THERAPIES; OUTCOMES;
WEIGHT; RISK
C1 [Drucker, Daniel J.] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Med, Toronto, ON M5G 1X5, Canada.
[Goldfine, Allison B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Drucker, DJ (reprint author), Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Med, Toronto, ON M5G 1X5, Canada.
EM d.drucker@utoronto.ca
RI Drucker, Daniel/A-4092-2010
NR 14
TC 19
Z9 20
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD MAR 19
PY 2011
VL 377
IS 9770
BP 977
EP 979
DI 10.1016/S0140-6736(10)62299-4
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 740FA
UT WOS:000288775800009
PM 21316097
ER
PT J
AU Pe'er, D
Hacohen, N
AF Pe'er, Dana
Hacohen, Nir
TI Principles and Strategies for Developing Network Models in Cancer
SO CELL
LA English
DT Article
ID HUMAN B-CELLS; TRANSCRIPTIONAL NETWORK; GENE-EXPRESSION; IDENTIFICATION;
INHIBITION; MAP; ACTIVATION; REGULATORS; PATHWAYS; DYNAMICS
AB The flood of genome-wide data generated by high-throughput technologies currently provides biologists with an unprecedented opportunity: to manipulate, query, and reconstruct functional molecular networks of cells. Here, we outline three underlying principles and six strategies to infer network models from genomic data. Then, using cancer as an example, we describe experimental and computational approaches to infer "differential" networks that can identify genes and processes driving disease phenotypes. In conclusion, we discuss how a network-level understanding of cancer can be used to predict drug response and guide therapeutics.
C1 [Pe'er, Dana] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
[Pe'er, Dana] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
[Hacohen, Nir] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
[Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Pe'er, D (reprint author), Columbia Univ, Dept Biol Sci, 1212 Amsterdam Ave, New York, NY 10027 USA.
EM dpeer@biology.columbia.edu
OI Pe'er, Dana/0000-0002-9259-8817
FU NIH [DP2-OD002414-01, DP2 OD002230]; NIAID [U54 AI057159]; Burroughs
Wellcome Fund; Packard Fellowship for Science and Engineering
FX The authors would like to thank Arnon Arazi, Andrea Califano, William
Hahn, Andreja Jovic, Oren Litvin, Neal Rosen, Sagi Shapira, and Cathy Wu
for valuable comments. The authors would like to thank Oren Litvin for
help with the illustrations. This research was supported by the NIH
Director's New Innovator Award Program through grant numbers
DP2-OD002414-01 (D.P.) and DP2 OD002230 (N.H.), as well as NIAID U54
AI057159 (N.H.). D.P. holds a Career Award at the Scientific Interface
from the Burroughs Wellcome Fund and Packard Fellowship for Science and
Engineering.
NR 48
TC 91
Z9 92
U1 3
U2 22
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 18
PY 2011
VL 144
IS 6
BP 864
EP 873
DI 10.1016/j.cell.2011.03.001
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 737BQ
UT WOS:000288543500006
PM 21414479
ER
PT J
AU Vidal, M
Cusick, ME
Barabasi, AL
AF Vidal, Marc
Cusick, Michael E.
Barabasi, Albert-Laszlo
TI Interactome Networks and Human Disease
SO CELL
LA English
DT Review
ID PROTEIN-PROTEIN INTERACTIONS; YEAST SACCHAROMYCES-CEREVISIAE; DNA
INTERACTION NETWORK; GENE-EXPRESSION; C-ELEGANS; CAENORHABDITIS-ELEGANS;
ESCHERICHIA-COLI; TRANSCRIPTION FACTORS; METABOLIC NETWORKS; INTERACTION
MAP
AB Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.
C1 [Vidal, Marc; Cusick, Michael E.; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, Boston, MA 02215 USA.
[Vidal, Marc; Cusick, Michael E.; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Vidal, Marc; Cusick, Michael E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res CCNR, Boston, MA 02115 USA.
[Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol & Comp Sci, Boston, MA 02115 USA.
[Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Vidal, M (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, Boston, MA 02215 USA.
EM marc_vidal@dfci.harvard.edu; alb@neu.edu
FU National Institutes of Health [R01-HG001715]
FX We thank David E. Hill, Matija Dreze, Anne-Ruxandra Carvunis, Benoit
Charloteaux, Quan Zhong, Balaji Santhanam, Sam Pevzner, Song Yi, Nidhi
Sahni, Jean Vandenhaute, and Roseann Vidal for careful reading of the
manuscript. Interactome mapping efforts at CCSB have been supported
mainly by National Institutes of Health grant R01-HG001715. M.V. is
grateful to Nadia Rosenthal for the peaceful Suttonian environment. We
apologize to those in the field whose important work was not cited here
due to space limitation.
NR 156
TC 550
Z9 563
U1 26
U2 194
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 18
PY 2011
VL 144
IS 6
BP 986
EP 998
DI 10.1016/j.cell.2011.02.016
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 737BQ
UT WOS:000288543500015
PM 21414488
ER
PT J
AU Uljon, SN
Richardson, PG
Schur, PH
Anderson, KC
Tanasijevic, MJ
Lindeman, NI
AF Uljon, Sacha N.
Richardson, Paul G.
Schur, Peter H.
Anderson, Kenneth C.
Tanasijevic, Milenko J.
Lindeman, Neal I.
TI Serial serum free light chain measurements do not detect changes in
disease status earlier than electrophoretic M-spike measurements in
patients with intact immunoglobulin myeloma
SO CLINICA CHIMICA ACTA
LA English
DT Article
DE Serum free light chains; Serum protein electrophoresis; Myeloma
ID MULTIPLE-MYELOMA; PROTEIN; CATABOLISM
AB Background: Serum free light chains (SFLC) are used to manage patients with light chain or hyposecretory myeloma, and may also be useful in patients with intact immunoglobulin myeloma (IIMM), because their shorter half-life may enable earlier indication of relapse/response than electrophoretic M-spikes or heavy chain (IgGA) immunonephelometry.
Methods: One thousand five SFLC, M-spike, and IgGA concentrations were compared at multiple time points during the treatment of 17 myeloma patients, followed over 7.7-63.4 months. Changes in these analytes were evaluated in context with changes in disease status and treatment.
Results: 14/17 (82%) patients showed synchrony between M-spike, IgGA, and SFLC measurements. SFLC changes preceded M-spike/IgGA in 1 patient, and lagged behind M-spike/IgGA in 2 patients. In eight patients, SFLC showed short-term fluctuations unaccompanied by changes in M-spike, IgGA, or clinical treatment.
Conclusions: In 16/17 intact immunoglobulin myeloma patients tested frequently over similar to 3 years, SFLC performed no better than M-spike and did not add value to conventional serum electrophoresis. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Uljon, Sacha N.; Tanasijevic, Milenko J.; Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Schur, Peter H.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Uljon, Sacha N.; Richardson, Paul G.; Schur, Peter H.; Anderson, Kenneth C.; Tanasijevic, Milenko J.; Lindeman, Neal I.] Harvard Univ, Sch Med, Boston, MA USA.
RP Lindeman, NI (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 2-217D, Boston, MA 02115 USA.
EM nlindeman@partners.org
NR 17
TC 7
Z9 7
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0009-8981
J9 CLIN CHIM ACTA
JI Clin. Chim. Acta
PD MAR 18
PY 2011
VL 412
IS 7-8
BP 562
EP 568
DI 10.1016/j.cca.2010.12.002
PG 7
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 727YZ
UT WOS:000287840600014
PM 21144845
ER
PT J
AU Illerhaus, G
Batchelor, T
AF Illerhaus, Gerald
Batchelor, Tracy
TI PCNSL: biomarker better than biopsy?
SO BLOOD
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 8
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 17
PY 2011
VL 117
IS 11
BP 2987
EP 2989
PG 5
WC Hematology
SC Hematology
GA 736LN
UT WOS:000288496300003
PM 21415274
ER
PT J
AU Ringman, JM
Gylys, KH
Medina, LD
Fox, M
Kepe, V
Flores, DL
Apostolova, LG
Barrio, JR
Small, G
Silverman, DH
Siu, E
Cederbaum, S
Hecimovic, S
Malnar, M
Chakraverty, S
Goate, AM
Bird, TD
Leverenz, JB
AF Ringman, John M.
Gylys, Karen H.
Medina, Luis D.
Fox, Michelle
Kepe, Vladimir
Flores, Deborah L.
Apostolova, Liana G.
Barrio, Jorge R.
Small, Gary
Silverman, Daniel H.
Siu, Erin
Cederbaum, Stephen
Hecimovic, Silva
Malnar, Martina
Chakraverty, Suma
Goate, Alison M.
Bird, Thomas D.
Leverenz, James B.
TI Biochemical, neuropathological, and neuroimaging characteristics of
early-onset Alzheimer's disease due to a novel PSEN1 mutation (vol 487,
pg 287, 2011)
SO NEUROSCIENCE LETTERS
LA English
DT Correction
C1 [Ringman, John M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA.
[Fox, Michelle; Cederbaum, Stephen] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA.
[Kepe, Vladimir; Barrio, Jorge R.; Silverman, Daniel H.; Siu, Erin] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Flores, Deborah L.] Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA.
[Small, Gary; Cederbaum, Stephen] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Psychiat, Los Angeles, CA 90095 USA.
[Hecimovic, Silva; Malnar, Martina] Rudjer Boskovic Inst, Dept Mol Med, Zogreb, Croatia.
[Chakraverty, Suma; Goate, Alison M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Bird, Thomas D.; Leverenz, James B.] Univ Washington, Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
RP Ringman, JM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Mary S Easton Ctr Alzheimers Dis Res, 10911 Weyburn Ave,200, Los Angeles, CA 90095 USA.
EM jringman@mednet.ucla.edu
NR 1
TC 0
Z9 0
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 17
PY 2011
VL 491
IS 2
BP 163
EP 163
DI 10.1016/j.neulet.2011.01.021
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 739QF
UT WOS:000288732200015
ER
PT J
AU Damrauer, SM
Studer, P
da Silva, CG
Longo, CR
Ramsey, HE
Csizmadia, E
Shrikhande, GV
Scali, ST
Libermann, TA
Bhasin, MK
Ferran, C
AF Damrauer, Scott M.
Studer, Peter
da Silva, Cleide G.
Longo, Christopher R.
Ramsey, Haley E.
Csizmadia, Eva
Shrikhande, Gautam V.
Scali, Salvatore T.
Libermann, Towia A.
Bhasin, Manoj K.
Ferran, Christiane
TI A20 Modulates Lipid Metabolism and Energy Production to Promote Liver
Regeneration
SO PLOS ONE
LA English
DT Article
ID ACTIVATED-RECEPTOR-ALPHA; NF-KAPPA-B; ENDOTHELIAL-CELL ACTIVATION;
GENE-EXPRESSION PATTERNS; ZINC-FINGER PROTEIN; PARTIAL-HEPATECTOMY; ACID
SYNTHESIS; MOUSE LIVERS; PPAR-ALPHA; MICE
AB Background: Liver Regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-kappa B inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice.
Methodology and Principal Findings: We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.beta galactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-kappa B, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV.
Conclusion: This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A20-based therapies to improve patients' outcomes in the context of extreme liver injury and extensive LR for tumor treatment or donation.
C1 [Damrauer, Scott M.; Studer, Peter; da Silva, Cleide G.; Longo, Christopher R.; Ramsey, Haley E.; Csizmadia, Eva; Shrikhande, Gautam V.; Scali, Salvatore T.; Ferran, Christiane] Harvard Univ, Sch Med, Div Vasc Surg, Vasc Biol Res Ctr, Boston, MA USA.
[Damrauer, Scott M.; Studer, Peter; da Silva, Cleide G.; Longo, Christopher R.; Ramsey, Haley E.; Csizmadia, Eva; Shrikhande, Gautam V.; Scali, Salvatore T.; Ferran, Christiane] Harvard Univ, Sch Med, Dept Surg, Beth Israel Deaconess Med Ctr,Transplant Inst, Boston, MA 02115 USA.
[Libermann, Towia A.; Bhasin, Manoj K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Interdisciplinary Med & Biotechnol,Dept Med, Boston, MA 02215 USA.
RP Damrauer, SM (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA.
EM mbhasin@bidmc.harvard.edu; cferran@bidmc.harvard.edu
OI Libermann, Towia/0000-0002-4006-8179
FU NIH [RO1 DK063275, RO1 HL080130, HL057791, T32 HL07734]; Juvenile
Diabetes Research Foundation [1-2007-567]; National Swiss Foundation
FX research was supported by NIH grants RO1 DK063275, RO1 HL080130,
HL057791 and Juvenile Diabetes Research Foundation grant 1-2007-567 to
CF. SMD, CRL, GVS, STS, are recipients of a fellowship award from the
NIH T32 HL07734. PS is the recipient of a grant from the National Swiss
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 72
TC 18
Z9 20
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 17
PY 2011
VL 6
IS 3
AR e17715
DI 10.1371/journal.pone.0017715
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 736SO
UT WOS:000288514600011
PM 21437236
ER
PT J
AU Zhao, Y
Sharma, N
Ledoux, MS
AF Zhao, Y.
Sharma, N.
Ledoux, M. S.
TI THE DYT1 CARRIER STATE INCREASES ENERGY DEMAND IN THE OLIVOCEREBELLAR
NETWORK
SO NEUROSCIENCE
LA English
DT Article
DE dystonia; globus pallidus; glucose utilization; cytochrome oxidase
histochemistry; inferior olive; Purkinje cells
ID CYTOCHROME-OXIDASE HISTOCHEMISTRY; CEREBRAL GLUCOSE-UTILIZATION;
GENETICALLY DYSTONIC RAT; INFERIOR OLIVE; 2-DEOXYGLUCOSE METHOD;
NEURONAL-ACTIVITY; BASAL GANGLIA; MOUSE MODEL; HORSERADISH-PEROXIDASE;
DESCENDING CONNECTIONS
AB DYT1 dystonia is caused by a GAG deletion in TOR1A, the gene which encodes torsinA. Gene expression studies in rodents and functional imaging studies in humans suggest that DYT1 dystonia may be a network disorder of neurodevelopmental origin. To generate high resolution metabolic maps of DYT1 dystonia and pinpoint dysregulated network elements, we performed 2-deoxyglucose autoradiography and cytochrome oxidase (CO) histochemistry in transgenic mice expressing human mutant (hMT1) torsinA and wild-type littermates. In comparison with controls, hMT1 mice showed increased glucose utilization (GU) in the inferior olive (IO) medial nucleus (IOM), IO dorsal accessory nucleus and substantia nigra compacta, and decreased GU in the medial globus pallidus (MGP) and lateral globus pallidus. The hMT1 mice showed increased CO activity in the IOM and Purkinje cell layer of cerebellar cortex, and decreased CO activity in the caudal caudate-putamen, substantia nigra reticulata and MGP. These findings suggest that (1) the DYT1 carrier state increases energy demand in the olivocerebellar network and (2) the IO may be a pivotal node for abnormal basal ganglia-cerebellar interactions in dystonia. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Zhao, Y.; Ledoux, M. S.] Univ Tennessee, Hlth Sci Ctr, Dept Neurol, Memphis, TN 38163 USA.
[Zhao, Y.; Ledoux, M. S.] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN 38163 USA.
[Sharma, N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sharma, N.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Ledoux, MS (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Neurol, Memphis, TN 38163 USA.
EM mledoux@uthsc.edu
RI LeDoux, Mark/I-1390-2013
OI LeDoux, Mark/0000-0002-1748-3390
FU Dystonia Medical Research Foundation; National Institute of Neurological
Diseases and Stroke [R01NS048458, R03NS050185, R01NS069936]
FX This work was supported by the Dystonia Medical Research Foundation and
National Institute of Neurological Diseases and Stroke (R01NS048458,
R03NS050185, R01NS069936).
NR 58
TC 15
Z9 15
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD MAR 17
PY 2011
VL 177
BP 183
EP 194
DI 10.1016/j.neuroscience.2011.01.015
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 734DR
UT WOS:000288313900018
PM 21241782
ER
PT J
AU Palumbo, A
Anderson, K
AF Palumbo, Antonio
Anderson, Kenneth
TI MEDICAL PROGRESS Multiple Myeloma
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID STEM-CELL TRANSPLANTATION; PREDNISONE PLUS THALIDOMIDE; RANDOMIZED
CONTROLLED-TRIAL; GROUP CONSENSUS STATEMENT; WORKING GROUP GUIDELINES;
HIGH-DOSE DEXAMETHASONE; LONG-TERM SURVIVAL; ELDERLY-PATIENTS;
PHASE-III; MOLECULAR CLASSIFICATION
AB Multiple myeloma is a neoplastic plasma-cell disorder that is characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment, monoclonal protein in the blood or urine, and associated organ dysfunction.(1) It accounts for approximately 1% of neoplastic diseases and 13% of hematologic cancers. In Western countries, the annual ageadjusted incidence is 5.6 cases per 100,000 persons.(2) The median age at diagnosis is approximately 70 years; 37% of patients are younger than 65 years, 26% are between the ages of 65 and 74 years, and 37% are 75 years of age or older.(2,3) In recent years, the introduction of autologous stem-cell transplantation and the availability of agents such as thalidomide, lenalidomide, and bortezomib have changed the management of myeloma and extended overall survival. 3-5 In patients presenting at an age under 60 years, 10-year survival is approximately 30%.(4)
C1 [Palumbo, Antonio] Univ Turin, Div Hematol, Myeloma Unit, AOU S Giovanni Battista, I-10126 Turin, Italy.
[Anderson, Kenneth] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematolg Neoplasia,Dept Med, Boston, MA 02115 USA.
RP Palumbo, A (reprint author), Univ Turin, Div Hematol, Myeloma Unit, AOU S Giovanni Battista, Via Genova 3, I-10126 Turin, Italy.
EM appalumbo@yahoo.com
FU Celgene; Janssen-Cilag; Merck; Amgen
FX Dr. Palumbo reports receiving fees for advisory board membership,
consulting fees, and payment for the development of educational
presentations from Celgene and Janssen-Cilag and lecture fees from
Celgene, Janssen-Cilag, Merck, and Amgen; and Dr. Anderson, receiving
fees for advisory board membership from Bristol-Myers Squibb, Celgene,
Novartis, Onyx, Merck, and Millennium and being a founder of Acetylon.
No other potential conflict of interest relevant to this article was
reported.
NR 103
TC 713
Z9 746
U1 10
U2 100
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 17
PY 2011
VL 364
IS 11
BP 1046
EP 1060
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA 735SX
UT WOS:000288439000010
PM 21410373
ER
PT J
AU Sims, KB
Cole, AJ
Sherman, JC
Caruso, PA
Snuderl, M
AF Sims, Katherine B.
Cole, Andrew J.
Sherman, Janet C.
Caruso, Paul A.
Snuderl, Matija
TI Case 8-2011: A 32-Year-Old Woman with Seizures and Cognitive Decline
Kufs' disease (autosomal dominant, Parry type, young-adult-onset
neuronal ceroid lipofuscinosis)
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PROGRESSIVE MYOCLONUS EPILEPSIES; THERAPEUTIC ASPECTS; DIAGNOSIS;
INHERITANCE; CHILDHOOD; GENES; FORM
C1 [Sims, Katherine B.; Cole, Andrew J.; Sherman, Janet C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sherman, Janet C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Caruso, Paul A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Snuderl, Matija] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sims, Katherine B.; Cole, Andrew J.; Sherman, Janet C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Caruso, Paul A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Snuderl, Matija] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Sims, KB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
NR 25
TC 7
Z9 7
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 17
PY 2011
VL 364
IS 11
BP 1062
EP 1074
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 735SX
UT WOS:000288439000013
PM 21410375
ER
PT J
AU Simpson, JL
Greene, MF
AF Simpson, Joe Leigh
Greene, Michael F.
TI Fetal Surgery for Myelomeningocele?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Simpson, Joe Leigh] Florida Int Univ, Herbert Wertheim Coll Med, Dept Human & Mol Genet, Miami, FL 33199 USA.
[Simpson, Joe Leigh] Florida Int Univ, Herbert Wertheim Coll Med, Dept Obstet & Gynecol, Miami, FL 33199 USA.
[Greene, Michael F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Simpson, JL (reprint author), Florida Int Univ, Herbert Wertheim Coll Med, Dept Human & Mol Genet, Miami, FL 33199 USA.
NR 5
TC 15
Z9 17
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 17
PY 2011
VL 364
IS 11
BP 1076
EP 1077
DI 10.1056/NEJMe1101228
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 735SX
UT WOS:000288439000014
PM 21306233
ER
PT J
AU Xu, J
Orkin, SH
AF Xu, Jian
Orkin, Stuart H.
TI The erythroid/myeloid lineage fate paradigm takes a new player
SO EMBO JOURNAL
LA English
DT Editorial Material
ID CELL FATE; ZEBRAFISH; PU.1
AB The erythroid versus myeloid lineage fate decision controlled by cross-antagonism between GATA1 and PU.1 serves as a mechanistic paradigm for transcription factor interplay during lineage specification. In this issue of The EMBO Journal, Monteiro et al (2011) examined this paradigm in blood populations in zebrafish embryos, and demonstrated that, unexpectedly, the regulatory interactions between GATA1 and PU.1 lead to different outcomes depending on the cellular contexts and the development stages. GATA1/PU.1 cross-antagonism is also modulated by a third factor transcriptional intermediate factor 1 gamma (TIF1 gamma), a chromatin-associated haematopoietic regulator.
C1 [Xu, Jian; Orkin, Stuart H.] Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA.
[Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Orkin, SH (reprint author), Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA.
EM stuart_orkin@dfci.harvard.edu
FU Howard Hughes Medical Institute
NR 10
TC 1
Z9 1
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD MAR 16
PY 2011
VL 30
IS 6
BP 983
EP 985
DI 10.1038/emboj.2011.45
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 752ER
UT WOS:000289672900001
PM 21407249
ER
PT J
AU Bot, AGJ
Doornberg, JN
Lindenhovius, ALC
Ring, D
Goslings, JC
van Dijk, CN
AF Bot, Arjan G. J.
Doornberg, Job N.
Lindenhovius, Anneluuk L. C.
Ring, David
Goslings, J. Carel
van Dijk, C. Niek
TI Long-Term Outcomes of Fractures of Both Bones of the Forearm
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID COMPRESSION-PLATE FIXATION; HEALTH-STATUS; CHILDREN; RADIUS; ULNA;
ADULTS; ARM; COMPLICATIONS; TRAUMA; VALUES
AB Background: Previous studies identified limited impairment and disability several years after diaphyseal fractures of both the radius and ulna, although the relationship between impairment and disability was inconsistent. This investigation studied skeletally mature and immature patients more than ten years after injury and addressed the hypotheses that (1) objective measurements of impairment correlate with disability, (2) depression and misinterpretation of nociception correlate with disability, and (3) patients injured when skeletally mature or immature have comparable impairment and disability.
Methods: Seventy-one patients with diaphyseal fractures of the radius and ulna were evaluated at an average of twenty-one years after injury. Twenty-five of the thirty-five patients who were skeletally immature at the time of injury were treated nonoperatively, and thirty-one of the thirty-six skeletally mature patients were treated operatively. Objective evaluation included radiographs, functional assessment, and grip strength. Validated questionnaires were used to measure arm-specific disability (the Disabilities of the Arm, Shoulder and Hand [DASH] score), misinterpretation of pain (Pain Catastrophizing Scale [PCS]), and depression (the validated Dutch form of the Center for Epidemiologic Studies-Depression scale [CES-D]).
Results: The average DASH score was 8 points (range, 0 to 54); 97% of patients had excellent or satisfactory results according to the criteria of Anderson et al., and 72% reported no pain. Both the forearm rotation and the writ flexion/extension arc was 91% of that seen on the uninjured side; grip strength was 94%. There were small but significant differences in rotation (151 versus 169, p = 0.004) and wrist flexion-extension (123 degrees versus 142 degrees, p = 0.002) compared with the results in the uninjured arm. There was no difference in disability between patients who were skeletally mature or immature at the time of injury. Pain, pain catastrophizing (misinterpretation of nociception), and grip strength were the most important predictors of disability.
Conclusions: An average of twenty-one years after sustaining diaphyseal fractures of both the radius and the ulna, patients who were skeletally immature or mature at the time of fracture have comparable disability. Disability correlates better with subjective and psychosocial aspects of illness, such as pain and pain catastrophizing, than with objective measurements of impairment.
C1 [Bot, Arjan G. J.; Doornberg, Job N.; Lindenhovius, Anneluuk L. C.; Ring, David; Goslings, J. Carel; van Dijk, C. Niek] Acad Med Ctr, Dept Orthopaed Surg, NL-1100 DD Amsterdam, Netherlands.
Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
Acad Med Ctr, Dept Surg, Trauma Unit, NL-1100 DD Amsterdam, Netherlands.
RP Bot, AGJ (reprint author), Acad Med Ctr, Dept Orthopaed Surg, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands.
EM a.g.j.bot@gmail.com
NR 32
TC 18
Z9 19
U1 0
U2 1
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 16
PY 2011
VL 93A
IS 6
BP 527
EP 532
DI 10.2106/JBJS.J.00581
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 734AN
UT WOS:000288305700003
PM 21411702
ER
PT J
AU Ozdinler, PH
Benn, S
Yamamoto, TH
Guzel, M
Brown, RH
Macklis, JD
AF Oezdinler, P. Hande
Benn, Susanna
Yamamoto, Ted H.
Guezel, Mine
Brown, Robert H., Jr.
Macklis, Jeffrey D.
TI Corticospinal Motor Neurons and Related Subcerebral Projection Neurons
Undergo Early and Specific Neurodegeneration in hSOD1(G93A) Transgenic
ALS Mice
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; HEREDITARY SPASTIC PARAPLEGIA; SPINAL
MUSCULAR-ATROPHY; SUBTYPE-SPECIFIC GENES; PROGRAMMED CELL-DEATH; MOUSE
MODEL; SUPEROXIDE-DISMUTASE; CEREBRAL-CORTEX; FAMILIAL ALS; IN-VIVO
AB Amyotrophic lateral sclerosis (ALS) is characterized by predominant vulnerability and central degeneration of both corticospinal/corticobulbar motor neurons (CSMN; "upper motor neurons") in cerebral cortex, and spinal/bulbar motor neurons (SMN; "lower motor neurons") in spinal cord and brainstem. Increasing evidence indicates broader cerebral cortex pathology in cognitive, sensory, and association systems in select cases. It remains unclear whether widely accepted transgenic ALS models, in particular hSOD1(G93A) mice, undergo degeneration of CSMN and molecularly/developmentally closely related populations of nonmotor projection neurons [e.g., other subcerebral projection neurons (SCPN)], and whether potential CSMN/SCPN degeneration is specific and early. This relative lack of knowledge regarding upper motor neuron pathology in these ALS model mice has hindered both molecular-pathophysiologic understanding of ALS and their use toward potential CSMN therapeutic approaches. Here, using a combination of anatomic, cellular, transgenic labeling, and newly available neuronal subtype-specific molecular analyses, we identify that CSMN and related nonmotor SCPN specifically and progressively degenerate in hSOD1(G93A) mice. Degeneration starts quite early and presymptomatically, by postnatal day 30. Other neocortical layers, cortical interneurons, and other projection neuron populations, even within layer V, are not similarly affected. Nonneuronal pathology in neocortex (activated astroglia and microglia) is consistent with findings in human ALS cortex and in affected mouse and human spinal cord. These results indicate previously unknown neuron type-specific vulnerability of CSMN/sensory and association SCPN, and identify that characteristic dual CSMN and SMN degeneration is conserved in hSOD1(G93A) mice. These results provide a foundation for detailed investigation of CSMN/SCPN vulnerability and toward potential CSMN therapeutics in ALS.
C1 [Oezdinler, P. Hande; Yamamoto, Ted H.; Guezel, Mine; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Dept Neurosurg, MGH HMS Ctr Nervous Syst Repair, Boston, MA 02114 USA.
[Oezdinler, P. Hande; Yamamoto, Ted H.; Guezel, Mine; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA.
[Oezdinler, P. Hande; Yamamoto, Ted H.; Guezel, Mine; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA.
[Oezdinler, P. Hande; Yamamoto, Ted H.; Guezel, Mine; Macklis, Jeffrey D.] Harvard Univ, Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA.
[Oezdinler, P. Hande; Yamamoto, Ted H.; Guezel, Mine; Macklis, Jeffrey D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA.
[Oezdinler, P. Hande; Yamamoto, Ted H.; Guezel, Mine; Macklis, Jeffrey D.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA.
[Benn, Susanna; Brown, Robert H., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGeneral Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
RP Macklis, JD (reprint author), Harvard Univ, Sch Med, Dept Neurosurg, MGH HMS Ctr Nervous Syst Repair, Boston, MA 02114 USA.
EM ozdinler@northwestern.edu; jeffrey_macklis@hms.harvard.edu
FU National Institutes of Health [NS49553, NS41590, NS45523]; ALS
Association; Harvard Stem Cell Institute; Les Turner ALS Foundation;
Harvard NeuroDiscovery Center
FX This work was supported by grants from the National Institutes of Health
(NS49553; additional infrastructure provided by NS41590 and NS45523),
the ALS Association, and the Harvard Stem Cell Institute to J.D.M., and
the Les Turner ALS Foundation to P.H.O. P.H.O. was partially supported
by a fellowship from the Harvard NeuroDiscovery Center, and by a program
grant from the Harvard Stem Cell Institute to J.D.M. We thank K.
Billmers, A. Palmer, A. Sanders, M. Jonathan for technical assistance;
members of the Macklis and Brown laboratories for important input and
suggestions; and E. Azim, S. Sohur, and J. Emsley for critical reading
of an earlier version of this manuscript.
NR 72
TC 59
Z9 59
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 16
PY 2011
VL 31
IS 11
BP 4166
EP 4177
DI 10.1523/JNEUROSCI.4184-10.2011
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 735YC
UT WOS:000288455700024
PM 21411657
ER
PT J
AU Luikart, BW
Schnell, E
Washburn, EK
Bensen, AL
Tovar, KR
Westbrook, GL
AF Luikart, Bryan W.
Schnell, Eric
Washburn, Eric K.
Bensen, AeSoon L.
Tovar, Kenneth R.
Westbrook, Gary L.
TI Pten Knockdown In Vivo Increases Excitatory Drive onto Dentate Granule
Cells
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID AUTISM SPECTRUM DISORDERS; LHERMITTE-DUCLOS-DISEASE; SOCIAL-INTERACTION;
SOMA SIZE; INHIBITION; MUTATION; GENE; MICE; PROLIFERATION; TRANSMISSION
AB Some cases of autism spectrum disorder have mutations in the lipid phosphatase, phosphatase and tensin homolog on chromosome 10 (Pten). Tissue specific deletion of Pten in the hippocampus and cortex of mice causes anatomical and behavioral abnormalities similar to human autism. However, the impact of reductions in Pten on synaptic and circuit function remains unexplored. We used in vivo stereotaxic injections of lentivirus expressing a short hairpin RNA to knock down Pten in mouse neonatal and young adult dentate granule cells. We then assessed the morphology and synaptic physiology between 2 weeks and 4 months later. Confocal imaging of the hippocampus revealed a marked increase in granule cell size and an increase in dendritic spine density. The onset of morphological changes occurred earlier in neonatal mice than in young adults. We used whole-cell recordings from granule cells in acute slices to assess synaptic function after Pten knockdown. Consistent with the increase in dendritic spines, the frequency of excitatory miniature and spontaneous postsynaptic currents increased. However, there was little or no effect on IPSCs. Thus, Pten knockdown results in an imbalance between excitatory and inhibitory synaptic activity. Because reductions in Pten affected mature granule cells as well as developing granule cells, we suggest that the disruption of circuit function by Pten hypofunction may be ongoing well beyond early development.
C1 [Luikart, Bryan W.; Washburn, Eric K.; Bensen, AeSoon L.; Tovar, Kenneth R.; Westbrook, Gary L.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
[Schnell, Eric] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA.
[Schnell, Eric] Oregon Hlth & Sci Univ, Dept Anesthesia & Perioperat Med, Portland, OR 97239 USA.
RP Luikart, BW (reprint author), Dartmouth Med Sch, Dept Neurobiol & Physiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM bryan.w.luikart@dartmouth.edu
RI Luikart, Bryan/D-2683-2012;
OI Schnell, Eric/0000-0002-5623-5015
FU National Institutes of Health [T32NS007381, F32MH079548, MH46613]
FX This work was supported by National Institutes of Health Grants
T32NS007381, F32MH079548 (B.W.L.), and MH46613 (G.L.W.). We thank Cooper
French, Stephen Magill, Mike Walogorsky, and Karin Mullendorff for their
contributions to this work.
NR 34
TC 61
Z9 61
U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 16
PY 2011
VL 31
IS 11
BP 4345
EP 4354
DI 10.1523/JNEUROSCI.0061-11.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 735YC
UT WOS:000288455700041
PM 21411674
ER
PT J
AU Sachs, DH
AF Sachs, David H.
TI Mark Pescovitz, M.D. (1955-2010) IN MEMORIAM
SO TRANSPLANTATION
LA English
DT Biographical-Item
C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA.
EM david.sachs@tbrc.mgh.harvard.edu
NR 1
TC 0
Z9 0
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 2011
VL 91
IS 5
BP 487
EP 488
DI 10.1097/TP.0b013e31821060d1
PG 2
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 722ZJ
UT WOS:000287474300001
PM 21343875
ER
PT J
AU Magnani, JW
Johnson, VM
Sullivan, LM
Gorodeski, EZ
Schnabel, RB
Lubitz, SA
Levy, D
Ellinor, PT
Benjamin, EJ
AF Magnani, Jared W.
Johnson, Victor M.
Sullivan, Lisa M.
Gorodeski, Eiran Z.
Schnabel, Renate B.
Lubitz, Steven A.
Levy, Daniel
Ellinor, Patrick T.
Benjamin, Emelia J.
TI P Wave Duration and Risk of Longitudinal Atrial Fibrillation in Persons
>= 60 Years Old (from the Framingham Heart Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID FAILURE; INTERVAL; PROFILE; INDEXES; DISEASE; STROKE
AB Long-term risk prediction is a priority for the prevention of atrial fibrillation (AF). P wave indices are electrocardiographic measurements describing atrial conduction. The role of P wave indices in the prospective determination of AF and mortality risk has had limited assessment. We quantified by digital caliper the P wave indices of maximum duration and dispersion in 1,550 Framingham Heart Study participants >= 60 years old (58% women) from single-channel electrocardiograms recorded from 1968 through 1971. We examined the association of selected P wave indices and long-term outcomes using Cox proportional hazards regression incorporating age, gender, body mass index, systolic blood pressure, treatment for hypertension, significant murmur, heart failure, and PR interval. Over a median follow-up of 15.8 years (range 0 to 38.7), 359 participants developed AF and 1,525 died. Multivariable-adjusted hazard ratios (HRs) per SD increase in maximum P wave duration were 1.15 (95% confidence interval [CI] 0.90 to 1.47, p = 0.27) for AF and 1.02 (95% CI 0.96 to 1.08, p = 0.18) for mortality. The upper 5% of P wave maximum duration had a multivariable-adjusted HR of 2.51 (95% CI 1.13 to 5.57, p = 0.024) for AF and an HR of 1.11 (95% CI 0.87 to 1.40, p = 0.20) for mortality. We found no significant associations between P wave dispersion with incidence of AF or mortality. In conclusion, maximum P wave duration at the upper fifth percentile was associated with long-term AF risk in an elderly community-based cohort. P wave duration is an electrocardiographic endophenotype for AF. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107: 917-921)
C1 [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Magnani, Jared W.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Johnson, Victor M.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Gorodeski, Eiran Z.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA.
[Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany.
[Schnabel, Renate B.] Gutenberg Heart Study Div Prevent Med, Mainz, Germany.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
EM jmagnani@bu.edu
RI Schnabel, Renate/F-6527-2014;
OI Gorodeski, Eiran/0000-0003-3756-8831; Sullivan,
Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336
FU American Heart Association, Dallas, Texas [09FTF2190028]; National
Institutes of Health, Bethesda, Maryland [N01-HC 25195, RC1HL101056,
1R01HL102214, 1HL104156, HL092577]
FX This research was funded by Award 09FTF2190028 from the American Heart
Association, Dallas, Texas to Dr. Magnani and Grants N01-HC 25195,
RC1HL101056, and 1R01HL102214 (Dr. Benjamin), 1HL104156 (Dr. Ellinor),
and HL092577 (Dr. Ellinor and Dr. Benjamin) from the National Institutes
of Health, Bethesda, Maryland.
NR 19
TC 60
Z9 64
U1 1
U2 7
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD MAR 15
PY 2011
VL 107
IS 6
BP 917
EP 921
DI 10.1016/j.amjcard.2010.10.075
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 740WO
UT WOS:000288825300019
PM 21255761
ER
PT J
AU Tsao, CW
Gona, P
Salton, C
Danias, PG
Blease, S
Hoffmann, U
Fox, CS
Albert, M
Levy, D
O'Donnell, CJ
Manning, WJ
Yeon, SB
AF Tsao, Connie W.
Gona, Philimon
Salton, Carol
Danias, Peter G.
Blease, Susan
Hoffmann, Udo
Fox, Caroline S.
Albert, Mark
Levy, Daniel
O'Donnell, Christopher J.
Manning, Warren J.
Yeon, Susan B.
TI Subclinical and Clinical Correlates of Left Ventricular Wall Motion
Abnormalities in the Community
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CORONARY-ARTERY CALCIUM; MAGNETIC-RESONANCE; MYOCARDIAL-INFARCTION;
HEART-DISEASE; PROGNOSTIC-SIGNIFICANCE; CARDIOVASCULAR-DISEASE;
COMPUTED-TOMOGRAPHY; FOLLOW-UP; POPULATION; ATHEROSCLEROSIS
AB The prevalence and clinical correlates of left ventricular (LV) wall motion abnormalities (WMAs), associated with morbidity and mortality, have not been well-characterized in the population. Framingham Heart Study Offspring Cohort participants (n = 1,794, 844 men, age 65 9 years) underwent cine cardiovascular magnetic resonance for evaluation of LV function. A subset (n = 1,009, 460 men) underwent cardiac multidetector computed tomography for analysis of coronary artery calcium. The presence of coronary heart disease and heart failure (CHD-HF) were assessed in relation to the presence of WMAs. WMAs were present in 117 participants (6.5%) and were associated with male gender, elevated hemoglobin Ale, LV mass, LV end-diastolic volume, and lower LV ejection fraction. Of the 1,637 participants without CHD-HF, 68 (4.2%) had WMAs. In this group, WMAs were associated with obesity, hypertension, and Framingham coronary heart disease risk score in the age- and gender-adjusted analyses and were associated with male gender and hypertension on multivariate analysis. Most subjects with WMAs were in the greatest coronary artery calcium groups. The presence of coronary artery calcium greater than the seventy-fifth percentile and Agatston score > 100. were associated with a greater than twofold risk of WMAs in the age- and gender-adjusted analysis but were no longer significant when additionally adjusted for CHD-HF. Previous Q-wave myocardial infarction was present in 29% of the 117 participants with WMAs. In conclusion, in the present longitudinally followed free-living population, 4.2% of the participants without CHD-HF had WMAs. WMAs were associated with the clinical parameters associated with cardiovascular disease risk. Aggressive risk factor modification may be prudent for subjects with WMAs, particularly those free of clinical CHD-HF. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:949-955)
C1 [Tsao, Connie W.; Salton, Carol; Danias, Peter G.; Manning, Warren J.; Yeon, Susan B.] Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Boston, MA 02215 USA.
[Tsao, Connie W.; Salton, Carol; Danias, Peter G.; Manning, Warren J.; Yeon, Susan B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA.
[Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Gona, Philimon] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Gona, Philimon; Blease, Susan; Fox, Caroline S.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA.
[Albert, Mark] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA.
[O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA.
RP Yeon, SB (reprint author), Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Boston, MA 02215 USA.
EM syeon@bidmc.harvard.edu
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[N01-HC-25195]; National Institutes of Health, Bethesda, Maryland [1RO1
HL70279, T32 HL07374]
FX The Framingham Heart Study was supported by contract N01-HC-25195 from
the National Heart, Lung, and Blood Institute, Bethesda, Maryland. The
present study was supported in part by grant 1RO1 HL70279 and training
grant T32 HL07374 (to C. W. Tsao) from the National Institutes of
Health, Bethesda, Maryland.
NR 25
TC 5
Z9 5
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD MAR 15
PY 2011
VL 107
IS 6
BP 949
EP 955
DI 10.1016/j.amjcard.2010.11.014
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 740WO
UT WOS:000288825300025
PM 21247548
ER
PT J
AU Maire, CL
Ligon, KL
AF Maire, Cecile L.
Ligon, Keith L.
TI Glioma Models: New GEMMs Add "Class" with Genomic and Expression
Correlations
SO CANCER CELL
LA English
DT Editorial Material
ID GLIOBLASTOMA; MEDULLOBLASTOMA; SUBTYPES
AB Malignant gliomas are characterized by accumulated aberrations affecting TP53, PTEN, and RB1 signaling. In this issue, Chow et al. discover that combinatorial loss of these tumor suppressors in mice induces gliomas with unexpected degrees of similarity to human pathologic, genomic, and expression subclasses recently revealed by large-scale genomic studies.
C1 [Maire, Cecile L.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02215 USA.
[Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA.
[Ligon, Keith L.] Childrens Hosp Boston, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA.
[Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Ligon, KL (reprint author), Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM keith_ligon@dfci.harvard.edu
OI Ligon, Keith/0000-0002-7733-600X
NR 10
TC 2
Z9 2
U1 0
U2 2
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 15
PY 2011
VL 19
IS 3
BP 295
EP 297
DI 10.1016/j.ccr.2011.02.018
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 738LY
UT WOS:000288642500001
PM 21397851
ER
PT J
AU Mehta, S
Huillard, E
Kesari, S
Maire, CL
Golebiowski, D
Harrington, EP
Alberta, JA
Kane, MF
Theisen, M
Ligon, KL
Rowitch, DH
Stiles, CD
AF Mehta, Shwetal
Huillard, Emmanuelle
Kesari, Santosh
Maire, Cecile L.
Golebiowski, Diane
Harrington, Emily P.
Alberta, John A.
Kane, Michael F.
Theisen, Matthew
Ligon, Keith L.
Rowitch, David H.
Stiles, Charles D.
TI The Central Nervous System-Restricted Transcription Factor Olig2 Opposes
p53 Responses to Genotoxic Damage in Neural Progenitors and Malignant
Glioma
SO CANCER CELL
LA English
DT Article
ID INTEGRATED GENOMIC ANALYSIS; GROWTH-FACTOR RECEPTOR; CANCER STEM-CELLS;
LOW-GRADE GLIOMAS; IN-VIVO; SUCCESSFUL CHEMOTHERAPY; SELF-RENEWAL;
GENES; PATHWAY; OLIGODENDROGLIOMA
AB High-grade gliomas are notoriously insensitive to radiation and genotoxic drugs. Paradoxically, the p53 gene is structurally intact in the majority of these tumors. Resistance to genotoxic modalities in p53-positive gliomas is generally attributed to attenuation of p53 functions by mutations of other components within the p53 signaling axis, such as p14(Arf), MDM2, and ATM, but this explanation is not entirely satisfactory. We show here that the central nervous system (CNS)-restricted transcription factor Olig2 affects a key posttranslational modification of p53 in both normal and malignant neural progenitors and thereby antagonizes the interaction of p53 with promoter elements of multiple target genes. In the absence of Olig2 function, even attenuated levels of p53 are adequate for biological responses to genotoxic damage.
C1 [Huillard, Emmanuelle; Harrington, Emily P.; Rowitch, David H.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Huillard, Emmanuelle; Harrington, Emily P.; Rowitch, David H.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
[Huillard, Emmanuelle; Harrington, Emily P.; Rowitch, David H.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
[Mehta, Shwetal; Golebiowski, Diane; Alberta, John A.; Kane, Michael F.; Stiles, Charles D.] Dept Canc Biol, Boston, MA 02115 USA.
[Kesari, Santosh; Maire, Cecile L.; Theisen, Matthew; Ligon, Keith L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA.
[Ligon, Keith L.] Brigham & Womens Hosp, Div Neuropathol, Dept Pathol, Boston, MA 02115 USA.
RP Rowitch, DH (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
EM rowitchd@peds.ucsf.edu; charles_stiles@dfci.harvard.edu
RI Kesari, Santosh/E-8461-2013
FU NINDS [NS05563, NS040511, NS057727, NS047213]; Pediatric Low-Grade
Astrocytoma Foundation
FX recipient of the NRSA fellowship NS05563 from NINDS. This work was
supported by grants from the NINDS (NS040511, NS057727, and NS047213 to
D.H.R., C.D.S., and K.L.L respectively) and from the Pediatric Low-Grade
Astrocytoma Foundation. D.H.R is a Howard Hughes Medical Institute
Investigator.
NR 70
TC 61
Z9 65
U1 1
U2 17
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 15
PY 2011
VL 19
IS 3
BP 359
EP 371
DI 10.1016/j.ccr.2011.01.035
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 738LY
UT WOS:000288642500009
PM 21397859
ER
PT J
AU Anderson, KC
AF Anderson, Kenneth C.
TI Oncogenomics to Target Myeloma in the Bone Marrow Microenvironment
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PROTEASOME INHIBITOR PS-341; DIAGNOSED MULTIPLE-MYELOMA; LENALIDOMIDE
PLUS DEXAMETHASONE; UNDETERMINED SIGNIFICANCE MGUS; RANDOMIZED
CONTROLLED-TRIAL; OVERCOMES DRUG-RESISTANCE; IN-VIVO CYTOTOXICITY;
MONOCLONAL GAMMOPATHY; PHASE-III; MOLECULAR CLASSIFICATION
AB Multiple myeloma (MM) is an example of rapid bench-to-bedside translation in new drug development. Bortezomib and lenalidamide target the tumor cell in the bone marrow microenvironment to overcome drug resistance in laboratory and animal models; each is effective to treat relapsed and/or refractory, relapsed, and newly diagnosed MM, and both are now showing promise as maintenance therapy. Major ongoing translational research efforts include improved classification and personalized therapies; identification and validation of next-generation agents targeting the tumor cell in its microenvironment; novel immune therapies; rationally based combination therapies; and use of novel agents to delay or prevent development of active MM. This paradigm of targeting the tumor in its microenvironment has already extended median survival in MM from 3 to 7 to 8 years and has great potential to improve patient outcome in other hematologic malignancies and solid tumors as well. Clin Cancer Res; 17(6); 1225-33. (C)2011 AACR.
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM kenneth_anderson@dfci.harvard.edu
NR 80
TC 38
Z9 41
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2011
VL 17
IS 6
BP 1225
EP 1233
DI 10.1158/1078-0432.CCR-10-3366
PG 9
WC Oncology
SC Oncology
GA 735RR
UT WOS:000288435300004
PM 21411438
ER
PT J
AU Munshi, NC
Avet-Loiseau, H
AF Munshi, Nikhil C.
Avet-Loiseau, Herve
TI Genomics in Multiple Myeloma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID IN-SITU HYBRIDIZATION; STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY;
ADVERSE PROGNOSTIC-FACTOR; GROWTH-FACTOR RECEPTOR-3; P53 GENE DELETION;
CHROMOSOME-13 ABNORMALITIES; MOLECULAR CLASSIFICATION; INTERGROUPE
FRANCOPHONE; COMPLETE REMISSIONS
AB Multiple myeloma (MM) is a complex disease that is driven by numerous genetic and epigenetic alterations. Comprehensive oncogenomic analysis indicates the presence of many highly recurrent and highly focal amplifications and/or deletions in the MM genome. Integrated oncogenomic analyses of human MM have identified candidates resident within regions of amplification and/or deletions that are predicted to be involved in MM pathogenesis and progression. The biological behavior and clinical outcome in MM are dependent on these molecular determinants, which are also attractive therapeutic targets. The data obtained from extensive analysis of patient samples, with annotated clinical outcomes, are providing insights into molecular mechanisms of disease behavior, helping to develop sensitive prognostic models, identifying novel therapeutic targets, providing the framework for the development of molecularly based therapies, and, eventually, will help in developing individualized therapy to improve outcomes, with reduced toxicity. Clin Cancer Res; 17(6); 1234-42. (C)2011 AACR.
C1 [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA.
[Avet-Loiseau, Herve] Univ Hosp, Hematol Lab, Nantes, France.
[Avet-Loiseau, Herve] INSERM, U892, Nantes, France.
RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,D1B28, Boston, MA 02115 USA.
EM nikhil_munshi@dfci.harvard.edu; havetloiseau@chu-nantes.fr
FU NIH [PO1 CA155258-01, RO1-124929, P50-100007, PO1-78378]; Department of
Veterans Affairs; Intergroupe Francophone du Myelome; French Institut
National du [R09076NN]
FX This study was supported in part by the NIH grant PO1 CA155258-01 (N.C.
Munshi and H. Avet-Loiseau), RO1-124929, P50-100007, PO1-78378, and
Department of Veterans Affairs Merit Review Awards (N.C. Munshi);
Intergroupe Francophone du Myelome; and the French Institut National du
Cancer grant R09076NN (H. Avet-Loiseau).
NR 60
TC 48
Z9 50
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2011
VL 17
IS 6
BP 1234
EP 1242
DI 10.1158/1078-0432.CCR-10-1843
PG 9
WC Oncology
SC Oncology
GA 735RR
UT WOS:000288435300005
PM 21411439
ER
PT J
AU Lonial, S
Mitsiades, CS
Richardson, PG
AF Lonial, Sagar
Mitsiades, Constantine S.
Richardson, Paul G.
TI Treatment Options for Relapsed and Refractory Multiple Myeloma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PEGYLATED LIPOSOMAL DOXORUBICIN; STEM-CELL TRANSPLANTATION;
BONE-MARROW-TRANSPLANTATION; EXTENDED FOLLOW-UP; HISTONE-DEACETYLASE
INHIBITORS; HIGH-DOSE DEXAMETHASONE; PHASE-II; ORAL CYCLOPHOSPHAMIDE;
CLINICAL-IMPLICATIONS; COMBINATION THERAPY
AB Treatment options for patients with relapsed myeloma have benefited from the development of new targeted agents. The use of bortezomib, thalidomide, and lenalidomide have dramatically changed outcomes for patients with relapsed myeloma. New agents are also in development, on the basis of preclinical rationale, as well as combinations of conventional and novel agents. Together each of these treatment approaches are being tested in phase I, II, and III clinical trials, with the goal of prolonged duration of remission and, ultimately, improved overall survival. Clin Cancer Res; 17(6); 1264-77. (C)2011 AACR.
C1 [Lonial, Sagar] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA.
[Mitsiades, Constantine S.; Richardson, Paul G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA.
RP Lonial, S (reprint author), 1365 Clifton Rd,Bldg C,Room 4004, Atlanta, GA 30322 USA.
EM sloni01@emory.edu
FU PharmaMar; OSI Pharmaceuticals, Amgen; AVEO Pharma; EMD Serono; Sunesis;
Gloucester Pharmaceuticals, Genzyme; Johnson Johnson; Rick Corman
Multiple Myeloma Research Fund
FX S. Lonial, consultant, Millennium, Celgene, BMS, Novartis, Merck, Onyx.
P.G. Richardson, consultant, Millennium, Celgene, Johnson & Johnson,
Novartis. C.S. Mitsiades, consultant honoraria from Millennium
Pharmaceuticals, Novartis Pharmaceuticals, Bristol-Myers Squibb, Merck &
Co., Kosan Pharmaceuticals, Pharmion and Centocor; licensing royalties
from PharmaMar; and research funding from OSI Pharmaceuticals, Amgen,
AVEO Pharma, EMD Serono, Sunesis, Gloucester Pharmaceuticals, Genzyme,
and Johnson & Johnson.; The authors would like to express their sincere
thanks to Katherine Redman for administrative and editorial assistance
with this article, which was in part supported by the Rick Corman
Multiple Myeloma Research Fund.
NR 142
TC 78
Z9 83
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2011
VL 17
IS 6
BP 1264
EP 1277
DI 10.1158/1078-0432.CCR-10-1805
PG 14
WC Oncology
SC Oncology
GA 735RR
UT WOS:000288435300008
PM 21411442
ER
PT J
AU Raje, N
Roodman, GD
AF Raje, Noopur
Roodman, G. David
TI Advances in the Biology and Treatment of Bone Disease in Multiple
Myeloma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; KAPPA-B LIGAND; CELL-ACTIVATING
FACTOR; MARROW STROMAL CELLS; IN-VIVO; OSTEOCLAST FORMATION; INHIBITS
OSTEOCLASTOGENESIS; MICRODAMAGE ACCUMULATION; THERAPEUTIC IMPLICATIONS;
RECEPTOR ACTIVATOR
AB Osteolytic bone disease is pathognomonic of multiple myeloma (MM) and affects more than 80% of patients. Bone disease results in skeletal-related events (SRE) such as vertebral compression fractures, which may cause cord compression, hypercalcemia, pathologic fractures that require radiation or surgical fixation, and severe pain. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. Osteolytic disease is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling. OC number and activity are increased in MM via cytokine deregulation within the bone marrow (BM) milieu, whereas negative regulators of OB differentiation suppress bone formation. Bisphosphonates are a well-established treatment of myeloma-related skeletal disease and are the current standard of care. However, complications arising from their long-term use have prompted studies of schedule optimization and alternate strategies. Several novel agents are currently under investigation for their positive effect on bone remodeling via OC inhibition. The identification of negative regulators of OB differentiation has prompted the use of anabolic agents. In addition to restoring bone remodeling, these drugs may inhibit tumor growth in vivo. Future studies will look to combine or sequence all of these agents with the goal of not only alleviating morbidity from bone disease but also capitalizing on the resultant antitumor activity. Clin Cancer Res; 17(6); 1278-86. (C)2011 AACR.
C1 [Raje, Noopur] Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol Oncol, Boston, MA 02114 USA.
[Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Roodman, G. David] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Pittsburgh, PA USA.
[Roodman, G. David] Virginia Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Raje, N (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol Oncol, 55 Fruit St, Boston, MA 02114 USA.
EM nraje@partners.org
FU Acetylon; AstraZeneca
FX N. Raje, commercial research grant, Acetylon, AstraZeneca; consultant,
Celgene, Amgen, Novartis. G. D. Roodman disclosed no potential conflicts
of interest.
NR 88
TC 68
Z9 73
U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2011
VL 17
IS 6
BP 1278
EP 1286
DI 10.1158/1078-0432.CCR-10-1804
PG 9
WC Oncology
SC Oncology
GA 735RR
UT WOS:000288435300009
PM 21411443
ER
PT J
AU Rudd, ML
Price, JC
Fogoros, S
Godwin, AK
Sgroi, DC
Merino, MJ
Bell, DW
AF Rudd, Meghan L.
Price, Jessica C.
Fogoros, Sarah
Godwin, Andrew K.
Sgroi, Dennis C.
Merino, Maria J.
Bell, Daphne W.
TI A Unique Spectrum of Somatic PIK3CA (p110 alpha) Mutations Within
Primary Endometrial Carcinomas
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HUMAN CANCER; TUMOR-SUPPRESSOR; POOR-PROGNOSIS; GENE-MUTATIONS;
HIGH-FREQUENCY; PATHWAY; DOMAIN; PTEN; CARCINOGENESIS; PHOSPHATASE
AB Purpose: The goal of this study was to comprehensively define the incidence of mutations in all exons of PIK3CA in both endometrioid endometrial cancer (EEC) and nonendometrioid endometrial cancer (NEEC).
Experimental Design: We resequenced all coding exons of PIK3CA and PTEN, and exons 1 and 2 of KRAS, from 108 primary endometrial tumors. Somatic mutations were confirmed by sequencing matched normal DNAs. The biochemical properties of a subset of novel PIK3CA mutations were determined by exogenously expressing wild type and mutant constructs in U2OS cells and measuring levels of AKT(Ser473) phosphorylation.
