FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Chou, YF
Chen, HH
Eijpe, M
Yabuuchi, A
Chenoweth, JG
Tesar, P
Lu, J
McKay, RDG
Geijsen, N
AF Chou, Yu-Fen
Chen, Hsu-Hsin
Eijpe, Maureen
Yabuuchi, Akiko
Chenoweth, Joshua G.
Tesar, Paul
Lu, Jun
Mckay, Ronald D. G.
Geijsen, Niels
TI The Growth Factor Environment Defines Distinct Pluripotent Ground States
in Novel Blastocyst-Derived Stem Cells
SO CELL
LA English
DT Article
ID PRIMORDIAL GERM-CELLS; HUMAN SOMATIC-CELLS; E-CADHERIN; REGULATORY
CIRCUITRY; MOUSE EMBRYOS; SELF-RENEWAL; FREE CULTURE; ES CELLS; LINES;
DIFFERENTIATION
AB Pluripotent stem cell lines can be derived from blastocyst embryos, which yield embryonic stem cell lines (ES cells), as well as the postimplantation epiblast, which gives rise to epiblast stem cell lines (EpiSCs). Remarkably, ES cells and EpiSCs display profound differences in the combination of growth factors that maintain their pluripotent state. Molecular and functional differences between these two stem cell types demonstrate that the tissue of origin and/or the growth factor milieu may be important determinants of the stem cell identity. We explored how developmental stage of the tissue of origin and culture growth factor conditions affect the stem cell pluripotent state. Our findings indicate that novel stem cell lines, with unique functional and molecular properties, can be generated from murine blastocyst embryos. We demonstrate that the culture growth factor environment and cell-cell interaction play a critical role in defining several unique and stable stem cell ground states.
C1 [Chou, Yu-Fen; Chen, Hsu-Hsin; Geijsen, Niels] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA.
[Eijpe, Maureen] Erasmus MC, Dept Cell Biol, NL-3015 GE Rotterdam, Netherlands.
[Yabuuchi, Akiko] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Chenoweth, Joshua G.; Mckay, Ronald D. G.] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Tesar, Paul] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
[Lu, Jun] Harvard Univ, Broad Inst, Cambridge, MA 02141 USA.
[Lu, Jun] MIT, Cambridge, MA 02141 USA.
RP Geijsen, N (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, CPZN-4256,185 Cambridge St, Boston, MA 02114 USA.
EM ngeijsen@mgh.harvard.edu
RI Tesar, Paul/C-9848-2014
OI Tesar, Paul/0000-0003-1532-3155
FU National Institutes of Health [RO1HD048769-01A1]; Harvard Stem Cell
Institute; Dutch Cancer Society (Koningin Wilhelmina Fonds)
FX The authors thank Dr. George Daley for his review of our manuscript and
help with the blastocyst injections; Dr. Paul Tesar for the EpiSC image;
Dr. Roger Tsien for the use of the tdTomato fluorescent reporter; Dr.
Keith Orford for critical review of the manuscript; Kelly Shea for
providing technical support; and Laura Prickett and Kat Folz-Donahue at
the HSCI/MGH Flow Cytometry Core Facility for help with cell
purifications. This work was supported by grants from the National
Institutes of Health (RO1HD048769-01A1) and the Harvard Stem Cell
Institute. M. E. was supported by the Dutch Cancer Society (Koningin
Wilhelmina Fonds).
NR 56
TC 148
Z9 155
U1 2
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 31
PY 2008
VL 135
IS 3
BP 449
EP 461
DI 10.1016/j.cell.2008.08.035
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367EW
UT WOS:000260536300016
PM 18984157
ER
PT J
AU Jin, W
Chen, Y
Di, GH
Miron, P
Hou, YF
Gao, H
Shao, ZM
AF Jin, Wei
Chen, Ying
Di, Gen-hong
Miron, Penelope
Hou, Yi-feng
Gao, Hui
Shao, Zhi-ming
TI Estrogen Receptor (ER)beta or p53 Attenuates ER alpha-mediated
Transcriptional Activation on the BRCA2 Promoter
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SPORADIC BREAST-CANCER; GENE-EXPRESSION; MESSENGER-RNA; CARCINOMAS;
MUTATIONS; P300; BETA; CBP; SUSCEPTIBILITY; COREGULATORS
AB BRCA2 is closely related to the pathogenesis of breast cancer. In the present study, we found that estrogen can activate BRCA2 transcription, which is estrogen receptor (ER) alpha-dependent. During estrogen treatment, ER alpha interacted with CREB-binding protein/p300, p68/p72, and MyoD and formed an activating transcriptional complex that could bind to many Sp1 sites on the BRCA2 promoter and activate its transcription by inducing histone acetylations. MyoD is a new component of ER alpha complex. ER beta or p53 attenuated ER alpha-mediated transcriptional activation by preventing the recruitment of ER alpha transcriptional complex and histone acetylations on the BRCA2 promoter. ER beta interacted with ER alpha and CREB-binding protein/p300 and formed a weak activating transcriptional complex that competed for binding to Sp1 sites with ER alpha transcriptional complex and slightly attenuated BRCA2 transcription. Different from ER beta, p53 interacted with HDAC1 and CtBP1 and formed an inhibiting transcriptional complex that could compete for binding to Sp1 sites with ER alpha transcriptional complex and inhibit BRCA2 transcription more significantly.
C1 [Jin, Wei; Chen, Ying; Di, Gen-hong; Hou, Yi-feng; Shao, Zhi-ming] Fudan Univ, Breast Canc Inst, Canc Hosp, Dept Oncol,Shanghai Med Coll,Inst Biomed Sci, Shanghai 200032, Peoples R China.
[Jin, Wei; Gao, Hui] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08901 USA.
[Miron, Penelope] Harvard Univ, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Shao, ZM (reprint author), Fudan Univ, Dept Breast Surg, Breast Canc Inst, Canc Hosp Canc Inst, 270 Dong Rd, Shanghai 200032, Peoples R China.
EM zhimingshao@yahoo.com
FU National Natural Science Foundation of China [30371580, 30572109];
Shanghai Science and Technology Committee [03J14019, 06DJ14004,
06DZ19504]; Cancer Hospital/Cancer Institute of Fudan University
[YJ200604]; Shanghai Pujiang Program; [2006CB0D0901]
FX This work was supported in part by 973 (Grant 2006CB0D0901), the
National Natural Science Foundation of China (Grants 30371580 and
30572109), the Shanghai Science and Technology Committee (Grants
03J14019, 06DJ14004, and 06DZ19504); the Cancer Hospital/Cancer
Institute of Fudan University (Grant YJ200604), and the Shanghai Pujiang
Program. The costs of publication of this article were defrayed in part
by the payment of page charges. This article must therefore be hereby
marked "advertisement" in accordance with 18 U. S. C. Section 1734
solely to indicate this fact.
NR 29
TC 20
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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 OCT 31
PY 2008
VL 283
IS 44
BP 29671
EP 29680
DI 10.1074/jbc.M802785200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 364WS
UT WOS:000260366900010
PM 18765668
ER
PT J
AU Sullivan, MD
Ciechanowski, PS
Russo, JE
Spertus, JA
Soine, LA
Jordan-Keith, K
Caldwell, JH
AF Sullivan, Mark D.
Ciechanowski, Paul S.
Russo, Joan E.
Spertus, John A.
Soine, Laurie A.
Jordan-Keith, Kier
Caldwell, James H.
TI Angina pectoris during daily activities and exercise stress testing: The
role of inducible myocardial ischemia and psychological distress
SO PAIN
LA English
DT Article
DE Health status; Quality of life; Coronary heart disease; Depression;
Anxiety; Somatization; Symptoms; Chest pain; Visceral pain
ID CORONARY-ARTERY-DISEASE; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED TRIAL;
CHRONIC REFRACTORY ANGINA; COPING STRATEGIES; CHEST-PAIN; INTERVENTION;
INVENTORY; MORTALITY; ANXIETY
AB Physicians often consider angina pectoris to be synonymous with myocardial ischemia. However, the relationship between angina and myocardial ischemia is highly variable and we have little insight into the Sources of this variability. We investigated the relationship of inducible myocardial ischemia oil SPECT stress perfusion imaging to angina reported with routine daily activities during the previous four weeks (N = 788) and to angina reported during an exercise stress test (N = 371) in individuals with confirmed or Suspected coronary disease referred for clinical testing. We found that angina experienced during daily lire is more strongly and consistently associated with psychological distress and the personal threat associated with angina than with inducible myocardial ischemia. In multivariable models, the presence of any angina during routine activities over the prior month was significantly associated with age, perceived risk of myocardial infarction, and anxiety when compared to those with no reported angina in the past month. Angina during daily life was not significantly associated with inducible myocardial ischemia oil stress perfusion imaging in bivariate or multivariable models. In contrast, angina experienced during exercise stress testing was significantly related to image and ECG ischemia, though it was also significantly associated with anxiety. These results suggest that angina frequency over the previous four weeks is more strongly associated with personal threat and psychosocial distress than with inducible myocardial ischemia. These results lend support to angina treatment strategies that aim to reduce threat and distress as well as to reduce myocardial ischemia. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 [Sullivan, Mark D.; Ciechanowski, Paul S.; Russo, Joan E.; Soine, Laurie A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Div Consultat Liaison Psychiat, Seattle, WA 98195 USA.
[Spertus, John A.] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA.
[Jordan-Keith, Kier; Caldwell, James H.] VA Puget Sound Hlth Care Syst, Dept Cardiol, Seattle, WA USA.
[Caldwell, James H.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA.
[Caldwell, James H.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
RP Sullivan, MD (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Div Consultat Liaison Psychiat, 1959 NE Pacific St,Box 356560, Seattle, WA 98195 USA.
EM sullimar@u.washington.edu
FU American Heart Association [0450094Z]
FX Dr. Sullivan thanks the American Heart Association For the grant that
supported this research 0450094Z. The authors have no conflicts of
interest to report.
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U1 2
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD OCT 31
PY 2008
VL 139
IS 3
BP 551
EP 561
DI 10.1016/j.pain.2008.06.009
PG 11
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 372IG
UT WOS:000260894700010
PM 18694624
ER
PT J
AU Keating, BJ
Tischfield, S
Murray, SS
Bhangale, T
Price, TS
Glessner, JT
Galver, L
Barrett, JC
Grant, SFA
Farlow, DN
Chandrupatla, HR
Hansen, M
Ajmal, S
Papanicolaou, GJ
Guo, YR
Li, MY
DerOhannessian, S
de Bakker, PIW
Bailey, SD
Montpetit, A
Edmondson, AC
Taylor, K
Gai, XW
Wang, SS
Fornage, M
Shaikh, T
Groop, L
Boehnke, M
Hall, AS
Hattersley, AT
Frackelton, E
Patterson, N
Chiang, CWK
Kim, CE
Fabsitz, RR
Ouwehand, W
Price, AL
Munroe, P
Caulfield, M
Drake, T
Boerwinkle, E
Reich, D
Whitehead, AS
Cappola, TP
Samani, NJ
Lusis, AJ
Schadt, E
Wilson, JG
Koenig, W
McCarthy, MI
Kathiresan, S
Gabriel, SB
Hakonarson, H
Anand, SS
Reilly, M
Engert, JC
Nickerson, DA
Rader, DJ
Hirschhorn, JN
FitzGerald, GA
AF Keating, Brendan J.
Tischfield, Sam
Murray, Sarah S.
Bhangale, Tushar
Price, Thomas S.
Glessner, Joseph T.
Galver, Luana
Barrett, Jeffrey C.
Grant, Struan F. A.
Farlow, Deborah N.
Chandrupatla, Hareesh R.
Hansen, Mark
Ajmal, Saad
Papanicolaou, George J.
Guo, Yiran
Li, Mingyao
DerOhannessian, Stephanie
de Bakker, Paul I. W.
Bailey, Swneke D.
Montpetit, Alexandre
Edmondson, Andrew C.
Taylor, Kent
Gai, Xiaowu
Wang, Susanna S.
Fornage, Myriam
Shaikh, Tamim
Groop, Leif
Boehnke, Michael
Hall, Alistair S.
Hattersley, Andrew T.
Frackelton, Edward
Patterson, Nick
Chiang, Charleston W. K.
Kim, Cecelia E.
Fabsitz, Richard R.
Ouwehand, Willem
Price, Alkes L.
Munroe, Patricia
Caulfield, Mark
Drake, Thomas
Boerwinkle, Eric
Reich, David
Whitehead, A. Stephen
Cappola, Thomas P.
Samani, Nilesh J.
Lusis, A. Jake
Schadt, Eric
Wilson, James G.
Koenig, Wolfgang
McCarthy, Mark I.
Kathiresan, Sekar
Gabriel, Stacey B.
Hakonarson, Hakon
Anand, Sonia S.
Reilly, Muredach
Engert, James C.
Nickerson, Deborah A.
Rader, Daniel J.
Hirschhorn, Joel N.
FitzGerald, Garret A.
TI Concept, Design and Implementation of a Cardiovascular Gene-Centric 50 K
SNP Array for Large-Scale Genomic Association Studies
SO PLOS ONE
LA English
DT Article
AB A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan'' tagging approach to capture the genetic diversity across similar to 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.
C1 [Keating, Brendan J.; Whitehead, A. Stephen; Reilly, Muredach; Rader, Daniel J.; FitzGerald, Garret A.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Tischfield, Sam; Farlow, Deborah N.; de Bakker, Paul I. W.; Patterson, Nick; Chiang, Charleston W. K.; Reich, David; Kathiresan, Sekar; Gabriel, Stacey B.; Hirschhorn, Joel N.] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA.
[Tischfield, Sam; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Endocrinol, Program Genom, Boston, MA USA.
[Murray, Sarah S.] Scripps Genom Med, La Jolla, CA USA.
[Bhangale, Tushar; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Price, Thomas S.] MRC SGDP Ctr, Inst Psychiat, London, England.
[Glessner, Joseph T.; Grant, Struan F. A.; Gai, Xiaowu; Shaikh, Tamim; Frackelton, Edward; Kim, Cecelia E.; Hakonarson, Hakon] CHOP, Dept Pediat, Div Human Genet, Ctr Applied Genom, Philadelphia, PA USA.
[Barrett, Jeffrey C.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
[Chandrupatla, Hareesh R.; Ajmal, Saad; Li, Mingyao; DerOhannessian, Stephanie; Edmondson, Andrew C.; Cappola, Thomas P.; Reilly, Muredach; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Galver, Luana; Hansen, Mark] Illumina Inc, San Diego, CA USA.
[Papanicolaou, George J.; Fabsitz, Richard R.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD USA.
[Guo, Yiran] Beijing Genom Inst Shenzhen, Shenzhen, Peoples R China.
[de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA USA.
[Taylor, Kent] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA USA.
[Wang, Susanna S.; Drake, Thomas; Lusis, A. Jake] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Fornage, Myriam] Univ Texas, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Groop, Leif] Lund Univ, Dept Clin Sci Malmoe, Diabetes & Endocrinol, S-22100 Lund, Sweden.
[Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Hall, Alistair S.] Univ Leeds, Leeds Inst Genet, Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England.
[Hattersley, Andrew T.] Peninsula Med Sch, Inst Biomed & Clin Sci, Diabetes Genet Grp, Exeter, Devon, England.
[Chiang, Charleston W. K.; Reich, David; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Munroe, Patricia] Barts & The London, Dept Clin Pharmacol, London, England.
[Ouwehand, Willem] Univ Cambridge, NHS Blood & Transplant, Dept Haematol, Cambridge CB2 1TN, England.
[Munroe, Patricia; Caulfield, Mark] Barts & The London, William Harvey Res Inst, London, England.
[Boerwinkle, Eric] Univ Texas, Hlth Sci Ctr, Human Genet Ctr, Houston, TX USA.
[Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England.
[Schadt, Eric] Merck & Co Inc, Rosetta Inpharmat LLC, Seattle, WA USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, VA Med Ctr, University, MS 38677 USA.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiol Div, Boston, MA USA.
[Anand, Sonia S.] McMaster Univ, Hamilton Gen Hosp, Hamilton Hlth Sci, Clin Epidemiol & Biostat, Populat Genom Program, Hamilton, ON L8S 4L8, Canada.
[Bailey, Swneke D.; Engert, James C.] McGill Univ, Dept Med & Human Genet, Montreal, PQ H3A 2T5, Canada.
[Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Cambridge, MA 02138 USA.
[McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford Ctr Diabetes, Endocrinol & Metabolism, Oxford OX1 2JD, England.
[Lusis, A. Jake] Univ Calif Los Angeles, Sch Med, Dept Microbiol, Immunol & Mol Genet, Los Angeles, CA 90024 USA.
[Montpetit, Alexandre] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
RP Keating, BJ (reprint author), Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
EM garret@spirit.gcrc.upenn.edu
RI FitzGerald, Garret/A-4222-2010; Price, Thomas/B-7372-2008; Guo,
Yiran/H-4120-2011; de Bakker, Paul/B-8730-2009;
OI Price, Thomas/0000-0001-7356-2109; Guo, Yiran/0000-0002-6549-8589; de
Bakker, Paul/0000-0001-7735-7858; Barrett, Jeffrey/0000-0002-1152-370X;
Chiang, Charleston/0000-0002-0668-7865
FU National Institute of Health Clinical and Translational Research Award
[RR U54 RR023567]; University of Pennsylvania; National Heart, Lung and
Blood Institute [N01-HC-65226, U01 HL66642]
FX Supported by a National Institute of Health Clinical and Translational
Research Award (RR U54 RR023567) to the University of Pennsylvania and
National Heart, Lung and Blood Institute (N01-HC-65226). Tushar
Bhangale's work was supported by the Program for Genomic Applications
supported by the NHLBI (U01 HL66642).
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U1 1
U2 22
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 OCT 31
PY 2008
VL 3
IS 10
AR e3583
DI 10.1371/journal.pone.0003583
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432KK
UT WOS:000265131700007
PM 18974833
ER
PT J
AU Zhao, J
Sun, BK
Erwin, JA
Song, JJ
Lee, JT
AF Zhao, Jing
Sun, Bryan K.
Erwin, Jennifer A.
Song, Ji-Joon
Lee, Jeannie T.
TI Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X
Chromosome
SO SCIENCE
LA English
DT Article
ID INACTIVE-X; XIST RNA; DOMAINS; RECRUITMENT; METHYLATION; TSIX
AB To equalize X- chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X- chromosome inactivation ( XCI) is initiated by expression of Xist, a 17- kb noncoding RNA ( ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6- kilobase ncRNA ( RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full- length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up- regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus.
C1 [Zhao, Jing; Sun, Bryan K.; Erwin, Jennifer A.; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Zhao, Jing; Sun, Bryan K.; Erwin, Jennifer A.; Song, Ji-Joon; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02493 USA.
[Zhao, Jing; Sun, Bryan K.; Erwin, Jennifer A.; Song, Ji-Joon; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Lee, JT (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA.
EM lee@molbio.mgh.harvard.edu
RI Song, Ji-Joon/C-1721-2011;
OI Sun, Bryan/0000-0002-0740-0125
FU Massachusetts General Hospital Fund for Medical Discovery; NSF
predoctoral award; Jane Coffin Childs Fellowship; NIH [R01GM58839]
FX We thank R. Spencer and Y. Jeon for unpublished data and technical
advice and Y. Ogawa for critical reading of the manuscript. Grant
support: Massachusetts General Hospital Fund for Medical Discovery
(J.Z.), NSF predoctoral award (J.A.E.), Jane Coffin Childs Fellowship
(J.J.S.), and NIH- R01GM58839 (J.T.L.). J.T.L. is an Investigator of the
HHMI. The transcript WRepAW for Repeat A has GenBank accession number
FJ361197.
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TC 746
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U1 7
U2 73
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 31
PY 2008
VL 322
IS 5902
BP 750
EP 756
DI 10.1126/science.1163045
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 368EW
UT WOS:000260605200052
PM 18974356
ER
PT J
AU Ross, JS
Nunez-Smith, M
Forsyth, BA
Rosenbaum, JR
AF Ross, Joseph S.
Nunez-Smith, Marcella
Forsyth, Beverly A.
Rosenbaum, Julie R.
TI Racial and ethnic differences in personal cervical cancer screening
amongst post-graduate physicians: Results from a cross-sectional survey
SO BMC PUBLIC HEALTH
LA English
DT Article
ID UNITED-STATES; HEALTH-SERVICES; NATIONAL-SURVEY; HISPANIC WOMEN; CARE;
BEHAVIORS; AMERICAN; BREAST; DISPARITIES; POPULATION
AB Background: Racial and ethnic disparities in cervical cancer screening have been attributed to socioeconomic, insurance, and cultural differences. Our objective was to explore racial and ethnic differences in adherence to cervical cancer screening recommendations among female post-graduate physicians.
Methods: We conducted a cross-sectional survey at one university hospital among a convenience sample of 204 female post-graduate physicians (52% of all potential participants), examining adherence to United States Preventive Services Task Force cervical cancer screening recommendations, perception of adherence to recommendations, and barriers to obtaining care.
Results: Overall, 83% of women were adherent to screening recommendations and 84% accurately perceived adherence or non-adherence. Women who self-identified as Asian were significantly less adherent when compared with women who self-identified as white (69% vs. 87%; Relative Risk [RR] = 0.79, 95% Confidence Interval [CI], 0.64-0.97; P < 0.01). Women who self-identified as East Indian were significantly less likely to accurately perceive adherence or non-adherence when compared to women who self-identified as white (64% vs. 88%; RR = 0.73, 95% CI, 0.49-1.09, P = 0.04). Women who self-identified as Asian were significantly more likely to report any barrier to obtaining care when compared with women who self-identified as white (60% vs. 35%; RR = 1.75, 95% CI, 1.24-2.47; P = 0.001) and there was a nonsignificant tendency toward women who self-identified as East Indian being more likely to report any barrier to obtaining care when compared with women who self-identified as white (60% vs. 34%; RR = 1.74, 95% CI, 1.06-2.83; P = 0.06).
Conclusion: Among a small group of insured, highly-educated physicians who have access to health care, we found racial and ethnic differences in adherence to cervical cancer screening recommendations, suggesting that culture may play a role in cervical cancer screening.
C1 [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, Bronx, NY USA.
[Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
[Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Targeted Res Enhancement Program, Bronx, NY USA.
[Nunez-Smith, Marcella] Yale Univ, Sch Med, Dept Internal Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA.
[Forsyth, Beverly A.] Mt Sinai Sch Med, Dept Med, Div Infect Dis, Bronx, NY USA.
[Rosenbaum, Julie R.] Yale Univ, Sch Med, Primary Care Internal Med Residency Program, New Haven, CT USA.
[Rosenbaum, Julie R.] Waterbury Hosp & Hlth Ctr, Ctr Hlth, Dept Med, New Haven, CT USA.
RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, Bronx, NY USA.
EM joseph.ross@mssm.edu; marcella.nunez-smith@yale.edu;
beverly.a.forsyth@mssm.edu; julie.rosenbaum@yale.edu
NR 29
TC 6
Z9 6
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD OCT 30
PY 2008
VL 8
AR 378
DI 10.1186/1471-2458-8-378
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 379PP
UT WOS:000261409000001
PM 18973674
ER
PT J
AU Rodrigues, GR
Walker, RH
Bader, B
Danek, A
Marques, W
Tumas, V
AF Rodrigues, Guilherme Riccioppo
Walker, Ruth H.
Bader, Benedikt
Danek, Adrian
Marques, Wilson, Jr.
Tumas, Vitor
TI Chorea-Acanthocytosis: Report of Two Brazilian Cases
SO MOVEMENT DISORDERS
LA English
DT Article
DE Chorea-acanthocytosis
ID PROTEIN; GENE
AB Chorea-acanthocytosis (ChAc) is a neurodegenerative disorder characterized by chorea, neuropsychiatric disturbances and acanthocytosis, caused by mutations of VPS13A. This gene produces the protein chorein which is absent in patients with ChAc on Western blot assay. We report the first two Brazilian patients with ChAc confirmed by chorein detection. Patient I is a 36-year-old man with chorea, epilepsy, myopathy. and suicidal ideation. Patient 2 is a 60-year-old woman with a 30 Year history of psychiatric disturbances, epilepsy, choreic movements, and myopathy. Both patients had acanthocytosis, elevated creatine kinase (CK), and absence (of chorein on Western blot analysis. The presence of chorea and neuropsychiatric disturbances associated with elevated CK levels, epilepsy, hyporeflexia, and acanthocytosis suggests the diagnosis of ChAc. Chorein assay of peripheral blood confirms the diagnosis. (C) 2008 Movement Disorder Society
C1 [Rodrigues, Guilherme Riccioppo; Marques, Wilson, Jr.; Tumas, Vitor] Ribeirao Preto Sch Med, Dept Neurol, BR-14049900 Ribeirao Preto, Brazil.
[Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA.
[Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA.
[Bader, Benedikt; Danek, Adrian] Univ Munich, Dept Neurol, D-8000 Munich, Germany.
RP Tumas, V (reprint author), Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurol Psychiat & Med Psychol, Campus Univ, BR-14049900 Ribeirao Preto, Brazil.
EM tumasv@rnp.fmrp.usp.br
RI Rodrigues, Guilherme/D-3547-2009; Danek, Adrian/G-7339-2011; Marques,
Wilson/G-4240-2012; Tumas, Vitor/C-9949-2014
OI Rodrigues, Guilherme/0000-0002-4296-1016; Danek,
Adrian/0000-0001-8857-5383; Marques, Wilson/0000-0002-4589-2749;
NR 10
TC 6
Z9 6
U1 1
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD OCT 30
PY 2008
VL 23
IS 14
BP 2090
EP 2093
DI 10.1002/mds.22305
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 374DA
UT WOS:000261021500020
PM 18785241
ER
PT J
AU Gerberding, JL
Romero, JM
Ferraro, MJ
Pisculli, M
Rosenberg, ES
Heller, HM
Atkins, EH
AF Gerberding, Julie L.
Romero, Javier M.
Ferraro, Mary Jane
Pisculli, Mary
Rosenberg, Eric S.
Heller, Howard M.
Atkins, Elisha H.
TI A woman with neck pain and fever - Laboratory-acquired infection with B.
melitensis, with cervical spinal osteomyelitis and epidural abscess
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID BRUCELLOSIS
C1 [Gerberding, Julie L.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Romero, Javier M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Ferraro, Mary Jane] Massachusetts Gen Hosp, Clin Microbiol Lab, Boston, MA 02114 USA.
[Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Romero, Javier M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Ferraro, Mary Jane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Gerberding, JL (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
FU General Electric
FX Dr. Romero reports receiving research grant support from General
Electric. No other potential conflict of interest relevant to this
article was reported.
NR 11
TC 3
Z9 3
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 30
PY 2008
VL 359
IS 18
BP 1942
EP 1949
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 366BL
UT WOS:000260454500011
PM 18971496
ER
PT J
AU Faustman, DL
AF Faustman, Denise L.
TI Immunotherapy on trial for new-onset type 1 diabetes
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CYCLOSPORINE; RESPONSES; PROGRESSION; MELLITUS; THERAPY; IDDM; MICE
C1 [Faustman, Denise L.] Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02114 USA.
[Faustman, Denise L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02114 USA.
NR 14
TC 3
Z9 3
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 30
PY 2008
VL 359
IS 18
BP 1956
EP 1958
DI 10.1056/NEJMe0807425
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 366BL
UT WOS:000260454500014
PM 18843119
ER
PT J
AU Papakostas, GI
McGrath, P
Stewart, J
Charles, D
Chen, Y
Mischoulon, D
Dording, C
Fava, M
AF Papakostas, George I.
McGrath, Patrick
Stewart, Jonathan
Charles, Dana
Chen, Ying
Mischoulon, David
Dording, Christina
Fava, Maurizio
TI Psychic and somatic anxiety symptoms as predictors of response to
fluoxetine in major depressive disorder
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Depression; Unipolar; SSRI; Clinical; Improvement; Pain
ID ATYPICAL DEPRESSION; IMIPRAMINE; PLACEBO; OUTPATIENTS; INHIBITORS;
PHENELZINE; REMISSION
AB The purpose of this study was to examine whether the presence/severity of psychic and somatic anxiety symptoms predicted clinical response following a 12-week, flexible-dose (20-60 mg daily), open-label trial of fluoxetine for major depressive disorder (MDD). The presence and severity of psychic and somatic anxiety symptoms were assessed with the use of select subscales of the Symptom Questionnaire and the Hopkins Symptom Checklist among 518 outpatients with MDD. With the use of separate logistic regressions, we tested for the relationship between clinical response, baseline Hamilton Depression Rating Scale (HAM-D-17) scores, and subscale scores at baseline entered separately as independent variables Overall completion, response and remission rates for the trial were 64.2%, 55.4%, and 48.9%, respectively. All subscale scores selected for this analysis significantly predicted treatment response to fluoxetine. The presence/severity of psychic and somatic anxiety symptoms of MDD at baseline predicted an increased likelihood of non-response to fluoxetine in MDD. Studies examining whether specific treatment strategies are more effective than the selective serotonin reuptake inhibitors for MDD patients with high levels of co-morbid psychic and somatic anxiety symptoms are warranted. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Papakostas, George I.] Harvard Univ, Dept Psychiat, Depress Clin & Res Program, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA.
[McGrath, Patrick; Stewart, Jonathan; Chen, Ying] Columbia Univ, New York State Psychiat Inst, Depress Evaluat Serv, New York, NY USA.
RP Papakostas, GI (reprint author), Harvard Univ, Dept Psychiat, Depress Clin & Res Program, Massachusetts Gen Hosp,Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA.
EM gpapakostas@partners.org
RI McGrath, Patrick/I-6410-2013; Papakostas, George/I-6905-2013
OI McGrath, Patrick/0000-0001-7217-7321; Papakostas,
George/0000-0002-2465-5103
NR 27
TC 20
Z9 21
U1 0
U2 1
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 OCT 30
PY 2008
VL 161
IS 1
BP 116
EP 120
DI 10.1016/j.psychres.2008.02.011
PG 5
WC Psychiatry
SC Psychiatry
GA 373CT
UT WOS:000260949300016
PM 18755514
ER
PT J
AU Sakimoto, T
Kim, TI
Ellenberg, D
Fukai, N
Jain, S
Azar, DT
Chang, JH
AF Sakimoto, Tohru
Kim, Tae-im
Ellenberg, David
Fukai, Naomi
Jain, Sandeep
Azar, Dimitri T.
Chang, Jin-Hong
TI Collagen XVIII and corneal reinnervation following keratectomy
SO FEBS LETTERS
LA English
DT Article
DE Extracellular matrix; Collagen XVIII
ID BASEMENT-MEMBRANES; PERIPHERAL-NERVE; SCHWANN-CELLS; REGENERATION;
INNERVATION; MICE; TRANSPLANTATION; ANGIOGENESIS; CLEAVAGE; DEFECTS
AB The significance of collagen XVIII in the regulation of corneal reinnervation remains largely unknown. We used whole-mount immunoconfocal microscopy to localize collagen XVIII to the nerve basement membrane of wild-type (WT) mouse corneas. Transmission electron microscopy showed corneal nerve disorganization in collagen XVIII knockout mice (col18a1(-/-)). Antibody 2H3-specific neuro. lament colocalized with collagens XVIII and IV and laminin-2 in WT mouse corneas, but did not colocalize with collagen IV and laminin-2 in col18a1(-/-)) mouse corneas. Following keratectomy, col18a1(-/-) mice displayed decreased corneal neurite extension compared to WT mice. Our data indicate that collagen XVIII may play an important role in corneal reinnervation after wounding. (c) 2008 Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.
C1 [Ellenberg, David; Jain, Sandeep; Azar, Dimitri T.; Chang, Jin-Hong] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA.
[Sakimoto, Tohru; Kim, Tae-im; Jain, Sandeep; Azar, Dimitri T.; Chang, Jin-Hong] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Sakimoto, Tohru; Kim, Tae-im; Jain, Sandeep; Azar, Dimitri T.; Chang, Jin-Hong] Harvard Univ, Schepens Eye Res Inst, Boston, MA 02115 USA.
[Fukai, Naomi] Harvard Univ, Sch Dent Med, Sch Med, Dept Oral & Dev Biol, Boston, MA 02115 USA.
RP Chang, JH (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA.
EM changr@uic.edu
RI 谭, 德华/D-1910-2009
FU NIH [EY14048, EY10101, EY001792]; Research to Prevent Blindness; Bausch
Lomb Japan/MEEI Research; apan Eye Bank Association Overseas Research
FX We thank Dr. Bjorn Olsen for providing col18a1-/- mice and
Patricia Pearson for TEM imaging. Supported by NIH EY14048 (J. H. C.),
EY10101 ( D. T. A.), EY 001792 ( D. T. A.), an unrestricted departmental
grant from Research to Prevent Blindness, the Bausch Lomb Japan/MEEI
Research Fellowship Award, and the Japan Eye Bank Association Overseas
Research Award ( T. S.).
NR 30
TC 6
Z9 6
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD OCT 29
PY 2008
VL 582
IS 25-26
BP 3674
EP 3680
DI 10.1016/j.febslet.2008.09.052
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 371BT
UT WOS:000260807500018
PM 18840438
ER
PT J
AU Temereanca, S
Brown, EN
Simons, DJ
AF Temereanca, Simona
Brown, Emery N.
Simons, Daniel J.
TI Rapid Changes in Thalamic Firing Synchrony during Repetitive Whisker
Stimulation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE thalamocortical; firing synchrony; somatosensory; barreloid; barrel
cortex; whiskers
ID RAT BARREL CORTEX; SOMATOSENSORY CORTEX; VENTROBASAL COMPLEX;
VISUAL-CORTEX; SPIKE TRAINS; NEURONS; DEFLECTIONS; SYSTEM; RELAY;
FREQUENCY
AB Thalamic firing synchrony is thought to ensure selective transmission of relevant sensory information to the recipient cortical neurons by rendering them more responsive to temporally correlated input spikes. However, direct evidence for a synchrony code in the thalamus is limited. Here, we directly measure thalamic firing synchrony and its stimulus-induced modulation over time, using simultaneous single unit recordings from individual thalamic barreloids in the rat somatosensory whisker/barrel system. Employing whisker deflections varying in velocity or frequency and a cross-correlation approach, we find systematic changes in both time course and strength of thalamic firing synchrony as a function of stimulus parameters and sensory adaptation. Synchrony develops faster and is greater with higher velocity deflections. Greater firing synchrony reflects stimulus-dependent increases in instantaneous firing rates, greater spike time precision relative to stimulus onset as well as common input that likely arises from divergent trigeminothalamic and corticothalamic neurons. With adaptation, synchrony decreases and takes longer to develop but is more dependent on the cells' common inputs. Rapid, sharp increases in thalamic synchrony mirroring quick increases in whisker velocity occur also during ongoing random, high-frequency whisker vibrations. Together, results demonstrate millisecond by millisecond changes in thalamic near-synchronous firing during complex patterns of ongoing vibrissa movements that may ensure transmission of preferred sensory information in local thalamocortical circuits during whisking and active touch.
C1 [Temereanca, Simona; Simons, Daniel J.] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15261 USA.
[Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Brown, Emery N.] Harvard Massachusetts Inst Technol, Dept Brain & Cognit Sci, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Temereanca, Simona] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, MIT,Med Sch, Charlestown, MA 02129 USA.
RP Temereanca, S (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, MIT,Med Sch, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM temerean@nmr.mgh.harvard.edu
FU Natinal Institutes of Health [NS19950, HD050627, DA015644, MH59733]
FX This work was supported by Natinal Institutes of Health Grants NS19950
(D.J.S), HD050627 (S. T.), DA015644 (E.N.B.), and MH59733 (E.N.B.).
Wethank Dr. Harold Kyriazi for expert technical assistance with data
recordings and Dr. Robert Haslinger for helpful discussions and
technical assistance with data analysis.
NR 39
TC 39
Z9 39
U1 0
U2 0
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD OCT 29
PY 2008
VL 28
IS 44
BP 11153
EP 11164
DI 10.1523/JNEUROSCI.1586-08.2008
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 366RZ
UT WOS:000260502400007
PM 18971458
ER
PT J
AU Mody, M
Wehner, DT
Ahlfors, SP
AF Mody, Maria
Wehner, Daniel T.
Ahlfors, Seppo P.
TI Auditory word perception in sentence context in reading-disabled
children
SO NEUROREPORT
LA English
DT Article
DE dyslexia; magnetoencephalography; N400; phonological mismatch
negativity; reading impairment
ID MAGNETOENCEPHALOGRAPHY MEG; DEVELOPMENTAL DYSLEXIA; DORSAL STREAM;
RECOGNITION; RESPONSES; COMPREHENSION; LOCALIZATION; SENSITIVITY;
POTENTIALS; ACTIVATION
AB Reading difficulties seem to be related to a phonological deficit that has its origin in poor speech perception. As such, disabled readers may use contextual cues to compensate for their weak speech perception abilities.We compared good and poor readers, 7-13 years old, on auditory perception of words varying in phonological contrast, in congruent versus incongruent sentence contexts. Both groups did worse in the phonologically similar than in the phonologically dissimilar incongruent condition. Magnetoencephalography revealed differential activation between the groups as a function of phonological contrast in left superior temporal gyrus between 200 and 300 ms, suggesting that poor readers may have processed phonologically similar incongruent stimuli as congruent. The results are consistent with a phonological account of reading disability. NeuroReport 19:1567-1571 (C) 2008 Wolters Kluwer Health | Lippincott Williams& Wilkins.
C1 [Mody, Maria; Wehner, Daniel T.; Ahlfors, Seppo P.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MIT, HMS, Charlestown, MA 02129 USA.
[Mody, Maria; Wehner, Daniel T.; Ahlfors, Seppo P.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Mody, M (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MIT, HMS, 149 13th St,Rm 2301, Charlestown, MA 02129 USA.
EM maria@nmr.mgh.harvard.edu
RI Ahlfors, Seppo/P-3644-2016
FU NIH [DC00159, HDO46171]; NCRR [P41RR14075]; MIND Institute; [DC00038];
[5T32EB001680]
FX There was no conflict of interest. The authors thank S. Basho, S.
Mosher, C. Sahyoun, D. Von Pechmann, and M. Hamalainen for various
aspects of data collection and analysis, and S. Shattuck-Hufnagel, K.
Stevens, and C. Perfetfi for helpful comments. Supported by NIH: DC00159
and HDO46171, and in part by NCRR P41RR14075 and the MIND Institute. DTW
was also supported by an NIH Training Grant DC00038, and 5T32EB001680
(PI: Bruce Rosen). We thank all the children and parents for their
willingness to participate in the study.
NR 25
TC 5
Z9 5
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
EI 1473-558X
J9 NEUROREPORT
JI Neuroreport
PD OCT 29
PY 2008
VL 19
IS 16
BP 1567
EP 1571
DI 10.1097/WNR.0b013e328311ca04
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 365VT
UT WOS:000260438100003
PM 18815588
ER
PT J
AU Li, X
Sapp, E
Valencia, A
Kegel, KB
Qin, ZH
Alexander, J
Masso, N
Reeves, P
Ritch, JJ
Zeitlin, S
Aronin, N
DiFiglia, M
AF Li, Xueyi
Sapp, Ellen
Valencia, Antonio
Kegel, Kimberly B.
Qin, Zheng-Hong
Alexander, Jonathan
Masso, Nicholas
Reeves, Patrick
Ritch, James J.
Zeitlin, Scott
Aronin, Neil
DiFiglia, Marian
TI A function of huntingtin in guanine nucleotide exchange on RabII
SO NEUROREPORT
LA English
DT Article
DE endosomes; huntingtin; nucleotide exchange factor; RabII
ID MEMBRANE; PROTEIN; SPECIFICITY; ENDOSOME; DISEASE; COMPLEX; BRAIN; GEF
AB Huntingtin is ubiquitously expressed and enriched in the brain. Deletion of the huntingtin gene in mice is lethal during early embryonic development. The function of huntingtin is, however, not clear. Here, we report that huntingtin is important for the function of RabII, a critical GTPase in regulating membrane traffic from recycling endosomes to the plasma membrane. In huntingtinnull embryonic cells, the levels of RabII on membranes nucleotide exchange activity on RabII were significantly reduced compared with normal embryonic stem cells. In brain membranes, an antibody against huntingtin immunoprecipitated a nucleoticle exchange activity on RabII and huntingtin was coprecipitated with RabII in the presence of guanosine diphosphate. These data suggest a role for huntingtin in a complex that activates RabII. NeuroReport 19:1643-1647 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Li, Xueyi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA.
[Li, Xueyi; Sapp, Ellen; Valencia, Antonio; Kegel, Kimberly B.; Qin, Zheng-Hong; Alexander, Jonathan; Masso, Nicholas; Reeves, Patrick; Ritch, James J.; DiFiglia, Marian] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Aronin, Neil] Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA USA.
[Zeitlin, Scott] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA.
RP Li, X (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA.
EM xlil2@partners.org; difiglia@helix.mgh.Harvard.edu
FU NIH; DANA Foundation; High Q Foundation; Huntingtin's Disease Society of
America; Hereditary Disease Foundation
FX This study was supported by grants from NIH (to M. D. and N. A.), DANA
Foundation (to M. D. and N. A.), High Q Foundation (to M. D.), and
Huntingtin's Disease Society of America (to M. D.). We thank Dr Meiqian
Weng for her generous gifts of fresh mouse brains. Xueyi Li is supported
by a John J. Wasmuth Postdoctoral Fellowship from the Hereditary Disease
Foundation. Authors declared no conflict of interests.
NR 16
TC 23
Z9 23
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD OCT 29
PY 2008
VL 19
IS 16
BP 1643
EP 1647
DI 10.1097/WNR.0b013e328315cd4c
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 365VT
UT WOS:000260438100017
PM 18845944
ER
PT J
AU Mathew, P
Thall, PF
Wen, S
Bucana, C
Jones, D
Horne, E
Oh, WK
Morris, MJ
Lee, YC
Logothetis, CJ
Lin, SH
Fidler, IJ
AF Mathew, P.
Thall, P. F.
Wen, S.
Bucana, C.
Jones, D.
Horne, E.
Oh, W. K.
Morris, M. J.
Lee, Y-C
Logothetis, C. J.
Lin, S-H
Fidler, I. J.