Results: Somatic PIK3CA mutations were detected in 52.4% of 42 EECs and 33.3% of 66 NEECs. Half (29 of 58) of all nonsynonymous PIK3CA mutations were in exons 1-7 and half were in exons 9 and 20. The exons 1-7 mutations localized to the ABD, ABD-RBD linker and C2 domains of p110 alpha. Within these regions, Arg88, Arg93, Gly106, Lys111, Glu365, and Glu453, were recurrently mutated; Arg88, Arg93, and Lys111 formed mutation hotspots. The p110 alpha-R93W, -G106R, -G106V, -K111E, -delP449-L455, and -E453K mutants led to increased levels of phospho-AKT(Ser473) compared to wild-type p110 alpha. Overall, 62% of exons 1-7 PIK3CA mutants and 64% of exons 9-20 PIK3CA mutants were activating; 72% of exon 1-7 mutations have not previously been reported in endometrial cancer.
Conclusions: Our study identified a new subgroup of endometrial cancer patients with activating mutations in the amino-terminal domains of p110 alpha; these patients might be appropriate for consideration in clinical trials of targeted therapies directed against the PI3K pathway. Clin Cancer Res; 17(6); 1331-40. (C)2011 AACR.
C1 [Rudd, Meghan L.; Price, Jessica C.; Fogoros, Sarah; Bell, Daphne W.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, NIH, Bethesda, MD 20892 USA.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA.
RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, 50 South Dr,MSC-8000, Bethesda, MD 20892 USA.
EM belldaph@mail.nih.gov
FU National Human Genome Research Institute/NIH; NIH [R01 CA140323, U01
CA113916, R01-1CA112021-01]; NCI SPORE in breast cancer at Massachusetts
General Hospital; Ovarian Cancer Research Fund; Avon Foundation
FX The Intramural Program of the National Human Genome Research
Institute/NIH (D. W. Bell); NIH R01 CA140323 (A. K. Godwin), U01
CA113916 (A. K. Godwin), NIH R01-1CA112021-01 (D. C. Sgroi), NCI SPORE
in breast cancer at Massachusetts General Hospital (D. C. Sgroi), the
Ovarian Cancer Research Fund (A. K. Godwin), and the Avon Foundation (D.
C. Sgroi).
NR 41
TC 99
Z9 99
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2011
VL 17
IS 6
BP 1331
EP 1340
DI 10.1158/1078-0432.CCR-10-0540
PG 10
WC Oncology
SC Oncology
GA 735RR
UT WOS:000288435300014
PM 21266528
ER
PT J
AU Liao, S
Liu, JQ
Lin, PC
Shi, T
Jain, RK
Xu, L
AF Liao, Shan
Liu, Jieqiong
Lin, Peichun
Shi, Tony
Jain, Rakesh K.
Xu, Lei
TI TGF-beta Blockade Controls Ascites by Preventing Abnormalization of
Lymphatic Vessels in Orthotopic Human Ovarian Carcinoma Models
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-BETA; ALTERED EXPRESSION; TUMOR VASCULATURE; MALIGNANT
ASCITES; INHIBITS TUMOR; CANCER MODEL; MOUSE MODEL; ANGIOGENESIS;
METASTASIS; THERAPY
AB Purpose: Ovarian cancer patients with malignant ascites have poor prognosis. The accumulation of ascites is caused by an imbalance between fluid extravasation from the blood vessels and reabsorption by lymphatic vessels. Whereas, the role of TGF-beta in tumor progression has been well studied, the role of TGF-beta in lymphatic vessel function is far from understood. Here, we sought to dissect the role of TGF-beta blockade in the formation of ascites.
Experimental Design: We used soluble TGF-beta Receptor II (sT beta RII) to block TGF-beta signaling in two orthotopic human ovarian carcinoma models: SKOV3ip1 and Hey-A8. We measured tumor proliferation, apoptosis, lymphangiogenesis, and angiogenesis by immunohistochemical staining, and examined diaphragm lymphatic vessel network by intraperitoneal injection of a fluorescent dye. Diaphragm lymphatic vessel function was assessed by tracking fluorescent beads in the diaphragm and measuring their drainage rate.
Results: TGF-beta blockade impaired tumor growth in both models, accompanied by a decreased tumor cell proliferation and angiogenesis. More strikingly, TGF-beta blockade almost completely abolished ascites formation. TGF-beta blockade significantly inhibited the expression of VEGF, which is the major contributor to ascites formation. At the same time, TGF-beta blockade prevent 'abnormalization' of diaphragm lymphatic vessels and improved ascites drainage.
Conclusions: TGF-beta blockade decreased ascites by both inhibiting ascites formation and improving ascites drainage. Based on our finding, it is reasonable to consider the use of TGF-beta blockade as a palliative treatment for symptomatic ascites. Clin Cancer Res; 17(6); 1415-24. (C)2011 AACR.
C1 [Liao, Shan; Liu, Jieqiong; Lin, Peichun; Jain, Rakesh K.; Xu, Lei] Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA.
[Liu, Jieqiong] Cent S Univ, Xiangya Hosp 2, Dept Breast Surg, Changsha, Hunan, Peoples R China.
[Shi, Tony] NYU, Coll Arts & Sci, New York, NY USA.
RP Xu, L (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, 100 Blossom St,Cox 734, Boston, MA 02114 USA.
EM lei@steele.mgh.harvard.edu
RI Lin, Pei-Chun/A-3200-2013
FU Genzyme; Noxxon; Harvard Medical School; NCI [P01-CA80124]; Federal
Share/NCI; Massachusetts Biomedical Research Corporation
FX R.K. Jain, consultant, Genzyme and Noxxon. Neither reagent nor financial
support from these two companies was used in the current study.; This
work was supported in part by Clafflin Distinguished Scholar Award,
Harvard Medical School (L. Xu), Program Project Grant P01-CA80124 from
NCI (to R.K. Jain) and Federal Share/NCI Proton Beam Program (R.K. Jain)
and Tosteson Postdoctoral Fellowship from the Massachusetts Biomedical
Research Corporation (S. Liao.).
NR 41
TC 25
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U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2011
VL 17
IS 6
BP 1415
EP 1424
DI 10.1158/1078-0432.CCR-10-2429
PG 10
WC Oncology
SC Oncology
GA 735RR
UT WOS:000288435300022
PM 21278244
ER
PT J
AU Morikawa, T
Baba, Y
Yamauchi, M
Kuchiba, A
Nosho, K
Shima, K
Tanaka, N
Huttenhower, C
Frank, DA
Fuchs, CS
Ogino, S
AF Morikawa, Teppei
Baba, Yoshifumi
Yamauchi, Mai
Kuchiba, Aya
Nosho, Katsuhiko
Shima, Kaori
Tanaka, Noriko
Huttenhower, Curtis
Frank, David A.
Fuchs, Charles S.
Ogino, Shuji
TI STAT3 Expression, Molecular Features, Inflammation Patterns, and
Prognosis in a Database of 724 Colorectal Cancers
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; GROWTH-SUPPRESSIVE ACTIVITY; COLON-CANCER;
MICROSATELLITE INSTABILITY; SIGNAL TRANSDUCER; TRANSCRIPTION-3
ACTIVATION; FACTOR RECEPTOR; BRAF MUTATION; BETA-CATENIN; CELLS
AB Purpose: STAT3 is a transcription factor that is constitutively activated in some cancers. It seems to play crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation, and suppression of antitumor host immune response in the tumor microenvironment. Although the STAT3 signaling pathway is a potential drug target, clinical, pathologic, molecular, or prognostic features of STAT3-activated colorectal cancer remain uncertain.
Experimental Design: Utilizing a database of 724 colon and rectal cancer cases, we evaluated phosphorylated STAT3 (p-STAT3) expression by immunohistochemistry. The Cox proportional hazards model was used to compute mortality HR, adjusting for clinical, pathologic, and molecular features, including microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), LINE-1 methylation, 18q LOH, TP53 (p53), CTNNB1 (beta-catenin), JC virus T-antigen, and KRAS, BRAF, and PIK3CA mutations.
Results: Among the 724 tumors, 131 (18%) showed high-level p-STAT3 expression (p-STAT3-high), 244 (34%) showed low-level expression (p-STAT3-low), and the remaining 349 (48%) were negative for p-STAT3. p-STAT3 overexpression was associated with significantly higher colorectal cancer-specific mortality [ log-rank P - 0.0020; univariate HR (p-STAT3-high vs. p-STAT3-negative): 1.85, 95% CI: 1.30-2.63, P(trend) = 0.0005; multivariate HR: 1.61, 95% CI: 1.11-2.34, P(trend) = 0.015]. p-STAT3 expression was positively associated with peritumoral lymphocytic reaction (multivariate OR: 3.23; 95% CI: 1.89-5.53, P < 0.0001). p-STAT3 expression was not associated with MSI, CIMP, or LINE-1 hypomethylation.
Conclusions: STAT3 activation in colorectal cancer is associated with adverse clinical outcome, supporting its potential roles as a prognostic biomarker and a chemoprevention and/or therapeutic target. Clin Cancer Res; 17(6); 1452-62. (C)2011 AACR.
C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Ctr Mol Oncol Pathol,Dept M, Boston, MA 02115 USA.
[Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA USA.
RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Ctr Mol Oncol Pathol,Dept M, 44 Binney St,Room JF-215C, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
OI Huttenhower, Curtis/0000-0002-1110-0096
FU U.S. NIH [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826, R01
CA151993]; Bennett Family Fund; Entertainment Industry Foundation
through National Colorectal Cancer Research Alliance; Japan Society for
Promotion of Science
FX This work was supported by U.S. NIH grants P01 CA87969 (to S.
Hankinson), P01 CA55075 (to W. Willett), P50 CA127003 (to C.S. Fuchs),
K07 CA122826 (to S. Ogino), and R01 CA151993 (to S. Ogino) and by grants
from the Bennett Family Fund and the Entertainment Industry Foundation
through National Colorectal Cancer Research Alliance. T. Morikawa and K.
Nosho were supported by fellowship grants from the Japan Society for
Promotion of Science.
NR 50
TC 75
Z9 79
U1 1
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 2011
VL 17
IS 6
BP 1452
EP 1462
DI 10.1158/1078-0432.CCR-10-2694
PG 11
WC Oncology
SC Oncology
GA 735RR
UT WOS:000288435300025
PM 21310826
ER
PT J
AU Sun, T
Lee, GSM
Oh, WK
Freedman, ML
Pomerantz, M
Pienta, KJ
Kantoff, PW
AF Sun, Tong
Lee, Gwo-Shu Mary
Oh, William K.
Freedman, Matthew L.
Pomerantz, Mark
Pienta, Kenneth J.
Kantoff, Philip W.
TI Inherited Variants in the Chemokine CCL2 Gene and Prostate Cancer
Aggressiveness in a Caucasian Cohort
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; ANDROGEN-DEPRIVATION THERAPY;
SINGLE-NUCLEOTIDE POLYMORPHISMS; CUMULATIVE ASSOCIATION; PROMOTER
POLYMORPHISM; PLASMA-CONCENTRATIONS; IN-VIVO; MCP-1; MACROPHAGE; GROWTH
AB Purpose: Though C-C chemokine ligand 2 (CCL2) has been shown to play a pivotal role in prostate cancer tumorigenesis and invasion, the role of inherited variation in the CCL2 gene in prostate cancer progression and metastases remains unanswered. This study is aimed to determine the influence of CCL2 germline variants on prostate cancer aggressiveness.
Experimental Design: We performed an association study between six single nucleotide polymorphisms (SNP) in the CCL2 gene and prostate cancer clinicopathologic variables in a large hospital-based Caucasian patient cohort (N = 4,073).
Results: Genetic variation at CCL2 is associated with markers of disease aggressiveness. Three SNPs, each in strong linkage disequilibrium, are associated with a higher (>7) biopsy Gleason score: CCL2 - 1811 A/G, -2835 A/C, and +3726 T/C (P = 0.01, 0.03, and 0.04, respectively). The CCL2 - 1811 G allele is addionally associated with advanced pathologic stages in patients who underwent radical prostatectomy (P = 0.04). In haplotype analysis, we found that the frequency of a common haplotype, H5, was higher among patients with D'Amico good risk features (P(permutation) = 0.04).
Conclusions: These results support the influence of CCL2 variants on prostate cancer development and progression. Clin Cancer Res; 17(6); 1546-52. (C) 2010 AACR.
C1 [Pienta, Kenneth J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Pienta, Kenneth J.] Michigan Ctr Translat Pathol, Dept Med & Urol, Ann Arbor, MI USA.
[Sun, Tong; Lee, Gwo-Shu Mary; Oh, William K.; Freedman, Matthew L.; Pomerantz, Mark; Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA.
[Sun, Tong; Lee, Gwo-Shu Mary; Oh, William K.; Freedman, Matthew L.; Pomerantz, Mark; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Pienta, KJ (reprint author), Univ Michigan, Ctr Comprehens Canc, Room 7308,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM kpienta@umich.edu; philip_kantoff@dfci.harvard.edu
RI Oh, William/B-9163-2012; Pienta, Kenneth/E-7679-2015
OI Oh, William/0000-0001-5113-8147; Pienta, Kenneth/0000-0002-4138-2186
FU SPORE in Prostate Cancer [2 P50 CA090381-06, 2 P50 CA69568-06]; Prostate
Cancer Foundation; Department of Defense (DoD) [W81XWH-09-1-0372]
FX This work was supported by a SPORE in Prostate Cancer 2 P50 CA090381-06,
SPORE in Prostate Cancer 2 P50 CA69568-06, the Prostate Cancer
Foundation, and Department of Defense (DoD) Prostate Cancer Training
Award W81XWH-09-1-0372.
NR 38
TC 8
Z9 9
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2011
VL 17
IS 6
BP 1546
EP 1552
DI 10.1158/1078-0432.CCR-10-2015
PG 7
WC Oncology
SC Oncology
GA 735RR
UT WOS:000288435300034
PM 21135144
ER
PT J
AU Janket, SJ
Jethwani, K
Meurman, JH
AF Janket, Sok-Ja
Jethwani, Kamal
Meurman, Jukka H.
TI Invasive Dental Treatment and Risk for Vascular Events
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID DISEASE
C1 [Janket, Sok-Ja] Boston Univ, Henry M Goldman Sch Dent Med, Boston, MA 02118 USA.
[Jethwani, Kamal] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Meurman, Jukka H.] Univ Helsinki, Cent Hosp, FIN-00290 Helsinki, Finland.
RP Janket, SJ (reprint author), Boston Univ, Henry M Goldman Sch Dent Med, Boston, MA 02118 USA.
OI Janket, Sok-Ja/0000-0003-0078-3992
NR 5
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 15
PY 2011
VL 154
IS 6
BP 441
EP 441
DI 10.7326/0003-4819-154-6-201103150-00014
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 734WA
UT WOS:000288370000012
PM 21403083
ER
PT J
AU Dotto, GP
AF Dotto, G. Paolo
TI Calcineurin Signaling as a Negative Determinant of Keratinocyte Cancer
Stem Cell Potential and Carcinogenesis
SO CANCER RESEARCH
LA English
DT Review
ID EPITHELIAL-CELLS; INHIBITOR DSCR1; TUMOR-GROWTH; SKIN-CANCER; P53; GENE;
NFAT; EXPRESSION; CARCINOMA; NOTCH1
AB Calcineurin is the only known serine-threonine phosphatase under calcium-calmodulin control and key regulator of the immune system. Treatment of patients with calcineurin-inhibitory drugs like cyclosporin A and FK506 to prevent graft rejection dramatically increases the risk of cutaneous squamous cell carcinoma, which is a major cause of death after organ transplants. Recent evidence indicates that suppression of calcineurin signaling, together with its impact on the immune system, exerts direct tumor-promoting effects in keratinocytes, enhancing cancer stem cell potential. The underlying mechanism involves interruption of a double negative regulatory axis, whereby calcineurin and nuclear factors of activated T-cell signaling inhibits expression of ATF3, a negative regulator of p53. The resulting suppression of keratinocyte cancer cell senescence is of likely clinical significance for the many patients under treatment with calcineurin inhibitors and may be of relevance for other cancer types in which altered calcium-calcineurin signaling plays a role. Cancer Res; 71(6); 2029-33. (C) 2011 AACR.
C1 [Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM Paolo.Dotto@unil.ch
FU NIH [AR39190, AR054856]; Swiss National Foundation; Oncosuisse
[02361-02-2009]
FX This work was supported by grants from NIH (grants AR39190 and
AR054856), the Swiss National Foundation, and Oncosuisse (grant
02361-02-2009).
NR 41
TC 11
Z9 11
U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2011
VL 71
IS 6
BP 2029
EP 2033
DI 10.1158/0008-5472.CAN-10-3750
PG 5
WC Oncology
SC Oncology
GA 734YZ
UT WOS:000288381300002
PM 21406393
ER
PT J
AU Wolfer, A
Ramaswamy, S
AF Wolfer, Anita
Ramaswamy, Sridhar
TI MYC and Metastasis
SO CANCER RESEARCH
LA English
DT Review
ID TO-MESENCHYMAL TRANSITION; BREAST-CANCER; COLORECTAL-CANCER;
GENE-EXPRESSION; STEM-CELLS; AMPLIFICATION; REPRESSION; OVEREXPRESSION;
TRANSFORMATION; PROLIFERATION
AB Aggressive primary tumors express transcriptional signatures that correlate with their metastatic propensity. A number of these signatures have been deployed in the clinic as risk stratification tools. However, the molecular basis of these clinically useful prognostic signatures has remained a largely unresolved area of controversy. We recently found that many prognostic signatures reflect the activity of the MYC oncogene, which in turn regulates tumor metastasis through specific effects on cancer cell invasion and migration. These findings offer a general framework for understanding the molecular basis of clinically prognostic transcriptional signatures and suggest potentially new avenues for studying metastasis. Cancer Res; 71(6); 2034-7. (C) 2011 AACR.
C1 [Wolfer, Anita; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Wolfer, Anita; Ramaswamy, Sridhar] Harvard Univ, Sch Med, Boston, MA USA.
[Ramaswamy, Sridhar] Broad Inst, Cambridge, MA USA.
[Ramaswamy, Sridhar] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Ramaswamy, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA.
EM sridhar@mgh.harvard.edu
FU Astra Zeneca
FX S. Ramaswamy is a recipient of a commercial research grant by Astra
Zeneca.
NR 39
TC 62
Z9 64
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2011
VL 71
IS 6
BP 2034
EP 2037
DI 10.1158/0008-5472.CAN-10-3776
PG 4
WC Oncology
SC Oncology
GA 734YZ
UT WOS:000288381300003
PM 21406394
ER
PT J
AU Hu, WG
Ge, XW
You, T
Xu, T
Zhang, JY
Wu, GX
Peng, ZH
Chorev, M
Aktas, BH
Halperin, JA
Brown, JR
Qin, XB
AF Hu, Weiguo
Ge, Xiaowen
You, Tao
Xu, Ting
Zhang, Jinyan
Wu, Gongxiong
Peng, Zhihai
Chorev, Michael
Aktas, Bertal H.
Halperin, Jose A.
Brown, Jennifer R.
Qin, Xuebin
TI Human CD59 Inhibitor Sensitizes Rituximab-Resistant Lymphoma Cells to
Complement-Mediated Cytolysis
SO CANCER RESEARCH
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; DECAY-ACCELERATING FACTOR; ANTI-CD20
MONOCLONAL-ANTIBODIES; DEPENDENT CELLULAR CYTOTOXICITY; IN-VIVO;
CANCER-IMMUNOTHERAPY; THERAPEUTIC ACTIVITY; EFFECTOR MECHANISMS;
REGULATORY PROTEIN; EXPRESSION
AB Rituximab efficacy in cancer therapy depends in part on induction of complement-dependent cytotoxicity (CDC). Human CD59 (hCD59) is a key complement regulatory protein that restricts the formation of the membrane attack complex, thereby inhibiting induction of CDC. hCD59 is highly expressed in B-cell non-Hodgkin's lymphoma (NHL), and upregulation of hCD59 is an important determinant of the sensitivity of NHL cells to rituximab treatment. Here, we report that the potent hCD59 inhibitor rILYd4 enhances CDC in vitro and in vivo, thereby sensitizing rituximab-resistant lymphoma cells and primary chronic lymphocytic leukemia cells (CLL) to rituximab treatment. By defining pharmcokinetic/pharmacodynamic profiles of rILYd4 in mice, we showed that by itself rILYd4 does not adversely mediate in vivo hemolysis of hCD59-expressing erythrocytes. Increasing expression levels of the complement regulators CD59 and CD55 in rituximab-resistant cells occur due to selection of preexisting clones rather than de novo induction of these proteins. Moreover, lymphoma cells overexpressing CD59 were directly responsible for the resistance to rituximab-mediated CDC therapy. Our results rationalize the use of rILYd4 as a therapeutic adjuvant for rituximab treatment of rituximab-resistant lymphoma and CLL. Furthermore, they suggest that preemptive elimination of CD59-overexpressing subpopulations along with rituximab treatment may be a useful approach to ablate or conquer rituximab resistance. Cancer Res; 71(6); 2298-307. (C)2011 AACR.
C1 [Hu, Weiguo; Ge, Xiaowen; You, Tao; Zhang, Jinyan; Wu, Gongxiong; Chorev, Michael; Aktas, Bertal H.; Halperin, Jose A.; Qin, Xuebin] Harvard Univ, Lab Translat Res, Sch Med, Cambridge, MA 02139 USA.
[Hu, Weiguo; Wu, Gongxiong; Chorev, Michael; Aktas, Bertal H.; Halperin, Jose A.; Qin, Xuebin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Xu, Ting] Sino Recombi Pharma, Suzhou, Peoples R China.
[Zhang, Jinyan; Peng, Zhihai] Shanghai Jiao Tong Univ, Dept Gen Surg, Shanghai Peoples Hosp 1, Sch Med, Shanghai 200030, Peoples R China.
RP Hu, WG (reprint author), Harvard Univ, Lab Translat Res, Sch Med, 1 Kendall Sq,Bldg 600,3rd Floor, Cambridge, MA 02139 USA.
EM weiguo_hu@hms.harvard.edu; xuebin_qin@hms.harvard.edu
FU Harvard Technology Development Accelerator Fund [NIHRO1AI061174,
NIHR21CA141324]; Natural Science Foundation of China [30972952]; China
National Key Technology RD Program [2008BAI60B03]; China Scholarship
Council [2009628090]; NIH [K23]; ASH; Leukemia and Lymphoma Society
FX NIHRO1AI061174 (to X.B. Qin) and NIHR21CA141324 (to X. B. Qin), Harvard
Technology Development Accelerator Fund (to X. B. Qin), and Natural
Science Foundation of China (30972952; to Z. Peng), China National Key
Technology R&D Program (2008BAI60B03; to Z. Peng), and China Scholarship
Council (2009628090 (to X. Ge). J.R. Brown is supported by NIH K23 and
an ASH Scholar Award and the Leukemia and Lymphoma Society Scholar in
Clinical Research Award.
NR 46
TC 35
Z9 39
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2011
VL 71
IS 6
BP 2298
EP 2307
DI 10.1158/0008-5472.CAN-10-3016
PG 10
WC Oncology
SC Oncology
GA 734YZ
UT WOS:000288381300029
PM 21252115
ER
PT J
AU Bin Hafeez, B
Zhong, WX
Weichert, J
Dreckschmidt, NE
Jamal, MS
Verma, AK
AF Bin Hafeez, Bilal
Zhong, Weixiong
Weichert, Jamey
Dreckschmidt, Nancy E.
Jamal, Mohammad Sarwar
Verma, Ajit K.
TI Genetic Ablation of PKC Epsilon Inhibits Prostate Cancer Development and
Metastasis in Transgenic Mouse Model of Prostate Adenocarcinoma
SO CANCER RESEARCH
LA English
DT Article
ID PROTEIN-KINASE-C; CONSTITUTIVE ACTIVATION; STAT3; PHOSPHORYLATION;
INTERACTS; SURVIVAL; INTERLEUKIN-6; STAT3SER727; PROGRESSION; EXPRESSION
AB Protein kinase C epsilon (PKC epsilon), a novel PKC isoform, is overexpressed in prostate cancer (PCa) and correlates with disease aggressiveness. However, the functional contribution of PKCe to development or progression of PCa remained to be determined. Here we present the first in vivo genetic evidence that PKCe is essential for both the development and metastasis of PCa in the transgenic mouse model of prostate adenocarcinoma (TRAMP). Heterozygous or homozygous genetic deletions of PKC epsilon in FVB/N TRAMP inhibited PCa development and metastasis as analyzed by positron emission tomography/computed tomography, tumor weight determinations, and histopathology. We also examined biomarkers associated with tumor progression in this model, including markers of survival, proliferation, angiogenesis, inflammation, and metastatic progression. To find clues about the genes regulated by PKC epsilon and linked to the Stat3 signaling pathway, we carried out focused PCR arrays of JAK/STAT signaling in excised PCa tissues from PKCe wild-type and nullizygous TRAMP mice. Notably, PKC epsilon loss was associated with significant downregulation of proliferative and metastatic genes C/EBP beta (CCAAT/enhancer binding protein beta), CRP (C-reactive protein), CMK, EGFR (epidermal growth factor receptor), CD64, Jun B, and gp130. Taken together, our findings offer the first genetic evidence of the role of PKCe in PCa development and metastasis. PKCe may be potential target for prevention and/or treatment of PCa. Cancer Res; 71(6); 2318-27. (C)2011 AACR.
C1 [Bin Hafeez, Bilal; Dreckschmidt, Nancy E.; Jamal, Mohammad Sarwar; Verma, Ajit K.] Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Paul Carbone Comprehens Canc Ctr,Wisconsin Inst M, Madison, WI 53792 USA.
[Zhong, Weixiong] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53792 USA.
[Zhong, Weixiong] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Weichert, Jamey] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53792 USA.
RP Verma, AK (reprint author), Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Paul Carbone Comprehens Canc Ctr,Wisconsin Inst M, Madison, WI 53792 USA.
EM akverma@facstaff.wisc.edu
RI Jamal, Mohammad/I-1230-2012; Jamal, Mohammad/K-3842-2013
FU DOD [W81XWH]; NIH [CA35368]; UWCCC Cancer Center [2 P30 CA014520-34]
FX This study was supported by DOD grant (W81XWH), NIH grant CA35368, and
UWCCC Cancer Center Support grant 2 P30 CA014520-34 for small animal
imaging facility.
NR 27
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2011
VL 71
IS 6
BP 2318
EP 2327
DI 10.1158/0008-5472.CAN-10-4170
PG 10
WC Oncology
SC Oncology
GA 734YZ
UT WOS:000288381300031
ER
PT J
AU Gavathiotis, E
Walensky, LD
AF Gavathiotis, Evripidis
Walensky, Loren D.
TI Tracking BAX once its trigger is pulled
SO CELL CYCLE
LA English
DT Editorial Material
ID MITOCHONDRIAL-MEMBRANE; ACTIVATION; APOPTOSIS; HELIX; PUMA
C1 [Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA.
Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA.
Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA.
RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM Loren_Walensky@dfci.harvard.edu
FU NCI NIH HHS [R01 CA050239]; NHLBI NIH HHS [K99 HL095929-01A1, K99
HL095929, K99 HL095929-02, R00 HL095929]
NR 11
TC 4
Z9 4
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 15
PY 2011
VL 10
IS 6
BP 868
EP 870
DI 10.4161/10.6.15034
PG 3
WC Cell Biology
SC Cell Biology
GA 734UX
UT WOS:000288366400006
PM 21325897
ER
PT J
AU Joukov, V
AF Joukov, Vladimir
TI Aurora kinases and spindle assembly Variations on a common theme?
SO CELL CYCLE
LA English
DT Article
DE aurora kinases; Cep192; chromosome passenger complex; spindle assembly;
microtubule-organizing center; centrosome; kinetochore
ID MICROTUBULE-ORGANIZING CENTERS; CHROMOSOMAL PASSENGER COMPLEX; MITOTIC
SPINDLE; CELL-DIVISION; B KINASE; A KINASE; CAENORHABDITIS-ELEGANS;
CENTROSOME MATURATION; INNER CENTROMERE; PROTEIN-KINASES
AB The Aurora A (AurA) serine/threonine kinase controls multiple aspects of cell division and plays a key role in centrosome maturation and bipolar spindle assembly. The pleiotropic functions of AurA depend on its interaction with several cofactors, the best known of which is TPX2. TPX2 targets AurA to spindle microtubules (MTs) and activates it, both allosterically and by protecting the activation loop (T-loop) of the kinase domain from dephosphorylation. Although several factors have been implicated in the regulation of AurA at centrosomes, the underlying mechanism has remained elusive, and the existence of a distinct centrosome-specific AurA activator has been proposed. Our recent study has identified this activator as Cep192/Spd-2, one of the key factors in centrosome biogenesis. Cep192 targets AurA to centrosomes, where it promotes its activation by a novel, oligomerization-dependent mechanism characterized by extensive T-loop phosphorylation and high kinase activity. This process is key to the function of centrosomes as microtubule-organizing centers. Here, our findings are discussed in the context of other recent studies on the Aurora kinases, with an emphasis on their role in spindle assembly. The collected evidence suggests that the 'hot spots' of MT nucleation, centrosomes and kinetochores, rely on the oligomerization-mediated mechanism of activation of AurA and Aurora B, respectively.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Genet, Boston, MA 02115 USA.
RP Joukov, V (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol,Dept Genet, 44 Binney St, Boston, MA 02115 USA.
EM vladimir_joukov@dfci.harvard.edu
NR 102
TC 11
Z9 11
U1 1
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 15
PY 2011
VL 10
IS 6
BP 895
EP 903
DI 10.4161/cc.10.6.14909
PG 9
WC Cell Biology
SC Cell Biology
GA 734UX
UT WOS:000288366400015
PM 21325891
ER
PT J
AU Chin, L
Hahn, WC
Getz, G
Meyerson, M
AF Chin, Lynda
Hahn, William C.
Getz, Gad
Meyerson, Matthew
TI Making sense of cancer genomic data
SO GENES & DEVELOPMENT
LA English
DT Review
ID ARRAY CGH DATA; CELL LUNG-CANCER; NUCLEOTIDE POLYMORPHISM ARRAYS;
CONSENSUS CODING SEQUENCES; LINEAGE-SURVIVAL ONCOGENE; AMINO-ACID
SUBSTITUTIONS; GENE-EXPRESSION ANALYSIS; ACUTE MYELOID-LEUKEMIA;
GROWTH-FACTOR RECEPTOR; TYROSINE KINASE JAK2
AB High-throughput tools for nucleic acid characterization now provide the means to conduct comprehensive analyses of all somatic alterations in the cancer genomes. Both large-scale and focused efforts have identified new targets of translational potential. The deluge of information that emerges from these genome-scale investigations has stimulated a parallel development of new analytical frameworks and tools. The complexity of somatic genomic alterations in cancer genomes also requires the development of robust methods for the interrogation of the function of genes identified by these genomics efforts. Here we provide an overview of the current state of cancer genomics, appraise the current portals and tools for accessing and analyzing cancer genomic data, and discuss emerging approaches to exploring the functions of somatically altered genes in cancer.
C1 [Chin, Lynda; Hahn, William C.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chin, Lynda; Hahn, William C.; Getz, Gad; Meyerson, Matthew] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Chin, Lynda; Hahn, William C.; Getz, Gad; Meyerson, Matthew] MIT, Cambridge, MA 02142 USA.
RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM lynda_chin@dfci.harvard.edu
RI Meyerson, Matthew/E-7123-2012
FU NIH [U24CA143845, U24CA144025, U24CA143867]; Cancer Target Discovery and
Development) network investigators [NIH RC2CA148268]
FX We apologize to colleagues whose studies, algorithms, or portals are not
cited in this review due to limitation in space. L.C., G.G., and M.M.
are TCGA-funded investigators (NIH U24CA143845, U24CA144025, and
U24CA143867). L.C. and W. C.H. are CTD2 (Cancer Target Discovery and
Development) network investigators (NIH RC2CA148268).
NR 224
TC 136
Z9 138
U1 3
U2 23
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 2011
VL 25
IS 6
BP 534
EP 555
DI 10.1101/gad.2017311
PG 22
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 734VA
UT WOS:000288366800002
PM 21406553
ER
PT J
AU Ng, ACY
Eisenberg, JM
Heath, RJW
Huett, A
Robinson, CM
Nau, GJ
Xavier, RJ
AF Ng, Aylwin C. Y.
Eisenberg, Jason M.
Heath, Robert J. W.
Huett, Alan
Robinson, Cory M.
Nau, Gerard J.
Xavier, Ramnik J.
TI Human leucine-rich repeat proteins: a genome-wide bioinformatic
categorization and functional analysis in innate immunity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE pathogen-response; anti-bacterial; inflammation; pathogen sensors;
autophagy
ID CROHNS-DISEASE; SUSCEPTIBILITY; RECOGNITION; DIVERSITY; GENES;
CONTRIBUTES; ASSOCIATION; ACTIVATION; EVOLUTION; REVEALS
AB In innate immune sensing, the detection of pathogen-associated molecular patterns by recognition receptors typically involve leucine-rich repeats (LRRs). We provide a categorization of 375 human LRR-containing proteins, almost half of which lack other identifiable functional domains. We clustered human LRR proteins by first assigning LRRs to LRR classes and then grouping the proteins based on these class assignments, revealing several of the resulting protein groups containing a large number of proteins with certain non-LRR functional domains. In particular, a statistically significant-number of LRR proteins in the typical (T) and bacterial + typical (S+T) categories have transmembrane domains, whereas most of the LRR proteins in the cysteine-containing (CC) category contain an F-box domain (which mediates interactions with the E3 ubiquitin ligase complex). Furthermore, by examining the evolutionary profiles of the LRR proteins, we identified a subset of LRR proteins exhibiting strong conservation in fungi and an enrichment for "nucleic acid-binding" function. Expression analysis of LRR genes identifies a subset of pathogen-responsive genes in human primary macrophages infected with pathogenic bacteria. Using functional RNAi, we show that MFHAS1 regulates Toll-like receptor (TLR)-dependent signaling. By using protein interaction network analysis followed by functional RNAi, we identified LRSAM1 as a component of the antibacterial autophagic response.
C1 [Ng, Aylwin C. Y.; Eisenberg, Jason M.; Heath, Robert J. W.; Huett, Alan; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Ng, Aylwin C. Y.; Eisenberg, Jason M.; Heath, Robert J. W.; Huett, Alan; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Ng, Aylwin C. Y.; Eisenberg, Jason M.; Heath, Robert J. W.; Huett, Alan; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ng, Aylwin C. Y.; Eisenberg, Jason M.; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA.
[Robinson, Cory M.; Nau, Gerard J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA.
RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
EM xavier@molbio.mgh.harvard.edu
OI Nau, Gerard/0000-0001-7921-8317
FU National Institutes of Health [AI062773, DK83756, DK060049]; Crohn's and
Colitis Foundation of America
FX We thank Mark Daly and Fred Ausubel for helpful discussions. This work
was supported by National Institutes of Health Grants AI062773, DK83756,
DK060049, and DK060049 (to R.J.X., R.J.W.H., and J.E.) and a Research
Fellowship Award from the Crohn's and Colitis Foundation of America (to
A.C.Y.N.).
NR 42
TC 52
Z9 54
U1 1
U2 12
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 15
PY 2011
VL 108
SU 1
BP 4631
EP 4638
DI 10.1073/pnas.1000093107
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735WM
UT WOS:000288451300017
PM 20616063
ER
PT J
AU Li, XA
Krishnan, L
Cherepanov, P
Engelman, A
AF Li, Xiang
Krishnan, Lavanya
Cherepanov, Peter
Engelman, Alan
TI Structural biology of retroviral DNA integration
SO VIROLOGY
LA English
DT Review
DE HIV-1; Prototype foamy virus; Integrase; Integration; AIDS; Integrase
strand transfer inhibitor; Raltegravir; Structural biology; X-ray
crystallography
ID HUMAN-IMMUNODEFICIENCY-VIRUS; STRAND TRANSFER INHIBITORS; PROTEIN
IN-VITRO; REFINED SOLUTION STRUCTURE; CARBOXYL-TERMINAL DOMAINS;
SITE-DIRECTED MUTAGENESIS; ZINC-BINDING DOMAIN; HIV-1 INTEGRASE;
CATALYTIC DOMAIN; AVIAN-SARCOMA
AB Three-dimensional macromolecular structures shed critical light on biological mechanism and facilitate development of small molecule inhibitors. Clinical success of raltegravir, a potent inhibitor of HIV-1 integrase, demonstrated the utility of this viral DNA recombinase as an antiviral target. A variety of partial integrase structures reported in the past 16 years have been instrumental and very informative to the field. Nonetheless, because integrase protein fragments are unable to functionally engage the viral DNA substrate critical for strand transfer inhibitor binding, the early structures did little to materially impact drug development efforts. However, recent results based on prototype foamy virus integrase have fully reversed this trend, as a number of X-ray crystal structures of active integrase-DNA complexes revealed key mechanistic details and moreover established the foundation of HIV-1 integrase strand transfer inhibitor action. In this review we discuss the landmarks in the progress of integrase structural biology during the past 17 years. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London W2 1PG, England.
[Li, Xiang; Krishnan, Lavanya; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA.
[Li, Xiang; Krishnan, Lavanya; Engelman, Alan] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA.
RP Cherepanov, P (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, St Marys Campus,Norfolk Pl, London W2 1PG, England.
EM p.cherepanov@imperial.ac.uk; alan_engelman@dfci.harvard.edu
RI Li, Xiang/C-4588-2011; Cherepanov, Peter/F-6859-2010
OI Cherepanov, Peter/0000-0002-0634-538X
FU UK Medical Research Council [G0900116]; US National Institutes of Health
[AI70042]
FX This work was supported by UK Medical Research Council Grant G0900116
(to P.C.) and US National Institutes of Health Grant AI70042 (to A.E.).
The content of this paper does not necessarily reflect the views or
policies of these funding agencies.
NR 142
TC 60
Z9 61
U1 2
U2 15
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 15
PY 2011
VL 411
IS 2
SI SI
BP 194
EP 205
DI 10.1016/j.virol.2010.12.008
PG 12
WC Virology
SC Virology
GA 734OI
UT WOS:000288343000005
PM 21216426
ER
PT J
AU Smoller, JW
AF Smoller, Jordan W.
TI Who's Afraid of Anxiety Genetics?
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
C1 [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Dept Psychiat, Boston, MA 02114 USA.
RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Simches Res Bldg,185 Cambridge St,Room 2298, Boston, MA 02114 USA.
EM jsmoller@hms.harvard.edu
NR 8
TC 7
Z9 7
U1 0
U2 4
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 2011
VL 69
IS 6
BP 506
EP 507
DI 10.1016/j.biopsych.2011.01.020
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 732NW
UT WOS:000288193400001
PM 21353834
ER
PT J
AU Apfel, BA
Ross, J
Hlavin, J
Meyerhoff, DJ
Metzler, TJ
Marmar, CR
Weiner, MW
Schuff, N
Neylan, TC
AF Apfel, Brigitte A.
Ross, Jessica
Hlavin, Jennifer
Meyerhoff, Dieter J.
Metzler, Thomas J.
Marmar, Charles R.
Weiner, Michael W.
Schuff, Norbert
Neylan, Thomas C.
TI Hippocampal Volume Differences in Gulf War Veterans with Current Versus
Lifetime Posttraumatic Stress Disorder Symptoms
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Depression; Gulf War veterans; hippocampus; magnetic resonance imaging;
posttraumatic stress disorder
ID MAJOR DEPRESSIVE DISORDER; ADMINISTERED PTSD SCALE; ANTIDEPRESSANT
TREATMENT; CHILDHOOD MALTREATMENT; PSYCHIATRIC-DISORDERS; ADULT
NEUROGENESIS; ALCOHOL DEPENDENCE; RAT HIPPOCAMPUS; DENTATE GYRUS;
METAANALYSIS
AB Background: Decreased hippocampal volume is described in posttraumatic stress disorder (PTSD) and depression. However, it is not known whether it is a risk factor for the development of PTSD or a consequence of PTSD. We sought to determine the effects of PTSD and depressive symptoms on hippocampal volume.
Methods: Clinical and magnetic resonance imaging data were collected in a cross sectional study of 244 Gulf War veterans. Measures included lifetime and current Clinician Administered PTSD Scale, Hamilton Depression Scale, Life Stressor Checklist, and Lifetime Drinking History. Magnetic resonance imaging data were acquired with a 1.5-T scanner and analyzed with automated and semiautomated image processing techniques.
Results: Eighty-two veterans had lifetime PTSD, 44 had current PTSD, and 38 had current depression. In the linear regression analysis, current PTSD symptoms (standardized coefficient beta = -.25, p = .03) but neither lifetime PTSD symptoms nor current depression were associated with smaller hippocampal volume. Gender, age, history of early life trauma, education, lifetime and current alcohol use, current marijuana use, and treatment with antidepressants did not have independent effects. Participants with chronic PTSD had, on average, a smaller hippocampus compared with those with remitted PTSD.
Conclusions: The finding that current but not lifetime PTSD symptom severity explains hippocampal size raises two possibilities: either a small hippocampus is a risk factor for lack of recovery from PTSD (trait) or PTSD effects on hippocampal volume are reversible once PTSD symptoms remit and the patient recovers (state).
C1 [Apfel, Brigitte A.; Ross, Jessica; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Meyerhoff, Dieter J.; Weiner, Michael W.; Schuff, Norbert] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Apfel, Brigitte A.; Ross, Jessica; Metzler, Thomas J.; Neylan, Thomas C.] Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA.
[Hlavin, Jennifer; Meyerhoff, Dieter J.; Weiner, Michael W.; Schuff, Norbert] Vet Affairs Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA.
[Marmar, Charles R.] NYU, Dept Psychiat, New York, NY 10016 USA.
RP Apfel, BA (reprint author), San Francisco VA Med Ctr, Dept Psychiat, 116A,4150 Clement St, San Francisco, CA 94121 USA.
EM brigitte.apfel@ucsf.edu
RI Schueter, nicos/A-3625-2014
FU Department of Defense [DAMD17-01-1-0764]; US Army Medical Research and
Materiel Command; National Institutes of Health/National Institute of
Environmental Health Sciences [ES09883]; Mental Illness Research,
Education, and Clinical Center of the Department of Veterans Affairs;
Office of Academic Affiliations; Department of Veterans Affairs; [R01
AA 10788]
FX This study was supported by Department of Defense Grant
DAMD17-01-1-0764, entitled, "Magnetic Resonance and Spectroscopy of the
Human Brain in GulfWarIllness," awarded to the Northern California
Institute for Research and Education from the Department of Defense Gulf
War Illnesses Research Program, US Army Medical Research and Materiel
Command. This study was also supported by National Institutes of
Health/National Institute of Environmental Health Sciences Grant ES09883
and the Mental Illness Research, Education, and Clinical Center of the
Department of Veterans Affairs. Resources and the use of facilities were
provided by the Veterans Administration Medical Center, San Francisco,
California. Writing of this manuscript was supported by the Office of
Academic Affiliations, Advanced Fellowship Program in Mental Illness
Research and Treatment, Department of Veterans Affairs, and R01 AA 10788
(DJM). We are grateful to Karl Friedl, Ph.D., for his support, and last
but not least we thank Diana Truran and her staff for MRI scanning. All
authors report no biomedical financial interests or potential conflicts
of interest.
NR 74
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Z9 47
U1 6
U2 20
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 2011
VL 69
IS 6
BP 541
EP 548
DI 10.1016/j.biopsych.2010.09.044
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 732NW
UT WOS:000288193400008
PM 21094937
ER
PT J
AU Anees, M
Horak, P
El-Gazzar, A
Susani, M
Heinze, G
Perco, P
Loda, M
Lis, R
Krainer, M
Oh, WK
AF Anees, Mariam
Horak, Peter
El-Gazzar, Ahmed
Susani, Martin
Heinze, Georg
Perco, Paul
Loda, Massimo
Lis, Rosina
Krainer, Michael
Oh, William K.
TI Recurrence-Free Survival in Prostate Cancer Is Related to Increased
Stromal TRAIL Expression
SO CANCER
LA English
DT Article
DE Prostate cancer; tumor necrosis factor-related apoptosis-inducing ligand
(TRAIL); death receptors; recurrence-free survival
ID NF-KAPPA-B; APOPTOSIS-INDUCING LIGAND; DEATH RECEPTORS; TARGETING DEATH;
OVARIAN-CANCER; CYTOCHROME-C; TRANSCRIPTION; INHIBITOR; PROTEIN; FLIP
AB BACKGROUND: TRAIL (tumor necrosis factor related apoptosis-inducing ligand) is involved in tumor immune surveillance and, thus, may be a potential cancer therapy. TRAIL expression in the tumor microenvironment has been shown to impact cancer survival in multiple tumor types, including ovarian cancer. We studied TRAIL expression and outcomes in patients with prostate cancer. METHODS: A tissue microarray (TMA) of 200 prostate cancer patients and benign prostate tissue controls was used to assess the epithelial and stromal protein expression of TRAIL, death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and the FLICE inhibitory protein (FLIP(L)). We correlated these expression patterns with clinicopathological parameters and determined its impact on recurrence-free survival. RESULTS: Nearly all (99.5%) prostate cancer tissues examined displayed either decreased expression of pro-apoptotic TRAIL receptors, increased FLIPL expression, or both. We observed elevated death receptor, decoy receptor, FLIP(L), and epithelial TRAIL expression in prostate cancer epithelium. TRAIL expression in the stromal tumor microenvironment surrounding the prostate cancer was markedly lower. Elevated TRAIL expression in the tumor microenvironment was also significantly associated with increased recurrence-free survival (P = .014), after controlling for other prognostic markers. In contrast, epithelial expression of TRAIL did not have an effect on overall survival. CONCLUSIONS: Expression of the components of the pro-apoptotic TRAIL pathway is altered in prostate cancer. Moreover, TRAIL expression in the tumor microenvironment may affect recurrence-free survival rate of prostate cancer patients. Consequently, these results may be useful in devising future therapeutic strategies targeting the TRAIL pathway in prostate cancer. Cancer 2011;117:1172-82. (C) 2070 American Cancer Society
C1 [Anees, Mariam; Horak, Peter; El-Gazzar, Ahmed; Krainer, Michael] Med Univ Vienna, Dept Med 1, Div Oncol, A-1090 Vienna, Austria.
[Susani, Martin] Med Univ Vienna, Dept Clin Pathol, A-1090 Vienna, Austria.
[Heinze, Georg] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, A-1090 Vienna, Austria.
[Perco, Paul] Univ Vienna, Inst Theoret Chem, Vienna, Austria.
[Loda, Massimo; Lis, Rosina] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY USA.
RP Krainer, M (reprint author), Med Univ Vienna, Dept Med 1, Div Oncol, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM michael.krainer@meduniwien.ac.at
RI Oh, William/B-9163-2012;
OI Oh, William/0000-0001-5113-8147; Krainer, Michael/0000-0002-7011-4957
FU FWF [P20715-B12]; HEC Pakistan
FX FWF Grant P20715-B12, HEC Pakistan Scholarship to M.A.
NR 45
TC 10
Z9 11
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2011
VL 117
IS 6
BP 1172
EP 1182
DI 10.1002/cncr.25504
PG 11
WC Oncology
SC Oncology
GA 734PZ
UT WOS:000288349300009
PM 21381010
ER
PT J
AU Chen, YZ
Kong, JA
Sun, T
Li, G
Szeto, FL
Liu, WC
Deb, DK
Wang, YL
Zhao, Q
Thadhani, R
Li, YC
AF Chen, Yunzi
Kong, Juan
Sun, Tao
Li, George
Szeto, Frances L.
Liu, Weicheng
Deb, Dilip K.
Wang, Youli
Zhao, Qun
Thadhani, Ravi
Li, Yan Chun
TI 1,25-Dihydroxyvitamin D-3 suppresses inflammation-induced expression of
plasminogen activator inhibitor-1 by blocking nuclear factor-kappa B
activation
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Vitamin D; PAI-1; NF-kappa B; Gene regulation
ID VITAMIN-D-RECEPTOR; CHRONIC KIDNEY-DISEASE; NECROSIS-FACTOR-ALPHA;
GROWTH-FACTOR-BETA; DIABETIC-NEPHROPATHY; GENE-EXPRESSION; D ANALOGS;
CARDIOVASCULAR-DISEASE; COMBINATION THERAPY; RENAL INFLAMMATION
AB Plasminogen activator inhibitor (PAI)-1 is a major fibrinolytic inhibitor. High PAI-1 is associated with increased renal and cardiovascular disease risk. Previous studies demonstrated PAI-1 down-regulation by 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), but the molecular mechanism remains unknown. Here we show that exposure of mouse embryonic fibroblasts to TNF alpha or LPS led to a marked induction of PAI-1, which was blunted by 1,25(OH)(2)D-3, NF-kappa B inhibitor or p65 siRNA, suggesting the involvement of NF-kappa B in 1,25(OH)(2)D-3-induced repression. In mouse Pai-1 promoter a putative cis-kappa B element was identified at -299. EMSA and ChIP assays showed that TNE-alpha increased p50/p65 binding to this kappa B site, which was disrupted by 1,25(OH)(2)D-3. Luciferase reporter assays showed that PAI-1 promoter activity was induced by TNF alpha or LPS, and the induction was blocked by 1,25(OH)(2)D-3. Mutation of the kappa B site blunted TNF alpha, LPS or 1,25(OH)(2)D-3 effects. 1,25(OH)(2)D-3 blocked 1 kappa B alpha degradation and arrested p50/p65 nuclear translocation. In mice LPS stimulated PAI-1 expression in the heart and macrophages, and the stimulation was blunted by pre-treatment with a vitamin D analog. Together these data demonstrate that 1,25(OH)(2)D-3 down-regulates PAI-1 by blocking NE-kappa B activation. Inhibition of PAI-1 production may contribute to the reno- and cardio-protective effects of vitamin D. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Li, Yan Chun] Univ Chicago, Dept Med, KCBD, Div Biol Sci, Chicago, IL 60637 USA.
[Szeto, Frances L.; Li, Yan Chun] Univ Chicago, Div Biol Sci, Comm Mol Metab & Nutr, Chicago, IL 60637 USA.
[Kong, Juan; Li, Yan Chun] China Med Univ, Lab Metab Dis Res & Drug Dev, Shenyang, Peoples R China.
[Zhao, Qun] China Med Univ, Key Lab Congenital Malformat, Minist Hlth, Shenyang, Peoples R China.
[Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA.
RP Li, YC (reprint author), Univ Chicago, Dept Med, KCBD, Div Biol Sci, 900 E 57th St,Mailbox 9-9110, Chicago, IL 60637 USA.
EM cyan@medicine.bsd.uchicago.edu
RI Sun, Tao/F-8233-2012; liu, weicheng/D-4173-2013
FU NIH [HL085793]; Center for D-Receptor Activation Research; Abbott
Laboratory; American Heart Association [10SDG4280066]
FX This work was supported in part by NIH grant HL085793, a research grant
from the Center for D-Receptor Activation Research (to YCL), and a
research grant from Abbott Laboratory (to RT). JK is support by American
Heart Association Scientist Development Grant (10SDG4280066).
NR 50
TC 40
Z9 42
U1 1
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-9861
J9 ARCH BIOCHEM BIOPHYS
JI Arch. Biochem. Biophys.
PD MAR 15
PY 2011
VL 507
IS 2
BP 241
EP 247
DI 10.1016/j.abb.2010.12.020
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 730TR
UT WOS:000288058000005
PM 21176770
ER
PT J
AU Campbell-Yesufu, OT
Gandhi, RT
AF Campbell-Yesufu, Omobolaji T.
Gandhi, Rajesh T.
TI Update on Human Immunodeficiency Virus (HIV)-2 Infection
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID PLASMA VIRAL LOAD; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY;
HIV-ASSOCIATED NEPHROPATHY; TO-CHILD TRANSMISSION; HIV-2-INFECTED
PATIENTS; GUINEA-BISSAU; ANTIRETROVIRAL THERAPY; WEST-AFRICA; IN-VITRO;
DRUG-RESISTANCE
AB Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges.
C1 [Gandhi, Rajesh T.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA.
[Gandhi, Rajesh T.] Harvard Univ, Boston, MA 02115 USA.
RP Gandhi, RT (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, GRJ 504,55 Fruit St, Boston, MA 02114 USA.
EM rgandhi@partners.org
FU Tibotec; Gilead; NIH [R01 AI066992-04A1, G08LM008830-01]; AIDS Clinical
Trials Group [NIH U01 AI 694722]; Harvard University Center for AIDS
Research [NIH 2P30 AI060354-06]
FX We would like to thank Drs Kimon Zachary and Joseph Yao for their review
of and comments on sections of this paper and Dr Eric Rosenberg for
information regarding HIV-1 and HIV-2 diagnostic testing. We would like
to acknowledge Betsy Wonderly and Rishabh Phukan for assistance in
preparing this paper. R.T.G. has received grant support from Tibotec and
Gilead.; R.T.G. is supported by NIH R01 AI066992-04A1 and NIH
G08LM008830-01 and by grants to the AIDS Clinical Trials Group (NIH U01
AI 694722) and the Harvard University Center for AIDS Research (NIH 2P30
AI060354-06).
NR 71
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U1 2
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 15
PY 2011
VL 52
IS 6
BP 780
EP 787
DI 10.1093/cid/ciq248
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 730FX
UT WOS:000288020300013
PM 21367732
ER
PT J
AU Kim, BM
Woo, J
Kanellopoulou, C
Shivdasani, RA
AF Kim, Byeong-Moo
Woo, Janghee
Kanellopoulou, Chryssa
Shivdasani, Ramesh A.
TI Regulation of mouse stomach development and Barx1 expression by specific
microRNAs
SO DEVELOPMENT
LA English
DT Article
DE Barx1; Stomach development; MicroRNA; Mouse
ID CAENORHABDITIS-ELEGANS; ANIMAL MICRORNAS; CELL FATE; DIFFERENTIATION;
INITIATION; EVOLUTION; MIR-145; IMPACT; GENES
AB Although microRNAs (miRNAs) are postulated to fine-tune many developmental processes, their relationships with specific targets and tissues remain largely undefined. The mesenchymal transcription factor Barx1 controls spleen and stomach morphogenesis and is required to specify stomach-specific epithelium in adjacent endoderm. Barx1 expression is precisely regulated in space and time, with a sharp drop in stomach levels after epithelial specification. We tested the hypothesis that specific miRNAs mediate this marked decline in Barx1 levels. Depletion of the miRNA-processing enzyme Dicer in cultured stomach mesenchyme and conditional Dicer gene deletion in mice significantly increased Barx1 levels, disrupted stomach and intestine development and caused spleen agenesis. Computational and experimental studies identified miR-7a and miR-203 as candidate miRNAs that regulate Barx1 and are expressed in inverse proportion to it in the fetal mouse stomach. Through specific interactions with cognate sequences in the Barx1 3' untranslated region, miR-7a and miR-203 repress Barx1 expression in stomach mesenchymal cells and its function in inducing gastric epithelium. These results indicate that miRNAs are required for proper digestive tract organogenesis and that miR-7a and miR-203 control expression of the stomach homeotic regulator Barx1.
C1 [Kim, Byeong-Moo; Woo, Janghee; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Kim, Byeong-Moo; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kim, Byeong-Moo; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Woo, Janghee] Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA 02115 USA.
[Kanellopoulou, Chryssa] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM ramesh_shivdasani@dfci.harvard.edu
FU National Institutes of Health [R01DK081113]; Harvard Stem Cell Institute
FX We thank Warren Zimmer for providing Bapx1+/Cre mice and
Andrew McMahon for providing the pCIG vector. Supported by National
Institutes of Health grant R01DK081113 (to R.A.S.) and a predoctoral
training grant from the Harvard Stem Cell Institute (to J.W.). Deposited
in PMC for release after 12 months.
NR 31
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Z9 13
U1 0
U2 4
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD MAR 15
PY 2011
VL 138
IS 6
BP 1081
EP 1086
DI 10.1242/dev.056317
PG 6
WC Developmental Biology
SC Developmental Biology
GA 724KP
UT WOS:000287575300006
PM 21307095
ER
PT J
AU Altfeld, M
Goulder, PJ
AF Altfeld, Marcus
Goulder, Philip J.
TI The STEP Study Provides a Hint That Vaccine Induction of the Right
CD8(+) T Cell Responses Can Facilitate Immune Control of HIV
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID IMMUNODEFICIENCY VIRUS-REPLICATION; RHESUS-MONKEYS; VIRAL LOAD; CLASS-I;
ESCAPE; TRANSMISSION; CHALLENGE; INFECTION; EXPANSION; FAILURE
C1 [Goulder, Philip J.] Univ Oxford, Dept Paediat, Oxford, England.
[Altfeld, Marcus] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA.
RP Altfeld, M (reprint author), Harvard Univ, Sch Med, Bldg 149,13th St,Rm 6003, Boston, MA 02129 USA.
EM maltfeld@partners.org
FU NIAID NIH HHS [R01 AI046995]
NR 30
TC 5
Z9 5
U1 0
U2 0
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 2011
VL 203
IS 6
BP 753
EP 755
DI 10.1093/infdis/jiq119
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 726RB
UT WOS:000287742700002
PM 21343145
ER
PT J
AU Chen, JJ
Rosas, HD
Salat, DH
AF Chen, J. Jean
Rosas, H. Diana
Salat, David H.
TI Age-associated reductions in cerebral blood flow are independent from
regional atrophy
SO NEUROIMAGE
LA English
DT Article
DE Cerebral blood flow (CBF); Aging; Arterial-spin labelling (ASL);
Magnetic resonance imaging (MRI); Quantitative perfusion; Alzheimer's
disease; Dementia; Cortical thickness; Cerebral cortex
ID VASCULAR RISK-FACTORS; MILD COGNITIVE IMPAIRMENT; MAGNETIC-RESONANCE
IMAGES; PARTIAL-VOLUME CORRECTION; BRAIN PERFUSION SPECT; SPIN-LABELING
MRI; ALZHEIMERS-DISEASE; WHITE-MATTER; AGING BRAIN; IN-VIVO
AB Prior studies have demonstrated decreasing cerebral blood flow (CBF) in normal aging, but the full spatial pattern and potential mechanism of changes in CBF remain to be elucidated. Specifically, existing data have not been entirely consistent regarding the spatial distribution of such changes, potentially a result of neglecting the effect of age-related tissue atrophy in CBF measurements. In this work, we use pulsed arterial-spin labelling to quantify regional CBF in 86 cognitively and physically healthy adults, aged 23 to 88 years. Surface-based analyses were utilized to map regional decline in CBF and cortical thickness with advancing age, and to examine the spatial associations and dissociations between these metrics. Our results demonstrate regionally selective age-related reductions in cortical perfusion, involving the superior-frontal, orbito-frontal, superior-parietal, middle-inferior temporal, insular, precuneus, supramarginal, lateral-occipital and cingulate regions, while subcortical CBF was relatively preserved in aging. Regional effects of age on CBF differed from that of grey-matter atrophy. In addition, the pattern of CBF associations with age displays an interesting similarity with the default-mode network These findings demonstrate the dissociation between regional CBF and structural alterations specific to normal aging, and augment our understanding of mechanisms of pathology in older adults. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Chen, J. Jean; Rosas, H. Diana; Salat, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,MGH MIT HMS, Charlestown, MA 02129 USA.
[Chen, J. Jean; Salat, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
[Rosas, H. Diana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA.
[Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA.
RP Chen, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,MGH MIT HMS, 149 13th St,Room 2301, Charlestown, MA 02129 USA.
EM jjchen@nmr.mgh.harvard.edu
RI Chen, J. Jean/A-2846-2013
OI Chen, J. Jean/0000-0001-5469-7542
FU NIH [K01AG024898, R01NR010827, NS042861, P41RR14075]; Canadian
Institutes of Health Research (CIHR); Athinoula A. Martinos Center for
Biomedical Imaging
FX This research was supported by NIH grants K01AG024898, R01NR010827,
NS042861, and P41RR14075, as well as the Canadian Institutes of Health
Research (CIHR) and the Athinoula A. Martinos Center for Biomedical
Imaging. We also thank Dr. Doug Greve for his input on multi-modal image
registration, and Mr. Robert McInnis for help with cognitive testing.
NR 127
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U1 3
U2 21
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 MAR 15
PY 2011
VL 55
IS 2
BP 468
EP 478
DI 10.1016/j.neuroimage.2010.12.032
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 724DL
UT WOS:000287556200005
PM 21167947
ER
PT J
AU Triantafyllou, C
Polimeni, JR
Wald, LL
AF Triantafyllou, Christina
Polimeni, Jonathan R.
Wald, Lawrence L.
TI Physiological noise and signal-to-noise ratio in fMRI with multi-channel
array coils
SO NEUROIMAGE
LA English
DT Article
DE Physiological noise; Parallel imaging; Array coils; fMRI; GRAPPA; SNR;
32-channel coil; Resolution
ID MRI; RECONSTRUCTIONS; IMAGES; GRAPPA
AB Sensitivity in BOLD fMRI is characterized by the signal to noise ratio (SNR) of the time-series (tSNR), which contains fluctuations from thermal and physiological noise sources. Alteration of an ecquisition parameter can affect the tSNR differently depending on the relative magnitude of the physiological and thermal noise, therefore knowledge of this ratio is essential for optimizing fMRI acquisitions. In this study, we compare image and time-series SNR from array coils at 3 T with and without parallel imaging (GRAPPA) as a function of image resolution and acceleration. We use the "absolute unit" SNR method of Kellman and McVeigh to calculate the image SNR (SNR(0)) in a way that renders it comparable to tSNR, allowing determination of the thermal to physiological noise ratio, and the pseudo-multiple replica method to quantify the image noise alterations due to the GRAPPA reconstruction. The Kruger and Glover noise model, in which the physiological noise standard deviation is proportional to signal strength, was found to hold for the accelerated and non-accelerated array coil data. Thermal noise dominated the EPI time-series for medium to large voxel sizes for single-channel and 12-channel head coil configurations, but physiological noise dominated the 32-channel array acquisition even at 1 mm x 1 mm x 3 mm resolution. At higher acceleration factors, image SNR is reduced and the time-series becomes increasingly thermal noise dominant. However, the tSNR reduction is smaller than the reduction in image SNR due to the presence of physiological noise. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Triantafyllou, Christina] MIT, AA Martinos Imaging Ctr, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
[Triantafyllou, Christina; Polimeni, Jonathan R.; Wald, Lawrence L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA.
[Wald, Lawrence L.] Harvard Massachusetts Inst Technol MIT, Div Hlth Sci & Technol, Cambridge, MA USA.
RP Triantafyllou, C (reprint author), MIT, AA Martinos Imaging Ctr, McGovern Inst Brain Res, 77 Massachusetts Ave,Bldg 46,Room 46-1165, Cambridge, MA 02139 USA.
EM ctrianta@mit.edu
RI Triantafyllou, Christina/E-7724-2011; Polimeni, Jonathan/P-1395-2014;
Wald, Lawrence/D-4151-2009
OI Polimeni, Jonathan/0000-0002-1348-1179;
FU McGovern Institute for Brain Research at MIT; NIH [P41RR14075]
FX The authors would like to thank the McGovern Institute for Brain
Research at MIT for the funding, Steve Shannon and Sheeba Arnold for the
technical support, and Michael Hamm and Thomas Witzel for their
assistance with computational resources. This work was supported by NIH
grant P41RR14075.
NR 18
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U1 1
U2 8
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 MAR 15
PY 2011
VL 55
IS 2
BP 597
EP 606
DI 10.1016/j.neuroimage.2010.11.084
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 724DL
UT WOS:000287556200018
PM 21167946
ER
PT J
AU Wilson, LB
Tregellas, JR
Slason, E
Pasko, BE
Rojas, DC
AF Wilson, Lisa B.
Tregellas, Jason R.
Slason, Erin
Pasko, Bryce E.
Rojas, Donald C.
TI Implicit phonological priming during visual word recognition
SO NEUROIMAGE
LA English
DT Article
DE fMRI; Phonology; Priming; Implicit memory; Superior temporal gyrus;
Supramarginal gyrus; Default-mode network
ID SUPERIOR TEMPORAL GYRUS; VERBAL WORKING-MEMORY; DEFAULT-MODE; FUNCTIONAL
NEUROANATOMY; SENTENCE COMPREHENSION; SPEECH PRODUCTION; LEXICAL ACCESS;
BRAIN-FUNCTION; TIME-COURSE; ACTIVATION
AB Phonology is a lower-level structural aspect of language involving the sounds of a language and their organization in that language. Numerous behavioral studies utilizing priming, which refers to an increased sensitivity to a stimulus following prior experience with that or a related stimulus, have provided evidence for the role of phonology in visual word recognition. However, most language studies utilizing priming in conjunction with functional magnetic resonance imaging (fMRI) have focused on lexical-semantic aspects of language processing. The aim of the present study was to investigate the neurobiological substrates of the automatic, implicit stages of phonological processing. While undergoing fMRI, eighteen individuals performed a lexical decision task (LOT) on prime-target pairs including word-word homophone and pseudoword-word pseudohomophone pairs with a prime presentation below perceptual threshold. Whole-brain analyses revealed several cortical regions exhibiting hemodynamic response suppression due to phonological priming including bilateral superior temporal gyri (STG), middle temporal gyri (MTG), and angular gyri (AG) with additional region of interest (ROI) analyses revealing response suppression in the left lateralized supramarginal gyrus (SMG). Homophone and pseudohomophone priming also resulted in different patterns of hemodynamic responses relative to one another. These results suggest that phonological processing plays a key role in visual word recognition. Furthermore, enhanced hemodynamic responses for unrelated stimuli relative to primed stimuli were observed in midline cortical regions corresponding to the default-mode network (DMN) suggesting that DMN activity can be modulated by task requirements within the context of an implicit task. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Wilson, Lisa B.; Tregellas, Jason R.; Slason, Erin; Pasko, Bryce E.; Rojas, Donald C.] Univ Colorado Denver, Dept Psychiat, Aurora, CO 80045 USA.
[Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA.
RP Rojas, DC (reprint author), Univ Colorado Denver, Dept Psychiat, 13001 E 17th Pl, Aurora, CO 80045 USA.
EM lisa.wilson@ucdenver.edu; jason.tregellas@ucdenver.edu;
erin.slason@gmail.com; bryce.pasko@ucdenver.edu; don.rojas@ucdenver.edu
RI Rojas, Don/F-4296-2012; Tregellas, Jason/J-3637-2015;
OI Rojas, Don/0000-0001-6560-9616
FU Autism Speaks [2090]; Autism Speaks Weatherstone [6291]; National
Institutes of Health (NIH) [PHS R01 MH082020]; NIH/NCRR Colorado CTSI
[TL1 RR025778]; National Institute of Child Health and Human Development
(NICHHD) [HD041697]
FX Funding for this study was provided by Autism Speaks Grant 2090, Autism
Speaks Weatherstone Grant 6291, the National Institutes of Health (NIH)
Grant PHS R01 MH082020, NIH/NCRR Colorado CTSI Grant TL1 RR025778, and
the National Institute of Child Health and Human Development (NICHHD)
Grant HD041697. The funding sources had no further role in the study
design; in the collection, analysis, and interpretation of data; in the
writing of the report; and in the decision to submit the paper for
publication.
NR 64
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U1 0
U2 13
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 MAR 15
PY 2011
VL 55
IS 2
BP 724
EP 731
DI 10.1016/j.neuroimage.2010.12.019
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 724DL
UT WOS:000287556200031
PM 21159322
ER
PT J
AU Majic, T
Rentzsch, J
Gudlowski, Y
Ehrlich, S
Juckel, G
Sander, T
Lang, UE
Winterer, G
Gallinat, J
AF Majic, Tomislav
Rentzsch, Johannes
Gudlowski, Yehonala
Ehrlich, Stefan
Juckel, Georg
Sander, Thomas
Lang, Undine E.
Winterer, Georg
Gallinat, Juergen
TI COMT Val(108/158)Met genotype modulates human sensory gating
SO NEUROIMAGE
LA English
DT Article
DE COMT polymorphism; P50; N100; Auditory sensory gating; Endophenotypes;
Dopamine
ID METHYLTRANSFERASE VAL(158)MET GENOTYPE; UNMEDICATED
SCHIZOPHRENIC-PATIENTS; AUDITORY-EVOKED POTENTIALS; EVENT-RELATED
POTENTIALS; TEST-RETEST RELIABILITY; POOR P50 SUPPRESSION; GAMMA-BAND
RESPONSES; PREPULSE INHIBITION; FRONTAL-CORTEX; PREFRONTAL CORTEX
AB Background: The catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism of the dopamine system is essential for prefrontal cortex processing capacity and efficiency. In addition, dopaminergic neurotransmission is also associated with the sensory gating phenomenon protecting the cerebral cortex from information overload. It is however unclear if COMT genotype as a predictor of prefrontal efficiency modulates sensory gating on the level of the auditory cortex, i.e. the gating of the auditory evoked P50 and N100 components.
Methods: P50 and N100 gating and COMT Val(108/158)Met genotype were determined in 282 healthy subjects of German descent carefully screened for psychiatric or neurological disorders.
Results: A significant effect of the COMT genotype was observed for N100 gating (F = 4.510, df = 2, p = 0.012) but not for P50 gating (F = 0.376, df = 2, p = 0.687). Contrast analysis showed that Met/Met individuals had poorer N100 gating compared to Val/Met (F = -12.931, p = 0.003) and the Val/Val individuals (F = -11.056, p = 0.057).
Conclusion: The results indicate that a high prefrontal efficiency as suggested by the COMT Met/Met genotype is associated with to a poor sensory gating of the N100 component. This would fit in a model where a high prefrontal processing capacity allows a pronounced afferent input of sensory information from the auditory cortex as reflected by a poor sensory gating. The more pronounced prefrontal contribution to the N100 compared to the P50 component may explain the exclusive genotype association with the N100 sensory gating. This preliminary model should be replicated and validated in future investigations. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Majic, Tomislav] Charite, Hosp St Hedwig, Dept Psychiat & Psychotherapy, Clin Psychiat & Psychotherapy, D-10115 Berlin, Germany.
[Rentzsch, Johannes; Gudlowski, Yehonala; Ehrlich, Stefan; Lang, Undine E.] Charite, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany.
[Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA.
[Juckel, Georg] Ruhr Univ Bochum, Dept Psychiat Psychotherapy Psychosomat & Prevent, LWL Univ Hosp, D-44791 Bochum, Germany.
[Sander, Thomas; Winterer, Georg] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany.
[Sander, Thomas; Winterer, Georg] Res Ctr Juelich, Inst Neurosci & Biophys, D-52425 Julich, Germany.
RP Majic, T (reprint author), Charite, Hosp St Hedwig, Dept Psychiat & Psychotherapy, Clin Psychiat & Psychotherapy, 2rosse Hamburger Str 5-11, D-10115 Berlin, Germany.
EM tomislav.majic@charite.de
RI Lang, Undine Emmi/K-5553-2015;
OI Lang, Undine Emmi/0000-0002-3585-6533; Ehrlich,
Stefan/0000-0003-2132-4445
NR 91
TC 14
Z9 14
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAR 15
PY 2011
VL 55
IS 2
BP 818
EP 824
DI 10.1016/j.neuroimage.2010.12.031
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 724DL
UT WOS:000287556200041
PM 21184832
ER
PT J
AU Shlipak, M
AF Shlipak, Michael
TI Diabetic Nephropathy: Preventing Progression
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Editorial Material
C1 San Francisco VA Med Ctr, San Francisco, CA USA.
RP Shlipak, M (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD MAR 15
PY 2011
VL 83
IS 6
BP 732
EP 733
PG 2
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 979ZM
UT WOS:000306863400011
ER
PT J
AU Weiss, A
Grueninger, S
Abramowski, D
Di Giorgio, FP
Lopatin, MM
Rosas, HD
Hersch, S
Paganetti, P
AF Weiss, Andreas
Grueninger, Stephan
Abramowski, Dorothee
Di Giorgio, Francesco Paolo
Lopatin, Miriam Moscovitch
Rosas, H. Diana
Hersch, Steven
Paganetti, Paolo
TI Microtiter plate quantification of mutant and wild-type huntingtin
normalized to cell count
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
ID DISEASE
AB Huntington's disease is caused by a gain-of-function neurotoxic mutation in normally neuroprotective huntingtin. Sensitive assays are required to discriminate mutant huntingtin from wild-type huntingtin. We have developed a normalized 384-plate assay for determination of mutant and wild-type huntingtin. Based on a single pipetting step, the sensitive assay uses two antibody pairs for simultaneous mutant and wild-type huntingtin time-resolved fluorescence resonance energy transfer detection combined with PicoGreen quantification of double-stranded DNA. The assay can be used for discovery of drugs reducing mutant huntingtin over wild-type huntingtin and for assessing the value of huntingtin as a disease progression marker, and it is adaptable to other proteins of interest. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Weiss, Andreas; Grueninger, Stephan; Abramowski, Dorothee; Di Giorgio, Francesco Paolo] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland.
[Lopatin, Miriam Moscovitch; Rosas, H. Diana; Hersch, Steven] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Paganetti, Paolo] AC Immune, CH-1015 Lausanne, Switzerland.
RP Weiss, A (reprint author), Novartis Inst Biomed Res, CH-4002 Basel, Switzerland.
EM andreas-1.weiss@novartis.com
FU NINDS NIH HHS [U01 NS071789]
NR 13
TC 7
Z9 7
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 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD MAR 15
PY 2011
VL 410
IS 2
BP 304
EP 306
DI 10.1016/j.ab.2010.11.044
PG 3
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 718EN
UT WOS:000287103900019
PM 21134349
ER
PT J
AU Johansen, KL
AF Johansen, Kirsten L.
TI Time to Rethink the Timing of Dialysis Initiation
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Johansen, Kirsten L.] Univ Calif San Francisco, Nephrol Sect, San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94121 USA.
RP Johansen, KL (reprint author), Univ Calif San Francisco, Nephrol Sect, San Francisco VA Med Ctr, 111J,4150 Clement St, San Francisco, CA 94121 USA.
EM Kirsten.johansen@ucsf.edu
NR 10
TC 4
Z9 4
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAR 14
PY 2011
VL 171
IS 5
BP 382
EP U182
DI 10.1001/archinternmed.2010.413
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 734IW
UT WOS:000288328800002
PM 21059965
ER
PT J
AU Zhang, YT
Zhou, L
Gellad, WF
AF Zhang, Yuting
Zhou, Lei
Gellad, Walid F.
TI Potential Savings From Greater Use of $4 Generic Drugs
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Zhang, Yuting; Zhou, Lei] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Gellad, Walid F.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Div Gen Med, Pittsburgh, PA 15261 USA.
[Gellad, Walid F.] RAND Corp, Santa Monica, CA 90406 USA.
RP Zhang, YT (reprint author), Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, 130 De Soto St,Crabtree Hall A664, Pittsburgh, PA 15261 USA.
EM ytzhang@pitt.edu
OI Zhang, Yuting/0000-0002-6460-6779
FU NCATS NIH HHS [KL2 TR000146]; NCRR NIH HHS [UL1 RR024153, KL2 RR024154,
KL2 RR024154-04]
NR 5
TC 9
Z9 9
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAR 14
PY 2011
VL 171
IS 5
BP 468
EP 469
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 734IW
UT WOS:000288328800018
PM 21403045
ER
PT J
AU Chang, J
Lindsay, RJ
Kulkarni, S
Lifson, JD
Carrington, M
Altfeld, M
AF Chang, Judy
Lindsay, Robert J.
Kulkarni, Smita
Lifson, Jeffrey D.
Carrington, Mary
Altfeld, Marcus
TI Polymorphisms in interferon regulatory factor 7 reduce interferon-alpha
responses of plasmacytoid dendritic cells to HIV-1
SO AIDS
LA English
DT Article
ID SIV INFECTION; IMMUNE ACTIVATION; VIRUS-INFECTIONS; NATURAL HOSTS; TLR7
AB Recognition of HIV-1 ssRNA by Toll-like receptor 7 induces the production of the pro-inflammatory cytokines that may contribute to the systemic immune activation associated with HIV-1 disease progression. Here, we describe a novel association between polymorphisms in interferon regulatory factor 7 (IRF7), a master regulator of interferon-alpha (IFN-alpha), and the ability of plasmacytoid dendritic cells to produce IFN-alpha in response to HIV-1. IRF7 polymorphisms may, therefore, affect the ability of individuals to respond to HIV-1 and modulate HIV-1 disease progression.
C1 [Chang, Judy; Lindsay, Robert J.; Carrington, Mary; Altfeld, Marcus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Kulkarni, Smita; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21701 USA.
[Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Bldg 149,13th St,6th Floor, Navy Yard, MA 02129 USA.
EM maltfeld@partners.org
FU Doris Duke Charitable Foundation; Phillip T. and Susan M. Ragon
Foundation; Bill and Melinda Gates Foundation; National Health and
Medical Research Council of Australia [519578]; Ragon Fellowship;
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; [RO1 216753]
FX The authors thank the Brigham and Women's Hospital PhenoGenetic Project
for providing DNA samples from healthy individuals that were used in the
replication effort of this study. These studies were supported by RO1
216753 and the Doris Duke Charitable Foundation. They also thank the
Phillip T. and Susan M. Ragon Foundation and the Bill and Melinda Gates
Foundation for their support. J.J.C. is supported by a fellowship
awarded from the National Health and Medical Research Council of
Australia (519578) and a Ragon Fellowship and M. A. is a Doris Duke
Distinguished Clinical Scientist. This project has been funded in whole
or in part with federal funds from the National Cancer Institute,
National Institutes of Health, under Contract No. HHSN261200800001E. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government. This research was supported in part by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 14
TC 12
Z9 12
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2011
VL 25
IS 5
BP 715
EP 717
DI 10.1097/QAD.0b013e328343c186
PG 3
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 729PT
UT WOS:000287963600023
PM 21297422
ER
PT J
AU Lin, NU
Burstein, HJ
AF Lin, Nancy U.
Burstein, Harold J.
TI EMBRACE, eribulin, and new realities of advanced breast cancer
SO LANCET
LA English
DT Editorial Material
ID HALICHONDRIN B ANALOG; PHASE-II; ANTHRACYCLINE; CHEMOTHERAPY; MESYLATE;
TAXANE
C1 [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA.
EM hburstein@partners.org
NR 7
TC 5
Z9 6
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD MAR 12
PY 2011
VL 377
IS 9769
BP 878
EP 880
DI 10.1016/S0140-6736(11)60280-8
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 738GR
UT WOS:000288628800005
PM 21376386
ER
PT J
AU Eekhoff, A
Bonakdar, N
Alonso, JL
Hoffmann, B
Goldmann, WH
AF Eekhoff, Alexander
Bonakdar, Navid
Alonso, Jose Luis
Hoffmann, Bernd
Goldmann, Wolfgang H.
TI Glomerular podocytes: A study of mechanical properties and
mechano-chemical signaling
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Podocytes; Cell mechanics and signaling; Magnetic tweezer; Magnetic
twisting cytometry; Cell stretcher; Actin cytoskeleton; AT1 receptor;
Angiotensin II; Calcium
ID SMOOTH-MUSCLE-CELLS; CULTURED ENDOTHELIAL-CELLS; CYCLIC STRETCH;
IN-VITRO; CYTOSKELETON; PROTEINURIA; ACTIN; EXPRESSION; INCREASES;
DYNAMICS
AB Kidney glomeruli function as filters, allowing the passage of small solutes and waste products into the urinary tract, while retaining essential proteins and macromolecules in the blood stream. These structures are under constant mechanical stress due to fluid pressure, driving filtration across the barrier. We mechanically stimulated adherent wildtype podocytes using the methods of magnetic tweezer and twisting as well as cell stretching. Attaching collagen IV-coated or poly-L-lysine-coated magnetic beads to cell receptors allowed for the determination of cellular stiffness. Angiotensin II-treated podocytes showed slightly higher stiffness than untreated cells, the cell fluidity (i.e. internal dynamics) remained similar, and showed an increase with force. The bead detachment (a measure of the binding strength) was higher in angiotensin II-treated compared to untreated podocytes. Magnetic twisting confirmed that angiotensin II treatment of podocytes increases and CDTA treatment decreases cell stiffness. However, treatment with both angiotensin II and CDTA increased the cell stiffness only slightly compared to solely CDTA-treated cells. Exposing podocytes to cyclic, uniaxial stretch showed an earlier onset of ERK(1/2) phosphorylation compared to MEF (control) cells. These results indicate that angiotensin II might free intracellularly stored calcium and affects actomyosin contraction, and that mechanical stimulation influences cell signaling. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Eekhoff, Alexander; Bonakdar, Navid; Goldmann, Wolfgang H.] Univ Erlangen Nurnberg, Ctr Med Phys & Technol, Biophys Grp, D-91052 Erlangen, Germany.
[Alonso, Jose Luis] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA.
[Hoffmann, Bernd] Forschungszentrum Julich GmbH, Inst Complex Syst 7, Biomech, Julich, Germany.
RP Goldmann, WH (reprint author), Univ Erlangen Nurnberg, Ctr Med Phys & Technol, Biophys Grp, Henkestr 91, D-91052 Erlangen, Germany.
EM wgoldmann@biomed.uni-erlangen.de
RI Alonso, Jose Luis/G-7961-2012; Goldmann, Wolfgang/H-5572-2013; Hoffmann,
Bernd/I-7237-2013;
OI Hoffmann, Bernd/0000-0002-3803-8835
FU Bayerisch-Franzosisches Hochschulzentrum; Deutscher Akademischer
Austausch Dienst, Bavaria California Technology Center; Deutsche
Forschungsgemeinschaft
FX We thank Drs. Ben Fabry, Rudolf Merkel, Gerold Diez, James Smith, and
Anna Klemm for helpful comments, Tim Feichtmeier for the cyclic stretch
experiments on human umbilical cord fibroblasts, Andrea Zang for helping
with OMTC, and Wolfgang Rubner for building a new cell stretcher. This
work was supported by grants from Bayerisch-Franzosisches
Hochschulzentrum, Deutscher Akademischer Austausch Dienst, Bavaria
California Technology Center, and Deutsche Forschungsgemeinschaft.
NR 29
TC 10
Z9 10
U1 1
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD MAR 11
PY 2011
VL 406
IS 2
BP 229
EP 233
DI 10.1016/j.bbrc.2011.02.022
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 738CF
UT WOS:000288616200013
PM 21315064
ER
PT J
AU Edderkaoui, M
Nitsche, C
Zheng, L
Pandol, SJ
Gukovsky, I
Gukovskaya, AS
AF Edderkaoui, Mouad
Nitsche, Claudia
Zheng, Ling
Pandol, Stephen J.
Gukovsky, Ilya
Gukovskaya, Anna S.
TI NADPH Oxidase Activation in Pancreatic Cancer Cells Is Mediated through
Akt-dependent Up-regulation of p22(phox)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NF-KAPPA-B; AORTIC SMOOTH-MUSCLE; FACTOR-I RECEPTOR; ENDOTHELIAL-CELLS;
GROWTH; NOX4; APOPTOSIS; ALPHA; EXPRESSION; GENERATION
AB We recently showed that Nox4 NADPH oxidase is highly expressed in pancreatic ductal adenocarcinoma and that it is activated by growth factors and plays a pro-survival, antiapoptotic role. Here we investigate the mechanisms through which insulin-like growth factor I and serum (FBS) activate NADPH oxidase in pancreatic cancer (PaCa) cells. We show that in PaCa cells, NADPH oxidase is composed of Nox4 and p22(phox) catalytic subunits, which are both required for NADPH oxidase activity. Insulin-like growth factor I and FBS activate NADPH oxidase through transcriptional up-regulation of p22(phox). This involves activation of the transcription factor NF-kappa B mediated by Akt kinase. Up-regulation of p22(phox) by the growth factors results in increased Nox4-p22(phox) complex formation and activation of NADPH oxidase. This mechanism is different from that for receptor-induced activation of phagocytic NADPH oxidase, which is mediated by phosphorylation of its regulatory subunits. Upregulation of p22(phox) represents a novel pro-survival mechanism through which growth factors and Akt inhibit apoptosis in PaCa cells.
C1 [Gukovskaya, Anna S.] Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Los Angeles, CA 90073 USA.
RP Gukovskaya, AS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA.
EM agukovsk@ucla.edu
FU National Institutes of Health through NCI [R01CA119025]; NCCAM
[AT003960]; Department of Veterans Affairs Merit Review; CURE-Digestive
Diseases Research Center
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01CA119025 through the NCI (to A. S. G.) and AT003960
through the NCCAM (to S. J. P.). This study was also supported by the
Department of Veterans Affairs Merit Review (to A. S. G.) and the
CURE-Digestive Diseases Research Center Pilot and Feasibility Award (to
M. E.).
NR 32
TC 34
Z9 34
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 11
PY 2011
VL 286
IS 10
BP 7779
EP 7787
DI 10.1074/jbc.M110.200063
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730DQ
UT WOS:000288013300009
PM 21118808
ER
PT J
AU Kim, DY
Gersbacher, MT
Inquimbert, P
Kovacs, DM
AF Kim, Doo Yeon
Gersbacher, Manuel T.
Inquimbert, Perrine
Kovacs, Dora M.
TI Reduced Sodium Channel Na(v)1.1 Levels in BACE1-null Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; BETA-SECRETASE BACE1; APP TRANSGENIC MICE;
ALZHEIMERS-DISEASE; MOLECULAR-MECHANISMS; MULTIPLE-SCLEROSIS;
NEURONAL-ACTIVITY; GAMMA-SECRETASE; CELL-ADHESION; MOUSE MODEL
AB The Alzheimer BACE1 enzyme cleaves numerous substrates, with largely unknown physiological consequences. We have previously identified the contribution of elevated BACE1 activity to voltage-gated sodium channel Na(v)1.1 density and neuronal function. Here, we analyzed physiological changes in sodium channel metabolism in BACE1-null mice. Mechanistically, we first confirmed that endogenous BACE1 requires its substrate, the beta-subunit Na-v beta 2, to regulate levels of the pore-forming alpha-subunit Na(v)1.1 in cultured primary neurons. Next, we analyzed sodium channel alpha-subunit levels in brains of BACE1-null mice at 1 and 3 months of age. At both ages, we found that Na(v)1.1 protein levels were significantly decreased in BACE1-null versus wild-type mouse brains, remaining unchanged in BACE1-heterozygous mouse brains. Interestingly, levels of Na(v)1.2 and Na(v)1.6 alpha-subunits also decreased in 1-month-old BACE1-null mice. In the hippocampus of BACE1-null mice, we found a robust 57% decrease of Na(v)1.1 levels. Next, we performed surface biotinylation studies in acutely dissociated hippocampal slices from BACE1-null mice. Hippocampal surface Na(v)1.1 levels were significantly decreased, but Na(v)1.2 surface levels were increased in BACE1-null mice perhaps as a compensatory mechanism for reduced surface Na(v)1.1. We also found that Na-v beta(2) processing and Na(v)1.1 mRNA levels were significantly decreased in brains of BACE1-null mice. This suggests a mechanism consistent with BACE1 activity regulating mRNA levels of the alpha-subunit Na(v)1.1 via cleavage of cell-surface Na-v beta(2). Together, our data show that endogenous BACE1 activity regulates total and surface levels of voltage-gated sodium channels in mouse brains. Both decreased Na(v)1.1 and elevated surface Na(v)1.2 may result in a seizure phenotype. Our data caution that therapeutic BACE1 activity inhibition in Alzheimer disease patients may affect Na(v)1 metabolism and alter neuronal membrane excitability in Alzheimer disease patients.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Neurobiol Dis Lab,Genet & Aging Res Unit, Massachusetts Gen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Inquimbert, Perrine] Childrens Hosp, Dept Neurol, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
EM dora_kovacs@hms.harvard.edu
FU National Institutes of Health, NIA
FX This work was supported, in whole or in part, by National Institutes of
Health grants from NIA (to D. M. K. and D. Y. K.).
NR 48
TC 40
Z9 40
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 11
PY 2011
VL 286
IS 10
BP 8106
EP 8116
DI 10.1074/jbc.M110.134692
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730DQ
UT WOS:000288013300041
PM 21190943
ER
PT J
AU Wang, XV
Verhaak, RGW
Purdom, E
Spellman, PT
Speed, TP
AF Wang, Xin Victoria
Verhaak, Roel G. W.
Purdom, Elizabeth
Spellman, Paul T.
Speed, Terence P.
TI Unifying Gene Expression Measures from Multiple Platforms Using Factor
Analysis
SO PLOS ONE
LA English
DT Article
ID PROBE LEVEL DATA; MICROARRAY DATA; REPRODUCIBILITY; DISCOVERY; GENOME
AB In the Cancer Genome Atlas (TCGA) project, gene expression of the same set of samples is measured multiple times on different microarray platforms. There are two main advantages to combining these measurements. First, we have the opportunity to obtain a more precise and accurate estimate of expression levels than using the individual platforms alone. Second, the combined measure simplifies downstream analysis by eliminating the need to work with three sets of expression measures and to consolidate results from the three platforms. We propose to use factor analysis (FA) to obtain a unified gene expression measure (UE) from multiple platforms. The UE is a weighted average of the three platforms, and is shown to perform well in terms of accuracy and precision. In addition, the FA model produces parameter estimates that allow the assessment of the model fit. The R code is provided in File S2. Gene-level FA measurements for the TCGA data sets are available from http://tcga-data.nci.nih.gov/docs/publications/unified_expression/.
C1 [Wang, Xin Victoria] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Wang, Xin Victoria] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Verhaak, Roel G. W.] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA USA.
[Purdom, Elizabeth] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
[Spellman, Paul T.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Speed, Terence P.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3050, Australia.
RP Wang, XV (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
EM vwang@jimmy.harvard.edu
FU National Institutes of Health [U24 CA126551]; Dutch Cancer Society KWF
FX This work was supported by the National Institutes of Health [U24
CA126551 to XVW, EP, PTS, and TPS] and Dutch Cancer Society KWF
[fellowship to RGWV]. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 24
TC 7
Z9 7
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 11
PY 2011
VL 6
IS 3
AR e17691
DI 10.1371/journal.pone.0017691
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 733FF
UT WOS:000288247800025
PM 21436879
ER
PT J
AU Feng, D
Liu, T
Sun, Z
Bugge, A
Mullican, SE
Alenghat, T
Liu, XS
Lazar, MA
AF Feng, Dan
Liu, Tao
Sun, Zheng
Bugge, Anne
Mullican, Shannon E.
Alenghat, Theresa
Liu, X. Shirley
Lazar, Mitchell A.
TI A Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls
Hepatic Lipid Metabolism
SO SCIENCE
LA English
DT Article
ID FATTY LIVER-DISEASE; RECEPTOR COREPRESSOR; CLOCK; TRANSCRIPTION; MICE;
OSCILLATOR; TISSUE
AB Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 ( HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent. Although amounts of HDAC3 are constant, its genomic recruitment in liver corresponds to the expression pattern of the circadian nuclear receptor Rev-erb alpha. Rev-erb alpha colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erb alpha in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erb alpha directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis.
C1 [Feng, Dan; Sun, Zheng; Bugge, Anne; Mullican, Shannon E.; Alenghat, Theresa; Lazar, Mitchell A.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Dept Genet, Philadelphia, PA 19104 USA.
[Feng, Dan; Sun, Zheng; Bugge, Anne; Mullican, Shannon E.; Alenghat, Theresa; Lazar, Mitchell A.] Univ Penn, Sch Med, Inst Diabet Obes & Metab IDOM, Philadelphia, PA 19104 USA.
[Liu, Tao; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Liu, Tao; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Lazar, MA (reprint author), Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Dept Genet, Philadelphia, PA 19104 USA.
EM lazar@mail.med.upenn.edu
RI Liu, Tao/G-3585-2010; Sun, Zheng/C-1146-2012; Feng, Dan/F-7205-2013;
OI Liu, Tao/0000-0002-8818-8313; Sun, Zheng/0000-0002-6858-0633; Liu,
Tao/0000-0003-0446-9001
FU NIH [DK19525, DK49210, DK45586, DK43806, RC1DK08623, HG4069]
FX ChIP-seq and microarray data have been deposited in the Gene Expression
Omnibus (GSE25937 and GSE26345) database. We thank B. Vennstrom for
providing Rev-erba KO mice; M. Brown, D. Steger, and members of the
Lazar lab for helpful discussions; D. Zhuo for technical assistance; the
Penn IDOM Metabolism Resource (J. Millar) for help with de novo
lipogenesis experiments; the Functional Genomics Core (J. Schug and K.
Kaestner) and the Viral Vector Core (J. Johnston) of the Penn Diabetes
Endocrinology Research Center (NIH DK19525) for deep sequencing and
virus preparation; the Morphology Core (J. Katz and G. Swain) (NIH
DK49210) for tissue preparation and staining; and the Penn
Bioinformatics Core (J. Tobias) and Microarray Core (D. Baldwin) for
gene expression analysis. Supported by the Cox Institute, NIH DK45586,
DK43806, and RC1DK08623 (to M. A. L.) and NIH HG4069 (to X. S. L.).
NR 30
TC 255
Z9 261
U1 8
U2 49
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 11
PY 2011
VL 331
IS 6022
BP 1315
EP 1319
DI 10.1126/science.1198125
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732UM
UT WOS:000288215200044
PM 21393543
ER
PT J
AU Shen, WL
Kwon, Y
Adegbola, AA
Luo, JJ
Chess, A
Montell, C
AF Shen, Wei L.
Kwon, Young
Adegbola, Abidemi A.
Luo, Junjie
Chess, Andrew
Montell, Craig
TI Function of Rhodopsin in Temperature Discrimination in Drosophila
SO SCIENCE
LA English
DT Article
ID NUCLEOTIDE-GATED CHANNEL; C-ELEGANS; CAENORHABDITIS-ELEGANS;
PHOSPHOLIPASE-C; G-PROTEIN; PHOTOTRANSDUCTION; THERMOSENSATION;
RECEPTORS; NEURONS
AB Many animals, including the fruit fly, are sensitive to small differences in ambient temperature. The ability of Drosophila larvae to choose their ideal temperature (18 degrees C) over other comfortable temperatures (19 degrees to 24 degrees C) depends on a thermosensory signaling pathway that includes a heterotrimeric guanine nucleotide-binding protein (G protein), a phospholipase C, and the transient receptor potential TRPA1 channel. We report that mutation of the gene (ninaE) encoding a classical G protein-coupled receptor (GPCR), Drosophila rhodopsin, eliminates thermotactic discrimination in the comfortable temperature range. This role for rhodopsin in thermotaxis toward 18 degrees C was light-independent. Introduction of mouse melanopsin restored normal thermotactic behavior in ninaE mutant larvae. We propose that rhodopsins represent a class of evolutionarily conserved GPCRs that are required for initiating thermosensory signaling cascades.
C1 [Shen, Wei L.; Kwon, Young; Luo, Junjie; Montell, Craig] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
[Shen, Wei L.; Kwon, Young; Luo, Junjie; Montell, Craig] Johns Hopkins Univ, Sch Med, Dept Neurosci, Ctr Sensory Biol, Baltimore, MD 21205 USA.
[Adegbola, Abidemi A.; Chess, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Adegbola, Abidemi A.; Chess, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
[Chess, Andrew] Broad Inst, Cambridge, MA 02142 USA.
[Chess, Andrew] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA.
[Chess, Andrew] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY 10029 USA.
RP Montell, C (reprint author), Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
EM cmontell@jhmi.edu
RI shen, wei/C-2311-2013;
OI Montell, Craig/0000-0001-5637-1482
FU National Institute of General Medical Sciences, NIH [GM085335]
FX We thank Y. Liu for advice with the statistical analyses, the
Bloomington Stock Center, FlyBase, and the Harvard TRiP. A. A. A.
received support from a NARSAD Young Investigator Award. This study was
supported by a grant to C. M. from the National Institute of General
Medical Sciences, NIH (GM085335).
NR 21
TC 78
Z9 80
U1 3
U2 30
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 11
PY 2011
VL 331
IS 6022
BP 1333
EP 1336
DI 10.1126/science.1198904
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732UM
UT WOS:000288215200049
PM 21393546
ER
PT J
AU Lin, AE
Alexander, ME
Colan, SD
Kerr, B
Rauen, KA
Noonan, J
Baffa, J
Hopkins, E
Sol-Church, K
Limongelli, G
Digilio, MC
Marino, B
Innes, AM
Aoki, Y
Silberbach, M
Delrue, MA
White, SM
Hamilton, RM
O'Connor, W
Grossfeld, PD
Smoot, LB
Padera, RF
Gripp, KW
AF Lin, Angela E.
Alexander, Mark E.
Colan, Steven D.
Kerr, Bronwyn
Rauen, Katherine A.
Noonan, Jacqueline
Baffa, Jeanne
Hopkins, Elizabeth
Sol-Church, Katia
Limongelli, Giuseppe
Digilio, Maria Christina
Marino, Bruno
Innes, A. Micheil
Aoki, Yoko
Silberbach, Michael
Delrue, Marie-Ange
White, Susan M.
Hamilton, Robert M.
O'Connor, William
Grossfeld, Paul D.
Smoot, Leslie B.
Padera, Robert F.
Gripp, Karen W.
TI Clinical, Pathological, and Molecular Analyses of Cardiovascular
Abnormalities in Costello Syndrome: A Ras/MAPK Pathway Syndrome
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE aortic dilation; arrhythmias; cardiovascular malformation; chaotic
atrial rhythm; congenital heart defect; ectopic atrial tachycardia;
HRAS; hypertrophic cardiomyopathy; multifocal atrial tachycardia;
Noonan-spectrum syndromes; RASopathy
ID FACIO-CUTANEOUS SYNDROME; CAUSE NOONAN-SYNDROME; GENOTYPE-PHENOTYPE
CORRELATION; GERMLINE KRAS MUTATIONS; OF-FUNCTION MUTATIONS;
HYPERTROPHIC CARDIOMYOPATHY; LEOPARD-SYNDROME; HRAS MUTATION; PTPN11
MUTATIONS; CARDIAC-HYPERTROPHY
AB Cardiovascular abnormalities are important features of Costello syndrome and other Ras/MAPK pathway syndromes ("RASopathies'"). We conducted clinical, pathological and molecular analyses of 146 patients with an HRAS mutation including 61 enrolled in an ongoing longitudinal study and 85 from the literature. In our study, the most common (84%) HRAS mutation was p.G12S. A congenital heart defect (CHD) was present in 27 of 61 patients(44%), usually non-progressive valvar pulmonary stenosis. Hypertrophic cardiomyopathy (HCM), typically subaortic septal hypertrophy, was noted in 37 (61%), and 5 also had a CHD (14% of those with HCM). HCM was chronic or progressive in 14 (37%), stabilized in 10 (27%), and resolved in 5 (15%) patients with HCM; follow-up data was not available in 8 (22%). Atrial tachycardia occurred in 29 (48%). Valvar pulmonary stenosis rarely progressed and atrial septal defect was uncommon. Among those with HCM, the likelihood of progressing or remaining stable was similar (37%, 41% respectively). The observation of myocardial fiber disarray in 7 of 10 (70%) genotyped specimens with Costello syndrome is consistent with sarcomeric dysfunction. Multifocal atrial tachycardia may be distinctive for Costello syndrome. Potentially serious atrial tachycardia may present in the fetus, and may continue or worsen in about one-fourth of those with arrhythmia, but is generally self-limited in the remaining three-fourths of patients. Physicians should be aware of the potential for rapid development of severe HCM in infants with Costello syndrome, and the need for cardiovascular surveillance into adulthood as the natural history continues to be delineated. (C) 2011 Wiley-Liss, Inc.
C1 [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA 02114 USA.
[Alexander, Mark E.; Colan, Steven D.; Smoot, Leslie B.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Kerr, Bronwyn] Cent Manchester Fdn Trust Manchester, Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Rauen, Katherine A.] Ctr Comprehens Canc, San Francisco, CA USA.
[Rauen, Katherine A.] Univ Calif San Francisco, Dept Pediat, Div Med Genet, San Francisco, CA 94143 USA.
[Noonan, Jacqueline] Univ Kentucky, Med Ctr, Dept Pediat, Lexington, KY USA.
[Baffa, Jeanne] Nemours Cardiac Ctr, Wilmington, DE USA.
[Hopkins, Elizabeth; Gripp, Karen W.] Div Med Genet, Wilmington, DE USA.
[Sol-Church, Katia] Alfred I DuPont Hosp Children, Dept Biomed Res, Wilmington, DE USA.
[Limongelli, Giuseppe] Univ Naples 2, Monaldi Hosp, Naples, Italy.
[Digilio, Maria Christina] Bambino Gesu Pediat Hosp, Rome, Italy.
[Marino, Bruno] Univ Roma La Sapienza, Dept Pediat, Rome, Italy.
[Innes, A. Micheil] Univ Calgary, Dept Med Genet, Calgary, AB, Canada.
[Aoki, Yoko] Tohoku Univ, Sch Med, Dept Med Genet, Sendai, Miyagi 980, Japan.
[Silberbach, Michael] Doernbecher Childrens Hosp, Dept Pediat, Div Cardiol, Portland, OR USA.
[Delrue, Marie-Ange] CHU Bordeaux, Serv Genet Med, Bordeaux, France.
[White, Susan M.] Royal Childrens Hosp, Genet Hlth Serv Victoria, Melbourne, Vic, Australia.
[Hamilton, Robert M.] Hosp Sick Children, Div Cardiol, Toronto, ON M5G 1X8, Canada.
[O'Connor, William] Univ Kentucky, Med Ctr, Dept Pathol, Lexington, KY 40536 USA.
[Grossfeld, Paul D.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Lin, AE (reprint author), MassGen Hosp Children, Genet Unit, 185 Cambridge St,Simches 2222, Boston, MA 02114 USA.
EM lin.angela@mgh.harvard.edu
RI innes, allan micheil/A-9955-2017;
OI Innes, Micheil/0000-0001-9881-5467; LImongelli,
Giuseppe/0000-0002-8291-9517
NR 109
TC 40
Z9 40
U1 1
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAR 11
PY 2011
VL 155A
IS 3
BP 486
EP 507
DI 10.1002/ajmg.a.33857
PG 22
WC Genetics & Heredity
SC Genetics & Heredity
GA 730KX
UT WOS:000288033300008
PM 21344638
ER
PT J
AU Hartman, RJ
Riehle-Colarusso, T
Lin, A
Frias, JL
Patel, SS
Duwe, K
Correa, A
Rasmussen, SA
AF Hartman, Robert J.
Riehle-Colarusso, Tiffany
Lin, Angela
Frias, Jaime L.
Patel, Sonali S.
Duwe, Kara
Correa, Adolfo
Rasmussen, Sonja A.
CA Natl Birth Defects Prevention
TI Descriptive Study of Nonsyndromic Atrioventricular Septal Defects in the
National Birth Defects Prevention Study, 1997-2005
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE atrioventricular septal defect; endocardial cushion defect;
atrioventricular canal defect; prevalence; congenital heart defect;
congenital abnormalities; birth defects; chromosomal abnormalities;
ethnicity; nonsyndromic
ID CONGENITAL HEART-DEFECTS; DOWN-SYNDROME; CANAL DEFECT; INFANTS; DISEASE;
MALFORMATIONS; POPULATIONS; PREVALENCE; ANOMALIES; REGION
AB Nonsyndromic atrioventricular septal defects (AVSDs) are serious congenital heart defects for which information on prevalence and descriptive characteristics based on large, geographically, and ethnically diverse populations has been limited. To describe the birth prevalence and phenotype of nonsyndromic AVSDs, we used data from the National Birth Defects Prevention Study (NBDPS), a multisite, population-based case-control study aimed at identifying genetic and environmental risk factors for birth defects. For this analysis, infants born during the period 1997-2005 and meeting the NBDPS case definition for AVSDs were included. Infants with an AVSD associated with recognized or strongly suspected chromosomal abnormalities or single-gene disorders (syndromic case infants) were excluded. We identified 302 infants with a nonsyndromic AVSD for a birth prevalence of 0.83/10,000 livebirths. Over 20% of infants with an AVSD had an additional major birth defect, with gastrointestinal, renal or urinary, and central nervous system defects being the most common. A lower prevalence of AVSDs was seen among infants born to Hispanic mothers compared with those born to non-Hispanic White mothers [prevalence ratio = 0.63 (95% confidence interval: 0.46-0.86)]. Understanding the prevalence of nonsyndromic AVSDs, demographic factors associated with their occurrence, and associated defects could help guide clinical care, as well as contribute to a better understanding of pathogenesis. (C) 2011 Wiley-Liss, Inc.
C1 [Hartman, Robert J.; Riehle-Colarusso, Tiffany; Frias, Jaime L.; Duwe, Kara; Correa, Adolfo; Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA.
[Hartman, Robert J.; Duwe, Kara] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA.
[Lin, Angela] Massachusetts Ctr Birth Defects Res & Prevent, Massachusetts Dept Publ Hlth, Boston, MA USA.
[Lin, Angela] MassGen Hosp Children, Genet Unit, Boston, MA USA.
[Frias, Jaime L.] McKing Consulting Corp, Fairfax, VA USA.
[Patel, Sonali S.] Univ Iowa, Childrens Hosp, Iowa City, IA USA.
RP Rasmussen, SA (reprint author), CDC, 1600 Clifton Rd,MS E-86, Atlanta, GA 30333 USA.
EM skr9@cdc.gov
RI Publications, NBDPS/B-7692-2013
FU Centers for Disease Control and Prevention (CDC)
FX We thank Chris Cosper and Dr. Suzanne Gilboa for their assistance in
data analysis. We thank Cathleen Higgins and Marques Merri-weather for
their assistance with the supplemental surveillance study. The authors
acknowledge the contributions and dedication of the abstractors from the
MACDP, the IRCID, and the MBDMP, as well as the staff and scientists who
contribute to the NBDPS. This research was supported in part by an
appointment to the Research Participation Program at the Centers for
Disease Control and Prevention (CDC) administered by the Oak Ridge
Institute for Science and Education through an interagency agreement
between the U.S. Department of Energy and CDC.
NR 31
TC 9
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAR 11
PY 2011
VL 155A
IS 3
BP 555
EP 564
DI 10.1002/ajmg.a.33874
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 730KX
UT WOS:000288033300015
PM 21337694
ER
PT J
AU Phulwani, P
Bergwitz, C
Jaureguiberry, G
Rasoulpour, M
Estrada, E
AF Phulwani, Priya
Bergwitz, Clemens
Jaureguiberry, Graciana
Rasoulpour, Majjid
Estrada, Elizabeth
TI Hereditary Hypophosphatemic Rickets With Hypercalciuria and
Nephrolithiasis-Identification of a Novel SLC34A3/NaPi-IIc Mutation
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE rickets; hypophosphatemia; hypercalciuria; NaPi
ID PHOSPHATE HOMEOSTASIS; SLC34A3; OSTEOMALACIA; CHILDREN
AB Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g. 4225_50del) and a novel splice mutation (g. 1226G > A) in SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaPi-IIc. The patient's mother and grandmother are carriers of g. 4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2-6 years old), who are also carriers of g. 4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. (C) 2011 Wiley-Liss, Inc.
C1 [Phulwani, Priya; Estrada, Elizabeth] Connecticut Childrens Med Ctr, Dept Pediat Endocrinol & Diabet, Hartford, CT 06106 USA.
[Bergwitz, Clemens; Jaureguiberry, Graciana] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Bergwitz, Clemens; Jaureguiberry, Graciana] Harvard Univ, Sch Med, Boston, MA USA.
[Rasoulpour, Majjid] Connecticut Childrens Med Ctr, Dept Pediat Nephrol, Hartford, CT 06106 USA.
RP Phulwani, P (reprint author), Connecticut Childrens Med Ctr, Dept Pediat Endocrinol & Diabet, 85 Seymour St,Suite 500, Hartford, CT 06106 USA.
EM pphulwa@ccmckids.org
FU NIDDK NIH HHS [K08 DK078361, R03 DK089127]
NR 22
TC 4
Z9 4
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD MAR 11
PY 2011
VL 155A
IS 3
BP 626
EP 633
DI 10.1002/ajmg.a.33832
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 730KX
UT WOS:000288033300029
PM 21344632
ER
PT J
AU Letai, A
AF Letai, Anthony
TI A new face of BCL-2 inhibition in CLL
SO BLOOD
LA English
DT Editorial Material
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; APOPTOSIS; RECEPTOR; ABT-737; MCL-1
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Letai, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 10
TC 2
Z9 2
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 10
PY 2011
VL 117
IS 10
BP 2750
EP 2751
DI 10.1182/blood-2011-01-328658
PG 3
WC Hematology
SC Hematology
GA 732SJ
UT WOS:000288209600005
PM 21393499
ER
PT J
AU Grass, S
Preuss, KD
Wikowicz, A
Terpos, E
Ziepert, M
Nikolaus, D
Yang, Y
Fadle, N
Regitz, E
Dimopoulos, MA
Treon, SP
Hunter, ZR
Pfreundschuh, M
AF Grass, Sandra
Preuss, Klaus-Dieter
Wikowicz, Alexandra
Terpos, Evangelos
Ziepert, Marita
Nikolaus, Diana
Yang, Yin
Fadle, Natalie
Regitz, Evi
Dimopoulos, Meletios A.
Treon, Steven P.
Hunter, Zachary R.
Pfreundschuh, Michael
TI Hyperphosphorylated paratarg-7: a new molecularly defined risk factor
for monoclonal gammopathy of undetermined significance of the IgM type
and Waldenstrom macroglobulinemia
SO BLOOD
LA English
DT Article
ID NON-HODGKIN-LYMPHOMA; MHC CLASS-I; MULTIPLE-MYELOMA; IDENTIFICATION;
GENE; IMMUNOGLOBULIN; PARAPROTEINS; STIMULATION; DISORDERS; PATTERNS
AB We recently described paratarg-7 (P-7), a protein of unknown function, as the target of 15% of immunoglobulin A (IgA) and IgG paraproteins in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. To determine the frequency of P-7 as a paraprotein target in IgM-MGUS and Waldenstrom macroglobulinemia (WM), sera from patients with IgM-MGUS/WM were tested for reactivity with recombinant P-7 by enzyme-linked immunoabsorbent assay. The specificity of the paraprotein-mediated reaction was shown by absorption studies and cloning of the respective B-cell receptor. The paraproteins of 18 (9 WM and 9 IgM-MGUS) of 161 patients (11%) reacted with P-7. Isoelectric focusing and phosphatase treatment showed that P-7 was hyperphosphorylated (pP-7) in all patients with an anti-P-7-specific IgM paraprotein tested. Because only 4 of 200 healthy controls (2%) were carriers of pP-7, pP-7 carrier state is associated with a significantly increased risk (odds ratio = 6.2; P = .001) for developing IgM-MGUS/MW. Family analyses showed that the pP-7 carrier state is inherited as a dominant trait. After IgA/IgG-MGUS and multiple myeloma, IgM-MGUS/WM is the second neoplasia associated with pP-7 carrier state. The dominant inheritance of pP-7 explains cases of familial IgM-MGUS/WM and enables the identification of family members at increased risk. (Blood. 2011;117(10):2918-2923)
C1 [Grass, Sandra; Preuss, Klaus-Dieter; Wikowicz, Alexandra; Nikolaus, Diana; Yang, Yin; Fadle, Natalie; Regitz, Evi; Pfreundschuh, Michael] Univ Saarland, Sch Med, Dept Internal Med 1, Jose Carreras Ctr Immuno & Gene Therapy, D-66421 Homburg, Saar, Germany.
[Terpos, Evangelos; Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece.
[Ziepert, Marita] Univ Leipzig, IMISE, Leipzig, Germany.
[Treon, Steven P.; Hunter, Zachary R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA.
RP Pfreundschuh, M (reprint author), Univ Saarland, Sch Med, Dept Internal Med 1, Jose Carreras Ctr Immuno & Gene Therapy, D-66421 Homburg, Saar, Germany.