TI Dynamic change in phosphorylated platelet-derived growth factor receptor
in peripheral blood leukocytes following docetaxel therapy predicts
progression-free and overall survival in prostate cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE prostate cancer; platelet-derived growth factor receptor; docetaxel;
survival
ID LOCALLY WEIGHTED REGRESSION; BONE METASTASES; FAMILY; VEGF
AB In a placebo-controlled randomised study of the platelet-derived growth factor receptor (PDGFR) inhibitor imatinib mesylate and docetaxel in metastatic prostate cancer with bone metastases (n = 116), no significant differences in progression-free and overall survival were observed. To evaluate pharmacodynamic correlates of outcomes, we assessed the association of plasma platelet-derived growth factor (PDGF) isoform kinetics and PDGFR inhibition with progression-free and overall survival by individual treatment arm. We found that in the docetaxel - placebo arm alone, the probability of decrease in PDGFR phosphorylation (Pr-Decr-pPDGFR) above 0.5 (vs <= 0.5) was associated with a sharp increase in all measured plasma PDGF isoforms (P = 0.006 for AA, 0.002 for BB, 0.045 for AB); a decreased median progression-free survival of 3.3 months vs 6.8 months (hazard ratio (HR) 2.5; P = 0.006 in log-rank test) and an inferior median overall survival of 20 months vs > 30 months (HR 3.1; P = 0.04 in log-rank test). By contrast, in the docetaxel plus imatinib arm, the association of Pr-Decr-pPDGFR > 0.5 with a rise in plasma PDGF isoform concentrations and inferior survival was not observed. The data suggest that dynamic changes in PDGFR phosphorylation in peripheral blood leukocytes predict docetaxel efficacy. Rising plasma PDGF concentrations may explain and/or mark docetaxel resistance. Validation and mechanistic studies addressing these unexpected findings should anticipate a confounding influence of concurrent PDGFR inhibitor therapy.
C1 [Mathew, P.; Jones, D.; Horne, E.; Logothetis, C. J.] MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA.
[Thall, P. F.; Wen, S.] Dept Biostat, Houston, TX 77030 USA.
[Bucana, C.; Fidler, I. J.] MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Oh, W. K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
[Morris, M. J.] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA.
[Lee, Y-C; Lin, S-H] MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA.
RP Mathew, P (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Unit 1374, 1155 Pressler, Houston, TX 77030 USA.
EM pmathew@mdanderson.org
RI Oh, William/B-9163-2012;
OI Oh, William/0000-0001-5113-8147; Morris, Michael J./0000-0002-9454-0096
FU Novartis Pharmaceuticals; National Cancer Institute [5-P50 CA090270-06]
FX This study was supported by Novartis Pharmaceuticals and the National
Cancer Institute 5-P50 CA090270-06 under an Inter-SPORE collaboration.
We acknowledge the assistance of Rebecca Fueger, Cynthia M. Carter,
Carol Oborn, Tamara Locke and Sherryl Smith.
NR 23
TC 11
Z9 11
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD OCT 28
PY 2008
VL 99
IS 9
BP 1426
EP 1432
DI 10.1038/sj.bjc.6604706
PG 7
WC Oncology
SC Oncology
GA 366SE
UT WOS:000260502900010
PM 18841158
ER
PT J
AU Jaffer, FA
Vinegoni, C
John, MC
Aikawa, E
Gold, HK
Finn, AV
Ntziachristos, V
Libby, P
Weissleder, R
AF Jaffer, Farouc A.
Vinegoni, Claudio
John, Michael C.
Aikawa, Elena
Gold, Herman K.
Finn, Aloke V.
Ntziachristos, Vasilis
Libby, Peter
Weissleder, Ralph
TI Real-Time Catheter Molecular Sensing of Inflammation in Proteolytically
Active Atherosclerosis
SO CIRCULATION
LA English
DT Article
DE atherosclerosis; catheters; fluorescence; imaging; inflammation;
cathepsins
ID IN-VIVO; CARDIOVASCULAR-DISEASE; CYSTEINE PROTEASES; MACROPHAGES;
TOMOGRAPHY; PLAQUES; CELLS; POOL
AB Background-To enable intravascular detection of inflammation in atherosclerosis, we developed a near-infrared fluorescence ( NIRF) catheter-based strategy to sense cysteine protease activity during vascular catheterization.
Methods and Results-The NIRF catheter design was based on a clinical coronary artery guidewire. In phantom studies of NIRF plaques, blood produced only a mild (<30%) attenuation of the fluorescence signal compared with saline, affirming the favorable optical properties of the NIR window. Catheter evaluation in vivo used atherosclerotic rabbits (n=11). Rabbits received an injection of a cysteine protease-activatable NIRF imaging agent (Prosense750; excitation/emission, 750/770 nm) or saline. Catheter pullbacks through the blood-filled iliac artery detected NIRF signals 24 hours after injection of the probe. In the protease agent group, the in vivo peak plaque target-to-background ratio was 558% greater than controls (6.8 +/- 1.9 versus 1.3 +/- 0.3, mean +/- SEM; P<0.05). Ex vivo fluorescence reflectance imaging corroborated these results (target-to-background ratio, 10.3 +/- 1.8 for agent versus 1.8 +/- 0.3 for saline group; P<0.01). In the protease group only, saline flush-modulated NIRF signal profiles further distinguished atheromata from normal segments in vivo (P<0.01). Good correlation between the in vivo and ex vivo plaque target-to-background ratio was present (r=0.82, P<0.01). Histopathological analyses demonstrated strong NIRF signal in plaques only from the protease agent group. NIRF signals colocalized with immunoreactive macrophages and the cysteine protease cathepsin B.
Conclusions-An intravascular fluorescence catheter can detect cysteine protease activity in vessels the size of human coronary arteries in real time with an activatable NIRF agent. This strategy could aid in the detection of inflammation and high-risk plaques in small arteries. (Circulation. 2008; 118: 1802-1809.)
C1 [Jaffer, Farouc A.; Vinegoni, Claudio; Aikawa, Elena; Ntziachristos, Vasilis; Weissleder, Ralph] Massachusetts Gen Hosp, CMIR, Boston, MA 02129 USA.
[Jaffer, Farouc A.; John, Michael C.; Gold, Herman K.; Finn, Aloke V.; Weissleder, Ralph] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA.
[Jaffer, Farouc A.; John, Michael C.; Gold, Herman K.; Finn, Aloke V.; Weissleder, Ralph] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA.
[Jaffer, Farouc A.; Libby, Peter] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA USA.
[Libby, Peter] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, CMIR, 149 13th St,Room 5406, Boston, MA 02129 USA.
EM fjaffer@mgh.harvard.edu
OI Jaffer, Farouc/0000-0001-7980-384X
FU Donald W. Reynolds Foundation [UO1 HL080731, HL-80472]; Siemens Medical
Solutions; American College of Cardiology Foundation Career Development;
Howard Hughes Medical Institute Career Development; American Heart
Association Scientist Development
FX This work was supported by the Donald W. Reynolds Foundation ( Drs
Weissleder, Libby, and Jaffer), UO1 HL080731 ( Drs Weissleder, Libby,
and Jaffer), HL-80472 (Dr Libby), Siemens Medical Solutions ( Dr
Weissleder), American College of Cardiology Foundation Career
Development Award (Dr Jaffer), Howard Hughes Medical Institute Career
Development Award (Dr Jaffer), and American Heart Association Scientist
Development Grant (Dr Jaffer).
NR 25
TC 104
Z9 107
U1 0
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP 1802
EP 1809
DI 10.1161/CIRCULATIONAHA.108.785881
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 365RT
UT WOS:000260426200006
PM 18852366
ER
PT J
AU Noseworthy, PA
Newton-Cheh, C
AF Noseworthy, Peter A.
Newton-Cheh, Christopher
TI Genetic Determinants of Sudden Cardiac Death
SO CIRCULATION
LA English
DT Review
DE death, sudden; epidemiology; genetics; heart arrest; tachyarrhythmias
ID LONG-QT-SYNDROME; IDIOPATHIC DILATED CARDIOMYOPATHY; RIGHT-VENTRICULAR
CARDIOMYOPATHY; CONGESTIVE-HEART-FAILURE; BRUGADA-TYPE
ELECTROCARDIOGRAM; ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION;
TORSADES-DE-POINTES; T-WAVE ALTERNANS; HYPERTROPHIC CARDIOMYOPATHY
C1 [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp,Ctr Human Genet Res, Boston, MA 02114 USA.
[Noseworthy, Peter A.; Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA.
RP Newton-Cheh, C (reprint author), Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp,Ctr Human Genet Res, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA.
EM cnewtoncheh@chgr.mgh.harvard.edu
NR 109
TC 38
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP 1854
EP 1863
DI 10.1161/CIRCULATIONAHA.108.783654
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 365RT
UT WOS:000260426200012
PM 18955676
ER
PT J
AU Abtahian, F
Olenchock, B
Ou, FS
Kontos, MC
Saucedo, J
Mega, JL
Scirica, B
Peterson, E
Cannon, CP
Wiviott, SD
AF Abtahian, Farhad
Olenchock, Benjamin
Ou, Fang-Shu
Kontos, Michael C.
Saucedo, Jorge
Mega, Jessica L.
Scirica, Benjamin
Peterson, Eric
Cannon, Christopher P.
Wiviott, Stephen D.
TI The Impact of Prior Stroke on the Use of Evidence-based Therapies, and
In-Hospital Outcomes in MI Patients: A Report of the NCDR ACTION GWTG
Registry
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Mega, Jessica L.; Scirica, Benjamin; Cannon, Christopher P.; Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Ou, Fang-Shu; Peterson, Eric] Duke Clin Rsch Inst, Durham, NC USA.
[Kontos, Michael C.] Virginia Commonwealth Univ, Richmond, VA USA.
[Saucedo, Jorge] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Mega, Jessica L.; Scirica, Benjamin; Cannon, Christopher P.; Wiviott, Stephen D.] TIMI Study Grp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S970
EP S970
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503594
ER
PT J
AU Ahmed, H
Neuzil, P
d'Avila, A
Laragy, M
Mares, K
Brugge, WR
Forcione, DG
Ruskin, JN
Reddy, VY
AF Ahmed, Humera
Neuzil, Petr
d'Avila, Andre
Laragy, Margaret
Mares, Karel
Brugge, William R.
Forcione, David G.
Ruskin, Jeremy N.
Reddy, Vivek Y.
TI Esophageal Temperature Monitoring during Balloon Cryoablation of the
Pulmonary Veins
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Ahmed, Humera; d'Avila, Andre; Reddy, Vivek Y.] Univ Miami, Miami, FL USA.
[Neuzil, Petr; Mares, Karel] Homolka Hosp, Prague, Czech Republic.
[Laragy, Margaret; Brugge, William R.; Forcione, David G.; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010
OI d'Avila, Andre Luiz/0000-0001-8769-1411
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S978
EP S978
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503626
ER
PT J
AU An, D
Toyoda, T
Taylor, EB
Hirshman, MF
Goodyear, LJ
AF An, Ding
Toyoda, Taro
Taylor, Eric B.
Hirshman, Michael F.
Goodyear, Laurie J.
TI Identification Of AS160 As An Insulin, Ischemia, And Exercise Regulated
Signaling Protein In The Heart
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [An, Ding; Toyoda, Taro; Taylor, Eric B.; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S485
EP S485
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501156
ER
PT J
AU Bailey, D
Chatur, S
Hafiane, A
Haidar, B
Juppner, H
Bastepe, M
Krimbou, L
Genest, J
AF Bailey, Dana
Chatur, Safia
Hafiane, Anouar
Haidar, Bassam
Jueppner, Harald
Bastepe, Murat
Krimbou, Larbi
Genest, Jacques
TI Deficiency Of The Stimulatory G Protein alpha-subunit Gs (alpha) Leads
To Reduced ApoA-I Mediated Cellular Lipid Efflux and Impaired
ABCA1-dependent Nascent HDL Biogenesis Pathway
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Bailey, Dana; Chatur, Safia; Hafiane, Anouar; Haidar, Bassam; Genest, Jacques] McGill Univ, Div Cardiol, Montreal, PQ, Canada.
[Jueppner, Harald; Bastepe, Murat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S558
EP S559
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501468
ER
PT J
AU Bamberg, F
Ferecik, M
Truong, Q
Rogers, I
Shapiro, M
Brady, TJ
Nagurney, JT
Hoffmann, U
AF Bamberg, Fabian
Ferecik, Maros
Truong, Quynh
Rogers, Ian
Shapiro, Michael
Brady, Thomas J.
Nagurney, John T.
Hoffmann, Udo
TI Characteristics of Atherosclerotic Plaque Burden In Patients With and
Without Acute Coronary Syndrome Presenting With Acute Chest Pain to the
Emergency Department
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Bamberg, Fabian; Ferecik, Maros; Truong, Quynh; Rogers, Ian; Shapiro, Michael; Brady, Thomas J.; Nagurney, John T.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S597
EP S597
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501635
ER
PT J
AU Bezerra, HG
Loureiro, R
Irlbeck, T
Bamberg, F
Schlett, CL
Rogers, I
Brady, T
Hoffmann, U
Cury, RC
AF Bezerra, Hiram G.
Loureiro, Ricardo
Irlbeck, Thomas
Bamberg, Fabian
Schlett, Christopher L.
Rogers, Ian
Brady, Thomas
Hoffmann, Udo
Cury, Ricardo C.
TI Additional Value of Myocardial Perfusion and Function over Coronary
Stenosis for the Detection of Patients with Acute Coronary Syndrome by
Cardiac CT
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Bezerra, Hiram G.; Loureiro, Ricardo; Irlbeck, Thomas; Bamberg, Fabian; Schlett, Christopher L.; Rogers, Ian; Brady, Thomas; Hoffmann, Udo; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S936
EP S937
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503462
ER
PT J
AU Bezerra, HG
Loureiro, R
Sarwar, A
Rocha, J
Pflederer, T
Marwan, M
Petranovic, M
Raffel, CO
Hoffmann, U
McNulty, IA
Brady, T
Jang, IK
Achenbach, S
Cury, RC
AF Bezerra, Hiram G.
Loureiro, Ricardo
Sarwar, Ammar
Rocha, Jose
Pflederer, T.
Marwan, M.
Petranovic, Milena
Raffel, Christopher O.
Hoffmann, Udo
McNulty, Iris A.
Brady, Thomas
Jang, I. K.
Achenbach, Stephan
Cury, Ricardo C.
TI Defining the Best Approach for Stenosis Quantification by Dual-Source CT
- A Comparative Study Involving Intravascular Ultrasound and Invasive
Coronary Angiography
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Bezerra, Hiram G.; Loureiro, Ricardo; Sarwar, Ammar; Rocha, Jose; Petranovic, Milena; Raffel, Christopher O.; Hoffmann, Udo; McNulty, Iris A.; Brady, Thomas; Jang, I. K.; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pflederer, T.; Marwan, M.; Achenbach, Stephan] Univ Erlangen Nurnberg, Erlangen, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S845
EP S845
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503098
ER
PT J
AU Blaha, MJ
Budoff, MJ
Rivera, JJ
Katz, R
O'Leary, DH
Polak, JF
Takasu, J
Blumenthal, RS
Nasir, K
AF Blaha, Michael J.
Budoff, Matthew J.
Rivera, Juan J.
Katz, Ronit
O'Leary, Dan H.
Polak, Jospeh F.
Takasu, Junchiro
Blumenthal, Roger S.
Nasir, Khurram
TI Relationship of Carotid Arterial Compliance and Thoracic Aorta
Calcification: Multi-Ethnic Study of Atherosclerosis (MESA)
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Blaha, Michael J.; Rivera, Juan J.; Blumenthal, Roger S.] Johns Hopkins, Baltimore, MD USA.
[Budoff, Matthew J.; Takasu, Junchiro] Harbor UCLA, Los Angeles BioMed Rsch Inst, Torrance, CA USA.
[Katz, Ronit] Univ Washington, Seattle, WA 98195 USA.
[O'Leary, Dan H.] Caritas Carney Hosp, Dorchester, MA USA.
[Polak, Jospeh F.] Tufts New England Med Cntr, Boston, MA USA.
[Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1156
EP S1156
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504587
ER
PT J
AU Blankstein, R
Budoff, M
Shaw, LJ
Goff, DC
Polack, JF
Lima, J
Blumenthal, RS
Nasir, K
AF Blankstein, Ron
Budoff, Matthew
Shaw, Leslee J.
Goff, David C., Jr.
Polack, Joseph F.
Lima, Joao
Blumenthal, Roger S.
Nasir, Khurram
TI Predictors of Coronary Heart Disease Events among Asymptomatic
Individuals with Low LDL: The Multi-Ethnic Study of Atherosclerosis
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Blankstein, Ron] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Budoff, Matthew] Harbor UCLA, Med Ctr, Los Angeles, CA USA.
[Shaw, Leslee J.] Emory Univ, Sch Med, Atlanta, GA USA.
[Goff, David C., Jr.] Wake Forest Univ, Sch Med, Winston Salen, NC USA.
[Polack, Joseph F.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Lima, Joao; Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MI USA.
[Nasir, Khurram] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1151
EP S1151
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504570
ER
PT J
AU Blankstein, R
Soni, AV
Sarwar, A
Rogers, I
Shturman, L
Petranovic, M
Mamuya, WS
Bezerra, H
Nasir, K
Loureiro, R
Okada, D
Hoffmann, U
Brady, TJ
Cury, RC
AF Blankstein, Ron
Soni, Arland V.
Sarwar, Ammar
Rogers, Ian
Shturman, Leon
Petranovic, Milena
Mamuya, Wilfred S.
Bezerra, Hiram
Nasir, Khurram
Loureiro, Ricardo
Okada, David
Hoffmann, Udo
Brady, Thomas J.
Cury, Ricardo C.
TI Adenosine Induced Stress Myocardial Perfusion Imaging using Dual Source
Cardiac CT:Initial Clinical Experience
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Blankstein, Ron; Soni, Arland V.; Sarwar, Ammar; Rogers, Ian; Shturman, Leon; Mamuya, Wilfred S.; Bezerra, Hiram; Loureiro, Ricardo; Okada, David; Hoffmann, Udo; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Petranovic, Milena] Harvard Univ, Sch Med, Boston, MA USA.
[Nasir, Khurram] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S837
EP S837
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503065
ER
PT J
AU Blankstein, R
Pale, R
Nasir, K
Shah, AB
Bezerra, H
Bolen, M
Gupta, R
Mamuya, WS
Abbara, S
Brady, TJ
Cury, RC
AF Blankstein, Ron
Pale, Rodrigo
Nasir, Khurram
Shah, Amar B.
Bezerra, Hiram
Bolen, Michael
Gupta, Rajiv
Mamuya, Wilfred S.
Abbara, Suhny
Brady, Thomas J.
Cury, Ricardo C.
TI Variability and Predictors of Patient Radiation Dose with Dual Source
Cardiac CT: Implications for Future Algorithms to Reduce Patient
Radiation Dose
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Nasir, Khurram] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Blankstein, Ron; Pale, Rodrigo; Shah, Amar B.; Bezerra, Hiram; Bolen, Michael; Gupta, Rajiv; Mamuya, Wilfred S.; Abbara, Suhny; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S599
EP S599
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501644
ER
PT J
AU Body, SC
Collard, CD
Shernan, SK
Fox, AA
Liu, KY
Ritchie, MD
Perry, TE
Muehischlegel, JD
Aranki, S
Seidman, CE
Seidman, JG
Donahue, BS
Hermann, D
Lichtner, P
Meitinger, T
Estrada, JC
Pretorius, M
Ellinor, PT
Newton-Cheh, C
Brown, NJ
Roden, DM
Darbar, D
AF Body, Simon C.
Collard, Charles D.
Shernan, Stanton K.
Fox, Amanda A.
Liu, Kuang-Yu
Ritchie, Marylyn D.
Perry, Tjorvi E.
Muehischlegel, Jochen D.
Aranki, Sary
Seidman, Christine E.
Seidman, Jonathan G.
Donahue, Brian S.
Hermann, Daniel
Lichtner, Peter
Meitinger, Thomas
Estrada, Juan-Carlos
Pretorius, Mias
Ellinor, Patrick T.
Newton-Cheh, Christopher
Brown, Nancy J.
Roden, Dan M.
Darbar, Dawood
TI Variation in the 4q25 Chromosomal Locus Predicts New-Onset Atrial
Fibrillation after Cardiac Surgery
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Body, Simon C.; Shernan, Stanton K.; Fox, Amanda A.; Liu, Kuang-Yu; Perry, Tjorvi E.; Muehischlegel, Jochen D.; Aranki, Sary; Seidman, Christine E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Collard, Charles D.] Baylor Coll Med, Houston, TX 77030 USA.
[Ritchie, Marylyn D.; Donahue, Brian S.; Estrada, Juan-Carlos; Pretorius, Mias; Brown, Nancy J.; Roden, Dan M.; Darbar, Dawood] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Lichtner, Peter; Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Ellinor, Patrick T.; Newton-Cheh, Christopher] 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S882
EP S882
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503245
ER
PT J
AU Bradley, SM
Gabriel, EE
Aufderheide, TP
Barnes, R
Christenson, J
Davis, DP
Stiell, IG
Nichol, G
AF Bradley, Steven M.
Gabriel, Erin E.
Aufderheide, Tom P.
Barnes, Roxy
Christenson, Jim
Davis, Daniel P.
Stiell, Ian G.
Nichol, Graham
CA Resuscitation Outcomes Consortium
TI Survival Increases with CPR Before Defibrillation of Out-of-Hospital
Ventricular Fibrillation or Ventricular Tachycardia: Observations from
the Resuscitation Outcomes Consortium
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Bradley, Steven M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Gabriel, Erin E.; Nichol, Graham] Univ Washington, Seattle, WA 98195 USA.
[Aufderheide, Tom P.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Barnes, Roxy] Vancouver Fire Dept, Vancouver, WA USA.
[Christenson, Jim] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Davis, Daniel P.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Stiell, Ian G.] Univ Ottawa, Ottawa, ON, Canada.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1445
EP S1445
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504664
ER
PT J
AU Briggs, LE
Takeda, M
Cuadra, AE
Wakimoto, H
Lu, JT
Yasui, K
Ikeda, Y
Chien, KR
Kasahara, H
AF Briggs, Laura E.
Takeda, Morihiko
Cuadra, Adolfo E.
Wakimoto, Hiroko
Lu, Jonathan T.
Yasui, Kenji
Ikeda, Yasuhiro
Chien, Kenneth R.
Kasahara, Hideko
TI Perinatal Loss of Nkx2-5 Results in Rapid Conduction and Contraction
Defects
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Briggs, Laura E.; Takeda, Morihiko; Cuadra, Adolfo E.; Kasahara, Hideko] Univ Florida, Gainesville, FL USA.
[Chien, Kenneth R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yasui, Kenji] Nagoya Univ, Aichi, Japan.
[Ikeda, Yasuhiro] Yamaguchi Univ, Sch Med, Ube, Yamaguchi 755, Japan.
[Lu, Jonathan T.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Wakimoto, Hiroko] Tokyo Med & Dent Univ, Tokyo, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S517
EP S517
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501292
ER
PT J
AU Brooks, WW
Conrad, CH
Robinson, KG
Bing, OH
AF Brooks, Wesley W.
Conrad, Chester H.
Robinson, Kathleen G.
Bing, Oscar H.
TI Synergistic Cardiotherapeutic Effect of Phenylbutyrate with Captopril or
Losartan in the Treatment of Heart Failure
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Brooks, Wesley W.; Conrad, Chester H.; Robinson, Kathleen G.; Bing, Oscar H.] VA Boston Healthcare Syst, Boston, MA USA.
[Brooks, Wesley W.; Conrad, Chester H.; Bing, Oscar H.] Boston Univ, Sch Med, Boston, MA 02118 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S946
EP S946
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503503
ER
PT J
AU Brouckaert, P
Thoonen, R
Buys, E
Nimmegeers, S
Rogge, E
Sips, P
Bloch, KD
de Voorde, JV
AF Brouckaert, Peter
Thoonen, Robrecht
Buys, Emmanuel
Nimmegeers, Sofie
Rogge, Elke
Sips, Patrick
Bloch, Kenneth D.
de Voorde, Johan Van
TI Phenotyping of NO-Insensitive Soluble Guanylate Cyclase beta1H105F
Knockin Mice
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Brouckaert, Peter; Thoonen, Robrecht; Sips, Patrick] Univ Ghent, VIB, B-9000 Ghent, Belgium.
[Buys, Emmanuel; Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S284
EP S285
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500080
ER
PT J
AU Cawley, SM
Buys, E
Ichinose, F
Brouckaert, P
Bloch, KD
AF Cawley, Sharon M.
Buys, Emannuel
Ichinose, Fumito
Brouckaert, Peter
Bloch, Kenneth D.
TI Contractile Defects In Cardiac Myocytes From sGCa1-Deficient Mice
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Cawley, Sharon M.; Buys, Emannuel; Ichinose, Fumito; Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Brouckaert, Peter] Univ Ghent, B-9000 Ghent, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S349
EP S349
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500361
ER
PT J
AU Chang, KY
Figueiredo, JL
Kohler, R
Francis, S
Patel, P
McCarthy, J
Weissleder, R
Plutzky, J
Jaffer, F
AF Chang, Kiyuk
Figueiredo, Jose-Luiz
Kohler, Rainer
Francis, Sanjeev
Patel, Purvish
McCarthy, Jason
Weissleder, Ralph
Plutzky, Jorge
Jaffer, Farouc
TI Peroxisome Proliferator-Activated Receptor-gamma Activation Reduces
Inflammation in Atherosclerosis as Assessed by Serial In Vivo
Fluorescence Molecular Imaging
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Chang, Kiyuk; Figueiredo, Jose-Luiz; Kohler, Rainer; Patel, Purvish; McCarthy, Jason; Weissleder, Ralph; Jaffer, Farouc] Massachusetts Gen Hosp, Charlestown, MA USA.
[Francis, Sanjeev; Plutzky, Jorge] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S556
EP S556
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501458
ER
PT J
AU Chaput, M
Handschumacher, MD
Guerrero, JL
Holmvang, G
Dal-Bianco, JP
Sullivan, S
Johnson, B
Vlahakes, GJ
Hung, J
Levine, RA
AF Chaput, Miguel
Handschumacher, Mark D.
Guerrero, J. L.
Holmvang, Godtfred
Dal-Bianco, Jacob P.
Sullivan, Suzanne
Johnson, Benjamin
Vlahakes, Gus J.
Hung, Judy
Levine, Robert A.
TI Mitral Leaflet Adaptation to Ventricular Remodeling: Prospective Changes
In a Model of Ischemic Mitral Regurgitation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Chaput, Miguel; Handschumacher, Mark D.; Guerrero, J. L.; Holmvang, Godtfred; Dal-Bianco, Jacob P.; Sullivan, Suzanne; Johnson, Benjamin; Vlahakes, Gus J.; Hung, Judy; Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S859
EP S859
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503153
ER
PT J
AU Cubeddu, RJ
Cruz-Gonzalez, I
Kiernan, TJ
Leinbach, RC
Truong, QA
Rosenfield, K
Cadigan, ME
Pomerantsev, EV
Palacios, IF
AF Cubeddu, Roberto J.
Cruz-Gonzalez, Ignacio
Kiernan, Thomas J.
Leinbach, Robert C.
Truong, Quynh A.
Rosenfield, Kenneth
Cadigan, Mary E.
Pomerantsev, Eugene V.
Palacios, Igor F.
TI Increased Mortality after Primary Percutaneous Coronary Intervention for
Acute ST Segment Elevation Myocardial Infarction During Off-Hours
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Cubeddu, Roberto J.; Cruz-Gonzalez, Ignacio; Kiernan, Thomas J.; Leinbach, Robert C.; Truong, Quynh A.; Rosenfield, Kenneth; Cadigan, Mary E.; Pomerantsev, Eugene V.; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1172
EP S1172
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504653
ER
PT J
AU Cury, RC
Loureiro, R
Bezerra, H
Petranovic, M
Sarwar, A
Rocha, J
Pflederer, T
Marwan, M
Raffel, OC
Hoffmann, U
Brady, T
Jang, IK
Achenbach, S
AF Cury, Ricardo C.
Loureiro, Ricardo
Bezerra, Hiram
Petranovic, Milena
Sarwar, Ammar
Rocha, Jose
Pflederer, Tobias
Marwan, Mohamed
Raffel, Owen C.
Hoffmann, Udo
Brady, Thomas
Jang, Ik-Kyung
Achenbach, Stephan
TI Detection, Quantification and Characterization of Coronary
Atherosclerotic Plaque by Dual-Source CT - A Comparison to Intravascular
Ultrasound
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Cury, Ricardo C.; Loureiro, Ricardo; Bezerra, Hiram; Petranovic, Milena; Sarwar, Ammar; Rocha, Jose; Raffel, Owen C.; Hoffmann, Udo; Brady, Thomas; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pflederer, Tobias; Marwan, Mohamed; Achenbach, Stephan] Univ Erlangen Nurnberg, Erlangen, Germany.
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S845
EP S845
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503097
ER
PT J
AU Dal-Blanco, JP
Alkawa, E
Bischoff, J
Guerrero, JL
Handschumacher, MD
Sullivan, S
Johnson, B
Titus, JS
Iwamoto, Y
Wylie-Sears, J
Carpentier, A
Levine, RA
AF Dal-Blanco, Jacob P.
Alkawa, Elena
Bischoff, Joyce
Guerrero, J. L.
Handschumacher, Mark D.
Sullivan, Suzanne
Johnson, Benjamin
Titus, James S.
Iwamoto, Yoshiko
Wylie-Sears, Jill
Carpentier, Alain
Levine, Robert A.
TI Active Adaptation of the Tethered Mitral Valve: Insights Into a
Compensatory Mechanism for Ischemic Mitral Regurgitation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Dal-Blanco, Jacob P.; Guerrero, J. L.; Handschumacher, Mark D.; Sullivan, Suzanne; Johnson, Benjamin; Titus, James S.; Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Alkawa, Elena; Iwamoto, Yoshiko] Massachusetts Gen Hosp, Charlestown, MA USA.
[Bischoff, Joyce; Wylie-Sears, Jill] Childrens Hosp, Boston, MA 02115 USA.
[Carpentier, Alain] Pompidou Hosp, Paris, France.
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S649
EP S649
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502063
ER
PT J
AU Das, S
Xiao, CY
Quintero, PP
Hessler, K
Rosenberg, M
Kusakari, Y
Matsui, T
Ellinor, PT
Rosenzweig, A
AF Das, Saumya
Xiao, Chunyang
Quintero, Pablo P.
Hessler, Katherine
Rosenberg, Michael
Kusakari, Yoichiro
Matsui, Takashi
Ellinor, Patrick T.
Rosenzweig, Anthony
TI The Serum and Glucocorticold Responsive Kinase-1 (SGK-1) is Activated in
Human Cardiomyopathy and Mediates Hypertrophy-associated Electrical
Remodeling and Left Ventricular Dysfunction
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Das, Saumya; Ellinor, Patrick T.] Mass Gen Hosp, Boston, MA USA.
[Xiao, Chunyang] Beth Israel Deaconess Med Cente, Boston, MA USA.
[Quintero, Pablo P.; Hessler, Katherine; Rosenberg, Michael; Kusakari, Yoichiro; Matsui, Takashi; Rosenzweig, Anthony] Beth Israel Deaconess Med Cntr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S339
EP S339
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500317
ER
PT J
AU DeFilippis, AP
Kramer, HJ
Katz, R
Wong, N
Bertoni, A
Carr, JJ
Budoff, MJ
Blumenthal, RS
Nasir, K
AF DeFilippis, Andrew P.
Kramer, Holly J.
Katz, Ronlt
Wong, Nathan
Bertoni, Alain
Carr, Jeffrey J.
Budoff, Matthew J.
Blumenthal, Roger S.
Nasir, Khurrarn
TI Microalbuminuria is Associated with Progression of Coronary
Atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA)
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Kramer, Holly J.] Loyola Univ, Maywood, IL 60153 USA.
[Katz, Ronlt] Univ Washington, Seattle, WA 98195 USA.
[Wong, Nathan] Univ Calif Irvine, Irvine, CA USA.
[Bertoni, Alain; Carr, Jeffrey J.; Budoff, Matthew J.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Nasir, Khurrarn] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1147
EP S1147
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504556
ER
PT J
AU Desai, NR
Morrow, DA
Jiang, ST
Bode, C
Rifai, N
Cannon, CP
Gerszten, RE
Sabatine, MS
AF Desai, Nihar R.
Morrow, David A.
Jiang, Songtao
Bode, Christoph
Rifai, Nader
Cannon, Christopher P.
Gerszten, Robert E.
Sabatine, Marc S.
CA TIMI Study Grp
TI Copeptin Predicts Cardiovascular Death in STEMI Independent of Clinical
Factors and NT-proBNP
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Desai, Nihar R.; Morrow, David A.; Cannon, Christopher P.; Sabatine, Marc S.; TIMI Study Grp] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Jiang, Songtao] Harvard Clin Rsch Inst, Boston, MA USA.
[Bode, Christoph] Univ Freiburg, Freiburg, Germany.
[Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
SU 2
BP S762
EP S762
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502522
ER
PT J
AU Dewland, TA
Pellegrini, CN
Wang, YF
Marcus, GM
Varosy, PD
AF Dewland, Thomas A.
Pellegrini, Cara N.
Wang, Yongfei
Marcus, Gregory M.
Varosy, Paul D.
TI Dual Chamber ICD Selection is Associated with Racial and Socioeconomic
Disparities and Increased Complication Rates Among Patients Enrolled in
the NCDR ICD Registry
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Dewland, Thomas A.; Pellegrini, Cara N.; Marcus, Gregory M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Wang, Yongfei] Yale Univ, Sch Med, New Haven, CT USA.
[Varosy, Paul D.] San Francisco VA Med Ctr, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S834
EP S835
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503055
ER
PT J
AU Dinh, T
Doupis, J
Greenman, R
Lima, C
Giurini, JM
Gnardellis, C
Khaodhiar, L
Lyons, TE
Veves, A
AF Dinh, Thanh
Doupis, John
Greenman, Robert
Lima, Christina
Giurini, John M.
Gnardellis, Charalambos
Khaodhiar, Lalita
Lyons, Thomas E.
Veves, Aristidis
TI Role of Vascular Reactivity and Inflammation In the Development and
Healing of Diabetic Foot Ulceration
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Doupis, John] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Dinh, Thanh; Greenman, Robert; Lima, Christina; Giurini, John M.; Lyons, Thomas E.; Veves, Aristidis] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Gnardellis, Charalambos] Lab Appl Stat & Informat, Messolonghl, Greece.
[Khaodhiar, Lalita] Boston Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S809
EP S809
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502711
ER
PT J
AU Duerschmled, D
Canult, M
Lievens, D
Brill, A
Cifuni, SM
Patten, I
Bader, M
Wagner, DD
AF Duerschmled, Daniel
Canult, Matthias
Lievens, Dirk
Brill, Alexander
Cifuni, Stephen M.
Patten, Ian
Bader, Michael
Wagner, Denise D.
TI Platelet Serotonin Receptor Stimulation Induces Shedding of the Adhesion
Molecule GPIb alpha
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Duerschmled, Daniel; Canult, Matthias; Lievens, Dirk; Brill, Alexander; Cifuni, Stephen M.; Patten, Ian; Wagner, Denise D.] Immune Dis Inst, Boston, MA USA.
[Bader, Michael] Max Delbruck Ctr Mol Med, Berlin, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S477
EP S477
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501116
ER
PT J
AU Ennis, C
McGuiness, M
Vohora, R
Ennis, S
Rosenthal, L
AF Ennis, Cynthia
McGuiness, Matthew
Vohora, Rishi
Ennis, Stephanie
Rosenthal, Lawrence
TI Factors Associated with Implantable Cardioverter-Defibrillator
Implantation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Ennis, Cynthia; Vohora, Rishi; Rosenthal, Lawrence] U Mass Mem Med Cntr, Worcester, MA USA.
[McGuiness, Matthew] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Ennis, Stephanie] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1484
EP S1484
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504840
ER
PT J
AU Ennis, C
McGuiness, M
Vohora, R
Ennis, S
Rosenthal, L
AF Ennis, Cynthia
McGuiness, Matthew
Vohora, Rishi
Ennis, Stephanie
Rosenthal, Lawrence
TI Implantable Cardioverter-Defibrillator Underutilization in Primay
Prevention Patients
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Ennis, Cynthia; Vohora, Rishi; Rosenthal, Lawrence] U Mass Mem Med Cntr, Worcester, MA USA.
[McGuiness, Matthew] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Ennis, Stephanie] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1464
EP S1464
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504748
ER
PT J
AU Feuchtner, G
Jodocy, D
Cury, RC
Friedrich, G
Blumenthal, RS
Budoff, M
Nasir, K
AF Feuchtner, Gudrun
Jodocy, Daniel
Cury, Ricardo C.
Friedrich, Guy
Blumenthal, Roger S.
Budoff, Matt
Nasir, Khurram
TI Atherosclerotic Plaque Composition Among patients with Stenotic Coronary
Artery Disease on Non Invasive Coronary CT Angiography
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Feuchtner, Gudrun; Jodocy, Daniel; Friedrich, Guy] Innsbruck Med Univ, Innsbruck, Austria.
[Cury, Ricardo C.; Nasir, Khurram] Boston Massachusetts Gen Hosp, Boston, MA USA.
[Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MD USA.
[Budoff, Matt] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S598
EP S598
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501639
ER
PT J
AU Finn, A
John, MC
Nakazawa, G
Raghunathan, C
Ezell, T
Lajoie, S
Xu, X
Cheng, Q
Kolodgie, F
Virmani, R
Gold, HK
AF Finn, Aloke
John, Michael C.
Nakazawa, Gaku
Raghunathan, Chitra
Ezell, Tucker
Lajoie, Scott
Xu, Xin
Cheng, Qi
Kolodgie, Frank
Virmani, Renu
Gold, Herman K.
TI Differential Healing in Paclitaxel and Sirolimus-Eluting Stents in
Combination with Oral PPAR Gamma Agents: The Role of Drug Interaction in
Delayed Healing
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [John, Michael C.; Lajoie, Scott; Gold, Herman K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Finn, Aloke; Raghunathan, Chitra; Ezell, Tucker] Emory Univ, Sch Med, Atlanta, GA USA.
[Nakazawa, Gaku; Xu, Xin; Cheng, Qi; Kolodgie, Frank; Virmani, Renu] CVPath, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S960
EP S960
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503560
ER
PT J
AU Forman, DE
Giugliano, RP
Cannon, CP
Morrow, DA
Qin, J
Antman, EM
Braunwald, E
AF Forman, Daniel E.
Giugliano, Robert P.
Cannon, Christopher P.
Morrow, David A.
Qin, Jie
Antman, Elliott M.
Braunwald, Eugene
TI A Simple TIMI Discharge Risk Score Post ACS Predicts CV Mortality at 2
Years
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Forman, Daniel E.; Giugliano, Robert P.; Cannon, Christopher P.; Morrow, David A.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Qin, Jie] TIMI Study Grp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1060
EP S1060
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504209
ER
PT J
AU Fox, CS
Gona, P
Hoffmann, U
Salton, CJ
Massaro, J
Levy, D
Larson, M
D'Agostino, RB
O'Donnell, CJ
Manning, WJ
AF Fox, Caroline S.
Gona, Philimon
Hoffmann, Udo
Salton, Carol J.
Massaro, Joseph
Levy, Daniel
Larson, Martin
D'Agostino, Ralph B.
O'Donnell, Christopher J.
Manning, Warren J.
TI Pericardial Fat, Intra-Thoracic Fat, and Left Ventricular Mass: The
Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Fox, Caroline S.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[Gona, Philimon; Massaro, Joseph; Larson, Martin; D'Agostino, Ralph B.] Boston Univ, Framingham, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1152
EP S1152
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504576
ER
PT J
AU Frangiskakis, JM
Nilles, KM
Grimley, SR
Gutmann, R
Bloom, HL
Dudley, SC
Ellinor, PT
Shalaby, A
Weiss, R
Saba, S
McNamara, DM
AF Frangiskakis, J. M.
Nilles, Kathy M.
Grimley, Sara R.
Gutmann, Rebecca
Bloom, Heather L.
Dudley, Samuel C.
Ellinor, Patrick T.
Shalaby, Alaa
Weiss, Raul
Saba, Samir
McNamara, Dennis M.
TI African-Americans with Congestive Heart Failure Have More Arrhythmias
than Caucasians Independent of the SCN5A S1103Y Genotype
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Frangiskakis, J. M.; Nilles, Kathy M.; Grimley, Sara R.; Gutmann, Rebecca; Shalaby, Alaa; McNamara, Dennis M.] Univ Pittsburgh, Med Cntr, Pittsburgh, PA USA.
[Bloom, Heather L.] Emory Univ, Sch Med, Atlanta, GA USA.
[Bloom, Heather L.] Atlanta VA Med Cntr, Atlanta, GA USA.
[Dudley, Samuel C.] Univ Illinois, Chicago, IL USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shalaby, Alaa] Pittsburgh VA Med Cntr, Pittsburgh, PA USA.
[Weiss, Raul] Ohio State Univ, Columbus, OH 43210 USA.
[Saba, Samir; McNamara, Dennis M.] Barry London, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S718
EP S718
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502342
ER
PT J
AU Gao, G
Shang, LL
Zhou, A
Zhe, J
Gaconnet, G
Dudley, SC
AF Gao, Go
Shang, Lijuan L.
Zhou, Anyu
Zhe, Jiao
Gaconnet, Georgia
Dudley, Samuel C., Jr.
TI The Possible Mechanism of Acquired Sodium Channel mRNA Splicing Variants
with Human Heart Failure
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Gao, Go; Shang, Lijuan L.; Zhe, Jiao; Gaconnet, Georgia; Dudley, Samuel C., Jr.] Univ Chicago, Chicago, IL 60637 USA.
[Zhou, Anyu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S873
EP S873
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503209
ER
PT J
AU Georgiopoulou, VV
Kalogeropoulos, AP
de Rekeneire, N
Rodondi, N
Smith, AL
Hoffmann, U
Kanaya, A
Newman, AB
Kritchevsky, SB
Vasan, RS
Wilson, PW
Harris, TB
Butler, J
AF Georgiopoulou, Vasiliki V.
Kalogeropoulos, Andreas P.
de Rekeneire, Nathalie
Rodondi, Nicolas
Smith, Andrew L.
Hoffmann, Udo
Kanaya, Alka
Newman, Anne B.
Kritchevsky, Stephen B.
Vasan, Ramachandran S.
Wilson, Peter W.
Harris, Tamara B.
Butler, Javed
TI Serum Resistin Concentrations and Risk of New Onset Heart Failure in the
Elderly
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Georgiopoulou, Vasiliki V.; Kalogeropoulos, Andreas P.; Smith, Andrew L.; Wilson, Peter W.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA.