EM michael.pfreundschuh@uks.eu
RI Hunter, Zachary/H-3018-2013
OI Hunter, Zachary/0000-0002-1689-1691
FU Forderverein Krebsforschung Saar-Pfalz-Mosel; HOMFOR; Wilhelm
Sander-Stiftung
FX This work was supported by Forderverein Krebsforschung Saar-Pfalz-Mosel,
HOMFOR, and Wilhelm Sander-Stiftung.
NR 28
TC 11
Z9 12
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 10
PY 2011
VL 117
IS 10
BP 2918
EP 2923
DI 10.1182/blood-2010-09-306076
PG 6
WC Hematology
SC Hematology
GA 732SJ
UT WOS:000288209600029
PM 21220746
ER
PT J
AU Sun, Y
Meijer, DH
Alberta, JA
Mehta, S
Kane, MF
Tien, AC
Fu, H
Petryniak, MA
Potter, GB
Liu, ZJ
Powers, JF
Runquist, IS
Rowitch, DH
Stiles, CD
AF Sun, Yu
Meijer, Dimphna H.
Alberta, John A.
Mehta, Shwetal
Kane, Michael F.
Tien, An-Chi
Fu, Hui
Petryniak, Magdalena A.
Potter, Gregory B.
Liu, Zijing
Powers, James F.
Runquist, I. Sophie
Rowitch, David H.
Stiles, Charles D.
TI Phosphorylation State of Olig2 Regulates Proliferation of Neural
Progenitors
SO NEURON
LA English
DT Article
ID LOOP-HELIX FACTORS; NERVOUS-SYSTEM; MOTOR-NEURON; STEM-CELLS;
OLIGODENDROCYTE DIFFERENTIATION; TRANSCRIPTION FACTORS; SPECIFICATION;
ACETYLATION; GLIOMA; GENES
AB The bHLH transcription factors that regulate early development of the central nervous system can generally be classified as either antineural or proneural. Initial expression of antineural factors prevents cell cycle exit and thereby expands the pool of neural progenitors. Subsequent (and typically transient) expression of proneural factors promotes cell cycle exit, subtype specification, and differentiation. Against this backdrop, the bHLH transcription factor Olig2 in the oligodendrocyte lineage is unorthodox, showing antineural functions in multipotent CNS progenitor cells but also sustained expression and proneural functions in the formation of oligodendrocytes. We show here that the proliferative function of Olig2 is controlled by developmentally regulated phosphorylation of a conserved triple serine motif within the amino-terminal domain. In the phosphorylated state, Olig2 maintains antineural (i.e., promitotic) functions that are reflected in human glioma cells and in a genetically defined murine model of primary glioma.
C1 [Tien, An-Chi; Petryniak, Magdalena A.; Potter, Gregory B.; Rowitch, David H.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Pediat, San Francisco, CA 94143 USA.
[Sun, Yu; Meijer, Dimphna H.; Alberta, John A.; Mehta, Shwetal; Kane, Michael F.; Fu, Hui; Liu, Zijing; Runquist, I. Sophie; Stiles, Charles D.] Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA.
[Sun, Yu; Meijer, Dimphna H.; Alberta, John A.; Mehta, Shwetal; Kane, Michael F.; Fu, Hui; Liu, Zijing; Runquist, I. Sophie; Stiles, Charles D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Powers, James F.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA.
[Tien, An-Chi; Petryniak, Magdalena A.; Potter, Gregory B.; Rowitch, David H.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Neurol Surg, San Francisco, CA 94143 USA.
RP Rowitch, DH (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Pediat, 513 Parnassus Ave, San Francisco, CA 94143 USA.
EM rowitchd@peds.ucst.edu; charles_stiles@dfci.harvard.edu
RI Fu, Hui/C-2881-2011;
OI Fu, Hui/0000-0003-0252-6009; Potter, Gregory/0000-0002-0585-6575; Liu,
Zijing/0000-0001-7790-0590
FU NINDS [NS040511, NS057727]; Pediatric Low-Grade Astrocytoma Foundation;
[KO8 NS062744]
FX The authors gratefully acknowledge Dr. Ross Tomaino at the Taplin
Biological Mass Spectrometry Facility of Harvard Medical School for
helpful suggestions in the proteolytic digestions and mass spectroscopy
analysis of Olig2. Excellent technical assistance was provided by Diane
Goleblowski, Maria Murray, Jessica Weatherbee, and Gizelle Robinson.
Finally, we are grateful to Drs. Qiufu Ma and Rosalind Segal at
Dana-Farber for support and helpful suggestions. M.A.P. acknowledges KO8
NS062744 for support. This work was supported by grants from the NINDS
(NS040511 and NS057727 to D.H.R. and C.D.S., respectively) and from the
Pediatric Low-Grade Astrocytoma Foundation. D.H.R is a Howard Hughes
Medical Institute Investigator.
NR 41
TC 56
Z9 59
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD MAR 10
PY 2011
VL 69
IS 5
BP 906
EP 917
DI 10.1016/j.neuron.2011.02.005
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 739RU
UT WOS:000288736500009
PM 21382551
ER
PT J
AU Chou, CW
Wong, GTC
Lim, G
McCabe, MF
Wang, SX
Irwin, MG
Mao, JR
AF Chou, Chiu-Wen
Wong, Gordon T. C.
Lim, Grewo
McCabe, Michael F.
Wang, Shuxing
Irwin, Michael G.
Mao, Jianren
TI Peripheral nerve injury alters the expression of NF-kappa B in the rat's
hippocampus
SO BRAIN RESEARCH
LA English
DT Article
DE Neuropathic pain; NF-kappa B; Hippocampus
ID DENTATE GYRUS; NEUROPATHIC PAIN; GENE-EXPRESSION; FORMALIN PAIN;
RECONSOLIDATION; MONONEUROPATHY; MICROINJECTION; STIMULATION; DISORDERS;
ANALGESIA
AB The hippocampus plays an important role in learning and memory and possibly contributes to the formation of pain-related memory and emotional responses. However, there is currently little data linking the hippocampus to neuropathic pain. It has been reported that NF-kappa B is an important regulatory factor in memory consolidation within the hippocampus. This study aims to examine a possible relationship between the hippocampal NF-kappa B expression and nerve injury-induced thermal hyperalgesia using a rat model of constriction sciatic nerve injury (CCI). Immunofluorescence and Western blot analysis were performed to detect and quantify the hippocampal NF-kappa B expression. Thermal hyperalgesia was examined on day 0 and postoperative days 1, 7 and 14. The nuclear portion of the p65 NF-kappa B expression was significantly increased on the contralateral side on days 7 and 14 as well as significantly increased on the ipsilateral side on day 14 as compared to the sham control group. Intraperitoneal administration of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, reduced hyperalgesia and modulated the NF-kappa B expression in the contralateral side of hippocampus. These results suggest an association between the hippocampal NF-kappa B expression and the behavioral manifestation of thermal hyperalgesia, which is likely to be mediated through activation of the NMDA receptor. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Chou, Chiu-Wen; Lim, Grewo; McCabe, Michael F.; Wang, Shuxing; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Sch Med, MGH Ctr Translat Pain Res,WACC 324, Boston, MA 02114 USA.
[Chou, Chiu-Wen; Wong, Gordon T. C.; Irwin, Michael G.] Univ Hong Kong, Dept Anaesthesiol, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China.
RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Sch Med, MGH Ctr Translat Pain Res,WACC 324, Boston, MA 02114 USA.
EM jmao@partners.org
FU NIH [DE18214, DE18538, N545681]
FX This study is supported by NIH RO1 grants DE18214, DE18538, and N545681.
The authors claim no conflict of interest.
NR 28
TC 12
Z9 13
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD MAR 10
PY 2011
VL 1378
BP 66
EP 71
DI 10.1016/j.brainres.2011.01.006
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 739PN
UT WOS:000288730300007
PM 21223950
ER
PT J
AU Groom, JR
Luster, AD
AF Groom, Joanna R.
Luster, Andrew D.
TI CXCR3 in T cell function
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Review
DE Chemokines; Chemokine receptors; T cell trafficking
ID CHEMOKINE RECEPTOR CXCR3; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
GAMMA-INDUCIBLE PROTEIN-10; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
CENTRAL-NERVOUS-SYSTEM; CHRONIC HEPATITIS-C; CARDIAC
ALLOGRAFT-REJECTION; MURINE CEREBRAL MALARIA; VIRUS TYPE-2 INFECTION;
IFN-GAMMA
AB CXCR3 is a chemokine receptor that is highly expressed on effector T cells and plays an important role in T cell trafficking and function. CXCR3 is rapidly induced on naive cells following activation and preferentially remains highly expressed on Th1-type CD4(+) T cells and effector CD8(+) T cells. CXCR3 is activated by three interferon-inducible ligands CXCL9 (MIG), CXCL10 (IP-10) and CXCL11 (I-TAC). Early studies demonstrated a role for CXCR3 in the trafficking of Th1 and CD8 T cells to peripheral sites of Th1-type inflammation and the establishment of a Thl amplification loop mediated by IFN gamma and the IFN gamma-inducible CXCR3 ligands. More recent studies have also suggested that CXCR3 plays a role in the migration of T cells in the microenvironment of the peripheral tissue and lymphoid compartment, facilitating the interaction of T cells with antigen presenting cells leading to the generation of effector and memory cells. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Groom, Joanna R.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA.
RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA.
EM aluster@mgh.harvard.edu
FU Australian Government National Health; Medical Research Counsel and
Overseas Biomedical Based Fellowship; NIH [CA69212]
FX JRG was supported by Australian Government National Health and Medical
Research Counsel and Overseas Biomedical Based Fellowship and ADL was
supported by NIH grant CA69212.
NR 166
TC 160
Z9 166
U1 7
U2 23
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD MAR 10
PY 2011
VL 317
IS 5
SI SI
BP 620
EP 631
DI 10.1016/j.yexcr.2010.12.017
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 735KU
UT WOS:000288414000008
PM 21376175
ER
PT J
AU Kumar, V
Ogilvy, CS
AF Kumar, Vishesh
Ogilvy, Christopher S.
TI Giant Intracranial Aneurysm
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Kumar, Vishesh] N Shore Med Ctr, Salem, MA USA.
[Ogilvy, Christopher S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Kumar, V (reprint author), N Shore Med Ctr, Salem, MA USA.
EM vkumar3@partners.org
NR 0
TC 2
Z9 2
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 10
PY 2011
VL 364
IS 10
BP 956
EP 956
DI 10.1056/NEJMicm1008509
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 732FL
UT WOS:000288170300012
PM 21388313
ER
PT J
AU Pallais, JC
Mackool, BT
Pitman, MB
AF Pallais, J. Carl
Mackool, Bonnie T.
Pitman, Martha Bishop
TI Case 7-2011: A 52-Year-Old Man with Upper Respiratory Symptoms and Low
Oxygen Saturation Levels
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GLUTEN-FREE DIET; DERMATITIS-HERPETIFORMIS; CELIAC-DISEASE;
DIABETIC-PATIENT; PULSE OXIMETRY; BLOOD-GLUCOSE; A1C ASSAY;
METHEMOGLOBINEMIA; DAPSONE; DIAGNOSIS
C1 [Pallais, J. Carl] Massachusetts Gen Hosp, Dept Med, Div Endocrinol, Boston, MA 02114 USA.
[Mackool, Bonnie T.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Pitman, Martha Bishop] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Mackool, Bonnie T.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Pallais, J. Carl] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Pitman, Martha Bishop] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Pallais, JC (reprint author), Massachusetts Gen Hosp, Dept Med, Div Endocrinol, Boston, MA 02114 USA.
NR 58
TC 10
Z9 10
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 10
PY 2011
VL 364
IS 10
BP 957
EP 966
DI 10.1056/NEJMcpc1013923
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 732FL
UT WOS:000288170300014
PM 21388314
ER
PT J
AU Liu, QS
Wang, JH
Kang, SA
Thoreen, CC
Hur, W
Ahmed, T
Sabatini, DM
Gray, NS
AF Liu, Qingsong
Wang, Jinhua
Kang, Seong A.
Thoreen, Carson C.
Hur, Wooyoung
Ahmed, Tausif
Sabatini, David M.
Gray, Nathanael S.
TI Discovery of
9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)-phenyl)benzo[h][1,6]napht
hyridin-2(1H)-one (Torin2) as a Potent, Selective, and Orally Available
Mammalian Target of Raparnycin (mTOR) Inhibitor for Treatment of Cancer
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID ANTITUMOR-ACTIVITY; RAPAMYCIN MTOR; THERAPY
AB The mTOR mediated PI3K/AKT/mTOR signal transduction pathway has been demonstrated to play a key role in a broad spectrum of cancers. Starting from the mTOR selective inhibitor 1 (Torin1), a focused medicinal chemistry effort led to the discovery of an improved mTOR inhibitor 3 (Torin2), which possesses an EC(50) of 0.25 nM for inhibiting cellular mTOR activity. Compound 3 exhibited 800-fold selectivity over PI3K (EC(50): 200 nM) and over 100-fold binding selectivity relative to 440 other protein kinases. Compound 3 has significantly improved bioavailability (54%), metabolic stability, and plasma exposure relative to compound 1.
C1 [Liu, Qingsong; Wang, Jinhua; Thoreen, Carson C.; Hur, Wooyoung; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Liu, Qingsong; Wang, Jinhua; Thoreen, Carson C.; Hur, Wooyoung; Gray, Nathanael S.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA.
[Kang, Seong A.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA.
[Ahmed, Tausif] Sai Advantium Pharma Ltd, Hyderabad 500033, Andhra Pradesh, India.
[Sabatini, David M.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
[Sabatini, David M.] MIT, Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA.
RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM Nathanael_gray@dfci.harvard.edu
FU NIH [GM079575-03]
FX We thank Life Technologies Corporation, SelectScreen Kinase Profiling
Service for performing enzymatic biochemical kinase profiling, and Ambit
Bioscience for performing KinomeScan profiling. We also want to thank
Sai Advantium Pharma Ltd. (India) for the pharmacokinetic studies and
Michael Cameron for performing in vitro microsome stability studies.
This work was partially supported by NIH Grant GM079575-03.
NR 24
TC 81
Z9 84
U1 4
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD MAR 10
PY 2011
VL 54
IS 5
BP 1473
EP 1480
DI 10.1021/jm101520v
PG 8
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 727WJ
UT WOS:000287833300033
PM 21322566
ER
PT J
AU Amin, SB
Shah, PK
Yan, AM
Adamia, S
Minvielle, S
Avet-Loiseau, H
Munshi, NC
Li, C
AF Amin, Samir B.
Shah, Parantu K.
Yan, Aimin
Adamia, Sophia
Minvielle, Stephane
Avet-Loiseau, Herve
Munshi, Nikhil C.
Li, Cheng
TI The dChip survival analysis module for microarray data
SO BMC BIOINFORMATICS
LA English
DT Article
ID COPY-NUMBER ALTERATIONS; GENE-EXPRESSION; BREAST-CANCER; MICRORNA
EXPRESSION; MULTIPLE-MYELOMA; PREDICTION; SIGNATURE; ARRAYS
AB Background: Genome-wide expression signatures are emerging as potential marker for overall survival and disease recurrence risk as evidenced by recent commercialization of gene expression based biomarkers in breast cancer. Similar predictions have recently been carried out using genome-wide copy number alterations and microRNAs. Existing software packages for microarray data analysis provide functions to define expression-based survival gene signatures. However, there is no software that can perform survival analysis using SNP array data or draw survival curves interactively for expression-based sample clusters.
Results: We have developed the survival analysis module in the dChip software that performs survival analysis across the genome for gene expression and copy number microarray data. Built on the current dChip software's microarray analysis functions such as chromosome display and clustering, the new survival functions include interactive exploring of Kaplan-Meier (K-M) plots using expression or copy number data, computing survival p-values from the log-rank test and Cox models, and using permutation to identify significant chromosome regions associated with survival.
Conclusions: The dChip survival module provides user-friendly way to perform survival analysis and visualize the results in the context of genes and cytobands. It requires no coding expertise and only minimal learning curve for thousands of existing dChip users. The implementation in Visual C++ also enables fast computation. The software and demonstration data are freely available at http://dchip-surv.chenglilab.org.
C1 [Amin, Samir B.; Shah, Parantu K.; Yan, Aimin; Li, Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Amin, Samir B.; Shah, Parantu K.; Yan, Aimin; Li, Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Amin, Samir B.; Adamia, Sophia; Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Minvielle, Stephane; Avet-Loiseau, Herve] Univ Hosp, Dept Hematol, Nantes, France.
[Minvielle, Stephane; Avet-Loiseau, Herve] INSERM, Ctr Rech Cancerol, U892, Nantes, France.
[Munshi, Nikhil C.] Vet Adm Boston Healthcare Syst, W Roxbury, MA 02132 USA.
[Munshi, Nikhil C.] Harvard Univ, Sch Med, W Roxbury, MA 02132 USA.
RP Li, C (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA.
EM lch3000@gmail.com
RI Minvielle, Stephane/K-8251-2015;
OI Amin, Samir/0000-0002-3207-9505
FU NIH [1R01GM077122]; Claudia Adams Barr Program in Innovative Basic
Cancer Research
FX We thank Cheng Li Lab members for constructive discussion. This work has
been supported by NIH grant 1R01GM077122. P. K. S. has been supported by
the Claudia Adams Barr Program in Innovative Basic Cancer Research.
NR 20
TC 6
Z9 6
U1 0
U2 2
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 9
PY 2011
VL 12
AR 72
DI 10.1186/1471-2105-12-72
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 742ZH
UT WOS:000288983600001
PM 21388547
ER
PT J
AU Meyer-Luehmann, M
Mora, JR
Mielke, M
Spires-Jones, TL
de Calignon, A
von Andrian, UH
Hyman, BT
AF Meyer-Luehmann, Melanie
Mora, J. Rodrigo
Mielke, Matthew
Spires-Jones, Tara L.
de Calignon, Alix
von Andrian, Ulrich H.
Hyman, Bradley T.
TI T cell mediated cerebral hemorrhages and microhemorrhages during passive
A beta immunization in APPPS1 transgenic mice
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE;
MOUSE MODEL; COGNITIVE DECLINE; MEMORY DEFICITS; IN-VIVO; PEPTIDE;
PLAQUES; NEUROPATHOLOGY
AB Background: Immunization against amyloid-beta (A beta), the peptide that accumulates in the form of senile plaques and in the cerebrovasculature in Alzheimer's disease (AD), causes a dramatic immune response that prevents plaque formation and clears accumulated A beta in transgenic mice. In a clinical trial of A beta immunization, some patients developed meningoencephalitis and hemorrhages. Neuropathological investigations of patients who died after the trial showed clearance of amyloid pathology, but also a powerful immune response involving activated T cells probably underlying the negative effects of the immunization.
Results: To define the impact of T cells on this inflammatory response we used passive immunization and adoptive transfer to separate the effect of IgG and T cell mediated effects on microhemorrhage in APPPS1 transgenic mice. Neither anti A beta IgG nor adoptively transferred T cells, alone, led to increased cerebrovascular damage. However, the combination of adoptively transferred T cells and passive immunization led to massive cerebrovascular bleeding that ranged from multiple microhemorrhages in the parenchyma to large hematomas.
Conclusions: Our results indicate that vaccination can lead to A beta and T cell induced cerebral micro-hemorrhages and acute hematomas, which are greatly exacerbated by T cell mediated activity.
C1 [Meyer-Luehmann, Melanie; Mielke, Matthew; Spires-Jones, Tara L.; de Calignon, Alix; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Med Sch,Dept Neurol,Alzheimers Dis Res Lab, Charlestown, MA 02129 USA.
[Meyer-Luehmann, Melanie] German Ctr Neurodegenerat Dis DZNE, D-80336 Munich, Germany.
[Meyer-Luehmann, Melanie] Univ Munich, Adolf Butenandt Inst, D-80336 Munich, Germany.
[Mora, J. Rodrigo; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Mora, J. Rodrigo; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Mora, J. Rodrigo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Med Sch,Dept Neurol,Alzheimers Dis Res Lab, Charlestown, MA 02129 USA.
EM bhyman@partners.org
RI von Andrian, Ulrich/A-5775-2008
FU NIH [AG08487, K99 AG033670-01A1]; Alzheimer's Association [EB00768];
Dana Foundation
FX This work was supported by NIH Grant AG08487, K99 AG033670-01A1 and the
Alzheimer's Association Pioneer Award EB00768 and the Dana Foundation.
NR 41
TC 11
Z9 11
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD MAR 9
PY 2011
VL 6
AR 22
DI 10.1186/1750-1326-6-22
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 742SS
UT WOS:000288965400001
PM 21388539
ER
PT J
AU Nelissen, K
Borra, E
Gerbella, M
Rozzi, S
Luppino, G
Vanduffel, W
Rizzolatti, G
Orban, GA
AF Nelissen, Koen
Borra, Elena
Gerbella, Marzio
Rozzi, Stefano
Luppino, Giuseppe
Vanduffel, Wim
Rizzolatti, Giacomo
Orban, Guy A.
TI Action Observation Circuits in the Macaque Monkey Cortex
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SUPERIOR TEMPORAL SULCUS; LATERAL INTRAPARIETAL AREA; CORTICAL
CONNECTIONS; PREMOTOR CORTEX; BIOLOGICAL MOTION; RETINOTOPIC
ORGANIZATION; FUNCTIONAL-ORGANIZATION; NEURAL REPRESENTATION;
POLYSENSORY AREA; VENTRAL PREMOTOR
AB In both monkeys and humans, the observation of actions performed by others activates cortical motor areas. An unresolved question concerns the pathways through which motor areas receive visual information describing motor acts. Using functional magnetic resonance imaging (fMRI), we mapped the macaque brain regions activated during the observation of grasping actions, focusing on the superior temporal sulcus region (STS) and the posterior parietal lobe. Monkeys viewed either videos with only the grasping hand visible or videos with the whole actor visible. Observation of both types of grasping videos activated elongated regions in the depths of both lower and upper banks of STS, as well as parietal areas PFG and anterior intraparietal (AIP). The correlation of fMRI data with connectional data showed that visual action information, encoded in the STS, is forwarded to ventral premotor cortex (F5) along two distinct functional routes. One route connects the upper bank of the STS with area PFG, which projects, in turn, to the premotor area F5c. The other connects the anterior part of the lower bank of the STS with premotor areas F5a/p via AIP. Whereas the first functional route emphasizes the agent and may relay visual information to the parieto-frontal mirror circuit involved in understanding the agent's intentions, the second route emphasizes the object of the action and may aid in understanding motor acts with respect to their immediate goal.
C1 [Nelissen, Koen; Vanduffel, Wim; Orban, Guy A.] Katholieke Univ Leuven, Sch Med, Neuro & Psychofysiol Lab, B-3000 Louvain, Belgium.
[Nelissen, Koen; Vanduffel, Wim] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Borra, Elena; Gerbella, Marzio; Rozzi, Stefano; Luppino, Giuseppe; Rizzolatti, Giacomo] Univ Parma, Dept Neurosci, I-43100 Parma, Italy.
[Rizzolatti, Giacomo] Italian Inst Technol, Brain Ctr Motor & Social Cognit, I-43100 Parma, Italy.
RP Nelissen, K (reprint author), Katholieke Univ Leuven, Sch Med, Neuro & Psychofysiol Lab, Herestr 49,Bus 1021, B-3000 Louvain, Belgium.
EM koen.nelissen@med.kuleuven.be
OI gerbella, marzio/0000-0002-1204-3484; Rozzi, Stefano/0000-0002-6147-1530
FU Fonds voor Wetenschappelijk Onderzoek (FWO) [G151.04, G.0.593.09];
Excellentie Financiering Katholieke Universiteit Leuven [EF 05/14];
Interuniversity Attraction Pole Grant [6/29]; National Institutes of
Health [R21 NS064432-01]; Ministero dell' Universita e della Ricerca
(MUR) [PRIN 2006052343-002]; Agenzia Spaziale Italiana; region Flanders
FX This work was supported by Fonds voor Wetenschappelijk Onderzoek (FWO)
Grant G151.04 (G.A.O.), Excellentie Financiering Katholieke Universiteit
Leuven Grant EF 05/14 (G.A.O.), Interuniversity Attraction Pole Grant
6/29 (G.A.O.); FWO Grant G.0.593.09 and National Institutes of Health
Grant R21 NS064432-01 (W. V., K.N.); Ministero dell' Universita e della
Ricerca (MUR) Grant PRIN 2006052343-002 (G. L.); and grants from Agenzia
Spaziale Italiana and MUR (G. R.). The 3T scanner was purchased with a
"Zware Apparatuur" 2004 grant from the region Flanders. Laboratoire
Guerbet (Roissy, France) provided the contrast agent Sinerem. K.N. is a
postdoctoral research fellow of the FWO. We thank A. Coeman, W. Depuydt,
M. De Paep, C. Fransen, P. Kayenbergh, G. Meulemans, R. Peeters, S.
Verstraeten, and Dr. H. Kolster for technical assistance.
NR 58
TC 87
Z9 87
U1 3
U2 20
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 9
PY 2011
VL 31
IS 10
BP 3743
EP 3756
DI 10.1523/JNEUROSCI.4803-10.2011
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 732CJ
UT WOS:000288160500024
PM 21389229
ER
PT J
AU Moulton, EA
Elman, I
Pendse, G
Schmahmann, J
Becerra, L
Borsook, D
AF Moulton, Eric A.
Elman, Igor
Pendse, Gautam
Schmahmann, Jeremy
Becerra, Lino
Borsook, David
TI Aversion-Related Circuitry in the Cerebellum: Responses to Noxious Heat
and Unpleasant Images
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID COGNITIVE-AFFECTIVE SYNDROME; HUMAN BRAIN; PAIN; INVOLVEMENT; EMOTION;
ACTIVATION; LESIONS; HUMANS; METAANALYSIS; ANXIETY
AB The cerebellum is reliably activated during both acute and chronic pain conditions, but it is unclear whether the response to aversive painful stimuli can be generalized to other aversive stimuli. We hypothesized that cerebellar activation during pain reflects higher-level encoding of aversive stimuli. We used functional magnetic resonance imaging (fMRI) to compare cerebellar responses in 11 healthy volunteers to noxious heat (46 degrees C) applied to the hand and to the passive viewing of images selected from the International Affective Picture System. Aversive stimuli in the form of noxious heat and unpleasant pictures (unpleasant vs neutral) activated overlapping areas in the posterior cerebellum, specifically in hemispheric lobule VI, Crus I, and VIIb. Pleasant pictures (pleasant vs neutral) did not share the same pattern of activation as observed with the aversive stimuli. Cerebellar areas that showed functional overlap with both heat pain and unpleasant picture viewing were significantly inversely correlated with fMRI signals measured in limbic system structures, including the anterior hypothalamus, subgenual anterior cingulate cortex, and the parahippocampal gyrus. Heat-specific functional connectivity was detected in many regions including primary motor cortex, secondary somatosensory cortex, anterior insula, and the periaqueductal gray. The overlap between cerebellar lobuli reactive to noxious heat and passive viewing of unpleasant images suggest that the cerebellum may contain specific regions involved in encoding generalized aversive processing. The separate cortical networks suggest that noxious heat-evoked responses in the cerebellum can be divided into sensorimotor and emotional networks.
C1 [Moulton, Eric A.; Pendse, Gautam; Becerra, Lino; Borsook, David] Harvard Univ, McLean Hosp, Sch Med, PAIN Grp, Belmont, MA 02478 USA.
[Elman, Igor] Harvard Univ, McLean Hosp, Sch Med, Clin Psychopathol Lab, Belmont, MA 02478 USA.
[Schmahmann, Jeremy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ataxia Unit,Cognit Behav Neurol Unit,Dept Neurol, Boston, MA 02114 USA.
RP Moulton, EA (reprint author), Harvard Univ, McLean Hosp, Sch Med, PAIN Grp, 115 Mill St, Belmont, MA 02478 USA.
EM emoulton@mclean.harvard.edu
FU National Institutes of Health (National Institute on Drug Abuse)
[K01DA024289, R01DA017959]; National Institutes of Health (National
Institute of Neurological Disorders and Stroke) [K24NS064050];
Birmingham and MINDlink Foundations
FX This work was supported by the National Institutes of Health (National
Institute on Drug Abuse Grant K01DA024289 to E.A.M. and Grant
R01DA017959 to I.E.; and National Institute of Neurological Disorders
and Stroke Grant K24NS064050 to D.B.), and the Birmingham and MINDlink
Foundations (J.S.). We acknowledge Susie Morris, Sadie Cole, and Won Chi
for their assistance in subject recruitment and data collection.
NR 73
TC 64
Z9 64
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 9
PY 2011
VL 31
IS 10
BP 3795
EP 3804
DI 10.1523/JNEUROSCI.6709-10.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 732CJ
UT WOS:000288160500029
PM 21389234
ER
PT J
AU Roseman, M
Milette, K
Bero, LA
Coyne, JC
Lexchin, J
Turner, EH
Thombs, BD
AF Roseman, Michelle
Milette, Katherine
Bero, Lisa A.
Coyne, James C.
Lexchin, Joel
Turner, Erick H.
Thombs, Brett D.
TI Reporting of Conflicts of Interest in Meta-analyses of Trials of
Pharmacological Treatments
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID CELL LUNG-CANCER; PHARMACEUTICAL-INDUSTRY; RANDOMIZED-TRIALS; DRUG
TRIALS; CARDIOVASCULAR-DISEASE; COMPETING INTERESTS; DIABETES-MELLITUS;
CLINICAL-TRIALS; FINANCIAL TIES; RISK
AB Context Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required to report COIs disclosed in original reports of included RCTs.
Objective To investigate whether meta-analyses of pharmacological treatments published in high-impact biomedical journals report COIs disclosed in included RCTs.
Data Sources and Study Selection We selected the 3 most recent meta-analyses of patented pharmacological treatments published January 2009 through October 2009 in each general medicine journal with an impact factor of at least 10; in high-impact journals in each of the 5 specialty medicine areas with the greatest 2008 global therapeutic sales (oncology, cardiology, respiratory medicine, endocrinology, and gastroenterology); and in the Cochrane Database of Systematic Reviews.
Data Extraction Two investigators independently extracted data on disclosed study funding, author-industry financial ties, and author employment from each meta-analysis, from RCTs included in each meta-analysis, and on whether meta-analyses reported disclosed COIs of included RCTs.
Results Of 29 meta-analyses reviewed, which included 509 RCTs, only 2 meta-analyses (7%) reported RCT funding sources; and 0 reported RCT author-industry ties or employment by the pharmaceutical industry. Of 318 meta-analyzed RCTs that reported funding sources, 219 (69%) were industry funded; and 91 of 132 (69%) that reported author financial disclosures had 1 or more authors with pharmaceutical industry financial ties. In 7 of the 29 meta-analyses reviewed, 100% of included RCTs had at least 1 form of disclosed COI (pharmaceutical industry funding, author-industry financial ties, or employment), yet only 1 of these 7 meta-analyses reported RCT funding sources, and 0 reported RCT author-industry ties or employment.
Conclusion Among a group of meta-analyses of pharmacological treatments published in high-impact biomedical journals, information concerning primary study funding and author COIs for the included RCTs were only rarely reported. JAMA. 2011;305(10):1008-1017 www.jama.com
C1 [Roseman, Michelle; Milette, Katherine; Thombs, Brett D.] Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E4, Canada.
[Roseman, Michelle; Milette, Katherine; Thombs, Brett D.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Dept Biostat, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Dept Occupat Hlth, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Bero, Lisa A.] Univ Calif San Francisco, Sch Pharm, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Bero, Lisa A.] Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA.
[Coyne, James C.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Coyne, James C.] Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci, Hlth Psychol Sect, NL-9700 AB Groningen, Netherlands.
[Lexchin, Joel] Univ Toronto, Univ Hlth Network, Emergency Dept, Toronto, ON, Canada.
[Lexchin, Joel] Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada.
[Lexchin, Joel] York Univ, Sch Hlth Policy & Management, N York, ON M3J 1P3, Canada.
[Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
[Turner, Erick H.] Portland VA Med Ctr, Portland, OR USA.
RP Thombs, BD (reprint author), Jewish Gen Hosp, Lady Davis Inst Med Res, 4333 Cote Ste Catherine Rd, Montreal, PQ H3T 1E4, Canada.
EM brett.thombs@mcgill.ca
OI Turner, Erick/0000-0002-3522-3357
FU Canadian Institutes of Health Research; McGill University; Canadian
Institutes of Health Research Strategic Training Initiative [SKI 83345];
Fonds de la Recherche en Sante Quebec; Etablissement de Jeunes
Chercheurs
FX Ms Roseman and Ms Milette were supported by Frederick Banting and
Charles Best Canadian Graduate Scholarships-Master's Awards from the
Canadian Institutes of Health Research. Ms Roseman was also supported by
a McGill University Provost's Graduate Fellowship and a McGill
University Principal's Graduate Fellowship. Ms. Milette was also
supported by a Canadian Scleroderma Research Group Studentship (Canadian
Institutes of Health Research Strategic Training Initiative in Health
Research Grant, SKI 83345) and a McGill University Provost's Graduate
Fellowship. Dr Thombs was supported by a New Investigator Award from the
Canadian Institutes of Health Research and an Etablissement de Jeunes
Chercheurs award from the Fonds de la Recherche en Sante Quebec. Funds
from the Etablissement de Jeunes Chercheurs award supported this
project.
NR 69
TC 68
Z9 69
U1 1
U2 10
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 9
PY 2011
VL 305
IS 10
BP 1008
EP 1017
DI 10.1001/jama.2011.257
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 731SM
UT WOS:000288129600020
PM 21386079
ER
PT J
AU Li, SQ
Moffett, HF
Lu, J
Werner, L
Zhang, H
Ritz, J
Neuberg, D
Wucherpfennig, KW
Brown, JR
Novina, CD
AF Li, Shuqiang
Moffett, Howell F.
Lu, Jun
Werner, Lillian
Zhang, Hao
Ritz, Jerome
Neuberg, Donna
Wucherpfennig, Kai W.
Brown, Jennifer R.
Novina, Carl D.
TI MicroRNA Expression Profiling Identifies Activated B Cell Status in
Chronic Lymphocytic Leukemia Cells
SO PLOS ONE
LA English
DT Article
ID CLL PATIENTS; DISEASE PROGRESSION; MIRNA EXPRESSION; DOWN-REGULATION;
PHENOTYPE; APOPTOSIS; LYMPHOMA; REVEALS; DIFFERENTIATION; PROLIFERATION
AB Chronic lymphocytic leukemia (CLL) is thought to be a disease of resting lymphocytes. However, recent data suggest that CLL cells may more closely resemble activated B cells. Using microRNA (miRNA) expression profiling of highly-enriched CLL cells from 38 patients and 9 untransformed B cells from normal donors before acute CpG activation and 5 matched B cells after acute CpG activation, we demonstrate an activated B cell status for CLL. Gene set enrichment analysis (GSEA) identified statistically-significant similarities in miRNA expression between activated B cells and CLL cells including upregulation of miR-34a, miR-155, and miR-342-3p and downregulation of miR-103, miR-181a and miR-181b. Additionally, decreased levels of two CLL signature miRNAs miR-29c and miR-223 are associated with ZAP70(+) and IgVH unmutated status and with shorter time to first therapy. These data indicate an activated B cell status for CLL cells and suggest that the direction of change of individual miRNAs may predict clinical course in CLL.
C1 [Li, Shuqiang; Moffett, Howell F.; Wucherpfennig, Kai W.; Novina, Carl D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Moffett, Howell F.] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA.
[Lu, Jun; Zhang, Hao; Novina, Carl D.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA.
[Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Ritz, Jerome; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ritz, Jerome; Brown, Jennifer R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Novina, Carl D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Li, SQ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM carl_novina@dfci.harvard.edu
OI Ritz, Jerome/0000-0001-5526-4669
FU NIH [PO1-CA081534, K23 CA115682]; NRSA [DFCI/NCI T32 CA70083]; Carreras
International Leukemia; Doris Duke Clinical Scientist Development Awards
FX The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The funders of
the study include NIH grant (PO1-CA081534), NIH grant (K23 CA115682),
NRSA Fellowship (DFCI/NCI T32 CA70083), Carreras International Leukemia
and Doris Duke Clinical Scientist Development Awards.
NR 43
TC 36
Z9 40
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 8
PY 2011
VL 6
IS 3
AR e16956
DI 10.1371/journal.pone.0016956
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732FI
UT WOS:000288170000012
PM 21408091
ER
PT J
AU Sasaki, AT
Carracedo, A
Locasale, JW
Anastasiou, D
Takeuchi, K
Kahoud, ER
Haviv, S
Asara, JM
Pandolfi, PP
Cantley, LC
AF Sasaki, Atsuo T.
Carracedo, Arkaitz
Locasale, Jason W.
Anastasiou, Dimitrios
Takeuchi, Koh
Kahoud, Emily Rose
Haviv, Sasson
Asara, John M.
Pandolfi, Pier Paolo
Cantley, Lewis C.
TI Ubiquitination of K-Ras Enhances Activation and Facilitates Binding to
Select Downstream Effectors
SO SCIENCE SIGNALING
LA English
DT Article
ID HUMAN COLORECTAL-CANCER; SIGNAL-TRANSDUCTION; COSTELLO-SYNDROME; KRAS
MUTATIONS; POINT MUTATION; H-RAS; PROTEINS; REGION; SWITCH; CODON-146
AB The guanosine triphosphate (GTP)-loaded form of the guanosine triphosphatase (GTPase) Ras initiates multiple signaling pathways by binding to various effectors, such as the kinase Raf and phosphatidylinositol 3-kinase (PI3K). Ras activity is increased by guanine nucleotide exchange factors that stimulate guanosine diphosphate release and GTP loading and is inhibited by GTPase-activating proteins that stimulate GTP hydrolysis. KRAS is the most frequently mutated RAS gene in cancer. Here, we report that monoubiquitination of lysine-147 in the guanine nucleotide-binding motif of wild-type K-Ras could lead to enhanced GTP loading. Furthermore, ubiquitination increased the binding of the oncogenic Gly12Val mutant of K-Ras to the downstream effectors PI3K and Raf. Thus, monoubiquitination could enhance GTP loading on K-Ras and increase its affinity for specific downstream effectors, providing a previously unidentified mechanism for Ras activation. Downloaded from stke. sciencemag. org on March 8, 2011
C1 [Sasaki, Atsuo T.; Locasale, Jason W.; Anastasiou, Dimitrios; Kahoud, Emily Rose; Haviv, Sasson; Asara, John M.; Cantley, Lewis C.] Harvard Univ, Sch Med, Div Signal Transduct, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Sasaki, Atsuo T.; Locasale, Jason W.; Anastasiou, Dimitrios; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Carracedo, Arkaitz; Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Beth Israel Deaconess Canc Ctr,Sch Med, Div Genet,Dept Med & Pathol,Canc Genet Program, Boston, MA 02215 USA.
[Carracedo, Arkaitz] Technol Pk Bizkaia, CIC bioGUNE, Derio 48160, Bizkaia, Spain.
[Takeuchi, Koh] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Takeuchi, Koh] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan.
[Asara, John M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Div Signal Transduct, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
EM lcantley@hms.harvard.edu
RI Carracedo, Arkaitz/F-7029-2011; cancer, biogune/H-7276-2012; Cantley,
Lewis/D-1800-2014;
OI Carracedo, Arkaitz/0000-0001-5957-1260; Cantley,
Lewis/0000-0002-1298-7653; Locasale, Jason/0000-0002-7766-3502
FU NCI NIH HHS [1P01CA120964-01A1, 5P01CA117969, 5P30CA006516-43, P01
CA089021, P01 CA117969, P01 CA120964, P01CA089021, P30 CA006516]; NIGMS
NIH HHS [R01 GM041890, R01 GM056203, R01-GM41890, R37 GM041890]
NR 31
TC 54
Z9 55
U1 2
U2 14
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD MAR 8
PY 2011
VL 4
IS 163
AR ra13
DI 10.1126/scisignal.2001518
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 731PS
UT WOS:000288122300001
PM 21386094
ER
PT J
AU Fradley, MG
Picard, MH
AF Fradley, Michael G.
Picard, Michael H.
TI Rupture of the Posteromedial Papillary Muscle Leading to Partial Flail
of the Anterior Mitral Leaflet
SO CIRCULATION
LA English
DT Editorial Material
ID ACUTE MYOCARDIAL-INFARCTION
C1 [Fradley, Michael G.; Picard, Michael H.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
RP Fradley, MG (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
EM mfradley@partners.org
OI Picard, Michael/0000-0002-9264-3243
NR 4
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAR 8
PY 2011
VL 123
IS 9
BP 1044
EP 1045
DI 10.1161/CIRCULATIONAHA.110.984724
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 731OL
UT WOS:000288118900019
PM 21382906
ER
PT J
AU Bhatt, DL
AF Bhatt, Deepak L.
TI Glycoprotein IIb/IIIa Inhibitors Do They Still Have a Role?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE adverse outcomes; glycoprotein IIb/IIIa inhibitors; meta-analysis;
myocardial infarction; PCI
ID PERCUTANEOUS CORONARY INTERVENTION; ACUITY TRIAL; MYOCARDIAL-INFARCTION;
RANDOMIZED-TRIAL; PCI; BIVALIRUDIN; MORTALITY; RISK; STRATEGIES;
ELEVATION
C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, Dept Cardiol, VA Boston Healthcare Syst, Boston, MA 02132 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02132 USA.
RP Bhatt, DL (reprint author), Brigham & Womens Hosp, Dept Cardiol, VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA.
EM DLBHATTMD@post.harvard.edu
NR 20
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 8
PY 2011
VL 57
IS 10
BP 1200
EP 1201
DI 10.1016/j.jacc.2010.10.031
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 729PI
UT WOS:000287962500005
PM 21371636
ER
PT J
AU Sun, QA
Chen, XX
Ma, JH
Peng, HY
Wang, F
Zha, XJ
Wang, YN
Jing, YL
Yang, HW
Chen, RR
Chang, L
Zhang, Y
Goto, J
Onda, H
Chen, T
Wang, MR
Lu, YY
You, H
Kwiatkowski, D
Zhang, HB
AF Sun, Qian
Chen, Xinxin
Ma, Jianhui
Peng, Haiyong
Wang, Fang
Zha, Xiaojun
Wang, Yanan
Jing, Yanling
Yang, Hongwang
Chen, Rongrong
Chang, Long
Zhang, Yu
Goto, June
Onda, Hiroaki
Chen, Tong
Wang, Ming-Rong
Lu, Youyong
You, Han
Kwiatkowski, David
Zhang, Hongbing
TI Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme
type M2 is critical for aerobic glycolysis and tumor growth
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE PTEN; tuberous sclerosis 1; hexokinase II; lactate dehydrogenase-B;
glyceraldehyde 3-phosphate dehydrogenase
ID TUBEROUS SCLEROSIS COMPLEX; CELL-GROWTH; SIGNALING PATHWAYS;
RENAL-CARCINOMA; VEGF EXPRESSION; CANCER-CELLS; NULL-CELLS; MTOR; TSC2;
METABOLISM
AB Although aerobic glycolysis (the Warburg effect) is a hallmark of cancer, key questions, including when, how, and why cancer cells become highly glycolytic, remain less clear. For a largely unknown regulatory mechanism, a rate-limiting glycolytic enzyme pyruvate kinase M2 (PKM2) isoform is exclusively expressed in embryonic, proliferating, and tumor cells, and plays an essential role in tumor metabolism and growth. Because the receptor tyrosine kinase/PI3K/AKT/mammalian target of rapamycin (RTK/PI3K/AKT/mTOR) signaling cascade is a frequently altered pathway in cancer, we explored its potential role in cancer metabolism. We identified mTOR as a central activator of the Warburg effect by inducing PKM2 and other glycolytic enzymes under normoxic conditions. PKM2 level was augmented in mouse kidney tumors due to deficiency of tuberous sclerosis complex 2 and consequent mTOR activation, and was reduced in human cancer cells by mTOR suppression. mTOR up-regulation of PKM2 expression was through hypoxia-inducible factor 1 alpha (HIF1 alpha)-mediated transcription activation, and c-Myc-heterogeneous nuclear ribonucleoproteins (hnRNPs)-dependent regulation of PKM2 gene splicing. Disruption of PKM2 suppressed oncogenic mTOR-mediated tumorigenesis. Unlike normal cells, mTOR hyperactive cells were more sensitive to inhibition of mTOR or glycolysis. Dual suppression of mTOR and glycolysis synergistically blunted the proliferation and tumor development of mTOR hyperactive cells. Even though aerobic glycolysis is not required for breach of senescence for immortalization and transformation, the frequently deregulated mTOR signaling during multistep oncogenic processes could contribute to the development of the Warburg effect in many cancers. Components of the mTOR/HIF1 alpha/Myc-hnRNPs/PKM2 glycolysis signaling network could be targeted for the treatment of cancer caused by an aberrant RTK/PI3K/AKT/mTOR signaling pathway.
C1 [Sun, Qian; Chen, Xinxin; Peng, Haiyong; Wang, Fang; Zha, Xiaojun; Wang, Yanan; Jing, Yanling; Yang, Hongwang; Chen, Rongrong; Chang, Long; Zhang, Hongbing] Peking Union Med Coll, Inst Basic Med Sci, Dept Physiol & Pathophysiol, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China.
[Sun, Qian; Chen, Xinxin; Peng, Haiyong; Wang, Fang; Zha, Xiaojun; Wang, Yanan; Jing, Yanling; Yang, Hongwang; Chen, Rongrong; Chang, Long; Zhang, Hongbing] Peking Union Med Coll, Sch Basic Med, Beijing 100005, Peoples R China.
[Sun, Qian; Chen, Xinxin; Peng, Haiyong; Wang, Fang; Zha, Xiaojun; Wang, Yanan; Jing, Yanling; Yang, Hongwang; Chen, Rongrong; Chang, Long; Zhang, Hongbing] Chinese Acad Med Sci, Beijing 100005, Peoples R China.
[Ma, Jianhui; You, Han] Xia Men Univ, Sch Life Sci, Xiamen 361005, Peoples R China.
[Zhang, Yu; Wang, Ming-Rong] Chinese Acad Med Sci, Beijing 100021, Peoples R China.
[Zhang, Yu; Wang, Ming-Rong] Peking Union Med Coll, Canc Inst Hosp, State Key Lab Mol Oncol, Beijing 100021, Peoples R China.
[Goto, June; Kwiatkowski, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Goto, June; Kwiatkowski, David] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Translat Med, Boston, MA 02115 USA.
[Onda, Hiroaki] Jackson Lab, Mouse Genome Informat Team, Bar Harbor, ME 04609 USA.
[Chen, Tong] Ohio State Univ, Dept Internal Med, Div Med Oncol, Columbus, OH 43210 USA.
[Lu, Youyong] Peking Univ, Sch Oncol, Beijing Canc Hosp Inst, Mol Oncol Lab, Beijing 100142, Peoples R China.
RP Zhang, HB (reprint author), Peking Union Med Coll, Inst Basic Med Sci, Dept Physiol & Pathophysiol, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China.
EM hyou@xmu.edu.cn; hbzhang2006@gmail.com
RI Chen, Tong/E-2879-2011; Peng, Haiyong/S-8045-2016
FU National Natural Science Foundation of China [30788004]; National Basic
Research Program of China 973 Program [2009CB522202, 2009CB522203];
Ministry of Education of China [B08007]
FX This study was supported by National Natural Science Foundation of China
Grant 30788004, the National Basic Research Program of China 973 Program
Grants 2009CB522202 and 2009CB522203, and Ministry of Education of China
111 Project B08007.
NR 51
TC 207
Z9 220
U1 9
U2 61
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 8
PY 2011
VL 108
IS 10
BP 4129
EP 4134
DI 10.1073/pnas.1014769108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 731PA
UT WOS:000288120400059
PM 21325052
ER
PT J
AU Valm, AM
Welch, JLM
Rieken, CW
Hasegawa, Y
Sogin, ML
Oldenbourg, R
Dewhirst, FE
Borisy, GG
AF Valm, Alex M.
Welch, Jessica L. Mark
Rieken, Christopher W.
Hasegawa, Yuko
Sogin, Mitchell L.
Oldenbourg, Rudolf
Dewhirst, Floyd E.
Borisy, Gary G.
TI Systems-level analysis of microbial community organization through
combinatorial labeling and spectral imaging
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cell biology; fluorescence; microbial diversity; oral biofilm
ID TARGETED OLIGONUCLEOTIDE PROBES; HUMAN ORAL BACTERIA; DENTAL PLAQUE;
COAGGREGATION; BIOFILMS; IDENTIFICATION; COADHESION; FISH
AB Microbes in nature frequently function as members of complex multitaxon communities, but the structural organization of these communities at the micrometer level is poorly understood because of limitations in labeling and imaging technology. We report here a combinatorial labeling strategy coupled with spectral image acquisition and analysis that greatly expands the number of fluorescent signatures distinguishable in a single image. As an imaging proof of principle, we first demonstrated visualization of Escherichia coli labeled by fluorescence in situ hybridization (FISH) with 28 different binary combinations of eight fluorophores. As a biological proof of principle, we then applied this Combinatorial Labeling and Spectral Imaging FISH (CLASI-FISH) strategy using genus-and family-specific probes to visualize simultaneously and differentiate 15 different phylotypes in an artificial mixture of laboratory-grown microbes. We then illustrated the utility of our method for the structural analysis of a natural microbial community, namely, human dental plaque, a microbial biofilm. We demonstrate that 15 taxa in the plaque community can be imaged simultaneously and analyzed and that this community was dominated by early colonizers, including species of Streptococcus, Prevotella, Actinomyces, and Veillonella. Proximity analysis was used to determine the frequency of inter- and intrataxon cell-to-cell associations which revealed statistically significant intertaxon pairings. Cells of the genera Prevotella and Actinomyces showed the most interspecies associations, suggesting a central role for these genera in establishing and maintaining biofilm complexity. The results provide an initial systems-level structural analysis of biofilm organization.
C1 [Valm, Alex M.; Welch, Jessica L. Mark; Rieken, Christopher W.; Hasegawa, Yuko; Sogin, Mitchell L.; Oldenbourg, Rudolf; Borisy, Gary G.] Marine Biol Lab, Woods Hole, MA 02543 USA.
[Valm, Alex M.; Hasegawa, Yuko; Sogin, Mitchell L.; Oldenbourg, Rudolf] Brown Univ, Providence, RI 02912 USA.
[Dewhirst, Floyd E.] Forsyth Inst, Cambridge, MA 02142 USA.
[Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
RP Borisy, GG (reprint author), Marine Biol Lab, Woods Hole, MA 02543 USA.
EM gborisy@mbl.edu
OI Borisy, Gary/0000-0002-0266-8018
FU Alfred P. Sloan Foundation [2007-3-13]; National Institutes of Health,
National Institute of Dental and Craniofacial Research (NIDCR)
[1RC1-DE020630, 1F31-DE019576]
FX We are grateful to Louis M. Kerr for invaluable assistance with
microscopy. We thank Nikon Instruments and Carl Zeiss for gracious
instrumentation support. This work was supported by Grant 2007-3-13 from
the Alfred P. Sloan Foundation (to G.G.B.), National Institutes of
Health Grant 1RC1-DE020630 from the National Institute of Dental and
Craniofacial Research (NIDCR) (to G.G.B. and F.E.D.) and by National
Institutes of Health Fellowship 1F31-DE019576 from NIDCR (to A.M.V.).
NR 32
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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 8
PY 2011
VL 108
IS 10
BP 4152
EP 4157
DI 10.1073/pnas.1101134108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 731PA
UT WOS:000288120400063
PM 21325608
ER
PT J
AU Ahveninen, J
Hamalainen, M
Jaaskelainen, IP
Ahlfors, SP
Huang, S
Lin, FH
Raij, T
Sams, M
Vasios, CE
Belliveau, JW
AF Ahveninen, Jyrki
Haemaelaeinen, Matti
Jaaskelainen, Iiro P.
Ahlfors, Seppo P.
Huang, Samantha
Lin, Fa-Hsuan
Raij, Tommi
Sams, Mikko
Vasios, Christos E.
Belliveau, John W.
TI Attention-driven auditory cortex short-term plasticity helps segregate
relevant sounds from noise
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE processing negativity; cocktail party phenomenon; event-related
potentials; negative difference; auditory scene analysis
ID SURFACE-BASED ANALYSIS; SELECTIVE ATTENTION; CORTICAL SURFACE;
RECEPTIVE-FIELDS; HUMAN BRAIN; COORDINATE SYSTEM; SPATIAL ATTENTION;
TASK-DIFFICULTY; SINGLE NEURONS; FREQUENCY
AB How can we concentrate on relevant sounds in noisy environments? A "gain model" suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A "tuning model" suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMRI) while subjects attended to tones delivered to one ear and ignored opposite-ear inputs. The attended ear was switched every 30 s to quantify how quickly the effects evolve. To produce overlapping inputs, the tones were presented alone vs. during white-noise masking notch-filtered +/- 1/6 octaves around the tone center frequencies. Amplitude modulation (39 vs. 41 Hz in opposite ears) was applied for "frequency tagging" of attention effects on maskers. Noise masking reduced early (50-150 ms; N1) auditory responses to unattended tones. In support of the tuning model, selective attention canceled out this attenuating effect but did not modulate the gain of 50-150 ms activity to nonmasked tones or steady-state responses to the maskers themselves. These tuning effects originated at nonprimary auditory cortices, purportedly occupied by neurons that, without attention, have wider frequency tuning than +/- 1/6 octaves. The attentional tuning evolved rapidly, during the first few seconds after attention switching, and correlated with behavioral discrimination performance. In conclusion, a simple gain model alone cannot explain auditory selective attention. In nonprimary auditory cortices, attention-driven short-term plasticity retunes neurons to segregate relevant sounds from noise.
C1 [Ahveninen, Jyrki; Haemaelaeinen, Matti; Ahlfors, Seppo P.; Huang, Samantha; Lin, Fa-Hsuan; Raij, Tommi; Vasios, Christos E.; Belliveau, John W.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA.
[Haemaelaeinen, Matti; Ahlfors, Seppo P.; Belliveau, John W.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Jaaskelainen, Iiro P.; Sams, Mikko] Aalto Univ, Dept Biomed Engn & Computat Sci, Mind & Brain Lab, FI-00076 Espoo, Finland.
[Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 106, Taiwan.
RP Ahveninen, J (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA.
EM jyrki@nmr.mgh.harvard.edu
RI Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012; Hamalainen,
Matti/C-8507-2013; Lin, Fa-Hsuan/G-6988-2012; Ahlfors, Seppo/P-3644-2016
OI Jaaskelainen, Iiro/0000-0001-6001-6950; Lin,
Fa-Hsuan/0000-0002-9539-1731;
FU National Institutes of Health [R01MH083744, R21DC010060, R01HD040712,
R01NS037462, R01NS057500, R01NS048279, S10RR014798, P41RR14075];
National Center for Research Resources; Academy of Finland
FX We thank Deirdre Foxe, Natsuko Mori, and Dan Wakeman for their help.
This work was supported by National Institutes of Health Awards
R01MH083744, R21DC010060, R01HD040712, R01NS037462, R01NS057500,
R01NS048279, S10RR014798, and P41RR14075, the National Center for
Research Resources, and the Academy of Finland.
NR 52
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U1 0
U2 16
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 8
PY 2011
VL 108
IS 10
BP 4182
EP 4187
DI 10.1073/pnas.1016134108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 731PA
UT WOS:000288120400068
PM 21368107
ER
PT J
AU Keliher, EJ
Reiner, T
Turetsky, A
Hilderbrand, SA
Weissleder, R
AF Keliher, Edmund J.
Reiner, Thomas
Turetsky, Anna
Hilderbrand, Scott A.
Weissleder, Ralph
TI High-Yielding, Two-Step F-18 Labeling Strategy for F-18-PARP1 Inhibitors
SO CHEMMEDCHEM
LA English
DT Article
DE F-18 labeling; cycloadditions; PARP1; PET imaging; tetrazines
ID POSITRON-EMISSION-TOMOGRAPHY; FREE CLICK CHEMISTRY; POLY(ADP-RIBOSE)
POLYMERASE-1; INTEGRATED MICROFLUIDICS; KINASE INHIBITORS; LIVING CELLS;
CYCLOADDITION; CANCER; ATHEROSCLEROSIS; NANOPARTICLES
C1 [Keliher, Edmund J.; Reiner, Thomas; Turetsky, Anna; Hilderbrand, Scott A.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol Dept, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol Dept, 185 Cambridge St, Boston, MA 02114 USA.
EM rweissleder@mgh.harvard.edu
OI Reiner, Thomas/0000-0002-7819-5480
FU US National Institutes of Health (NIH) [CA86355, EB-010011]; NIGMS [T32
GM008313]; German National Academy of Sciences Leopoldina [LPDS 2009-24]
FX We thank Drs. Ralph Mazitschek and Neal Devaraj for helpful discussions.
This research was supported in part by the US National Institutes of
Health (NIH) (grants CA86355 and EB-010011). AT was supported by NIH
grant NIGMS T32 GM008313. TR was supported by a grant from the German
National Academy of Sciences Leopoldina (LPDS 2009-24).
NR 39
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U1 0
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD MAR 7
PY 2011
VL 6
IS 3
BP 424
EP 427
DI 10.1002/cmdc.201000426
PG 4
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 737WG
UT WOS:000288599600005
PM 21360818
ER
PT J
AU Chen, X
Tukachinsky, H
Huang, CH
Jao, C
Chu, YR
Tang, HY
Mueller, B
Schulman, S
Rapoport, TA
Salic, A
AF Chen, Xin
Tukachinsky, Hanna
Huang, Chih-Hsiang
Jao, Cindy
Chu, Yue-Ru
Tang, Hsiang-Yun
Mueller, Britta
Schulman, Sol
Rapoport, Tom A.
Salic, Adrian
TI Processing and turnover of the Hedgehog protein in the endoplasmic
reticulum
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID INTEGRAL MEMBRANE-PROTEINS; ER-ASSOCIATED DEGRADATION; UBIQUITIN LIGASE
COMPLEX; HMG-COA REDUCTASE; SONIC-HEDGEHOG; MISFOLDED GLYCOPROTEINS;
AUTOPROCESSING DOMAIN; QUALITY-CONTROL; DISLOCATION; CYTOSOL
AB T he Hedgehog (Hh) signaling pathway has important functions during metazoan development. The Hh ligand is generated from a precursor by self-cleavage, which requires a free cysteine in the C-terminal part of the protein and results in the production of the cholesterol-modified ligand and a C-terminal fragment. In this paper, we demonstrate that these reactions occur in the endoplasmic reticulum (ER). The catalytic cysteine needs to form a disulfide bridge with a conserved cysteine, which is subsequently reduced by protein disulfide isomerase. Generation of the C-terminal fragment is followed by its ER-associated degradation (ERAD), providing the first example of an endogenous luminal ERAD substrate that is constitutively degraded. This process requires the ubiquitin ligase Hrd1, its partner Sel1, the cytosolic adenosine triphosphatase p97, and degradation by the proteasome. Processing-defective mutants of Hh are degraded by the same ERAD components. Thus, processing of the Hh precursor competes with its rapid degradation, explaining the impaired Hh signaling of processing-defective mutants, such as those causing human holoprosencephaly.
C1 [Chen, Xin; Schulman, Sol; Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Chen, Xin; Tukachinsky, Hanna; Jao, Cindy; Salic, Adrian] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Mueller, Britta] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA.
[Chen, Xin; Huang, Chih-Hsiang; Chu, Yue-Ru; Tang, Hsiang-Yun] Natl Hlth Res Inst, Div Biotechnol & Pharmaceut Res, Miaoli 115, Taiwan.
RP Salic, A (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM asalic@hms.harvard.edu
RI Chen, Xin/D-2073-2010;
OI schulman, sol/0000-0002-5229-3592
FU American Heart Association; National Science Foundation; National
Institutes of Health [GM052586]; Howard Hughes Medical Institute;
National Research Program for Genomic Medicine; National Science
Council; National Health Research Institutes (Taiwan); Rita Allen
Foundation; Beckman Foundation
FX H. Tukachinsky and C. Jao are supported by predoctoral fellowships from
the American Heart Association and from the National Science Foundation,
respectively. T.A. Rapoport is supported by the National Institutes of
Health grant GM052586 and is a Howard Hughes Medical Institute
Investigator. X. Chen is supported by funds from the National Research
Program for Genomic Medicine, National Science Council, and National
Health Research Institutes (Taiwan). A. Salic acknowledges the support
from the Rita Allen Foundation and the Beckman Foundation.
NR 56
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U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD MAR 7
PY 2011
VL 192
IS 5
BP 825
EP 838
DI 10.1083/jcb.201008090
PG 14
WC Cell Biology
SC Cell Biology
GA 730XI
UT WOS:000288070300011
PM 21357747
ER
PT J
AU Ackerman, ME
Moldt, B
Wyatt, RT
Dugast, AS
McAndrew, E
Tsoukas, S
Jost, S
Berger, CT
Sciaranghella, G
Liu, QQ
Irvine, DJ
Burton, DR
Alter, G
AF Ackerman, Margaret E.
Moldt, Brian
Wyatt, Richard T.
Dugast, Anne-Sophie
McAndrew, Elizabeth
Tsoukas, Stephen
Jost, Stephanie
Berger, Christoph T.
Sciaranghella, Gaia
Liu, Qingquan
Irvine, Darrell J.
Burton, Dennis R.
Alter, Galit
TI A robust, high-throughput assay to determine the phagocytic activity of
clinical antibody samples
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Phagocytosis; Antibody; ADCC; Antibody-dependent phagocytosis;
Monocytes; Fc receptor; Effector function
ID FC-GAMMA-RI; HUMAN MONOCYTIC CELLS; MYCOBACTERIUM-TUBERCULOSIS; CYTOKINE
PRODUCTION; IMMUNOGLOBULIN-G; THP-1 CELLS; ENHANCING ANTIBODIES;
GENE-EXPRESSION; TUMOR-CELLS; LINE THP-1
AB Phagocytosis can be induced via the engagement of Fc gamma receptors by antibody-opsonized material. Furthermore, the efficiency of antibody-induced effector functions has been shown to be dramatically modulated by changes in antibody glycosylation. Because infection can modulate antibody glycans, which in turn modulate antibody functions, assays capable of determining the induction of effector functions rather than neutralization or titer provide a valuable opportunity to more fully characterize the quality of the adaptive immune response. Here we describe a robust and high-throughput flow cytometric assay to define the phagocytic activity of antigen-specific antibodies from clinical samples. This assay employs a monocytic cell line that expresses numerous Fc receptors: including inhibitory and activating, and high and low affinity receptors allowing complex phenotypes to be studied. We demonstrate the adaptability of this high-throughput, flow-based assay to measure antigen-specific antibody-mediated phagocytosis against an array of viruses, including influenza, HIV, and dengue. The phagocytosis assay format further allows for simultaneous analysis of cytokine release, as well as determination of the role of specific Fry-receptor subtypes, making it a highly useful system for parsing differences in the ability of clinical and vaccine induced antibody samples to recruit this critical effector function. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Moldt, Brian; Wyatt, Richard T.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Moldt, Brian; Wyatt, Richard T.; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Consortium, La Jolla, CA 92037 USA.
[Ackerman, Margaret E.; Dugast, Anne-Sophie; McAndrew, Elizabeth; Tsoukas, Stephen; Jost, Stephanie; Berger, Christoph T.; Sciaranghella, Gaia; Liu, Qingquan; Irvine, Darrell J.; Burton, Dennis R.; Alter, Galit] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA.
[Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
RP Ackerman, ME (reprint author), 149 13th St,Room 6616, Charlestown, MA 02129 USA.
EM meackerman@partners.org
RI Ackerman, Margaret/B-5944-2012; Dugast, AnneSophie/L-9541-2015
FU International AIDS Vaccine Initiative through the Neutralizing Antibody
Consortium; Ragon Institute of MGH; MIT; Harvard; NIH [A1055332,
A1080289]; NIAID
FX The authors wish to acknowledge funding from the International AIDS
Vaccine Initiative through the Neutralizing Antibody Consortium; NIAID,
NIH A1055332, NIH A1080289, and The Ragon Institute of MGH, MIT, and
Harvard. BM acknowledges fellowship support from the Alfred Benzon
Foundation. We thank the Phillip T and Susan M Ragon Foundation for
their support.
NR 49
TC 61
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U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
EI 1872-7905
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD MAR 7
PY 2011
VL 366
IS 1-2
BP 8
EP 19
DI 10.1016/j.jim.2010.12.016
PG 12
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 749FY
UT WOS:000289450600002
PM 21192942
ER
PT J
AU Kacimi, R
Giffard, RG
Yenari, MA
AF Kacimi, Rachid
Giffard, Rona G.
Yenari, Midori A.
TI Endotoxin-activated microglia injure brain derived endothelial cells via
NF-kappa B, JAK-STAT and JNK stress kinase pathways
SO JOURNAL OF INFLAMMATION-LONDON
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; INDUCED INOS EXPRESSION; EXPERIMENTAL STROKE;
MILD HYPOTHERMIA; PROTEIN-KINASE; IMMUNE-SYSTEM; INFLAMMATION; DISEASES;
HYPOXIA; BARRIER
AB Background: We previously showed that microglia damage blood brain barrier (BBB) components following ischemic brain insults, but the underlying mechanism(s) is/are not well known. Recent work has established the contribution of toll-like receptor 4 (TLR4) activation to several brain pathologies including ischemia, neurodegeneration and sepsis. The present study established the requirement of microglia for lipopolysaccharide (LPS) mediated endothelial cell death, and explored pathways involved in this toxicity. LPS is a classic TLR4 agonist, and is used here to model aspects of brain conditions where TLR4 stimulation occurs.
Methods/Results: In monocultures, LPS induced death in microglia, but not brain derived endothelial cells (EC). However, LPS increased EC death when cocultured with microglia. LPS led to nitric oxide (NO) and inducible NO synthase (iNOS) induction in microglia, but not in EC. Inhibiting microglial activation by blocking iNOS and other generators of NO or blocking reactive oxygen species (ROS) also prevented injury in these cocultures. To assess the signaling pathway(s) involved, inhibitors of several downstream TLR-4 activated pathways were studied. Inhibitors of NF-kappa B, JAK-STAT and JNK/SAPK decreased microglial activation and prevented cell death, although the effect of blocking JNK/SAPK was rather modest. Inhibitors of PI3K, ERK, and p38 MAPK had no effect.
Conclusions: We show that LPS-activated microglia promote BBB disruption through injury to endothelial cells, and the specific blockade of JAK-STAT, NF-kappa B may prove to be especially useful anti-inflammatory strategies to confer cerebrovascular protection.
C1 [Kacimi, Rachid; Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Kacimi, Rachid; Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Giffard, Rona G.] Stanford Univ, Med Ctr, Dept Anesthesia Dept, Stanford, CA 94305 USA.
RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
EM yenari@alum.mit.edu
FU Department of Veterans Affairs [NIH P50 NS014543, R01 NS 40156,
GM049831]; Department of Defense [DAMD17-03-1-0532]
FX This work was supported by the Department of Veterans Affairs (MAY),
grants from the NIH P50 NS014543 (RGG, MAY), R01 NS 40156 (MAY),
GM049831 (RGG) and the Department of Defense DAMD17-03-1-0532 (MAY).
NR 40
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U1 0
U2 21
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-9255
J9 J INFLAMM-LOND
JI J. Inflamm.-Lond.
PD MAR 7
PY 2011
VL 8
AR 7
DI 10.1186/1476-9255-8-7
PG 15
WC Immunology
SC Immunology
GA 738BT
UT WOS:000288615000001
PM 21385378
ER
PT J
AU Scott, JA
AF Scott, James A.
TI Loneliness
SO LANCET
LA English
DT Letter
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Scott, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM scott@helix.mgh.harvard.edu
NR 1
TC 0
Z9 0
U1 1
U2 1
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 5
PY 2011
VL 377
IS 9768
BP 812
EP 812
DI 10.1016/S0140-6736(11)60308-5
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 738GO
UT WOS:000288628500027
PM 21377570
ER
PT J
AU Fizazi, K
Carducci, M
Smith, M
Damiao, R
Brown, J
Karsh, L
Milecki, P
Shore, N
Rader, M
Wang, HI
Jiang, Q
Tadros, S
Dansey, R
Goessl, C
AF Fizazi, Karim
Carducci, Michael
Smith, Matthew
Damiao, Ronaldo
Brown, Janet
Karsh, Lawrence
Milecki, Piotr
Shore, Neal
Rader, Michael
Wang, Huei
Jiang, Qi
Tadros, Sylvia
Dansey, Roger
Goessl, Carsten
TI Denosumab versus zoledronic acid for treatment of bone metastases in men
with castration-resistant prostate cancer: a randomised, double-blind
study
SO LANCET
LA English
DT Article
ID CONTROLLED PHASE-II; BREAST-CANCER; SKELETAL COMPLICATIONS;
CONTROLLED-TRIALS; LONG-TERM; THERAPY; MULTICENTER; PREVENTION;
CARCINOMA; SURVIVAL
AB Background Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer.
Methods In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal. related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed.
Findings 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12.2 months (IQR 5.9-18.5) for patients on denosumab and 11.2 months (IQR 5.6-17.4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20.7 months (95% CI 18.8-24.9) with denosumab compared with 17.1 months (15-0-19.4) with zoledronic acid (hazard ratio 0.82, 95% CI 0.71-0.95; p=0.0002 for non-inferiority; p=0.008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and 918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13%]) than in the zoledronic acid group (55 [6%]; p<0.0001). Osteonecrosis of the jaw occurred infrequently (22 [2%] vs 12 [1%]; p=0.09).
Interpretation Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer.
C1 [Fizazi, Karim] Univ Paris 11, Inst Gustave Roussy, Dept Canc Med, F-94805 Villejuif, France.
[Carducci, Michael] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Smith, Matthew] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Damiao, Ronaldo] Hosp Univ Pedro Ernesto, Rio De Janeiro, Brazil.
[Brown, Janet] Canc Res UK Clin Ctr, Leeds, W Yorkshire, England.
[Karsh, Lawrence] Urol Ctr Colorado, Denver, CO USA.
[Milecki, Piotr] Wielkopolskie Ctr Onkol, Poznan, Poland.
[Shore, Neal] Carolina Urol Res Ctr, Myrtle Beach, SC USA.
[Rader, Michael] Nyack Hosp, Union State Bank, Ctr Canc, Nyack, NY USA.
[Wang, Huei; Jiang, Qi; Tadros, Sylvia; Dansey, Roger; Goessl, Carsten] Amgen Inc, Thousand Oaks, CA USA.
RP Fizazi, K (reprint author), Univ Paris 11, Inst Gustave Roussy, Dept Canc Med, 39 Rue Camille Desmoulins, F-94805 Villejuif, France.
EM fizazi@igr.fr
OI Krainer, Michael/0000-0002-7011-4957
FU Amgen; Novartis; Center of Research in Urology Sergio Aguinaga (CEPUSA);
Amgen, Thousand Oaks, CA, USA
FX KF has received consultancy fees and travel support from Amgen for this
study and from Novartis; participated in speakers' bureaux and advisory
boards for Amgen and Novartis; and provided expert testimony for Amgen.
MC has received consultancy fees from Amgen for this study and for other
agents in development, and from Novartis; and received research funding
from Amgen. MS has received consultancy fees from Amgen; and
participated in sponsored clinical research with Amgen and Novartis.
RDam has received research funding from Amgen and the Center of Research
in Urology Sergio Aguinaga (CEPUSA). JB has received travel support and
payment for lectures from Amgen and Novartis; JB has received payment
for membership of advisory boards from Amgen. Novartis, and
GlaxoSmithKline; and JB and JB's institution have received consultancy
fees from Amgen. LK has received consultancy fees, travel support, and
honoraria for lectures and development of educational presentations from
Amgen; and LK's institution has received research funding from Amgen. PM
has received research funding from Amgen; and been a board member and
principal investigator for, and received travel support from, Amgen. NS
has received consultancy fees and travel support from Amgen for this
study; and received research funding and honoraria from Amgen. MR has
received travel support and honoraria for membership of advisory boards
and lectures from Amgen; and MR's institution has received research
funding from Amgen for this study. HW, QJ, ST, RDan, and CG are
employees of Amgen, and have received stock or stock options from
Amgen.; We thank the patients and investigators at all participating
sites who made important contributions to this study; Geoffrey Smith,
supported by Amgen, for medical writing assistance in preparation of
this report; and the DMC for its diligence in monitoring of the study.
The DMC wishes to remain anonymous because it is monitoring other trials
of denosumab. This report is presented in memory of study investigator
Lina Barbosa Cassol and study coordinator Carla Fioratti. This study was
funded by Amgen, Thousand Oaks, CA, USA. Primary results of the data in
this report were presented on June, 6, 2010, at the American Society of
Clinical Oncology Annual Meeting in Chicago, IL, USA.
NR 33
TC 715
Z9 732
U1 11
U2 84
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 5
PY 2011
VL 377
IS 9768
BP 813
EP 822
DI 10.1016/S0140-6736(10)62344-6
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 738GO
UT WOS:000288628500029
PM 21353695
ER
PT J
AU Vunjak-Novakovic, G
Scadden, DT
AF Vunjak-Novakovic, Gordana
Scadden, David T.
TI Biomimetic Platforms for Human Stem Cell Research
SO CELL STEM CELL
LA English
DT Article
ID HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW; EXTRACELLULAR-MATRIX;
ADULT-MOUSE; ELECTRICAL-STIMULATION; SKELETAL-MUSCLE; PRECURSOR CELLS;
HAIR FOLLICLE; SELF-RENEWAL; IN-VITRO
AB Stem cells are central to developing new treatment options for tissue regeneration and constructing controllable models for biological research. Bioengineered cell culture environments that combine microenvironmental control with tissue-specific transport and signaling are critical tools in our efforts to study tissue development, regeneration, and disease under conditions that predict the human in vivo context. We propose that experimentation at the interfaces of biology, engineering, and medical sciences is critical for unlocking the full potential of stem cells. Here, we focus on the design and utilization of in vitro platforms that recapitulate the environments associated with tissue development, disease, and regeneration.
C1 [Vunjak-Novakovic, Gordana] Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA.
[Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA.
RP Vunjak-Novakovic, G (reprint author), Columbia Univ, Dept Biomed Engn, New York, NY 10032 USA.
EM gv2131@columbia.edu
RI vunjak-novakovic, gordana/J-9279-2012;
OI Vunjak-Novakovic, Gordana/0000-0002-9382-1574
FU NIH [HL076485, DE16525, HL089913, EB002520, HL044851, HL097794,
HL100402, DK050234]
FX The fusion of the fields of cell biology and bioengineering has been
driven by the pioneering efforts of many contributors working at the
interface of the two disciplines. We acknowledge their collective
contributions and regret that space constraints prevented us from citing
many meritorious studies that will continue to inspire future efforts.
We also acknowledge research funding by NIH (HL076485, DE16525,
HL089913, and EB002520 to G.V.-N. and HL044851, HL097794, HL100402, and
DK050234 to D.T.S.) and thank Dr. N. Mirkovic for his expert help with
illustrations.
NR 90
TC 59
Z9 61
U1 2
U2 36
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 4
PY 2011
VL 8
IS 3
BP 252
EP 261
DI 10.1016/j.stem.2011.02.014
PG 10
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 735HI
UT WOS:000288404400007
PM 21362565
ER
PT J
AU Chen, MH
Colan, SD
Diller, L
AF Chen, Ming Hui
Colan, Steven D.
Diller, Lisa
TI Cardiovascular Disease Cause of Morbidity and Mortality in Adult
Survivors of Childhood Cancers
SO CIRCULATION RESEARCH
LA English
DT Review
DE anthracycline; radiation; cardiotoxicity; cancer survivor; childhood
ID LONG-TERM SURVIVORS; ANTHRACYCLINE-INDUCED CARDIOTOXICITY; ACUTE
LYMPHOBLASTIC-LEUKEMIA; CONGESTIVE-HEART-FAILURE; DOXORUBICIN-INDUCED
CARDIOTOXICITY; LEFT-VENTRICULAR DYSFUNCTION; ASSOCIATION TASK-FORCE;
RABBIT EAR ARTERY; HODGKINS-DISEASE; BREAST-CANCER
AB Although important advances have been made in curing childhood cancer in the last several decades, long-term survivors face considerable morbidity and mortality because of late effects from their initial anticancer therapy. By 30 years after treatment, the cumulative mortality from treatment-related medical illness actually exceeds that of mortality from cancer recurrence. Cardiovascular disease, in particular, is a leading threat to the well-being of adult survivors of childhood cancers. Unfortunately, the mechanisms of these late cardiac effects are understudied and poorly understood. This article reviews cardiotoxicity associated with 2 major anticancer regimens used in treating childhood cancer patients: anthracycline treatment and radiation therapy. The known pathophysiology and clinical cardiac risk factors that further predispose these patients to late-onset cardiac events are discussed. Basic and translational research is urgently needed to clarify pathophysiologic mechanisms of late cardiac effects and to develop therapies to improve both long-term survival and quality of life of adults cured of pediatric cancers. (Circ Res. 2011; 108: 619-628.)
C1 [Chen, Ming Hui; Colan, Steven D.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Diller, Lisa] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[Chen, Ming Hui] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA.
[Chen, Ming Hui] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA.
[Chen, Ming Hui] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Diller, Lisa] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Chen, Ming Hui] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Colan, Steven D.; Diller, Lisa] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Chen, MH (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA.
EM minghui.chen@cardio.chboston.org
FU Translational Fund for Cardiology and Oncology; Department of Cardiology
at Children's Hospital Boston
FX M.H.C. is supported by the Translational Fund for Cardiology and
Oncology and the Department of Cardiology at Children's Hospital Boston.
NR 104
TC 43
Z9 45
U1 0
U2 7
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 4
PY 2011
VL 108
IS 5
BP 619
EP 628
DI 10.1161/CIRCRESAHA.110.224519
PG 10
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 729PW
UT WOS:000287963900015
PM 21372293
ER
PT J
AU Sengupta, A
Molkentin, JD
Paik, JH
DePinho, RA
Yutzey, KE
AF Sengupta, Arunima
Molkentin, Jeffery D.
Paik, Ji-Hye
DePinho, Ronald A.
Yutzey, Katherine E.
TI FoxO Transcription Factors Promote Cardiomyocyte Survival upon Induction
of Oxidative Stress
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; ISCHEMIA-REPERFUSION INJURY; TRANSGENIC MICE;
HEART-FAILURE; MOUSE HEART; CELL-DEATH; IN-VIVO; HYPERTROPHY; APOPTOSIS;
PROLIFERATION
AB Transcriptional regulatory mechanisms of cardiac oxidative stress resistance are not well defined. FoxO transcription factors are critical mediators of oxidative stress resistance in multiple cell types, but cardioprotective functions have not been reported previously. FoxO function in oxidative stress resistance was investigated in cultured cardiomyocytes and in mice with cardiomyocyte-specific combined deficiency of FoxO1 and FoxO3 subjected to myocardial infarction (MI) or acute ischemia/reperfusion (I/R) injury. Induction of oxidative stress in cardiomyocytes promotes FoxO1 and FoxO3 nuclear localization and target gene activation. Infection of cardiomyocytes with a dominant-negative FoxO1(Delta 256) adenovirus results in a significant increase in reactive oxygen species and cell death, whereas increased FoxO1 or FoxO3 expression reduces reactive oxygen species and cell death. Mice generated with combined conditional deletion of FoxO1 and FoxO3 specifically in cardiomyocytes were subjected to I/R or MI. Loss of FoxO1 and FoxO3 in cardiomyocytes results in a significant increase in infarct area with decreased expression of the antiapoptotic molecules, PTEN-induced kinase1 (PINK1) and CBP/P300-interacting transactivator (CITED2). Expressions of the antioxidants catalase and manganese superoxide dismutase-2 (SOD2) and the autophagy-related proteins LC3II and Gabarapl1 also are decreased following I/R compared with controls. Mice with cardiomyocyte-specific FoxO deficiency subjected to MI have reduced cardiac function, increased scar formation, induction of stress-responsive signaling, and increased apoptotic cell death relative to controls. These data support a critical role for FoxOs in promoting cardiomyocyte survival during conditions of oxidative stress through induction of antioxidants and cell survival pathways.
C1 [Sengupta, Arunima; Molkentin, Jeffery D.; Yutzey, Katherine E.] Cincinnati Childrens Med Ctr, Div Mol Cardiovasc Biol, Inst Heart, Cincinnati, OH 45229 USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Med Oncol, Boston, MA 02115 USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Med, Boston, MA 02115 USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Genet, Boston, MA 02115 USA.
RP Yutzey, KE (reprint author), Cincinnati Childrens Med Ctr ML 7020, Div Mol Cardiovasc Biol, 240 Albert Sabin Way, Cincinnati, OH 45229 USA.
EM katherine.yutzey@cchmc.org
FU National Institutes of Health [PO1 HL069779]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant PO1 HL069779 (to K. E. Y. and J. D. M.).
NR 42
TC 126
Z9 133
U1 5
U2 22
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 4
PY 2011
VL 286
IS 9
BP 7468
EP 7478
DI 10.1074/jbc.M110.179242
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726PH
UT WOS:000287737300061
PM 21159781
ER
PT J
AU Ando, K
Uemura, K
Kuzuya, A
Maesako, M
Asada-Utsugi, M
Kubota, M
Aoyagi, N
Yoshioka, K
Okawa, K
Inoue, H
Kawamata, J
Shimohama, S
Arai, T
Takahashi, R
Kinoshita, A
AF Ando, Koichi
Uemura, Kengo
Kuzuya, Akira
Maesako, Masato
Asada-Utsugi, Megumi
Kubota, Masakazu
Aoyagi, Nobuhisa
Yoshioka, Katsuji
Okawa, Katsuya
Inoue, Haruhisa
Kawamata, Jun
Shimohama, Shun
Arai, Tetsuaki
Takahashi, Ryosuke
Kinoshita, Ayae
TI N-cadherin Regulates p38 MAPK Signaling via Association with
JNK-associated Leucine Zipper Protein IMPLICATIONS FOR NEURODEGENERATION
IN ALZHEIMER DISEASE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AMYLOID-BETA; SCAFFOLDING PROTEIN; MISSENSE MUTATIONS; NEURITE
OUTGROWTH; SYNAPSE LOSS; KINASE; ACTIVATION; PATHWAY; ADHESION;
PRESENILIN-1
AB Synaptic loss, which strongly correlates with the decline of cognitive function, is one of the pathological hallmarks of Alzheimer disease. N-cadherin is a cell adhesion molecule essential for synaptic contact and is involved in the intracellular signaling pathway at the synapse. Here we report that the functional disruption of N-cadherin-mediated cell contact activated p38 MAPK in murine primary neurons, followed by neuronal death. We further observed that treatment with A beta(42) decreased cellular N-cadherin expression through NMDA receptors accompanied by increased phosphorylation of both p38 MAPK and Tau in murine primary neurons. Moreover, expression levels of phosphorylated p38 MAPK were negatively correlated with that of N-cadherin in human brains. Proteomic analysis of human brains identified a novel interaction between N-cadherin and JNK-associated leucine zipper protein (JLP), a scaffolding protein involved in the p38 MAPK signaling pathway. We demonstrated that N-cadherin expression had an inhibitory effect on JLP-mediated p38 MAPK signal activation by decreasing the interaction between JLP and p38 MAPK in COS7 cells. Also, this study demonstrated a novel physical and functional association between N-cadherin and p38 MAPK and suggested neuroprotective roles of cadherin-based synaptic contact. The dissociation of N-cadherin-mediated synaptic contact by A beta may underlie the pathological basis of neurodegeneration such as neuronal death, synaptic loss, and Tau phosphorylation in Alzheimer disease brain.
C1 [Kinoshita, Ayae] Kyoto Univ, Grad Sch Med, Sch Human Hlth Sci, Sakyo Ku, Kyoto 6068507, Japan.
[Aoyagi, Nobuhisa; Kawamata, Jun; Takahashi, Ryosuke] Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto 6068507, Japan.
[Uemura, Kengo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Yoshioka, Katsuji] Kanazawa Univ, Canc Res Inst, Div Mol Cell Signaling, Kanazawa, Ishikawa 9201192, Japan.
[Okawa, Katsuya] Kyowa Hakko Kirin Co, Tokyo 1008185, Japan.
[Inoue, Haruhisa] Kyoto Univ, Ctr iPS Cell Res & Applicat, Kyoto 6068507, Japan.
[Shimohama, Shun] Sapporo Med Univ, Dept Neurol, Sapporo, Hokkaido 0608556, Japan.
[Arai, Tetsuaki] Tokyo Inst Psychiat, Tokyo 1568585, Japan.
RP Kinoshita, A (reprint author), Kyoto Univ, Grad Sch Med, Sch Human Hlth Sci, Sakyo Ku, 53 Shogoinkawahara Cho, Kyoto 6068507, Japan.
EM akinoshita@hs.med.kyoto-u.ac.jp
NR 40
TC 28
Z9 32
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 4
PY 2011
VL 286
IS 9
BP 7619
EP 7628
DI 10.1074/jbc.M110.158477
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726PH
UT WOS:000287737300075
PM 21177868
ER
PT J
AU Stamm, LM
Goldberg, MB
AF Stamm, Luisa M.
Goldberg, Marcia B.
TI Establishing the Secretion Hierarchy
SO SCIENCE
LA English
DT Editorial Material
ID III SECRETION; SALMONELLA-TYPHIMURIUM; SYSTEM
C1 [Stamm, Luisa M.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA.
Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
RP Stamm, LM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA.
EM mgoldberg1@partners.org
FU NIAID NIH HHS [R01 AI081724, T32 AI007061]
NR 9
TC 12
Z9 12
U1 0
U2 5
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 4
PY 2011
VL 331
IS 6021
BP 1147
EP 1148
DI 10.1126/science.1203195
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729SN
UT WOS:000287971200030
PM 21385706
ER
PT J
AU Schlegelmilch, K
Mohseni, M
Kirak, O
Pruszak, J
Rodriguez, JR
Zhou, DW
Kreger, BT
Vasioukhin, V
Avruch, J
Brummelkamp, TR
Camargo, FD
AF Schlegelmilch, Karin
Mohseni, Morvarid
Kirak, Oktay
Pruszak, Jan
Rodriguez, J. Renato
Zhou, Dawang
Kreger, Bridget T.
Vasioukhin, Valera
Avruch, Joseph
Brummelkamp, Thijn R.
Camargo, Fernando D.
TI Yap1 Acts Downstream of alpha-Catenin to Control Epidermal Proliferation
SO CELL
LA English
DT Article
ID ORGAN SIZE CONTROL; TUMOR-SUPPRESSOR; CELL-PROLIFERATION; PROMOTES
APOPTOSIS; SIGNALING PATHWAY; HIPPO PATHWAY; PROGENITOR CELLS; TEAD/TEF
FAMILY; PROTEIN-KINASE; GROWTH-CONTROL
AB During development and regeneration, proliferation of tissue-specific stem cells is tightly controlled to produce organs of a predetermined size. The molecular determinants of this process remain poorly understood. Here, we investigate the function of Yap1, the transcriptional effector of the Hippo signaling pathway, in skin biology. Using gain- and loss-of-function studies, we show that Yap1 is a critical modulator of epidermal stem cell proliferation and tissue expansion. Yap1 mediates this effect through interaction with TEAD transcription factors. Additionally, our studies reveal that alpha-catenin, a molecule previously implicated in tumor suppression and cell density sensing in the skin, is an upstream negative regulator of Yap1. alpha-catenin controls Yap1 activity and phosphorylation by modulating its interaction with 14-3-3 and the PP2A phosphatase. Together, these data identify Yap1 as a determinant of the proliferative capacity of epidermal stem cells and as an important effector of a "crowd control" molecular circuitry in mammalian skin.
C1 [Schlegelmilch, Karin; Mohseni, Morvarid; Camargo, Fernando D.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
[Schlegelmilch, Karin; Mohseni, Morvarid; Camargo, Fernando D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Schlegelmilch, Karin; Mohseni, Morvarid; Pruszak, Jan; Camargo, Fernando D.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Schlegelmilch, Karin] FU Berlin, Inst Chem Biochem, D-14195 Berlin, Germany.
[Kirak, Oktay; Pruszak, Jan; Rodriguez, J. Renato; Brummelkamp, Thijn R.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Zhou, Dawang; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol & Cellular Biol, Boston, MA 02114 USA.
[Kreger, Bridget T.; Vasioukhin, Valera] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
RP Camargo, FD (reprint author), Childrens Hosp, Stem Cell Program, 300 Longwood Ave, Boston, MA 02115 USA.
EM fernando.camargo@childrens.harvard.edu
RI Kirak, Oktay/H-6347-2013; Pruszak, Jan/G-6972-2015;
OI Kirak, Oktay/0000-0002-6524-4685; Pruszak, Jan/0000-0003-4297-4009;
Zhou, Dawang/0000-0002-9053-5249
FU Stand Up to Cancer-AACR initiative, NIH [R01 CA131426]; Whitehead
Institute
FX We thank K. Shrestha and S. Zaghlul for their technical assistance; L.
Zon and A. von Giese and members of the Camargo lab for critical
discussion; and members of the Gregory laboratory for advice on mass
spectrometry experiments. This work was supported by grants from the
Stand Up to Cancer-AACR initiative, NIH grant R01 CA131426, and funds
from the Whitehead Institute Fellows Program. F. D. C. is a V Foundation
Scholar and Pew Scholar in the Biomedical Sciences.
NR 58
TC 354
Z9 366
U1 11
U2 66
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 4
PY 2011
VL 144
IS 5
BP 782
EP 795
DI 10.1016/j.cell.2011.02.031
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 730CE
UT WOS:000288007100016
PM 21376238
ER
PT J
AU Suzuki, A
Stern, SA
Bozdagi, O
Huntley, GW
Walker, RH
Magistretti, PJ
Alberini, CM
AF Suzuki, Akinobu
Stern, Sarah A.
Bozdagi, Ozlem
Huntley, George W.
Walker, Ruth H.
Magistretti, Pierre J.
Alberini, Cristina M.
TI Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory
Formation
SO CELL
LA English
DT Article
ID ELEMENT-BINDING PROTEIN; IMMEDIATE-EARLY GENE; D-SERINE; RAT
HIPPOCAMPUS; GLYCOGEN; GLUCOSE; POTENTIATION; PLASTICITY; ACTIN;
CONSOLIDATION
AB We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation.
C1 [Magistretti, Pierre J.] Univ Lausanne CHUV, Lab Neuroenerget & Cellular Dynam, Brain Mind Inst, EPFL, Lausanne, Switzerland.
[Magistretti, Pierre J.] Univ Lausanne CHUV, Ctr Psychiat Neurosci, Lausanne, Switzerland.
[Suzuki, Akinobu; Stern, Sarah A.; Bozdagi, Ozlem; Huntley, George W.; Alberini, Cristina M.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
[Bozdagi, Ozlem; Alberini, Cristina M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Walker, Ruth H.] James J Peters VAMC, Dept Neurol, Bronx, NY 10468 USA.
[Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
RP Magistretti, PJ (reprint author), Univ Lausanne CHUV, Lab Neuroenerget & Cellular Dynam, Brain Mind Inst, EPFL, Lausanne, Switzerland.
EM pierre.magistretti@epfl.ch; cristina.alberini@mssm.edu
FU Department of Veterans Affairs; [R01-MH065635]; [R01-MH074736];
[T32-MH087004]
FX This work was supported by grants R01-MH065635 and R01-MH074736 to C. M.
A., Department of Veterans Affairs Merit Award to R. H. W. and
T32-MH087004 to S. A. S. We thank Rick Koch, Dhananjay Bambah-Mukku,
Dillon Chen, Gabriella Pollonini, and Virginia Gao for technical
support; and Reginald Miller and the Center for Comparative Medicine and
Surgery facility at Mount Sinai School of Medicine for technical
support. P.J.M. is the recipient of the Asterion Chair at Ecole
Polytechnique Federale de Lausanne (EPFL).
NR 64
TC 374
Z9 390
U1 7
U2 52
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 4
PY 2011
VL 144
IS 5
BP 810
EP 823
DI 10.1016/j.cell.2011.02.018
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 730CE
UT WOS:000288007100018
PM 21376239
ER
PT J
AU Leuschner, F
Nahrendorf, M
AF Leuschner, Florian
Nahrendorf, Matthias
TI Molecular Imaging of Coronary Atherosclerosis and Myocardial Infarction
Considerations for the Bench and Perspectives for the Clinic
SO CIRCULATION RESEARCH
LA English
DT Review
DE molecular imaging; hybrid imaging; atherosclerosis; myocardial
infarction; heart failure
ID POSITRON-EMISSION-TOMOGRAPHY; CARDIOVASCULAR MAGNETIC-RESONANCE;
MATRIX-METALLOPROTEINASE ACTIVITY; AMERICAN-HEART-ASSOCIATION;
CELL-ADHESION MOLECULE-1; IN-VIVO; CONTRAST AGENT; VASCULAR
INFLAMMATION; NONINVASIVE DETECTION; COMPUTED-TOMOGRAPHY
AB Motivated by the promise to transform preclinical research and clinical care, cardiovascular molecular imaging has made advances toward targeting coronary atherosclerosis and heart failure. Here, we discuss recent progress in the field, highlight how molecular imaging may facilitate preventive patient care, and review specific challenges associated with coronary and heart failure imaging. Practical considerations stress the potential of fluorescence imaging for basic research and discuss hybrid protocols such as FMT-CT and PET-MRI. (Circ Res. 2011; 108: 593-606.)
C1 [Leuschner, Florian; Nahrendorf, Matthias] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
RP Nahrendorf, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.
EM mnahrendorf@mgh.harvard.edu
FU NIH [R01HL095629, R01HL096576, R01EB006432, HHSN268201000044C]; American
Heart Association [SDG0835623D]; Deutsche Herzstiftung e. V.
FX This work was supported, in part, by NIH grants R01HL095629,
R01HL096576, R01EB006432, HHSN268201000044C; American Heart Association
Grant SDG0835623D; and the Deutsche Herzstiftung e. V.
NR 114
TC 58
Z9 59
U1 1
U2 18
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 4
PY 2011
VL 108
IS 5
BP 593
EP 606
DI 10.1161/CIRCRESAHA.110.232678
PG 14
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 729PW
UT WOS:000287963900013
PM 21372291
ER
PT J
AU Pitman, RK
AF Pitman, Roger K.
TI Will reconsolidation blockade offer a novel treatment for posttraumatic
stress disorder?
SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE
LA English
DT Editorial Material
C1 [Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
[Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Pitman, RK (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
EM roger_pitman@hms.harvard.edu
NR 15
TC 18
Z9 18
U1 0
U2 3
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5153
J9 FRONT BEHAV NEUROSCI
JI Front. Behav. Neurosci.
PD MAR 4
PY 2011
VL 5
AR 11
DI 10.3389/fnbeh.2011.00011
PG 2
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA V29VS
UT WOS:000208776500001
PM 21427793
ER
PT J
AU Nakamura, K
Kato, A
Kobayashi, J
Yanagihara, H
Sakamoto, S
Oliveira, DVNP
Shimada, M
Tauchi, H
Suzuki, H
Tashiro, S
Zou, L
Komatsu, K
AF Nakamura, Kyosuke
Kato, Akihiro
Kobayashi, Junya
Yanagihara, Hiromi
Sakamoto, Shuichi
Oliveira, Douglas V. N. P.
Shimada, Mikio
Tauchi, Hiroshi
Suzuki, Hidekazu
Tashiro, Satoshi
Zou, Lee
Komatsu, Kenshi
TI Regulation of Homologous Recombination by RNF20-Dependent H2B
Ubiquitination
SO MOLECULAR CELL
LA English
DT Article
ID DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; CHROMATIN REMODELING
COMPLEXES; REPAIR PROTEINS; HISTONE H2B; DISTINCT ROLES; CELL-CYCLE;
IN-VIVO; UBIQUITYLATION; TRANSCRIPTION
AB The E3 ubiquitin ligase RNF20 regulates chromatin structure by monoubiquitinating histone H2B in transcription. Here, we show that RNF20 is localized to double-stranded DNA breaks (DSBs) independently of H2AX and is required for the DSB-induced H2B ubiquitination. In addition, RNF20 is required for the methylation of H3K4 at DSBs and the recruitment of the chromatin-remodeling factor SNF2h. Depletion of RNF20, depletion of SNF2h, or expression of the H2B mutant lacking the ubiquitination site (K120R) compromises resection of DNA ends and recruitment of RAD51 and BRCA1. Consequently, cells lacking RNF20 or SNF2h and cells expressing H2B K120R exhibit pronounced defects in homologous recombination repair (HRR) and enhanced sensitivity to radiation. Finally, the function of RNF20 in HRR can be partially bypassed by forced chromatin relaxation. Thus, the RNF20-mediated H2B ubiquitination at DSBs plays a critical role in HRR through chromatin remodeling.
C1 [Nakamura, Kyosuke; Kato, Akihiro; Kobayashi, Junya; Yanagihara, Hiromi; Sakamoto, Shuichi; Oliveira, Douglas V. N. P.; Shimada, Mikio; Komatsu, Kenshi] Kyoto Univ, Ctr Radiat Biol, Sakyo Ku, Kyoto 6068501, Japan.
[Tauchi, Hiroshi] Ibaraki Univ, Dept Biol Sci, Mito, Ibaraki 3108512, Japan.
[Suzuki, Hidekazu; Tashiro, Satoshi] Hiroshima Univ, Res Inst Radiat Biol & Med, Minami Ku, Hiroshima 7348553, Japan.
[Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
RP Komatsu, K (reprint author), Kyoto Univ, Ctr Radiat Biol, Sakyo Ku, Yoshida Konoecho, Kyoto 6068501, Japan.
EM komatsu@house.rbc.kyoto-u.ac.jp
RI Shimada, Mikio/E-1565-2015
OI Shimada, Mikio/0000-0003-1980-9187
FU Ministry of Education, Culture, Sports, Science and Technology, Japan
FX The authors thank S.J. Elledge and H. Kimura for providing the anti-MDC1
antibody and the cDNA for H2B used in this study. We also thank Y.
Hayuka and M. Hiraga for their excellent technical assistance in this
work. This work was supported in part by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
NR 55
TC 133
Z9 135
U1 3
U2 31
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 4
PY 2011
VL 41
IS 5
BP 515
EP 528
DI 10.1016/j.molcel.2011.02.002
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 731ZU
UT WOS:000288150700005
PM 21362548
ER
PT J
AU Vitek, WS
Akers, A
Meyn, LA
Switzer, GE
Lee, BY
Beigi, RH
AF Vitek, Wendy S.
Akers, Aletha
Meyn, Leslie A.
Switzer, Galen E.
Lee, Bruce Y.
Beigi, Richard H.
TI Vaccine eligibility and acceptance among ambulatory obstetric and
gynecologic patients
SO VACCINE
LA English
DT Article; Proceedings Paper
CT 35th Annual Scientific Meeting of the
Infectious-Diseases-Society-for-Obstetrics-and-Gynecology
CY AUG 14-16, 2008
CL Seattle, WA
SP Infect Dis Soc Obstetr & Gynecol
DE Patient acceptance of health care; Vaccine; Obstetrics; Gynecology
ID PREGNANCY
AB Objective: To assess vaccine eligibility and factors associated with vaccine acceptance among ambulatory obstetric and gynecologic patients.
Methods: An anonymous office-based survey was administered to women seeking ambulatory obstetric and gynecologic care at a large women's hospital from December 2007 to July 2008. Information collected included: demographics, medical and vaccination history, interest in receiving vaccines and attitudes towards vaccine providers. Vaccine eligibility was based on age and/or self-reported risk factors in accord with the 2007-2008 Center for Disease Control and Prevention (CDC) adult immunization schedule. Vaccine eligibility was examined using descriptive statistics, and demographic characteristics were compared using chi-squared analysis. A multivariable logistic regression model was developed to assess factors associated with participants' willingness to accept vaccines from their obstetrician-gynecologist.
Results: A total of 1441 women completed the survey. The majority of participants (87%) would accept vaccines if recommended by their obstetrician-gynecologist. The primary factors associated with vaccine acceptance were having less than a high school education, being privately insured, currently being pregnant, reporting a history of vaccinations and previously receiving vaccinations from an obstetrician-gynecologist. A significant portion of participants were eligible for the hepatitis B. influenza and HPV vaccines (>= 50% for each). The type of vaccine did not influence willingness to accept vaccines from an obstetrician-gynecologist.
Conclusion: A majority of women appear eligible for, and will accept, vaccinations regardless of specific vaccine, if recommended by their obstetrician-gynecologist. These findings justify ongoing efforts to expand immunization services offered by obstetrician-gynecologists. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Vitek, Wendy S.] Women & Infants Hosp Rhode Isl, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Providence, RI 02908 USA.
[Akers, Aletha; Beigi, Richard H.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Med Ctr,Div Gynecol Specialties, Pittsburgh, PA 15213 USA.
[Akers, Aletha; Beigi, Richard H.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Med Ctr,Div Reprod Infect Dis, Pittsburgh, PA 15213 USA.
[Meyn, Leslie A.] Magee Womens Res Inst, Pittsburgh, PA USA.
[Switzer, Galen E.] Univ Pittsburgh, Sch Med, Dept Med & Psychiat, Pittsburgh, PA USA.
[Switzer, Galen E.] Univ Pittsburgh, Sch Med, Dept Clin & Translat Sci, Pittsburgh, PA USA.
[Switzer, Galen E.] VA Pittsburgh Hlth Syst, Ctr Hlth Equ & Promot, Pittsburgh, PA USA.
[Lee, Bruce Y.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Lee, Bruce Y.] Univ Pittsburgh, Dept Epidemiol, Sch Med, Pittsburgh, PA 15261 USA.
[Lee, Bruce Y.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
RP Vitek, WS (reprint author), Women & Infants Hosp Rhode Isl, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, 90 Plain St, Providence, RI 02908 USA.
EM wvitek@wihri.org
NR 16
TC 13
Z9 13
U1 1
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD MAR 3
PY 2011
VL 29
IS 11
BP 2024
EP 2028
DI 10.1016/j.vaccine.2011.01.026
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 739PU
UT WOS:000288731000007
PM 21272604
ER
PT J
AU Smith, AR
Majhail, NS
MacMillan, ML
DeFor, TE
Jodele, S
Lehmann, LE
Krance, R
Davies, SM
AF Smith, Angela R.
Majhail, Navneet S.
MacMillan, Margaret L.
DeFor, Todd E.
Jodele, Sonata
Lehmann, Leslie E.
Krance, Robert
Davies, Stella M.
TI Hematopoietic cell transplantation comorbidity index predicts
transplantation outcomes in pediatric patients
SO BLOOD
LA English
DT Article
ID HCT-CI; REDUCED-INTENSITY; MORBIDITY; MORTALITY; RISK; VALIDATION;
LYMPHOMA; MYELOMA; MODELS
AB Quantifying the risk of hematopoietic cell transplantation (HCT)-related mortality for pediatric patients is challenging. The HCT-specific comorbidity index (HCT-CI) has been confirmed as a useful tool in adults, but has not yet been validated in children. We conducted a retrospective cohort study of 252 pediatric patients undergoing their first allogeneic HCT between January 2008 and May 2009. Pretransplantation comorbidities were scored prospectively using the HCT-CI. Median age at transplantation was 6 years (range, 0.1-20) and median follow-up was 343 days (range, 110-624). HCT-CI scores were distributed as follows: 0, n = 139; 1-2, n = 52; and 3+, n = 61. The 1-year cumulative incidence of nonrelapse mortality (NRM) increased (10%, 14%, and 28%, respectively; P < .01) and overall survival (OS) decreased (88%, 67%, and 62%, respectively; P < .01) with increasing HCT-CI score. Multivariate analysis showed that compared with score 0, those with scores of 1-2 and 3+ had relative risks of NRM of 1.5 (95% confidence interval, 0.5-4.3, P = .48) and 4.5 (95% confidence interval, 1.7-12.1, P < .01), respectively. These results indicate that the HCT-CI score predicts NRM and OS in pediatric patients undergoing HCT and is a useful tool to assess risk, guide counseling in the pre-transplantation setting, and devise innovative therapies for the highest risk groups. (Blood. 2011; 117(9): 2728-2734)
C1 [Smith, Angela R.; Majhail, Navneet S.; MacMillan, Margaret L.; DeFor, Todd E.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA.
[Jodele, Sonata; Davies, Stella M.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplant & Immune Deficiency, Cincinnati, OH USA.
[Lehmann, Leslie E.] Childrens Hosp, Dana Farber Canc Inst, Pediat Stem Cell Transplant Program, Boston, MA 02115 USA.
[Krance, Robert] Texas Childrens Canc Ctr, Pediat Stem Cell Transplant Program, Houston, TX USA.
RP Smith, AR (reprint author), Univ Minnesota, Blood & Marrow Transplant Program, 420 Delaware St SE,MMC 484, Minneapolis, MN 55455 USA.
EM smith719@umn.edu
NR 17
TC 25
Z9 26
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 3
PY 2011
VL 117
IS 9
BP 2728
EP 2734
DI 10.1182/blood-2010-08-303263
PG 7
WC Hematology
SC Hematology
GA 732RR
UT WOS:000288207400025
PM 21228326
ER
PT J
AU Ring, DC
Herndon, JH
Meyer, GS
AF Ring, David C.
Herndon, James H.
Meyer, Gregg S.
TI Case 34-2010: A Woman with an Incorrect Operation REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Ring, David C.; Herndon, James H.; Meyer, Gregg S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Ring, DC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 3
PY 2011
VL 364
IS 9
BP 883
EP 883
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 729DJ
UT WOS:000287928400023
ER
PT J
AU Farrar, CT
Kamoun, WS
Ley, CD
Kim, YR
Catana, C
Kwon, SJ
Rosen, BR
Jain, RK
Sorensen, AG
AF Farrar, Christian T.
Kamoun, Walid S.
Ley, Carsten D.
Kim, Young R.
Catana, Ciprian
Kwon, Seon J.
Rosen, Bruce R.
Jain, Rakesh K.
Sorensen, A. Gregory
TI Sensitivity of MRI Tumor Biomarkers to VEGFR Inhibitor Therapy in an
Orthotopic Mouse Glioma Model
SO PLOS ONE
LA English
DT Article
ID CEREBRAL BLOOD-VOLUME; CONTRAST-ENHANCED MRI; BRAIN-BARRIER
PERMEABILITY; TYROSINE KINASE INHIBITOR; ARTERIAL INPUT FUNCTION; EARLY
SURROGATE MARKER; IN-VIVO; GRADIENT-ECHO; VESSEL SIZE; GLIOBLASTOMA
PATIENTS
AB MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI) and a slight decrease in the water apparent diffusion coefficient (ADC) were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV), relative microvascular blood volume (rMBV), transverse relaxation time (T2), blood vessel permeability (K(trans)), and extravascular-extracellular space (v(e)). The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.
C1 [Farrar, Christian T.; Kim, Young R.; Catana, Ciprian; Kwon, Seon J.; Rosen, Bruce R.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Kamoun, Walid S.; Ley, Carsten D.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Charlestown, MA USA.
RP Farrar, CT (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
EM cfarrar@nmr.mgh.harvard.edu
FU National Institutes of Health [P41-RR14075, P01-CA80124, R01-CA115767];
AstraZeneca Pharmaceuticals; National Cancer Institute [T32-CA009502];
National Institute on Aging [K25-AG029415]
FX This research was supported by the National Institutes of Health
(P41-RR14075, P01-CA80124, R01-CA115767) and by AstraZeneca
Pharmaceuticals. CTF gratefully acknowledges support from the National
Cancer Institute (T32-CA009502) and the National Institute on Aging
(K25-AG029415). WSK gratefully acknowledges support from the Susan G.
Komen foundation. CDL gratefully acknowledges support from the Harboe
Foundation, the A.P. Moller Foundation, and the Dagmar-Marshall
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 50
TC 19
Z9 20
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 3
PY 2011
VL 6
IS 3
AR e17228
DI 10.1371/journal.pone.0017228
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729QI
UT WOS:000287965200013
PM 21390238
ER
PT J
AU McKinney, SM
Thien, TDV
Buxton, OM
Solet, JM
Ellenbogen, JM
AF McKinney, Scott M.
Thien Thanh Dang-Vu
Buxton, Orfeu M.
Solet, Jo M.
Ellenbogen, Jeffrey M.
TI Covert Waking Brain Activity Reveals Instantaneous Sleep Depth
SO PLOS ONE
LA English
DT Article
ID AROUSAL THRESHOLD; ALPHA OSCILLATIONS; STIMULUS DETECTION; POWER
SPECTRUM; HUMAN CORTEX; EEG SPECTRA; PERFORMANCE; ELECTROENCEPHALOGRAM;
FREQUENCY; COHERENCE
AB The neural correlates of the wake-sleep continuum remain incompletely understood, limiting the development of adaptive drug delivery systems for promoting sleep maintenance. The most useful measure for resolving early positions along this continuum is the alpha oscillation, an 8-13 Hz electroencephalographic rhythm prominent over posterior scalp locations. The brain activation signature of wakefulness, alpha expression discloses immediate levels of alertness and dissipates in concert with fading awareness as sleep begins. This brain activity pattern, however, is largely ignored once sleep begins. Here we show that the intensity of spectral power in the alpha band actually continues to disclose instantaneous responsiveness to noise-a measure of sleep depth-throughout a night of sleep. By systematically challenging sleep with realistic and varied acoustic disruption, we found that sleepers exhibited markedly greater sensitivity to sounds during moments of elevated alpha expression. This result demonstrates that alpha power is not a binary marker of the transition between sleep and wakefulness, but carries rich information about immediate sleep stability. Further, it shows that an empirical and ecologically relevant form of sleep depth is revealed in real-time by EEG spectral content in the alpha band, a measure that affords prediction on the order of minutes. This signal, which transcends the boundaries of classical sleep stages, could potentially be used for real-time feedback to novel, adaptive drug delivery systems for inducing sleep.
C1 [McKinney, Scott M.; Thien Thanh Dang-Vu; Ellenbogen, Jeffrey M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Thien Thanh Dang-Vu; Buxton, Orfeu M.; Solet, Jo M.; Ellenbogen, Jeffrey M.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA.
[Thien Thanh Dang-Vu] Univ Liege, Cyclotron Res Ctr, Liege, Belgium.
[Buxton, Orfeu M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Solet, Jo M.] Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA.
RP McKinney, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM jeffrey_ellenbogen@hms.harvard.edu
RI Sanguansri, Luz/B-6630-2011;
OI Sanguansri, Luz/0000-0003-1908-7604; Dang Vu, Thien
Thanh/0000-0002-7235-2721
FU Academy of Architecture for Health; Facilities Guidelines Institute;
Center for Health Design; Massachusetts General Hospital
FX This study was funded by the Academy of Architecture for Health, the
Facilities Guidelines Institute, the Center for Health Design, and the
Massachusetts General Hospital. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 22
Z9 22
U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 3
PY 2011
VL 6
IS 3
AR e17351
DI 10.1371/journal.pone.0017351
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729QI
UT WOS:000287965200014
PM 21408616
ER
PT J
AU Nehme, NT
Quintin, J
Cho, JH
Lee, J
Lafarge, MC
Kocks, C
Ferrandon, D
AF Nehme, Nadine T.