[de Rekeneire, Nathalie] EpiCntr, Paris, France.
[Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland.
[Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kanaya, Alka] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Vasan, Ramachandran S.] Boston Univ, Boston, MA 02215 USA.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1021
EP S1021
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504058
ER
PT J
AU Gibson, CM
Pride, YB
Mohanavelu, S
Wiviott, SD
Antman, EM
Braunwald, E
AF Gibson, C. Michael
Pride, Yuri B.
Mohanavelu, Satishkumar
Wiviott, Stephen D.
Antman, Elliott M.
Braunwald, Eugene
TI Angiographic and Clinical Outcomes Among Patients with Acute Coronary
Syndrome Presenting with Isolated Anterior ST-Segment Depressions
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Gibson, C. Michael; Mohanavelu, Satishkumar; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene] Beth Israel Deaconess Med Ctr, TIMI Study Grp, Boston, MA 02215 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S654
EP S654
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502079
ER
PT J
AU Go, AS
Fang, MC
Udaltsova, N
Chang, Y
Borowsky, LH
Pomernacki, NK
Singer, DE
AF Go, Alan S.
Fang, Margaret C.
Udaltsova, Natalia
Chang, Yuchiao
Borowsky, Leila H.
Pomernacki, Niela K.
Singer, Daniel E.
TI Proteinuria and Reduced Glomerular Filtration Rate Independently
Increase Risk of Thromboembolism In Atrial Fibrillation: The ATRIA Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Go, Alan S.; Udaltsova, Natalia; Pomernacki, Niela K.] Kaiser Permanente No Calif, Oakland, CA USA.
[Fang, Margaret C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Chang, Yuchiao; Borowsky, Leila H.; Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S915
EP S915
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503378
ER
PT J
AU Goebel, JR
Doering, LV
Shugarman, LR
Asch, SM
Sherbourne, CD
Lanto, AB
Evangelista, LS
Nyamathi, AM
Maliski, SL
Lorenz, KA
AF Goebel, Joy R.
Doering, Lynn V.
Shugarman, Lisa R.
Asch, Steven M.
Sherbourne, Cathy D.
Lanto, Andy B.
Evangelista, Lorraine S.
Nyamathi, Adeline M.
Maliski, Sally L.
Lorenz, Karl A.
TI Heart Failure, the Hidden Problem of Pain
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Goebel, Joy R.] Calif State Univ Long Beach, Long Beach, CA 90840 USA.
[Doering, Lynn V.; Asch, Steven M.; Evangelista, Lorraine S.; Nyamathi, Adeline M.; Maliski, Sally L.; Lorenz, Karl A.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Shugarman, Lisa R.; Sherbourne, Cathy D.] RAND Corp, Santa Monica, CA USA.
[Lanto, Andy B.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S823
EP S824
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503011
ER
PT J
AU Green, SM
Selzer, F
Mulukutla, S
Lee, A
Joon, LS
Kelsey, SF
Kip, KE
Marroquin, OC
AF Green, Sandy M.
Selzer, Faith
Mulukutla, Suresh
Lee, Ashley
Joon, Lee S.
Kelsey, Sherry F.
Kip, Kevin E.
Marroquin, Oscar C.
TI The Effect of Gender and Race on Outcomes in Patients Undergoing PCI for
Proximal Coronary Artery Lesions: A Report from the NHLBI Dynamic
Registry of PCI
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Green, Sandy M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Selzer, Faith; Mulukutla, Suresh; Lee, Ashley; Joon, Lee S.; Kelsey, Sherry F.; Marroquin, Oscar C.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kip, Kevin E.] Univ S Florida, Tampa, FL USA.
RI Marroquin, Oscar/F-2214-2015
OI Marroquin, Oscar/0000-0002-0909-0319
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S632
EP S632
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501774
ER
PT J
AU Ho, PM
Maddox, TM
Wang, L
Fihn, SD
Jesse, RL
Peterson, ED
Rumsfeld, JS
AF Ho, P. Michael
Maddox, Thomas M.
Wang, Li
Fihn, Stephan D.
Jesse, Robert L.
Peterson, Eric D.
Rumsfeld, John S.
TI Proton Pump Inhibitors May Attenuate the Benefits of Clopidogrel among
ACS Patients: Empirical Evidence from 3,311 ACS Patients
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.] Denver Va Med Ctr, Denver, CO USA.
[Wang, Li; Fihn, Stephan D.] Puget Sound VA Med Cntr, Seattle, WA USA.
[Jesse, Robert L.] Richmond VA Med Cntr, Richmond, VA USA.
[Peterson, Eric D.] Duke Clin Rsch Inst, Durham, NC USA.
NR 0
TC 3
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1165
EP S1165
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504623
ER
PT J
AU Jacobson, AF
AF Jacobson, Arnold F.
TI Impact of Right Ventricular Function on Long-term Survival of Patients
with Left Ventricular Dysfunction
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Jacobson, Arnold F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S953
EP S953
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503529
ER
PT J
AU Januzzi, JL
Bajwa, E
Khah, U
Gong, M
Thompson, BT
Christiani, D
AF Januzzi, James L., Jr.
Bajwa, Ednan
Khah, Uzma
Gong, Michelle
Thompson, B. T.
Christiani, David
TI An Inflammatory Paradox In Acute Respiratory Distress Syndrome? Plasma
C-reactive Protein Concentrations are Strongly Associated with Survival
In ARDS
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Januzzi, James L., Jr.; Bajwa, Ednan; Khah, Uzma; Gong, Michelle; Thompson, B. T.; Christiani, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S767
EP S767
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502542
ER
PT J
AU Jensen, JK
Januzzi, JL
Atar, D
Mickley, H
AF Jensen, Jasper K.
Januzzi, James L.
Atar, Dan
Mickley, Hans
TI Prevalence and Importance of Cardiac Arrhythmias after Acute Ischemic
Stroke
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Jensen, Jasper K.; Mickley, Hans] Odense Univ Hosp, DK-5000 Odense C, Denmark.
[Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Atar, Dan] Aker Univ Hosp, Div Cardiol, Oslo, Norway.
[Atar, Dan] Univ Oslo, Fac Med, Oslo, Norway.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S759
EP S759
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502512
ER
PT J
AU Koenig, W
Bamberg, F
Lee, H
Truong, QA
Nichols, JH
Trischler, G
Morrow, DA
Nagurney, TJ
Hoffmann, U
AF Koenig, Wolfgang
Bamberg, Fabian
Lee, Hang
Truong, Quynh A.
Nichols, John H.
Trischler, Gerlinde
Morrow, David A.
Nagurney, Tobias J.
Hoffmann, Udo
TI High-Sensitivity Troponin Reliably Excludes Acute Coronary Syndrome In
Patients with Acute Chest Pain: Results from the Rule Out Myocardial
Infarction by Computed Tomography (ROMICAT) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Koenig, Wolfgang; Trischler, Gerlinde] Univ Ulm, Ulm, Germany.
[Bamberg, Fabian; Lee, Hang; Truong, Quynh A.; Nichols, John H.; Nagurney, Tobias J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Morrow, David A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S637
EP S637
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502017
ER
PT J
AU Kolm, P
Jiang, XZ
Spertus, JA
Maron, DJ
O'Rourke, R
Teo, KK
Zhang, W
Boden, WE
Weintraub, WS
AF Kolm, Paul
Jiang, Xiaozhang
Spertus, John A.
Maron, David J.
O'Rourke, Robert
Teo, Koon K.
Zhang, Wei
Boden, William E.
Weintraub, William S.
TI Baseline Physical Limitation is Related to Death and MI in the COURAGE
Trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Kolm, Paul; Jiang, Xiaozhang; Zhang, Wei; Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA.
[Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Maron, David J.] Vanderbilt Univ Med Cntr, Nashville, TN USA.
[O'Rourke, Robert] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Teo, Koon K.] McMaster Univ, Med Ctr, Hamilton, ON, Canada.
[Boden, William E.] Buffalo Gen Hosp, Buffalo, NY 14203 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1162
EP S1162
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504610
ER
PT J
AU Kristo, F
Anderson, TJ
Hardy, GJ
Sinha, S
Shen, SQ
Tager, AM
Gerszten, RE
AF Kristo, Fjoralba
Anderson, Thomas J.
Hardy, Gregory J.
Sinha, Sumita
Shen, Shiqian
Tager, Andrew M.
Gerszten, Robert E.
TI Both leukocyte and non-leukocyte Blt1 contribute to atherogenesis
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Kristo, Fjoralba; Anderson, Thomas J.; Hardy, Gregory J.; Sinha, Sumita; Shen, Shiqian; Tager, Andrew M.; Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S450
EP S450
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500811
ER
PT J
AU Lehman, SJ
Bamberg, F
Schleft, CL
Lee, H
Shturman, L
Donnelly, PM
Rogers, IS
Brady, TJ
Hoffmann, U
AF Lehman, Sam J.
Bamberg, Fabian
Schleft, Christopher L.
Lee, Hang
Shturman, Leon
Donnelly, Patrick M.
Rogers, Ian S.
Brady, Thomas J.
Hoffmann, Udo
TI Progression of Coronary Artery Disease as Assessed by Serial 64-Slice
Contrast Enhanced Computed Tomography
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Lehman, Sam J.; Bamberg, Fabian; Schleft, Christopher L.; Lee, Hang; Shturman, Leon; Donnelly, Patrick M.; Rogers, Ian S.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S776
EP S777
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502579
ER
PT J
AU Levine, YC
Michel, T
AF Levine, Yehoshua C.
Michel, Thomas
TI Simvastatin Regulates Insulin Signaling in Endothelial Cells via
Activation of AMP-Activated Protein Kinase
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Levine, Yehoshua C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Michel, Thomas] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S404
EP S404
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500606
ER
PT J
AU Lewis, GD
Shah, RV
Martinovic, M
Bloch, KD
Semigran, MJ
AF Lewis, Gregory D.
Shah, Ravi V.
Martinovic, Maryann
Bloch, Kenneth D.
Semigran, Marc J.
TI Pulmonary Vasoconstriction Occurs out of Proportion to Increases in
Pulmonary Capillary Wedge Pressure During Exercise in Heart Failure
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Lewis, Gregory D.; Shah, Ravi V.; Martinovic, Maryann; Bloch, Kenneth D.; Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S953
EP S954
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503532
ER
PT J
AU Lipshultz, SE
Scully, RE
Lipsitz, SR
Sallan, SE
Silverman, LB
Miller, TL
Barry, EV
Asselin, BL
Athale, U
Clavell, LA
Larsen, E
Moghrabi, A
Samson, Y
Schorin, MA
Orav, EJ
Colan, SD
AF Lipshultz, Steven E.
Scully, Rebecca E.
Lipsitz, Stuart R.
Sallan, Stephen E.
Silverman, Lewis B.
Miller, Tracie L.
Barry, Elly V.
Asselin, Barbara L.
Athale, Uma
Clavell, Luis A.
Larsen, Eric
Moghrabi, Albert
Samson, Yvan
Schorin, Marshall A.
Orav, E. John
Colan, Steven D.
TI Dexrazoxane Cardioprotection In Doxorubicin-Treated Children with Acute
Lymphoblastic Leukemia: Dana-Farber Cancer Institute Acute Lymphoblastic
Leukemia Consortium Protocol 95-01 Randomized Controlled
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Lipshultz, Steven E.; Scully, Rebecca E.; Miller, Tracie L.] Univ Miami, Miami, FL USA.
[Lipsitz, Stuart R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Barry, Elly V.] Genzyme Corp, Cambridge, MA USA.
[Asselin, Barbara L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Athale, Uma] McMaster Univ, Hamilton, ON, Canada.
[Clavell, Luis A.] San Jorge Childrens Hosp, Santurce, PR USA.
[Larsen, Eric] Maine Childrens Canc Program, Portland, ME USA.
[Moghrabi, Albert] Hop St Justine, Montreal, PQ H3T 1C5, Canada.
[Samson, Yvan] Univ Quebec, Ctr Hosp, Quebec City, PQ, Canada.
[Schorin, Marshall A.] Inova Fairfax Hosp, Fairfax, VA USA.
[Orav, E. John] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Colan, Steven D.] Childrens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1055
EP S1056
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504193
ER
PT J
AU Ly, H
Hoshino, K
Pomerantseva, I
Kawase, Y
Yoneyama, R
Takewa, Y
Vooght, C
Frangioni, JV
Hajjar, RJ
AF Ly, Hung
Hoshino, Kozo
Pomerantseva, Irina
Kawase, Yoshiaki
Yoneyama, Ryuichi
Takewa, Yoshiaki
Vooght, Carrie
Frangioni, John V.
Hajjar, Roger J.
TI In Vivo Myocardial Distribution of Adult Stem Cells Immediately
Following Intracoronary Delivery In a Swine Model of Myocardial
Infarction
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Ly, Hung] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Hoshino, Kozo; Kawase, Yoshiaki; Yoneyama, Ryuichi; Takewa, Yoshiaki; Hajjar, Roger J.] Mt Sinai Sch Med, New York, NY USA.
[Pomerantseva, Irina] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vooght, Carrie; Frangioni, John V.] Beth Israel Deaconess Med Cntr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S537
EP S537
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501375
ER
PT J
AU Maree, AO
Vangjeli, C
Jneid, H
Cox, D
Shields, DC
Fitzgerald, DJ
AF Maree, Andrew O.
Vangjeli, Ciara
Jneid, Hani
Cox, Dermot
Shields, Denis C.
Fitzgerald, Desmond J.
TI G-Protein Beta3 Subunit Polymorphism (GNB3 825T) Carriage is Associated
with Increased Bleeding in the Orbofiban in Patients with Unstable
Coronary Syndromes-Thrombolysis in Myocardial Infarction (OPUS-TIMI) 16
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Maree, Andrew O.] Boston Univ, Med Ctr, Boston, MA USA.
[Vangjeli, Ciara; Cox, Dermot] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Jneid, Hani] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shields, Denis C.; Fitzgerald, Desmond J.] Univ Coll Dublin, Dublin 2, Ireland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S816
EP S816
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502738
ER
PT J
AU Marques, J
Mendoza, I
Mendoza-Britto, I
Palacios, I
Noya, B
Moleiro, F
AF Marques, Juan
Mendoza, Ivan
Mendoza-Britto, Ivan
Palacios, Igo
Noya, Belkisyole
Moleiro, Federico
TI A New Epidemic of Myocarditis. Acute Chagas Disease due to Oral
Infection in a Major Latin America City. Electrocardiographic Changes in
121 Cases
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Marques, Juan; Mendoza, Ivan; Noya, Belkisyole; Moleiro, Federico] Cent Univ Venezuela, Caracas, Venezuela.
[Mendoza-Britto, Ivan] Albert Einstein Hosp, Philadelphia, PA USA.
[Palacios, Igo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S676
EP S676
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502170
ER
PT J
AU Marroquin, OC
Selzer, F
Mulukutla, SR
Green, SM
Lee, JS
Anderson, WD
Smith, C
Kelsey, SF
Kip, KE
AF Marroquin, Oscar C.
Selzer, Faith
Mulukutla, Suresh R.
Green, Sandy M.
Lee, Joon S.
Anderson, William D.
Smith, Conrad
Kelsey, Sherry F.
Kip, Kevin E.
TI Incremental Benefit of Drug-Eluting Stents when Used for Proximal
Coronary Artery Lesions: A Report from the NHLBI Dynamic Registry
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Marroquin, Oscar C.; Mulukutla, Suresh R.; Lee, Joon S.; Anderson, William D.; Smith, Conrad] Presbyterian Univ Hosp, UPMC, Pittsburgh, PA 15213 USA.
[Selzer, Faith; Kelsey, Sherry F.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kip, Kevin E.] Univ S Florida, Tampa, FL USA.
[Green, Sandy M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Marroquin, Oscar/F-2214-2015
OI Marroquin, Oscar/0000-0002-0909-0319
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S631
EP S632
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501773
ER
PT J
AU Mega, JL
Wiviott, SD
Mohanavolu, S
Nicolau, JC
McCabe, CH
Antman, EM
Braunwald, E
AF Mega, Jessica L.
Wiviott, Stephen D.
Mohanavolu, Satishkumar
Nicolau, Jose C.
McCabe, Carolyn H.
Antman, Elliott M.
Braunwald, Eugene
TI Cardiovascular Outcomes of Women and Men with Acute Coronary Syndromes
and Angiographically Confirmed Epicardial Coronary Artery Disease In
TRITON-TIMI 38
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Mega, Jessica L.; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Mohanavolu, Satishkumar; McCabe, Carolyn H.] TIMI Study Grp, Boston, MA USA.
[Nicolau, Jose C.] Univ Sao Paulo, Heart Inst InCor HC, Sao Paulo, Brazil.
RI Nicolau, Jose/E-1487-2012
NR 0
TC 2
Z9 2
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 OCT 28
PY 2008
VL 118
IS 18
BP S967
EP S967
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503583
ER
PT J
AU Mehta, RH
Sheng, S
O'Brien, SM
Gammie, JS
Grover, FL
Ferguson, TB
Peterson, ED
AF Mehta, Rajendra H.
Sheng, Shubin
O'Brien, Sean M.
Gammie, James S.
Grover, Frederick L.
Ferguson, T. Bruce, Jr.
Peterson, Eric D.
CA Soc Thoracic Surg Natl Cardiac Dat
TI Reoperation for Bleeding among 528,279 Patients Undergoing Coronary
Artery Bypass Surgery: The Society of Thoracic Surgeons National
Database Experience
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Mehta, Rajendra H.; Sheng, Shubin; O'Brien, Sean M.; Peterson, Eric D.] Duke Clin Rsch Inst, Durham, NC USA.
[Gammie, James S.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Grover, Frederick L.] Denver VA Med Ctr, Denver, CO USA.
[Grover, Frederick L.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Ferguson, T. Bruce, Jr.] E Carolina Univ, Brodie Sch Med, Greenville, NC USA.
RI O'Brien, Sean/H-6268-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S940
EP S940
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503477
ER
PT J
AU Memisoglu, A
Wittes, J
Iskandrian, AE
Kaul, S
Porter, TR
Senior, R
Monaghan, MJ
Udelson, JE
Walovitch, RC
Picard, MH
AF Memisoglu, Asli
Wittes, Janet
Iskandrian, Ami E.
Kaul, Sanjiv
Porter, Thomas R.
Senior, Roxy
Monaghan, Mark J.
Udelson, James E.
Walovitch, Richard C.
Picard, Michael H.
TI Perfusion Stress Echocardiography with Perflubutane Polymer Microspheres
Provides Incremental Predictive Value for Coronary Artery Disease Over
Clinical Risk Factors
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Memisoglu, Asli; Walovitch, Richard C.] Acusphere Inc, Watertown, MA USA.
[Wittes, Janet] Stat Collaborat, Washington, DC USA.
[Iskandrian, Ami E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Kaul, Sanjiv] Oregon Hlth & Sci Univ, Portland, OR USA.
[Porter, Thomas R.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, Harrow, Middx, England.
[Monaghan, Mark J.] Kings Coll Hosp London, London, England.
[Udelson, James E.] Tufts New England Med Cntr, Boston, MA USA.
[Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
SU 2
BP S934
EP S934
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503451
ER
PT J
AU Minamishima, S
De Yu, J
Bougaki, M
Adrie, C
Minamishima, YA
Lefer, DJ
Ichinose, F
AF Minamishima, Shizuka
De Yu, Jia
Bougaki, Masahiko
Adrie, Christophe
Minamishima, Yoji A.
Lefer, David J.
Ichinose, Fumito
TI Hydrogen Sulfide Improves Outcome after Cardiac Arrest and
Cardiopulmonary Resuscitation in Mouse
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Minamishima, Shizuka; De Yu, Jia; Bougaki, Masahiko; Adrie, Christophe; Ichinose, Fumito] Massachusetts Gen Hosp, Charlestown, MA USA.
[Minamishima, Yoji A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lefer, David J.] Albert Einstein Coll Med, New York, NY USA.
RI Minamishima, Yoji/E-5380-2010
OI Minamishima, Yoji/0000-0001-7995-9318
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1446
EP S1447
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504672
ER
PT J
AU Nallamshetty, S
Yi, BA
Stone, J
O'Gara, PT
MaCare, CA
AF Nallamshetty, Shriram
Yi, Byungdoo A.
Stone, James
O'Gara, Patrick T.
MaCare, Calurn A.
TI Biatrial Enlargement and Recurrent Cardioembolism in a 55 Year-Old Man
with Atrial Fibrillation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Nallamshetty, Shriram; Yi, Byungdoo A.; Stone, James; MaCare, Calurn A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[O'Gara, Patrick T.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S648
EP S648
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502060
ER
PT J
AU Noseworthy, PA
Rosenberg, M
Ruskin, JN
Palacios, IF
Mela, T
Fifer, MA
Das, S
AF Noseworthy, Peter A.
Rosenberg, Michael
Ruskin, Jeremy N.
Palacios, Igor F.
Mela, Theofanie
Fifer, Michael A.
Das, Saumya
TI Ventricular Arrhythmia Following Alcohol Septal Ablation for
Hypertrophic Obstructive Cardiomyopathy: Clinical Predictors of Events
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Noseworthy, Peter A.; Ruskin, Jeremy N.; Palacios, Igor F.; Mela, Theofanie; Fifer, Michael A.; Das, Saumya] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rosenberg, Michael] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S594
EP S594
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501624
ER
PT J
AU Owens, DS
Budoff, MJ
Nasir, K
Katz, R
Takasu, J
Carr, JJ
Shavelle, DM
Kronmal, RA
Probstfield, JL
O'Brien, KD
AF Owens, David S.
Budoff, Matthew J.
Nasir, Khurram
Katz, Ronit
Takasu, Junichiro
Carr, J. J.
Shavelle, David M.
Kronmal, Richard A.
Probstfield, Jeffrey L.
O'Brien, Kevin D.
TI Aortic Valve Calcification Is Prospectively Associated with Primary
Cardiovascular Events Independent of Subclinical Coronary Artery Disease
Severity: the Multi-Ethnic Study of Atherosclerosis (MESA)
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Owens, David S.; Katz, Ronit; Kronmal, Richard A.; Probstfield, Jeffrey L.; O'Brien, Kevin D.] Univ Washington, Seattle, WA 98195 USA.
[Budoff, Matthew J.; Takasu, Junichiro; Shavelle, David M.] Harbor UCLA Med Ctr, Los Angeles BioMed Rsch Inst, Los Angeles, CA USA.
[Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Carr, J. J.] Wake Forest Univ, Winston Salem, NC 27109 USA.
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S995
EP S995
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503694
ER
PT J
AU Patel, AM
D'Avila, A
Neuzil, P
Kim, SJ
Morgan, D
Afonso, V
Ruskin, JN
Reddy, VY
AF Patel, Anshul M.
D'Avila, Andre
Neuzil, Petr
Kim, Steven J.
Morgan, Dennis
Afonso, Valtino
Ruskin, Jeremy N.
Reddy, Vivek Y.
TI The Effect of Step-Wise Atrial Ablation on the Substrate for Persistent
Atrial Fibrillation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Patel, Anshul M.] St Josephs Hosp, Atlanta, GA USA.
[D'Avila, Andre; Reddy, Vivek Y.] Univ Miami, Miami, FL USA.
[Neuzil, Petr] Na Homolce Hosp, Prague, Czech Republic.
[Kim, Steven J.; Morgan, Dennis; Afonso, Valtino] St Jude Med, St Paul, MN USA.
[Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010
OI d'Avila, Andre Luiz/0000-0001-8769-1411
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S588
EP S589
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501601
ER
PT J
AU Perry, KJ
Bloch, KD
MacRae, CA
Shin, JT
AF Perry, Kenneth J.
Bloch, Kenneth D.
MacRae, Calum A.
Shin, Jordan T.
TI Paradoxical Augmentation Of BMP-signaling In Vivo Following Loss Of
BMPR2 In Zebrafish Is Mediated Through Recruitment Of An Alternative
Type 2 Receptor
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Perry, Kenneth J.; MacRae, Calum A.; Shin, Jordan T.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S506
EP S506
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501246
ER
PT J
AU Pijnappels, DA
Stadtfeld, M
Zeng, M
Yu, E
Fujiwara, Y
Wang, GW
Orkin, SH
Jackson-Grusby, L
Hochedlinger, K
Wu, SM
AF Pijnappels, Daniel A.
Stadtfeld, Matthias
Zeng, Min
Yu, Esther
Fujiwara, Yuko
Wang, Guangwen
Orkin, Stuart H.
Jackson-Grusby, Laurie
Hochedlinger, Konrad
Wu, Sean M.
TI Derivation and Functional Characterization of Nkx2.5+Cardiac Progenitor
Cells from Mouse Induced Pluripotent Stem Cells
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Pijnappels, Daniel A.; Zeng, Min; Yu, Esther] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA 02114 USA.
[Stadtfeld, Matthias; Hochedlinger, Konrad] Massachusetts Gen Hosp, Cntr Regenerat Med, Boston, MA 02114 USA.
[Fujiwara, Yuko; Orkin, Stuart H.] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA.
[Wang, Guangwen; Jackson-Grusby, Laurie] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S428
EP S428
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500714
ER
PT J
AU Potente, M
Guarani, V
Baldessari, D
Ejaz, S
Mostoslavsky, R
Fleming, I
Mione, M
Alt, FW
Zeiher, AM
Dimmeler, S
AF Potente, Michael
Guarani, Virginia
Baldessari, Danila
Ejaz, Sohail
Mostoslavsky, Raul
Fleming, Ingrid
Mione, Marina
Alt, Frederick W.
Zeiher, Andreas M.
Dimmeler, Stefanie
TI Signal-Responsive Repression of Notch1 Signaling by the Sirt1
Deacetylase Regulates Sprouting Angiogenesis
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Baldessari, Danila; Mione, Marina] IFOM FIRC Inst Mol Oncol, Milan, Italy.
[Mostoslavsky, Raul] Massachusetts Gen Hosp Canc Cntr, Boston, MA USA.
[Alt, Frederick W.] CBR Inst BioMed Rsch, Howard Hughes Med Inst, Boston, MA 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S460
EP S461
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501045
ER
PT J
AU Pride, YB
Canto, JG
Frederick, PD
Gibson, CM
AF Pride, Yuri B.
Canto, John G.
Frederick, Paul D.
Gibson, C. Michael
TI Outcomes Among Patients with Non-ST-Segment Elevation Myocardial
Infarction Presenting to Interventional Hospitals With and Without
On-Site Cardiac Surgery: A NRMI 5 Analysis
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Pride, Yuri B.; Gibson, C. Michael] BIDMC, Boston, MA USA.
[Canto, John G.] Cntr Cardiovascular Prevent, Watson Clin, Lakeland, FL USA.
[Frederick, Paul D.] ICON Lifecycle Sci Grp, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1163
EP S1163
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504617
ER
PT J
AU Raffel, OC
Tearney, GJ
Chia, S
Gauthier, DD
Bouma, BE
Jang, IK
AF Raffel, Owen C.
Tearney, Guillermo J.
Chia, Stanley
Gauthier, Denise DeJoseph
Bouma, Brett E.
Jang, Ik-Kyung
TI Distance From the Coronary Ostium as a Predictor of Vulnerable Plaque
Morphology; An In-vivo Optical Coherence Tomography Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S627
EP S627
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501755
ER
PT J
AU Reddy, VY
Doshi, SK
d'Avila, A
Neuzil, P
Kim, YH
AF Reddy, Vivek Y.
Doshi, Shephal K.
d'Avila, Andre
Neuzil, Petr
Kim, Young-Hoon
TI Visually-Guided Ablation of the Pulmonary Venous Antrum Using a
Compliant Balloon Catheter
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Reddy, Vivek Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Doshi, Shephal K.] St Johns Hosp, Santa Monica, CA USA.
[d'Avila, Andre] Univ Miami, Miami, FL USA.
[Neuzil, Petr] Homolka Hosp, Prague, Czech Republic.
[Kim, Young-Hoon] Massachusetts Gen Hosp, Seoul, South Korea.
RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010
OI d'Avila, Andre Luiz/0000-0001-8769-1411
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S923
EP S924
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503410
ER
PT J
AU Rehman, SR
van Kimmenade, RR
Januzzi, JL
AF Rehman, Shafiq R.
van Kimmenade, Roland R.
Januzzi, James L.
TI Combining Amino-Terminal Pro-B Type Natriuretic Peptide with the
Interleukin Receptor Family Member ST2 for Optimal Long-Term Risk
Prediction in Acute Dyspnea: Multimarker Results at 4 Years from the
ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE)
Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Rehman, Shafiq R.; van Kimmenade, Roland R.; Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Kimmenade, R.R.J./L-4432-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S871
EP S871
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503200
ER
PT J
AU Ren, B
Mukhopadhyay, A
Lanahan, AA
Zhuang, ZW
Moodie, KL
Peterson, RT
Simons, M
AF Ren, Bin
Mukhopadhyay, Arpita
Lanahan, Anthony A.
Zhuang, Zhen W.
Moodie, Karen L.
Peterson, Randall T.
Simons, Michael
TI Recovery of Erk Signaling Restores Defective Angiogenesis and
Arteriogenesis in Synectin-Deficient Animals
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Ren, Bin; Lanahan, Anthony A.; Zhuang, Zhen W.; Moodie, Karen L.; Simons, Michael] Dartmouth Med Sch, Lebanon, NH USA.
[Mukhopadhyay, Arpita; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S576
EP S576
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501547
ER
PT J
AU Rengifo-Moreno, P
Cruz-Gonzalez, I
Cubeddu, RJ
Sanchez-Ledezma, M
Ning, MM
McNamara, M
Buonanno, F
Lnglessis-Azuaje, I
Demirjian, Z
Palacios, IF
AF Rengifo-Moreno, Pablo
Cruz-Gonzalez, Ignacio
Cubeddu, Roberto J.
Sanchez-Ledezma, Maria
Ning, Mingming
McNamara, Maryellen
Buonanno, Ferdinando
Lnglessis-Azuaje, Ignacio
Demirjian, Zareh
Palacios, Igor F.
TI Efficacy And Safety Of Percutaneous Patent Foramen Ovate Closure In
Patients With Thrombophilia
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Rengifo-Moreno, Pablo; Cruz-Gonzalez, Ignacio; Cubeddu, Roberto J.; Sanchez-Ledezma, Maria; Ning, Mingming; McNamara, Maryellen; Buonanno, Ferdinando; Lnglessis-Azuaje, Ignacio; Demirjian, Zareh; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S904
EP S904
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503333
ER
PT J
AU Rieber, J
Hoffmann, U
Hetterich, H
Bamberg, F
Achenbach, S
AF Rieber, Johannes
Hoffmann, Udo
Hetterich, Holger
Bamberg, Fabian
Achenbach, Stefan
TI Impact of Different Post-Processing Techniques on Inter-Observer
Agreement for Coronary CTA. Results from a Multicenter Trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Hoffmann, Udo; Bamberg, Fabian] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rieber, Johannes; Hetterich, Holger] Dept Cardiol, Munich, Germany.
[Achenbach, Stefan] Univ Erlangen Nurnberg, Erlangen, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1063
EP S1063
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504224
ER
PT J
AU Rivera, JJ
Nasir, K
Blumenthal, RS
Yoon, YE
Chang, SA
Choi, EK
Choi, SI
Chun, EJ
Choi, DJ
Chang, HJ
AF Rivera, Juan J.
Nasir, Khurram
Blumenthal, Roger S.
Yoon, Yeonyee E.
Chang, Song A.
Choi, Eue-Keun
Choi, Sang-Il
Chun, Eun-Ju
Choi, Dong-Joo
Chang, Hyuk-Jae
TI Traditional Risk Factors & Coronary Plaque Composition Assessed by Non
Invasive CT Angiography in Asymptomatic Individuals
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rivera, Juan J.; Blumenthal, Roger S.] Johns Hopkins Univ, Baltimore, MD USA.
[Yoon, Yeonyee E.; Chang, Song A.; Choi, Eue-Keun; Choi, Sang-Il; Chun, Eun-Ju; Choi, Dong-Joo; Chang, Hyuk-Jae] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S776
EP S776
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502577
ER
PT J
AU Rivera, JJ
Nasir, K
Yoon, Y
Chang, SA
Choi, EK
Choi, SI
Chun, EJ
Chol, DJ
Blumenthal, R
Chang, HJ
AF Rivera, Juan J.
Nasir, Khurram
Yoon, Yeonyee
Chang, Song A.
Choi, Eue-Keun
Choi, Sang-Il
Chun, Eun-Ju
Chol, Dong-Joo
Blumenthal, Roger
Chang, Hyuk-Jae
TI Cardiac CT Assessment of Atherosclerotic Plaque
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Rivera, Juan J.; Blumenthal, Roger] Johns Hopkins Univ, Baltimore, MD USA.
[Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yoon, Yeonyee; Chang, Song A.; Choi, Eue-Keun; Choi, Sang-Il; Chun, Eun-Ju; Chol, Dong-Joo; Chang, Hyuk-Jae] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S775
EP S776
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502575
ER
PT J
AU Rodriguez, A
Maree, A
Tarragona, S
Fernandez-Pereira, C
Rodriguez-Granillo, AM
Rodriguez-Granillo, GA
Santaera, O
Mieres, J
Kukreja, N
Antoniucci, D
Palacios, IF
Serruys, PW
AF Rodriguez, Alfredo
Maree, Andrew
Tarragona, Sonia
Fernandez-Pereira, Carlos
Rodriguez-Granillo, Alfredo M.
Rodriguez-Granillo, Gaston A.
Santaera, Omar
Mieres, Juan
Kukreja, Neville
Antoniucci, David
Palacios, Igor F.
Serruys, Patrick W.
TI Percutaneous Coronary Intervention with Bare Metal Stents and Oral
Sirolimus has Comparable Safety and Efficacy to Treatment with Drug
Eluting Stents but with Significant Cost Saving : Long Term Follow Up
Results From the Randomized, Controlled ORAR III (Oral Rapamycin in
Argentina) Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Maree, Andrew] Boston Univ, Boston, MA 02215 USA.
[Rodriguez, Alfredo] Otamendi Hosp, Buenos Aires, DF, Argentina.
[Tarragona, Sonia] Argentina Minist Hlth, Buenos Aires, DF, Argentina.
[Fernandez-Pereira, Carlos] Adrogue Clin, Buenos Aires, DF, Argentina.
[Rodriguez-Granillo, Alfredo M.] Cardiovasc Rsch Cntr CECI, Buenos Aires, DF, Argentina.
[Rodriguez-Granillo, Gaston A.; Mieres, Juan] Otamendi Hosp, Buenos Aires, DF, Argentina.
[Santaera, Omar] Argentina Soc Cardiovasc Intervent CACI, Buenos Aires, DF, Argentina.
[Kukreja, Neville; Serruys, Patrick W.] Erasmus Thorax Cntr, Rotterdam, Netherlands.
[Antoniucci, David] Careggi Hosp, Florence, Italy.
[Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1051
EP S1051
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504175
ER
PT J
AU Rogers, IS
Moloo, J
Chae, CU
Blankstein, R
Bamberg, F
Pena, AJ
Seneviratne, SK
Truong, QA
Nichols, JH
Ferencik, M
Brown, DF
Nagurney, JT
Brady, TJ
Hoffmann, U
AF Rogers, Ian S.
Moloo, Jamaluddin
Chae, Claudia U.
Blankstein, Ron
Bamberg, Fabian
Pena, Antonio J.
Seneviratne, Sujith K.
Truong, Quynh A.
Nichols, John H.
Ferencik, Maros
Brown, David F.
Nagurney, John T.
Brady, Thomas J.
Hoffmann, Udo
TI Cardiac CT Angiography vs. SPECT Perfusion Imaging for the Evaluation of
Patients with Acute Chest Pain
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Rogers, Ian S.; Moloo, Jamaluddin; Chae, Claudia U.; Blankstein, Ron; Bamberg, Fabian; Pena, Antonio J.; Seneviratne, Sujith K.; Truong, Quynh A.; Nichols, John H.; Ferencik, Maros; Brown, David F.; Nagurney, John T.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S995
EP S995
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503697
ER
PT J
AU Rosenfield, KA
White, CJ
Jones, PG
Spertus, JA
Cates, CU
Ho, KK
Jeff, MA
Kcroshetz, WJ
Caldwell, SP
Brindis, RG
Anderson, HV
AF Rosenfield, K. A.
White, C. J.
Jones, P. G.
Spertus, J. A.
Cates, C. U.
Ho, K. K.
Jeff, M. A.
Kcroshetz, W. J.
Caldwell, S. P.
Brindis, R. G.
Anderson, H. V.
TI Relationship Between Procedure Indications and Outcomes of Carotid
Artery Stenting: Preliminary Results from the CARE Registry
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Rosenfield, K. A.; Jeff, M. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[White, C. J.] Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA.
[Jones, P. G.; Spertus, J. A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Cates, C. U.] Emory Univ, Atlanta, GA 30322 USA.
[Ho, K. K.] Beth Israel Hosp, Boston, MA USA.
[Kcroshetz, W. J.] NINDS, Bethesda, MD 20892 USA.
[Caldwell, S. P.] Amer Coll Cardiol, Washington, DC USA.
[Brindis, R. G.] Kaiser Permanente, Oakland, CA USA.
[Anderson, H. V.] Univ Texas HSC, Houston, TX USA.
RI White, Christopher/J-6686-2012
OI White, Christopher/0000-0001-8618-7539
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S907
EP S907
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503343
ER
PT J
AU Schnabel, RB
Sullivan, LM
Levy, D
Pencina, MJ
Massaro, JM
D'Agostino, RB
Newton-Cheh, C
Magnani, JW
Tadros, TM
Kennel, W
Wang, TJ
Ellinor, PT
Wolf, PA
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate B.
Sullivan, Lisa M.
Levy, Daniel
Pencina, Michael J.
Massaro, Joseph M.
D'Agostino, Ralph B.
Newton-Cheh, Christopher
Magnani, Jared W.
Tadros, Thomas M.
Kennel, William
Wang, Thomas J.
Ellinor, Patrick T.
Wolf, Philip A.
Vasan, Ramachandran S.
Benjamin, Emella J.
TI Development of a Risk Score for Incident Atrial Fibrillation in the
Community; the Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Schnabel, Renate B.; Pencina, Michael J.; Tadros, Thomas M.; Kennel, William; Wang, Thomas J.; Wolf, Philip A.; Vasan, Ramachandran S.; Benjamin, Emella J.] NHLBI, Framingham Heart Study, Boston, MA USA.
[Sullivan, Lisa M.; D'Agostino, Ralph B.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard, Cambridge, MA USA.
[Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA.
[Magnani, Jared W.] Boston Univ, Dept Cardiol, Boston, MA 02215 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Rsch Ctr, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1089
EP S1090
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504328
ER
PT J
AU Schulz, C
Leuschen, NV
Frohlich, T
Lorenz, M
Arnold, GJ
Massberg, S
AF Schulz, Christian
Leuschen, Nina V.
Froehlich, Thomas
Lorenz, Michael
Arnold, Georg J.
Massberg, Steffen
TI Differential Platelet Proteome Analysis Following Specific Activation Of
Glycoprotein VI
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Schulz, Christian; Lorenz, Michael; Massberg, Steffen] Tech Univ Munich, Ctr Heart, Munich, Germany.
[Leuschen, Nina V.] Univ Cologne, Inst Genet, D-5000 Cologne, Germany.
[Froehlich, Thomas; Arnold, Georg J.] Univ Munich, Gene Cntr, Lab Funct Genome Anal, Munich, Germany.
[Massberg, Steffen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA.
[Massberg, Steffen] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RI Frohlich, Thomas/C-6735-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S477
EP S477
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501117
ER
PT J
AU Schulz, C
Schafer, A
von Bruhl, ML
Pelisek, J
Stolla, M
Bauersachs, J
Massberg, S
AF Schulz, Christian
Schaefer, Andreas
von Bruehl, Marie L.
Pelisek, Jaroslav
Stolla, Moritz
Bauersachs, Johann
Massberg, Steffen
TI Fractalkine Modulates Recruitment Of Monocytic Cells Following Rupture
Of Atherosclerotic Plaque
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Schulz, Christian; von Bruehl, Marie L.; Stolla, Moritz; Massberg, Steffen] Tech Univ Munich, Ctr Heart, Munich, Germany.
[Schaefer, Andreas; Bauersachs, Johann] Univ Wurzburg, Univ Klinikum, Med Klin & Poliklin 1, Wurzburg, Germany.
[Pelisek, Jaroslav] Tech Univ Munich, Klinikum Rechts Isar, Clin Vasc Surg, Munich, Germany.
[Massberg, Steffen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA.
[Massberg, Steffen] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S471
EP S472
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501093
ER
PT J
AU Seneviratne, SK
Rogers, IS
Bamberg, F
Shapiro, MD
Truong, Q
Lehman, SJ
Nichols, JH
Chae, CU
Hoffmann, U
AF Seneviratne, Sujith K.
Rogers, Ian S.
Bamberg, Fabian
Shapiro, Michael D.
Truong, Quynh
Lehman, Sam J.
Nichols, John H.
Chae, Claudia U.
Hoffmann, Udo
TI Resting Regional Left Ventricular Function by 64-slice Cardiac CT adds
Incremental Value to Coronary Plaque and Stenosis In Predicting Acute
Coronary Syndrome in Patients with Acute Chest Pain
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Seneviratne, Sujith K.; Rogers, Ian S.; Bamberg, Fabian; Shapiro, Michael D.; Truong, Quynh; Lehman, Sam J.; Nichols, John H.; Chae, Claudia U.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S993
EP S993
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503688
ER
PT J
AU Sherwood, MW
Morrow, DA
Scirica, BM
Jiang, S
Bode, C
Rifai, N
Gerszten, RE
Cannon, CP
Braunwald, E
Sabatine, MS
AF Sherwood, Matthew W.
Morrow, David A.
Scirica, Benjamin M.
Jiang, Songtao
Bode, Christoph
Rifai, Nader
Gerszten, Robert E.
Cannon, Christopher P.
Braunwald, Eugene
Sabatine, Marc S.
TI Baseline Troponin Levels Predict 30 Day CV Mortality in STEMI
Independent of Clinical and Electrocardiographic Factors: Analysis from
CLARITY-TIMI 28
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Sherwood, Matthew W.; Morrow, David A.; Scirica, Benjamin M.; Jiang, Songtao; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TMI Study Grp, Boston, MA 02115 USA.
[Bode, Christoph] Univ Freiburg, Freiburg, Germany.
[Rifai, Nader] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA.
[Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S636
EP S636
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502014
ER
PT J
AU Singer, DE
Chang, YC
Fang, MC
Borowsky, LH
Pomernacki, NK
Udaltsova, N
Go, AS
AF Singer, Daniol E.
Chang, Yuchiao
Fang, Margaret C.
Borowsky, Leila H.
Pomernacki, Niels K.
Udaltsova, Natalia
Go, Alan S.
TI Warfarin INR-Response Curves in Subgroups of Patients with Nonvalvular
Atrial Fibrillation: Should Target Anticoagulation Intensity be Adjusted
for Patient Characteristics?: The ATRIA Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Singer, Daniol E.; Chang, Yuchiao; Borowsky, Leila H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fang, Margaret C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Pomernacki, Niels K.; Udaltsova, Natalia; Go, Alan S.] Kaiser Permanente, Div Rsch, Oakland, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S757
EP S757
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502504
ER
PT J
AU Singh, SM
Heist, EK
Donaldson, DM
Mela, T
Ruskin, JN
Mansour, MC
AF Singh, Sheldon M.
Heist, E. Kevin
Donaldson, David M.
Mela, Theofanie
Ruskin, Jeremy N.
Mansour, Moussa C.
TI Intracardiac Echocardiography From Within the Left Atrium Improves the
Accuracy of Image Integration During Catheter Ablation of Atrial
Fibrillation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Singh, Sheldon M.; Heist, E. Kevin; Donaldson, David M.; Mela, Theofanie; Ruskin, Jeremy N.; Mansour, Moussa C.] 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S980
EP S980
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503632
ER
PT J
AU Singh, TP
Givertz, M
Semigran, M
Costantino, F
DeNofrio, D
Gauvreau, K
AF Singh, Tajinder P.
Givertz, Michael
Semigran, Marc
Costantino, Fred
DeNofrio, David
Gauvreau, Kimberlee
TI Association of Race and Socioeconomic Position with Graft Failure in
Heart Transplant Recipients
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Singh, Tajinder P.; Gauvreau, Kimberlee] Childrens Hosp, Boston, MA 02115 USA.
[Givertz, Michael] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Semigran, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Costantino, Fred] New Engalnd Organ Bank, Newton, MA USA.
[DeNofrio, David] Tufts Mod Cntr, Newton, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S801
EP S801
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502677
ER
PT J
AU Solis-Martin, J
Johnson, B
Guerrero, JL
Handschumacher, M
Sullivan, S
Braithwaite, GJC
Muratoglu, OK
Vlahakes, GJ
Levine, RA
Hung, J
AF Solis-Martin, Jorge
Johnson, Benjamin
Guerrero, J. Luis
Handschumacher, Mark
Sullivan, Suzanne
Braithwaite, G. J. C.
Muratoglu, O. K.
Vlahakes, G. J.
Levine, Robert A.
Hung, Judy
TI Polymer Injection Therapy to Reverse Remodel the Papillary Muscles:
Efficacy In Reducing Mitral Regurgitation in a Chronic Ischemic Model
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Solis-Martin, Jorge; Johnson, Benjamin; Guerrero, J. Luis; Handschumacher, Mark; Sullivan, Suzanne; Muratoglu, O. K.; Vlahakes, G. J.; Levine, Robert A.; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Braithwaite, G. J. C.] Cambridge Polymer INC, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S647
EP S647
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502055
ER
PT J
AU Spreafico, M
Peyvandi, F
Foco, L
Bernardinelli, L
Duga, S
Asselta, R
Ardissino, D
Kathiresan, S
Merlini, PA
Mannucci, PM
AF Spreafico, Marta
Peyvandi, Flora
Foco, Luisa
Bernardinelli, Luisa
Duga, Stefano
Asselta, Rosanna
Ardissino, Diego
Kathiresan, Sekar
Merlini, Piera A.
Mannucci, Pier M.
TI Factor V Leiden, But Not Prothrombin G20120A, Is Associated With
Premature Myocardial Infarction
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Spreafico, Marta; Peyvandi, Flora; Duga, Stefano; Asselta, Rosanna; Mannucci, Pier M.] Univ Milan, Milan, Italy.
[Spreafico, Marta; Peyvandi, Flora; Mannucci, Pier M.] Maggiore Hosp, IRCCS, Milan, Italy.
[Foco, Luisa; Bernardinelli, Luisa] Univ Pavia, I-27100 Pavia, Italy.
[Ardissino, Diego] Univ Parma, I-43100 Parma, Italy.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Merlini, Piera A.] Osped Niguarda Ca Granda, Milan, Italy.
RI Mannucci, Pier/C-3102-2014
NR 0
TC 1
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S956
EP S956
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503543
ER
PT J
AU Stewart, GC
Lipes, MA
Anello, MS
Pratibhu, PP
Gottumukkala, R
Winters, GL
Towbin, JA
Baughman, KL
AF Stewart, Garrick C.
Lipes, Myra A.
Anello, Mary Susan
Pratibhu, Parakash P.
Gottumukkala, Raju
Winters, Gayle L.
Towbin, Jeffrey A.
Baughman, Kenneth L.
TI Parvovirus B19 and Cardiomyopathy - The New Coxsackievirus
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Stewart, Garrick C.; Anello, Mary Susan; Pratibhu, Parakash P.; Winters, Gayle L.; Baughman, Kenneth L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lipes, Myra A.; Gottumukkala, Raju] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Towbin, Jeffrey A.] Baylor Coll Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S720
EP S720
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502352
ER
PT J
AU Syed, Z
Scirica, BM
Morrow, DA
Mohanavelu, S
Stultz, CM
Guttag, JV
AF Syed, Zeeshan
Scirica, Benjamin M.
Morrow, David A.
Mohanavelu, Satishkumar
Stultz, Collin M.
Guttag, John V.
TI ECG Markers to Predict Cardiovascular Death: Heart Rate Variability,
Deceleration Capacity and Morphologic Variability in Non-ST-Elevation
ACS from the MERLIN-TIMI 36 Trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Syed, Zeeshan; Stultz, Collin M.; Guttag, John V.] MIT, Cambridge, MA 02139 USA.
[Scirica, Benjamin M.; Morrow, David A.; Mohanavelu, Satishkumar] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S670
EP S670
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502146
ER
PT J
AU Tamehim, N
Fitzgerald, ML
AF Tamehim, Norimasa
Fitzgerald, Michael L.
TI The Sphingolipid Synthesis Regulator SPTLC1 is Bound by PARD3 through a
Type II PDZ Protein-Protein Interaction
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Tamehim, Norimasa; Fitzgerald, Michael L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S376
EP S377
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500481
ER
PT J
AU Thibault, H
Raher, MJ
Buys, E
Cawley, S
Derumeaux, G
Janssens, S
Picard, MH
Bloch, KD
Scherrer-Crosbie, M
AF Thibault, Helene
Raher, Michael J.
Buys, Emmanuel
Cawley, Sharon
Derumeaux, Genevieve
Janssens, Stefan
Picard, Michael H.
Bloch, Kenneth D.
Scherrer-Crosbie, Marielle
TI Nitric Oxide Synthase 3 Predisposes to Adverse Left Ventricular
Remodeling in Insulin Resistance
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Thibault, Helene; Raher, Michael J.; Buys, Emmanuel; Cawley, Sharon; Picard, Michael H.; Bloch, Kenneth D.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Derumeaux, Genevieve] Lyon Hosp, Lyon, France.
[Janssens, Stefan] Katholieke Univ Leuven, Louvain, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S945
EP S945
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503495
ER
PT J
AU Truong, QA
Bamberg, F
Mahabadi, AA
Toepker, MH
Rogers, IS
Seneviratne, S
Nichols, JH
Lehman, SJ
Schlett, CL
Brady, TJ
Hoffmann, U
AF Truong, Quynh A.
Bamberg, Fabian
Mahabadi, Amir A.
Toepker, Michael H.
Rogers, Ian S.
Seneviratne, Sujith
Nichols, John H.
Lehman, Sam J.
Schlett, Christopher L.
Brady, Thomas J.
Hoffmann, Udo
TI Predictive Value of Left Atrial Volume and Function by MDCT for Acute
Coronary Syndrome in Patients with Acute Chest Pain: ROMICAT Substudy
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Truong, Quynh A.; Bamberg, Fabian; Mahabadi, Amir A.; Toepker, Michael H.; Rogers, Ian S.; Seneviratne, Sujith; Nichols, John H.; Lehman, Sam J.; Schlett, Christopher L.; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S761
EP S761
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502519
ER
PT J
AU van Kimmenade, RR
Rehman, S
Januzzi, JL
AF van Kimmenade, Roland R.
Rehman, Shafiq
Januzzi, James L., Jr.
TI Do We Need More than One Biomarker for Risk Prediction in Acute Dyspnea?
Concentrations of ST2 Strongly Predict 4 Year Prognosis in Acutely
Dyspneic Patients with Very Low NT-proBNP Values
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [van Kimmenade, Roland R.] Univ Hosp Maastricht, Maastricht, Netherlands.
[Rehman, Shafiq; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Kimmenade, R.R.J./L-4432-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S866
EP S867
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104503182
ER
PT J
AU Wang, T
Peterson, ED
Ou, FS
Nallamothu, BK
Rumsfeld, JS
Roe, MT
AF Wang, Tracy
Peterson, Eric D.
Ou, Fang-Shu
Nallamothu, Brahmajee K.
Rumsfeld, John S.
Roe, Matthew T.
TI Do Hospitals that Improve "Direct Arrival" Door to Balloon Times for
Primary Percutaneous Coronary Intervention Also Improve "Transfer In"
Door to Balloon Times?
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Wang, Tracy; Peterson, Eric D.; Ou, Fang-Shu; Roe, Matthew T.] Duke Univ, Durham, NC USA.
[Nallamothu, Brahmajee K.] Univ Michigan, Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA.
[Rumsfeld, John S.] Univ Colorado, Denver VA Med Ctr, Denver, CO 80202 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1108
EP S1108
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504400
ER
PT J
AU Xu, R
Wojcik, J
Gervino, EV
Hauser, TH
Amundsen, CA
Powers, C
Matthews, BP
Warram, JH
Doria, A
AF Xu, Rui
Wojcik, Joanna
Gervino, Ernest V.
Hauser, Thomas H.
Amundsen, Celeste A.
Powers, Christine
Matthews, Brian P.
Warram, James H.
Doria, Alessandro
TI A Common Allele at the GRB14 Locus is Associated with Increased
Cardiovascular Risk in Type 2 Diabetes: Evidence from a Pooled DNA GWA
Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Xu, Rui; Wojcik, Joanna; Amundsen, Celeste A.; Powers, Christine; Matthews, Brian P.; Warram, James H.; Doria, Alessandro] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Gervino, Ernest V.; Hauser, Thomas H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S622
EP S623
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104501735
ER
PT J
AU Yalamarti, B
Ke, QG
Bodyak, N
Stillman, I
Tamez, H
Karumanchi, SA
Thadhani, R
Kang, PM
AF Yalamarti, Bhargavi
Ke, Qingen
Bodyak, Natalya
Stillman, Isaac
Tamez, Hector
Karumanchi, S. A.
Thadhani, Ravi
Kang, Peter M.
TI Activated Vitamin D Regresses Cardiac Hypertrophy and Attenuates
Progression to Heart Failure in Dahl Salt-Sensitive Rats
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Yalamarti, Bhargavi; Ke, Qingen; Bodyak, Natalya; Stillman, Isaac; Karumanchi, S. A.; Thadhani, Ravi; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Tamez, Hector] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S335
EP S335
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104500300
ER
PT J
AU Yen, R
Fernandes, V
Cushman, M
Bahrami, H
Nasir, K
Tracy, R
Bluemke, DA
Lima, JA
AF Yen, Raymond
Fernandes, Veronica
Cushman, Mary
Bahrami, Hossein
Nasir, Khurram
Tracy, Russell
Bluemke, David A.
Lima, Joao A.
TI Relationship of Fibrinogen with Regional Left Ventricular Dysfunction In
Asymptomatic Individuals Without Clinical Cardiovascular Disease: The
Multi-Ethnic Study of Atherosclerosis
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Yen, Raymond; Fernandes, Veronica; Bluemke, David A.; Lima, Joao A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Cushman, Mary; Tracy, Russell] Univ Vermont, Colchester, VT USA.
[Bahrami, Hossein] Johns Hopkins Sch Med, Baltimore, MD USA.
[Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S1103
EP S1104
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104504381
ER
PT J
AU Zahid, M
Good, CB
Sonel, AF
AF Zahid, Maliha
Good, Chester B.
Sonel, Ali F.
TI Clinical Significance of Borderline Elevated Troponin-1 Levels Across
Different Assays
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Zahid, Maliha] Univ Pittsburgh, Pittsburgh, PA USA.
[Good, Chester B.; Sonel, Ali F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S636
EP S636
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502015
ER
PT J
AU Zhao, XH
Cai, JM
Underhill, H
OiKawa, M
Dong, L
Ota, H
Hatsukami, T
Yuan, C
AF Zhao, Xihai
Cai, Jianming
Underhill, Hunter
OiKawa, Minako
Dong, Li
Ota, Hideki
Hatsukami, Thomas
Yuan, Chun
TI Prevalence of Carotid Atherosclerotic Plaque Composition and Surface
Disruption for Different Categories of Normalized Wall Index as Measured
by Magnetic Resonance Imaging
SO CIRCULATION
LA English
DT Meeting Abstract
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
C1 [Zhao, Xihai; Underhill, Hunter; OiKawa, Minako; Dong, Li; Ota, Hideki; Yuan, Chun] Univ Washington, Seattle, WA 98195 USA.
[Cai, Jianming] Peoples Liberat Army Gen Hosp, Beijing, Peoples R China.
[Hatsukami, Thomas] VA Puget Sound Healthcare Syst, Seattle, WA USA.
RI Ota, Hideki/A-3717-2012
OI Ota, Hideki/0000-0002-7239-3152
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2008
VL 118
IS 18
BP S688
EP S688
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 389ON
UT WOS:000262104502220
ER
PT J
AU Bustos, RI
Forget, MA
Settleman, JE
Hansen, SH
AF Bustos, Rodrigo I.
Forget, Marie-Annick
Settleman, Jeffrey E.
Hansen, Steen H.
TI Coordination of Rho and Rac GTPase Function via p190B RhoGAP
SO CURRENT BIOLOGY
LA English
DT Article
ID ACTIN POLYMERIZATION; ACTIVATING PROTEIN; CELL-ADHESION; RND PROTEINS;
KINASE; DOMAIN; PATHWAY; BIOLOGY; BINDING; FAMILY
AB The Rac GTPase regulates Rho signaling in a broad range of physiological settings and in oncogenic transformation [1-3]. Here, we report a novel mechanism by which crosstalk between Rac and Rho GTPases is achieved. Activated Rac1 binds directly to p190B Rho GTPase-activating protein (RhoGAP), a major modulator of Rho signaling. p190B colocalizes with constitutively active Rac1 in membrane ruffles. Moreover, activated Rac1 is sufficient to recruit p190B into a detergent-insoluble membrane fraction, a process that is accompanied by a decrease in GTP-bound RhoA from membranes. p19013 is recruited to the plasma membrane in response to integrin engagement [4]. We demonstrate that collagen type 1, a potent inducer of Rac1-dependent cell motility in HeLa cells, counteracts cytoskeletal collapse resulting from overexpression of wild-type p190B, but not that resulting from overexpression of a p19013 mutant specifically lacking the Rac1-binding sequence. Furthermore, this p190B mutant exhibits dramatically enhanced RhoGAP activity, consistent with a model whereby binding of Rac1 relieves autoinhibition of p19013 RhoGAP function. Collectively, these observations establish that activated Rac1, through direct interaction with p190B, modulates subcellular RhoGAP localization and activity, thereby providing a novel mechanism for Rac control of Rho signaling in a broad range of physiological processes.
C1 [Bustos, Rodrigo I.; Forget, Marie-Annick; Hansen, Steen H.] Childrens Hosp Boston, GI Cell Biol Lab, Boston, MA 02115 USA.
[Bustos, Rodrigo I.; Forget, Marie-Annick; Hansen, Steen H.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Settleman, Jeffrey E.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Settleman, Jeffrey E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Hansen, SH (reprint author), Childrens Hosp Boston, GI Cell Biol Lab, Boston, MA 02115 USA.
EM steen.hansen@childrens.harvard.edu
FU NIH [CA62142, CA092354]; Roy and Lynne Frank Foundation and Children's
Hospital
FX We are grateful to Tobias Meyer, Martin A. Schwartz, and Arthur S.
Alberts for providing reagents, to Ashley D. Pollock and Jessica Wagner
for technical assistance, and to Lynne Coluccio and Scott R. Frank for
helpful discussions. This work was funded by R01 NIH CA62142 to J.S.,
R01 NIH CA092354 to S.H.H., and funds from The Roy and Lynne Frank
Foundation and Children's Hospital to S.H.H.
NR 26
TC 44
Z9 45
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD OCT 28
PY 2008
VL 18
IS 20
BP 1606
EP 1611
DI 10.1016/j.cub.2008.09.019
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367KR
UT WOS:000260551400033
PM 18948007
ER
PT J
AU Lee, JT
AF Lee, Jeannie T.
TI Jeannie T. Lee
SO CURRENT BIOLOGY
LA English
DT Editorial Material
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA.
RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA.
EM lee@molbio.mgh.harvard.edu
FU Howard Hughes Medical Institute
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD OCT 28
PY 2008
VL 18
IS 20
BP R940
EP R941
DI 10.1016/j.cub.2008.07.087
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367KR
UT WOS:000260551400007
PM 18983954
ER
PT J
AU Rehman, SU
Mueller, T
Januzzi, JL
AF Rehman, Shafiq U.
Mueller, Thomas
Januzzi, James L., Jr.
TI Characteristics of the Novel Interleukin Family Biomarker ST2 in
Patients With Acute Heart Failure
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE heart failure; ST2; NT-proBNP; mortality
ID BRAIN NATRIURETIC PEPTIDE; CRITICALLY-ILL PATIENTS; AMINO-TERMINAL
PROBNP; SOLUBLE ST2; SEPTIC SHOCK; MYOCARDIAL-INFARCTION;
EMERGENCY-DEPARTMENT; 1-YEAR MORTALITY; RESPONSE GENE; MEMBER ST2
AB Objectives The purpose of this study was to examine the patient-specific characteristics of the interleukin-1 receptor family member ST2 in patients with acute heart failure (HF).
Background ST2 signaling is involved in the process of cardiac fibrosis and hypertrophy.
Methods In all, 346 patients with acute HF had ST2 measured. Associations between ST2 and demographics, severity/ type of HF, and other biomarkers were examined. Receiver-operator characteristic curves and multivariable Cox proportional hazards analyses evaluated the prognostic ability of ST2.
Results The ST2 values correlated with the severity of HF p < 0.001), left ventricular ejection fraction (r = -0.134; p = 0.014), creatinine clearance (r = -0.224; p < 0.001), B-type natriuretic peptide (r = 0.293; p < 0.001), amino terminal B-type natriuretic peptide ( r = 0.413; p < 0.001), and C-reactive protein ( r = 0.429; p < 0.001). ST2 was not associated with age, prior HF, or body mass index. The ST2 levels at presentation were higher among patients who died by 1 year. The area under the receiver-operator characteristic for death at 1 year was 0.71 (p < 0.001). In a multivariable Cox model containing established clinical and biochemical predictors (including natriuretic peptides), ST2 remained a predictor of mortality (hazard ratio: 2.04, 95% confidence interval: 1.30 to 3.24, p = 0.003), and was equally predictive in patients with HF and preserved or impaired systolic function. When both ST2 and natriuretic peptides were elevated, the highest rates of death were observed in cumulative hazard analysis (p < 0.001). In the presence of a low ST2 level, natriuretic peptides did not predict mortality.
Conclusions Consistent with its proposed role in a myocardial-specific response to stretch, ST2 has strong clinical and biochemical correlates in patients with acute HF. Prognostically, ST2 is powerful in acute HF and is synergistic with natriuretic peptides for this use. (J Am Coll Cardiol 2008; 52: 1458-65) (C) 2008 by the American College of Cardiology Foundation
C1 [Rehman, Shafiq U.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Rehman, Shafiq U.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Mueller, Thomas] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria.
RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA.
EM JJanuzzi@partners.org
NR 34
TC 138
Z9 157
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 28
PY 2008
VL 52
IS 18
BP 1458
EP 1465
DI 10.1016/j.jacc.2008.07.042
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 363HQ
UT WOS:000260258800005
PM 19017513
ER
PT J
AU Smith, EE
Vijayappa, M
Lima, F
Delgado, P
Wendell, L
Rosand, J
Greenberg, SM
AF Smith, E. E.
Vijayappa, M.
Lima, F.
Delgado, P.
Wendell, L.
Rosand, J.
Greenberg, S. M.
TI Impaired visual evoked flow velocity response in cerebral amyloid
angiopathy
SO NEUROLOGY
LA English
DT Article
ID WHITE-MATTER LESIONS; LOBAR INTRACEREBRAL HEMORRHAGE; TRANSCRANIAL
DOPPLER; PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; VASOMOTOR REACTIVITY;
TRANSGENIC MICE; DEMENTIA; BRAIN; PROGRESSION
AB Objective: Animal models of cerebral amyloid angiopathy (CAA) exhibit abnormal vascular reactivity. We determined whether vascular reactivity, measured by transcranial Doppler ultrasound (TCD), is reduced in humans with CAA.
Methods: Cases were recruited from an established prospective study of CAA. Healthy controls were recruited from a study of normal aging. Evoked mean flow velocity increase in the posterior cerebral artery (PCA) was measured while subjects viewed a flashing alternating checkerboard stimulus. In a separate but partially overlapping cohort we measured the mean flow velocity increase in the middle cerebral artery (MCA) while subjects inhaled carbon dioxide.
Results: The visual evoked mean flow velocity increase was 8.0 +/- 6.1% in CAA (n = 11) compared to 17.4 +/- 5.7% in controls (n = 9, p = 0.002). The PCA pulsatility index, a marker of distal vascular resistance, was higher in CAA (CAA 1.35 +/- 0.35, control 1.04 +/- 0.14, p = 0.03). Among CAA subjects, lower visual evoked mean flow velocity increase was associated with a higher number of hemorrhages seen on MRI (r = -0.87, p = 0.0005) and higher MRI white matter hyperintensity volume (r = -0.67, p = 0.02). The MCA response to carbon dioxide did not differ between CAA and control in 20 subjects (9 CAA, 11 control, p = 0.54).
Conclusions: Cerebral amyloid angiopathy (CAA) was associated with decreased vascular reactivity in response to visual stimulation, possibly reflecting the occipital predilection of the disease. The association of posterior cerebral artery (PCA) evoked flow velocity response with elevated PCA pulsatility index and MRI markers of small vessel disease suggests that abnormal PCA evoked flow velocity in CAA is caused by pathology of the distal resistance vessels. Neurology r 2008; 71:1424-1430
C1 [Smith, E. E.; Vijayappa, M.; Lima, F.; Delgado, P.; Wendell, L.; Rosand, J.; Greenberg, S. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Hemorrhag Stroke Res Program, Boston, MA 02114 USA.
[Rosand, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Smith, EE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Hemorrhag Stroke Res Program, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM eesmith@partners.org
OI Smith, Eric/0000-0003-3956-1668
FU United States National Institute of Neurological Disorders and Stroke
[K23 NS046327]; National Institute of Aging [R01 AG026484]
FX Funded by grants from the United States National Institute of
Neurological Disorders and Stroke K23 NS046327 (E.E.S.) and the National
Institute of Aging R01 AG026484 (S.M.G.).
NR 40
TC 50
Z9 50
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 28
PY 2008
VL 71
IS 18
BP 1424
EP 1430
DI 10.1212/01.wnl.0000327887.64299.a4
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 365RS
UT WOS:000260426100008
PM 18955685
ER
PT J
AU Grueneberg, DA
Degott, S
Pearlberg, J
Li, W
Davies, JE
Baldwin, A
Endege, W
Doench, J
Sawyer, J
Hu, Y
Boyce, F
Xian, J
Munger, K
Harlow, E
AF Grueneberg, Dorre A.
Degott, Sebastien
Pearlberg, Joseph
Li, Wenliang
Davies, Joan E.
Baldwin, Amy
Endege, Wilson
Doench, John
Sawyer, Jacqueline
Hu, Yanhui
Boyce, Frederick
Xian, Jun
Munger, Karl
Harlow, Ed
TI Kinase requirements in human cells: I. Comparing kinase requirements
across various cell types
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer; essential kinases; shRNA screens; fingerprints
ID MAMMALIAN-CELLS; GENETIC SCREEN; RNAI SCREEN; EXPRESSION; THERAPY
AB shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: (i) in repeat experiments using the same cells, (ii) with multiple populations of freshly prepared primary, epithelial cells isolated from the same tissue source, and (iii) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this study suggest that the control of proliferation and survival may be significantly different between cell lines and that simple comparisons from any one cell to another may be misleading. Although the regulation of cell proliferation and survival are heavily studied areas, we did not see a bias in these screens toward the identification of previously known and well studied kinases, suggesting that our knowledge of molecular events in these areas is still meager.
C1 [Grueneberg, Dorre A.; Degott, Sebastien; Pearlberg, Joseph; Li, Wenliang; Davies, Joan E.; Endege, Wilson; Doench, John; Sawyer, Jacqueline; Hu, Yanhui; Xian, Jun; Harlow, Ed] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Baldwin, Amy; Munger, Karl] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Boyce, Frederick] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Harlow, E (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA.
EM eharlow@hms.harvard.edu
RI Li, Wenliang/A-1022-2010;
OI Munger, Karl/0000-0003-3288-9935; Doench, John/0000-0002-3707-9889
FU AstraZeneca Pharmaceuticals
FX The authors would like to thank L. Bergeron and L. Ronco for their
advice and support in the generation of the screening data for lung
cancer cell lines. The work in Figures 2, 4, and S7 was supported by a
sponsored research agreement from AstraZeneca Pharmaceuticals.
NR 25
TC 53
Z9 54
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 28
PY 2008
VL 105
IS 43
BP 16472
EP 16477
DI 10.1073/pnas.0808019105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PM
UT WOS:000260913500015
PM 18948591
ER
PT J
AU Bommi-Reddy, A
Almeciga, I
Sawyer, J
Geisen, C
Li, WL
Harlow, E
Kaelin, WG
Grueneberg, DA
AF Bommi-Reddy, Archana
Almeciga, Ingrid
Sawyer, Jacqueline
Geisen, Christoph
Li, Wenliang
Harlow, Ed
Kaelin, William G., Jr.
Grueneberg, Dorre A.
TI Kinase requirements in human cells: III. Altered kinase requirements in
VHL-/- cancer cells detected in a pilot synthetic lethal screen
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE essential kinases; shRNA screens; VHL; kidney cancer; therapeutics
ID RENAL-CARCINOMA CELLS; TUMOR-SUPPRESSOR GENE; HYPOXIA-INDUCIBLE
FACTOR-1-ALPHA; HIPPEL-LINDAU-DISEASE; CYCLIN D1; GROWTH; PROTEIN;
TARGETS; RNAI; PHOSPHORYLATION
AB Clear cell renal carcinomas are the most common form of kidney cancer and frequently are linked to biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene product, pVHL, has multiple functions including directing the polyubiquitylation of the HIF transcription factor. We screened 100 shRNA vectors, directed against 88 kinases, for their ability to inhibit the viability of VHL-/- renal carcinoma cells preferentially compared with isogenic cells in which pVHL function was restored. shRNAs for "hits" identified in the primary screen were interrogated in secondary screens that included shRNA titration studies. Multiple shRNAs against CDK6, MET, and MAP2K1 (also known as MEK1) preferentially inhibited the viability of 786-O and RCC4 VHL-/- cells compared with their wild-type pVHL-reconstituted counterparts. The sensitivity of pVHL-proficient cells to these shRNAs was not restored upon HIF activation, suggesting that loss of an hypoxia-inducible factor (HIF)-independent pVHL function formed the basis for selectivity. A small-molecule Cdk4/6 inhibitor displayed enhanced activity against VHL-/- renal carcinoma cells, suggesting that in some cases hits from shRNA screens such as described here might translate into therapeutic targets.
C1 [Sawyer, Jacqueline; Li, Wenliang; Harlow, Ed; Grueneberg, Dorre A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Bommi-Reddy, Archana; Almeciga, Ingrid; Geisen, Christoph; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Geisen, Christoph; Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Harlow, E (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM eharlow@hms.harvard.edu; william_kaelin@dfci.harvard.edu
FU National Institutes of Health [R21CA104940]
FX We thank Donna Neuberg for help with statistical analysis. A.B.-R. was
supported by the American Foundation for Urologic Disease and the Tisch
Family Fund for research in solid tumors. W.G.K. is a Howard Hughes
Medical Institute investigator and was supported by the Murray
Foundation. This work is supported by National Institutes of Health
Grant R21CA104940 (to W.G.K and A.B-R.).
NR 35
TC 83
Z9 86
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 28
PY 2008
VL 105
IS 43
BP 16484
EP 16489
DI 10.1073/pnas.0806574105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PM
UT WOS:000260913500017
PM 18948595
ER
PT J
AU Okazaki, M
Ferrandon, S
Vilardaga, JP
Bouxsein, ML
Potts, JT
Gardella, TJ
AF Okazaki, Makoto
Ferrandon, Sebastien
Vilardaga, Jean-Pierre
Bouxsein, Mary L.
Potts, John T., Jr.
Gardella, Thomas J.
TI Prolonged signaling at the parathyroid hormone receptor by peptide
ligands targeted to a specific receptor conformation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID PROTEIN-RECEPTOR; FUNCTIONAL SELECTIVITY; BINDING MECHANISM; CANCELLOUS
BONE; PTH; RAT; INTERNALIZATION; OSTEOPOROSIS; INTERMITTENT; INFUSION
AB The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both the amino-terminal extracellular (N) domain, and transmembrane/extracellular loop, or juxtamembrane (J) regions of the receptor. Recently, we found that PTH(1-34), but not PTH-related protein, PTHrP(1-36), or M-PTH(1-14) (M = Ala/ Aib(1),Aib(3),Gln(10),Har(11),Ala(12),Trp(14),Arg(19)), binds to the PTHR in a largely GTP gamma S-resistant fashion, suggesting selective binding to a novel, high-affinity conformation (R-0), distinct from the GTP gamma S-sensitive conformation (RG). We examined the effects in vitro and in vivo of introducing the M substitutions, which enhance interaction to the J domain, into IPTH analogs extended C-terminally to incorporate residues involved in the N domain interaction. As compared with PTH(1-34), M-PTH(1-28) and M-PTH(1-34) bound to R-0 with higher affinity, produced more sustained cAMP responses in cells, formed more stable complexes with the PTHR in FRET and subcellular localization assays, and induced more prolonged calcemic and phosphate responses in mice. Moreover, after 2 weeks of daily injection in mice, M-PTH(1-34) induced larger increases in trabecular bone volume and greater increases in cortical bone turnover, than did PTH(1-34). Thus, the putative R-0 PTHR conformation can form highly stable complexes with certain PTH ligand analogs and thereby mediate surprisingly prolonged signaling responses in bone and/or kidney PTH target cells. Controlling, via ligand analog design, the selectivity with which a PTH ligand binds to R-0, versus RG, may be a strategy for optimizing signaling duration time, and hence therapeutic efficacy, of PTHR agonist ligands.
C1 [Okazaki, Makoto; Ferrandon, Sebastien; Vilardaga, Jean-Pierre; Potts, John T., Jr.; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Ferrandon, Sebastien; Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Bouxsein, Mary L.] Harvard Univ, Sch Med, Orthopad Biomech Lab, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA.
RP Potts, JT (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
EM potts.john@mgh.harvard.edu; gardella@helix.mgh.harvard.edu
FU National Institutes of Health [DK-11794]
FX We thank Ashok Khatri of the Massachusetts General Hospital
BiopolymerCore Facility for peptide synthesis and Dr. Ernestina Schipani
of the Massachusetts General Hospital Skeletal Phenotyping Core Facility
for bone histology. This work was supported by National Institutes of
Health Grant DK-11794.
NR 35
TC 52
Z9 52
U1 1
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 28
PY 2008
VL 105
IS 43
BP 16525
EP 16530
DI 10.1073/pnas.0808750105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PM
UT WOS:000260913500024
PM 18946036
ER
PT J
AU Morokuma, J
Blackiston, D
Adams, DS
Seebohm, G
Trimmer, B
Levin, M
AF Morokuma, Junji
Blackiston, Douglas
Adams, Dany S.
Seebohm, Guiscard
Trimmer, Barry
Levin, Michael
TI Modulation of potassium channel function confers a hyperproliferative
invasive phenotype on embryonic stem cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer; ion channel; melanocyte; neural crest; KCNQ
ID HUMAN BREAST-CANCER; NERVOUS-SYSTEM; ELECTRICAL-STIMULATION;
PROTEIN-SYNTHESIS; FROG ERYTHROCYTE; PROGENITOR CELLS; XENOPUS-LAEVIS;
K+ CURRENT; EXPRESSION; VOLTAGE
AB Ion transporters, and the resulting voltage gradients and electric fields, have been implicated in embryonic development and regeneration. These biophysical signals are key physiological aspects of the microenvironment that epigenetically regulate stem and tumor cell behavior. Here, we identify a previously unrecognized function for KCNQ1, a potassium channel known to be involved in human Romano-Ward and Jervell-Lange-Nielsen syndromes when mutated. Misexpression of its modulatory wild-type beta-subunit XKCNE1 in the Xenopus embryo resulted in a striking alteration of the behavior of one type of embryonic stem cell: the pigment cell lineage of the neural crest. Depolarization of embryonic cells by misexpression of KCNE1 non-cell-autonomously induced melanocytes to overproliferate, spread out, and become highly invasive of blood vessels, liver, gut, and neural tube, leading to a deeply hyperpigmented phenotype. This effect is mediated. by the up-regulation of Sox10 and Slug genes, thus linking alterations in ion channel function to the control of migration, shape, and mitosis rates during embryonic morphogenesis. Taken together, these data identify a role for the KCNQ1 channel in regulating key cell behaviors and reveal the molecular identity of a biophysical switch, by means of which neoplastic-like properties can be conferred upon a specific embryonic stem cell subpopulation.
C1 [Morokuma, Junji; Blackiston, Douglas; Adams, Dany S.; Levin, Michael] Harvard Univ, Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, Boston, MA 02115 USA.
[Morokuma, Junji; Blackiston, Douglas; Adams, Dany S.; Levin, Michael] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Seebohm, Guiscard] Univ Tubingen, Inst Physiol 1, D-72076 Tubingen, Germany.
[Seebohm, Guiscard] Ruhr Univ Bochum, D-44780 Bochum, Germany.
[Trimmer, Barry] Tufts Univ, Dept Biol, Medford, MA 02155 USA.
RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, 140 Fenway, Boston, MA 02115 USA.
EM mlevin@forsyth.org
FU NIDCR NIH HHS [5T32DE007327-07, 5K22DE16633, K22 DE016633-04, K22
DE016633, T32 DE007327]; NIGMS NIH HHS [R01-GM07742]
NR 70
TC 52
Z9 54
U1 2
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 OCT 28
PY 2008
VL 105
IS 43
BP 16608
EP 16613
DI 10.1073/pnas.0808328105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PM
UT WOS:000260913500038
PM 18931301
ER
PT J
AU Joos, B
Fischer, M
Kuster, H
Pillai, SK
Wong, JK
Boni, J
Hirschel, B
Weber, R
Trkola, A
Gunthard, HF
AF Joos, Beda
Fischer, Marek
Kuster, Herbert
Pillai, Satish K.
Wong, Joseph K.
Boeni, Juerg
Hirschel, Bernard
Weber, Rainer
Trkola, Alexandra
Guenthard, Huldrych F.
CA Swiss HIV Cohort Study
TI HIV rebounds from latently infected cells, rather than from continuing
low-level replication
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HIV-1; latent reservoir; structured treatment interruption; viral
diversity; coreceptor usage
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; STRUCTURED
TREATMENT INTERRUPTIONS; IN-VIVO; PLASMA VIREMIA; INTRINSIC STABILITY;
CELLULAR RESERVOIRS; TYPE-1 REPLICATION; VIRAL CONTROL; T-CELLS
AB Rapid rebound of plasma viremia in patients after interruption of long-term combination antiretroviral therapy (cART) suggests persistence of low-level replicating cells or rapid reactivation of latently infected cells. To further characterize rebounding virus, we performed extensive longitudinal clonal evolutionary studies of HIV env C2-V3-C3 regions and exploited the temporal relationships of rebounding plasma viruses with regard to pretreatment sequences in 20 chronically HIV-1-infected patients having undergone multiple 2-week structured treatment interruptions (STI). Rebounding virus during the short STI was homogeneous, suggesting mono- or oligoclonal origin during reactivation. No evidence for a temporal structure of rebounding virus in regard to pretreatment sequences was found. Furthermore, expansion of distinct lineages at different STI cycles emerged. Together, these findings imply stochastic reactivation of different clones from long-lived latently infected cells rather than expansion of viral populations replicating at low levels. After treatment was stopped, diversity increased steadily, but pretreatment diversity was, on average, achieved only >2.5 years after the start of STI when marked divergence from preexisting quasispecies also emerged. In summary, our results argue against persistence of ongoing low-level replication in patients on suppressive cART. Furthermore, a prolonged delay in restoration of pretreatment viral diversity after treatment interruption demonstrates a surprisingly sustained evolutionary bottleneck induced by punctuated antiretroviral therapy.
C1 [Joos, Beda; Fischer, Marek; Kuster, Herbert; Weber, Rainer; Trkola, Alexandra; Guenthard, Huldrych F.] Univ Zurich Hosp, Div Infect Dis, Dept Med, CH-8091 Zurich, Switzerland.
[Joos, Beda; Fischer, Marek; Kuster, Herbert; Weber, Rainer; Trkola, Alexandra; Guenthard, Huldrych F.] Univ Zurich Hosp, Hosp Epidemiol, CH-8091 Zurich, Switzerland.
[Pillai, Satish K.; Wong, Joseph K.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
[Boeni, Juerg] Univ Zurich, Natl Ctr Retroviruses, CH-8028 Zurich, Switzerland.
[Hirschel, Bernard] Univ Hosp Geneva, Div Infect Dis, CH-1211 Geneva, Switzerland.
RP Joos, B (reprint author), Univ Zurich Hosp, Div Infect Dis, Dept Med, CH-8091 Zurich, Switzerland.
EM beda.joos@usz.ch; huldrych.guenthard@usz.ch
RI gunthard, huldrych/F-1724-2011; Joos, Beda/D-5547-2009; Kuster,
Herbert/A-3912-2013; Infektiologie, USZ/A-6921-2011; SHCS,
all/G-4072-2011; SHCS, ch/G-4077-2011; SHCS, only/G-4080-2011; Weber,
Rainer/D-5175-2012; Pantaleo, Giuseppe/K-6163-2016; Trkola,
Alexandra/K-2115-2012
OI gunthard, huldrych/0000-0002-1142-6723; Joos, Beda/0000-0002-3082-8875;
Trkola, Alexandra/0000-0003-1013-876X
FU Swiss National Science Foundation (SNF) [3345-65168, 3100AO-103748/1,
PP00B-102647, 320000-116035]; Swiss HIV Cohort Study (SHCS) [290]; SNF
[33CSC0-10878]; EMDO Foundation; Elizabeth Glaser Pediatric AIDS
Foundation; National Institutes of Health [R01 NS51132]
FX We thank the participating patients for their commitment; Christine
Schneider, Christina Grube, and Roland Hafner for excellent patient
care; Esther Beerli, Friederike Burgener, Christine Leemann, Tuyet Trinh
Lu, Barbara Niederost, and Barbel Sauer for laboratory support; and
Ingrid Nievergelt and Christine Vogtli for administrative assistance.
This work was supported by Swiss National Science Foundation (SNF)
Grants 3345-65168 and 3100AO-103748/1 (to H.F.G. and A.T.), PP00B-102647
(to A.T.), and 320000-116035 (to H.F.G.); the Swiss HIV Cohort Study
(SHCS) (SNF Grant 33CSC0-10878) SHCS Project No. 290 (to H.F.G.); a
grant from the EMDO Foundation (to H.F.G., and a research grant from the
Kanton of Zurich. A.T. is the Elizabeth Glaser Scientist supported by
the Elizabeth Glaser Pediatric AIDS Foundation. J.K.W. was supported by
National Institutes of Health Grant R01 NS51132.
NR 62
TC 150
Z9 151
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 28
PY 2008
VL 105
IS 43
BP 16725
EP 16730
DI 10.1073/pnas.0804192105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 372PM
UT WOS:000260913500058
PM 18936487
ER
PT J
AU Nathan, DA
AF Nathan, David A.
TI Glycemic Management of Type 2 Diabetes How Tight Is Right and How to Get
There
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID BLOOD-GLUCOSE CONTROL; MYOCARDIAL-INFARCTION; CONSENSUS ALGORITHM; RISK;
COMPLICATIONS; MELLITUS; ROSIGLITAZONE; THERAPY; UKPDS;
THIAZOLIDINEDIONES
C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
RP Nathan, DA (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St,Ste 340, Boston, MA 02114 USA.
EM dnathan@Partners.org
NR 23
TC 4
Z9 6
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD OCT 27
PY 2008
VL 168
IS 19
BP 2064
EP 2066
DI 10.1001/archinte.168.19.2064
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 364JQ
UT WOS:000260332400001
PM 18955633
ER
PT J
AU Nezam, SMRM
Joo, C
Tearney, GJ
de Boer, JF
AF Nezam, S. M. R. Motaghian
Joo, C.
Tearney, G. J.
de Boer, J. F.