Quintin, Jessica
Cho, Ju Hyun
Lee, Janice
Lafarge, Marie-Celine
Kocks, Christine
Ferrandon, Dominique
TI Relative Roles of the Cellular and Humoral Responses in the Drosophila
Host Defense against Three Gram-Positive Bacterial Infections
SO PLOS ONE
LA English
DT Article
ID PEPTIDOGLYCAN RECOGNITION PROTEIN; IMMUNE-RESPONSE; TOLL-PATHWAY;
PSEUDOMONAS-AERUGINOSA; ANTIMICROBIAL PEPTIDES; FUNGAL-INFECTIONS; IMD
PATHWAYS; PGRP-SD; PHAGOCYTOSIS; RESISTANCE
AB Background: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense.
Methodology/Principal Findings: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different Gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response.
Conclusions/Significance: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.
C1 [Nehme, Nadine T.; Quintin, Jessica; Cho, Ju Hyun; Lee, Janice; Lafarge, Marie-Celine; Kocks, Christine; Ferrandon, Dominique] Univ Strasbourg, CNRS, Inst Biol Mol & Cellulaire, Equipe Fdn Rech Med,UPR 9022, Strasbourg, France.
[Cho, Ju Hyun; Lee, Janice; Kocks, Christine] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Nehme, NT (reprint author), Hop Necker Enfants Malad, INSERM, U768, Paris, France.
EM D.Ferrandon@ibmc.u-strasbg.fr
OI FERRANDON, Dominique/0000-0001-7680-7773
FU Conseil National de la Recherche Scientifique du Liban; CNRS; NIH [PO1
AI44220]; Fondation pour la Recherche Medicale
FX N.N. was partially supported by a fellowship from the Conseil National
de la Recherche Scientifique du Liban. This work was supported
financially by the CNRS, a NIH Program grant PO1 AI44220, and a
DROSELEGANS grant from the Agence Nationale de la Recherche. The
Strasbourg team is an "Equipe FRM", a label awarded by the Fondation
pour la Recherche Medicale. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 58
TC 37
Z9 38
U1 2
U2 19
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 3
PY 2011
VL 6
IS 3
AR e14743
DI 10.1371/journal.pone.0014743
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729QI
UT WOS:000287965200003
PM 21390224
ER
PT J
AU Dutt, S
Narla, A
Lin, K
Mullally, A
Abayasekara, N
Megerdichian, C
Wilson, FH
Currie, T
Khanna-Gupta, A
Berliner, N
Kutok, JL
Ebert, BL
AF Dutt, Shilpee
Narla, Anupama
Lin, Katherine
Mullally, Ann
Abayasekara, Nirmalee
Megerdichian, Christine
Wilson, Frederick H.
Currie, Treeve
Khanna-Gupta, Arati
Berliner, Nancy
Kutok, Jeffery L.
Ebert, Benjamin L.
TI Haploinsufficiency for ribosomal protein genes causes selective
activation of p53 in human erythroid progenitor cells
SO BLOOD
LA English
DT Article
ID DIAMOND-BLACKFAN ANEMIA; HUMAN 5Q-SYNDROME; PIFITHRIN-ALPHA;
CANCER-THERAPY; MARROW FAILURE; P73 FUNCTION; DNA-DAMAGE; PATHWAY;
CLASSIFICATION; IDENTIFICATION
AB Haploinsufficiency for ribosomal protein genes has been implicated in the pathophysiology of Diamond-Blackfan anemia (DBA) and the 5q- syndrome, a subtype of myelodysplastic syndrome. The p53 pathway is activated by ribosome dysfunction, but the molecular basis for selective impairment of the erythroid lineage in disorders of ribosome function has not been determined. We found that p53 accumulates selectively in the erythroid lineage in primary human hematopoietic progenitor cells after expression of shRNAs targeting RPS14, the ribosomal protein gene deleted in the 5q- syndrome, or RPS19, the most commonly mutated gene in DBA. Induction of p53 led to lineage-specific accumulation of p21 and consequent cell cycle arrest in erythroid progenitor cells. Pharmacologic inhibition of p53 rescued the erythroid defect, whereas nutlin-3, a compound that activates p53 through inhibition of HDM2, selectively impaired erythropoiesis. In bone marrow biopsies from patients with DBA or del(5q) myelodysplastic syndrome, we found an accumulation of nuclear p53 staining in erythroid progenitor cells that was not present in control samples. Our findings indicate that the erythroid lineage has a low threshold for the induction of p53, providing a basis for the failure of erythropoiesis in the 5q- syndrome, DBA, and perhaps other bone marrow failure syndromes. (Blood. 2011; 117(9): 2567-2576)
C1 [Dutt, Shilpee; Narla, Anupama; Lin, Katherine; Mullally, Ann; Abayasekara, Nirmalee; Megerdichian, Christine; Wilson, Frederick H.; Khanna-Gupta, Arati; Berliner, Nancy; Ebert, Benjamin L.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Narla, Anupama; Ebert, Benjamin L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Narla, Anupama] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[Currie, Treeve; Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ebert, Benjamin L.] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Ebert, BL (reprint author), 1 Blackfan Circle,Karp 5-210, Boston, MA 02115 USA.
EM bebert@partners.org
FU National Institutes of Health [5R01 HL082945, P01 CA108631];
Burroughs-Wellcome Fund
FX This work was supported by the National Institutes of Health (grants
5R01 HL082945 and P01 CA108631) and the Burroughs-Wellcome Fund (Career
Award for Medical Scientists; B.L.E.).
NR 42
TC 148
Z9 153
U1 1
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 3
PY 2011
VL 117
IS 9
BP 2567
EP 2576
DI 10.1182/blood-2010-07-295238
PG 10
WC Hematology
SC Hematology
GA 732RR
UT WOS:000288207400008
PM 21068437
ER
PT J
AU Ehrlich, LIR
Serwold, T
Weissman, IL
AF Ehrlich, Lauren I. Richie
Serwold, Thomas
Weissman, Irving L.
TI In vitro assays misrepresent in vivo lineage potentials of murine
lymphoid progenitors
SO BLOOD
LA English
DT Article
ID T-CELL PROGENITORS; BONE-MARROW; STEM-CELLS; HEMATOPOIETIC PROGENITORS;
CONVERSION; DIFFERENTIATION; SPECIFICATION; GENERATION; ALPHA; BLOOD
AB The identity of T-cell progenitors that seed the thymus has remained controversial, largely because many studies differ over whether these progenitors retain myeloid potential. Contradictory reports diverge in their use of various in vitro and in vivo assays. To consolidate these discordant findings, we compared the myeloid potential of 2 putative thymus seeding populations, common lymphoid progenitors (CLPs) and multipotent progenitors (MPPs), and the earliest intrathymic progenitor (DN1), using 2 in vitro assays and in vivo readouts. These assays gave contradictory results: CLP and DN1 displayed surprisingly robust myeloid potential on OP9-DL1 in vitro stromal cocultures but displayed little myeloid potential in vivo, as well as in methylcellulose cultures. MPP, on the other hand, displayed robust myeloid potential in all settings. We conclude that stromal cocultures reveal cryptic, but non-physiologic, myeloid potentials of lymphoid progenitors, providing an explanation for contradictory findings in the field and underscoring the importance of using in vivo assays for the determination of physiologic lineage potentials. (Blood. 2011; 117(9): 2618-2624)
C1 [Ehrlich, Lauren I. Richie; Serwold, Thomas; Weissman, Irving L.] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
[Serwold, Thomas] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Ehrlich, LIR (reprint author), 2506 Speedway,NMS 2-314, Austin, TX 78712 USA.
EM lehrlich@mail.utexas.edu
FU Leukemia & Lymphoma Society; National Institutes of Health
[5R01A1047457, 5R01A1047458]; Joslin Diabetes Endocrinology Research
Center [P30DK36836]
FX This work was supported by the Leukemia & Lymphoma Society (Special
Fellow Career Development award; L.I.R.E.) and the National Institutes
of Health grants 5R01A1047457 and 5R01A1047458 (to I.L.W.) and Joslin
Diabetes Endocrinology Research Center grant P30DK36836 (to T.S.).
NR 21
TC 34
Z9 34
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 3
PY 2011
VL 117
IS 9
BP 2618
EP 2624
DI 10.1182/blood-2010-05-287102
PG 7
WC Hematology
SC Hematology
GA 732RR
UT WOS:000288207400014
ER
PT J
AU Gore, A
Li, Z
Fung, HL
Young, JE
Agarwal, S
Antosiewicz-Bourget, J
Canto, I
Giorgetti, A
Israel, MA
Kiskinis, E
Lee, JH
Loh, YH
Manos, PD
Montserrat, N
Panopoulos, AD
Ruiz, S
Wilbert, ML
Yu, JY
Kirkness, EF
Belmonte, JCI
Rossi, DJ
Thomson, JA
Eggan, K
Daley, GQ
Goldstein, LSB
Zhang, K
AF Gore, Athurva
Li, Zhe
Fung, Ho-Lim
Young, Jessica E.
Agarwal, Suneet
Antosiewicz-Bourget, Jessica
Canto, Isabel
Giorgetti, Alessandra
Israel, Mason A.
Kiskinis, Evangelos
Lee, Je-Hyuk
Loh, Yuin-Han
Manos, Philip D.
Montserrat, Nuria
Panopoulos, Athanasia D.
Ruiz, Sergio
Wilbert, Melissa L.
Yu, Junying
Kirkness, Ewen F.
Izpisua Belmonte, Juan Carlos
Rossi, Derrick J.
Thomson, James A.
Eggan, Kevin
Daley, George Q.
Goldstein, Lawrence S. B.
Zhang, Kun
TI Somatic coding mutations in human induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID IPS CELLS; GENOME; DNA; TRANSFORMATION; FIBROBLASTS; GENERATION;
SEQUENCES; EFFICIENT; SELECTION; VARIANTS
AB Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use.
C1 [Young, Jessica E.; Canto, Isabel; Israel, Mason A.; Wilbert, Melissa L.; Goldstein, Lawrence S. B.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[Young, Jessica E.; Canto, Isabel; Israel, Mason A.; Wilbert, Melissa L.; Goldstein, Lawrence S. B.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
[Gore, Athurva; Li, Zhe; Fung, Ho-Lim; Zhang, Kun] Univ Calif San Diego, Inst Genom Med, Dept Bioengn, La Jolla, CA 92093 USA.
[Gore, Athurva; Li, Zhe; Fung, Ho-Lim; Zhang, Kun] Univ Calif San Diego, Inst Engn Med, La Jolla, CA 92093 USA.
[Agarwal, Suneet; Loh, Yuin-Han; Manos, Philip D.; Daley, George Q.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Agarwal, Suneet; Loh, Yuin-Han; Manos, Philip D.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Antosiewicz-Bourget, Jessica; Yu, Junying; Thomson, James A.] Univ Wisconsin, Dept Anat, Madison, WI 53705 USA.
[Giorgetti, Alessandra; Montserrat, Nuria; Izpisua Belmonte, Juan Carlos] Ctr Regenerat Med, Barcelona 08003, Spain.
[Kiskinis, Evangelos; Eggan, Kevin] Harvard Univ, Howard Hughes Med Inst, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Lee, Je-Hyuk] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02135 USA.
[Panopoulos, Athanasia D.; Ruiz, Sergio; Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
[Kirkness, Ewen F.] J Craig Venter Inst, Rockville, MD 20850 USA.
[Rossi, Derrick J.] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA.
RP Goldstein, LSB (reprint author), Univ Calif San Diego, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM lgoldstein@ucsd.edu; kzhang@bioeng.ucsd.edu
RI Loh, Yuin-Han/E-1096-2014; Montserrat, Nuria/F-3136-2016; Ruiz,
Sergio/G-1561-2016; Giorgetti, Alessandra/D-3784-2016
OI Loh, Yuin-Han/0000-0002-4715-6454; Montserrat,
Nuria/0000-0002-1603-1755; Ruiz, Sergio/0000-0002-0177-6965; Giorgetti,
Alessandra/0000-0002-2747-6514
FU NIH [R01 HL094963]; UCSD; California Institute for Regenerative Medicine
[TG2-01154]; CIRM [RC1-00116]; Focht-Powell Fellowship; National
Institute of General Medical Sciences [T32 GM008666]; A*Star Institute
of Medical Biology; Singapore Stem Cell Consortium; MICINN;
Sanofi-Aventis; G. Harold and Leila Y. Mathers Foundation; Cellex
Foundation
FX We thank J. M. Akey, G. M. Church, S. Ding, J. B. Li and J. Shendure for
discussions and suggestions, S. Vassallo for assistance with DNA
shearing, and G. L. Boulting and S. Ratansirintrawoot for assistance
with hiPS cell culture. This study is supported by NIH R01 HL094963 and
a UCSD new faculty start-up fund (to K.Z.), a training grant from the
California Institute for Regenerative Medicine (TG2-01154) and a CIRM
grant (RC1-00116) (to L.S.B.G.). L.S.B.G. is an Investigator of the
Howard Hughes Medical Institute. A. Gore is supported by the
Focht-Powell Fellowship and a CIRM predoctoral fellowship. M.L.W. is
supported by an institutional training grant from the National Institute
of General Medical Sciences (T32 GM008666). Y.-H.L. is supported by the
A*Star Institute of Medical Biology and the Singapore Stem Cell
Consortium. Work in the laboratory of J.C.I.B. was supported by grants
from MICINN, Sanofi-Aventis, the G. Harold and Leila Y. Mathers
Foundation and the Cellex Foundation. G.Q.D. is an investigator of the
Howard Hughes Medical Institute and supported by grants from the NIH.
NR 41
TC 627
Z9 661
U1 18
U2 147
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 3
PY 2011
VL 471
IS 7336
BP 63
EP U76
DI 10.1038/nature09805
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100034
PM 21368825
ER
PT J
AU Inuzuka, H
Shaik, S
Onoyama, I
Gao, DM
Tseng, A
Maser, RS
Zhai, B
Wan, LX
Gutierrez, A
Lau, AW
Xiao, YH
Christie, AL
Aster, J
Settleman, J
Gygi, SP
Kung, AL
Look, T
Nakayama, KI
DePinho, RA
Wei, WY
AF Inuzuka, Hiroyuki
Shaik, Shavali
Onoyama, Ichiro
Gao, Daming
Tseng, Alan
Maser, Richard S.
Zhai, Bo
Wan, Lixin
Gutierrez, Alejandro
Lau, Alan W.
Xiao, Yonghong
Christie, Amanda L.
Aster, Jon
Settleman, Jeffrey
Gygi, Steven P.
Kung, Andrew L.
Look, Thomas
Nakayama, Keiichi I.
DePinho, Ronald A.
Wei, Wenyi
TI SCFFBW7 regulates cellular apoptosis by targeting MCL1 for
ubiquitylation and destruction
SO NATURE
LA English
DT Article
ID FBW7 UBIQUITIN LIGASE; TUMOR-SUPPRESSOR; PHOSPHORYLATION; DEGRADATION;
DIFFERENTIATION; COMPLEX; CANCERS; PROTEIN
AB The effective use of targeted therapy is highly dependent on the identification of responder patient populations. Loss of FBW7, which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast cancer, colon cancer(1) and T-cell acute lymphoblastic leukaemia (T-ALL)(2). In line with these genomic data, engineered deletion of Fbw7 in mouse T cells results in T-ALL(3-5), validating FBW7 as a T-ALL tumour suppressor. Determining the precise molecular mechanisms by which FBW7 exerts antitumour activity is an area of intensive investigation. These mechanisms are thought to relate in part to FBW7-mediated destruction of key proteins relevant to cancer, including Jun(6), Myc(7), cyclin E-8 and notch 1 (ref. 9), all of which have oncoprotein activity and are overexpressed in various human cancers, including leukaemia. In addition to accelerating cell growth(10), overexpression of Jun, Myc or notch 1 can also induce programmed cell death(11). Thus, considerable uncertainty surrounds how FBW7-deficient cells evade cell death in the setting of upregulated Jun, Myc and/or notch 1. Here we show that the E3 ubiquitin ligase SCFFBW7 (a SKP1-cullin-1-F-box complex that contains FBW7 as the F-box protein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylation and destruction in a manner that depends on phosphorylation by glycogen synthase kinase 3. Human T-ALL cell lines showed a close relationship between FBW7 loss and MCL1 overexpression. Correspondingly, T-ALL cell lines with defective FBW7 are particularly sensitive to the multi-kinase inhibitor sorafenib but resistant to the BCL2 antagonist ABT-737. On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mechanism that enables FBW7-deficient cells to evade apoptosis. Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7-deficient T-ALL.
C1 [Inuzuka, Hiroyuki; Shaik, Shavali; Gao, Daming; Tseng, Alan; Wan, Lixin; Lau, Alan W.; Wei, Wenyi] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Onoyama, Ichiro; Nakayama, Keiichi I.] Kyushu Univ, Dept Mol & Cellular Biol, Med Inst Bioregulat, Fukuoka 8128582, Japan.
[Maser, Richard S.; Xiao, Yonghong; DePinho, Ronald A.] Harvard Univ, Belfer Inst Appl Canc Sci, Dana Farber Canc Inst, Dept Med Oncol,Sch Med, Boston, MA 02115 USA.
[Maser, Richard S.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Zhai, Bo; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Gutierrez, Alejandro; Christie, Amanda L.; Kung, Andrew L.; Look, Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Christie, Amanda L.; Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA.
[Aster, Jon] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Settleman, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Med, Boston, MA 02129 USA.
RP Wei, WY (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
EM wwei2@bidmc.harvard.edu
RI Maser, Richard/B-2970-2012; Wan, Lixin/F-2124-2011;
OI Gutierrez, Alejandro/0000-0002-0249-9007; Kung,
Andrew/0000-0002-9091-488X
FU Emerald Foundation; Leukemia and Lymphoma Society; National Institutes
of Health [GM089763]; Robert A. and Renee E. Belfer Foundation Institute
for Applied Cancer Science
FX We thank J. Lawler, C. Schorl, Q. Zhang and S. Glueck for critical
reading of the manuscript, J. DeCaprio, M.-C. Hung, M. A. Kelliher, W.
Harper and W. Hahn for providing reagents, L. Cantley and A. Toker for
suggestions, I. Wertz and V. Dixit for sharing unpublished data, and
members of the Wei and DePinho labs for useful discussions. W.W. is a
Kimmel Scholar and V Scholar. This work was supported in part by the
Emerald Foundation New Investigator award (W.W.), the Leukemia and
Lymphoma Society Special Fellow award (W.W.) and a grant from the
National Institutes of Health (W.W.; GM089763). R.A.D. is an American
Cancer Society Research Professor and is supported by the Robert A. and
Renee E. Belfer Foundation Institute for Applied Cancer Science.
NR 29
TC 246
Z9 255
U1 5
U2 37
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 3
PY 2011
VL 471
IS 7336
BP 104
EP U128
DI 10.1038/nature09732
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729BY
UT WOS:000287924100043
PM 21368833
ER
PT J
AU Felker, GM
Lee, KL
Bull, DA
Redfield, MM
Stevenson, LW
Goldsmith, SR
LeWinter, MM
Deswal, A
Rouleau, JL
Ofili, EO
Anstrom, KJ
Hernandez, AF
McNulty, SE
Velazquez, EJ
Kfoury, AG
Chen, HH
Givertz, MM
Semigran, MJ
Bart, BA
Mascette, AM
Braunwald, E
O'Connor, CM
AF Felker, G. Michael
Lee, Kerry L.
Bull, David A.
Redfield, Margaret M.
Stevenson, Lynne W.
Goldsmith, Steven R.
LeWinter, Martin M.
Deswal, Anita
Rouleau, Jean L.
Ofili, Elizabeth O.
Anstrom, Kevin J.
Hernandez, Adrian F.
McNulty, Steven E.
Velazquez, Eric J.
Kfoury, Abdallah G.
Chen, Horng H.
Givertz, Michael M.
Semigran, Marc J.
Bart, Bradley A.
Mascette, Alice M.
Braunwald, Eugene
O'Connor, Christopher M.
CA NHLBI Heart Failure Clinical Res N
TI Diuretic Strategies in Patients with Acute Decompensated Heart Failure
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CONTINUOUS-INFUSION; LOOP DIURETICS; INTRAVENOUS DIURETICS;
RENAL-FUNCTION; ESCAPE TRIAL; FUROSEMIDE; OUTCOMES; DIURESIS; REGISTRY;
DYSPNEA
AB BACKGROUND
Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use.
METHODS
In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.
RESULTS
In the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236 +/- 1440 and 4373 +/- 1404, respectively; P = 0.47) or in the mean change in the creatinine level (0.05 +/- 0.3 mg per deciliter [4.4 +/- 26.5 mu mol per liter] and 0.07 +/- 0.3 mg per deciliter [6.2 +/- 26.5 mu mol per liter], respectively; P = 0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430 +/- 1401 vs. 4171 +/- 1436; P = 0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08 +/- 0.3 mg per deciliter [7.1 +/- 26.5 mu mol per liter] with the high-dose strategy and 0.04 +/- 0.3 mg per deciliter [3.5 +/- 26.5 mu mol per liter] with the low-dose strategy, P = 0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.
CONCLUSIONS
Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose.
C1 [Felker, G. Michael; Lee, Kerry L.; Anstrom, Kevin J.; Hernandez, Adrian F.; McNulty, Steven E.; Velazquez, Eric J.] Duke Clin Res Inst, Durham, NC 27705 USA.
[Felker, G. Michael; O'Connor, Christopher M.] Duke Univ, Sch Med, Durham, NC USA.
[Felker, G. Michael; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA.
[Bull, David A.; Kfoury, Abdallah G.] Univ Utah, Salt Lake City, UT USA.
[Redfield, Margaret M.; Chen, Horng H.] Mayo Clin, Rochester, MN USA.
[Stevenson, Lynne W.; Givertz, Michael M.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Goldsmith, Steven R.; Bart, Bradley A.] Univ Minnesota, Minneapolis, MN USA.
[LeWinter, Martin M.] Univ Vermont, Burlington, VT 05405 USA.
[Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA.
[Deswal, Anita] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Rouleau, Jean L.] Univ Montreal, Montreal, PQ, Canada.
[Rouleau, Jean L.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Ofili, Elizabeth O.] Morehouse Sch Med, Atlanta, GA 30310 USA.
[Mascette, Alice M.] NHLBI, Bethesda, MD 20892 USA.
RP Felker, GM (reprint author), Duke Clin Res Inst, 2400 Pratt St,Rm 0311 Terrace Level, Durham, NC 27705 USA.
EM michael.felker@duke.edu
RI Hernandez, Adrian F./A-7818-2016
OI Hernandez, Adrian F./0000-0003-3387-9616
FU National Heart, Lung, and Blood Institute [HL084861, HL084875, HL084877,
HL084889, HL084890, HL084891, HL084899, HL084904, HL084907, HL084931];
Amgen; Cytokinetics; Corthera; Otsuka; Novartis; Roche Diagnostics;
Medtronic; Johnson Johnson; Pfizer; Boehringer Ingelheim; XDx; Scios;
Anexon; Nile Therapeutics; GE Healthcare; Forest Pharmaceuticals;
Novella Clinical; Medpace; Roche; Actelion Pharmaceuticals; Trevena;
Martek Biosciences
FX The Heart Failure Clinical Research Network is supported by grants
(HL084861, HL084875, HL084877, HL084889, HL084890, HL084891, HL084899,
HL084904, HL084907, and HL084931) from the National Heart, Lung, and
Blood Institute.; Dr. Felker reports receiving consulting fees from
Amgen, Cytokinetics, Corthera, Otsuka, Novartis, and Roche Diagnostics
and grant support from Amgen, Cytokinetics, Otsuka, and Roche
Diagnostics; Dr. LeWinter, receiving consulting fees from Novartis,
grant support from Medtronic, and lecture fees from Medtronic and
Novartis; Dr. Anstrom, receiving consulting fees from Johnson & Johnson
and Pfizer; Dr. Hernandez, receiving consulting fees from Amgen and
grant support from Johnson & Johnson and serving on a clinical end
points committee for Corthera; Dr. Velazquez, receiving consulting fees
from Novartis and Boehringer Ingelheim, grant support from Johnson &
Johnson, and lecture fees from Novartis; Dr. Kfoury, receiving grant
support from Novartis and XDx; Dr. Chen, receiving grant support from
Scios, Anexon, and Nile Therapeutics, being named as a coinventor on
patents for chimeric natriuretic peptides, and receiving royalties from
Nile Therapeutics; and Dr. O'Connor, receiving consulting fees from
Merck, GE Healthcare, Forest Pharmaceuticals, Medtronic, Novella
Clinical, Medpace, Roche, Actelion Pharmaceuticals, Amgen, Trevena, and
Martek Biosciences and grant support from Johnson & Johnson. No other
potential conflict of interest relevant to this article was reported.
NR 26
TC 418
Z9 438
U1 2
U2 27
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 3
PY 2011
VL 364
IS 9
BP 797
EP 805
DI 10.1056/NEJMoa1005419
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 729DJ
UT WOS:000287928400005
PM 21366472
ER
PT J
AU Rosenheck, RA
Krystal, JH
Lew, R
Barnett, PG
Fiore, L
Valley, D
Thwin, SS
Vertrees, JE
Liang, MH
AF Rosenheck, Robert A.
Krystal, John H.
Lew, Robert
Barnett, Paul G.
Fiore, Louis
Valley, Danielle
Thwin, Soe Soe
Vertrees, Julia E.
Liang, Matthew H.
CA CSP555 Res Grp
TI Long-Acting Risperidone and Oral Antipsychotics in Unstable
Schizophrenia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID INJECTABLE RISPERIDONE; OPEN-LABEL; SCALE; EFFICACY; SAFETY;
RELIABILITY; THERAPY; RELAPSE; DEPOT; ACCEPTABILITY
AB BACKGROUND
Long-acting injectable risperidone, a second-generation antipsychotic agent, may improve adherence to treatment and outcomes in schizophrenia, but it has not been tested in a long-term randomized trial involving patients with unstable disease.
METHODS
We randomly assigned patients in the Veterans Affairs (VA) system who had schizophrenia or schizoaffective disorder and who had been hospitalized within the previous 2 years or were at imminent risk for hospitalization to 25 to 50 mg of long-acting injectable risperidone every two weeks or to a psychiatrist's choice of an oral antipsychotic. All patients were followed for up to 2 years. The primary end point was hospitalization in a VA or non-VA psychiatric hospital. Symptoms, quality of life, and functioning were assessed in blinded videoconference interviews.
RESULTS
Of 369 participants, 40% were hospitalized at randomization, 55% were hospitalized within the previous 2 years, and 5% were at risk for hospitalization. The rate of hospitalization after randomization was not significantly lower among patients who received long-acting injectable risperidone than among those who received oral antipsychotics (39% after 10.8 months vs. 45% after 11.3 months; hazard ratio, 0.87; 95% confidence interval, 0.63 to 1.20). Psychiatric symptoms, quality of life, scores on the Personal and Social Performance scale of global functioning, and neurologic side effects were not significantly improved with long-acting injectable risperidone as compared with control treatments. Patients who received long-acting injectable risperidone reported more adverse events at the injection site and more extrapyramidal symptoms.
CONCLUSIONS
Long-acting injectable risperidone was not superior to a psychiatrist's choice of oral treatment in patients with schizophrenia and schizoaffective disorder who were hospitalized or at high risk for hospitalization, and it was associated with more local injection-site and extrapyramidal adverse effects.
C1 [Rosenheck, Robert A.; Krystal, John H.] VA Connecticut Healthcare Syst, Res Educ & Clin Ctr, VA New England Mental Illness, West Haven, CT USA.
[Rosenheck, Robert A.; Krystal, John H.] Yale Univ, Sch Med, New Haven, CT USA.
[Lew, Robert; Fiore, Louis; Valley, Danielle; Thwin, Soe Soe; Liang, Matthew H.] Massachusetts Vet Epidemiol & Res Informat Ctr, VA Cooperat Studies Program, Coordinating Ctr, Boston, MA USA.
[Barnett, Paul G.] VA Hlth Econ Resource Ctr, Menlo Pk, CA USA.
[Vertrees, Julia E.] Clin Res Pharm Coordinating Ctr, VA Cooperat Studies Program, Albuquerque, NM USA.
RP Rosenheck, RA (reprint author), VA Connecticut Healthcare Syst 151D, Res Educ & Clin Ctr, VA New England Mental Illness, 950 Campbell Ave, West Haven, CT 06516 USA.
EM robert.rosenheck@va.gov
FU Veterans Affairs Cooperative Studies Program; Ortho-McNeil Janssen
Scientific Affairs
FX Supported by the Veterans Affairs Cooperative Studies Program and an
unrestricted grant from Ortho-McNeil Janssen Scientific Affairs.
NR 36
TC 118
Z9 121
U1 5
U2 14
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 3
PY 2011
VL 364
IS 9
BP 842
EP 851
DI 10.1056/NEJMoa1005987
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 729DJ
UT WOS:000287928400009
PM 21366475
ER
PT J
AU Eguchi, J
Wang, X
Yu, ST
Kershaw, EE
Chiu, PC
Dushay, J
Estall, JL
Klein, U
Maratos-Flier, E
Rosen, ED
AF Eguchi, Jun
Wang, Xun
Yu, Songtao
Kershaw, Erin E.
Chiu, Patricia C.
Dushay, Joanne
Estall, Jennifer L.
Klein, Ulf
Maratos-Flier, Eleftheria
Rosen, Evan D.
TI Transcriptional Control of Adipose Lipid Handling by IRF4
SO CELL METABOLISM
LA English
DT Article
ID INTERFERON-REGULATORY FACTOR-4; INSULIN-INDUCED PHOSPHORYLATION;
ACTIVATED PROTEIN-KINASE; BINDING-PROTEIN; TRIGLYCERIDE LIPASE;
GENE-EXPRESSION; PHOSPHODIESTERASE 3B; PPAR-GAMMA; ADIPOCYTES; LIPOLYSIS
AB Adipocytes store triglyceride during periods of nutritional affluence and release free fatty acids during fasting through coordinated cycles of lipogenesis and lipolysis. While much is known about the acute regulation of these processes during fasting and feeding, less is understood about the transcriptional basis by which adipocytes control lipid handling. Here, we show that interferon regulatory factor 4 (IRF4) is a critical determinant of the transcriptional response to nutrient availability in adipocytes. Fasting induces IRF4 in an insulin- and FoxO1-dependent manner. IRF4 is required for lipolysis, at least in part due to direct effects on the expression of adipocyte triglyceride lipase and hormone-sensitive lipase. Conversely, reduction of IRF4 enhances lipid synthesis. Mice lacking adipocyte IRF4 exhibit increased adiposity and deficient lipolysis. These studies establish a link between IRF4 and the disposition of calories in adipose tissue, with consequences for systemic metabolic homeostasis.
C1 [Eguchi, Jun; Wang, Xun; Chiu, Patricia C.; Dushay, Joanne; Maratos-Flier, Eleftheria; Rosen, Evan D.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA.
[Yu, Songtao] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Dept Pediat, Chicago, IL 60614 USA.
[Kershaw, Erin E.] Univ Pittsburgh, Div Endocrinol, Pittsburgh, PA 15261 USA.
[Estall, Jennifer L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Klein, Ulf] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
RP Rosen, ED (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA.
EM erosen@bidmc.harvard.edu
RI Kershaw, Erin/G-9587-2013
FU Kanae Foundation for the Promotion of Medical Science; American Heart
Association [AHA0825928D]; National Institutes of Health [NIH R01
DK63906, NIH R01 DK085171]
FX The authors wish to thank C.R. Kahn for use of samples from FIRKO mice,
Tak Mak for Irf4-/- mice, Shingo Kajimura, Tetsuya Hosooka,
Choel Son, Junji Kawashima, Linh Vong, and Mark Herman for technical
advice, Domenico Accili for FoxO1 adenoviral constructs, and members of
the Rosen lab for helpful discussion. We thank Leo Otterbein and Eva
Csizmadia for help with alveolar lavage and immunohistochemistry. This
work was funded by the Kanae Foundation for the Promotion of Medical
Science, American Heart Association Award AHA0825928D (to J.E.), and
National Institutes of Health grants NIH R01 DK63906 and NIH R01
DK085171 (to E.D.R.).
NR 53
TC 139
Z9 140
U1 1
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD MAR 2
PY 2011
VL 13
IS 3
BP 249
EP 259
DI 10.1016/j.cmet.2011.02.005
PG 11
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 731ZQ
UT WOS:000288150200006
PM 21356515
ER
PT J
AU Brink, JA
Goske, MJ
Patti, JA
AF Brink, James A.
Goske, Marilyn J.
Patti, John A.
TI Informed Consent for Radiologic Procedures
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Brink, James A.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Goske, Marilyn J.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Patti, John A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Brink, JA (reprint author), Yale Univ, Sch Med, New Haven, CT 06520 USA.
EM james.brink@yale.edu
NR 5
TC 6
Z9 6
U1 0
U2 0
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 2
PY 2011
VL 305
IS 9
BP 888
EP 889
DI 10.1001/jama.2011.222
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 728DP
UT WOS:000287854700015
PM 21364135
ER
PT J
AU Moye, J
Naik, AD
AF Moye, Jennifer
Naik, Aanand D.
TI Preserving Rights for Individuals Facing Guardianship
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Moye, Jennifer] VA Boston Healthcare Syst, Boston, MA USA.
[Moye, Jennifer] Harvard Univ, Sch Med, Boston, MA USA.
[Naik, Aanand D.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Naik, Aanand D.] Baylor Coll Med, Houston, TX 77030 USA.
RP Moye, J (reprint author), VA Boston Healthcare Syst, Psychiat, Brockton Campus,940 Belmont St, Brockton, MA 02301 USA.
EM jennifer.moye@va.gov
RI Moye, Jennifer/F-2240-2017
OI Moye, Jennifer/0000-0002-3434-347X
FU NIA NIH HHS [K23 AG027144, K23AG027144]; NIMH NIH HHS [R29 MH057104]
NR 9
TC 17
Z9 17
U1 0
U2 3
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 2
PY 2011
VL 305
IS 9
BP 936
EP 937
DI 10.1001/jama.2011.247
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 728DP
UT WOS:000287854700029
PM 21364144
ER
PT J
AU Henderson, ER
Groundland, JS
Pala, E
Dennis, JA
Wooten, R
Cheong, D
Windhager, R
Kotz, RI
Mercuri, M
Funovics, PT
Hornicek, FJ
Temple, HT
Ruggieri, P
Letson, GD
AF Henderson, Eric R.
Groundland, John S.
Pala, Elisa
Dennis, Jeremy A.
Wooten, Rebecca
Cheong, David
Windhager, Reinhard
Kotz, Rainer I.
Mercuri, Mario
Funovics, Philipp T.
Hornicek, Francis J.
Temple, H. Thomas
Ruggieri, Pietro
Letson, G. Douglas
TI Failure Mode Classification for Tumor Endoprostheses: Retrospective
Review of Five Institutions and a Literature Review
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Review
ID PROXIMAL FEMORAL REPLACEMENT; TOTAL KNEE ARTHROPLASTY; TOTAL
HIP-ARTHROPLASTY; LIMB SALVAGE SURGERY; TOTAL FEMUR REPLACEMENT;
MALIGNANT BONE-TUMOR; MORREY TOTAL ELBOW; QUALITY-OF-LIFE;
TERM-FOLLOW-UP; PROSTHETIC REPLACEMENT
AB Background: Massive endoprostheses provide orthopaedic oncologists with many reconstructive options after tumor resection, although failure rates are high. Because the number of these procedures is limited, failure of these devices has not been studied or classified adequately. This investigation is a multicenter review of the use of segmental endoprostheses with a focus on the modes, frequency, and timing of failure.
Methods: Retrospective reviews of the operative databases of five institutions identified 2174 skeletally mature patients who received a large endoprosthesis for tumor resection. Patients who had failure of the endoprosthesis were identified, and the etiology and timing of failure were noted. Similar failures were tabulated and classified on the basis of the risk of amputation and urgency of treatment. Statistical analysis was performed to identify dependent relationships among mode of failure, anatomic location, and failure timing. A literature review was performed, and similar analyses were done for these data.
Results: Five hundred and thirty-four failures were identified. Five modes of failure were identified and classified: soft-tissue failures (Type 1), aseptic loosening (Type 2), structural failures (Type 3), infection (Type 4), and tumor progression (Type 5). The most common mode of failure in this series was infection; in the literature, it was aseptic loosening. Statistical dependence was found between anatomic location and mode of failure and between mode of failure and time to failure. Significant differences were found in the incidence of failure mode Types 1, 2, 3, and 4 when polyaxial and uniaxial joints were compared. Significant dependence was also found between failure mode and anatomic location in the literature data.
Conclusions: There are five primary modes of endoprosthetic failure, and their relative incidences are significantly different and dependent on anatomic location. Mode of failure and time to failure also show a significant dependence. Because of these relationships, cumulative reporting of segmental failures should be avoided because anatomy-specific trends will be missed. Endoprosthetic design improvements should address failure modes specific to the anatomic location.
C1 [Henderson, Eric R.] H Lee Moffitt Canc Ctr & Res Inst, Sarcoma Program, Tampa, FL 33612 USA.
Univ Bologna, Ist Ortoped Rizzoli, I-40136 Bologna, Italy.
Univ Miami, Orthopaed Oncol Div, Dept Orthopaed Surg, Miami, FL 33136 USA.
Med Univ Vienna, Dept Orthopaed Surg, A-1090 Vienna, Austria.
Massachusetts Gen Hosp, Div Orthopaed Oncol, Boston, MA 02114 USA.
RP Henderson, ER (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Sarcoma Program, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM eric.r.henderson@gmail.com
FU DePuy; Johnson Johnson; Stryker
FX The authors did not receive any outside funding or grants in support of
their research for or preparation of this work. One or more of the
authors, or a member of his or her immediate family, received, in any
one year, payments or other benefits in excess of $10,000 or a
commitment or agreement to provide such benefits from commercial
entities (DePuy [Johnson & Johnson] and Stryker).
NR 93
TC 98
Z9 104
U1 7
U2 24
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 2
PY 2011
VL 93A
IS 5
BP 418
EP 429
DI 10.2106/JBJSJ.00834
PG 12
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 727UB
UT WOS:000287827000002
PM 21368074
ER
PT J
AU Buijze, GA
Richardson, S
Jupiter, JB
AF Buijze, Geert A.
Richardson, Shawn
Jupiter, Jesse B.
TI Successful Reconstruction for Complex Malunions and Nonunions of the
Tibia and Femur
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID TRAUMA-RELATED AMPUTATIONS; LOWER-EXTREMITY TRAUMA; FREE-TISSUE
TRANSFER; LOWER-LIMB INJURY; SALVAGE; FRACTURES; AMPUTEES; OUTCOMES;
REHABILITATION; SATISFACTION
AB Background: Information regarding the long-term outcomes of the treatment of lower-extremity fracture malunion and nonunion is lacking.
Methods: Twenty-nine secondarily referred patients with complex malunion or nonunion of the tibia or femur, treated by a single surgeon, were followed for a median of twenty years (range, twelve to thirty-five years) after injury. The patients were referred at a median of twenty months (range, 1.5 to 360 months) postinjury and had undergone a median of three prior surgical procedures (range, zero to twenty-eight). At the time of final follow-up, patient-based outcomes, patient satisfaction, and pain were evaluated.
Results: All twenty-nine patients had healing following treatment of the complex malunion or nonunion of the tibia or femur and were able to bear full weight and walk one block or more. The Lower Extremity Functional Scale (LEES) outcome tool revealed that twenty patients (69%) experienced moderate-to-severe difficulties in carrying out activities because of their lower-limb disability. The median Short Form-36 (SF-36) score was 67, with a median physical component score of 61 and a median mental component score of 71, indicating substantial impact on physical health status when compared with the norm.
Conclusions: Reconstruction can be a worthwhile endeavor and should be considered for all patients with complex malunion or nonunion of the tibia or femur.
C1 [Buijze, Geert A.] Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Boston, MA 02114 USA.
RP Buijze, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM gbuijze@partners.org
FU Netherlands Organisation for Scientific Research (NWO)
FX In support of their research for or preparation of this work, one or
more of the authors received, in any one year, outside funding or grants
in excess of $10,000 from the Netherlands Organisation for Scientific
Research (NWO). Neither they nor a member of their immediate families
received payments or other benefits or a commitment or agreement to
provide such benefits from a commercial entity.
NR 30
TC 4
Z9 6
U1 0
U2 1
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 2
PY 2011
VL 93A
IS 5
BP 485
EP 492
DI 10.2106/JBJS.J.00342
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 727UB
UT WOS:000287827000010
PM 21368081
ER
PT J
AU Rask-Madsen, C
King, GL
AF Rask-Madsen, Christian
King, George L.
TI Endothelium-Dependent Delivery of Insulin to Muscle Interstitium
SO CELL METABOLISM
LA English
DT Editorial Material
ID RESISTANCE; TRANSPORT; CELLS; MICE
AB Insulin contributes to skeletal muscle glucose uptake by increasing blood flow and recruiting perfused capillaries. In this issue of Cell Metabolism, Kubota et al. (2011) show that deletion of IRS-2 in endothelial cells in mice causes impaired transcapillary insulin transport, decreased insulin-stimulated glucose uptake in muscle, and mild glucose intolerance.
C1 [Rask-Madsen, Christian; King, George L.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
RP King, GL (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM george.king@joslin.harvard.edu
FU NEI NIH HHS [K08 EY018677-04, K08 EY018677]; NIDDK NIH HHS [R01
DK053105, R01 DK053105-11]
NR 10
TC 7
Z9 7
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD MAR 2
PY 2011
VL 13
IS 3
BP 236
EP 238
DI 10.1016/j.cmet.2011.02.008
PG 3
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 731ZQ
UT WOS:000288150200003
PM 21356512
ER
PT J
AU Michael, I
Walton, DS
Levenberg, S
AF Michael, Inbal
Walton, David S.
Levenberg, Shulamit
TI Infantile Aphakic Glaucoma: A Proposed Etiologic Role of IL-4 and VEGF
SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS
LA English
DT Article
ID LENS EPITHELIAL-CELLS; TRABECULAR MESHWORK CELLS; ENDOTHELIAL
GROWTH-FACTOR; CONGENITAL CATARACT-SURGERY; AQUEOUS-HUMOR; SURVIVAL;
EXPRESSION; CYTOKINES; BETA; PROLIFERATION
AB Purpose: To identify the factors secreted by lens epithelial cells (LECs) responsible for the altered trabecular meshwork (TM) cells and to compare their effect on monocultured TM cells with that of TM cells co-cultured with LECs.
Methods: Such factors were isolated using cytokine antibody array membranes, and their effect on TM cells was assessed by analyzing changes in morphology and gene expression. In addition, inhibition of the isolated factors was performed in the co-culture model by adding specific antibodies to the cell culture media.
Results: Transforming growth factor beta-2, interleukin-4 (IL-4), and vascular endothelial growth factor (VEGF) are presented as candidate cytokines responsible for the observed changes in LEC-TM co-cultures. Culturing TM cells in the presence of VEGF and IL-4 triggered alterations closely reflecting those observed in the LEC-TM co-culture model, where their inhibition significantly hindered the alteration of the TM cells.
Conclusion: These findings suggest a possible explanation for the development of infantile aphakic glaucoma, based on residual LECs secreting IL-4 and VEGF after removal of congenital cataract, which then alter trabecular meshwork cell morphology and gene expression. [J Pediatr Ophthalmol Strabismus 2011;48:98-107.]
C1 [Michael, Inbal; Levenberg, Shulamit] Technion Israel Inst Technol, Fac Biomed Engn, IL-32000 Haifa, Israel.
[Walton, David S.] Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Levenberg, S (reprint author), Technion Israel Inst Technol, Fac Biomed Engn, IL-32000 Haifa, Israel.
FU Children's Glaucoma Foundation, Boston, Massachusetts
FX Supported by The Children's Glaucoma Foundation, Boston, Massachusetts.
NR 32
TC 3
Z9 4
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0191-3913
J9 J PEDIAT OPHTH STRAB
JI J. Pediatr. Ophthalmol. Strabismus.
PD MAR-APR
PY 2011
VL 48
IS 2
BP 98
EP 107
DI 10.3928/01913913-20100518-04
PG 10
WC Ophthalmology; Pediatrics
SC Ophthalmology; Pediatrics
GA 879PM
UT WOS:000299343900006
PM 20506964
ER
PT J
AU Tefferi, A
Abdel-Wahab, O
Cervantes, F
Crispino, JD
Finazzi, G
Girodon, F
Gisslinger, H
Gotlib, J
Kiladjian, JJ
Levine, RL
Licht, JD
Mullally, A
Odenike, O
Pardanani, A
Silver, RT
Solary, E
Mughal, T
AF Tefferi, A.
Abdel-Wahab, O.
Cervantes, F.
Crispino, J. D.
Finazzi, G.
Girodon, F.
Gisslinger, H.
Gotlib, J.
Kiladjian, J-J
Levine, R. L.
Licht, J. D.
Mullally, A.
Odenike, O.
Pardanani, A.
Silver, R. T.
Solary, E.
Mughal, T.
TI Mutations with epigenetic effects in myeloproliferative neoplasms and
recent progress in treatment: Proceedings from the 5th International
Post-ASH Symposium
SO BLOOD CANCER JOURNAL
LA English
DT Article
DE myeloproliferative; myelofibrosis; polycythemia; thrombocythemia;
mastocytosis
ID ACUTE MYELOID-LEUKEMIA; JAK2 46/1 HAPLOTYPE; CHRONIC MYELOMONOCYTIC
LEUKEMIA; METHYLTRANSFERASE GENE EZH2; WORLD-HEALTH-ORGANIZATION;
TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA;
PRIMARY MYELOFIBROSIS; MYELODYSPLASTIC SYNDROMES
AB Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7-8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-alpha, midostaurin and cladribine. In addition, the new 'Dynamic International Prognostic Scoring System (DIPSS)-plus' prognostic model for primary myelofibrosis (PMF) and the clinical relevance of distinguishing essential thrombocythemia from prefibrotic PMF are discussed. Blood Cancer Journal (2011) 1, e7; doi:10.1038/bcj.2011.4; published online 4 March 2011
C1 [Tefferi, A.; Pardanani, A.] Mayo Clin, Dept Med, Div Hematol, Rochester, MN 55905 USA.
[Abdel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Dept Med, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Abdel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10021 USA.
[Cervantes, F.] Univ Barcelona, Dept Hematol, Hosp Clin, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain.
[Crispino, J. D.; Licht, J. D.] Northwestern Univ, Dept Hematol, Chicago, IL 60611 USA.
[Finazzi, G.] Osped Riuniti Bergamo, Dept Hematol, I-24100 Bergamo, Italy.
[Girodon, F.] Hop Bocage, Hematol Lab, Dijon, France.
[Gisslinger, H.] Med Univ Vienna, Dept Internal Med 1, Div Hematol & Blood Coagulat, Vienna, Austria.
[Gotlib, J.] Stanford Univ, Sch Med, Div Hematol, Stanford, CA 94305 USA.
[Kiladjian, J-J] Univ Paris 07, Hop St Louis, AP HP, Ctr Invest Clin 9504, Paris, France.
[Mullally, A.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Hematol,Dept Med,Med Sch, Boston, MA 02115 USA.
[Odenike, O.] Univ Chicago, Sect Hematol & Oncol, Chicago, IL 60637 USA.
[Silver, R. T.] Cornell Univ, Div Hematol & Med Oncol, Dept Med, Weill Med Coll, New York, NY 10021 USA.
[Solary, E.] Univ Paris 11, Inst Gustave Roussy, INSERM, U1009, Villejuif, France.
[Mughal, T.] Guys Hosp, Sch Med, Dept Haematol, London SE1 9RT, England.
RP Tefferi, A (reprint author), Mayo Clin, Dept Med, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA.
EM tefferi.ayalew@mayo.edu
OI Abdel-Wahab, Omar/0000-0002-3907-6171; Kiladjian,
Jean-Jacques/0000-0002-8121-438X; Crispino, John/0000-0002-8182-8306
NR 147
TC 4
Z9 4
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2044-5385
J9 BLOOD CANCER J
JI Blood Cancer J.
PD MAR
PY 2011
VL 1
AR e7
DI 10.1038/bcj.2011.4
PG 10
WC Oncology
SC Oncology
GA 872NC
UT WOS:000298815400001
PM 23471017
ER
PT J
AU Harris, RD
Marks, WM
AF Harris, Robert D.
Marks, William M.
TI Donation and Training of Medical Personnel in Compact Ultrasound in
Low-Resource Settings How We Do It
SO ULTRASOUND QUARTERLY
LA English
DT Article
DE compact ultrasound; portable ultrasound; obstetric ultrasound screening;
low-resource settings; ultrasound training; perinatal mortality;
maternal morbidity and mortality; rural clinics
AB The authors offer a concise summary of dos and don'ts for the radiologist/sonologist wishing to expand his horizons and join those physicians donating ultrasound equipment and training medical personnel in low-resource countries. Topics include choosing a site, obtaining ultrasound equipment, preparing to travel, and starting a training program. The most important points to keep in mind are: (1) be prepared for any circumstance; (2) do your homework ahead of time; (3) make sure there is a local group "on the ground" that can ensure the machine's sustainability; and (4) allow for much more time to get things accomplished than in the developed world.
C1 [Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Radiol, Lebanon, NH 03756 USA.
[Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept OB GYN, Lebanon, NH 03756 USA.
[Marks, William M.] Massachusetts Gen Hosp, Div Global Hlth & Human Right, Boston, MA 02114 USA.
[Marks, William M.] Radia Imaging Inc, Swedish Med Ctr, Seattle, WA USA.
RP Harris, RD (reprint author), Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Radiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM Robert.D.Harris@hitchcock.org
NR 4
TC 4
Z9 4
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-8771
J9 ULTRASOUND Q
JI Ultrasound Q.
PD MAR
PY 2011
VL 27
IS 1
BP 3
EP 6
DI 10.1097/RUQ.0b013e31820e1598
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 854XD
UT WOS:000297527200002
PM 21343798
ER
PT J
AU Manchikanti, L
Giordano, J
Fellows, B
Hirsch, JA
AF Manchikanti, Laxmaiah
Giordano, James
Fellows, Bert
Hirsch, Joshua A.
TI Placebo and Nocebo in Interventional Pain Management: A Friend or a Foe
- Or Simply Foes?
SO PAIN PHYSICIAN
LA English
DT Review
DE Placebo; placebo analgesia; placebo treatment; placebo effect; nocebo;
nocebo hyperalgesia; psychophysiological mediators; neurobiological
mediators; inert agent
ID LOW-BACK-PAIN; EVIDENCE-BASED MEDICINE; CAUDAL EPIDURAL INJECTIONS;
LUMBAR SURGERY SYNDROME; MEDIAL BRANCH BLOCKS; CLINICAL-PRACTICE
GUIDELINE; FACET JOINT INTERVENTIONS; TRIALS COMPARING PLACEBO;
IRRITABLE-BOWEL-SYNDROME; ACTIVE CONTROLLED-TRIAL
AB The present evidence illustrates that the placebo effect depends on a variety of neurochemical and neurophysiological mechanisms, which are measurable and modifiable. However, the placebo response is inexorably tied to the treatment context. All medical treatments take place in a particular context; this context includes the therapist's attitudes, psychosocial factors affecting the therapeutic relationship, and the patient's mindset. Therapeutic efficacy at least in part is attributable to the concordance between the proposed treatment and the patient's belief system. It is this fraction of the therapeutic response that is commonly called the placebo effect. More formally, the placebo effect is defined as that part of the therapeutic response that is not attributable to the properties of active ingredients.
A proposed model of the placebo effect includes a complex reaction with induction, psychophysiological mediators, neurobiological mediators, and actualization of effects. Similarly, nocebo hyperalgesia is also explained by neurobiological mechanisms resulting in anxiety and nocebo hyperalgesia. Functional neuroanatomy of placebo indicates an anticipation phase and modulation phase or placebo response.
In modern medicine it is well recognized that the treatment effect of many active interventions is related to both an active treatment component and the placebo component. Thus, clinical implications are enormous as such placebo analgesia and nocebo hyperalgesia are not simply response biases. Instead, they are the product of neurophysiological processes that modulate the integration of the nociceptive signals throughout the central nervous system. Thus, it has been suggested that clinicians should not try to avoid the placebo effect. On the contrary, they should try to potentiate it, since this is a very important clinical implication.
From the research perspective, the emerging knowledge of placebo continues to cast doubts on the appropriateness of the double-blind placebo-control design in assessing efficacy of treatment - specifically involving interventional techniques or surgery. The research setting itself may introduce nocebo hyperalgesia.
C1 [Manchikanti, Laxmaiah; Fellows, Bert] Pain Management Ctr Paducah, Paducah, KY USA.
[Giordano, James] Potomac Inst Policy Studies, Ctr Neurotechnol Studies, Arlington, VA USA.
[Giordano, James] Univ Oxford, Wellcome Ctr Neuroeth, Oxford, England.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
NR 192
TC 55
Z9 57
U1 3
U2 17
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD MAR-APR
PY 2011
VL 14
IS 2
BP E157
EP E175
PG 19
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 857IV
UT WOS:000297712700005
PM 21412379
ER
PT J
AU Boehmer, A
Pfafferott, K
Humphreys, IS
Lucas, M
Swadling, L
Lauer, GM
Gaudieri, S
Klenerman, P
Barnes, E
AF Boehmer, A.
Pfafferott, K.
Humphreys, I. S.
Lucas, M.
Swadling, L.
Lauer, G. M.
Gaudieri, S.
Klenerman, P.
Barnes, E.
TI MULTIPLE NOVEL PEPTIDE EPITOPES IN HCV GENOTYPE-3A IDENTIFIED USING TWO
PARALLEL APPROACHES
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 46th Annual Meeting of the
European-Association-for-the-Study-of-the-Liver (EASL)
CY 2011
CL Berlin, GERMANY
SP European Assoc Study Liver (EASL)
C1 [Boehmer, A.; Humphreys, I. S.; Swadling, L.; Klenerman, P.; Barnes, E.] Univ Oxford, Nuffield Dept Clin Med, Oxford, England.
[Pfafferott, K.; Lucas, M.; Gaudieri, S.] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia.
[Pfafferott, K.; Lucas, M.; Gaudieri, S.] Murdoch Univ, Perth, WA, Australia.
[Lauer, G. M.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA.
[Lauer, G. M.] Harvard Univ, Sch Med, Boston, MA USA.
[Gaudieri, S.] Univ Western Australia, Sch Anat & Human Biol, Perth, WA 6009, Australia.
[Gaudieri, S.] Univ Western Australia, Ctr Forens Sci, Perth, WA 6009, Australia.
[Klenerman, P.; Barnes, E.] Univ Oxford, Oxford NIHR Biomed Res Ctr, Oxford, England.
EM annette.boehmer@chch.ox.ac.uk
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2011
VL 54
SU 1
MA 276
BP S113
EP S113
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 856GC
UT WOS:000297625600277
ER
PT J
AU Corradini, E
Meynard, D
Montosi, G
Garuti, C
Wu, Q
Ventura, P
Babitt, JL
Lin, HY
Pietrangelo, A
AF Corradini, E.
Meynard, D.
Montosi, G.
Garuti, C.
Wu, Q.
Ventura, P.
Babitt, J. L.
Lin, H. Y.
Pietrangelo, A.
TI THE MOLECULAR BASIS FOR THE HEPATIC REGULATION OF HEPCIDIN, THE IRON
HORMONE, BY BONE MORPHOGENETIC PROTEINS
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 46th Annual Meeting of the
European-Association-for-the-Study-of-the-Liver (EASL)
CY 2011
CL Berlin, GERMANY
SP European Assoc Study Liver (EASL)
C1 [Corradini, E.; Montosi, G.; Garuti, C.; Ventura, P.; Pietrangelo, A.] Univ Modena & Reggio Emilia, Dept Internal Med, Ctr Hemochromatosis, Modena, Italy.
[Meynard, D.; Wu, Q.; Babitt, J. L.; Lin, H. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol,Div Nephrol,Program Membrane Biol, Boston, MA USA.
EM elena.corradini75@unimore.it
RI meynard, delphine/B-4236-2014; Corradini, Elena/O-4167-2016;
Pietrangelo, Antonello/K-1517-2016
OI Corradini, Elena/0000-0001-9477-2164; Pietrangelo,
Antonello/0000-0002-7411-935X
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2011
VL 54
SU 1
MA 92
BP S41
EP S41
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 856GC
UT WOS:000297625600093
ER
PT J
AU Hu, W
Nevzorova, YA
Nowak, JR
Haas, U
Moro, N
Geng, Y
Sicinski, P
Barbacid, M
Trautwein, C
Liedtke, C
AF Hu, W.
Nevzorova, Y. A.
Nowak, J. R.
Haas, U.
Moro, N.
Geng, Y.
Sicinski, P.
Barbacid, M.
Trautwein, C.
Liedtke, C.
TI CYCLIN E1 AND D1 CAN DRIVE LIVER REGENERATION IN MICE WITHOUT CDK2
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 46th Annual Meeting of the
European-Association-for-the-Study-of-the-Liver (EASL)
CY 2011
CL Berlin, GERMANY
SP European Assoc Study Liver (EASL)
C1 [Hu, W.; Nevzorova, Y. A.; Nowak, J. R.; Haas, U.; Moro, N.; Trautwein, C.; Liedtke, C.] Rhein Westfal TH Aachen, Univ Hosp Aachen, Dept Med 3, Aachen, Germany.
[Geng, Y.; Sicinski, P.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Barbacid, M.] CNIO, Madrid, Spain.
EM whu@ukaachen.de
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2011
VL 54
SU 1
MA 1084
BP S428
EP S428
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 856GC
UT WOS:000297625602223
ER
PT J
AU Kuntzen, T
Neumann-Haefelin, C
Lennon, N
Talal, AH
Carlson, J
Brumme, C
Timm, J
Schmidt, J
Wunsch, K
Berical, A
Berlin, AM
Adams, S
Young, SK
Reyor, LL
Kleyman, M
McMahon, CM
Birch, C
zur Wiesch, JS
Ledlie, T
Michael, K
Kodira, C
Roberts, AD
Schneidewind, A
Lauer, GM
Kim, AY
Rosen, HR
Bihl, F
Cerny, A
Spengler, U
Brander, C
Galagan, JE
Nusbaum, C
Walker, BD
Lake-Bakaar, GV
Daar, ES
Jacobson, IM
Gomperts, ED
Edlin, BR
Donfield, SM
Chung, RT
Marion, T
Birren, BW
Marincola, F
Thimme, R
Carrington, M
Heckerman, D
Henn, MR
Allen, TM
AF Kuntzen, T.
Neumann-Haefelin, C.
Lennon, N.
Talal, A. H.
Carlson, J.
Brumme, C.
Timm, J.
Schmidt, J.
Wunsch, K.
Berical, A.
Berlin, A. M.
Adams, S.
Young, S. K.
Reyor, L. L.
Kleyman, M.
McMahon, C. M.
Birch, C.
zur Wiesch, J. Schulze
Ledlie, T.
Michael, K.
Kodira, C.
Roberts, A. D.
Schneidewind, A.
Lauer, G. M.
Kim, A. Y.
Rosen, H. R.
Bihl, F.
Cerny, A.
Spengler, U.
Brander, C.
Galagan, J. E.
Nusbaum, C.
Walker, B. D.
Lake-Bakaar, G. V.
Daar, E. S.
Jacobson, I. M.
Gomperts, E. D.
Edlin, B. R.
Donfield, S. M.
Chung, R. T.
Marion, T.
Birren, B. W.
Marincola, F.
Thimme, R.
Carrington, M.
Heckerman, D.
Henn, M. R.
Allen, T. M.
TI POPULATIONAL ANALYSIS REVEALS A LINK BETWEEN COMPLEX VIRAL ESCAPE FROM
CD8+T-CELL RESPONSES AND PROTECTION IN HCV INFECTION
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 46th Annual Meeting of the
European-Association-for-the-Study-of-the-Liver (EASL)
CY 2011
CL Berlin, GERMANY
SP European Assoc Study Liver (EASL)
C1 [Kuntzen, T.; Berical, A.; Reyor, L. L.; Kleyman, M.; McMahon, C. M.; Birch, C.; Schneidewind, A.; Lauer, G. M.; Kim, A. Y.; Walker, B. D.; Carrington, M.; Allen, T. M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Kuntzen, T.] Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland.
[Neumann-Haefelin, C.; Schmidt, J.; Wunsch, K.; Thimme, R.] Univ Freiburg, Freiburg, Germany.
[Lennon, N.; Berlin, A. M.; Young, S. K.; Michael, K.; Kodira, C.; Roberts, A. D.; Nusbaum, C.; Birren, B. W.; Henn, M. R.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Talal, A. H.; Lake-Bakaar, G. V.; Jacobson, I. M.; Edlin, B. R.] Weill Cornell Med Coll, New York, NY USA.
[Carlson, J.; Heckerman, D.] Microsoft Res, Redmond, WA USA.
[Brumme, C.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada.
[Timm, J.; Ledlie, T.] Univ Essen Gesamthsch, Essen, Germany.
[Adams, S.; Marincola, F.] NIH, Bethesda, MD 20892 USA.
[zur Wiesch, J. Schulze] Univ Hamburg Eppendorf, Hamburg, Germany.
[Rosen, H. R.] Univ Cologne, Denver, CO USA.
[Bihl, F.] Univ Geneva, Geneva, Switzerland.
[Cerny, A.] Clin Moncucco, Lugano, Switzerland.
[Spengler, U.] Univ Bonn, D-5300 Bonn, Germany.
[Brander, C.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain.
[Daar, E. S.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Gomperts, E. D.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Donfield, S. M.] Rho Inc, Chapel Hill, NC USA.
[Chung, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Marion, T.] Univ Tennessee, Memphis, TN USA.
EM christoph.neumann-haefelin@uniklinik-freiburg.de
RI Neumann-Haefelin, Christoph/E-5550-2011
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2011
VL 54
SU 1
MA 3
BP S2
EP S2
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 856GC
UT WOS:000297625600004
ER
PT J
AU O'Brien, TR
Morgan, TR
Pfeiffer, RM
Chung, RT
Lok, AS
Shiffman, ML
Dotrang, M
Sninsky, JJ
Bonkovsky, HL
AF O'Brien, T. R.
Morgan, T. R.
Pfeiffer, R. M.
Chung, R. T.
Lok, A. S.
Shiffman, M. L.
Dotrang, M.
Sninsky, J. J.
Bonkovsky, H. L.
CA HALT-C Trial Grp
TI IL28B GENETIC ATTRIBUTABLE RISK IN HEPATITIS C-ASSOCIATED HEPATOCELLULAR
CARCINOMA AND DECOMPENSATED LIVER DISEASE
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 46th Annual Meeting of the
European-Association-for-the-Study-of-the-Liver (EASL)
CY 2011
CL Berlin, GERMANY
SP European Assoc Study Liver (EASL)
C1 [O'Brien, T. R.; Pfeiffer, R. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Morgan, T. R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, T. R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
[Chung, R. T.] Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA.
[Chung, R. T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Lok, A. S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA.
[Shiffman, M. L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA.
[Dotrang, M.] CSC, Rockville, MD USA.
[Sninsky, J. J.] Celera Corp, Alameda, CA USA.
[Bonkovsky, H. L.] Univ Connecticut, Dept Med, Ctr Hlth, Farmington, CT 06032 USA.
[Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA.
[Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA.
[Bonkovsky, H. L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
EM timothy.morgan@va.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2011
VL 54
SU 1
MA 1336
BP S527
EP S528
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 856GC
UT WOS:000297625603020
ER
PT J
AU Rodriguez-Torres, M
Bacon, B
Gordon, S
Rubin, R
Box, T
Kugelmas, M
Vierling, J
Yoffe, B
Pockros, P
Everson, G
Jonas, M
Balart, L
Bohm, O
Castelloe, E
Huyghe, MR
Mento, S
Spada, A
Fox, AW
Chojkier, M
AF Rodriguez-Torres, M.
Bacon, B.
Gordon, S.
Rubin, R.
Box, T.
Kugelmas, M.
Vierling, J.
Yoffe, B.
Pockros, P.
Everson, G.
Jonas, M.
Balart, L.
Bohm, O.
Castelloe, E.
Huyghe, M. R.
Mento, S.
Spada, A.
Fox, A. W.
Chojkier, M.
TI UNIQUE PATTERN OF VIROLOGIC RESPONSE IN PATIENTS WITH GENOTYPE-1 HCV: A
PHASE II STUDY OF CTS-1027 IN COMBINATION WITH PEGINTERFERON/RIBAVIRIN
(SOC) IN NULL RESPONDERS
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 46th Annual Meeting of the
European-Association-for-the-Study-of-the-Liver (EASL)
CY 2011
CL Berlin, GERMANY
SP European Assoc Study Liver (EASL)
C1 [Rodriguez-Torres, M.] Fdn Invest Diego, San Juan, PR USA.
[Bacon, B.] St Louis Univ, St Louis, MO 63103 USA.
[Gordon, S.] Henry Ford Hosp, Detroit, MI 48202 USA.
[Rubin, R.] Liver Ctr Atlanta, Atlanta, GA USA.
[Box, T.] Univ Utah, Salt Lake City, UT USA.
[Kugelmas, M.] S Denver Gastroenterol, Denver, CO USA.
[Vierling, J.] Baylor Coll Med, Houston, TX 77030 USA.
[Yoffe, B.] VA Med Ctr, Houston, TX USA.
[Pockros, P.] Scripps Clin, La Jolla, CA USA.
[Everson, G.] Univ Colorado, Aurora, CO USA.
[Jonas, M.] Consultants Clin Res, Cincinnati, OH USA.
[Balart, L.] Tulane Univ Hlth Serv, New Orleans, LA USA.
[Bohm, O.] FGK Clin Res, Munich, Germany.
[Fox, A. W.] EBD Grp, Carlsbad, CA USA.
[Castelloe, E.; Huyghe, M. R.; Mento, S.; Spada, A.] Conatus Pharmaceut, San Diego, CA USA.
[Chojkier, M.] Univ Calif San Diego, San Diego, CA 92103 USA.
EM rodztorres@coqui.net
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2011
VL 54
SU 1
MA 468
BP S191
EP S191
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 856GC
UT WOS:000297625601048
ER
PT J
AU Unal-Cevik, I
Oaklander, AL
AF Unal-Cevik, Isin
Oaklander, Anne Louise
TI Comparing Partial and Total Tibial-Nerve Axotomy: Long-Term Effects on
Prevalence and Location of Evoked Pain Behaviors
SO PAIN PRACTICE
LA English
DT Article
DE rat; preclinical pain model; human; complex regional pain syndrome;
neuropathic pain; diagnostic criteria; hyperalgesia; tibial neuropathy;
partial tibial axotomy
ID NEUROPATHIC PAIN; SCIATIC-NERVE; DORSAL-HORN; SPINAL-CORD; PERIPHERAL
MONONEUROPATHY; POSTHERPETIC NEURALGIA; ADULT-RAT; INJURY; MODEL; SKIN
AB Monophasic (one-time) nerve injuries heal without clinically significant residua in most cases, but rare individuals are left with neuropathic pain, even after seemingly minor lesions. The effects of lesion size on risk for chronic pain persistence are not well understood, particularly as concerns the complex regional pain syndrome, which is defined in part by pain "disproportionate" to the severity of the causative lesion, and extending outside the autonomous territory of a single nerve. To better clarify the expected prevalence of pain behaviors after nerve injury, we compared the effects in rats of different-sized axotomies on the prevalence and location of evoked pain behaviors. To highlight clinical relevance, we also describe a patient with iatrogenic tibial-nerve injury causing similar chronic neuralgia. Adult male Sprague-Dawley rats were anesthetized and had either 1/3, 2/3 or their entire left tibial nerves tightly ligated at two sites just below the sciatic trifurcation and the interposed nerve was cut. Unoperated rats provided controls. Sensory function in the tibial and sural-innervated territories of both plantar hindpaws was assessed for as long as 6 months post-operatively. Soon after surgery, evoked pain behavior developed in the ipsilesional sural-innervated site in a subset of axotomized rats and recovery was variable. The relationship between lesion size and prevalence and severity of hyperalgesia varied for different pain behaviors, with pinprick hyperalgesia clearly more likely after larger axotomies. In summary, partial tibial-nerve injury in rats models human disease and suggests that expectations of proportionality between lesion size and development of neuropathic pain may need revision.
C1 Harvard Univ, Sch Med, Dept Neurol, Nerve Injury Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Pathol, Nerve Injury Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Unal-Cevik, I (reprint author), Ufuk Univ, Dept Neurol, Fac Med, TR-06520 Ankara, Turkey.
EM isin.unalcevik@gmail.com
FU Reflex Sympathetic Dystrophy Association; National Organization for Rare
Disorders; Public Health Service [R01NS42866, K24NS059892]
FX This study is supported in part by the Reflex Sympathetic Dystrophy
Association, the National Organization for Rare Disorders, the Public
Health Service (R01NS42866, K24NS059892). It was presented in abstract
form to the Society for Neuroscience. The technical assistance of Ralph
Gott, MA, and the statistical assistance of E. Burcu Mamak-Ekinci, MS,
are greatly appreciated.
NR 32
TC 1
Z9 1
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1530-7085
J9 PAIN PRACT
JI Pain Pract.
PD MAR-APR
PY 2011
VL 11
IS 2
BP 109
EP 119
DI 10.1111/j.1533-2500.2010.00429.x
PG 11
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 840UD
UT WOS:000296465900002
PM 21199309
ER
PT J
AU Mohamad, T
Bernal, JM
Kondur, A
Hari, P
Nelson, K
Niraj, A
Badheka, A
Hassna, S
Kiernan, T
Elder, MD
Gardi, D
Schreiber, T
AF Mohamad, Tamam
Bernal, Juan M.
Kondur, Ashok
Hari, Pawan
Nelson, Katrina
Niraj, Ashutosh
Badheka, Apurva
Hassna, Samer
Kiernan, Tom
Elder, Mahir D.
Gardi, Delair
Schreiber, Theodore
TI Coronary Revascularization Strategy for ST Elevation Myocardial
Infarction with Multivessel Disease: Experience and Results at 1-Year
Follow-Up
SO AMERICAN JOURNAL OF THERAPEUTICS
LA English
DT Article
DE ST elevation myocardial infarction (STEMI); coronary revascularization;
culprit lesions; nonculprit (non-CL) lesions
ID ISCHEMIC-HEART-DISEASE; ARTERY-DISEASE; UNSTABLE ANGINA;
CARDIOGENIC-SHOCK; INVASIVE THERAPY; CULPRIT LESION; ANGIOPLASTY;
VESSEL; INTERVENTION; REGISTRY
AB Primary percutaneous coronary intervention (PCI) of culprit lesions (CLs) is the standard of care in patients presenting with ST elevation myocardial infarction (STEMI). However, optimal revascularization strategy for significant nonculprit lesions (non-CLs) in the setting of STEMI remains controversial. The importance of defining of such a strategy lies in the fact that approximately 50% of patients with STEMI have multivessel disease (MVD). The aim of this study was to describe characteristics, therapeutic strategies, and 1-year outcomes in a cohort of patients with STEMI and MVD. We retrospectively analyzed a cohort of 63 patients with STEMI and MVD obtained from a 5-year catheterization database. MVD was defined as >= 70% stenosis of >= 2 epicardial coronary arteries. This cohort was followed for a period of 1 year for major adverse cardiac events (MACE was defined as acute coronary syndrome, new onset heart failure, or death) and all-cause mortality. PCI with stent placement was the major therapeutic procedure (87.5%) performed for CLs. Non-CLs did not undergo interventions in a majority of individuals (47.6%), while the remaining patients underwent PCI (29%) and coronary artery bypass graft surgery (22%) for non-CLs. At 1-year follow-up, prevalence of MACE events and death in the entire cohort were 30% and 15%, respectively. A trend for better outcomes (1-year cumulative MACE events but not mortality) was observed in CL-only intervention cohort compared with non-CL intervention. The PCI and Coronary artery bypass graft surgery cohorts did not show any significant difference in clinical outcomes. In this retrospective cohort of patients with MVD who presented with STEMI, no intervention of noncritical lesions was the prevalent approach, reflecting guideline recommendations. CL-only intervention strategy showed a better clinical outcome than non-CL intervention. Intervention of noncritical lesions therefore did not seem to improve MACEs or all-cause mortality at 1-year of follow-up and might in fact have had a detrimental effect on outcomes.
C1 [Mohamad, Tamam; Kondur, Ashok; Hari, Pawan; Nelson, Katrina; Niraj, Ashutosh; Badheka, Apurva; Hassna, Samer; Elder, Mahir D.; Gardi, Delair; Schreiber, Theodore] Wayne State Univ, Detroit, MI 48201 USA.
[Bernal, Juan M.; Kiernan, Tom] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Mohamad, T (reprint author), Wayne State Univ, Div Cardiol, Harper Univ Hosp, 8 Brush,3990 John R, Detroit, MI 48201 USA.
EM tamamns@yahoo.com
OI Hari, Pawan/0000-0003-1579-8476
NR 42
TC 17
Z9 19
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1075-2765
J9 AM J THER
JI Am. J. Ther.
PD MAR-APR
PY 2011
VL 18
IS 2
BP 92
EP 100
DI 10.1097/MJT.0b013e3181b809ee
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 733CP
UT WOS:000288238300006
PM 20027110
ER
PT J
AU Conrad, C
Husemann, Y
Niess, H
von Luettichau, I
Huss, R
Bauer, C
Jauch, KW
Klein, CA
Bruns, C
Nelson, PJ
AF Conrad, Claudius
Huesemann, Yves
Niess, Hanno
von Luettichau, Irene
Huss, Ralf
Bauer, Christian
Jauch, Karl-Walter
Klein, Christoph A.
Bruns, Christiane
Nelson, Peter J.
TI Linking Transgene Expression of Engineered Mesenchymal Stem Cells and
Angiopoietin-1-induced Differentiation to Target Cancer Angiogenesis
SO ANNALS OF SURGERY
LA English
DT Article
ID TUMOR ANGIOGENESIS; PERIPHERAL-BLOOD; GENE; THERAPY; DELIVERY; VECTORS;
PROGENITORS; TISSUE; GLIOMA; NICHE
AB Objective: To specifically target tumor angiogenesis by linking transgene expression of engineered mesenchymal stem cells to angiopoietin-1-induced differentiation.
Background: Mesenchymal stem cells (MSCs) have been used to deliver therapeutic genes into solid tumors. These strategies rely on their homing mechanisms only to deliver the therapeutic agent.
Methods: We engineered murine MSC to express reporter genes or therapeutic genes under the selective control of the Tie2 promoter/enhancer. This approach uses the differentiative potential of MSCs induced by the tumor microenvironment to drive therapeutic gene expression only in the context of angiogenesis.
Results: When injected into the peripheral circulation of mice with either, orthotopic pancreatic or spontaneous breast cancer, the engineered MSCs were actively recruited to growing tumor vasculature and induced the selective expression of either reporter red florescent protein or suicide genes [herpes simplex virus-thymidine kinase (TK) gene] when the adoptively transferred MSC developed endothelial-like characteristics. The TK gene product in combination with the prodrug ganciclovir (GCV) produces a potent toxin, which affects replicative cells. The homing of engineered MSC with selective induction of TK in concert with GCV resulted in a toxic tumor-specific environment. The efficacy of this approach was demonstrated by significant reduction in primary tumor growth and prolongation of life in both tumor models.
Conclusion: This "Trojan Horse" combined stem cell/gene therapy represents a novel treatment strategy for tailored therapy of solid tumors.
C1 [Conrad, Claudius] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Conrad, Claudius] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Boston, MA 02114 USA.
[Huesemann, Yves; Klein, Christoph A.] Univ Regensburg, Chair Expt Med, Dept Pathol, D-8400 Regensburg, Germany.
[Niess, Hanno; Jauch, Karl-Walter; Bruns, Christiane] Univ Munich, Dept Surg, Munich, Germany.
[von Luettichau, Irene] Tech Univ Munich, Dept Pediat, D-8000 Munich, Germany.
[von Luettichau, Irene] Tech Univ Munich, Pediat Oncol Ctr, D-8000 Munich, Germany.
[Huss, Ralf] Univ Munich, Inst Pathol, D-8000 Munich, Germany.
[Bauer, Christian] Univ Munich, Med Klin Innenstadt, Gastroenterol Sect, D-8000 Munich, Germany.
[Nelson, Peter J.] Univ Munich, Med Policlin, Clin Biochem Grp, D-8000 Munich, Germany.
RP Conrad, C (reprint author), Harvard Univ, Sch Med, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA.
EM CConrad1@partners.org
FU Deutsche Forschungsgemeinschaft [SFB 571 C2, SFB-TR36/B6, SPP1190];
Sander Stiftung
FX Supported by grants from the Deutsche Forschungsgemeinschaft (SFB 571 C2
and SFB-TR36/B6 to PJN, and SPP1190 to CAK, CB, and PJN). This work has
been supported by a grant from Sander Stiftung.
NR 35
TC 17
Z9 19
U1 3
U2 12
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 MAR
PY 2011
VL 253
IS 3
BP 566
EP 571
DI 10.1097/SLA.0b013e3181fcb5d8
PG 6
WC Surgery
SC Surgery
GA 719VF
UT WOS:000287238900019
PM 21169810
ER
PT J
AU Raval, MV
Hamilton, BH
Ingraham, AM
Ko, CY
Hall, BL
AF Raval, Mehul V.
Hamilton, Barton H.
Ingraham, Angela M.
Ko, Clifford Y.
Hall, Bruce L.
TI The Importance of Assessing Both Inpatient and Outpatient Surgical
Quality
SO ANNALS OF SURGERY
LA English
DT Article
ID IMPROVEMENT PROGRAM; RISK ADJUSTMENT; PATIENT SAFETY; AMERICAN-COLLEGE;
SURGERY; CARE; MORTALITY; HOSPITALS; MORBIDITY; CENTERS
AB Objective: We aimed to determine whether hospital-level surgical performance was similar across outpatient and inpatient settings.
Background: The majority of surgical procedures in the United States are performed in an outpatient setting but most quality improvement focuses on inpatient care.
Methods: Using data from the 2006 to 2008 American College of Surgeons-National Surgical Quality Improvement Program, risk-adjusted hospital observed to expected ratios for morbidity and mortality were compared for inpatient and outpatient cases. In addition, hospital outpatient performance in each year was compared with performances in subsequent years.
Results: Hospitals demonstrated variation in outcomes for outpatient morbidity with both good and poor outliers in each year. Outpatient mortality was so rare as to not support robust modeling. There was a lack of congruence between hospital performance for outpatient morbidity and either inpatient morbidity or inpatient mortality in each year, indicating that inpatient performance is not interchangeable with outpatient performance. Outpatient morbidity performance correlation between years was only moderate (correlations 0.449-0.534, all P < 0.001) indicating that although outcomes from 1 year mildly predict subsequent years, substitution of data would likely lead to missed opportunities for improvement.
Conclusions: Assessments of risk-adjusted hospital-level outpatient morbidity performance demonstrate (1) variability across American College of Surgeons-National Surgical Quality Improvement Program sites; (2) a lack of congruence between outpatient morbidity performance and either inpatient morbidity or mortality performance; (3) year-to-year variation of outpatient morbidity performance at individual institutions. Continuing evaluation of both outpatient and inpatient outcomes is supported. Given the substantial volume of outpatient care delivered, outpatient assessments are likely to be an important component of ongoing quality improvement efforts.
C1 [Raval, Mehul V.; Ingraham, Angela M.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA.
[Raval, Mehul V.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA.
[Hamilton, Barton H.; Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA.
[Ingraham, Angela M.] Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45267 USA.
[Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Hall, Bruce L.] Washington Univ, Dept Surg, John Cochran Vet Affairs Med Ctr, Ctr Hlth Policy, St Louis, MO USA.
[Hall, Bruce L.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
RP Raval, MV (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair,22nd Floor, Chicago, IL 60611 USA.
EM mraval@facs.org
RI Hamilton, Barton/P-5187-2015;
OI Raval, Mehul/0000-0002-1527-2661
FU John Gray Research Fellowship; Daniel F. and Ada L. Rice Foundation;
Health Policy
FX M.V.R is supported by the John Gray Research Fellowship and the Daniel
F. and Ada L. Rice Foundation. B. L. H was supported by the Center for
Health Policy, under the direction of Dr. William Peck, Washington
University in St. Louis, St. Louis, MO.
NR 37
TC 30
Z9 30
U1 0
U2 4
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 MAR
PY 2011
VL 253
IS 3
BP 611
EP 618
DI 10.1097/SLA.0b013e318208fd50
PG 8
WC Surgery
SC Surgery
GA 719VF
UT WOS:000287238900026
PM 21183845
ER
PT J
AU Kim, SJ
Giugliano, RP
Jang, IK
AF Kim, Soo-Joong
Giugliano, Robert P.
Jang, Ik-Kyung
TI Adjunctive pharmacologic therapy in percutaneous coronary intervention:
Part I antiplatelet therapy
SO CORONARY ARTERY DISEASE
LA English
DT Article
DE angioplasty; anticoagulant; antiplatelet therapy; antithrombotic
therapy; platelet; thrombin
ID PLATELET GLYCOPROTEIN-IIB/IIIA; ELEVATION MYOCARDIAL-INFARCTION;
PLACEBO-CONTROLLED TRIAL; RANDOMIZED-TRIAL; UNSTABLE ANGINA;
DOUBLE-BLIND; CLOPIDOGREL PRETREATMENT; CARDIOVASCULAR-DISEASE; ASPIRIN
RESISTANCE; PRASUGREL CS-747
AB Ischemic heart disease is a major cause of morbidity and mortality throughout the world. Percutaneous coronary intervention (PCI) has rapidly evolved from balloon angioplasty to drug-eluting stents over the past 25 years and has become an important treatment option for coronary heart disease. During PCI, atherosclerotic plaque disruption and the endothelium denudation stimulate both platelet aggregation and the thrombus generation. Therefore, pharmacological adjuvant therapies to protect the procedure-related thrombotic complication during PCI are indispensable. In addition to aspirin, whose benefit has been clearly shown in ischemic heart disease, clopidogrel and prasugrel have shown to dramatically reduce the rate of thrombosis after stent placement. The introduction of glycoprotein IIb/IIIa inhibitors has further improved the results of PCI especially in high-risk patients. In addition, several new drugs with antiplatelet or with antithrombin activities are currently under development. Coron Artery Dis 22:100-112 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
[Kim, Soo-Joong] Kyung Hee Univ, Coll Med, Dept Cardiol, Seoul, South Korea.
[Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02114 USA.
RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA.
EM ijang@partners.org
NR 58
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0954-6928
EI 1473-5830
J9 CORONARY ARTERY DIS
JI Coronary Artery Dis.
PD MAR
PY 2011
VL 22
IS 2
BP 100
EP 112
DI 10.1097/MCA.0b013e32833729e3
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 719GD
UT WOS:000287188700010
PM 20926950
ER
PT J
AU Schwab, P
Scalapino, K
AF Schwab, Pascale
Scalapino, Kenneth
TI Exercise for bone health: rationale and prescription
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE bone mass; exercise; mechano-transduction; osteocyte; osteoporosis
ID RANDOMIZED CONTROLLED-TRIALS; QUALITY-OF-LIFE; MECHANICAL SIGNALS;
HIGH-FREQUENCY; OSTEOPOROTIC FRACTURES; PHYSICAL-ACTIVITY;
MUSCLE-ACTIVITY; RISK-FACTORS; IN-VIVO; STRENGTH
AB Purpose of review
Patients frequently inquire about exercise as a means to improve bone strength and reduce osteoporotic fracture. Understanding the biologic mechanisms and the available clinical evidence supporting the role of exercise in bone health is the key to an educated discussion.
Recent findings
Exercise downregulates sclerostin expression by the osteocyte favoring osteoblastogenesis. These changes are enhanced by dynamic cyclical load with rest periods and may be promoted by low-amplitude high-frequency stimuli. In the prepubertal years, exercise results in periosteal gains, whereas exercise later in life maintains bone mass, reduces falls and probably associated fractures, and improves quality-of-life measures.
Summary
Future studies should examine the effect of exercise on bone strength and determine the minimum quantity and frequency and the exercise type most effective to reduce osteoporotic fractures.
C1 [Schwab, Pascale; Scalapino, Kenneth] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA.
RP Schwab, P (reprint author), 3710 SW Vet Hosp Rd, Portland, OR 97239 USA.
EM schwabp@ohsu.edu
NR 44
TC 8
Z9 8
U1 0
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8711
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD MAR
PY 2011
VL 23
IS 2
BP 137
EP 141
DI 10.1097/BOR.0b013e3283434501
PG 5
WC Rheumatology
SC Rheumatology
GA 715JB
UT WOS:000286879200003
PM 21178629
ER
PT J
AU Campling, BG
Collins, BN
Algazy, KM
Schnoll, RA
Lam, M
AF Campling, Barbara G.
Collins, Bradley N.
Algazy, Kenneth M.
Schnoll, Robert A.
Lam, Miu
TI Spontaneous Smoking Cessation Before Lung Cancer Diagnosis
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Lung neoplasms; Prostate cancer; Myocardial infarction; Smoking
cessation; Veterans
ID CELL-LINES; NICOTINE DEPENDENCE; MORTALITY; CARCINOMA; GROWTH; RISK;
ACETYLCHOLINE; ANGIOGENESIS; TACHYKININS; EXPRESSION
AB Introduction: We have observed that many patients with lung cancer stop smoking before diagnosis, usually before clinical symptoms, and often without difficulty. This led us to speculate that spontaneous smoking cessation may be a presenting symptom of lung cancer.
Methods: Patients from the Philadelphia Veterans Affairs Medical Center with lung cancer and for comparison, prostate cancer and myocardial infarction underwent a structured interview about their smoking habits preceding diagnosis. Severity of nicotine addiction was graded using the Fagerstrom Test for Nicotine Dependence. Among former smokers, dates of cessation, onset of symptoms, and diagnosis were recorded. Difficulty quitting was rated on a scale of 0 to 10. Distributions of intervals from cessation to diagnosis were compared between groups.
Results: All 115 patients with lung cancer had been smokers. Fifty-five (48%) quit before diagnosis, and only six of these (11%) were symptomatic at quitting. Patients with lung cancer who quit were as dependent on nicotine, when smoking the most, as those who continued to smoke, unlike the other groups. Despite this, 31% quit with no difficulty. The median interval from cessation to diagnosis was 2.7 years for lung cancer, 24.3 years for prostate cancer, and 10.0 years for patients with myocardial infarction.
Conclusions: These results challenge the notion that patients with lung cancer usually quit smoking because of disease symptoms. The hypothesis that spontaneous smoking cessation may be a presenting symptom of lung cancer warrants further investigation.
C1 [Campling, Barbara G.; Algazy, Kenneth M.] Univ Penn, Dept Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Collins, Bradley N.] Temple Univ, Dept Publ Hlth, Philadelphia, PA 19122 USA.
[Collins, Bradley N.] Temple Univ, Dept Pediat, Philadelphia, PA 19122 USA.
[Schnoll, Robert A.] Univ Penn, Dept Psychiat, Transdisciplinary Tobacco Use Res Ctr, Philadelphia, PA 19104 USA.
[Lam, Miu] Queens Univ, Dept Community Hlth & Epidemiol, Kingston, ON, Canada.
RP Campling, BG (reprint author), 834 Chestnut St,Suite 314, Philadelphia, PA 19107 USA.
EM Campling@jefferson.edu
FU Veterans Affairs Healthcare Network
FX Supported by a Veterans Affairs Healthcare Network Competitive Pilot
Project Grant. The sponsor had no involvement in the study design,
interpretation of results, or preparation of the manuscript. The
opinions expressed herein are those of the authors and do not represent
the views of the Department of Veterans Affairs or the United States
Government.
NR 36
TC 4
Z9 4
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD MAR
PY 2011
VL 6
IS 3
BP 517
EP 524
DI 10.1097/JTO.0b013e318208c7da
PG 8
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 719VR
UT WOS:000287240100015
PM 21258255
ER
PT J
AU Lo, K
Nguyen, J
Fay, A
AF Lo, Kristine
Nguyen, John
Fay, Aaron
TI Customized Jones Tube Using a Surgical Drill
SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
AB Purpose: To describe a technique for modifying a Jones tube length in the operating room.
Methods: The required length of the Jones tube is determined using an 18-gauge needle passed from the conjunctiva posterior to the caruncle to the middle meatus. A longer Jones tube is ground to the proper length with a 4-mm diamond burr on a saber drill.
Results: This procedure results in shortening of an oversized Jones tube in the operating room with no gross or microscopic defects in the glass surface.
Conclusions: This technique allows modification of a Jones tube when the appropriate size is not available and may reduce the number of sizes that must be maintained in the operating room.
C1 [Lo, Kristine; Nguyen, John; Fay, Aaron] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
RP Fay, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM aaron_fay@meei.harvard.edu
NR 2
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0740-9303
J9 OPHTHAL PLAST RECONS
JI Ophthalmic Plast. Reconstr. Surg.
PD MAR-APR
PY 2011
VL 27
IS 2
BP 130
EP 131
DI 10.1097/IOP.0b013e3181cd6320
PG 2
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 730BL
UT WOS:000288003800016
PM 20639784
ER
PT J
AU Windsor, JS
Rodway, GW
Mukherjee, R
Firth, PG
Shattock, M
Montgomery, HE
AF Windsor, J. S.
Rodway, G. W.
Mukherjee, R.
Firth, P. G.
Shattock, M.
Montgomery, H. E.
TI Prolongation of the Corrected QT Complex - A Cause of Sudden Cardiac
Death in the Mountain Environment?
SO JOURNAL OF THE ROYAL ARMY MEDICAL CORPS
LA English
DT Article
ID HIGH-RISK PATIENTS; HIGH-ALTITUDE; DYNAMIC ELECTROCARDIOGRAPHY;
UNITED-STATES; WEIGHT-LOSS; HEART-RATE; LONG; INTERVAL; MANAGEMENT;
HYPOTHERMIA
AB In the mountain environment sudden cardiac death (SCD) has been shown to be responsible for the deaths of up to 52% of downhill skiers and 30% of hikers. The majority of SCD's are precipitated by a ventricular arrhythmia. Although most are likely to result from structural abnormalities associated with conditions such as ischaemic heart disease, a small but significant number may be due to abnormalities in ion channel activity, commonly known as, "channelopathies". Channelopathies have the potential to lengthen the time between ventricular depolarisation and repolarisation that can result in prolongation of the corrected QT interval (QTc) and episodes of polymorphic ventricular tachycardia (PVT) and eventually, ventricular fibrillation. This review examines the factors that prolong the QTc interval in the mountain environment and outlines a practical framework for preventing the life threatening arrhythmias that are associated with this condition.
C1 [Windsor, J. S.; Mukherjee, R.; Montgomery, H. E.] UCL, UCL Ctr Altitude Space & Extreme Environm Med, Inst Human Hlth & Performance, London N19 5LW, England.
[Rodway, G. W.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA.
[Rodway, G. W.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Firth, P. G.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Shattock, M.] St Thomas Hosp, Div Cardiovasc, Rayne Inst, London, England.
RP Windsor, JS (reprint author), UCL, UCL Ctr Altitude Space & Extreme Environm Med, Inst Human Hlth & Performance, Charterhouse Bldg,Archway Campus,Highgate Hill, London N19 5LW, England.
RI Montgomery, Hugh/C-2592-2008;
OI Montgomery, Hugh/0000-0001-8797-5019; Family Name Deactivated, Given
Names Deactivated/0000-0001-6242-7585
NR 50
TC 0
Z9 0
U1 2
U2 2
PU RAMC JOURNAL PUBLICATIONS
PI CAMBERELY SURREY
PA HQ AMS, FASC, SLIM RD, CAMBERELY SURREY, GU15 4NP, ENGLAND
SN 0035-8665
J9 J ROY ARMY MED CORPS
JI J. R. Army Med. Corps
PD MAR
PY 2011
VL 157
IS 1
BP 63
EP 67
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 812FN
UT WOS:000294276600012
PM 21465913
ER
PT J
AU Neto, JFL
Kuhl, G
Smith, MM
de Souza, PA
Vieira, LR
AF Lubianca Neto, Jose Faibes
Kuhl, Gabriel
Smith, Mariana Magnus
de Souza, Person Antunes
Vieira, Leonardo Raduenz
TI Association between congenital nasolacrimal duct cyst and bilateral
choanal atresia
SO BRAZILIAN JOURNAL OF OTORHINOLARYNGOLOGY
LA English
DT Editorial Material
DE nasal obstruction; choanal atresia; nasolacrimal duct
C1 [Lubianca Neto, Jose Faibes] Univ Fed Rio Grande do Sul, UFRGS, BR-90046900 Porto Alegre, RS, Brazil.
[Lubianca Neto, Jose Faibes] Hosp Clin Porto Alegre, ENT Residency, Porto Alegre, RS, Brazil.
[Lubianca Neto, Jose Faibes] Harvard Univ, Massachusetts Eye & Ear Infirm, Pediat ENT Div, Sch Med, Boston, MA 02114 USA.
[Lubianca Neto, Jose Faibes] Fed Univ Hlth Sci, Porto Alegre, RS, Brazil.
[Lubianca Neto, Jose Faibes] Univ Fed Rio Grande do Sul, Grad Program Med Sci, Porto Alegre, RS, Brazil.
[Kuhl, Gabriel] Univ Coimbra, P-3000 Coimbra, Portugal.
[Kuhl, Gabriel] Univ Caxias Sul, Caxias Do Sul, RS, Brazil.
[Kuhl, Gabriel] Soc Otorhinolaryngol Rio Grande Sul, Porto Alegre, RS, Brazil.
[Smith, Mariana Magnus] Pontificia Univ Catolica Rio Grande do Sul, Porto Alegre, RS, Brazil.
[de Souza, Person Antunes] Univ Fed Pelotas, Pelotas, Brazil.
[Vieira, Leonardo Raduenz] Univ Fed Ciencias Saude Porto Alegre, Porto Alegre, RS, Brazil.
RP Neto, JFL (reprint author), Univ Fed Rio Grande do Sul, UFRGS, BR-90046900 Porto Alegre, RS, Brazil.
NR 5
TC 3
Z9 4
U1 0
U2 2
PU ASSOC BRASILEIRA OTORRINOLARINGOLOGIA & CIRURGIA CERVICOFACIAL
PI SAO PAULO
PA AV INDIANOPOLOS 740, MOEMA, SAO PAULO, SP 04062-001, BRAZIL
SN 1808-8694
J9 BRAZ J OTORHINOLAR
JI Braz. J. Otorhinolaryngol.
PD MAR-APR
PY 2011
VL 77
IS 2
BP 267
EP 267
PG 1
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 803JV
UT WOS:000293578500019
PM 21537631
ER
PT J
AU Shin, JJ
Rauch, SD
Wasserman, J
Coblens, O
Randolph, GW
AF Shin, Jennifer J.
Rauch, Steven D.
Wasserman, Jared
Coblens, Orly
Randolph, Gregory W.
TI Evidence-Based Medicine in Otolaryngology, Part 2: The Current State of
Affairs
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
DE evidence-based medicine; evidence-based practice; otolaryngology;
systematic reviews; levels of evidence
ID CLINICAL-PRACTICE GUIDELINE; RANDOMIZED CONTROLLED-TRIALS; JOURNALS;
PERCEPTIONS; ASSOCIATION; COMPETENCE; SURGEONS
AB What is the current state of evidence-based medicine in otolaryngology? This question inquires about the state of our literature, our attitudes and capabilities, and our patients' desires. Thus, this installment of "Evidence-Based Medicine in Otolaryngology" focuses on these 3 topics. First, the authors consider the literature relative to benchmarks for study design. Second, the data regarding otolaryngologists' and other surgical specialists' attitudes and understanding of clinical data are discussed. Third, patient-based efforts to promote and participate in evidence-based practice are explored. In addition, a discussion of the relevant supportive efforts made by our professional organizations is included.
C1 [Shin, Jennifer J.] Harvard Univ, Sch Med, Div Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Shin, Jennifer J.] So Calif Permanente Med Grp, Los Angeles Med Ctr, Div Head & Neck Surg, Los Angeles, CA 90027 USA.
[Rauch, Steven D.] Harvard Univ, Sch Med, Div Otol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Wasserman, Jared] ENT & Allergy Associates, Englewood, NJ USA.
[Coblens, Orly] New York State Amer Program, Sackler Sch Med, New York, NY USA.
[Randolph, Gregory W.] Harvard Univ, Sch Med, Div Gen Otolaryngol & Endocrine Surg, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Shin, JJ (reprint author), Harvard Univ, Sch Med, Div Otolaryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM jennifer_shin@meei.harvard.edu
RI Shin, Jennifer/A-3169-2016
FU Springer; Otonomy, Inc
FX Jennifer J. Shin is an editor of Evidence-Based Otolaryngology and
receives book royalties from Springer. Steven D. Rauch received grant
support from Otonomy, Inc and is a section editor of Evidence-Based
Otolaryngology. Gregory W. Randolph is an editor of Evidence-Based
Otolaryngology. (Shin J, Hartnick CJ, Randolph G, eds. Evidence-Based
Otolaryngology. New York, NY: Springer Science + Business Media, LLC;
2008.)
NR 47
TC 6
Z9 6
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD MAR
PY 2011
VL 144
IS 3
BP 331
EP 337
DI 10.1177/0194599810393856
PG 7
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 808RZ
UT WOS:000293997400001
PM 21493192
ER
PT J
AU Divi, V
Lin, DT
Emerick, K
Rocco, J
Deschler, DG
AF Divi, Vasu
Lin, Derrick T.
Emerick, Kevin
Rocco, James
Deschler, Daniel G.
TI Primary TEP Placement in Patients with Laryngopharyngeal Free Tissue
Reconstruction and Salivary Bypass Tube Placement
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
DE voice; head and neck cancer; reconstructive surgery; free flaps
ID PHARYNGOESOPHAGEAL RECONSTRUCTION; FLAP
AB The authors examined the feasibility and advantages of primary tracheoesophageal puncture (TEP) with intraoperative placement of the voice prosthesis for patients undergoing laryngopharyngectomy requiring free tissue reconstruction and salivary bypass tube placement. Six patients were identified; 4 underwent total laryngopharyngectomy, and 2 underwent total laryngectomy with partial pharyngectomy. All 6 required free tissue reconstruction, and a salivary bypass tube was placed in all cases. All patients had a 20F Indwelling Blom-Singer prosthesis (InHealth Technologies, Carpinteria, California) placed. No complications were noted with intraoperative prosthesis placement. No prostheses were dislodged in the postoperative period. At 6 months, 4 patients available for evaluation had successful voice outcomes, and 3 were disease free. This study demonstrates the effectiveness of voice prosthesis placement at the time of primary TEP associated with free tissue reconstruction of a laryngopharyngeal defect with salivary bypass tube placement.
C1 [Divi, Vasu; Lin, Derrick T.; Emerick, Kevin; Rocco, James; Deschler, Daniel G.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA.
RP Divi, V (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA.
EM vasudivi@med.umich.edu
NR 4
TC 6
Z9 6
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD MAR
PY 2011
VL 144
IS 3
BP 474
EP 476
DI 10.1177/0194599810391960
PG 3
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 808RZ
UT WOS:000293997400025
PM 21493216
ER
PT J
AU Naramura, M
Nadeau, S
Mohapatra, B
Ahmad, G
Mukhopadhyay, C
Sattler, M
Raja, SM
Natarajan, A
Band, V
Band, H
AF Naramura, Mayumi
Nadeau, Scott
Mohapatra, Bhopal
Ahmad, Gulzar
Mukhopadhyay, Chandrani
Sattler, Martin
Raja, Srikumar M.
Natarajan, Amarnath
Band, Vimla
Band, Hamid
TI Mutant Cbl proteins as oncogenic drivers in myeloproliferative disorders
SO ONCOTARGET
LA English
DT Article
DE Cbl; E3 ubiquitin ligase; leukemia; protein tyrosine kinase; signal
transduction
ID JUVENILE MYELOMONOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACQUIRED
UNIPARENTAL DISOMY; HEMATOPOIETIC STEM-CELLS; GROWTH-FACTOR RECEPTOR;
LIGASE C-CBL; RING FINGER; TYROSINE PHOSPHORYLATION; NEGATIVE
REGULATION; MUTATIONS
AB Casitas B-lineage lymphoma (Cbl) family proteins are evolutionarily-conserved attenuators of protein tyrosine kinase (PTK) signaling. Biochemical analyses over the past two decades have firmly established that the negative regulatory functions of Cbl proteins are mediated through their ability to facilitate ubiquitination and thus promote degradation of PTKs. As aberrant activation of PTKs is frequently associated with oncogenesis, it has long been postulated that loss of normal Cbl functions may lead to unregulated activation of PTKs and cellular transformation. In the last few years, mutations in the CBL gene have been identified in a subset of human patients with myeloid malignancies. Here we discuss insights gained from the analyses of Cbl mutants both in human patients and in animal models and propose potential mechanisms of oncogenesis through this pathway.
C1 [Naramura, Mayumi; Nadeau, Scott; Mohapatra, Bhopal; Ahmad, Gulzar; Mukhopadhyay, Chandrani; Raja, Srikumar M.; Natarajan, Amarnath; Band, Vimla; Band, Hamid] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
[Naramura, Mayumi; Nadeau, Scott; Band, Vimla; Band, Hamid] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Coll Med, Omaha, NE USA.
[Mohapatra, Bhopal; Band, Hamid] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Coll Med, Omaha, NE USA.
[Natarajan, Amarnath] Univ Nebraska Med Ctr, Dept Pharmaceut Sci, Coll Pharm, Omaha, NE USA.
[Sattler, Martin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Naramura, M (reprint author), Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
EM mnaramura@unmc.edu; hband@unmc.edu
FU US National Institutes of Health [CA87986, CA99163, CA105489, CA116552,
CA96844, CA127239, CA134660]; US Department of Defense
[W81XWH-11-1-0166, W81XWH-07-1-0351, W81XWH-11-1-0171,
W81XWH-10-1-0740]; University of Nebraska Medical Center (UNMC)-Eppley
Cancer Center; Nebraska Department of Health and Human Services
[LB-506]; Nebraska Center for Nanomedicine-Center for Biomedical
Research Excellence (NCN-COBRE)
FX Work in the authors' laboratories was supported by grants from the US
National Institutes of Health (CA87986, CA99163, CA105489 and CA116552
to H.B.; CA96844 to V.B.; CA127239 to A.N.; CA134660 to M.S.), the US
Department of Defense Breast Cancer Research Program (W81XWH-11-1-0166
to H.B; W81XWH-07-1-0351 and W81XWH-11-1-0171 to V.B; W81XWH-10-1-0740
to M.N.), University of Nebraska Medical Center (UNMC)-Eppley Cancer
Center (Pilot Grants to M.N. and V.B.), Nebraska Department of Health
and Human Services (LB-506 grant to S.M.R.) and Nebraska Center for
Nanomedicine-Center for Biomedical Research Excellence (NCN-COBRE; seed
grant to S.M.R.).
NR 44
TC 22
Z9 23
U1 0
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2011
VL 2
IS 3
BP 245
EP 250
PG 6
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 802KH
UT WOS:000293509000016
PM 21422499
ER
PT J
AU Ory, B
Ellisen, LW
AF Ory, Benjamin
Ellisen, Leif W.
TI A microRNA-dependent circuit controlling p63/p73 homeostasis: p53 family
cross-talk meets therapeutic opportunity
SO ONCOTARGET
LA English
DT Article
DE p63; p73; microRNA; apoptosis; cisplatin; squamous cell carcinoma;
triple-negative breast cancer; chemosensitivity
ID SQUAMOUS-CELL CARCINOMA; DNA-DAMAGE; P63; P73; APOPTOSIS; NETWORK;
CANCER; EXPRESSION; CISPLATIN; CHEMOSENSITIVITY
AB The p53 family transcription factors p53, p63 and p73 make diverse contributions in development and cancer. Mutation or deletion of p53 is observed in the majority of human cancers. In contrast, p63 and p73 are not lost in cancer but mediate distinct genetic roles in normal and tumor-specific contexts: p73 promotes genome stability and mediates chemosensitivity, while p63 largely lacks these p53-like functions and instead promotes proliferation and cell survival. We recently uncovered a mechanism which maintains p63/p73 homeostasis within the epithelium through direct transcriptional regulation of microRNAs (miRs). We discovered that several of the top p63-regulated miRs target p73 for inhibition, including miR-193a-5p, a direct p63/p73 transcriptional target which is repressed by p63 and activated by p73 both in vitro and in vivo. The resulting feed-forward circuit involving p63, miR-193a-5p and p73 controls p73 levels, cell viability and DNA damage susceptibility in certain cancers including squamous cell carcinoma. Here, we discuss the evolutionary implications of this regulatory circuit, which may point to a general mechanism of miR-mediated cross-talk within transcription factor gene families. Additionally, we suggest that inducible chemoresistance mediated by this miR-dependent mechanism might be an attractive target for therapeutic intervention.
C1 [Ory, Benjamin] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Ellisen, LW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM ellisen@helix.mgh.harvard.edu
RI Xie, Huangming/B-2260-2012; ory, benjamin/K-8231-2015
FU NIH [RO1 DE-015945]; Avon Foundation; Susan G. Komen for the Cure
[KG091277]
FX The work described herein was supported by NIH RO1 DE-015945, by the
Avon Foundation, and by Susan G. Komen for the Cure KG091277. We thank
members of the Ellisen laboratory for helpful comments on the
manuscript.
NR 38
TC 37
Z9 41
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2011
VL 2
IS 3
BP 259
EP 264
PG 6
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 802KH
UT WOS:000293509000018
PM 21436470
ER
PT J
AU Erkan, EP
Breakefield, XO
Saydam, O
AF Erkan, Erdogan Pekcan
Breakefield, Xandra O.
Saydam, Okay
TI miRNA signature of schwannomas: Possible role(s) of "tumor suppressor"
miRNAs in benign tumors
SO ONCOTARGET
LA English
DT Article
DE miR-7; Tumor suppressor miRNAs; Benign tumors; Schwannomas;
Neurofibromatosis 2 (NF2); Ack1
ID GROWTH-FACTOR RECEPTOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; BREAST-CANCER
CELLS; P21-ACTIVATED KINASES; MICROPROCESSOR COMPLEX; EXPRESSION;
MICRORNAS; GENE; FAMILY; MYC
AB miRNAs have been recently implicated as drivers in several carcinogenic processes, where they can act either as oncogenes or as tumor suppressors. Schwannomas arise from Schwann cells, the myelinating cells of the peripheral nervous system. These benign tumors typically result from loss of the neurofibromatosis type 2 (NF2) tumor suppressor gene. We have recently carried out high-throughput miRNA expression profiling of human vestibular schwannomas using an array representing 407 known miRNAs in order to explore the role of miRNAs in the tumorigenesis of schwannomas. We found that miR-7 functions as a "tumor suppressor" by targeting proteins in three major oncogenic pathways - EGFR, Pak1, and Ack1. Interestingly, in this study, we also observed that several previously described potential tumor suppressor miRNAs that are down-regulated in malignant tumors were up-regulated in schwannomas. Here we discuss the possibility that "tumor suppressor" miRNAs may play a role in the transition stage(s) of cancer from benign to malignant forms.
C1 [Erkan, Erdogan Pekcan; Saydam, Okay] Med Univ Vienna, Mol Oncol Res Unit, Div Oncol, Dept Pediat, A-1090 Vienna, Austria.
[Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA.
[Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA.
[Breakefield, Xandra O.] Harvard Univ, Neurosci Program, Sch Med, Boston, MA 02129 USA.
RP Saydam, O (reprint author), Med Univ Vienna, Mol Oncol Res Unit, Div Oncol, Dept Pediat, A-1090 Vienna, Austria.
EM okay.saydam@meduniwien.ac.at
FU Children's Tumor Foundation [2007-01-043, NINDS NS24279, NCI CA69246,
CA86355]; Forschungsgesellschaft for Brain Tumors
FX This study was supported by the Children's Tumor Foundation "Young
Investigator Award" 2007-01-043 (O.S.), NINDS NS24279 (X.O.B., O.S.),
NCI CA69246 (X.O.B.), CA86355 (X.O.B.) and Forschungsgesellschaft for
Brain Tumors (O. S.).
NR 47
TC 13
Z9 15
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2011
VL 2
IS 3
BP 265
EP 270
PG 6
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 802KH
UT WOS:000293509000019
PM 21454924
ER
PT J
AU Zhang, ZG
Kolm, P
Boden, WE
Hartigan, PM
Maron, DJ
Spertus, JA
O'Rourke, RA
Shaw, LJ
Sedlis, SP
Mancini, GBJ
Berman, DS
Dada, M
Teo, KK
Weintraub, WS
AF Zhang, Zugui
Kolm, Paul
Boden, William E.
Hartigan, Pamela M.
Maron, David J.
Spertus, John A.
O'Rourke, Robert A.
Shaw, Leslee J.
Sedlis, Steven P.
Mancini, G. B. John
Berman, Daniel S.
Dada, Marcin
Teo, Koon K.
Weintraub, William S.
TI The Cost-Effectiveness of Percutaneous Coronary Intervention as a
Function of Angina Severity in Patients With Stable Angina
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE angina; cost effectiveness; quality of life; questionnaires
ID EVALUATION COURAGE TRIAL; OUTCOMES UTILIZING REVASCULARIZATION; OPTIMAL
MEDICAL THERAPY; QUALITY-OF-LIFE; ARTERY-DISEASE; MYOCARDIAL-INFARCTION;
HEART-DISEASE; ANGIOPLASTY; ECONOMICS; SURVIVAL
AB Background-The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial compared percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) to OMT alone in reducing the risk of cardiovascular events in 2287 patients with stable coronary disease. We examined the cost-effectiveness of PCI as a function of angina severity at the time of randomization.
Methods and Results-Angina severity was assessed with the Seattle Angina Questionnaire (SAQ). Patients were grouped into tertiles based on the distribution of baseline scores such that higher tertiles represented better health status. Clinically significant improvement from baseline within individual patients was defined as score increases of > 8 for physical limitation, > 20 for angina frequency, and > 16 for quality-of-life domains. The incremental cost-effectiveness ratio for PCI was calculated as the difference in costs divided by the difference in proportion of patients with clinically significant improvement. Improvement in angina severity was significantly greater for PCI patients in the lowest and middle tertiles. The number of patients needed to treat was much larger for the highest tertile. The added in-trial cost of PCI ranged from $7300 to $13 000. Incremental cost-effectiveness ratios ranged from $80 000 to $330 000 for the lowest and middle tertiles and from $520 000 to > $3 million for the highest tertile for 1 additional patient to achieve significant clinical improvement in health status.
Conclusions-The incremental cost of PCI to provide meaningful clinical benefit above that achieved by OMT alone was lower for patients with severe angina than for those with mild or no angina. However, it is uncertain that at any level of angina severity that PCI as an initial strategy would achieve a socially acceptable cost threshold.
C1 [Zhang, Zugui; Kolm, Paul; Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA.
[Boden, William E.] Western New York Vet Affairs Healthcare Network, Buffalo, NY USA.
[Hartigan, Pamela M.] VA Connecticut Healthcare, Cooperat Studies Program Coordinating Ctr, West Haven, CT USA.
[Maron, David J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Spertus, John A.] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA.
[O'Rourke, Robert A.] San Antonio Vet Affairs Med Ctr, San Antonio, TX USA.
[Shaw, Leslee J.] Emory Univ, Atlanta, GA 30322 USA.
[Sedlis, Steven P.] NYU, New York, NY USA.
[Sedlis, Steven P.] Vet Affairs New York Harbor Hlth Care Network, New York, NY USA.
[Mancini, G. B. John] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Berman, Daniel S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA.
[Teo, Koon K.] McMaster Univ, Hamilton, ON, Canada.
[Boden, William E.] Kaleida Hlth Syst, Buffalo, NY USA.
RP Zhang, ZG (reprint author), Christiana Care Ctr Outcomes Res, 131 Continental Dr,Ste 202, Newark, DE 19713 USA.