TI Application of maximum likelihood estimator in nano-scale optical path
length measurement using spectral-domain optical coherence phase
microscopy
SO OPTICS EXPRESS
LA English
DT Article
ID TOMOGRAPHY; INTERFEROMETRY; SUBWAVELENGTH; DYNAMICS; IMAGES
AB Spectral-domain optical coherence phase microscopy (SD-OCPM) measures minute phase changes in transparent biological specimens using a common path interferometer and a spectrometer based optical coherence tomography system. The Fourier transform of the acquired interference spectrum in spectral-domain optical coherence tomography (SD-OCT) is complex and the phase is affected by contributions from inherent random noise. To reduce this phase noise, knowledge of the probability density function (PDF) of data becomes essential. In the present work, the intensity and phase PDFs of the complex interference signal are theoretically derived and the optical path length (OPL) PDF is experimentally validated. The full knowledge of the PDFs is exploited for optimal estimation (Maximum Likelihood estimation) of the intensity, phase, and signal-to-noise ratio (SNR) in SD-OCPM. Maximum likelihood (ML) estimates of the intensity, SNR, and OPL images are presented for two different scan modes using Bovine Pulmonary Artery Endothelial (BPAE) cells. To investigate the phase accuracy of SD-OCPM, we experimentally calculate and compare the cumulative distribution functions (CDFs) of the OPL standard deviation and the square root of the Cramer-Rao lower bound (1/2SNR) over 100 BPAE images for two different scan modes. The correction to the OPL measurement by applying ML estimation to SD-OCPM for BPAE cells is demonstrated. (C) 2008 Optical Society of America
C1 [Nezam, S. M. R. Motaghian] Harvard Univ, Sch Med, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
RP Nezam, SMRM (reprint author), Harvard Univ, Sch Med, 55 Fruit St,BAR 7, Boston, MA 02114 USA.
EM rmotaghi@caltech.edu
RI de Boer, Johannes/B-7590-2012
OI de Boer, Johannes/0000-0003-1253-4950
FU National Institute of Health [NCRR 19768]; CIMIT; Center for the
Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]
FX This research was supported in part by the National Institute of Health
under grant number NCRR 19768, and CIMIT, the Center for the Integration
of Medicine and Innovative Technology with funding from the Department
of the Army under its Cooperative Agreement DAMD17-02-2-0006. S. M. R.
Motaghiannezam is currently with the California Institute of Technology,
Pasadena, CA. C. Joo is currently with General Electric Global Research
Lab, Niskayuna, NY. J.F. de Boer is currently with VU University, De
Boelelaan 1081, T-0.67, Amsterdam, The Netherlands, jfdeboer@few.vu.nl.
NR 18
TC 4
Z9 4
U1 0
U2 1
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD OCT 27
PY 2008
VL 16
IS 22
BP 17186
EP 17195
DI 10.1364/OE.16.017186
PG 10
WC Optics
SC Optics
GA 371XL
UT WOS:000260865900006
ER
PT J
AU Horner, BM
Eberlin, KR
Ferguson, KK
Hirsh, EL
Randolph, MA
Butler, PEM
AF Horner, Benjamin M.
Eberlin, Kyle R.
Ferguson, Kelly K.
Hirsh, Erica L.
Randolph, Mark A.
Butler, Peter E. M.
TI Recipient Damage After Musculocutaneous Transplant Rejection
SO TRANSPLANTATION
LA English
DT Article
DE Composite; Tissue; Retransplantation; Recipient; Damage
ID COMPOSITE TISSUE-TRANSPLANTATION; PRIMARY ALLOGRAFT NEPHRECTOMY;
INTERNATIONAL REGISTRY; HAND; RATS; CYCLOSPORINE; TOLERANCE; FK-506
AB Background. In the event of a composite allograft failure, damage to the recipient tissues may make retransplantation impossible. This study aimed to quantify the damage after composite allograft failure to assess whether retransplantation is feasible.
Methods. Rats (n=6) in the group I received composite musculocutaneous flap allotransplants (WF-Lew) with immunosuppression allowing healing-in of the allograft before being tapered allowing rejection. At full rejection, the recipient vascular pedicle was examined, biopsies of the recipient tissue bed were taken and graded for damage, and in vitro assays were performed. Groups II (allograft without immunosuppression, n=7), III (isograft with immunosuppression, n=5), and IV (isograft without inummosuppression, n=6) were included to attempt to identify the contributions of the rejection process, inummosuppression, and healing to recipient tissue damage.
Results. The vascular pedicle was patent to within 1 mm of the anastomosis in all rejected allografts. Furthermore, it was possible to retransplant after full rejection. There was minimal damage to the recipient tissues at the time of full rejection in group I. In contrast, group II had significantly more damage (P < 0.05) to recipient muscle and skin. This correlated with more severe immune reaction with more than 100 times antibody production in group II compared with group I. Groups III and IV had little recipient tissue damage.
Conclusions. These results suggest that it is possible to retransplant after rejection of a musculocutaneous transplant while on immunosuppression. Furthermore, the second transplant will not be limited in form or function by recipient tissue bed damage.
C1 [Horner, Benjamin M.; Eberlin, Kyle R.; Randolph, Mark A.] Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, Boston, MA 02114 USA.
[Horner, Benjamin M.; Ferguson, Kelly K.; Hirsh, Erica L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,CNY, Boston, MA USA.
[Horner, Benjamin M.; Butler, Peter E. M.] UCL, Royal Free Hosp, Dept Plast Surg, London, England.
RP Randolph, MA (reprint author), Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, WAC 435, Boston, MA 02114 USA.
EM marandolph@partners.org
OI Ferguson, Kelly/0000-0001-8467-3250; Butler, Peter/0000-0001-7419-1493
FU Fulbright Commission Postgraduate Award; Royal College of Surgeons of
England Research Fellowship; Berkeley Research Fellowship; Plastic
Surgery Education Foundation Research Award
FX This work was supported by Fulbright Commission Postgraduate Award,
Royal College of Surgeons of England Research Fellowship, Berkeley
Research Fellowship, Plastic Surgery Education Foundation Research Award
(B.H.).
NR 20
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 OCT 27
PY 2008
VL 86
IS 8
BP 1104
EP 1110
DI 10.1097/TP.0b013e3181872ac3
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 367LY
UT WOS:000260554700014
PM 18946349
ER
PT J
AU Ganzini, L
Goy, ER
Dobscha, SK
AF Ganzini, Linda
Goy, Elizabeth R.
Dobscha, Steven K.
TI Prevalence of depression and anxiety in patients requesting physicians'
aid in dying: cross sectional survey
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID MENTAL STATUS QUESTIONNAIRE; REDUCING SUICIDAL IDEATION; TERMINALLY-ILL
PATIENTS; PRIMARY-CARE PATIENTS; ASSISTED SUICIDE; HASTENED DEATH; OLDER
PATIENTS; CANCER; HOPELESSNESS; DESIRE
AB Objective To determine the prevalence of depression and anxiety in terminally ill patients pursuing aid in dying from physicians.
Design Cross sectional survey.
Setting State of Oregon, USA.
Participants 58 Oregonians, most terminally ill with cancer or amyotrophic lateral sclerosis, who had either requested aid in dying from a physician or contacted an aid in dying advocacy organisation.
Main outcome measures Diagnosis of depression or anxiety according to the hospital anxiety and depression scale and the structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders.
Results 15 study participants met "caseness" criteria for depression, and 13 met criteria for anxiety. 42 patients died by the end of the study; 18 received a prescription fora lethal drug under the Death with Dignity Act, and nine died by lethal ingestion. 15 participants who received a prescription for a lethal drug did not meet criteria for depression; three did. All three depressed participants died by legal ingestion within two months of the research interview.
Conclusion Although most terminally ill Oregonians who receive aid in dying do not have depressive disorders, the current practice of the Death with Dignity Act may fail to protect some patients whose choices are influenced by depression from receiving a prescription for a lethal drug.
C1 [Ganzini, Linda; Goy, Elizabeth R.; Dobscha, Steven K.] Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Mental & Phys D, Hlth Serv Res & Dev, Portland, OR 97239 USA.
[Ganzini, Linda; Goy, Elizabeth R.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
RP Ganzini, L (reprint author), Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Mental & Phys D, Hlth Serv Res & Dev, POB 1034, Portland, OR 97239 USA.
EM Linda.Ganzini@va.gov
FU Northwest Health Foundation
FX Northwest Health Foundation. The funding source had no role in any
aspect of the study or this paper.
NR 37
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U1 2
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PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD OCT 25
PY 2008
VL 337
IS 7676
AR a1682
DI 10.1136/bmj.a1682
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 363WS
UT WOS:000260298800034
PM 18842645
ER
PT J
AU Shen, J
Brugge, WR
Dimaio, CJ
Pitman, MB
AF Shen, Jian
Brugge, William R.
Dimaio, Christopher J.
Pitman, Martha B.
TI Molecular Analysis of Pancreatic Cyst Fluid
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Shen, Jian; Brugge, William R.; Dimaio, Christopher J.; Pitman, Martha B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2008
VL 114
IS 5
SU S
BP 346
EP 347
PG 2
WC Oncology; Pathology
SC Oncology; Pathology
GA 361PY
UT WOS:000260140800008
ER
PT J
AU Moriarty, AT
Darragh, TM
Souers, R
Fatheree, LA
Wilbur, DC
AF Moriarty, Ann T.
Darragh, Teresa M.
Souers, Rhona
Fatheree, Lisa A.
Wilbur, David C.
TI Performance of Herpes Simplex Challenges in Proficiency Testing:
Observations from the College of American Pathologists (CAP) Proficiency
Testing (PAP PT) Program
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Moriarty, Ann T.] Ameripath Indiana, Indianapolis, IN USA.
[Darragh, Teresa M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Souers, Rhona] Coll Amer Pathologists, Northfield, IL USA.
[Fatheree, Lisa A.] Coll Amer Pathologists, Indianapolis, IL USA.
[Wilbur, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2008
VL 114
IS 5
SU S
BP 394
EP 394
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 361PY
UT WOS:000260140800083
ER
PT J
AU Reyes, CV
Jensen, JD
AF Reyes, Cesar V.
Jensen, Joanne D.
TI On-Site Evaluation of Bronchial Brushing cytology
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Reyes, Cesar V.] Morris Hosp, Morris, IL USA.
[Reyes, Cesar V.] Vet Affairs Edward Hines Jr Hosp, Morris, IL USA.
[Jensen, Joanne D.] Morris Hosp, Hines, IL USA.
[Jensen, Joanne D.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2008
VL 114
IS 5
SU S
BP 408
EP 408
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 361PY
UT WOS:000260140800103
ER
PT J
AU Knoepp, SM
Mino-Kenudson, M
Balassanian, R
AF Knoepp, Stewart M.
Mino-Kenudson, Mari
Balassanian, Ronald
TI Distinguishing Squamous Cell Carcinoma from Adenocarcinoma in Lung Fine
Needle Aspiration Biopsy. A Cytologic/Histologic Review of 109 Cases
SO CANCER CYTOPATHOLOGY
LA English
DT Meeting Abstract
C1 [Knoepp, Stewart M.; Mino-Kenudson, Mari; Balassanian, Ronald] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2008
VL 114
IS 5
SU S
BP 409
EP 410
PG 2
WC Oncology; Pathology
SC Oncology; Pathology
GA 361PY
UT WOS:000260140800105
ER
PT J
AU Theodore, S
Cao, SW
McLean, P
Standaert, D
AF Theodore, Shaji
Cao Shuwen
McLean, Pamela
Standaert, David
TI Microglial activation and adaptive immune response in a mouse model of
Parkinson's disease
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Theodore, Shaji; Cao Shuwen; Standaert, David] Univ Alabama, Birmingham, W Midlands, England.
[McLean, Pamela] Massachusetts Gen Hosp, Charlestown, MA USA.
RI Cao, Shuwen/E-1924-2016
NR 0
TC 1
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U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 25
PY 2008
VL 203
IS 2
BP 188
EP 189
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600175
ER
PT J
AU Offner, H
AF Offner, Halina
TI Immunoregulatory and neuroprotective effect of sex steroids on EAE and
MS
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Meeting Abstract
C1 [Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA.
[Offner, Halina] Portland VA Med Ctr, Portland, OR USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD OCT 25
PY 2008
VL 203
IS 2
BP 205
EP 206
PG 2
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 377SJ
UT WOS:000261270600220
ER
PT J
AU Lin, HH
Murray, M
Cohen, T
Colijn, C
Ezzati, M
AF Lin, Hsien-Ho
Murray, Megan
Cohen, Ted
Colijn, Caroline
Ezzati, Majid
TI Effects of smoking and solid-fuel use on COPD, lung cancer, and
tuberculosis in China: a time-based, multiple risk factor, modelling
study
SO LANCET
LA English
DT Article
ID AIR-POLLUTION; HEALTH SYSTEM; RURAL CHINA; HONG-KONG; MORTALITY;
INTERVENTIONS; DISEASE; TOBACCO; BURDEN; CESSATION
AB Background Chronic obstructive pulmonary disease (COPD), lung cancer, and tuberculosis are three leading causes of death in China, where prevalences of smoking and solid-fuel use are also high. We aimed to predict the effects of risk-factor trends on COPD, lung cancer, and tuberculosis.
Methods We used representative data sources to estimate past trends in smoking and household solid-fuel use and to construct a range of future scenarios. We obtained the aetiological effects of risk factors on diseases from meta-analyses of epidemiological studies and from large studies in China. We modelled future COPD and lung cancer mortality and tuberculosis incidence, taking into account the accumulation of hazardous effects of risk factors on COPD and lung cancer over time, and dependency of the risk of tuberculosis infection on the prevalence of disease. We quantified the sensitivity of our results to methods and data choices.
Findings If smoking and solid-fuel use remain at current levels between 2003 and 2033, 65 million deaths from COPD and 18 million deaths from lung cancer are predicted in China; 82% of COPD deaths and 75% of lung cancer deaths will be attributable to the combined effects of smoking and solid-fuel use. Complete gradual cessation of smoking and solid-fuel use by 2033 could avoid 26 million deaths from COPD and 6.3 million deaths from lung cancer; interventions of intermediate magnitude would reduce deaths by 6-31% (COPD) and 8-26% (lung cancer). Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence in 2033 by 1.4-52% if 80% DOTS coverage is sustained, 27-62% if 50% coverage is sustained, or 33-71% if 20% coverage is sustained.
Interpretation Reducing smoking and solid-fuel use can substantially lower predictions of COPD and lung cancer burden and would contribute to effective tuberculosis control in China.
Funding International Union Against Tuberculosis and Lung Disease.
C1 [Ezzati, Majid] Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02115 USA.
[Lin, Hsien-Ho; Murray, Megan; Cohen, Ted] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Ezzati, Majid] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Lin, Hsien-Ho] Mennonite Christian Hosp, Community Hlth Soc, Hualien, Taiwan.
[Murray, Megan] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Murray, Megan; Cohen, Ted] Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA.
[Colijn, Caroline] Univ Bristol, Dept Engn Math, Bristol, Avon, England.
[Ezzati, Majid] Harvard Univ, Initiat Global Hlth, Cambridge, MA 02138 USA.
RP Ezzati, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM majid_ezzati@harvard.edu
RI Cohen, Ted/G-8101-2011;
OI LIN, HSIEN-HO/0000-0002-7481-6016
FU International Union Against Tuberculosis and Lung Disease; World Bank
FX This research was funded by the International Union Against Tuberculosis
and Lung Disease, through a grant from the World Bank. We thank
Cheng-Yuan Chiang, Donald Enarson, Ems Baris, and Ziad Obermeyer for
Valuable discussion on methods and models, Colin Mathers for mortality
projections, Zheng Zhou for help with data on smoking and fuel use,
Jonathan Sinton for discussions on fuels use trends in China, and the
Chinese Ministry of Health for tuberculosis prevalence data. We thank
the China Health and Nutrition Survey, Jill Boreham, Rachel Huxley, and
Zhengming Chen for valuable information and data on risk factor exposure
and effects.
NR 79
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U1 3
U2 27
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD OCT 25
PY 2008
VL 372
IS 9648
BP 1473
EP 1483
DI 10.1016/S0140-6736(08)61345-8
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 370ZJ
UT WOS:000260801300024
PM 18835640
ER
PT J
AU Bhattacharya, D
Hoover, S
Falk, SP
Weisblum, B
Vestling, M
Striker, R
AF Bhattacharya, Dipankar
Hoover, Spencer
Falk, Shaun P.
Weisblum, Bernard
Vestling, Martha
Striker, Rob
TI Phosphorylation of yellow fever virus NS5 alters methyltransferase
activity
SO VIROLOGY
LA English
DT Article
DE Phosphorylation; Methyltransferase; RNA cap; Flavivirus
ID RNA CAP; CRYSTAL-STRUCTURE; PROTEINS; SEQUENCE; SUBSTRATE;
TRANSCOMPLEMENTATION; HYPERPHOSPHORYLATION; TRANSCRIPTION; METHYLATIONS;
REPLICATION
AB Serine/threonine phosphorylation of the nonstructural protein 5 (NS5) is conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. Mass spectrometry was used to characterize phosphorylated residues of yellow fever virus (YFV) NS5 expressed in mammalian cells. Multiple different phosphopeptides were detected. Mutational and additional mass spectrometry data implicated serine 56 (S56), a conserved residue near the active site in the NS5 methyltransferase domain, as one of the phosphorylation sites. Methyltransferase activity is required to form a methylated RNA cap structure and for translation of the YFV polyprotein. We show the 2'-O methylation reaction requires the hydroxyl side chain of S56, and replacement with a negative charge inhibits enzymatic activity. Furthermore mutational alteration of S56, S56A or S56D, prevents amplification in a viral replicon system. Collectively our data suggest phosphorylation of NS5 S56 may act to shut down capping in the viral life cycle. Published by Elsevier Inc.
C1 [Bhattacharya, Dipankar; Hoover, Spencer; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI 53706 USA.
[Falk, Shaun P.; Weisblum, Bernard] Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA.
[Vestling, Martha] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA.
[Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP Striker, R (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53706 USA.
EM rtstriker@wisc.edu
FU NIH/NIAID Regional Center of Excellence
FX This work was sponsored by the NIH/NIAID Regional Center of Excellence
for Biodefense and Emerging Infectious Diseases Research (RCE) Program.
The authors wish to acknowledge membership within and support from the
Region V 'Great Lakes' RCE (NIH award 1-U54-AI-057153). We thank the UW
Madison Biotechnology mass spectrometry facility and the Human
Proteomics Mass Spectrometry Facility supported by the "The Wisconsin
Partnership Fund for a Healthy Future" for technical assistance. We also
thank Janet Smith and Richard Kuhn for helpful discussions, and Deane
Mosher for comments on drafts of this manuscript.
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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 OCT 25
PY 2008
VL 380
IS 2
BP 276
EP 284
DI 10.1016/j.virol.2008.07.013
PG 9
WC Virology
SC Virology
GA 361SW
UT WOS:000260148400013
PM 18757072
ER
PT J
AU Chudakova, DA
Zeidan, YH
Wheeler, BW
Yu, J
Novgorodov, SA
Kindy, MS
Hannun, YA
Gudz, TI
AF Chudakova, Daria A.
Zeidan, Youssef H.
Wheeler, Brian W.
Yu, Jin
Novgorodov, Sergei A.
Kindy, Mark S.
Hannun, Yusuf A.
Gudz, Tatyana I.
TI Integrin-associated Lyn Kinase Promotes Cell Survival by Suppressing
Acid Sphingomyelinase Activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SRC FAMILY KINASES; OLIGODENDROCYTE PROGENITOR MIGRATION; CYTOPLASMIC
DOMAIN; CEREBRAL-ISCHEMIA; TYROSINE KINASES; SALVAGE PATHWAY; FACTOR
RECEPTOR; BRAIN-INJURY; C-DELTA; CERAMIDE
AB Integrins govern cellular adhesion and transmit signals leading to activation of intracellular signaling pathways aimed to prevent apoptosis. Herein we report that attachment of oligodendrocytes (OLs) to fibronectin via alpha(v)beta(3) integrin receptors rendered the cells more resistant to apoptosis than the cells attached to laminin via alpha(6)beta(1) integrins. Investigation of molecular mechanisms involved in alpha(v)beta(3) integrin-mediated cell survival revealed that ligation of the integrin with fibronectin results in higher expression of activated Lyn kinase. Both in OLs and in the mouse brain, Lyn selectively associates with alpha(v)beta(3) integrin, not with alpha(v)beta(5) integrin, leading to suppression of acid sphingomyelinase activity and preventing ceramide-mediated apoptosis. In OLs, knockdown of Lyn with small interfering RNA resulted in OL apoptosis with concomitant accumulation of C-16-ceramide due to activation of acid sphingomyelinase (ASMase) and sphingomyelin hydrolysis. Knocking down ASMase partially protected OLs from apoptosis. In the brain, ischemia/reperfusion (IR) triggered rearrangements in the alpha(v)beta(3) integrin-Lyn kinase complex leading to disruption of Lyn kinase-mediated suppression of ASMase activity. Thus, co-immunoprecipitation studies revealed an increased association of alpha(v)beta(3) integrin-Lyn kinase complex with ionotropic glutamate receptor subunits, GluR2 and GluR4, after cerebral IR. Sphingolipid analysis of the brain demonstrated significant accumulation of ceramide and sphingomyelin hydrolysis. The data suggest a novel mechanism for regulation of ASMase activity during cell adhesion in which Lyn acts as a key upstream kinase that may play a critical role in cerebral IR injury.
C1 [Chudakova, Daria A.; Wheeler, Brian W.; Yu, Jin; Kindy, Mark S.; Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Kindy, Mark S.; Gudz, Tatyana I.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
[Novgorodov, Sergei A.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Zeidan, Youssef H.; Novgorodov, Sergei A.; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
RP Gudz, TI (reprint author), Med Univ S Carolina, Dept Neurosci, 114 Doughty St, Charleston, SC 29425 USA.
EM gudz@musc.edu
FU National Institutes of Health/NCCR COBRE in Lipidomics and Pathobiology
[P20 RR 17677-04]; National Institutes of Health [P01-CA97132, AG16583];
National Science Foundation EPSCOR [EPS0132573]; Veterans Affairs Merit
Awards
FX This work was supported, in whole or in part, by National Institutes of
Health/NCCR COBRE in Lipidomics and Pathobiology Grant P20 RR 17677-04
(to T. I. G.) and National Institutes of Health Grant P01-CA97132 (to
Y.A.H.). This work was also supported by National Science Foundation
EPSCOR Grant EPS0132573 (to M. S. K.), and Veterans Affairs Merit Awards
(to T. I. G. and M. S. K.). The costs of publication of this article
were defrayed in part by the payment of page charges. This article must
therefore be hereby marked "advertisement" in accordance with 18 U. S.
C. Section 1734 solely to indicate this fact.; Supported by National
Institutes of Health Grant AG16583.
NR 63
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U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2008
VL 283
IS 43
BP 28806
EP 28816
DI 10.1074/jbc.M803301200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 362EB
UT WOS:000260179900005
PM 18682390
ER
PT J
AU Makino, CL
Peshenko, IV
Wen, XH
Olshevskaya, EV
Barrett, R
Dizhoor, AM
AF Makino, Clint L.
Peshenko, Igor V.
Wen, Xiao-Hong
Olshevskaya, Elena V.
Barrett, Ronald
Dizhoor, Alexander M.
TI A Role for GCAP2 in Regulating the Photoresponse GUANYLYL CYCLASE
ACTIVATION AND ROD ELECTROPHYSIOLOGY IN GUCA1B KNOCK-OUT MICE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RETINAL RODS; PHOTOTRANSDUCTION CASCADE; CGMP-PHOSPHODIESTERASE;
PROTEINS GCAPS; CALCIUM; PHOTORECEPTORS; EXPRESSION; DEGENERATION;
CLONING; DOMAIN
AB Cyclic GMP serves as the second messenger in visual transduction, linking photon absorption by rhodopsin to the activity of ion channels. Synthesis of cGMP in photoreceptors is supported by a pair of retina-specific guanylyl cyclases, retGC1 and -2. Two neuronal calcium sensors, GCAP1 and GCAP2, confer Ca2+ sensitivity to guanylyl cyclase activity, but the importance and the contribution of each GCAP is controversial. To explore this issue, the gene GUCA1B, coding for GCAP2, was disrupted in mice, and the capacity for knock-out rods to regulate retGC and generate photoresponses was tested. The knock-out did not compromise rod viability or alter outer segment ultrastructure. Levels of retGC1, retGC2, and GCAP-1 expression did not undergo compensatory changes, but the absence of GCAP2 affected guanylyl cyclase activity in two ways; (a) the maximal rate of cGMP synthesis at low [Ca2+] dropped 2-fold and (b) the half-maximal rate of cGMP synthesis was attained at a higher than normal [Ca2+]. The addition of an antibody raised against mouse GCAP2 produced similar effects on the guanylyl cyclase activity in wild type retinas. Flash responses of GCAP2 knockout rods recovered more slowly than normal. Knock-out rods became more sensitive to flashes and to steps of illumination but tended to saturate at lower intensities, as compared with wild type rods. Therefore, GCAP2 regulation of guanylyl cyclase activity quickens the recovery of flash and step responses and adjusts the operating range of rods to higher intensities of ambient illumination.
C1 [Peshenko, Igor V.; Olshevskaya, Elena V.; Dizhoor, Alexander M.] Salus Univ, PA Coll Optometry, Basic Sci & Hafter Res Labs, Elkins Pk, PA 19027 USA.
[Makino, Clint L.; Wen, Xiao-Hong] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Makino, Clint L.; Wen, Xiao-Hong] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Barrett, Ronald] Wayne State Univ, Dept Anat & Cell Biol, Detroit, MI 48201 USA.
RP Dizhoor, AM (reprint author), Salus Univ, PA Coll Optometry, Basic Sci & Hafter Res Labs, 8360 Old York Rd, Elkins Pk, PA 19027 USA.
EM adizhoor@salus.edu
OI Makino, Clint/0000-0002-6005-9069
FU National Institutes of Health [EY11522, EY011358, EY014104];
Massachusetts Lions Eye Research Fund; Pennsylvania Lions Sight
Conservation and Eye Research Foundation; Pennsylvania Department of
Health
FX This work was supported, in whole or in part, by National Institutes of
Health Grants EY11522, EY011358, and EY014104. This work was also
supported by the Massachusetts Lions Eye Research Fund, the Pennsylvania
Lions Sight Conservation and Eye Research Foundation, and the
Pennsylvania Department of Health. The costs of publication of this
article were defrayed in part by the payment of page charges. This
article must therefore be hereby marked "advertisement" in accordance
with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 52
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U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2008
VL 283
IS 43
BP 29135
EP 29143
DI 10.1074/jbc.M804445200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 362EB
UT WOS:000260179900041
PM 18723510
ER
PT J
AU Larade, K
Jiang, ZG
Zhang, YZ
Wang, WF
Bonner-Weir, S
Zhu, H
Bunn, HF
AF Larade, Kevin
Jiang, Zhigang
Zhang, Yongzhao
Wang, WenFang
Bonner-Weir, Susan
Zhu, Hao
Bunn, H. Franklin
TI Loss of Ncb5or Results in Impaired Fatty Acid Desaturation, Lipoatrophy,
and Diabetes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STEAROYL-COA DESATURASE-1; PANCREATIC BETA-CELLS; ENDOPLASMIC-RETICULUM
STRESS; COENZYME-A DESATURASE; BREAST-CANCER CELLS; FACTOR-KAPPA-B;
CONGENITAL METHEMOGLOBINEMIA; CYTOCHROME-B5 REDUCTASE; GENERALIZED
DEFICIENCY; MENTAL-RETARDATION
AB Targeted ablation of the novel flavoheme reductase Ncb5or knock-out (KO) results in progressive loss of pancreatic beta-cells and white adipose tissue over time. Lipoatrophy persisted in KO animals in which the confounding metabolic effects of diabetes were eliminated by islet transplantation (transplanted knockout (TKO)). Lipid profiles in livers prepared from TKO animals were markedly deficient in triglycerides and diacylglycerides. Despite enhanced expression of stearoyl-Co-A desaturase-1, levels of palmitoleic and oleic acids (Delta 9 fatty acid desaturation) were decreased in TKO relative to wild type controls. Treatment of KO hepatocytes with palmitic acid reduced cell viability and increased apoptosis, a response blunted by coincubation with oleic acid. The results presented here support the hypothesis that Ncb5or supplies electrons for fatty acid desaturation, offer new insight into the regulation of a crucial step in fatty acid biosynthesis, and provide a plausible explanation for both the diabetic and the lipoatrophic phenotype in Ncb5or(-/-) mice.
C1 [Larade, Kevin; Jiang, Zhigang; Zhang, Yongzhao; Bunn, H. Franklin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Wang, WenFang; Zhu, Hao] Univ Kansas, Med Ctr, Sch Allied Hlth, Kansas City, KS 66160 USA.
[Bonner-Weir, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Bunn, HF (reprint author), CHRB 5-215,75 Francis St, Boston, MA 02115 USA.
EM hfbunn@rics.bwh.harvard.edu
FU National Institutes of Health [DK067355, AI56374]; Juvenile Diabetes
Research Foundation [1-2005-121, 3-2005-232]; American Diabetes
Association [7-04-RA-15]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK067355 and AI56374. This work was also supported by
Juvenile Diabetes Research Foundation Grants 1-2005-121 and 3-2005-232
and American Diabetes Association Grant 7-04-RA-15. The costs of
publication of this article were defrayed in part by the payment of page
charges. This article must therefore be hereby marked " advertisement"
in accordance with 18 U. S. C. Section 1734 solely to indicate this
fact.
NR 52
TC 20
Z9 20
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 OCT 24
PY 2008
VL 283
IS 43
BP 29285
EP 29291
DI 10.1074/jbc.M804645200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 362EB
UT WOS:000260179900055
PM 18682384
ER
PT J
AU Pierce, A
Mirzaei, H
Muller, F
De Waal, E
Taylor, AB
Leonard, S
Van Remmen, H
Regnier, F
Richardson, A
Chaudhuri, A
AF Pierce, Anson
Mirzaei, Hamid
Muller, Florian
De Waal, Eric
Taylor, Alexander B.
Leonard, Shanique
Van Remmen, Holly
Regnier, Fred
Richardson, Arlan
Chaudhuri, Asish
TI GAPDH Is Conformationally and Functionally Altered in Association with
Oxidative Stress in Mouse Models of Amyotrophic Lateral Sclerosis
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE protein oxidation; amyotrophic lateral sclerosis; BisANS; protein
unfolding; GAPDH
ID MOTOR-NEURON DEGENERATION; COPPER-BINDING-SITE;
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; SUPEROXIDE-DISMUTASE; PROTEIN
OXIDATION; CREATINE-KINASE; SKELETAL-MUSCLE; TRANSGENIC MICE; SELECTIVE
DEGRADATION; HYDROGEN-PEROXIDE
AB It is proposed that conformational changes induced in proteins by oxidation can lead to loss of activity or protein aggregation through exposure of hydrophobic residues and alteration in surface hydrophobicity. Because increased oxidative stress and protein aggregation are consistently observed in amyotrophic lateral sclerosis (ALS), we used a 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (BisANS) photolabeling approach to monitor changes in protein unfolding in vivo in skeletal muscle proteins in ALS mice. We find two major proteins, creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), conformationally affected in the ALS G93A mouse model concordant with a 43% and 41% reduction in enzyme activity, respectively. This correlated with changes in conformation and activity that were detected in CK and GAPDH with in vitro oxidation. Interestingly, we found that GAPDH, but not CK, is conformationally and functionally affected in a longer-lived ALS model (H46R/H48Q), exhibiting a 22%, reduction in enzyme activity. We proposed a reaction mechanism for BisANS with nucleophilic amino acids Such as lysine, serine, threonine, and tyrosine, and BisANS was found to be primarily incorporated to lysine residues in GAPDH. We identified the specific BisANS incorporation sites on GAPDH in nontransgenic (NTg), G93A, and H46R/H48Q mice using liquid chromatography-tandem mass spectrometry analysis. Four BisANS-containing sites (K52, K104, K212, and K248) were found in NTg GAPDH, while three out of four of these sites were lost in either G93A or H46R/H48Q GAPDH. Conversely, eight new sites (K2, K63, K69, K114, K183, K251, S330, and K331) were found on GAPDH for G93A, including one common site (K114) for H46R/H48Q, which is not found on GAPDH from NTg mice. These data show that GAPDH is differentially affected structurally and functionally in vivo in accordance with the degree of oxidative stress associated with these two models of ALS. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Pierce, Anson; Muller, Florian; Van Remmen, Holly; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Mirzaei, Hamid; Regnier, Fred] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[De Waal, Eric; Taylor, Alexander B.; Chaudhuri, Asish] Univ Texas San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
[Leonard, Shanique; Van Remmen, Holly; Richardson, Arlan; Chaudhuri, Asish] Univ Texas San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Van Remmen, Holly; Richardson, Arlan; Chaudhuri, Asish] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA.
[Taylor, Alexander B.] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA.
RP Chaudhuri, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA.
EM Chaudhuria@uthscsa.edu
RI Pierce, Anson/D-1079-2012
OI Pierce, Anson/0000-0002-1383-0180
FU Veterans Affairs (VA)-Veterans Integrated Service Network; Amyotrophic
Lateral Sclerosis Association; VA Merit; MDA 3879; National Institutes
of Health [AG025362, AG23843, R37 AG26557]; Department of VA; VA CDA-2
FX We would like to thank Dr. David Borchelt for kindly providing us with
the H46R/H48Q mice for use in this study. We would also like to thank
Dr. Susan Weintraub and the Mass Spectrometry Core for access to their
facility and tlieir assistance in the identification of proteins by
MALDI-TOF MS. This work was supported by Veterans Affairs (VA)-Veterans
Integrated Service Network, Amyotrophic Lateral Sclerosis Association,
and VA Merit grants (A.C.); VA Merit and MDA 3879 (H.V.R.); National
Institutes of Health grant AG025362 (F.R. and H.V.R.); National
Institutes of Health grants AG23843 and R37 AG26557 (A.R.); a Research
Enhancement Award Program grant from the Department of VA (to A.R.,
H.V.R., and A.C.); and a VA CDA-2 grant (to A.P.).
NR 51
TC 44
Z9 45
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 24
PY 2008
VL 382
IS 5
BP 1195
EP 1210
DI 10.1016/j.jmb.2008.07.088
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 363LY
UT WOS:000260270000009
PM 18706911
ER
PT J
AU Gillespie, K
Kodani, I
Dickinson, DP
Ogbureke, KUE
Camba, AM
Wu, MJ
Looney, S
Chu, TC
Qin, HY
Bisch, F
Sharawy, M
Schuster, GS
Hsu, SD
AF Gillespie, Kevin
Kodani, Isamu
Dickinson, Douglas P.
Ogbureke, Kalu U. E.
Camba, Amy M.
Wu, Mengjie
Looney, Stephen
Chu, Tin-Chun
Qin, Haiyan
Bisch, Frederick
Sharawy, Mohamed
Schuster, George S.
Hsu, Stephen D.
TI Effects of oral consumption of the green tea polyphenol EGCG in a murine
model for human Sjogren's syndrome, an autoimmune disease
SO LIFE SCIENCES
LA English
DT Article
DE Sjogren's syndrome; Green tea; EGCG; Autoimmune disease; Non-obese
diabetic mice
ID SALIVARY-GLAND; CELLS; PATHOGENESIS; EXPRESSION; THERAPIES
AB Significance: Protection of glandular cells from autoimmune-induced damage would be of significant clinical benefit to Sjogren's syndrome (SS) patients. Epigallocatechin-3-gallate (EGCG) possesses anti-apoptotic, anti-inflammatory, and autoantigen-inhibitory properties.
Aims: To investigate if EGCG protects against certain autoimmune-induced pathological changes in the salivary glands of the non-obese diabetic (NOD) mouse model for SS.
Main methods: Animals were provided with either water or water containing 0.2% EGCG. At the age of 8,16 and 22 weeks, submandibular salivary gland tissue and serum samples were collected for pathological and serological analysis.
Key findings: Significant lymphocyte infiltration was observed in the salivary glands of the water-fed group at the age of 16 weeks, while the EGCG group showed reduced lymphocyte infiltration. By 22 weeks of age, water-fed animals demonstrated elevated levels of apoptotic activity within the lymphocytic infiltrates, and high levels of serum total anti-nuclear antibody, compared to EGCG-fed animals. Remarkably, proliferating cell nuclear antigen (PCNA) and Ki-67 levels in the salivary glands of water-fed NOD mice were significantly elevated in comparison to BALB/c control mice; in contrast, PCNA and Ki-67 levels in EGCC-fed NOD animals were similar to BALB/c mice. These results indicate that EGCG protects the NOD mouse submandibular glands from autoimmune-induced inflammation, and reduces serum autoantibody levels. Abnormal proliferation, rather than apoptosis, appears to be a characteristic of the NOD mouse gland that is normalized by EGCG. The evidence suggests that EGCG could be useful in delaying or managing SS-like autoimmune disorders. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Dickinson, Douglas P.; Ogbureke, Kalu U. E.; Camba, Amy M.; Looney, Stephen; Qin, Haiyan; Sharawy, Mohamed; Schuster, George S.; Hsu, Stephen D.] Med Coll Georgia, Sch Dent, Dept Oral Biol, Augusta, GA 30912 USA.
[Gillespie, Kevin; Bisch, Frederick] USA, Dept Periodontol, Ft Gordon, GA USA.
[Kodani, Isamu] Tottori Univ, Fac Med, Tottori Univ Hosp, Dept Oral & Maxillofacial Surg, Yonago, Tottori 683, Japan.
[Wu, Mengjie] Zhejiang Univ, Sch Dent, Hosp Stomotol, Hangzhou 310003, Zhejiang, Peoples R China.
[Chu, Tin-Chun] Seton Hall Univ, Coll Arts & Sci, Dept Biol Sci, S Orange, NJ USA.
[Hsu, Stephen D.] US Dept Vet Affairs, VA Med Ctr, Augusta, GA USA.
RP Hsu, SD (reprint author), Med Coll Georgia, Sch Dent, Dept Oral Biol, AD1443, Augusta, GA 30912 USA.
EM shsu@mail.mcg.edu
RI Dickinson, Douglas/B-9111-2009;
OI Chu, Tinchun/0000-0002-6314-1009
FU MCG; US Army Periodontics; Department of Oral Biology; School of
Dentistry
FX The authors thank Ms. Vera B. Larke for her technical assistance. This
study was supported in part by funds from a grant from MCG, a fund from
US Army Periodontics, and from Department of Oral Biology, School of
Dentistry to S.H.
NR 28
TC 34
Z9 37
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
J9 LIFE SCI
JI Life Sci.
PD OCT 24
PY 2008
VL 83
IS 17-18
BP 581
EP 588
DI 10.1016/j.lfs.2008.08.011
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 365JJ
UT WOS:000260401700001
PM 18809413
ER
PT J
AU Hoffman, AN
Cheng, JP
Zafonte, RD
Kline, AE
AF Hoffman, Ann N.
Cheng, Jeffrey P.
Zafonte, Ross D.
Kline, Anthony E.
TI Administration of haloperidol and risperidone after neurobehavioral
testing hinders the recovery of traumatic brain injury-induced deficits
SO LIFE SCIENCES
LA English
DT Article
DE Antipsychotics; Brain injury; Functional recovery; Water maze
ID CONTROLLED CORTICAL IMPACT; WATER MAZE PERFORMANCE; RAT FRONTAL-CORTEX;
ISCHEMIA IN-VIVO; ATYPICAL ANTIPSYCHOTICS; SIGMA(1) RECEPTOR;
WORKING-MEMORY; DOPAMINERGIC TRANSMISSION; METHYLPHENIDATE TREATMENT;
CHOLINERGIC MARKERS
AB Aims: Agitation and aggression are common behavioral sequelae of traumatic brain injury (TBI). The management of these symptoms is critical for effective patient care and therefore antipsychotics are routinely administered even though the benefits vs. risks of this approach on functional outcome after TBI are unclear. A recent study from our group revealed that both haloperidol and risperidone impaired recovery when administered prior to testing. However, the results may have been confounded by drug-induced sedation. Hence, the current study reevaluated the behavioral effects of haloperidol and risperidone when provided after daily testing, thus circumventing the potential sedative effect.
Main methods: Fifty-four isoflurane-anesthetized mate rats received a cortical impact or sham injury and then were randomly assigned to three TBI and three sham groups that received haloperidol (0.5 mg/kg), risperidone (0.45 nng/kg), or vehicle (1.0 mL/kg). Treatments began 24 h after surgery and were administered (i.p.) every day thereafter for 19 days. Motor and cognitive function was assessed on post-operative days 1-5 and 14-19, respectively. Hippocampal CA(1)/CA(3) neurons and cortical lesion volume were quantified at 3 weeks.
Key findings: Only risperidone delayed motor recovery, but both antipsychotics impaired spatial learning relative to vehicle (p<0.05). Neither swim speed nor histological outcomes were affected. No differences were observed between the haloperidol and risperidone groups in any task. Significance: These data support our previous finding that chronic haloperidol and risperidone hinder the recovery of TBI-induced deficits, and augment those data by demonstrating that the effects are not mediated by drug-induced sedation. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Kline, Anthony E.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA.
[Hoffman, Ann N.; Cheng, Jeffrey P.; Kline, Anthony E.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15213 USA.
[Kline, Anthony E.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15213 USA.
[Kline, Anthony E.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA.
[Zafonte, Ross D.] Harvard Univ, Sch Med, Boston, MA 02144 USA.
[Zafonte, Ross D.] Spaulding Rehabil Hosp, Boston, MA 02114 USA.
[Zafonte, Ross D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Kline, AE (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 3471 5th Ave,Suite 201, Pittsburgh, PA 15213 USA.
EM klineae@upmc.edu
OI Cheng, Jeffrey/0000-0001-8285-3207
FU NIH [HD046700]
FX This work was supported, in part, by NIH grant HD046700 (AEK).
NR 48
TC 42
Z9 43
U1 2
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
J9 LIFE SCI
JI Life Sci.
PD OCT 24
PY 2008
VL 83
IS 17-18
BP 602
EP 607
DI 10.1016/j.lfs.2008.08.007
PG 6
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 365JJ
UT WOS:000260401700004
PM 18801378
ER
PT J
AU Basu, U
Wang, YB
Alt, FW
AF Basu, Uttiya
Wang, Yabin
Alt, Frederick W.
TI Evolution of Phosphorylation-Dependent Regulation of Activation-Induced
Cytidine Deaminase
SO MOLECULAR CELL
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; ANTIBODY
DIVERSIFICATION ENZYME; KINASE-A PHOSPHORYLATION; SOMATIC HYPERMUTATION;
B-CELLS; AID; MICRORNA-155; MECHANISMS; REGIONS
AB Interaction of activation-induced cytidine deaminase (AID) with replication protein A (RPA) has been proposed to promote AID access to transcribed double-stranded (ds) DNA during immunoglobulin light chain and heavy chain class switch recombination (CSR). Mouse AID (mAID) interaction with RPA and transcription-dependent dsDNA deamination in vitro requires protein kinase A (PKA) phosphorylation at serine 38 (S38), and normal mAID CSR activity depends on S38. However, zebrafish AID (zAID) catalyzes robust CSR in mouse cells despite lacking an S38-equivalent PKA site. Here, we show that aspartate 44 (D44) in zAID provides similar in vitro and in vivo functionality as mAID S38 phosphorylation. Moreover, introduction of a PKA site into a zAID D44 mutant made it PKA dependent for in vitro activities and restored normal CSR activity. Based on these findings, we generated mAID mutants that similarly function independently of S38 phosphorylation. Comparison of bony fish versus amphibian and mammalian AlDs suggests evolutionary divergence from constitutive to PKA-regulated RPA/AID interaction.
C1 [Basu, Uttiya; Wang, Yabin; Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Basu, Uttiya; Wang, Yabin; Alt, Frederick W.] Immune Dis Inst, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
FU National Institutes of Health
FX We thank David Schatz, Jayanta Chaudhuri, Andrew Franklin, Jing Wang,
Vivian Choi, Abhishek Datta, and Ting Ting Zhang for evaluation of the
manuscript. We thank Tasuku Honjo for AID-deficient mice, and Vasco
Barrette and Michel Nussenzweig for a retroviral construct expressing WT
zebrafish AID. Tiffany Bel and Lisa Aquaviva provided technical
assistance in maintenance of AID-deficient mice. U.B. was a fellow of
the Irvington Institute of Immunology program of the Cancer Research
Institute, and is current y a Special Fellow of the Leukemia and
Lymphoma Society of America. This work was supported by a National
Institutes of Health grant to F.W.A., who is an investigator of the
Howard Hughes Medical Institute.
NR 36
TC 23
Z9 26
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD OCT 24
PY 2008
VL 32
IS 2
BP 285
EP 291
DI 10.1016/j.molcel.2008.08.019
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 367IX
UT WOS:000260546800016
PM 18951095
ER
PT J
AU Chen, YI
Wang, FN
Nelson, AJ
Xu, HB
Kim, Y
Rosen, BR
Kwong, KK
AF Chen, Y. Iris
Wang, Fu-Nien
Nelson, Aimee J.
Xu, Haibo
Kim, Young
Rosen, Bruce R.
Kwong, Kenneth K.
TI Electrical stimulation modulates the amphetamine-induced hemodynamic
changes: An fMRI study to compare the effect of stimulating locations
and frequencies on rats
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Amphetamine; fMRI; rCBV; Acupuncture; Electroacupuncture; Forepaw
stimulation
ID INDUCED PLACE PREFERENCE; SOMATOTOPIC ORGANIZATION; SOMATOSENSORY
CORTEX; MORPHINE-WITHDRAWAL; DOPAMINE RELEASE; BASAL GANGLIA; MOTOR
CORTEX; HUMAN BRAIN; ACUPUNCTURE; ELECTROACUPUNCTURE
AB Our previous fMRI and microdialysis measurements showed that electroacupuncture (EA) at LI4 was effective in alleviating excessive cerebral dopamine release induced by D-amphetamine (AMPH) in rats. We now compare the effect of EA in adjusting excess dopamine release at two stimulating frequencies (2 Hz versus 100 Hz at LI4) and at two acupoints (forepaw (LI4) versus hindpaw (ST36), at 2 Hz). fMRI measurements of relative cerebral blood volume (rCBV) were used to monitor the brain activity of "rest", followed by AMPH challenge, 10 min "rest", and then 20 min of EA. Results: EA at LI4 and ST36 significantly attenuated the AMPH-induced rCBV increases in the striatum, S1 cortex, and thalamus. Frequency: EA at 100 Hz induced greater attenuation of rCBV than EA at 2 Hz in the S1, insula, anterior cingulate cortices, dorsolateral striatum, and thalamus. Acupoints: EA at LI4 modulated a broader area in the medial anterior striatum while EA at ST36 modulated a more site-specific area in the dorsolateral striatum. in the thalamus, EA at LI4 showed greater attenuating effect than EA at ST36 did. However, in the insular cortex, EA at ST36 showed stronger attenuation. Conclusion: EA at both LI4 and ST36 was effective in restoring dopamine homeostasis from an excess state, with the most effective response at LI4 with 100 Hz, while the responses to 2 Hz EA at LI4 and ST36 showed slightly different spatial distribution of MR signal. This therefore provided insight into the neurophysiological basis of electroacupuncture effects in cortical and subcortical circuits. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Chen, Y. Iris; Wang, Fu-Nien; Xu, Haibo; Kim, Young; Rosen, Bruce R.; Kwong, Kenneth K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA.
[Wang, Fu-Nien] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu, Taiwan.
[Nelson, Aimee J.] Univ Waterloo, Waterloo, ON N2L 3G1, Canada.
[Xu, Haibo] Union Hosp, Wuhan, Peoples R China.
RP Chen, YI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA.
EM iris@nmr.mgh.harvard.edu
FU NIH/NCCAM [P01 AT002048]
FX Funding agency: sponsored by NIH/NCCAM grant P01 AT002048.
NR 37
TC 4
Z9 4
U1 2
U2 6
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 OCT 24
PY 2008
VL 444
IS 2
BP 117
EP 121
DI 10.1016/j.neulet.2008.08.033
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 366XG
UT WOS:000260516300002
PM 18722508
ER
PT J
AU Kahn, CR
AF Kahn, C. Ronald
TI Medicine - Can we nip obesity in its vascular bud?
SO SCIENCE
LA English
DT Editorial Material
ID ADIPOSE-TISSUE; STEM-CELLS; NEURAL CREST; BROWN; FAT; ORIGIN;
PREADIPOCYTES; ADIPOGENESIS; ADIPOCYTES
C1 [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM c.ronald.kahn@joslin.harvard.edu
FU NIDDK NIH HHS [R01 DK082659, P30 DK036836]
NR 21
TC 21
Z9 21
U1 0
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 24
PY 2008
VL 322
IS 5901
BP 542
EP 543
DI 10.1126/science.1165667
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363WV
UT WOS:000260299100029
PM 18948531
ER
PT J
AU Pettigrew, LC
Kindy, MS
Scheff, S
Springer, JE
Kryscio, RJ
Li, Y
Grass, DS
AF Pettigrew, L. Creed
Kindy, Mark S.
Scheff, Stephen
Springer, Joe E.
Kryscio, Richard J.
Li, Yizhao
Grass, David S.
TI Focal cerebral ischemia in the TNFalpha-transgenic rat
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; BRAIN-INJURY; PROINFLAMMATORY
CYTOKINES; INDUCED APOPTOSIS; ARTERY OCCLUSION; FACTOR RECEPTOR; MICE
LACKING; TNF-ALPHA; STROKE
AB Background: To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNF alpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia.
Methods: Transgenic (TNF alpha-Tg) rats overexpressing the murine TNF alpha gene in brain were prepared by injection of mouse DNA into rat oocytes. Brain levels of TNF alpha mRNA and protein were measured and compared between TNF alpha-Tg and non-transgenic (non-Tg) littermates. Mean infarct volume was calculated 24 hours or 7 days after one hour of reversible middle cerebral artery occlusion (MCAO). Cortical perfusion was monitored by laser-Doppler flowmetry (LDF) during MCAO. Cortical vascular density was quantified by stereology. Post-ischemic cell death was assessed by immunohistochemistry and regional measurement of caspase-3 activity or DNA fragmentation. Unpaired t tests or analysis of variance with post hoc tests were used for comparison of group means.
Results: In TNF alpha-Tg rat brain, the aggregate mouse and rat TNF alpha mRNA level was fourfold higher than in non-Tg littermates and the corresponding TNF alpha protein level was increased fivefold (p <= 0.01). Infarct volume was greater in TNF alpha-Tg rats than in non-Tg controls at 24 hours (p <= 0.05) and 7 days (p <= 0.01). Within the first 10 minutes of MCAO, cortical perfusion measured by LDF was reduced in TNF alpha-Tg rats (p <= 0.05). However, regional vascular density was equivalent between TNF alpha-Tg and non-Tg animals (p = NS). Neural cellular apoptosis was increased in transgenic animals as shown by elevated caspase-3 activity (p = 0.05) and DNA fragmentation (p <= 0.001) at 24 hours.
Conclusion: Chronic elevation of TNF alpha protein in brain increases susceptibility to ischemic injury but has no effect on vascular density. TNF alpha-Tg animals are more susceptible to apoptotic cell death after MCAO than are non-Tg animals. We conclude that the TNF alpha-Tg rat is a valuable new tool for the study of cytokine-mediated ischemic brain injury.
C1 [Pettigrew, L. Creed; Scheff, Stephen] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
[Pettigrew, L. Creed] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA.
[Pettigrew, L. Creed] Vet Adm Med Ctr, Lexington, KY 40511 USA.
[Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Springer, Joe E.] Univ Kentucky, Dept Phys Med & Rehabil, Lexington, KY 40536 USA.
[Kryscio, Richard J.] Univ Kentucky, Dept Stat, Lexington, KY 40536 USA.
[Kryscio, Richard J.] Univ Kentucky, Sch Publ Hlth, Lexington, KY 40536 USA.
[Li, Yizhao] Jinan Great Wall Hosp, Jinan, Shandong, Peoples R China.
[Grass, David S.] Xenogen Biosci, Cranbury, NJ USA.
RP Pettigrew, LC (reprint author), Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
EM cpetti@uky.edu; kindyms@musc.edu; sscheff@email.uky.edu;
joe.springer@uky.edu; kryscio@email.uky.edu; swillia@uky.edu;
David.Grass@xenogen.com
FU NIH/NINDS [R01 NS047395, R01 NS039588]; Shandong University, China
FX Financial support was provided by NIH/NINDS grants R01 NS047395 (LCP)
and R01 NS039588 (MSK) and by a Visiting Research Scientist Award
provided by Shandong University, China (YL) for training at the
University of Kentucky in Lexington, Kentucky. Dr. George Kollias
prepared the microinjection construct containing the murine TNF alpha
gene and its promoter that was used to make the transgenic animal. Mr.
Richard Coffee constructed the animal at Xenogen Biosciences in
Cranbury, New Jersey. We thank Mary Louise Holtz, Ph. D., Xaio-Hong
Song, M. D., Susan D. Craddock, and Ravikumar Rao for technical
contributions to this work and Sherry Chandler Williams, ELS, for
editing the manuscript and preparing the illustrations.
NR 48
TC 32
Z9 32
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD OCT 23
PY 2008
VL 5
AR 47
DI 10.1186/1742-2094-5-47
PG 19
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 371YZ
UT WOS:000260869900001
PM 18947406
ER
PT J
AU Chin, L
Meyerson, M
Aldape, K
Bigner, D
Mikkelsen, T
VandenBerg, S
Kahn, A
Penny, R
Ferguson, ML
Gerhard, DS
Getz, G
Brennan, C
Taylor, BS
Winckler, W
Park, P
Ladanyi, M
Hoadley, KA
Verhaak, RGW
Hayes, DN
Spellman, PT
Absher, D
Weir, BA
Ding, L
Wheeler, D
Lawrence, MS
Cibulskis, K
Mardis, E
Zhang, JH
Wilson, RK
Donehower, L
Wheeler, DA
Purdom, E
Wallis, J
Laird, PW
Herman, JG
Schuebel, KE
Weisenberger, DJ
Baylin, SB
Schultz, N
Yao, J
Wiedemeyer, R
Weinstein, J
Sander, C
Gibbs, RA
Gray, J
Kucherlapati, R
Lander, ES
Myers, RM
Perou, CM
McLendon, R
Friedman, A
Van Meir, EG
Brat, DJ
Mastrogianakis, GM
Olson, JJ
Lehman, N
Yung, WKA
Bogler, O
Berger, M
Prados, M
Muzny, D
Morgan, M
Scherer, S
Sabo, A
Nazareth, L
Lewis, L
Hall, O
Zhu, YM
Ren, YR
Alvi, O
Yao, JQ
Hawes, A
Jhangiani, S
Fowler, G
San Lucas, A
Kovar, C
Cree, A
Dinh, H
Santibanez, J
Joshi, V
Gonzalez-Garay, ML
Miller, CA
Milosavljevic, A
Sougnez, C
Fennell, T
Mahan, S
Wilkinson, J
Ziaugra, L
Onofrio, R
Bloom, T
Nicol, R
Ardlie, K
Baldwin, J
Gabriel, S
Fulton, RS
McLellan, MD
Larson, DE
Shi, XQ
Abbott, R
Fulton, L
Chen, K
Koboldt, DC
Wendl, MC
Meyer, R
Tang, YZ
Lin, L
Osborne, JR
Dunford-Shore, BH
Miner, TL
Delehaunty, K
Markovic, C
Swift, G
Courtney, W
Pohl, C
Abbott, S
Hawkins, A
Leong, S
Haipek, C
Schmidt, H
Wiechert, M
Vickery, T
Scott, S
Dooling, DJ
Chinwalla, A
Weinstock, GM
O'Kelly, M
Robinson, J
Alexe, G
Beroukhim, R
Carter, S
Chiang, D
Gould, J
Gupta, S
Korn, J
Mermel, C
Mesirov, J
Monti, S
Nguyen, H
Parkin, M
Reich, M
Stransky, N
Garraway, L
Golub, T
Protopopov, A
Perna, I
Aronson, S
Sathiamoorthy, N
Ren, G
Kim, H
Kong, SK
Xiao, YH
Kohane, IS
Seidman, J
Cope, L
Pan, F
Van Den Berg, D
Van Neste, L
Yi, JM
Li, JZ
Southwick, A
Brady, S
Aggarwal, A
Chung, T
Sherlock, G
Brooks, JD
Jakkula, LR
Lapuk, AV
Marr, H
Dorton, S
Choi, YG
Han, J
Ray, A
Wang, V
Durinck, S
Robinson, M
Wang, NJ
Vranizan, K
Peng, V
Van Name, E
Fontenay, GV
Ngai, J
Conboy, JG
Parvin, B
Feiler, HS
Speed, TP
Socci, ND
Olshen, A
Lash, A
Reva, B
Antipin, Y
Stukalov, A
Gross, B
Cerami, E
Wang, WQ
Qin, LX
Seshan, VE
Villafania, L
Cavatore, M
Borsu, L
Viale, A
Gerald, W
Topal, MD
Qi, Y
Balu, S
Shi, Y
Wu, G
Bittner, M
Shelton, T
Lenkiewicz, E
Morris, S
Beasley, D
Sanders, S
Sfeir, R
Chen, J
Nassau, D
Feng, L
Hickey, E
Schaefer, C
Madhavan, S
Buetow, K
Barker, A
Vockley, J
Compton, C
Vaught, J
Fielding, P
Collins, F
Good, P
Guyer, M
Ozenberger, B
Peterson, J
Thomson, E
AF Chin, L.
Meyerson, M.
Aldape, K.
Bigner, D.
Mikkelsen, T.
VandenBerg, S.
Kahn, A.
Penny, R.
Ferguson, M. L.
Gerhard, D. S.
Getz, G.
Brennan, C.
Taylor, B. S.
Winckler, W.
Park, P.
Ladanyi, M.
Hoadley, K. A.
Verhaak, R. G. W.
Hayes, D. N.
Spellman, Paul T.
Absher, D.
Weir, B. A.
Ding, L.
Wheeler, D.
Lawrence, M. S.
Cibulskis, K.
Mardis, E.
Zhang, Jinghui
Wilson, R. K.
Donehower, L.
Wheeler, D. A.
Purdom, E.
Wallis, J.
Laird, P. W.
Herman, J. G.
Schuebel, K. E.
Weisenberger, D. J.
Baylin, S. B.
Schultz, N.
Yao, Jun
Wiedemeyer, R.
Weinstein, J.
Sander, C.
Gibbs, R. A.
Gray, J.
Kucherlapati, R.
Lander, E. S.
Myers, R. M.
Perou, C. M.
McLendon, Roger
Friedman, Allan
Van Meir, Erwin G
Brat, Daniel J
Mastrogianakis, Gena Marie
Olson, Jeffrey J
Lehman, Norman
Yung, W. K. Alfred
Bogler, Oliver
Berger, Mitchel
Prados, Michael
Muzny, Donna
Morgan, Margaret
Scherer, Steve
Sabo, Aniko
Nazareth, Lynn
Lewis, Lora
Hall, Otis
Zhu, Yiming
Ren, Yanru
Alvi, Omar
Yao, Jiqiang
Hawes, Alicia
Jhangiani, Shalini
Fowler, Gerald
San Lucas, Anthony
Kovar, Christie
Cree, Andrew
Dinh, Huyen
Santibanez, Jireh
Joshi, Vandita
Gonzalez-Garay, Manuel L.
Miller, Christopher A.
Milosavljevic, Aleksandar
Sougnez, Carrie
Fennell, Tim
Mahan, Scott
Wilkinson, Jane
Ziaugra, Liuda
Onofrio, Robert
Bloom, Toby
Nicol, Rob
Ardlie, Kristin
Baldwin, Jennifer
Gabriel, Stacey
Fulton, Robert S.
McLellan, Michael D.
Larson, David E.
Shi, Xiaoqi
Abbott, Rachel
Fulton, Lucinda
Chen, Ken
Koboldt, Daniel C.
Wendl, Michael C.
Meyer, Rick
Tang, Yuzhu
Lin, Ling
Osborne, John R.
Dunford-Shore, Brian H.
Miner, Tracie L.
Delehaunty, Kim
Markovic, Chris
Swift, Gary
Courtney, William
Pohl, Craig
Abbott, Scott
Hawkins, Amy
Leong, Shin
Haipek, Carrie
Schmidt, Heather
Wiechert, Maddy
Vickery, Tammi
Scott, Sacha
Dooling, David J.
Chinwalla, Asif
Weinstock, George M.
O'Kelly, Michael
Robinson, Jim
Alexe, Gabriele
Beroukhim, Rameen
Carter, Scott
Chiang, Derek
Gould, Josh
Gupta, Supriya
Korn, Josh
Mermel, Craig
Mesirov, Jill
Monti, Stefano
Nguyen, Huy
Parkin, Melissa
Reich, Michael
Stransky, Nicolas
Garraway, Levi
Golub, Todd
Protopopov, Alexei
Perna, Ilana
Aronson, Sandy
Sathiamoorthy, Narayan
Ren, Georgia
Kim, Hyunsoo
Kong, Sek Won
Xiao, Yonghong
Kohane, Isaac S.
Seidman, Jon
Cope, Leslie
Pan, Fei
Van Den Berg, David
Van Neste, Leander
Yi, Joo Mi
Li, Jun Z.
Southwick, Audrey
Brady, Shannon
Aggarwal, Amita
Chung, Tisha
Sherlock, Gavin
Brooks, James D.
Jakkula, Lakshmi R.
Lapuk, Anna V.
Marr, Henry
Dorton, Shannon
Choi, Yoon Gi
Han, Ju
Ray, Amrita
Wang, Victoria
Durinck, Steffen
Robinson, Mark
Wang, Nicholas J.
Vranizan, Karen
Peng, Vivian
Van Name, Eric
Fontenay, Gerald V.
Ngai, John
Conboy, John G.
Parvin, Bahram
Feiler, Heidi S.
Speed, Terence P.
Socci, Nicholas D.
Olshen, Adam
Lash, Alex
Reva, Boris
Antipin, Yevgeniy
Stukalov, Alexey
Gross, Benjamin
Cerami, Ethan
Wang, Wei Qing
Qin, Li-Xuan
Seshan, Venkatraman E.
Villafania, Liliana
Cavatore, Magali
Borsu, Laetitia
Viale, Agnes
Gerald, William
Topal, Michael D.
Qi, Yuan
Balu, Sai
Shi, Yan
Wu, George
Bittner, Michael
Shelton, Troy
Lenkiewicz, Elizabeth
Morris, Scott
Beasley, Debbie
Sanders, Sheri
Sfeir, Robert
Chen, Jessica
Nassau, David
Feng, Larry
Hickey, Erin
Schaefer, Carl
Madhavan, Subha
Buetow, Ken
Barker, Anna
Vockley, Joseph
Compton, Carolyn
Vaught, Jim
Fielding, Peter
Collins, Francis
Good, Peter
Guyer, Mark
Ozenberger, Brad
Peterson, Jane
Thomson, Elizabeth
CA Canc Genome Atlas Res Network
Tissue Source Sites
Genome Sequencing Ctr
Canc Genome Characterization Ctr
Project Teams
TI Comprehensive genomic characterization defines human glioblastoma genes
and core pathways
SO NATURE
LA English
DT Article
ID NF1 GENE; MISMATCH REPAIR; NEUROFIBROMATOSIS TYPE-1; SOMATIC MUTATIONS;
MALIGNANT GLIOMAS; ALKYLATING-AGENTS; HIGH-FREQUENCY; PIK3CA GENE;
CELL-LINES; TUMORS
AB Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
C1 [Chin, L.; Meyerson, M.; Winckler, W.; Verhaak, R. G. W.; Weir, B. A.; Wiedemeyer, R.; Beroukhim, Rameen; Chiang, Derek; Mermel, Craig; Garraway, Levi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chin, L.; Yao, Jun; Protopopov, Alexei; Perna, Ilana; Ren, Georgia; Xiao, Yonghong] Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Inst innovat Canc Sci, Boston, MA 02115 USA.
[Chin, L.; Robinson, Jim; Alexe, Gabriele; Carter, Scott] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Meyerson, M.; Getz, G.; Winckler, W.; Verhaak, R. G. W.; Weir, B. A.; Lawrence, M. S.; Lander, E. S.; O'Kelly, Michael; Beroukhim, Rameen; Chiang, Derek; Gould, Josh; Gupta, Supriya; Korn, Josh; Mermel, Craig; Mesirov, Jill; Monti, Stefano; Nguyen, Huy; Parkin, Melissa; Reich, Michael; Stransky, Nicolas; Garraway, Levi; Golub, Todd] Harvard Univ, Cambridge, MA 02142 USA.
[Bigner, D.; McLendon, Roger] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Friedman, Allan] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Mikkelsen, T.] Henry Ford Hosp, Dept Neurol Surg, Detroit, MI 48202 USA.
[VandenBerg, S.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Aldape, K.] Univ Texas Houston MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Yung, W. K. Alfred] Univ Texas Houston MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Bogler, Oliver] Univ Texas Houston MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA.
[Kahn, A.; Sfeir, Robert; Chen, Jessica; Nassau, David; Feng, Larry; Hickey, Erin] SRA Int, Fairfax, VA 22033 USA.
NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA.
[Collins, Francis; Good, Peter; Guyer, Mark; Ozenberger, Brad; Peterson, Jane; Thomson, Elizabeth] NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA.
[Gerhard, D. S.; Barker, Anna; Vockley, Joseph; Compton, Carolyn; Vaught, Jim; Fielding, Peter] NCI, NIH, Bethesda, MD 20892 USA.
[Penny, R.; Shelton, Troy; Lenkiewicz, Elizabeth; Morris, Scott; Beasley, Debbie; Sanders, Sheri] Int Genom Consortium, Phoenix, AZ 85004 USA.
[Ferguson, M. L.] MLF Consulting, Arlington, MA 02474 USA.
[Ding, L.; Mardis, E.; Wilson, R. K.; Wallis, J.; Fennell, Tim; Baldwin, Jennifer; Fulton, Robert S.; McLellan, Michael D.; Larson, David E.; Shi, Xiaoqi; Abbott, Rachel; Fulton, Lucinda; Chen, Ken; Koboldt, Daniel C.; Wendl, Michael C.; Meyer, Rick; Tang, Yuzhu; Lin, Ling; Osborne, John R.; Dunford-Shore, Brian H.; Miner, Tracie L.; Delehaunty, Kim; Markovic, Chris; Swift, Gary; Courtney, William; Pohl, Craig; Abbott, Scott; Hawkins, Amy; Leong, Shin; Haipek, Carrie; Schmidt, Heather; Wiechert, Maddy; Vickery, Tammi; Scott, Sacha; Dooling, David J.; Chinwalla, Asif; Weinstock, George M.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA.
[Park, P.; Aronson, Sandy; Sathiamoorthy, Narayan; Kim, Hyunsoo; Kohane, Isaac S.] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA 02115 USA.
[Park, P.; Kucherlapati, R.; Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Park, P.; Kong, Sek Won; Kohane, Isaac S.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
[Brennan, C.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
[Taylor, B. S.; Schultz, N.; Sander, C.; Socci, Nicholas D.; Lash, Alex; Reva, Boris; Antipin, Yevgeniy; Stukalov, Alexey; Gross, Benjamin; Cerami, Ethan; Wang, Wei Qing; Gerald, William] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
[Taylor, B. S.] Weill Cornell Grad Sch Med Sci, Dept Physiol & Biophys, New York, NY 10065 USA.
[Ladanyi, M.; Borsu, Laetitia] Mem Sloan Kettering Canc Ctr, Dept Pathol, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Spellman, Paul T.; Gray, J.; Jakkula, Lakshmi R.; Lapuk, Anna V.; Marr, Henry; Dorton, Shannon; Han, Ju; Ray, Amrita; Durinck, Steffen; Wang, Nicholas J.; Fontenay, Gerald V.; Conboy, John G.; Parvin, Bahram; Feiler, Heidi S.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Purdom, E.; Wang, Victoria; Speed, Terence P.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 95720 USA.
[Choi, Yoon Gi; Vranizan, Karen; Peng, Vivian; Van Name, Eric; Ngai, John] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 95720 USA.
[Robinson, Mark; Speed, Terence P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
[Southwick, Audrey; Brady, Shannon; Aggarwal, Amita; Chung, Tisha; Sherlock, Gavin] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Brooks, James D.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA.
[Wheeler, D.; Donehower, L.; Wheeler, D. A.] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Perou, C. M.; Miller, Christopher A.; Milosavljevic, Aleksandar] Baylor Coll Med, Grad Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA.
[Perou, C. M.; Milosavljevic, Aleksandar] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
Univ N Carolina, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Hoadley, K. A.; Topal, Michael D.] Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Qi, Yuan] Univ N Carolina, Dept Internal Med, Lineberger Comprehens Canc Ctr, Div Med Oncol, Chapel Hill, NC 27599 USA.
[Hayes, D. N.; Herman, J. G.; Schuebel, K. E.; Baylin, S. B.; Yi, Joo Mi] Johns Hopkins Univ, Div Canc Biol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
[Cope, Leslie] Johns Hopkins Univ, Biometry & Clin Trials Div, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
[Van Neste, Leander] Univ Ghent, Fac Biosci & Engn, Dept Mol Biotechnol, B-9000 Ghent, Belgium.
[Van Meir, Erwin G; Mastrogianakis, Gena Marie; Olson, Jeffrey J] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA.
[Van Meir, Erwin G; Olson, Jeffrey J] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA.
[Van Meir, Erwin G; Brat, Daniel J; Olson, Jeffrey J] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA.
[Brat, Daniel J] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Laird, P. W.; Weisenberger, D. J.; Pan, Fei; Van Den Berg, David] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA 90089 USA.
[Lehman, Norman] Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA.
[Berger, Mitchel; Prados, Michael] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA.
[Cibulskis, K.; Sougnez, Carrie] MIT, Eli & Edythe L Broad Inst, Canc Genome Project, Cambridge, MA 02142 USA.
[Sougnez, Carrie] MIT, Eli & Edythe L Broad Inst, Med Resequencing Project, Cambridge, MA 02142 USA.
[Lander, E. S.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Lander, E. S.] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA.
[Golub, Todd] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Seidman, Jon] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Absher, D.; Myers, R. M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Olshen, Adam; Qin, Li-Xuan; Seshan, Venkatraman E.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
[Villafania, Liliana; Cavatore, Magali; Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10065 USA.
[Bittner, Michael] Translat Genom Res Inst, Computat Biol Div, Phoenix, AZ 85004 USA.
[Zhang, Jinghui; Schaefer, Carl; Madhavan, Subha; Buetow, Ken] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA.
[Weinstein, J.] Univ Texas Houston MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Li, Jun Z.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Kong, Sek Won] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM lynda_chin@dfci.harvard.edu; matthew_meyerson@dfci.harvard.edu
RI Wendl, Michael/A-2741-2008; Speed, Terence /B-8085-2009; leng,
xianwei/F-9073-2011; sander, chris/H-1452-2011; Meyerson,
Matthew/E-7123-2012; Sherlock, Gavin/E-9110-2012; Miller,
Christopher/A-1060-2009; Kohane, Isaac Kohane/K-3716-2012; Robinson,
Mark/A-6432-2015; Laird, Peter/G-8683-2012; Lehman, Norman/A-7351-2015;
Chiang, Daisy/C-9481-2011; Reva, Boris/B-6436-2014
OI Van Meir, Erwin G./0000-0003-2444-7707; Lehman,
Norman/0000-0001-8394-2607; Bogler, Oliver/0000-0002-3700-0480; Brennan,
Cameron/0000-0003-4064-8891; Lash, Alex/0000-0003-3787-1590; Hayes, D.
Neil/0000-0001-6203-7771; Sherlock, Gavin/0000-0002-1692-4983; Perou,
Charles/0000-0001-9827-2247; Speed, Terence /0000-0002-5403-7998;
Miller, Christopher/0000-0003-4266-6700; Kohane, Isaac
Kohane/0000-0003-2192-5160; Robinson, Mark/0000-0002-3048-5518; Chiang,
Daisy/0000-0002-8205-4285; Reva, Boris/0000-0002-8805-389X
FU United States National Institutes of Health [U54HG003067, U54HG003079,
U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551,
U24CA126554, U24CA126561, U24CA126563]
FX We thank the members of TCGA's External Scientific Committee, the
Glioblastoma Disease Working Group (http://
cancergenome.nih.gov/components) and D. N. Louis for discussions; A.
Mirick, J. Melone and C. Collins for administrative coordination of TCGA
activities; and L. Gaffney for graphic art. This work was supported by
the following grants from the United States National Institutes of
Health: U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544,
U24CA126546, U24CA126551, U24CA126554, U24CA126561 and U24CA126563.
NR 50
TC 2301
Z9 2332
U1 45
U2 311
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1061
EP 1068
DI 10.1038/nature07385
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600035
ER
PT J
AU Ding, L
Getz, G
Wheeler, DA
Mardis, ER
McLellan, MD
Cibulskis, K
Sougnez, C
Greulich, H
Muzny, DM
Morgan, MB
Fulton, L
Fulton, RS
Zhang, QY
Wendl, MC
Lawrence, MS
Larson, DE
Chen, K
Dooling, DJ
Sabo, A
Hawes, AC
Shen, H
Jhangiani, SN
Lewis, LR
Hall, O
Zhu, YM
Mathew, T
Ren, YR
Yao, JQ
Scherer, SE
Clerc, K
Metcalf, GA
Ng, B
Milosavljevic, A
Gonzalez-Garay, ML
Osborne, JR
Meyer, R
Shi, XQ
Tang, YZ
Koboldt, DC
Lin, L
Abbott, R
Miner, TL
Pohl, C
Fewell, G
Haipek, C
Schmidt, H
Dunford-Shore, BH
Kraja, A
Crosby, SD
Sawyer, CS
Vickery, T
Sander, S
Robinson, J
Winckler, W
Baldwin, J
Chirieac, LR
Dutt, A
Fennell, T
Hanna, M
Johnson, BE
Onofrio, RC
Thomas, RK
Tonon, G
Weir, BA
Zhao, XJ
Ziaugra, L
Zody, MC
Giordano, T
Orringer, MB
Roth, JA
Spitz, MR
Wistuba, II
Ozenberger, B
Good, PJ
Chang, AC
Beer, DG
Watson, MA
Ladanyi, M
Broderick, S
Yoshizawa, A
Travis, WD
Pao, W
Province, MA
Weinstock, GM
Varmus, HE
Gabriel, SB
Lander, ES
Gibbs, RA
Meyerson, M
Wilson, RK
AF Ding, Li
Getz, Gad
Wheeler, David A.
Mardis, Elaine R.
McLellan, Michael D.
Cibulskis, Kristian
Sougnez, Carrie
Greulich, Heidi
Muzny, Donna M.
Morgan, Margaret B.
Fulton, Lucinda
Fulton, Robert S.
Zhang, Qunyuan
Wendl, Michael C.
Lawrence, Michael S.
Larson, David E.
Chen, Ken
Dooling, David J.
Sabo, Aniko
Hawes, Alicia C.
Shen, Hua
Jhangiani, Shalini N.
Lewis, Lora R.
Hall, Otis
Zhu, Yiming
Mathew, Tittu
Ren, Yanru
Yao, Jiqiang
Scherer, Steven E.
Clerc, Kerstin
Metcalf, Ginger A.
Ng, Brian
Milosavljevic, Aleksandar
Gonzalez-Garay, Manuel L.
Osborne, John R.
Meyer, Rick
Shi, Xiaoqi
Tang, Yuzhu
Koboldt, Daniel C.
Lin, Ling
Abbott, Rachel
Miner, Tracie L.
Pohl, Craig
Fewell, Ginger
Haipek, Carrie
Schmidt, Heather
Dunford-Shore, Brian H.
Kraja, Aldi
Crosby, Seth D.
Sawyer, Christopher S.
Vickery, Tammi
Sander, Sacha
Robinson, Jody
Winckler, Wendy
Baldwin, Jennifer
Chirieac, Lucian R.
Dutt, Amit
Fennell, Tim
Hanna, Megan
Johnson, Bruce E.
Onofrio, Robert C.
Thomas, Roman K.
Tonon, Giovanni
Weir, Barbara A.
Zhao, Xiaojun
Ziaugra, Liuda
Zody, Michael C.
Giordano, Thomas
Orringer, Mark B.
Roth, Jack A.
Spitz, Margaret R.
Wistuba, Ignacio I.
Ozenberger, Bradley
Good, Peter J.
Chang, Andrew C.
Beer, David G.
Watson, Mark A.
Ladanyi, Marc
Broderick, Stephen
Yoshizawa, Akihiko
Travis, William D.
Pao, William
Province, Michael A.
Weinstock, George M.
Varmus, Harold E.
Gabriel, Stacey B.
Lander, Eric S.
Gibbs, Richard A.
Meyerson, Matthew
Wilson, Richard K.
TI Somatic mutations affect key pathways in lung adenocarcinoma
SO NATURE
LA English
DT Article
ID HUMAN BREAST; MENDELIAN-INHERITANCE; HOMOZYGOUS DELETIONS; COLORECTAL
CANCERS; EGFR MUTATIONS; TOBACCO-SMOKE; KRAS MUTATION; NEVER SMOKERS;
RECEPTOR GENE; GEFITINIB
AB Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
C1 [Ding, Li; Mardis, Elaine R.; McLellan, Michael D.; Fulton, Lucinda; Fulton, Robert S.; Wendl, Michael C.; Larson, David E.; Chen, Ken; Dooling, David J.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
[Getz, Gad; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Lawrence, Michael S.; Winckler, Wendy; Baldwin, Jennifer; Dutt, Amit; Fennell, Tim; Hanna, Megan; Onofrio, Robert C.; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Gabriel, Stacey B.; Lander, Eric S.; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Genome Biol Program, Cambridge, MA 02142 USA.
[Wheeler, David A.; Muzny, Donna M.; Morgan, Margaret B.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Greulich, Heidi; Winckler, Wendy; Dutt, Amit; Hanna, Megan; Johnson, Bruce E.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Zhang, Qunyuan; Kraja, Aldi; Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA.
[Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Chirieac, Lucian R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Chirieac, Lucian R.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Thomas, Roman K.] Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany.
[Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany.
[Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany.
[Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany.
[Giordano, Thomas] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Orringer, Mark B.; Chang, Andrew C.; Beer, David G.] Univ Michigan, Thorac Surg Sect, Dept Surg, Ann Arbor, MI 48109 USA.
[Roth, Jack A.; Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA.
[Spitz, Margaret R.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Ozenberger, Bradley; Good, Peter J.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Watson, Mark A.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63108 USA.
[Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
[Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William] Mem Sloan Kettering Canc Ctr, Dept Computat Biol, New York, NY 10065 USA.
[Ladanyi, Marc; Pao, William] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Varmus, Harold E.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
RP Wilson, RK (reprint author), Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
EM matthew_meyerson@dfci.harvard.edu; rwilson@wustl.edu
RI Wendl, Michael/A-2741-2008; Chen, Ken/A-1074-2009; Meyerson,
Matthew/E-7123-2012; Dutt, Amit/I-1911-2013;
OI Dutt, Amit/0000-0002-1119-4774; Chang, Andrew/0000-0001-9506-0425;
Giordano, Thomas/0000-0003-0641-8873
FU National Human Genome Research Institute
FX We thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual
contributions, and many members of the Baylor Human Genome Sequencing
Center, the Broad Institute of Harvard and MIT, and the Genome Center at
Washington University for support. This work was funded by grants from
the National Human Genome Research Institute to E.S.L., R.A.G. and
R.K.W.
NR 50
TC 1294
Z9 1335
U1 29
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1069
EP 1075
DI 10.1038/nature07423
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600036
PM 18948947
ER
PT J
AU Gavathiotis, E
Suzuki, M
Davis, ML
Pitter, K
Bird, GH
Katz, SG
Tu, HC
Kim, H
Cheng, EHY
Tjandra, N
Walensky, LD
AF Gavathiotis, Evripidis
Suzuki, Motoshi
Davis, Marguerite L.
Pitter, Kenneth
Bird, Gregory H.
Katz, Samuel G.
Tu, Ho-Chou
Kim, Hyungjin
Cheng, Emily H. -Y.
Tjandra, Nico
Walensky, Loren D.
TI BAX activation is initiated at a novel interaction site
SO NATURE
LA English
DT Article
ID MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; STABILIZED ALPHA-HELICES;
BCL-X-L; BH3-ONLY PROTEINS; CELL-DEATH; INTRACELLULAR-LOCALIZATION;
PROAPOPTOTIC ACTIVITY; BH3 DOMAINS; APOPTOSIS; FAMILY
AB BAX is a pro- apoptotic protein of the BCL- 2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti- apoptotic proteins such as BCL- 2 counteract BAX- mediated cell death. Although an interaction site that confers survival functionality has been defined for anti- apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha- helix of BCL- 2 domains ( SAHBs) that directly initiate BAX- mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti- apoptotic proteins. The specificity of the human BIM- SAHB - BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.
C1 [Suzuki, Motoshi; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Tu, Ho-Chou; Kim, Hyungjin; Cheng, Emily H. -Y.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Tu, Ho-Chou; Kim, Hyungjin; Cheng, Emily H. -Y.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Gavathiotis, Evripidis; Suzuki, Motoshi; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA.
[Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov; loren_walensky@dfci.harvard.edu
FU National Cancer Institute [5P01CA92625, 5RO1CA50239, 5RO1CA125562];
Burroughs Wellcome Fund Career Award; Culpeper Scholarship in Medical
Science; American Society of Hematology Junior Faculty Scholar Award;
William Lawrence Children's Foundation; Intramural Research Program of
the National Heart, Lung and Blood Institute; Searle Scholars Program
FX We thank E. Smith for editorial and graphics assistance, W. Beavers for
amino acid analyses, A. Perry for technical assistance, C. Turner and A.
Bielecki of the MIT/Harvard Center for Magnetic Resonance for NMR
technical advice, and R. Youle for feedback on the manuscript. We
acknowledge the indelible contributions of the late S.J. Korsmeyer, who
inspired this work. L.D.W. is supported by National Cancer Institute
(NCI) grant 5P01CA92625, a Burroughs Wellcome Fund Career Award in the
Biomedical Sciences, a Culpeper Scholarship in Medical Science from the
Goldman Philanthropic Partnerships, an American Society of Hematology
Junior Faculty Scholar Award, and a grant from the William Lawrence
Children's Foundation. This research was also supported by NCI grant
5RO1CA50239. N.T. is supported by the Intramural Research Program of the
National Heart, Lung and Blood Institute, NIH. E.H.-Y.C. is supported by
the Searle Scholars Program and NCI grant 5RO1CA125562.
NR 50
TC 374
Z9 384
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 OCT 23
PY 2008
VL 455
IS 7216
BP 1076
EP U6
DI 10.1038/nature07396
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600037
PM 18948948
ER
PT J
AU Zheng, HW
Ying, HQ
Yan, HY
Kimmelman, AC
Hiller, DJ
Chen, AJ
Perry, SR
Tonon, G
Chu, GC
Ding, ZH
Stommel, JM
Dunn, KL
Wiedemeyer, R
You, MJJ
Brennan, C
Wang, YA
Ligon, KL
Wong, WH
Chin, L
DePinho, RA
AF Zheng, Hongwu
Ying, Haoqiang
Yan, Haiyan
Kimmelman, Alec C.
Hiller, David J.
Chen, An-Jou
Perry, Samuel R.
Tonon, Giovanni
Chu, Gerald C.
Ding, Zhihu
Stommel, Jayne M.
Dunn, Katherine L.
Wiedemeyer, Ruprecht
You, Mingjian J.
Brennan, Cameron
Wang, Y. Alan
Ligon, Keith L.
Wong, Wing H.
Chin, Lynda
DePinho, Ronald A.
TI p53 and Pten control neural and glioma stem/progenitor cell renewal and
differentiation
SO NATURE
LA English
DT Article
ID CANCER STEM-CELLS; SELF-RENEWAL; INITIATING CELLS; C-MYC; TUMORS;
GLIOBLASTOMA; EXPRESSION; RECEPTOR; PATHWAYS; BIOLOGY
AB Glioblastoma ( GBM) is a highly lethal brain tumour presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as a high-grade disease that typically harbours mutations in EGFR, PTEN and INK4A/ARF ( also known as CDKN2A), and the secondary GBM subtype evolves from the slow progression of a low- grade disease that classically possesses PDGF and TP53 events(1-3). Here we show that concomitant central nervous system (CNS)- specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute- onset high- grade malignant glioma phenotype with notable clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted TP53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of TP53 as well as the expected PTEN mutations. Integrated transcriptomic profiling, in silico promoter analysis and functional studies of murine neural stem cells ( NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives increased Myc protein levels and its associated signature. Functional studies validated increased Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of NSCs doubly null for p53 and Pten (p53(-/-) Pten(-/-)) as well as tumour neurospheres (TNSs) derived from this model. Myc also serves to maintain robust tumorigenic potential of p53(-/-) Pten(-/-) TNSs. These murine modelling studies, together with confirmatory transcriptomic/ promoter studies in human primary GBM, validate a pathogenetic role of a common tumour suppressor mutation profile in human primary GBM and establish Myc as an important target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/ progenitor cell differentiation, self- renewal and tumorigenic potential.