EM zzgfang@hotmail.com
RI Library, Woodruff Health/A-6096-2012;
OI Sedlis, Steven/0000-0002-8194-8017
FU Sanofi-Aventis; AstraZeneca; Institutions Network for Biomedical
Research Excellence; Bristol-Myers Squibb; Pfizer; Merck; PDL Biopharma;
Abbott; Cardiovascular Therapeutics; Kos Pharmaceuticals; Novartis; CAD;
United Healthcare; Amgen; Lilly; GlaxoSmithKline; Merck Frosst-Schering
(Canada); Boehringer-Ingelheim; Indigo Pharmaceuticals; Otsuka
FX Dr Kolm reports receiving grant support from Sanofi-Aventis,
AstraZeneca, Institutions Network for Biomedical Research Excellence,
Otsuka, and Bristol-Myers Squibb. Dr Boden reports receiving consulting
fees from Pfizer, Merck, PDL Biopharma, Bristol-Myers Squibb, Abbott,
and Cardiovascular Therapeutics and receiving lecture fees from
Sanofi-Aventis, Kos Pharmaceuticals, and Novartis. Dr Maron reports
receiving fees from reviewing a case for a defendant who recommended
medical therapy for patients with CAD. Dr Spertus reports receiving
consulting fees from Otsuka and United Healthcare and grant support from
Amgen, Bristol-Myers Squibb, Sanofi-Aventis, and Lilly and holds a
copyright to the SAQ. Dr Mancini reports receiving grant support from
GlaxoSmithKline, Pfizer, AstraZeneca, and Merck Frosst-Schering
(Canada). Dr Teo reports receiving grant support from
Boehringer-Ingelheim. Dr Weintraub reports receiving consulting fees
from Sanofi-Aventis, GlaxoSmithKline, Indigo Pharmaceuticals, and
Cardiovascular Therapeutics and receiving grant support from
Sanofi-Aventis, AstraZeneca, Otsuka, and Bristol-Myers Squibb. Drs
Zhang, Hartigan, O'Rourke, Shaw, Sedlis, Berman, Dada, and Weintraub
report no conflicts.
NR 29
TC 7
Z9 7
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAR
PY 2011
VL 4
IS 2
BP 172
EP U72
DI 10.1161/CIRCOUTCOMES.110.940502
PG 22
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 734WN
UT WOS:000288372200008
PM 21304091
ER
PT J
AU Ganis, G
Rosenfeld, JP
Meixner, J
Kievit, RA
Schendan, HE
AF Ganis, Giorgio
Rosenfeld, J. Peter
Meixner, John
Kievit, Rogier A.
Schendan, Haline E.
TI Lying in the scanner: Covert countermeasures disrupt deception detection
by functional magnetic resonance imaging
SO NEUROIMAGE
LA English
DT Article
ID EVENT-RELATED FMRI; CONCEALED INFORMATION; PREFRONTAL CORTEX; MEMORY
IMPAIRMENT; GUILTY KNOWLEDGE; BRAIN ACTIVITY; LIE DETECTION;
NEUROSCIENCE; PROTOCOL; TESTS
AB Functional magnetic resonance imaging (fMRI) studies have documented differences between deceptive and honest responses. Capitalizing on this research, companies marketing fMRI-based lie detection services have been founded, generating methodological and ethical concerns in scientific and legal communities. Critically, no fMRI study has examined directly the effect of countermeasures, methods used by prevaricators to defeat deception detection procedures. An fMRI study was conducted to fill this research gap using a concealed information paradigm in which participants were trained to use countermeasures. Robust group fMRI differences between deceptive and honest responses were found without, but not with countermeasures. Furthermore, in single participants, deception detection accuracy was 100% without countermeasures, using activation in ventrolateral and medial prefrontal cortices, but fell to 33% with countermeasures. These findings show that fMRI-based deception detection measures can be vulnerable to countermeasures, calling for caution before applying these methods to real-world situations. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Ganis, Giorgio; Schendan, Haline E.] Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA.
[Ganis, Giorgio; Schendan, Haline E.] Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England.
[Rosenfeld, J. Peter; Meixner, John] Northwestern Univ, Dept Psychol, Evanston, IL 60208 USA.
[Kievit, Rogier A.] Univ Amsterdam, Dept Psychol, NL-1018 WB Amsterdam, Netherlands.
RP Ganis, G (reprint author), Massachusetts Gen Hosp, Martinos Ctr, Bldg 149, Charlestown, MA 02129 USA.
EM ganis@nmr.mgh.harvard.edu
OI Ganis, Giorgio/0000-0001-6175-2618; Schendan,
Haline/0000-0001-8925-5605; Kievit, Rogier/0000-0003-0700-4568
FU National Science Foundation [BCS0322611]
FX This research was supported in part by the National Science Foundation
(BCS0322611).
NR 47
TC 51
Z9 56
U1 3
U2 39
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 MAR 1
PY 2011
VL 55
IS 1
BP 312
EP 319
DI 10.1016/j.neuroimage.2010.11.025
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 716YH
UT WOS:000287008900030
PM 21111834
ER
PT J
AU Fujitani, S
George, WL
Murthy, AR
AF Fujitani, Shigeki
George, W. Lance
Murthy, A. Rekha
TI Comparison of Clinical Severity Score Indices for Clostridium difficile
Infection
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article
ID HOSPITALIZED-PATIENTS; DISEASE; DIARRHEA; STRAIN; METRONIDAZOLE;
VANCOMYCIN; MORTALITY; EPIDEMIC; OUTBREAK; COLITIS
AB OBJECTIVE. To compare 8 severity score indices for Clostridium difficile infection (CDI).
DESIGN. Prospective observational study.
METHODS. This study was conducted from July through October 2006. All hospitalized patients in 3 university-affiliated hospitals with a positive fecal Clostridium difficile toxin assay result were evaluated. Infection was considered severe if patients had at least 1 of the following clinical events during their hospitalization: (1) death attributed to CDI within 30 days after diagnosis, (2) colectomy necessitated by CDI, or (3) intensive care unit admission for management of complications attributed to CDI. Severity was assessed on the basis of 8 severity score indices, using published criteria for severe CDI as the benchmark. The 8 severity score indices studied were Beth Israel, University of Pittsburgh Medical Center version 1, University of Pittsburgh Medical Center version 2, Hines VA, modified University of Illinois, University of Calgary version 1, University of Calgary version 2, and University of Temple.
RESULTS. Of 184 patients with CDI evaluated, 19 had severe cases and 165 had nonsevere cases, as assessed on the basis of the defined severe CDI criteria. Sensitivities of the 8 severity score indices studied ranged from 63.2% to 84.2%, and specificities ranged from 59.4% to 93.9%. The Hines VA index had the highest kappa score (0.69 [95% confidence interval, 0.54-0.83]), followed by the University of Pittsburgh Medical Center version 1 index. Independent risk factors for severe CDI determined by multivariate analysis were abdominal distention (P=.007), fever (temperature, 38.0 degrees C or above; P=.042), white blood cell count of at least 20,000 cells/mm(3) (P=.035), and hypoalbuminemia (serum albumin level less than 3 mg/dL; P=.029).
CONCLUSION. The Hines VA CDI severity score index appeared to display the strongest correlation for predicting more severe forms of CDI.
C1 [Fujitani, Shigeki] Marianna Univ Hosp, Dept Emergency & Crit Care Med, Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan.
[George, W. Lance] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA.
[George, W. Lance; Murthy, A. Rekha] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Murthy, A. Rekha] Cedars Sinai Med Ctr, Div Infect Dis, Dept Hosp Epidemiol, Los Angeles, CA 90048 USA.
RP Fujitani, S (reprint author), Marianna Univ Hosp, Dept Emergency & Crit Care Med, Miyamae Ku, 2-16-1 Sugao, Kawasaki, Kanagawa 2168511, Japan.
EM shigekifujitani@hotmail.com
NR 20
TC 56
Z9 56
U1 1
U2 4
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD MAR
PY 2011
VL 32
IS 3
BP 220
EP 228
DI 10.1086/658336
PG 9
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 790UH
UT WOS:000292614200004
PM 21460506
ER
PT J
AU Irazoqui, JE
AF Irazoqui, Javier E.
TI Transparent worms help survey the fortress of innate immunity
SO VIRULENCE
LA English
DT Editorial Material
ID CAENORHABDITIS-ELEGANS; PSEUDOMONAS-AERUGINOSA; C. ELEGANS; INFECTION;
SALMONELLA; INFLAMMATION
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol,Dept Pediat, Boston, MA 02115 USA.
RP Irazoqui, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol,Dept Pediat, Boston, MA 02115 USA.
EM javier@molbio.mgh.harvard.edu
RI Irazoqui, Javier/A-8028-2013;
OI Irazoqui, Javier/0000-0001-6553-1329
NR 26
TC 1
Z9 1
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2150-5594
J9 VIRULENCE
JI Virulence
PD MAR-APR
PY 2011
VL 2
IS 2
BP 83
EP 85
DI 10.4161/viru.2.2.15665
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 789NW
UT WOS:000292523500001
PM 21460640
ER
PT J
AU Muhammed, M
Coleman, JJ
Carneiro, HA
Mylonakis, E
AF Muhammed, Maged
Coleman, Jeffrey J.
Carneiro, Herman A.
Mylonakis, Eleftherios
TI The challenge of managing fusariosis
SO VIRULENCE
LA English
DT Review
DE amphotericin B; fusariosis; Fusarium; invasive fungal infection;
posaconazole; voriconazole
ID INVASIVE FUNGAL-INFECTIONS; ACUTE LYMPHOBLASTIC-LEUKEMIA; LIPOSOMAL
AMPHOTERICIN-B; CELL TRANSPLANT RECIPIENTS; IN-VITRO; ANTIFUNGAL
SUSCEPTIBILITY; HEMATOLOGIC MALIGNANCIES; IMMUNOCOMPROMISED PATIENTS;
MOLD INFECTIONS; LIPID COMPLEX
AB Fusarium is the second most frequent mold involved in fungal infections and is particularly important among immunocompromised patients. Culture methods and microscopy are still routinely used in clinical laboratories to identify Fusarium spp., and more sophisticated, timely, and effective methods for detecting Fusarium spp. in laboratory samples could improve the outcome for the patient. These investigational diagnostic approaches include serological assays and specific nested PCR assays that can yield positive and negative predictive values of over 90%. Other assays in development, such as mass spectroscopy techniques, can provide accurate and consistent results. The treatment of fusariosis in immunocompromised patients remains a challenge and the prognosis of systemic fusariosis in this population remains poor. Successful treatment is highly dependent on the particular Fusarium species involved in the infection. High dose intravenous amphotericin B formulation is recommended as the first line of therapy in management of fusariosis in patients. Voriconazole is also effective in treating fusariosis. Intolerance, contraindication, or failure of the amphotericin B formulation warrants the use of voriconazole as an alternative agent, and posaconazole is licensed as salvage therapy against invasive fusariosis. Adjunctive therapies such as surgical debridement of infected tissue, granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) infusions, or granulocyte transfusions are also tools for managing fusariosis. In conclusion, Fusarium infection is considered an emerging problem and should be suspected in immunocompromised patients experiencing systemic infection and should be treated accordingly.
C1 [Muhammed, Maged; Coleman, Jeffrey J.; Carneiro, Herman A.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Coleman, JJ (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM jjcoleman@partners.org
RI Coleman, Jeffrey/E-2981-2015
FU NIH [P01 AI 083214, R01 AI075286, R21 AI079569, T32 AI007061]
FX This work was supported by NIH grants P01 AI 083214, R01 AI075286 and
R21 AI079569 to E.M. and a T32 AI007061 to J.J.C.
NR 77
TC 34
Z9 36
U1 1
U2 11
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2150-5594
J9 VIRULENCE
JI Virulence
PD MAR-APR
PY 2011
VL 2
IS 2
BP 91
EP 96
DI 10.4161/viru.2.2.15015
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 789NW
UT WOS:000292523500003
PM 21304267
ER
PT J
AU Mendez, MF
Shapira, JS
Saul, RE
AF Mendez, Mario F.
Shapira, Jill S.
Saul, Ronald E.
TI The Spectrum of Sociopathy in Dementia
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
ID VENTROMEDIAL PREFRONTAL CORTEX; ANTISOCIAL PERSONALITY-DISORDER;
POSITRON-EMISSION-TOMOGRAPHY; INCREASED GREY-MATTER; FRONTOTEMPORAL
DEMENTIA; ALZHEIMERS-DISEASE; BRAIN ABNORMALITIES; CONDUCT PROBLEMS;
DECISION-MAKING; MORAL JUDGMENTS
AB Although well-known from head trauma and acute strokes, sociopathic behavior from dementia is less known and understood. This study reviewed 33 dementia patients who had been in trouble with the law. They were divided into two groups: 22 who committed impulsive sociopathic acts and 11 who committed non-impulsive acts. The impulsive patients demonstrated nonviolent acts, such as dis-inhibited sexual behavior or pathological stealing, and had disproportionate frontal-caudate atrophy on neuroimaging. The majority of non-impulsive patients demonstrated agitation-paranoia, sometimes with reactive aggression, delusional beliefs, or aphasic paranoia, and had advanced memory and other cognitive impairment. The impulsive patients tended to have frontally predominant illnesses such as frontotemporal dementia or Huntington's disease, whereas the non-impulsive group tended to have Alzheimer's disease or prominent aphasia. Sociopathy has different causes in dementia. Two common mechanisms are disinhibition, with frontally predominant disease, and agitation-paranoia, with greater cognitive impairment. These forms of sociopathy differ significantly from the antisocial/psychopathic personality. (The Journal of Neuropsychiatry and Clinical Neurosciences 2011; 23: 132-140)
C1 [Mendez, Mario F.] VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM mmendez@UCLA.edu
FU NIMH [R01AG034499-02]
FX This work was supported by NIMH Grant # R01AG034499-02.
NR 69
TC 9
Z9 10
U1 7
U2 16
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0895-0172
J9 J NEUROPSYCH CLIN N
JI J. Neuropsychiatr. Clin. Neurosci.
PD SPR
PY 2011
VL 23
IS 2
BP 132
EP 140
PG 9
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 777VF
UT WOS:000291652500127
PM 21677240
ER
PT J
AU Ducharme, S
Flaherty, AW
Seiner, SJ
Dougherty, DD
Morales, OG
AF Ducharme, Simon
Flaherty, Alice W.
Seiner, Stephen J.
Dougherty, Darin D.
Morales, Oscar G.
TI Temporary Interruption of Deep Brain Stimulation for Parkinson's Disease
During Outpatient Electroconvulsive Therapy for Major Depression: A
Novel Treatment Strategy
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
ID TREATMENT-RESISTANT DEPRESSION; PATIENT; ECT; EFFICACY; DAMAGE
AB The safety of electroconvulsive therapy (ECT) in patients with deep brain stimulation (DBS) has not been established. Cases reported had no adverse events, but DBS was withheld throughout the weeks of the ECT course. The authors report the first case of temporary interruption of DBS only during the minutes of each outpatient ECT. (The Journal of Neuropsychiatry and Clinical Neurosciences 2011; 23: 194-197)
C1 [Morales, Oscar G.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02478 USA.
McGill Univ, Montreal, PQ, Canada.
Harvard Univ, Sch Med, Dept Psychiat, Div Neurotherapeut,Massachusetts Gen Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Morales, OG (reprint author), Harvard Univ, McLean Hosp, Sch Med, 115 Mill St, Belmont, MA 02478 USA.
EM ogmorales@partners.org
FU NIMH; NARSAD; TSA; OCF; Wyeth; Jazz Pharmaceuticals; Bristol-Myers
Squibb; Medtronic; Eli Lilly; Northstar; McNeil; Brand Ideas; Reed
Elsevier; Cyberonics
FX Dr. Ducharme, Dr. Flaherty, and Dr. Seiner have no disclosure or
conflict of interest related to this topic. Dr. Dougherty's research has
been funded by NIMH, NARSAD, TSA, and OCF. He has received honoraria,
consultation fees, and/or royalties from Wyeth, Jazz Pharmaceuticals,
Bristol-Myers Squibb, Medtronic, Eli Lilly, Northstar, McNeil, Brand
Ideas, and Reed Elsevier. He has also participated in research funded by
Medtronic, Cyberonics, Eli Lilly, McNeil and Northstar.
NR 19
TC 13
Z9 13
U1 0
U2 5
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0895-0172
J9 J NEUROPSYCH CLIN N
JI J. Neuropsychiatr. Clin. Neurosci.
PD SPR
PY 2011
VL 23
IS 2
BP 194
EP 197
PG 4
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 777VF
UT WOS:000291652500136
PM 21677249
ER
PT J
AU Yeh, B
Ferrucci, S
AF Yeh, Brenda
Ferrucci, Steven
TI Retinal pigment epithelium tears after bevacizumab injection
SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION
LA English
DT Article
DE Age-related macular degeneration; Bevacizumab; Avastin; Choroidal
neovascularization (CNV); Vascular endothelial growth factor; Pigment
epithelial detachment; Retinal pigment epithelial tear
ID OPTICAL COHERENCE TOMOGRAPHY; CHOROIDAL NEOVASCULARIZATION SECONDARY;
INTRAVITREAL BEVACIZUMAB; MACULAR DEGENERATION; RANIBIZUMAB THERAPY;
LASER TREATMENT; DETACHMENT; AVASTIN; PATHOGENESIS; PREDICTORS
AB BACKGROUND: The advent of anti-vascular endothelial growth factor (VEGF) treatment for choroidal neovascularization has become the standard of care for wet age-related macular degeneration (AMD). Among the choices, intravitreal bevacizumab, for off-label use, has gained popularity. Recent attention has been on the complications of anti-VEGF treatment, one of them being a retinal pigment epithelial (RPE) tear. A tear in the RPE is a visually devastating complication, most commonly associated with fibrovascular pigment epithelial detachments (PED) in AMD, and may develop during the course of intravitreal bevacizumab treatment.
CASE REPORT: We report a case of an 85-year-old white man with decreased visual acuities of 20/70 in the right eye (O.D.) and 20/150 in the left eye (O.S.) secondary to dry AMD O.D. and wet AMD with a fibrovascular PED O.S. The patient underwent treatment with an intravitreal bevacizumab injection O.S. Six weeks after the initial injection, the patient returned with further declining vision in the left eye secondary to an RPE tear.
CONCLUSION: Intravitreal bevacizumab has proven to be an effective treatment for choroidal neovascularization and shows a significant improvement of vision for wet AMD patients. However, there are risks associated with the procedure. One of the most visually significant is an RPE tear, which can occur at an incidence rate as high as 17%. Optometrists should be aware of this rare, but serious, complication associated with anti-VEGF treatment for wet AMD. Optometry 2011;82:152-157
C1 [Yeh, Brenda; Ferrucci, Steven] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Yeh, Brenda; Ferrucci, Steven] Sepulveda Vet Affairs Ambulatory Care Ctr Nursing, Sepulveda, CA USA.
[Ferrucci, Steven] So Calif Coll Optometry, Fullerton, CA USA.
RP Ferrucci, S (reprint author), Sepulveda Vet Affairs Ambulatory Care Ctr, 16111 Plummer St 112E, Sepulveda, CA 91343 USA.
EM Steven.Ferrucci@va.gov
NR 44
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-1839
J9 OPTOMETRY
JI Optometry
PD MAR
PY 2011
VL 82
IS 3
BP 152
EP 157
DI 10.1016/j.optm.2010.09.010
PG 6
WC Ophthalmology
SC Ophthalmology
GA 778MO
UT WOS:000291708600006
PM 21130699
ER
PT J
AU Shahlaie, K
Larson, PS
Starr, PA
AF Shahlaie, Kiarash
Larson, Paul S.
Starr, Philip A.
TI Intraoperative Computed Tomography for Deep Brain Stimulation Surgery:
Technique and Accuracy Assessment
SO NEUROSURGERY
LA English
DT Article
DE Computed tomography; Deep brain stimulation; Intraoperative imaging;
Lead location; Neuronavigation
ID SUBTHALAMIC NUCLEUS; ELECTRODE PLACEMENT; PARKINSONS-DISEASE;
LOCALIZATION; IMPLANTATION; CANCER; EXPERIENCE; LOCATIONS; OUTCOMES;
SHIFT
AB BACKGROUND: The efficacy of deep brain stimulation (DBS) is highly dependent on the accuracy of lead placement.
OBJECTIVE: To describe the use of intraoperative computed tomography (iCT) to confirm lead location before surgical closure and to study the accuracy of this technique.
METHODS: Fifteen patients underwent awake microelectrode-guided DBS surgery in a stereotactic frame. A portable iCT scanner (Medtronic O-arm) was positioned around the patient's head throughout the procedure and was used to confirm lead location before fixation of the lead to the skull. Images were computationally fused with pre-operative magnetic resonance imaging (MRI), and lead tip coordinates with respect to the midpoint of the anterior commissure-posterior commissure line were measured. Tip coordinates were compared with those obtained from postoperative MRI.
RESULTS: iCT was integrated into standard frame-based microelectrode-guided DBS surgery with a minimal increase in surgical time or complexity. Technically adequate 2-dimensional and 3-dimensional images were obtained in all cases. Head positioning and fixation techniques that allow unobstructed imaging are described. Lead tip measurements on iCT fused with preoperative MRI were statistically indistinguishable from those obtained with postoperative MRI.
CONCLUSION: iCT can be easily incorporated into standard DBS surgery, replaces the need for C-arm fluoroscopy, and provides accurate intraoperative 3-dimensional confirmation of electrode tip locations relative to preoperative images and surgical plans. iCT fused to preoperative MRI may obviate the need for routine postoperative MRI in DBS surgery. Technical nuances that must be mastered for the efficient use of iCT during DBS implantation are described.
C1 [Starr, Philip A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Care Ctr, San Francisco, CA USA.
RP Starr, PA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 533 Parnassus Ave,Box 0445, San Francisco, CA 94143 USA.
EM starrp@neurosurg.ucsf.edu
NR 25
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD MAR
PY 2011
VL 68
SU 1
AR ons114
DI 10.1227/NEU.0b013e31820781bc
PG 11
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 773KU
UT WOS:000291307000032
ER
PT J
AU Basko-Plluska, JL
Thyssen, JP
Schalock, PC
AF Basko-Plluska, Juliana L.
Thyssen, Jacob P.
Schalock, Peter C.
TI Cutaneous and Systemic Hypersensitivity Reactions to Metallic Implants
SO DERMATITIS
LA English
DT Review
ID TOTAL KNEE REPLACEMENT; TOTAL HIP-ARTHROPLASTY; PACEMAKER CONTACT
SENSITIVITY; CORONARY-ARTERY-DISEASE; GOLD SODIUM THIOSULFATE; FORAMEN
OVALE OCCLUDER; BONE-CEMENT COMPONENTS; ORAL LICHENOID LESIONS; BURNING
MOUTH SYNDROME; IN-STENT RESTENOSIS
AB Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals lie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field.
C1 [Basko-Plluska, Juliana L.] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA.
Univ Copenhagen, Gentofte Hosp, Natl Allergy Res Ctr, Dept Dermato Allergol, DK-1168 Copenhagen, Denmark.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA.
RP Basko-Plluska, JL (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
NR 130
TC 54
Z9 56
U1 3
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1710-3568
EI 2162-5220
J9 DERMATITIS
JI Dermatitis
PD MAR-APR
PY 2011
VL 22
IS 2
BP 65
EP 79
DI 10.2310/6620.2011.10055
PG 15
WC Dermatology
SC Dermatology
GA 768XS
UT WOS:000290973500001
PM 21504692
ER
PT J
AU Chandra, A
Jena, AB
Skinner, JS
AF Chandra, Amitabh
Jena, Anupam B.
Skinner, Jonathan S.
TI The Pragmatist's Guide to Comparative Effectiveness Research
SO JOURNAL OF ECONOMIC PERSPECTIVES
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; STABLE CORONARY-DISEASE; COST-EFFECTIVENESS
ANALYSIS; US HEALTH-CARE; DRUG DEVELOPMENT; REIMBURSEMENT; MORTALITY;
MEDICINE; IMPACT; TRIAL
C1 [Chandra, Amitabh] Harvard Univ, Harvard Kennedy Sch Govt, Cambridge, MA 02138 USA.
[Jena, Anupam B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[Skinner, Jonathan S.] Dartmouth Coll, Dartmouth Inst Hlth Care Policy & Clin Practice, Hanover, NH 03755 USA.
[Chandra, Amitabh; Skinner, Jonathan S.] Natl Bur Econ Res, Cambridge, MA 02138 USA.
RP Chandra, A (reprint author), Harvard Univ, Harvard Kennedy Sch Govt, Cambridge, MA 02138 USA.
EM amitabh_chandra@harvard.edu; jena.anupam@mgh.harvard.edu;
jonathan.skinner@dartmouth.edu
FU NIA NIH HHS [P01 AG019783, P01 AG019783-10, P01 AG19783]
NR 60
TC 25
Z9 26
U1 3
U2 8
PU AMER ECONOMIC ASSOC
PI NASHVILLE
PA 2014 BROADWAY, STE 305, NASHVILLE, TN 37203 USA
SN 0895-3309
EI 1944-7965
J9 J ECON PERSPECT
JI J. Econ. Perspect.
PD SPR
PY 2011
VL 25
IS 2
BP 27
EP 46
DI 10.1257/jep.25.2.27
PG 20
WC Economics
SC Business & Economics
GA 764GW
UT WOS:000290618900002
PM 21595324
ER
PT J
AU LeBoeuf, NR
Schmults, CD
AF LeBoeuf, Nicole R.
Schmults, Chrysalyne D.
TI Update on the Management of High-Risk Squamous Cell Carcinoma
SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY
LA English
DT Article
ID NONMELANOMA SKIN-CANCER; ORGAN TRANSPLANT RECIPIENTS;
POSITRON-EMISSION-TOMOGRAPHY; CHRONIC LYMPHOCYTIC-LEUKEMIA; PHASE-II
TRIAL; BASAL-CELL; EPIDERMOLYSIS-BULLOSA; PERINEURAL INVASION;
CALCINEURIN INHIBITORS; PROGNOSTIC FACTORS
AB Cutaneous squamous cell carcinoma (CSCC) is the second most common malignancy occurring in white patients in the United States and incidence rates are increasing. While the majority of the 87,000-760,000 cases that occur yearly in the U.S. are curable, 4% develop lymph node metastases and 1.5% die from the disease. Given the frequency of occurrence of CSCC, it is estimated to cause as many deaths yearly as melanoma, with the majority occurring in patients with high risk tumors or in those at high risk for metastasis due to a variety of host factors, most commonly systemic immunosuppression. There are currently no standardized prognostic or treatment models to assist clinicians in most effectively identifying and managing these patients. Identification of patients at risk for poor outcomes as well as standardization regarding classification, staging, and treatment of high-risk tumors is critical for optimizing patient care. In this article, available literature on the classification and management of high risk CSCC is briefly summarized, emphasizing new information. Semin Cutan Med Surg 30:26-34 (C) 2011 Elsevier Inc. All rights reserved.
C1 [LeBoeuf, Nicole R.; Schmults, Chrysalyne D.] Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA.
RP Schmults, CD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Dermatol, 1153 Ctr St, Jamaica Plain, MA 02130 USA.
EM cschmults@partners.org
NR 102
TC 11
Z9 14
U1 1
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1085-5629
J9 SEMIN CUTAN MED SURG
JI Semin. Cutan. Med. Surg.
PD MAR
PY 2011
VL 30
IS 1
BP 26
EP 34
DI 10.1016/j.sder.2011.02.002
PG 9
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 764RL
UT WOS:000290649900005
PM 21540018
ER
PT J
AU Boruta, D
McCann, C
Growdon, W
AF Boruta, D.
McCann, C.
Growdon, W.
TI Single-incision laparoscopic staging surgery for endometrial cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Boruta, D.; McCann, C.; Growdon, W.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 16
BP S9
EP S9
DI 10.1016/j.ygyno.2010.12.023
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300017
ER
PT J
AU Campos, S
Atkinson, T
Berlin, S
Roche, M
Whalen, C
Matulonis, U
Horowitz, N
Birrer, M
Penson, R
AF Campos, S.
Atkinson, T.
Berlin, S.
Roche, M.
Whalen, C.
Matulonis, U.
Horowitz, N.
Birrer, M.
Penson, R.
TI STAC: A phase II study of carboplatin/paclitaxel/bevacizumab followed by
randomization to either bevacizumab alone or erlotinib and bevacizumab
in the upfront management of patients with ovarian, fallopian tube or
peritoneal cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Campos, S.; Atkinson, T.; Berlin, S.; Whalen, C.; Matulonis, U.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Roche, M.; Birrer, M.; Penson, R.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Horowitz, N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 181
BP S79
EP S79
DI 10.1016/j.ygyno.2010.12.188
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300182
ER
PT J
AU Garrett, L
Zhang, L
Guo, L
Therrien, V
Growdon, W
Foster, R
Rueda, B
AF Garrett, L.
Zhang, L.
Guo, L.
Therrien, V.
Growdon, W.
Foster, R.
Rueda, B.
TI Influence of the novel histone deacetylase inhibitor panobinostat
(LBH589) on the growth of ovarian cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Garrett, L.; Zhang, L.; Guo, L.; Therrien, V.; Growdon, W.; Foster, R.; Rueda, B.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 163
BP S71
EP S71
DI 10.1016/j.ygyno.2010.12.170
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300164
ER
PT J
AU Growdon, W
Garrett, L
Rousel, B
Scialabba, V
Ellisen, L
Dias-Santagata, D
Foster, R
Tambouret, R
Rueda, B
Borger, D
AF Growdon, W.
Garrett, L.
Rousel, B.
Scialabba, V.
Ellisen, L.
Dias-Santagata, D.
Foster, R.
Tambouret, R.
Rueda, B.
Borger, D.
TI Activating PIK3CA and RAS mutations identified exclusively in
carcinosarcomas of uterine origin
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Growdon, W.; Garrett, L.; Rousel, B.; Scialabba, V.; Ellisen, L.; Dias-Santagata, D.; Foster, R.; Tambouret, R.; Rueda, B.; Borger, D.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 97
BP S42
EP S43
DI 10.1016/j.ygyno.2010.12.104
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300098
ER
PT J
AU McCann, C
Bradford, L
Boruta, D
Del Carmen, M
Goodman, A
Growdon, W
Schorge, J
AF McCann, C.
Bradford, L.
Boruta, D.
Del Carmen, M.
Goodman, A.
Growdon, W.
Schorge, J.
TI Secondary cytoreductive surgery for recurrent endometrial cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [McCann, C.; Bradford, L.; Boruta, D.; Del Carmen, M.; Goodman, A.; Growdon, W.; Schorge, J.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 215
BP S93
EP S94
DI 10.1016/j.ygyno.2010.12.222
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300216
ER
PT J
AU Moore, R
Miller, C
DiSilvestro, P
Landrum, L
Gajewski, W
Renneisen, P
Skates, S
AF Moore, R.
Miller, C.
DiSilvestro, P.
Landrum, L.
Gajewski, W.
Renneisen, P.
Skates, S.
TI Evaluation of the risk of ovarian malignancy algorithm in women with a
pelvic mass presenting to general gynecologists
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Moore, R.; DiSilvestro, P.] Brown Univ, Women & Infants Hosp, Providence, RI USA.
[Landrum, L.] Univ Oklahoma, Oklahoma City, OK USA.
[Gajewski, W.] New Hanover Reg Med Ctr, Wilmington, NC USA.
[Renneisen, P.] Fujirebio Diagnost, Malvern, PA USA.
[Skates, S.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 156
BP S68
EP S68
DI 10.1016/j.ygyno.2010.12.163
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300157
ER
PT J
AU Rauh-Hain, I
Growdon, W
Rodriguez, N
Goodman, A
Boruta, D
Horowitz, N
Del Carmen, M
Schorge, J
AF Rauh-Hain, I.
Growdon, W.
Rodriguez, N.
Goodman, A.
Boruta, D.
Horowitz, N.
Del Carmen, M.
Schorge, J.
TI Primary debulking surgery versus neoadjuvant chemotherapy in stage IV
ovarian cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Rauh-Hain, I.; Growdon, W.; Goodman, A.; Boruta, D.; Del Carmen, M.; Schorge, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rauh-Hain, I.; Rodriguez, N.; Horowitz, N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Rauh-Hain, I.; Growdon, W.; Rodriguez, N.; Goodman, A.; Boruta, D.; Horowitz, N.; Del Carmen, M.; Schorge, J.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 26
BP S12
EP S13
DI 10.1016/j.ygyno.2010.12.033
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300027
ER
PT J
AU Rauh-Hain, J
Growdon, W
Rodriguez, N
Goodman, A
Schorge, J
Boruta, D
Horowitz, N
Del Carmen, M
AF Rauh-Hain, J.
Growdon, W.
Rodriguez, N.
Goodman, A.
Schorge, J.
Boruta, D.
Horowitz, N.
Del Carmen, M.
TI Carcinosarcoma of the ovary: A case-control study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Rauh-Hain, J.; Growdon, W.; Goodman, A.; Schorge, J.; Boruta, D.; Del Carmen, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rauh-Hain, J.; Rodriguez, N.; Horowitz, N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Rauh-Hain, J.; Growdon, W.; Rodriguez, N.; Goodman, A.; Schorge, J.; Boruta, D.; Horowitz, N.; Del Carmen, M.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 149
BP S65
EP S65
DI 10.1016/j.ygyno.2010.12.156
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300150
ER
PT J
AU Rodriguez, N
Rauh-Hain, J
Feltmate, C
Del Carmen, M
Penson, R
Goodman, A
Matulonis, U
Muto, M
Schorge, J
Horowitz, N
AF Rodriguez, N.
Rauh-Hain, J.
Feltmate, C.
Del Carmen, M.
Penson, R.
Goodman, A.
Matulonis, U.
Muto, M.
Schorge, J.
Horowitz, N.
TI CA-125 changes can predict optimal interval cytoreduction in patients
with advanced-stage epithelial ovarian cancer treated with neoadjuvant
chemotherapy
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Rodriguez, N.; Rauh-Hain, J.; Feltmate, C.; Muto, M.; Horowitz, N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Rauh-Hain, J.; Del Carmen, M.; Penson, R.; Goodman, A.; Schorge, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Del Carmen, M.; Penson, R.; Goodman, A.; Schorge, J.] Harvard Univ, Boston, MA 02115 USA.
[Matulonis, U.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 146
BP S63
EP S64
DI 10.1016/j.ygyno.2010.12.153
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300147
ER
PT J
AU Spencer, R
Schorge, J
Del Carmen, M
Goodman, A
Growdon, W
Boruta, D
AF Spencer, R.
Schorge, J.
Del Carmen, M.
Goodman, A.
Growdon, W.
Boruta, D.
TI Laparoscopic surgery for endometrial cancer: Why don't all patients go
home the day after surgery?
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Spencer, R.; Schorge, J.; Del Carmen, M.; Goodman, A.; Growdon, W.; Boruta, D.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 205
BP S89
EP S89
DI 10.1016/j.ygyno.2010.12.212
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300206
ER
PT J
AU Zaid, T
Thompson, M
Wong, K
Yeung, T
Yeung, Z
Kwan, S
Co, C
Schmandt, R
Birrer, M
Mok, S
AF Zaid, T.
Thompson, M.
Wong, K.
Yeung, T.
Yeung, Z.
Kwan, S.
Co, C.
Schmandt, R.
Birrer, M.
Mok, S.
TI Overexpression of fibroblast growth factor 1 and fibroblast growth
factor receptor 4 in high-grade serous ovarian carcinoma: Correlation
with survival and implications for therapeutic targeting
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Zaid, T.; Thompson, M.; Wong, K.; Yeung, T.; Yeung, Z.; Kwan, S.; Co, C.; Schmandt, R.; Mok, S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2011
VL 121
IS 1
SU 1
MA 120
BP S52
EP S52
DI 10.1016/j.ygyno.2010.12.127
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 760AF
UT WOS:000290292300121
ER
PT J
AU Ahmadi, N
Nabavi, V
Hajsadeghi, F
Flores, F
Azmoon, S
Ismaeel, H
Shavelle, D
Mao, SS
Ebrahimi, R
Budoff, MJ
AF Ahmadi, Naser
Nabavi, Vahid
Hajsadeghi, Fereshteh
Flores, Ferdinand
Azmoon, Shahdad
Ismaeel, Hussain
Shavelle, David
Mao, Song S.
Ebrahimi, Ramin
Budoff, Matthew J.
TI Impaired aortic distensibility measured by computed tomography is
associated with the severity of coronary artery disease
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Aortic distensibility index; Computed tomographic angiography; Coronary
artery calcium score; 2D Trans-thoracic echocardiography
ID HEART-DISEASE; ENDOTHELIAL DYSFUNCTION; ELASTIC PROPERTIES;
CLINICAL-PRACTICE; PROGNOSTIC VALUE; III GUIDELINES; ELECTRON-BEAM;
SMOOTH-MUSCLE; STIFFNESS; ATHEROSCLEROSIS
AB Impaired aortic distensibility index (ADI) is associated with cardiovascular risk factors. This study evaluates the relation of ADI measured by computed tomographic angiography (CTA) with the severity of coronary atherosclerosis in subjects with suspected coronary artery disease (CAD). Two hundred and twenty-nine subjects,age 63 +/- A 9 years, 42% female, underwent coronary artery calcium (CAC) scanning and CTA, and their ADI and Framingham risk score (FRS) were measured. End-systolic and end-diastolic (ED) cross-sectional-area(CSA) of ascending-aorta (AAo) was measured 15-mm above the left-main coronary ostium. ADI was defined as: [(Delta lumen-CSA)/(lumen-CSA in ED x systemic-pulse-pressure) x 10(3)]. ADI measured by 2D-trans-thoracic echocardiography (TTE) was compared with CTA-measured ADI in 26 subjects without CAC. CAC was defined as 0, 1-100, 101-400 and 400+. CAD was defined as luminal stenosis 0, 1-49% and 50%+. There was an excellent correlation between CTA- and TTE-measured ADI (r (2) = 0.94, P = 0.0001). ADI decreased from CAC 0 to CAC 400+; similarly from FRS 1-9% to FRS 20% + (P < 0.05). After adjustment for risk factors, the relative risk for each standard deviation decrease in ADI was 1.66 for CAC 1-100, 2.26 for CAC 101-400 and 2.32 for CAC 400+ as compared to CAC 0; similarly, 2.36 for non-obstructive CAD and 2.67 for obstructive CAD as compared to normal coronaries. The area under the ROC-curve to predict significant CAD was 0.68 for FRS, 0.75 for ADI, 0.81 for CAC and 0.86 for the combination (P < 0.05). Impaired aortic distensibility strongly correlates with the severity of coronary atherosclerosis. Addition of ADI to CAC and traditional risk factors provides incremental value to predict at-risk individuals.
C1 [Ahmadi, Naser; Nabavi, Vahid; Hajsadeghi, Fereshteh; Flores, Ferdinand; Ismaeel, Hussain; Mao, Song S.; Budoff, Matthew J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.
[Ebrahimi, Ramin] Univ Calif Los Angeles, Sch Med, Greater Los Angeles VA Med Ctr, Los Angeles, CA USA.
[Shavelle, David] Univ So Calif, Los Angeles, CA USA.
[Azmoon, Shahdad] New York Med Coll, Valhalla, NY 10595 USA.
RP Ahmadi, N (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, 1124 W Carson St,RB2, Torrance, CA 90502 USA.
EM nahmadi@labiomed.org
NR 52
TC 14
Z9 15
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD MAR
PY 2011
VL 27
IS 3
BP 459
EP 469
DI 10.1007/s10554-010-9680-6
PG 11
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 762OU
UT WOS:000290490100017
PM 20711815
ER
PT J
AU Wang, JC
Cunningham, MJ
AF Wang, James C.
Cunningham, Michael J.
TI Congenital dacryocystocele: Is there a familial predisposition?
SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY
LA English
DT Article
DE Dacryocystocele; Congenital nasolacrimal obstruction; Familial
ID NASOLACRIMAL DUCT; OBSTRUCTION; MANAGEMENT; MUCOCELE
AB Congenital impatency of the nasolacrimal drainage system is relatively common. Dacryocystocele formation is an infrequent variant of such congenital nasolacrimal duct obstruction (NLDO). Congenital dacryocystocele typically manifests as a mass in the medial canthal region; alternatively the nasolacrimal expansion may present solely intranasally as a nasolacrimal duct cyst. Despite the relative frequency of congenital NLDO, there have been few reported familial cases. We report here two female siblings with congenital dacryocystocele, and review the etiology and potential inherited predisposition to this comparatively rare entity. Published by Elsevier Ireland Ltd.
C1 [Wang, James C.; Cunningham, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Dept Otolaryngol,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Cunningham, MJ (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Dept Otolaryngol,Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM Michael_Cunningham@meei.harvard.edu
NR 15
TC 8
Z9 10
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-5876
J9 INT J PEDIATR OTORHI
JI Int. J. Pediatr. Otorhinolaryngol.
PD MAR
PY 2011
VL 75
IS 3
BP 430
EP 432
DI 10.1016/j.ijporl.2010.11.026
PG 3
WC Otorhinolaryngology; Pediatrics
SC Otorhinolaryngology; Pediatrics
GA 764BY
UT WOS:000290604600025
PM 21185090
ER
PT J
AU Mimiaga, MJ
Thomas, B
Mayer, KH
Reisner, SL
Menon, S
Swaminathan, S
Periyasamy, M
Johnson, CV
Safren, SA
AF Mimiaga, M. J.
Thomas, B.
Mayer, K. H.
Reisner, S. L.
Menon, S.
Swaminathan, S.
Periyasamy, M.
Johnson, C. V.
Safren, S. A.
TI Alcohol use and HIV sexual risk among MSM in Chennai, India
SO INTERNATIONAL JOURNAL OF STD & AIDS
LA English
DT Article
DE men who have sex with men (MSM); alcohol; HIV; sexually transmitted
infections (STI); prevention; intervention; India
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BASE-LINE DATA; BRIEF INTERVENTIONS;
TRANSMITTED INFECTIONS; WINE SHOPS; URBAN-POOR; CONDOM USE; MEN;
PREVENTION; HEALTH
AB Men who have sex with men (MSM) in India are a core risk group for HIV. Heavy alcohol consumption is associated with increased sexual risk-taking behaviours in many cultures, in particular among MSM. However, no studies to date have explored alcohol use and HIV risk among MSM in India. MSM in Chennai, India (n = 210) completed an interviewer-administered behavioural and psychosocial assessment. Bivariate and multivariable logistic regression procedures examined behavioural and demographic associations with weekly alcohol consumption. Twenty-eight percent of the sample (n = 58) reported using alcohol at least weekly to the point of being buzzed/intoxicated, which was associated with older age, being married to a woman, being panthi (masculine appearing, predominantly insertive partners) versus kothi (feminine acting/appearing and predominantly receptive partners), weekly tobacco use, unprotected anal sex and unprotected vaginal sex in the three months prior to study enrolment (all P < 0.05). In a multivariable model, unprotected vaginal sex in the previous three months and being married to a women were unique variables associated with weekly alcohol use (all P < 0.01). Further investigation of alcohol use within the context of sexual risk taking is warranted among Indian MSM. Panthis and MSM who are married to women may be particularly likely to benefit from interventions to decrease alcohol intake and concurrent unsafe sex.
C1 [Mimiaga, M. J.; Reisner, S. L.; Safren, S. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
[Mimiaga, M. J.; Mayer, K. H.; Johnson, C. V.; Safren, S. A.] Fenway Community Hlth, Fenway Inst, Boston, MA USA.
[Thomas, B.; Swaminathan, S.; Periyasamy, M.] Indian Council Med Res, TB Res Ctr, Madras, Tamil Nadu, India.
[Mayer, K. H.] Brown Univ, Miriam Hosp, Providence, RI USA.
[Menon, S.] Sahodaran, Madras, Tamil Nadu, India.
RP Mimiaga, MJ (reprint author), MGH Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM mmimiaga@partners.org
FU Lifespan/Tufts/Brown University Center for AIDS [NIH P30 AI42853];
[P30A1060354]
FX Funding for this project was supported by a supplement to parent grant
P30A1060354 on which Bruce Walker MD is the PI, and Steven A Safren PhD
was the PI of the supplement. Support for some staff time (Mayer) was
from the Lifespan/Tufts/Brown University Center for AIDS Research grant:
NIH P30 AI42853.
NR 42
TC 26
Z9 26
U1 1
U2 5
PU ROYAL SOC MEDICINE PRESS LTD
PI LONDON
PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND
SN 0956-4624
J9 INT J STD AIDS
JI Int. J. STD AIDS
PD MAR
PY 2011
VL 22
IS 3
BP 121
EP 125
DI 10.1258/ijsa.2009.009059
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 761UL
UT WOS:000290426400001
PM 21464447
ER
PT J
AU Weintraub, D
Morgan, JC
AF Weintraub, Daniel
Morgan, John C.
TI Both the Body and Brain Benefit from Exercise: Potential Win-Win for
Parkinson's Disease Patients
SO MOVEMENT DISORDERS
LA English
DT Editorial Material
ID COGNITIVE IMPAIRMENT; HIPPOCAMPAL; DEMENTIA
C1 [Weintraub, Daniel] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Morgan, John C.] Georgia Hlth Sci Univ, Augusta, GA USA.
RP Weintraub, D (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
RI AUDIFFREN, MICHEL/H-5649-2011
NR 10
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD MAR
PY 2011
VL 26
IS 4
BP 607
EP 607
DI 10.1002/mds.23726
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 762AO
UT WOS:000290444800008
PM 21506145
ER
PT J
AU Gallagher, CL
Oakes, TR
Johnson, SC
Chung, MK
Holden, JE
Bendlin, BB
McLaren, DG
Xu, GF
Nickles, RJ
Pyzalski, R
DeJesus, O
Brown, WD
AF Gallagher, Catherine L.
Oakes, Terrence R.
Johnson, Sterling C.
Chung, Moo K.
Holden, James E.
Bendlin, Barbara B.
McLaren, Donald G.
Xu, Guofan
Nickles, Robert J.
Pyzalski, Robert
DeJesus, Onofre
Brown, W. Douglas
TI Rate of 6-[18F]Fluorodopa Uptake Decline in Striatal Subregions in
Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; Fluorodopa positron emission tomography; disease
progression; aging; gender
ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN TRANSFER CONSTANTS; TIME UPTAKE
DATA; GRAPHICAL EVALUATION; DOPAMINE TURNOVER; CLINICAL-TRIALS;
PROGRESSION; PET; LEVODOPA
AB Background: Rate of decline in 6-L[(18)F]fluorodopa (FDOPA) uptake within the striatum has been reported as showing regional differences in Parkinson's disease (PD).
Methods: We acquired longitudinal brain FDOPA positron emission tomography (PET) studies in 26 PD subjects and 11 controls over 4.5 years. We analyzed both spatially normalized voxel-wise maps of radiotracer influx (Kocc) and average Kocc values for six non-overlapping volumes of interest (VOIs) encompassing the striatum.
Results: The voxel-wise analysis showed that in PD, FDOPA Kocc decline spanned the striatum but was greatest in the posterior putamen ipsilateral and anterior putamen contralateral to initial symptoms. The VOI approached showed that absolute rates of Kocc decline were significantly greater in PD than control subjects, but that the slope of decline did not differ between subregions. In PD, ratios of uptake between subregions did not change during the study with the exception of the ipsilateral putamen/caudate ratio. Decline rates were marginally greater during earlier time segments. Both male gender and advancing age were associated with lower baseline FDOPA uptake, but no difference in decline rates. VOI Kocc values were significantly correlated with disease duration, but only moderately correlated with clinical measures.
Discussion: We conclude that FDOPA uptake in subregions of the striatum is strongly correlated with disease duration and age, and declines approximately equally from symptom onset in PD. This implies that in idiopathic PD, relative preservation of uptake in the anterior striatum reflects a delay in pathologic involvement of nigrostriatal projections to this region. (C)2011 Movement Disorder Society
C1 [Gallagher, Catherine L.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Gallagher, Catherine L.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Oakes, Terrence R.; Chung, Moo K.] Univ Wisconsin, Waisman Ctr Brain Imaging Lab, Madison, WI USA.
[Johnson, Sterling C.; Bendlin, Barbara B.; Xu, Guofan] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA.
[Johnson, Sterling C.; Bendlin, Barbara B.; McLaren, Donald G.; Xu, Guofan] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA.
[Chung, Moo K.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA.
[Holden, James E.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA.
[McLaren, Donald G.; Nickles, Robert J.; DeJesus, Onofre] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA.
[Pyzalski, Robert] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA.
[Brown, W. Douglas] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA.
RP Gallagher, CL (reprint author), William S Middleton VA Hosp, 6112B,2500 Overlook Terrace Dr, Madison, WI 53792 USA.
EM gallagher@neurology.wisc.edu
RI McLaren, Donald/G-9906-2011;
OI Bendlin, Barbara/0000-0002-0580-9875; Johnson,
Sterling/0000-0002-8501-545X
FU William S. Middleton Memorial Veterans Hospital Geriatric Research
Education and Clinical Center; Waisman Laboratory for Brain Imaging and
Behavior, Madison, WI, USA
FX This work was supported with use of facilities at the William S.
Middleton Memorial Veterans Hospital Geriatric Research Education and
Clinical Center, and the Waisman Laboratory for Brain Imaging and
Behavior, Madison, WI, USA. Figure preparation by Jennifer Broihahn,
University of Wisconsin Department of Neurology Media Specialist.
NR 31
TC 6
Z9 6
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD MAR
PY 2011
VL 26
IS 4
BP 614
EP 620
DI 10.1002/mds.23503
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 762AO
UT WOS:000290444800010
PM 21449008
ER
PT J
AU Byers, AL
Vittinghoff, E
Lui, LY
Hoang, T
Covinsky, KE
Cauley, JA
Ensrud, KE
Hillier, TA
Fredman, L
Yaffe, K
AF Byers, Amy L.
Vittinghoff, Eric
Lui, Li-Yung
Hoang, Tina
Covinsky, Kenneth E.
Cauley, Jane A.
Ensrud, Kristine E.
Hillier, Teresa A.
Fredman, Lisa
Yaffe, Kristine
TI Characterization of Long-term Depressive Trajectories Among Elderly
Women
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry
CY MAR 18-21, 2011
CL San Antonio, TX
SP Amer Assoc Geriat Psychiat
C1 [Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Vittinghoff, Eric; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Byers, Amy L.; Hoang, Tina; Covinsky, Kenneth E.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Ensrud, Kristine E.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA.
[Fredman, Lisa] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Lui, Li-Yung] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2011
VL 19
IS 3
SU 1
BP S104
EP S105
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 753PD
UT WOS:000289791000117
ER
PT J
AU Calleo, JS
Bush, A
Kraus-Schuman, C
Snow, L
Wilson, N
Kunik, ME
Pauker, A
Stanley, MA
AF Calleo, Jessica S.
Bush, Amy
Kraus-Schuman, Cynthia
Snow, Lynn
Wilson, Nancy
Kunik, Mark E.
Pauker, Amber
Stanley, Melinda A.
TI Clinical Characteristics and Associated Anxiety Symptoms in Anxious
Patients with Dementia
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry
CY MAR 18-21, 2011
CL San Antonio, TX
SP Amer Assoc Geriat Psychiat
C1 [Calleo, Jessica S.; Bush, Amy; Wilson, Nancy; Kunik, Mark E.; Stanley, Melinda A.] Houston VA HSR&D Ctr Excellence, Houston, TX USA.
[Kraus-Schuman, Cynthia; Kunik, Mark E.] Michael E Debakay Vet Affairs Med Ctr, Houston, TX USA.
[Calleo, Jessica S.; Bush, Amy; Wilson, Nancy; Stanley, Melinda A.] Baylor Coll Med, Houston, TX 77030 USA.
[Snow, Lynn] Univ Alabama, Tuscaloosa, AL USA.
[Pauker, Amber] Puget Sound Hlth Care Syst, Dept Vet Affairs, Seatle, WA USA.
[Snow, Lynn] Tuscaloosa Vet Affairs Med Ctr, Tuscaloosa, AL USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2011
VL 19
IS 3
SU 1
BP S79
EP S80
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 753PD
UT WOS:000289791000084
ER
PT J
AU Calleo, JS
York, M
Bush, A
Wilson, N
Kraus-Schuman, C
Kunik, ME
Stanley, MA
AF Calleo, Jessica S.
York, Michele
Bush, Amy
Wilson, Nancy
Kraus-Schuman, Cynthia
Kunik, Mark E.
Stanley, Melinda A.
TI Problem Solving Confidence and Executive Functioning in Older Adults
with Generalized Anxiety Disorder
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry
CY MAR 18-21, 2011
CL San Antonio, TX
SP Amer Assoc Geriat Psychiat
C1 [Calleo, Jessica S.; York, Michele; Bush, Amy; Wilson, Nancy; Kraus-Schuman, Cynthia; Kunik, Mark E.; Stanley, Melinda A.] Baylor Coll Med, Houston, TX 77030 USA.
[Calleo, Jessica S.; York, Michele; Kraus-Schuman, Cynthia] Michael E Debakay Vet Affairs Med Ctr, Houston, TX USA.
[Bush, Amy; Wilson, Nancy; Kunik, Mark E.; Stanley, Melinda A.] Houston VA HRS&D Ctr Excellence, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2011
VL 19
IS 3
SU 1
BP S65
EP S66
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 753PD
UT WOS:000289791000063
ER
PT J
AU Chu, SH
Ferrell, R
Roeder, K
Devlin, B
DeMichele-Sweet, MAA
Lopez, OL
Sweet, RA
AF Chu, Su H.
Ferrell, Robert
Roeder, Kathryn
Devlin, Bernie
DeMichele-Sweet, Mary Ann A.
Lopez, Oscar L.
Sweet, Robert A.
TI TOMM40 Poly-T Repeat Length Polymorphism is Independently Associated
with Psychosis Risk, But Not Age of Onset, in Late Onset Alzheimer
Disease
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry
CY MAR 18-21, 2011
CL San Antonio, TX
SP Amer Assoc Geriat Psychiat
C1 [Chu, Su H.; Roeder, Kathryn] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
[Ferrell, Robert; Devlin, Bernie; DeMichele-Sweet, Mary Ann A.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Pittsburgh, PA USA.
[Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2011
VL 19
IS 3
SU 1
BP S125
EP S125
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 753PD
UT WOS:000289791000149
ER
PT J
AU Espinoza, R
Jarvik, L
Read, S
Kaufman, AH
AF Espinoza, Randall
Jarvik, Lissy
Read, Stephen
Kaufman, Aaron H.
TI EDUCATING THE NEXT GENERATION OF PHYSICIANS IN GERIATRIC PSYCHIATRY
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry
CY MAR 18-21, 2011
CL San Antonio, TX
SP Amer Assoc Geriat Psychiat
C1 [Espinoza, Randall; Kaufman, Aaron H.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Jarvik, Lissy; Read, Stephen] Greater Los Angeles VA Hlth Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2011
VL 19
IS 3
SU 1
BP S9
EP S9
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 753PD
UT WOS:000289791000003
ER
PT J
AU Feil, D
Rajan, M
Soroka, O
Miller, DR
Pogach, L
AF Feil, Denise
Rajan, Mangala
Soroka, Orysya
Miller, Donald R.
Pogach, Leonard
TI Increased Risk of Hypoglycemia in Older Patients with Dementia and
Cognitive Impairment: Is More Intensive Glycemic Control at the Expense
of Safety?
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry
CY MAR 18-21, 2011
CL San Antonio, TX
SP Amer Assoc Geriat Psychiat
C1 [Feil, Denise] W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
[Feil, Denise; Rajan, Mangala; Soroka, Orysya; Miller, Donald R.; Pogach, Leonard] East Orange REAP, E Orange, NJ USA.
[Miller, Donald R.] Bedford VA Ctr Hlth Outcomes, Bedford, MA 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 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2011
VL 19
IS 3
SU 1
BP S114
EP S114
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 753PD
UT WOS:000289791000133
ER
EF