C1 [Zheng, Hongwu; Ying, Haoqiang; Yan, Haiyan; Kimmelman, Alec C.; Chen, An-Jou; Perry, Samuel R.; Tonon, Giovanni; Chu, Gerald C.; Ding, Zhihu; Stommel, Jayne M.; Dunn, Katherine L.; Wiedemeyer, Ruprecht; You, Mingjian J.; Wang, Y. Alan; Ligon, Keith L.; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Perry, Samuel R.; Chu, Gerald C.; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Fdn Inst Innovat Canc Sci, Boston, MA 02115 USA.
[Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Kimmelman, Alec C.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
[Chu, Gerald C.; Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Ligon, Keith L.] Harvard Univ, Sch Med, Div Neuropathol, Boston, MA 02115 USA.
[Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Hiller, David J.; Wong, Wing H.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
[Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
[Brennan, Cameron] Weill Cornell Med Coll, Dept Neurosurg, New York, NY 10065 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM ron_depinho@dfci.harvard.edu
RI leng, xianwei/F-9073-2011;
OI Zheng, Hongwu/0000-0002-5823-4913; Brennan, Cameron/0000-0003-4064-8891
FU Helen Hay Whitney Foundation; Marsha Mae Moeslein Fellowship; American
Brain Tumor Association; Leonard B. Holman Research Pathway Fellowship;
Damon Runyon Cancer Research Foundation; Ruth L. Kirschstein National
Research Service Award Fellowship; Mildred Scheel Fellowship (Deutsche
Krebshilfe); Goldhirsh Foundation; NIH [U01 CA84313, RO1CA99041,
5P01CA95616]; Robert A. and Renee E. Belfer Foundation Institute for
Innovative Cancer Science
FX We thank A. Berns for providing p53 L mice; S. Zhou and S. Jiang for
mouse husbandry and care; R. T. Bronson for discussion on pathology
analysis; K. Montgomery for discussion on sequencing; and Y.- H. Xiao,
B. Feng and J. Zhang for bioinformatic help. H. Z. was supported by
Helen Hay Whitney Foundation. H. Ying is a recipient of the Marsha Mae
Moeslein Fellowship from the American Brain Tumor Association. A. C. K.
is a recipient of the Leonard B. Holman Research Pathway Fellowship. Z.
D. is supported by the Damon Runyon Cancer Research Foundation. J. M. S.
is supported by a Ruth L. Kirschstein National Research Service Award
Fellowship. R. W. is supported by a Mildred Scheel Fellowship ( Deutsche
Krebshilfe). Grant support comes from the Goldhirsh Foundation (R.A.D.),
and NIH grants U01 CA84313 (R.A.D.), RO1CA99041 ( L. C.) and 5P01CA95616
(R.A.D., L.C., W.H.W., C.B. and K.L.L.). R.A.D. is an American Cancer
Society Research Professor supported by the Robert A. and Renee E.
Belfer Foundation Institute for Innovative Cancer Science.
NR 35
TC 358
Z9 366
U1 4
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 23
PY 2008
VL 455
IS 7216
BP 1129
EP U13
DI 10.1038/nature07443
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363FG
UT WOS:000260252600049
PM 18948956
ER
PT J
AU Joshi, PS
Molyneaux, BJ
Feng, L
Xie, XL
Macklis, JD
Gan, L
AF Joshi, Pushkar S.
Molyneaux, Bradley J.
Feng, Liang
Xie, Xiaoling
Macklis, Jeffrey D.
Gan, Lin
TI Bhlhb5 Regulates the Postmitotic Acquisition of Area Identities in
Layers II-V of the Developing Neocortex
SO NEURON
LA English
DT Article
ID CORTICOSPINAL MOTOR-NEURONS; DEVELOPING CEREBRAL-CORTEX; GREEN
FLUORESCENT PROTEIN; MOUSE BARREL CORTEX; COUP-TFI; DIFFERENTIAL
EXPRESSION; AXONAL PROJECTIONS; DROSOPHILA EMBRYO; MAMMALIAN CORTEX;
SPINAL-CORD
AB While progenitor-restricted factors broadly specify area identities in developing neocortex, the downstream regulatory elements involved in acquisition of those identities in postmitotic neurons are largely unknown. Here, we identify Bhlhb5, a transcription factor expressed in layers II-V, as a postmitotic regulator of area identity. Bhlhb5 is initially expressed in a high caudomedial to low rostrolateral gradient that transforms into a sharp border between sensory and rostral motor cortices. Bhlhb5 null mice exhibit aberrant expression of area-specific genes and structural organization in the somatosensory and caudal motor cortices. In somatosensory cortex, Bhlhb5 null mice display postsynaptic disorganization of vibrissal barrels. In caudal motor cortex, Bhlhb5 null mice exhibit anomalous differentiation of corticospinal motor neurons, accompanied by failure of corticospinal tract formation. Together, these results demonstrate Bhlhb5's function as an area-specific transcription factor that regulates the postmitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and postmitotic neurons driving neocortical arealization.
C1 [Molyneaux, Bradley J.; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurol, Cambridge, MA 02138 USA.
[Molyneaux, Bradley J.; Macklis, Jeffrey D.] Harvard Univ, Sch Med, Program Neurosci, Cambridge, MA 02138 USA.
[Macklis, Jeffrey D.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA.
[Macklis, Jeffrey D.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA.
[Macklis, Jeffrey D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Boston, MA 02114 USA.
[Joshi, Pushkar S.; Feng, Liang; Xie, Xiaoling; Gan, Lin] Univ Rochester, Dept Ophthalmol, Rochester, NY 14642 USA.
[Gan, Lin] Univ Rochester, Ctr Neural Dev & Dis, Rochester, NY 14642 USA.
[Gan, Lin] Univ Rochester, Dept Neurobiol & Anat, Rochester, NY 14642 USA.
[Molyneaux, Bradley J.; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Cambridge, MA 02138 USA.
RP Macklis, JD (reprint author), Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Cambridge, MA 02138 USA.
EM jeffrey_macklis@hms.harvard.edu; lin_gan@urmc.rochester.edu
OI Molyneaux, Bradley/0000-0002-3377-1229
FU NIH [EY013426, EY015551, NS45523, NS49553]; Harvard M.S.T.P; United
Sydney Association
FX We thank Drs. J. Rubenstein. R. Hevner. S. McConnell. T. Mori, T.
Rabbitts, M. Tsai, C. Learry, and K-F. Lee for generous sharing of
antibodies and cDNA clones; Y. Yanagawa, V. Cuzon, and H. Yeh for
providing GAD67-GFP knockin brains: J. Zhang, A. Majewska, and K.
Billmers for technical help with corticospinal tracing. This work was
supported by NIH grants EY013426 and EY015551 to L.G.. NIH grants
NS45523 and NS49553 to J.D.M., the Research to Prevent Blindness
challenge grant to the Department of Ophthalmology at the University of
Rochester (L.G.), the Harvard Stem Cell Institute (J.D.M.), the Spastic
Paraplegia Foundation (J.D.M.), and the ALS Association (J.D.M.). B.J.M.
was supported by the Harvard M.S.T.P. and United Sydney Association.
NR 68
TC 83
Z9 85
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD OCT 23
PY 2008
VL 60
IS 2
BP 258
EP 272
DI 10.1016/j.neuron.2008.08.006
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 367JW
UT WOS:000260549300009
PM 18957218
ER
PT J
AU Wiener, CM
Muse, VV
Mark, EJ
Tinsley, A
Harris, NL
Kanarek, DJ
Korzenik, J
AF Wiener, Charles M.
Muse, Victorine V.
Mark, Eugene J.
Tinsley, Andrew
Harris, Nancy Lee
Kanarek, David J.
Korzenik, Joshua
TI A woman with dyspnea on exertion - Interstitial lymphocytic pneumonitis
and histiocytic pneumonia with eosinophils, findings that are consistent
with drug or hypersensitivity reactions, possibly due to infliximab
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID LUNG-DISEASE; BRONCHOALVEOLAR LAVAGE; INFECTIOUS-DISEASES; CT
C1 [Wiener, Charles M.] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA.
[Wiener, Charles M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Muse, Victorine V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Wiener, CM (reprint author), Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA.
NR 16
TC 6
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 OCT 23
PY 2008
VL 359
IS 17
BP 1823
EP 1832
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 363DJ
UT WOS:000260245800011
PM 18946068
ER
PT J
AU Goodyear, LJ
AF Goodyear, Laurie J.
TI The exercise pill - Too good to be true?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CHRONIC ACTIVATION; GLYCOGEN; MUSCLE
C1 [Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA.
NR 5
TC 57
Z9 60
U1 1
U2 9
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 23
PY 2008
VL 359
IS 17
BP 1842
EP 1844
DI 10.1056/NEJMcibr0806723
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 363DJ
UT WOS:000260245800015
PM 18946072
ER
PT J
AU Mehta, RH
Liang, L
Karve, AM
Hernandez, AF
Rumsfeld, JS
Fonarow, GC
Peterson, ED
AF Mehta, Rajendra H.
Liang, Li
Karve, Amrita M.
Hernandez, Adrian F.
Rumsfeld, John S.
Fonarow, Gregg C.
Peterson, Eric D.
TI Association of patient case-mix adjustment, hospital process performance
rankings, and eligibility for financial incentives
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; COOPERATIVE CARDIOVASCULAR PROJECT; ACUTE
MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; ELDERLY-PATIENTS; UNSTABLE
ANGINA; HEALTH-CARE; DISPARITIES; CRUSADE; PREVENTION
AB Context While most comparisons of hospital outcomes adjust for patient characteristics, process performance comparisons typically do not.
Objective To evaluate the degree to which hospital process performance ratings and eligibility for financial incentives are altered after accounting for hospitals' patient demographics, clinical characteristics, and mix of treatment opportunities.
Design, Setting, and Patients Using data from the American Heart Association's Get With the Guidelines program between January 2, 2000, and March 28, 2008, we analyzed hospital process performance based on the Centers for Medicare & Medicaid Services' defined core measures for acute myocardial infarction. Hospitals were initially ranked based on crude composite process performance and then ranked again after accounting for hospitals' patient demographics, clinical characteristics, and eligibility for measures using a hierarchical model. We then compared differences in hospital performance rankings and pay-for-performance financial incentive categories (top 20%, middle 60%, and bottom 20% institutions).
Main Outcome Measures Hospital process performance ranking and pay-for-performance financial incentive categories.
Results A total of 148 472 acute myocardial infarction patients met the study criteria from 449 centers. Hospitals for which crude composite acute myocardial infarction performance was in the bottom quintile (n=89) were smaller nonacademic institutions that treated a higher percentage of patients from racial or ethnic minority groups and also patients with greater comorbidities than hospitals ranked in the top quintile (n=90). Although there was overall agreement on hospital rankings based on observed vs adjusted composite scores (weighted kappa, 0.74), individual hospital ranking changed with adjustment (median, 22 ranks; range, 0-214; interquartile range, 9-40). Additionally, 16.5% of institutions (n=74) changed pay-for-performance financial status categories after accounting for patient and treatment opportunity mix.
Conclusion Our findings suggest that accounting for hospital differences in patient characteristics and treatment opportunities is associated with modest changes in hospital performance rankings and eligibility for financial benefits in pay-for-performance programs for treatment of myocardial infarction.
C1 [Mehta, Rajendra H.; Liang, Li; Karve, Amrita M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27715 USA.
[Mehta, Rajendra H.; Liang, Li; Karve, Amrita M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC USA.
[Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA.
RP Mehta, RH (reprint author), Duke Clin Res Inst, Box 17969, Durham, NC 27715 USA.
EM mehta007@dcri.duke.edu
RI Hernandez, Adrian F./A-7818-2016
OI Hernandez, Adrian F./0000-0003-3387-9616
FU GlaxoSmithKline; Medtronic; Merck; Pfizer; National Institutes of
Health; AHA; American Heart Association Pharmaceutical Roundtable
[0675060N]; Elliot Corday (Los Angeles, California) Foundation; Ahmanson
(Los Angeles, California) Foundation
FX Dr Hernandez reports receiving research support from GlaxoSmithKline,
Johnson & Johnson (Scios Inc), Medtronic, Novartis, and Roche
Diagnostics; and honoraria from AstraZeneca, Novartis, Sanofi-Aventis,
and Thoratec Corporation. Dr Peterson reports receiving research support
from Schering Plough, BMS/Sanofi; and serving as the principal
investigator for the American Heart Association's (AHA's) Get With the
Guidelines Analytical Center. Drs Hernandez and Peterson report detailed
listings of financial disclosures at
http://www.dcri.duke.edu/research/coi.jsp. Dr Rumsfeld reports receiving
an honorariun for participating on the scientific research advisory
board of United Healthcare. Dr Fonarow reports receiving research grants
from GlaxoSmithKline, Medtronic, Merck, Pfizer, and the National
Institutes of Health; consulting for AstraZeneca, Bristol-Myers Squibb,
GlaxoSmithKline, Medtronic, Merck, Novartis, Pfizer, Sanofi-Aventis, and
Schering Plough; receiving honoraria from AstraZeneca, Abbott,
Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Merck, Novartis,
Pfizer, Sanofi-Aventis, and Schering Plough; and serving as chair of the
AHA's Get With the Guidelines Steering Committee. Drs Mehta and Liang
and Ms Karve report no disclosures. The Get With the Guidelines program
is supported by the AHA in part through an unrestricted education grant
from Merck-Schering Plough. Dr Hernandez reports receiving support from
an American Heart Association Pharmaceutical Roundtable grant 0675060N.
Dr Fonarow reports receiving support from the Elliot Corday (Los
Angeles, California) and Ahmanson (Los Angeles, California) Foundations.
NR 30
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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 OCT 22
PY 2008
VL 300
IS 16
BP 1897
EP 1903
DI 10.1001/jama.300.16.1897
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 362UR
UT WOS:000260223100019
PM 18940976
ER
PT J
AU Ross, JS
Detsky, AS
AF Ross, Joseph S.
Detsky, Allan S.
TI Comparison of the US and Canadian health care systems - A tale of 2
Mount Sinai's
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID UNITED-STATES; COUNTRIES
C1 [Detsky, Allan S.] Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada.
[Detsky, Allan S.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada.
[Detsky, Allan S.] Univ Toronto, Dept Med & Hlth Policy, Toronto, ON, Canada.
[Detsky, Allan S.] Univ Toronto, Dept Management, Toronto, ON, Canada.
[Detsky, Allan S.] Univ Toronto, Dept Evaluat, Toronto, ON, Canada.
[Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA.
[Ross, Joseph S.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA.
[Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
RP Detsky, AS (reprint author), Mt Sinai Hosp, Dept Med, 427-600 Univ Ave, Toronto, ON M5G 1X5, Canada.
EM adetsky@mtsinai.on.ca
NR 13
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Z9 6
U1 0
U2 2
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 OCT 22
PY 2008
VL 300
IS 16
BP 1934
EP 1936
DI 10.1001/jama.300.16.1934
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 362UR
UT WOS:000260223100026
PM 18940983
ER
PT J
AU Loeffler, JS
Halperin, EC
AF Loeffler, Jay S.
Halperin, Edward C.
TI Selling a medical school's name - Ethical and practical dilemmas
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Loeffler, Jay S.] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Halperin, Edward C.] Univ Louisville, Sch Med, Louisville, KY 40292 USA.
RP Loeffler, JS (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, 100 Blossom St,Cox 347, Boston, MA 02114 USA.
EM jloeffler@partners.org
NR 10
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Z9 4
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 OCT 22
PY 2008
VL 300
IS 16
BP 1937
EP 1938
DI 10.1001/jama.300.16.1937
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 362UR
UT WOS:000260223100027
PM 18940984
ER
PT J
AU van Zundert, B
Peuscher, MH
Hynynen, M
Chen, A
Neve, RL
Brown, RH
Constantine-Paton, M
Bellingham, MC
AF van Zundert, Brigitte
Peuscher, Marieke H.
Hynynen, Meri
Chen, Adam
Neve, Rachael L.
Brown, Robert H., Jr.
Constantine-Paton, Martha
Bellingham, Mark C.
TI Neonatal Neuronal Circuitry Shows Hyperexcitable Disturbance in a Mouse
Model of the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral
Sclerosis
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE action potential; brainstem; dendrite; EPSP; IPSP; motor neuron;
interneuron; locomotor activity; sodium channel; synaptic transmission;
superior colliculus
ID PROTEIN-KINASE-C; RAT HYPOGLOSSAL MOTONEURONS; PERSISTENT NA+ CURRENT;
MOTOR-NEURONS; SPINAL MOTONEURONS; CORTICAL HYPEREXCITABILITY;
PHOSPHATASE EXPRESSION; SUPERIOR COLLICULUS; RECEPTOR CURRENTS; CALCIUM
CURRENTS
AB Distinguishing the primary from secondary effects and compensatory mechanisms is of crucial importance in understanding adult-onset neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Transgenic mice that overexpress the G93A mutation of the human Cu-Zn superoxide dismutase 1 gene (hSOD1(G93A) mice) are a commonly used animal model of ALS. Whole-cell patch-clamp recordings from neurons in acute slice preparations from neonatal wild-type and hSOD1(G93A) mice were made to characterize functional changes in neuronal activity. Hypoglossal motoneurons (HMs) in postnatal day 4 (P4)-P10 hSOD1(G93A) mice displayed hyperexcitability, increased persistent Na+ current (PCNa), and enhanced frequency of spontaneous excitatory and inhibitory transmission, compared with wild-type mice. These functional changes in neuronal activity are the earliest yet reported for the hSOD1(G93A) mouse, and are present 2-3 months before motoneuron degeneration and clinical symptoms appear in these mice. Changes in neuronal activity were not restricted to motoneurons: superior colliculus interneurons also displayed hyperexcitability and synaptic changes (P10-P12). Furthermore, in vivo viral-mediated GFP (green fluorescent protein) overexpression in hSOD1(G93A) HMs revealed precocious dendritic remodeling, and behavioral assays revealed transient neonatal neuromotor deficits compared with controls. These findings underscore the widespread and early onset of abnormal neural activity in this mouse model of the adult neurodegenerative disease ALS, and suggest that suppression of PCNa and hyperexcitability early in life might be one way to mitigate or prevent cell death in the adult CNS.
C1 [Bellingham, Mark C.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia.
[van Zundert, Brigitte; Peuscher, Marieke H.; Constantine-Paton, Martha; Bellingham, Mark C.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
[van Zundert, Brigitte; Hynynen, Meri; Chen, Adam; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Dept Neurol, Day Lab Neuromuscular Res, Charlestown, MA 02429 USA.
[Neve, Rachael L.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA.
RP Bellingham, MC (reprint author), Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia.
EM mark.bellingham@uq.edu.au
RI Bellingham, Mark/G-1697-2011
OI Bellingham, Mark/0000-0001-9189-4430
FU National Institutes of Health [EY06039]; Pierre L. de Bourgknecht ALS
Research Foundation; National Institute of Neurological Disorders and
Stroke; National Institute on Aging; ALS Association; Angel Fund;
Project ALS; Al-Athel ALS Foundation; ALS Therapy Alliance (CVS
Pharmacy); Motor Neuron Disease Research Institute of Australia;
National Health and Medical Research Council of Australia
FX This work was supported by National Institutes of Health Grant EY06039
(M.C.-P.); The Pierre L. de Bourgknecht ALS Research Foundation (B.v.Z.,
R. H. B.); the National Institute of Neurological Disorders and Stroke,
the National Institute on Aging, the ALS Association, the Angel Fund,
Project ALS, the Al-Athel ALS Foundation (R. H. B.), and the ALS Therapy
Alliance (CVS Pharmacy) (R. H. B., M. C. B.); and The Motor Neuron
Disease Research Institute of Australia and the National Health and
Medical Research Council of Australia (M.C.B.). We thank A.J. Berger, J.
Sebe, and R. Power for advice on hypoglossal motoneuron
electrophysiological experiments and J. Durand for advice on the
behavioral studies. B.v.Z. and M.C.B. performed all the
electrophysiological experiments and analysis of electrophysiological
data. M. H. P. performed all the HM structural analyses using HSV-GFP
p1003, which was constructed and packaged by R.L.N. Behavioral testing
was performed and analyzed by M. H. and A. C. B.v.Z., R. H. B., M.C.-P.,
and M. C. B all contributed to the experimental design and the writing
of this manuscript.
NR 69
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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 OCT 22
PY 2008
VL 28
IS 43
BP 10864
EP 10874
DI 10.1523/JNEUROSCI.1340-08.2008
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 363KH
UT WOS:000260265700010
PM 18945894
ER
PT J
AU Famous, KR
Kumaresan, V
Sadri-Vakili, G
Schmidt, HD
Mierke, DF
Cha, JHJ
Pierce, RC
AF Famous, Katie R.
Kumaresan, Vidhya
Sadri-Vakili, Ghazaleh
Schmidt, Heath D.
Mierke, Dale F.
Cha, Jang-Ho J.
Pierce, R. Christopher
TI Phosphorylation-Dependent Trafficking of GluR2-Containing AMPA Receptors
in the Nucleus Accumbens Plays a Critical Role in the Reinstatement of
Cocaine Seeking
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE relapse; addiction; psychostimulant; glutamate; CNQX; Pep2-EVKI
ID INDUCED PLACE PREFERENCE; PRIMING-INDUCED REINSTATEMENT; GLUTAMATE
TRANSMISSION; SYNAPTIC PLASTICITY; BEHAVIORAL SENSITIZATION; NMDA
RECEPTOR; DRUG-SEEKING; RATS; ANTAGONIST; SHELL
AB A growing body of evidence indicates that enhanced AMPA-mediated glutamate transmission in the core of the nucleus accumbens is critically involved in cocaine priming-induced reinstatement of drug seeking, an animal model of relapse. However, the extent to which increased glutamate transmission in the other major subregion of the nucleus accumbens, the shell, contributes to the reinstatement of cocaine seeking remains unclear. In the present experiments, administration of the AMPA/kainate receptor antagonist CNQX (0, 0.03, or 0.3 mu g) into either the core or the shell of the nucleus accumbens before a systemic cocaine priming injection (10 mg/kg, i.p.) dosedependently attenuated the reinstatement of drug seeking. Cocaine priming-induced reinstatement of cocaine seeking also was associated with increases in GluR2-pSer880 in the nucleus accumbens shell. The phosphorylation of GluR2 by PKC at Ser880 plays an important role in the trafficking of GluR2-containing AMPA receptors from the plasma membrane. The current results showed that administration of a cell-permeable peptide that disrupts GluR2 trafficking (Pep2-EVKI) into either the accumbens core or shell attenuated cocaine-induced reinstatement of drug seeking. Together, these findings indicate that changes in AMPA receptor-mediated glutamate transmission in both the nucleus accumbens core and shell are necessary for the reinstatement of drug seeking induced by a priming injection of cocaine. The present results also demonstrate that the reinstatement of cocaine seeking is associated with increases in the phosphorylation-dependent trafficking of GluR2-containing AMPA receptors in the nucleus accumbens.
C1 [Famous, Katie R.; Kumaresan, Vidhya; Schmidt, Heath D.; Pierce, R. Christopher] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA.
[Pierce, R. Christopher] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Sadri-Vakili, Ghazaleh; Cha, Jang-Ho J.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA.
[Mierke, Dale F.] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA.
RP Pierce, RC (reprint author), Univ Penn, Dept Psychiat, Sch Med, 125 S 31st St, Philadelphia, PA 19104 USA.
EM rcpierce@mail.med.upenn.edu
FU National Institutes of Health (NIH) [R01 DA22339, R01 DA15214, K02
DA18678]; National Research Service Award (NRSA) from the NIH [F30
DA19304]; NIH Training [T32 GM008541-7]; Glendorn Foundation; [R01
DA18428]; [DA16824]
FX This work was supported by National Institutes of Health (NIH) Grants
R01 DA22339, R01 DA15214, K02 DA18678 (R.C.P.), and R01 DA18428
(D.F.M.). K.R.F. was partially supported by a National Research Service
Award (NRSA) from the NIH (F30 DA19304), as well as NIH Training Grant
T32 GM008541-7. H. D. S. was also partially supported by a NRSA from the
NIH (DA16824). J.-H.J.C. and G.S.V. received support from the Glendorn
Foundation. We thank Audrey Pierce for administrative assistance and Dr.
Marina Wolf for comments on previous versions of this manuscript.
NR 59
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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 OCT 22
PY 2008
VL 28
IS 43
BP 11061
EP 11070
DI 10.1523/JNEUROSCI.1221-08.2008
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 363KH
UT WOS:000260265700029
PM 18945913
ER
PT J
AU Hebert, PL
Sisk, JE
Wang, JJ
Tuzzio, L
Casabianca, JM
Chassin, MR
Horowitz, C
McLaughlin, MA
AF Hebert, Paul L.
Sisk, Jane E.
Wang, Jason J.
Tuzzio, Leah
Casabianca, Jodi M.
Chassin, Mark R.
Horowitz, Carol
McLaughlin, Mary Ann
TI Cost-Effectiveness of Nurse-Led Disease Management for Heart Failure in
an Ethnically Diverse Urban Community
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RANDOMIZED-TRIAL; SF-12; CARE; QUALITY; HEALTH; POPULATION; UTILITY;
TRENDS; RISK
AB Background: Randomized, controlled trials have shown that nurse-led disease management for patients with heart failure can reduce hospitalizations. Less is known about the cost-effectiveness of these interventions.
Objective: To estimate the cost-effectiveness of a nurse-led disease management intervention over 12 months, implemented in a randomized, controlled effectiveness trial.
Design: Cost-effectiveness analysis conducted alongside a randomized trial.
Data Sources: Medical costs from administrative records, and self-reported quality of life and nonmedical costs from patient surveys.
Participants: Patients with systolic dysfunction recruited from ambulatory clinics in Harlem, New York.
Time Horizon: 12 months.
Perspective: Societal and payer.
Intervention: 12-month program that involved 1 face-to-face encounter with a nurse and regular telephone follow- up.
Outcome Measures: Quality of life as measured by the Health Utilities Index Mark 3 and EuroQol-5D and cost-effectiveness as measured by the incremental cost-effectiveness ratio ( ICER).
Results of Base-Case Analysis: Costs and quality of life were higher in the nurse-managed group than the usual care group. The ICERs over 12 months were $17 543 per EuroQol-5D-based quality-adjusted life-year ( QALY) and $15 169 per Health Utilities Index Mark 3-based QALY ( in 2001 U. S. dollars).
Results of Sensitivity Analysis: From a payer perspective, the ICER ranged from $3673 to $4495 per QALY. Applying national prices in place of New York City prices yielded a societal ICER of $13 460 to $ 15 556 per QALY. Cost-effectiveness acceptability curves suggest that the intervention was most likely cost-effective for patients with less severe ( New York Heart Association classes I to II) heart failure.
Limitation: The trial was conducted in an ethnically diverse, inner-city neighborhood; thus, results may not be generalizable to other communities.
Conclusion: Over 12 months, the nurse-led disease management program was a reasonably cost-effective way to reduce the burden of heart failure in this community.
C1 Univ Washington, Sch Publ Hlth & Community Med, Vet Adm Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA.
Mt Sinai Sch Med, New York, NY USA.
Fordham Univ, Bronx, NY 10458 USA.
Joint Commiss, Oak Brook Terrace, IL USA.
RP Hebert, PL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM Paul.Hebert2@va.gov
FU Agency for Healthcare Research and Quality [R01 HS10402-01]
FX Grant Support: Dr. Sisk was supported by a grant from the Agency for
Healthcare Research and Quality (R01 HS10402-01).
NR 39
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U2 17
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD OCT 21
PY 2008
VL 149
IS 8
BP 540
EP W105
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 367XJ
UT WOS:000260585600003
PM 18936502
ER
PT J
AU Eikelboom, JW
Hankey, GJ
Thom, J
Bhatt, DL
Steg, PG
Montalescot, G
Johnston, SC
Steinhubl, SR
Mak, KH
Easton, JD
Hamm, C
Hu, TF
Fox, KAA
Topol, EJ
AF Eikelboom, John W.
Hankey, Graeme J.
Thom, Jim
Bhatt, Deepak L.
Steg, P. Gabriel
Montalescot, Gilles
Johnston, S. Claiborne
Steinhubl, Steven R.
Mak, Koon-Hou
Easton, J. Donald
Hamm, Christian
Hu, Tingfei
Fox, Keith A. A.
Topol, Eric J.
CA CHARISMA Investigators
TI Incomplete Inhibition of Thromboxane Biosynthesis by Acetylsalicylic
Acid Determinants and Effect on Cardiovascular Risk
SO CIRCULATION
LA English
DT Article
DE aspirin; aspirin resistance; atherosclerosis
ID LOW-DOSE ASPIRIN; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION;
PLATELET-FUNCTION; PRIMARY PREVENTION; RANDOMIZED-TRIALS; CHARISMA
TRIAL; THERAPY; DISEASE; CLOPIDOGREL
AB Background -Incomplete inhibition of platelet thromboxane generation, as measured by elevated urinary 11-dehydro thromboxane B(2) concentrations, has been associated with an increased risk of cardiovascular events. We aimed to determine the external validity of this association in aspirin-treated patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial and to determine whether there are any modifiable factors or interventions that lower urinary 11-dehydro thromboxane B2 concentrations that could thereby reduce cardiovascular risk.
Methods and Results -Urinary 11-dehydro thromboxane B2 concentrations were measured in 3261 aspirin-treated patients at least 1 month after they had been randomly assigned to placebo or clopidogrel. Baseline urinary 11-dehydro thromboxane B2 concentrations in the highest quartile were associated with an increased risk of stroke, myocardial infarction, or cardiovascular death compared with the lowest quartile (adjusted hazard ratio 1.66, 95% CI 1.06 to 2.61, P = 0.03). Increasing age, female sex, history of peripheral artery disease, current smoking, and oral hypoglycemic or angiotensin-converting enzyme inhibitor therapy were independently associated with higher urinary concentrations of 11-dehydro thromboxane B2, whereas aspirin dose >= 150 mg/d, history of treatment with nonsteroidal antiinflammatory drugs, history of hypercholesterolemia, and statin treatment were associated with lower concentrations. Randomization to clopidogrel (versus placebo) did not reduce the hazard of cardiovascular events in patients in the highest quartile of urinary 11-dehydro thromboxane B2 levels.
Conclusions -In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 are an externally valid and potentially modifiable determinant of stroke, myocardial infarction, or cardiovascular death in patients at risk for atherothrombotic events. (Circulation. 2008; 118: 1705-1712.)
C1 [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Stroke Unit, Perth, WA 6000, Australia.
[Eikelboom, John W.] McMaster Univ, Hamilton, ON, Canada.
[Thom, Jim] Royal Perth Hosp, Dept Haematol, Perth, WA 6000, Australia.
[Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Hu, Tingfei] Cleveland Clin, Cleveland, OH 44106 USA.
[Steg, P. Gabriel] Univ Paris 07, INSERM, AP HP, U698, Paris, France.
[Montalescot, Gilles] Hop La Pitie Salpetriere, Inst Cardiol, APHP, Paris, France.
[Montalescot, Gilles] Hop La Pitie Salpetriere, INSERM, U856, Paris, France.
[Johnston, S. Claiborne] UCSF Neurol, San Francisco, CA USA.
[Steinhubl, Steven R.] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA.
[Mak, Koon-Hou] Gleneagles Med Ctr, Singapore, Singapore.
[Easton, J. Donald] Brown Univ, Providence, RI 02912 USA.
[Hamm, Christian] Kerckhoff Heart Ctr, Bad Nauheim, Germany.
[Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
[Topol, Eric J.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Topol, Eric J.] Scripps Clin, La Jolla, CA 92037 USA.
RP Hankey, GJ (reprint author), Royal Perth Hosp, Dept Neurol, Stroke Unit, 197 Wellington St, Perth, WA 6000, Australia.
EM gjhankey@cyllene.uwa.edu.au
RI Walker, Philip/F-3034-2010; Hankey, Graeme /H-4968-2014;
OI Hankey, Graeme /0000-0002-6044-7328; Eikelboom,
John/0000-0003-4126-1285; Topol, Eric/0000-0002-1478-4729
NR 35
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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 OCT 21
PY 2008
VL 118
IS 17
BP 1705
EP 1712
DI 10.1161/CIRCULATIONAHA.108.768283
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 362HQ
UT WOS:000260189200004
PM 18838564
ER
PT J
AU Bell, BD
Giovagnoli, AR
AF Bell, Brian D.
Giovagnoli, Anna R.
TI Memory after temporal lobe epilepsy surgery Risk and reward
SO NEUROLOGY
LA English
DT Editorial Material
ID LOBECTOMY
C1 [Bell, Brian D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53792 USA.
[Bell, Brian D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Giovagnoli, Anna R.] Ist Nazl Neurol Carlo Besta, Dept Clin Neurosci, Neuropsychol Lab, Milan, Italy.
RP Bell, BD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, 600 Highland Ave, Madison, WI 53792 USA.
EM bell@neurology.wisc.edu
NR 6
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 21
PY 2008
VL 71
IS 17
BP 1302
EP 1303
DI 10.1212/01.wnl.0000326065.70180.03
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 362IJ
UT WOS:000260191100002
PM 18784375
ER
PT J
AU Grimm, SA
McCannel, CA
Omuro, AMP
Ferreri, AJM
Blay, JY
Neuwelt, EA
Siegal, T
Batchelor, T
Jahnke, K
Shenkier, TN
Hall, AJ
Graus, F
Herrlinger, U
Schiff, D
Raizer, J
Rubenstein, J
Laperriere, N
Thiel, E
Doolittle, N
Iwamoto, FM
Abrey, LE
AF Grimm, S. A.
McCannel, C. A.
Omuro, A. M. P.
Ferreri, A. J. M.
Blay, J. -Y.
Neuwelt, E. A.
Siegal, T.
Batchelor, T.
Jahnke, K.
Shenkier, T. N.
Hall, A. J.
Graus, F.
Herrlinger, U.
Schiff, D.
Raizer, J.
Rubenstein, J.
Laperriere, N.
Thiel, E.
Doolittle, N.
Iwamoto, F. M.
Abrey, L. E.
TI Primary CNS lymphoma with intraocular involvement International PCNSL
Collaborative Group Report
SO NEUROLOGY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; HIGH-DOSE METHOTREXATE; RADIATION-THERAPY;
CHEMOTHERAPY; RADIOTHERAPY; EXPERIENCE; BIOPSY
AB Objective: To describe the demographics, diagnostic details, therapeutic management, and outcome in patients with primary CNS lymphoma (PCNSL) with ocular involvement.
Methods: A retrospective study of 221 patients was assembled from 16 centers in seven countries. Only HIV-negative, immunocompetent patients with brain and ocular lymphoma were included; none had systemic lymphoma.
Results: Median age at diagnosis was 60. Fifty-seven percent were women. Median Eastern Cooperative Oncology Group performance status was 2. Ocular disturbance and behavioral/cognitive changes were the most common presenting symptoms. Diagnosis of lymphoma was made by brain biopsy (147), vitrectomy (65), or CSF cytology (11). Diagnosis of intraocular lymphoma was made by vitrectomy/choroidal/retinal biopsy (90) or clinical ophthalmic examination (141). CSF cytology was positive in 23%. Treatment information was available for 176 patients. A total of 102 received dedicated ocular therapy (ocular radiotherapy 79, intravitreal methotrexate 22, and both 1) in addition to treatment for their brain lymphoma. Sixty-nine percent progressed at a median of 13 months; sites of progression included brain 52%, eyes 19%, brain and eyes 12%, and systemic 2%. Patients treated with local ocular therapy did not have a statistically significant decreased risk of failing in the eyes (p = 0.7). Median progression free survival and overall survival for the entire cohort were 18 and 31 months.
Conclusion: This is the largest reported series of primary CNS lymphoma (PCNSL) with intraocular involvement. Progression free and overall survival was similar to that reported with PCNSL. Dedicated ocular therapy improved disease control but did not affect overall survival. Neurology (R) 2008; 71: 1355-1360
C1 [Abrey, L. E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
[McCannel, C. A.] Mayo Clin, Rochester, MN USA.
[Omuro, A. M. P.] Grp Hosp Pitie Salpetriere, F-75634 Paris, France.
[Neuwelt, E. A.; Doolittle, N.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Siegal, T.] Hadassah Hebrew Univ Hosp, Jerusalem, Israel.
[Batchelor, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jahnke, K.; Thiel, E.] Charite Univ Med Berlin, D-13353 Berlin, Germany.
[Shenkier, T. N.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Hall, A. J.] Royal Melbourne Hosp, Melbourne, Vic, Australia.
[Hall, A. J.] Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3002, Australia.
[Graus, F.] Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Barcelona, Spain.
[Herrlinger, U.] Univ Tubingen, D-72074 Tubingen, Germany.
[Schiff, D.] Univ Virginia, Charlottesville, VA USA.
[Raizer, J.] NW Mem Hosp, Chicago, IL 60611 USA.
[Rubenstein, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Laperriere, N.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
RP Abrey, LE (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA.
EM abreyl@mskcc.org
RI Ferreri, Andres Jose Maria/A-6662-2013; Blay, Jean-Yves/N-3966-2016;
OI Ferreri, Andres Jose Maria/0000-0001-9606-6124; Blay,
Jean-Yves/0000-0001-7190-120X; McCannel, Colin/0000-0003-0774-6414
FU NCI NIH HHS [K23 CA100291, R13 CA124293]
NR 20
TC 68
Z9 73
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 21
PY 2008
VL 71
IS 17
BP 1355
EP 1360
DI 10.1212/01.wnl.0000327672.04729.8c
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 362IJ
UT WOS:000260191100010
PM 18936428
ER
PT J
AU Koulmanda, M
Bhasin, M
Hoffman, L
Fan, ZG
Qipo, AD
Shi, H
Bonner-Weir, S
Putheti, P
Degauque, N
Libermann, TA
Auchincloss, H
Flier, JS
Strom, TB
AF Koulmanda, Maria
Bhasin, Manoj
Hoffman, Lauren
Fan, Zhigang
Qipo, Andi
Shi, Hang
Bonner-Weir, Susan
Putheti, Prabhakar
Degauque, Nicolas
Libermann, Towia A.
Auchincloss, Hugh, Jr.
Flier, Jeffrey S.
Strom, Terry B.
TI Curative and beta cell regenerative effects of alpha 1-antitrypsin
treatment in autoimmune diabetic NOD mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE autoimmunity; type 1 diabetes; inflammation
ID REGULATORY T-CELLS; INSULIN-RESISTANCE; PANCREATIC-ISLETS;
MESSENGER-RNA; TGF-BETA; TYPE-1; ONSET; INFLAMMATION; REJECTION;
APOPTOSIS
AB Invasive insulitis is a destructive T cell-dependent autoimmune process directed against insulin-producing beta cells that is central to the pathogenesis of type 1 diabetes mellitus (T1DM) in humans and the clinically relevant nonobese diabetic (NOD) mouse model. Few therapies have succeeded in restoring long-term, drug-free euglycemia and immune tolerance to beta cells in overtly diabetic NOD mice, and none have demonstrably enabled enlargement of the functional beta cell mass. Recent studies have emphasized the impact of inflammatory cytokines on the commitment of antigen-activated T cells to various effector or regulatory T cell phenotypes and insulin resistance and defective insulin signaling. Hence, we tested the hypothesis that inflammatory mechanisms trigger insulitis, insulin resistance, faulty insulin signaling, and the loss of immune tolerance to islets. We demonstrate that treatment with alpha 1-antitrypsin (AAT), an agent that dampens inflammation, does not directly inhibit T cell activation, ablates invasive insulitis, and restores euglycemia, immune tolerance to beta cells, normal insulin signaling, and insulin responsiveness in NOD mice with recent-onset T1DM through favorable changes in the inflammation milieu. Indeed, the functional mass of beta cells expands in AAT-treated diabetic NOD mice.
C1 [Koulmanda, Maria; Hoffman, Lauren; Fan, Zhigang; Qipo, Andi; Shi, Hang; Auchincloss, Hugh, Jr.; Strom, Terry B.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Bhasin, Manoj; Putheti, Prabhakar; Degauque, Nicolas; Libermann, Towia A.; Flier, Jeffrey S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Bhasin, Manoj; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, Genom Ctr, Boston, MA 02115 USA.
[Koulmanda, Maria; Fan, Zhigang; Qipo, Andi; Putheti, Prabhakar; Degauque, Nicolas; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Transplant Res Ctr, Boston, MA 02115 USA.
[Hoffman, Lauren; Shi, Hang; Flier, Jeffrey S.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02115 USA.
[Bonner-Weir, Susan] Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Strom, TB (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
EM strom@bidmc.harvard.edu
RI Libermann, Towia/F-9866-2010;
OI Degauque, Nicolas/0000-0003-2990-3513; Libermann,
Towia/0000-0002-4006-8179
NR 41
TC 101
Z9 109
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 21
PY 2008
VL 105
IS 42
BP 16242
EP 16247
DI 10.1073/pnas.0808031105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 368BX
UT WOS:000260597400033
PM 18852471
ER
PT J
AU Cohen, T
Colijn, C
Murray, M
AF Cohen, Ted
Colijn, Caroline
Murray, Megan
TI Modeling the effects of strain diversity and mechanisms of strain
competition on the potential performance of new tuberculosis vaccines
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE bacillus Calmette-Guerin; mathematical model; strain replacement
ID MYCOBACTERIUM-TUBERCULOSIS; BEIJING GENOTYPE; RESISTANT TUBERCULOSIS;
IMPERFECT VACCINES; CLINICAL ISOLATE; IMMUNE-RESPONSE; VACCINATION;
EVOLUTION; VIRULENCE; POLYMORPHISM
AB While bacillus Calmette-Guerin vaccination plays an important role in reducing the morbidity of tuberculosis (TB) infection during childhood, new tuberculosis vaccines are necessary to disrupt the transmission of disease and improve global control of this pathogen. Growing evidence of the presence of meaningful Mycobacterium tuberculosis strain diversity, coupled with the possibility that new vaccines may differentially protect against infection or disease with circulating M. tuberculosis strains, suggest that these vaccines may have complicated effects on disease dynamics. We use a mathematical model to explore the potential effects of strain diversity on the performance of vaccines and find that vaccines offer great promise for improving tuberculosis control, but the expected benefits of mass vaccination will be eroded if strain replacement with M. tuberculosis variants that are not effectively targeted by vaccines occurs. Determining the likelihood of strain replacement will require additional knowledge of the strain specificities of current vaccine candidates, and an improved understanding of the mechanisms of strain interaction, which are responsible for maintaining the diversity of M. tuberculosis within communities.
C1 [Cohen, Ted; Murray, Megan] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
[Cohen, Ted; Colijn, Caroline; Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Colijn, Caroline] Univ Bristol, Dept Engn Math, Bristol BS8 1TR, Avon, England.
[Murray, Megan] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Cohen, T (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA.
EM tcohen@hsph.harvard.edu
RI Cohen, Ted/G-8101-2011
FU National Institutes of Health [K08 AI055985-06]
FX We thank Gary Schoolnik and Barun Mathema for comments on an early draft
and Hana Akselrod for assistance with manuscript preparation. This work
was supported by National Institutes of Health Grant K08 AI055985-06
NR 49
TC 18
Z9 18
U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 21
PY 2008
VL 105
IS 42
BP 16302
EP 16307
DI 10.1073/pnas.0808746105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 368BX
UT WOS:000260597400043
PM 18849476
ER
PT J
AU Sorror, ML
Storer, BE
Sandmaier, BM
Maris, M
Shizuru, J
Maziarz, R
Agura, E
Chauncey, TR
Pulsipher, MA
McSweeney, PA
Wade, JC
Bruno, B
Langston, A
Radich, J
Niederwieser, D
Blume, KG
Storb, R
Maloney, DG
AF Sorror, Mohamed L.
Storer, Barry E.
Sandmaier, Brenda M.
Maris, Michael
Shizuru, Judith
Maziarz, Richard
Agura, Edward
Chauncey, Thomas R.
Pulsipher, Michael A.
McSweeney, Peter A.
Wade, James C.
Bruno, Benedetto
Langston, Amelia
Radich, Jerald
Niederwieser, Dietger
Blume, Karl G.
Storb, Rainer
Maloney, David G.
TI Five-Year Follow-Up of Patients With Advanced Chronic Lymphocytic
Leukemia Treated With Allogeneic Hematopoietic Cell Transplantation
After Nonmyeloablative Conditioning
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT Tandem Bone Marrow Transplantation Meeting
CY FEB 16, 2007
CL Keystone, CO
SP Amer Soc Bone Marrow Transplant
ID VERSUS-HOST-DISEASE; MINIMAL RESIDUAL DISEASE;
BONE-MARROW-TRANSPLANTATION; TREATMENT-RELATED MORTALITY;
VARIABLE-REGION MUTATIONS; HEAVY-CHAIN GENE; GENOMIC ABERRATIONS;
CLINICAL-EFFICACY; ZAP-70 EXPRESSION; CD38 EXPRESSION
AB Purpose
We reported encouraging early results of allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning in 64 patients who had advanced chronic lymphocytic leukemia (CLL). Here, we have extended the follow-up to a median of 5 years and have included data on an additional 18 patients.
Patients and Methods
Eighty-two patients, age 42 to 72 years, who had fludarabine-refractory CLL were conditioned with 2 Gy total-body irradiation alone or combined with fludarabine followed by HCT from related (n = 52) or unrelated (n = 30) donors.
Results
Complete remission (CR) and partial remission were achieved in 55% and 15% of patients, respectively. Higher CR rates were noted after unrelated HCT (67% v 48%). The 5-year incidences of nonrelapse mortality (NRM), progression/relapse, overall survival, and progression-free survival were 23%, 38%, 50%, and 39%, respectively. Among 25 patients initially reported in CR, 8% relapsed and 8% died as a result of NRM, whereas 84% have remained alive and in CR. Among 14 responding patients who were tested and who had molecular eradication of their disease, two died as a result of NRM, two relapsed, and 10 have remained negative. At 5 years, 76% of living patients were entirely well, whereas 24% continued to receive immunosuppression for chronic graft-versus-host disease; the median performance status in each group was 100% and 90%, respectively. Lymphadenopathy >= 5 cm, but not cytogenetic abnormalities at HCT, predicted relapse. In a risk-stratification model, patients who had lymphadenopathy less than 5 cm and no comorbidities had a 5-year OS of 71%.
Conclusion
Nonmyeloablative HCT resulted in a median survival of 5 years for patients who had fludarabine-refractory CLL with sustained remissions and in the continued resolution of chronic graft-versus-host disease in surviving patients.
C1 [Sorror, Mohamed L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
Stanford Univ, Stanford, CA 94305 USA.
Univ Leipzig, Leipzig, Germany.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Baylor Univ, Baylor, TX USA.
Univ Utah, Salt Lake City, UT USA.
Univ Colorado, Boulder, CO 80309 USA.
Med Coll Wisconsin, Milwaukee, WI 53226 USA.
Univ Turin, Turin, Italy.
Emory Univ, Atlanta, GA 30322 USA.
RP Sorror, ML (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA.
EM msorror@fhcrc.org
FU NCI NIH HHS [CA15704, CA18029, CA78902, P01 CA018029, P01 CA078902]
NR 51
TC 169
Z9 173
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2008
VL 26
IS 30
BP 4912
EP 4920
DI 10.1200/JCO.2007.15.4757
PG 9
WC Oncology
SC Oncology
GA 361FT
UT WOS:000260113600013
PM 18794548
ER
PT J
AU Baer, MR
George, SL
Caligiuri, MA
Sanford, BL
Bothun, SM
Mrozek, K
Kolitz, JE
Powell, BL
Moore, JO
Stone, RM
Anastasi, J
Bloomfield, CD
Larson, RA
AF Baer, Maria R.
George, Stephen L.
Caligiuri, Michael A.
Sanford, Ben L.
Bothun, Sandra M.
Mrozek, Krzysztof
Kolitz, Jonathan E.
Powell, Bayard L.
Moore, Joseph O.
Stone, Richard M.
Anastasi, John
Bloomfield, Clara D.
Larson, Richard A.
TI Low-Dose Interleukin-2 Immunotherapy Does Not Improve Outcome of
Patients Age 60 Years and Older With Acute Myeloid Leukemia in First
Complete Remission: Cancer and Leukemia Group B Study 9720
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 12th International Symposium on Acute Leukemias
CY FEB 16-20, 2008
CL Munich, GERMANY
ID COLONY-STIMULATING FACTOR; ACUTE MYELOGENOUS LEUKEMIA; PHASE-III TRIAL;
RECOMBINANT INTERLEUKIN-2; ELDERLY-PATIENTS; ONCOLOGY-GROUP; IN-VIVO;
CHEMOTHERAPY; CELLS; AML
AB Purpose
Cancer and Leukemia Group B (CALGB) 9720 evaluated subcutaneous low-dose recombinant interleukin-2 (rIL-2) maintenance immunotherapy as a strategy for prolonging remission in older patients with acute myeloid leukemia (AML).
Patients and Methods
AML patients age 60 years and older in first complete remission after induction and consolidation chemotherapy were randomly assigned to no further therapy or a 90-day regimen of 14-day cycles of low-dose rIL-2, aimed at expanding natural killer (NK) cells, followed by 3-day higher doses aimed at activating cytotoxicity of expanded NK cells to lyse residual AML cells. All randomly assigned patients were included in an intention-to-treat analysis.
Results
A total of 163 (64%) of 254 patients who completed induction and consolidation chemotherapy on CALGB 9720 were randomly assigned to rIL-2 (n = 81) or no further therapy (n = 82); the most common reasons for lack of random assignment were patient refusal and relapse. Fifteen patients randomly assigned to rIL-2 never initiated it because of refusal, intercurrent medical problems, or relapse, and 24 patients initiated rIL-2 but stopped early because of toxicity or relapse. Grade 4 toxicities during rIL-2 therapy included thrombocytopenia (65%) and neutropenia (64%), and grade 3 toxicities included anemia (33%), infection (24%) and malaise/fatigue (14%). Forty-two patients (52%) randomly assigned to rIL-2 completed the full 90-day course. Patients in both arms had similar distributions of both disease-free (combined median = 6.1 months; P = .47) and overall survival (combined median = 14.7 months; P = .61) after random assignment. Moreover, the 42 patients who completed all planned therapy did not show prolongation of disease-free or overall survival.
Conclusion
Low-dose rIL-2 maintenance immunotherapy is not a successful strategy in older AML patients.
C1 [Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
N Shore Univ Hosp, Manhasset, NY USA.
Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA.
Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Chicago, Chicago, IL 60637 USA.
RP Baer, MR (reprint author), Univ Maryland, Greenebaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA.
EM mbaer@umm.edu
RI Mrozek, Krzysztof/A-3142-2008;
OI Larson, Richard/0000-0001-9168-3203
FU NCI NIH HHS [CA02599, CA03927, CA31946, CA31983, CA32291, CA33601,
CA35279, CA41287, CA47577, CA77658, U10 CA033601]
NR 32
TC 62
Z9 66
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2008
VL 26
IS 30
BP 4934
EP 4939
DI 10.1200/JCO.2008.17.0472
PG 6
WC Oncology
SC Oncology
GA 361FT
UT WOS:000260113600016
PM 18591543
ER
PT J
AU Chen, RC
Lin, NU
Golshan, M
Harris, JR
Bellon, JR
AF Chen, Ronald C.
Lin, Nancy U.
Golshan, Mehra
Harris, Jay R.
Bellon, Jennifer R.
TI Internal Mammary Nodes in Breast Cancer: Diagnosis and Implications for
Patient Management - A Systematic Review
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID EXTENDED RADICAL-MASTECTOMY; RECEIVING ADJUVANT CHEMOTHERAPY; POSITIVE
AXILLARY NODES; SENTINEL LYMPH-NODES; HIGH-RISK; RANDOMIZED-TRIAL;
CLINICAL-RELEVANCE; DRAINAGE PATTERNS; TUMOR LOCATION; RADIATION-THERAPY
AB The management of internal mammary nodes (IMNs) in breast cancer is controversial. Surgical series from the 1950s showed that one third of breast cancer patients had IMN involvement, with a higher risk in patients with medial tumors and/or positive axillary nodes. IMN metastasis has similar prognostic importance as axillary nodal involvement. However, after three randomized trials showed no survival benefit from extended mastectomy compared with radical or modified radical mastectomy, IMN dissection was largely abandoned. Recently, lymphoscintigraphy studies have renewed interest in IMN evaluation. Approximately one fifth of internal mammary sentinel nodes are pathologic, although most centers do not perform IMN biopsies because of concerns about morbidity and lack of established survival benefit. In addition, results from randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic therapy, which was not routinely administered in the earlier surgical studies, although the contribution from IMN treatment is unclear. IMN irradiation has also been shown to cause increased cardiac morbidity. Before mature results from current randomized trials assessing the benefit of IMN irradiation become available, lymphoscintigraphy may be used to help guide decisions regarding systemic and local-regional treatment. However, even in patients with visualized primary IMN drainage, the potential benefit of treatment should be balanced against the risk of added morbidity.
C1 Harvard Radiat Oncol Program, Boston, MA 02115 USA.
[Bellon, Jennifer R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Bellon, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM jbellon@lroc.harvard.edu
NR 88
TC 102
Z9 110
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 20
PY 2008
VL 26
IS 30
BP 4981
EP 4989
DI 10.1200/JCO.2008.17.4862
PG 9
WC Oncology
SC Oncology
GA 361FT
UT WOS:000260113600023
PM 18711171
ER
PT J
AU Nanda, A
Mamon, HJ
Fuchs, CS
AF Nanda, Akash
Mamon, Harvey J.
Fuchs, Charles S.
TI Sign of Leser-Trelat in Newly Diagnosed Advanced Gastric Adenocarcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ERUPTIVE SEBORRHEIC KERATOSES; ACANTHOSIS NIGRICANS; YOUNG WOMAN; TRIPE
PALMS; MALIGNANCIES
C1 [Nanda, Akash] Harvard Radiat Oncol Program, Boston, MA USA.
[Mamon, Harvey J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Fuchs, Charles S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
RP Nanda, A (reprint author), Harvard Radiat Oncol Program, Boston, MA USA.
NR 20
TC 1
Z9 3
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 OCT 20
PY 2008
VL 26
IS 30
BP 4992
EP 4993
DI 10.1200/JCO.2008.17.9143
PG 2
WC Oncology
SC Oncology
GA 361FT
UT WOS:000260113600025
PM 18809604
ER
PT J
AU Ajani, AE
Reid, CM
Duffy, SJ
Andrianopoulos, N
Lefkovits, J
Black, A
New, G
Lew, R
Shaw, JA
Yan, BP
Gurvitch, R
Al-Fiadh, A
Brennan, AL
Clark, DJ
AF Ajani, Andrew E.
Reid, Christopher M.
Duffy, Stephen J.
Andrianopoulos, Nick
Lefkovits, Jeffrey
Black, Alexander
New, Gishel
Lew, Robert
Shaw, James A.
Yan, Bryan P.
Gurvitch, Ronen
Al-Fiadh, Ali
Brennan, Angela L.
Clark, David J.
TI Outcomes after percutaneous coronary intervention in contemporary
Australian practice: insights from a large multicentre registry
SO MEDICAL JOURNAL OF AUSTRALIA
LA English
DT Article
ID DRUG-ELUTING STENTS; BARE-METAL STENTS; RANDOMIZED CONTROLLED-TRIAL;
AMERICAN-HEART-ASSOCIATION; COLLEGE-OF-CARDIOLOGY; LATE THROMBOSIS;
ARTERY-DISEASE; SLOW-RELEASE; DOUBLE-BLIND; TASK-FORCE
AB Objective: To examine short-and medium-term outcomes of percutaneous coronary interventions (PCIs), with a focus on comparing drug-eluting stents (DESs) with bare-metal stents (BMSs).
Design, setting and participants: Retrospective analysis of data from the Melbourne Interventional Group (MIG) registry, a large multicentre Australian registry. The study cohort consisted of 6364 consecutive patients undergoing 7167 PCIs between April 2004 and August 2007.
Main outcome measures; Clinical events including death, myocardial infarction.(MI), target lesion revascularisation (TLR), target vessel revascularisation (TVR) and major adverse cardiac events (MACE) (a composite of death, MI and TVR), at 30 days and at 12 months.
Results: The cohort was predominantly male (74%), with a mean age of 64.7 years (SD, 12.0 years). DESs were used in 3482 (51.4%) of PCIs. In the overall cohort, rates of clinical events were low at 30 days: mortality (1.9%), MI (2.4%), TLR (2.0%), TVR (2.4%) and MACE (5.7%). At 12 months, event rates were: mortality (5.2%), MI (6.0%), TLR (5.8%), TVR (8.2%) and MACE (16.2%). Patients receiving DESs had similar mortality rates to those receiving BMSs (4.0% v 6.0%; P = 0.62 [propensity score-adjusted]); late thrombosis rates were also similar in the two groups (0.8% v 1.1%; P = 0.38). The proportion of patients receiving DESs fell significantly over time, from 54.9% in the first 24 months to 44.7% in the last 15 months of the study period (P < 0.01). Independent predictors of 12-month mortality included diabetes, renal failure, ST-segment-elevation MI and cardiogenic shock.
Conclusion: Our clinical event rates were comparable with international registry outcomes. Rates of mortality and stent thrombosis were no higher in patients with DESs than those with BMSs. Although DESs were used in about half the procedures (preferentially for higher-risk lesions), recent trends suggest their use is in decline.
C1 [Ajani, Andrew E.] Univ Melbourne, Melbourne, Vic, Australia.
[Lew, Robert] Frankston Hosp, Melbourne, Vic, Australia.
[New, Gishel] Box Hill Hosp, Melbourne, Vic, Australia.
[Black, Alexander] Geelong Hosp, Geelong, Vic, Australia.
[Duffy, Stephen J.; Shaw, James A.] Alfred Hosp, Melbourne, Vic, Australia.
[Yan, Bryan P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yan, Bryan P.] Harvard Univ, Sch Med, Boston, MA USA.
[Al-Fiadh, Ali; Clark, David J.] Austin Hosp, Melbourne, Vic 3084, Australia.
[Reid, Christopher M.; Andrianopoulos, Nick; Brennan, Angela L.] Monash Univ, Dept Epidemiol & Prevent Med, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia.
[Ajani, Andrew E.] Royal Melbourne Hosp, Melbourne, Vic, Australia.
RP Ajani, AE (reprint author), Royal Melbourne Hosp, Melbourne, Vic, Australia.
EM andrew.ajani@mh.org.au
RI Yan, Bryan/C-3390-2008; Shaw, James/F-1522-2010; Yan, Bryan/P-5928-2015
FU AstraZeneca; BIOTRONIK; Boston Scientific; Johnson Johnson; Medtronic;
Pfizer; Sanofi-Aventis; Schering-Plough; Servier; St Jude Medical and
Terumo; National Health and Medical Research Council Centre
FX The MIG acknowledges funding from AstraZeneca, BIOTRONIK, Boston
Scientific, Johnson & Johnson, Medtronic, Pfizer, Sanofi-Aventis,
Schering-Plough, Servier, St Jude Medical and Terumo. These companies do
not have access to the data and do not have the right to review articles
before publication. The work of Stephen Duffy and Catherine Farrington
is supported by a National Health and Medical Research Council Centre of
Clinical Research Excellence grant to the Alfred and Baker Medical Unit.
NR 30
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U1 1
U2 2
PU AUSTRALASIAN MED PUBL CO LTD
PI PYRMONT
PA LEVEL 2, 26-32 PYRMONT BRIDGE RD, PYRMONT, NSW 2009, AUSTRALIA
SN 0025-729X
J9 MED J AUSTRALIA
JI Med. J. Aust.
PD OCT 20
PY 2008
VL 189
IS 8
BP 423
EP 428
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 380CE
UT WOS:000261442500003
PM 18928433
ER
PT J
AU Lutskiy, MI
Park, JY
Remold, SK
Remold-O'Donnell, E
AF Lutskiy, Maxim I.
Park, Jun Y.
Remold, Susanna K.
Remold-O'Donnell, Eileen
TI Evolution of Highly Polymorphic T Cell Populations in Siblings with the
Wiskott-Aldrich Syndrome
SO PLOS ONE
LA English
DT Article
AB Population level evolutionary processes can occur within a single organism when the germ line contains a mutation that confers a cost at the level of the cell. Here we describe how multiple compensatory mutations arose through a within-individual evolutionary process in two brothers with the immune deficiency Wiskott-Aldrich Syndrome (WAS). As a result, both brothers have T lymphocyte populations that are highly polymorphic at the locus of the germ line defect, and no single allele achieves fixation. WASP, the gene product affected in this disease, is specific to white blood cells where it is responsible for regulating actin cytoskeleton dynamics in a wide range of cellular responses. The brothers inherited a rare allele predicted to result in truncated WASP lacking the carboxy-terminal VCA domains, the region that directly catalyzes actin filament generation. Although the brothers' T cell populations are highly polymorphic, all share a corrective effect relative to the inherited allele in that they restore the VCA domain. This indicates massive selection against the truncated germ line allele. No single somatic allele becomes fixed in the circulating T cell population of either brother, indicating that a regulated step in maturation of the affected cell lineage is severely compromised by the germ line allele. Based on the finding of multiple somatic mutations, the known maturation pathway for T-lineage cells and the known defects of T cells and precursor thymocytes in mice with truncated WASP, we hypothesize that the presence of truncated WASP (WASP Delta VCA) confers an extreme disadvantage in early developing thymocytes, above and beyond the known cost of absence of full-length WASP, and that the disadvantage likely occurs through dominant negative competition of WASP Delta VCA with N-WASP, a protein that otherwise partially compensates for WASP absence in developing thymocytes.
C1 [Lutskiy, Maxim I.; Park, Jun Y.; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Lutskiy, Maxim I.; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA.
[Remold, Susanna K.] Univ Louisville, Dept Biol, Program Dis Evolution, Louisville, KY 40292 USA.
RP Lutskiy, MI (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
EM remold@cbrinstitute.org
FU National Institutes of Health [HL59561, AI39574, HL081407]; National
Science Foundation [DEB-0452163]; Jeffrey Modell Foundation
FX This work was supported by National Institutes of Health grants HL59561,
AI39574 and HL081407, National Science Foundation grant DEB-0452163, and
the Jeffrey Modell Foundation.
NR 42
TC 15
Z9 15
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 20
PY 2008
VL 3
IS 10
AR e3444
DI 10.1371/journal.pone.0003444
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432IB
UT WOS:000265125600006
PM 18941616
ER
PT J
AU Leleu, X
Roccaro, AM
Moreau, AS
Dupire, S
Robu, D
Gay, J
Hatjiharissi, E
Burwik, N
Ghobrial, IM
AF Leleu, Xavier
Roccaro, Aldo M.
Moreau, Anne-Sophie
Dupire, Sophie
Robu, Daniela
Gay, Julie
Hatjiharissi, Evdoxia
Burwik, Nicholas
Ghobrial, Irene M.
TI Waldenstrom Macroglobulinemia
SO CANCER LETTERS
LA English
DT Review
DE Waldenstrom Macroglobulinemia; novel therapy; transplantation
ID CONSENSUS PANEL RECOMMENDATIONS; CHRONIC LYMPHOCYTIC-LEUKEMIA; 2ND
INTERNATIONAL WORKSHOP; IGM MONOCLONAL GAMMOPATHY; MARGINAL ZONE
LYMPHOMA; EXTENDED RITUXIMAB THERAPY; MULTIPLE-MYELOMA CELLS;
NON-HODGKIN-LYMPHOMA; OF-THE-LITERATURE; PROGNOSTIC-FACTORS
AB In the past years, new developments have occurred both in the understanding of the biology of Waldenstrom Macroglobulinemia (WM) and in therapeutic options for WM. WM is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with demonstration of an IgM monoclonal gammopathy. Despite advances in therapy, WM remains incurable, with 5-6 years median overall survival of patients in symptomatic WM. Therapy is postponed for asymptomatic patients, and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. No specific agent or regimen has been shown to be superior to another for treatment of WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of several novel agents including the proteasome inhibitor bortezomib, and several Akt/mTor inhibitors, perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Studies with monoclonal antibodies are ongoing and promising including the use of alemtuzumab, SGN-70, and the APRIL/BLYS blocking protein TACI-Ig atacicept. Other agents currently being tested in clinical trials include the PKC inhibitor enzastaurin, the natural product resveratrol, as well as the statin simvastatin. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM. (c) 2008 Published by Elsevier Ireland Ltd.
C1 [Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Hatjiharissi, Evdoxia; Burwik, Nicholas; Ghobrial, Irene M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Leleu, Xavier; Roccaro, Aldo M.; Moreau, Anne-Sophie; Hatjiharissi, Evdoxia; Burwik, Nicholas; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Leleu, Xavier; Moreau, Anne-Sophie; Dupire, Sophie; Robu, Daniela; Gay, Julie] CHRU, Hop Huriez, Serv Malad Sang, Lille, France.
[Roccaro, Aldo M.] Univ Bari, Sch Med, Dept Internal Med & Oncol, Bari, Italy.
RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM Irene_ghobrial@dfcri.harvard.edu
OI Roccaro, Aldo/0000-0002-1872-5128
FU International Waldenstrom Macroglobulinemia Foundation (IWMF);
Franco-American Fulbright Foundation
FX Supported in part by International Waldenstrom Macroglobulinemia
Foundation (IWMF) grant, XL is supported by a grant from the
Franco-American Fulbright Foundation.
NR 104
TC 12
Z9 14
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD OCT 18
PY 2008
VL 270
IS 1
BP 95
EP 107
DI 10.1016/j.canlet.2008.04.040
PG 13
WC Oncology
SC Oncology
GA 357LL
UT WOS:000259847200010
PM 18555588
ER
PT J
AU Hao, ZY
Duncan, GS
Seagal, J
Su, YW
Hong, C
Haight, J
Chen, NJ
Elia, A
Wakeham, A
Li, WY
Liepa, J
Wood, GA
Casola, S
Rajewsky, K
Mak, TW
AF Hao, Zhenyue
Duncan, Gordon S.
Seagal, Jane
Su, Yu-Wen
Hong, Claire
Haight, Jillian
Chen, Nien-Jung
Elia, Andrew
Wakeham, Andrew
Li, Wanda Y.
Liepa, Jennifer
Wood, Geoffrey A.
Casola, Stefano
Rajewsky, Klaus
Mak, Talk W.
TI Fas Receptor Expression in Germinal-Center B Cells Is Essential for T
and B Lymphocyte Homeostasis
SO IMMUNITY
LA English
DT Article
ID LYMPHOPROLIFERATIVE SYNDROME; NEGATIVE SELECTION; IMMUNE-RESPONSES;
CLONAL SELECTION; GENE; ANTIGEN; MICE; CD28; AUTOIMMUNITY; MUTATIONS
AB Fas is highly expressed in activated and germinal center (GC) B cells but can potentially be inactivated by misguided somatic hypermutation. We employed conditional Fas-deficient mice to investigate the physiological functions of Fas in various B cell subsets. B cell-specific Fas-deficient mice developed fatal lymphoproliferation due to activation of B cells and T cells. Ablation of Fas specifically in GC B cells reproduced the phenotype, indicating that the lymphoproliferation initiates in the GC environment. B cell-specific Fas-deficient mice also showed an accumulation of IgG1(+) memory B cells expressing high amounts of CD80 and the expansion of CD28-expressing CD4(+) Th cells. Blocking T cell-B cell interaction and GC formation completely prevented the fatal lymphoproliferation. Thus, Fas-mediated selection of GC B cells and the resulting memory B cell compartment is essential for maintaining the homeostasis of both T and B lymphocytes.
C1 [Hao, Zhenyue; Duncan, Gordon S.; Su, Yu-Wen; Hong, Claire; Haight, Jillian; Chen, Nien-Jung; Elia, Andrew; Wakeham, Andrew; Li, Wanda Y.; Liepa, Jennifer; Mak, Talk W.] Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Canc Res, Toronto, ON M5G 2C1, Canada.
[Seagal, Jane; Rajewsky, Klaus] Immune Dis Inst Biomed Res, Boston, MA 02115 USA.
[Seagal, Jane; Rajewsky, Klaus] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Wood, Geoffrey A.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada.
[Casola, Stefano] IFOM FIRC Inst Mol Oncol Fdn, Milan, Italy.
[Mak, Talk W.] Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada.
[Mak, Talk W.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada.
RP Hao, ZY (reprint author), Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Canc Res, Toronto, ON M5G 2C1, Canada.
EM zhenyuehao@gmail.com; tmak@uhnres.utoronto.ca
RI Su, Yu-Wen/E-8804-2010
FU Terry Fox Cancer Foundation; Canadian Institutes of Health Research,;
Leukemia and Lymphoma Society; Deutsche Forschungsgemeinschaft [SFB
243]; National Institutes of Health (USA)
FX We thank various Mak lab members for technical assistance, T. Calzascia
for help with Th 17 cell differentiation, Toronto Centre for
Phenogenomics for help with histology, and M. Saunders for scientific
editing. This work was supported by grants to T.W.M. from the Terry Fox
Cancer Foundation, Canadian Institutes of Health Research, and Leukemia
and Lymphoma Society; to Z.H. from Canadian Institutes of Health
Research; and to K.R. from the Deutsche Forschungsgemeinschaft through
SFB 243 and the National Institutes of Health (USA).
NR 41
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U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD OCT 17
PY 2008
VL 29
IS 4
BP 615
EP 627
DI 10.1016/j.immuni.2008.07.016
PG 13
WC Immunology
SC Immunology
GA 364DP
UT WOS:000260316700014
PM 18835195
ER
PT J
AU Hasler, U
Leroy, V
Jeon, US
Bouley, R
Dimitrov, M
Kim, JA
Brown, D
Kwon, HM
Martin, PY
Feraille, E
AF Hasler, Udo
Leroy, Valeeie
Jeon, Un Sil
Bouley, Richard
Dimitrov, Mitko
Kim, Jeong Ah
Brown, Dennis
Kwon, H. Moo
Martin, Pierre-Yves
Feraille, Eric
TI NF-kappa B modulates aquaporin-2 transcription in renal collecting duct
principal cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INDUCED NEPHROTIC SYNDROME; ENHANCER-BINDING PROTEIN; WATER CHANNEL
EXPRESSION; DOWN-REGULATION; NULL MICE; ACTIVATION; MECHANISM; GENE;
HYPERTONICITY; PERMEABILITY
AB Renal tubulo-interstitial inflammation is frequently associated with polyuria and urine concentration defects. This led us to investigate the effects of the major pro-inflammatory nuclear factor kappa B (NF-kappa B) pathway on aquaporin 2 (AQP2) expression by the collecting duct. Using immortalized collecting duct principal cells (mpkCCD(c14)), we found that, acting independently of vasopressin, activation of NF-kappa B by lipopolysaccharide (LPS) decreased AQP2 mRNA and protein levels in a time-and dose-dependent manner but did not decrease AQP2 mRNA stability. Consistently, constitutively active I kappa B kinase beta decreased AQP2 expression. The LPS-induced decrease in AQP2 mRNA levels was confirmed in rat kidney slices and was reproduced both under conditions of elevated cAMP concentration and V-2 receptor antagonism. Computer analysis of the AQP2 promoter revealed two putative kappa B elements. Mutation of either kappa B element abolished the LPS-induced decrease of luciferase activity in cells expressing AQP2 promoter-luciferase plasmid constructs. Chromatin immunoprecipitation revealed that LPS challenge decreased p65, increased p50 and p52, and had no effect on RelB and c-Rel binding to kappa B elements of the AQP2 promoter. RNA-mediated interference silencing of p65, p50, and p52 confirmed controlled AQP2 transcription by these NF-kappa B subunits. We additionally found that hypertonicity activated NF-kappa B in mpkCCD(c14) cells, an effect that may counteract the Tonicity-responsive enhancer binding protein (TonEBP)-dependent increase in AQP2 gene transcription. Taken together, these findings indicate that NF-kappa B is an important physiological regulator of AQP2 transcription.
C1 [Hasler, Udo; Leroy, Valeeie; Dimitrov, Mitko; Martin, Pierre-Yves; Feraille, Eric] Fdn Rech Med, Serv Nephrol, CH-1211 Geneva 4, Switzerland.
[Hasler, Udo; Leroy, Valeeie; Dimitrov, Mitko; Martin, Pierre-Yves; Feraille, Eric] Univ Geneva, CH-1211 Geneva, Switzerland.
[Jeon, Un Sil; Kim, Jeong Ah; Kwon, H. Moo] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
[Bouley, Richard; Brown, Dennis] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Bouley, Richard; Brown, Dennis] Massachusetts Gen Hosp, MGH Ctr Syst Biol, Program Membrane Biol, Boston, MA USA.
[Bouley, Richard; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA USA.
RP Feraille, E (reprint author), Fdn Rech Med, Serv Nephrol, 64 Ave Roseraie, CH-1211 Geneva 4, Switzerland.
EM Eric.Feraille@medecine.unige.ch
RI Dimitrov, Mitko/C-9822-2009; Lee-Kwon, Whaseon/D-6021-2011
FU National Institutes of Health [R01-DK-42479, DK38452]; Swiss National
Foundation [31-67878.02, 31-109473]; Elsie de Reuter Foundation; Ernest
Boninchi Foundation; Fondation pour la Recherche Medicale
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01-DK-42479 (to H. M. K.) and DK38452 (to D. B). This
work was also supported in part by Swiss National Foundation Grants
31-67878.02 and 31-109473, a Carlos and Elsie de Reuter Foundation
grant, a Ernest Boninchi Foundation grant (to E. F.), and a Fondation
pour la Recherche Medicale grant (to U. H.). The costs of publication of
this article were defrayed in part by the payment of page charges. This
article must therefore be hereby marked "advertisement" in accordance
with 18 U. S. C. Section 1734 solely to indicate this fact.
NR 54
TC 31
Z9 32
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2008
VL 283
IS 42
BP 28095
EP 28105
DI 10.1074/jbc.M708350200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 359EN
UT WOS:000259969300012
PM 18703515
ER
PT J
AU Humbert, M
Rasmussen, RA
Song, RJ
Ong, H
Sharma, P
Chenine, AL
Kramer, VG
Siddappa, NB
Xu, WD
Else, JG
Novembre, FJ
Strobert, E
O'Neil, SP
Ruprecht, RM
AF Humbert, Michael
Rasmussen, Robert A.
Song, Ruijiang
Ong, Helena
Sharma, Prachi
Chenine, Agnes L.
Kramer, Victor G.
Siddappa, Nagadenahalli B.
Xu, Weidong
Else, James G.
Novembre, Francis J.
Strobert, Elizabeth
O'Neil, Shawn P.
Ruprecht, Ruth M.
TI SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env
cause AIDS in rhesus monkeys
SO RETROVIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 SUBTYPE-C; PERINATAL TRANSMISSION;
BIOLOGICAL PHENOTYPE; MACACA-NEMESTRINA; CHALLENGE VIRUSES;
ANTIBODY-RESPONSE; CORECEPTOR SWITCH; ENVELOPE PROTEIN; MACAQUES
AB Background: Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide.
Results: We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123-270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis.
Conclusion: These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described ( Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.
C1 [Humbert, Michael; Rasmussen, Robert A.; Song, Ruijiang; Ong, Helena; Chenine, Agnes L.; Kramer, Victor G.; Siddappa, Nagadenahalli B.; Xu, Weidong; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Humbert, Michael; Rasmussen, Robert A.; Song, Ruijiang; Chenine, Agnes L.; Siddappa, Nagadenahalli B.; Xu, Weidong; O'Neil, Shawn P.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Sharma, Prachi; Else, James G.; Novembre, Francis J.; Strobert, Elizabeth] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
[O'Neil, Shawn P.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA.
RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM michael_humbert@dfci.harvard.edu; robert_rasmussen@dfci.harvard.edu;
rsong@adarc.org; helena_ong@dfci.harvard.edu; psharm9@emory.edu;
achenine@hivresearch.org; victor_kramer@dfci.harvard.edu;
nb_siddappa@dfci.harvard.edu; wxu@health.usf.edu; jelse@emory.edu;
fnovembr@rmy.emory.edu; eliz@rmy.emory.edu; Shawn.O'Neil@pfizer.com;
ruth_ruprecht@dfci.harvard.edu
OI Byrareddy, Siddappa /0000-0002-7423-1763
FU NIH [P01 AI048240, RR-00165]
FX The authors thank Susan Sharp for assistance in the preparation of this
manuscript. This work was supported by NIH grant P01 AI048240 to RAR,
JGE and RMR and NIH grant RR-00165 providing base grant support to the
Yerkes National Primate Research Center.
NR 45
TC 47
Z9 47
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD OCT 17
PY 2008
VL 5
AR 94
DI 10.1186/1742-4690-5-94
PG 12
WC Virology
SC Virology
GA 372DM
UT WOS:000260881900001
PM 18928523
ER
PT J
AU George, RE
Sanda, T
Hanna, M
Frohling, S
Luther, W
Zhang, JM
Ahn, Y
Zhou, WJ
London, WB
McGrady, P
Xue, LQ
Zozulya, S
Gregor, VE
Webb, TR
Gray, NS
Gilliland, DG
Diller, L
Greulich, H
Morris, SW
Meyerson, M
Look, AT
AF George, Rani E.
Sanda, Takaomi
Hanna, Megan
Frohling, Stefan
Luther, William, II
Zhang, Jianming
Ahn, Yebin
Zhou, Wenjun
London, Wendy B.
McGrady, Patrick
Xue, Liquan
Zozulya, Sergey
Gregor, Vlad E.
Webb, Thomas R.
Gray, Nathanael S.
Gilliland, D. Gary
Diller, Lisa
Greulich, Heidi
Morris, Stephan W.
Meyerson, Matthew
Look, A. Thomas
TI Activating mutations in ALK provide a therapeutic target in
neuroblastoma
SO NATURE
LA English
DT Article
ID ANAPLASTIC LYMPHOMA KINASE; HIGH-RISK NEUROBLASTOMA; EML4-ALK FUSION
GENE; CELL LUNG-CANCER; GEFITINIB; IDENTIFICATION; INHIBITOR;
TRANSPLANTATION; TRANSFORMATION; PLEIOTROPHIN
AB Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer(1). High- risk neuroblastomas are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal(2,3). Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non- synonymous sequence variations were identified in the kinase domain of ALK, of which three were somatic and two were germ line. The most frequent mutation, F1174L, was also identified in three different neuroblastoma cell lines. ALK complementary DNAs encoding the F1174L and R1275Q variants, but not the wild- type ALK cDNA, transformed interleukin-3-dependent murine haematopoietic Ba/F3 cells to cytokine-independent growth. Ba/F3 cells expressing these mutations were sensitive to the small- molecule inhibitor of ALK, TAE684 (ref. 4). Furthermore, two human neuroblastoma cell lines harbouring the F1174L mutation were also sensitive to the inhibitor. Cytotoxicity was associated with increased amounts of apoptosis as measured by TdT-mediated dUTP nick end labelling ( TUNEL). Short hairpin RNA (shRNA)- mediated knockdown of ALK expression in neuroblastoma cell lines with the F1174L mutation also resulted in apoptosis and impaired cell proliferation. Thus, activating alleles of the ALK receptor tyrosine kinase are present in primary neuroblastoma tumours and in established neuroblastoma cell lines, and confer sensitivity to ALK inhibition with small molecules, providing a molecular rationale for targeted therapy of this disease.
C1 [George, Rani E.; Sanda, Takaomi; Luther, William, II; Ahn, Yebin; Diller, Lisa; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Zhang, Jianming; Zhou, Wenjun; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Hanna, Megan; Greulich, Heidi; Meyerson, Matthew] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA.
[Frohling, Stefan; Gilliland, D. Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[London, Wendy B.; McGrady, Patrick] Univ Florida, Childrens Oncol Grp Stat & Data Ctr, Gainesville, FL 32601 USA.
[Xue, Liquan; Morris, Stephan W.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Xue, Liquan; Morris, Stephan W.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Webb, Thomas R.] St Jude Childrens Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA.
[Zozulya, Sergey; Gregor, Vlad E.] ChemBridge Res Labs Inc, San Diego, CA 92127 USA.
RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM matthew_meyerson@dfci.harvard.edu; thomas_look@dfci.harvard.edu
RI Meyerson, Matthew/E-7123-2012; Webb, Thomas/J-4511-2013;
OI Zozulya, Sergey/0000-0002-1179-2993
FU National Institutes of Health; Friends for Life Neuroblastoma Fund;
Children's Oncology Group; Alex's Lemonade Stand Foundation; NCI
[CA69129]; Cancer Center Core [CA21765]; American Lebanese Syrian
Associated Charities; St. Jude Children's Research Hospital
FX We thank J. Elechko and L. Moreau for technical assistance, A. Azarova
for help with cell culture and cell growth assays, Q. Jiang and X. Cui
for assistance during ALK small-molecule inhibitor development, and A.
Kung for Ba/F3 cells and retroviral vectors. Weacknowledge the
Children's Oncology Group for provision of neuroblastoma tumour and
matched normal DNAs, and tumour touch prep slides. We thank J. Maris for
neuroblastoma cell lines. We thank Abbott Molecular International for
the Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe. This work
was supported by grants from the National Institutes of Health (R.E.G.),
the Friends for Life Neuroblastoma Fund (R.E.G.), the Children's
Oncology Group (R.E.G.), Alex's Lemonade Stand Foundation (M.H. and
M.M.), NCI CA69129 (L.X. and S.W.M.), Cancer Center Core grant CA21765
(T.R.W., L.X. and S.W.M.), the American Lebanese Syrian Associated
Charities and St. Jude Children's Research Hospital (T.R.W., L.X. and
S.W.M.).
NR 27
TC 408
Z9 420
U1 3
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 16
PY 2008
VL 455
IS 7215
BP 975
EP 978
DI 10.1038/nature07397
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 360DW
UT WOS:000260038300052
PM 18923525
ER
PT J
AU Blumenthal, D
AF Blumenthal, David
TI Election 2008 - Primum non nocere - The McCain plan for health
insecurity
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID INSURANCE
C1 [Blumenthal, David] Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA.
RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA.
NR 5
TC 2
Z9 2
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 16
PY 2008
VL 359
IS 16
BP 1645
EP 1647
DI 10.1056/NEJMp0806563
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 360EY
UT WOS:000260041400001
PM 18815391
ER
PT J
AU Rosenbaum, L
AF Rosenbaum, Lisa
TI Becoming a physician: Living unlabeled - Diagnosis and disorder
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Rosenbaum, Lisa] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Rosenbaum, L (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 4
Z9 4
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 OCT 16
PY 2008
VL 359
IS 16
BP 1650
EP 1653
DI 10.1056/NEJMp0804984
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 360EY
UT WOS:000260041400003
PM 18923169
ER
PT J
AU Dinulos, JGH
Zembowicz, A
Burnett, MM
Harris, NL
AF Dinulos, James G. H.
Zembowicz, Artur
Burnett, Melissa M.
Harris, Nancy Lee
TI A girl with recurrent oral lesions and cutaneous bullae - Dermatitis due
to zinc deficiency (acrodermatitis enteropathica-like syndrome)
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ERYTHEMA MULTIFORME; EPIDERMOLYSIS-BULLOSA; DISEASE; CLASSIFICATION
C1 [Dinulos, James G. H.] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA.
[Dinulos, James G. H.] Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA.
[Dinulos, James G. H.] Dartmouth Med Sch, Dept Med, Hanover, NH USA.
[Dinulos, James G. H.] Dartmouth Med Sch, Dept Pediat, Hanover, NH USA.
[Zembowicz, Artur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Zembowicz, Artur] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Dinulos, JGH (reprint author), Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA.
FU SkinMedica; Barrier Pharmaceuticals; Connetics; Novartis; Merck
FX Dr. Dinulos reports receiving consulting fees from SkinMedica, Barrier
Pharmaceuticals, and Connetics and lecture fees from Novartis. Dr.
Zembowicz reports receiving consulting fees from Merck. No other
potential conflict of interest relevant to this article was reported.
NR 20
TC 2
Z9 2
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 16
PY 2008
VL 359
IS 16
BP 1718
EP 1724
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 360EY
UT WOS:000260041400012
PM 18923175
ER
PT J
AU DaSilva, AF
Becerra, L
Pendse, G
Chizh, B
Tully, S
Borsook, D
AF DaSilva, Alexandre F.
Becerra, Lino
Pendse, Gautam
Chizh, Boris
Tully, Shannon
Borsook, David
TI Colocalized Structural and Functional Changes in the Cortex of Patients
with Trigeminal Neuropathic Pain
SO PLOS ONE
LA English
DT Article
AB Background: Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level - BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy.
Methodology/Principal Findings: Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional (DLPFC, Frontal, Anterior Insula, Cingulate) processing of pain. Both structural and functional (to brush-induced allodynia) scans were obtained and averaged from two different imaging sessions separated by 2-6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions.
Conclusions: Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions.
C1 [DaSilva, Alexandre F.; Becerra, Lino; Pendse, Gautam; Tully, Shannon; Borsook, David] Harvard Univ, Med Sch, Mclean Hosp, Brain Imag Ctr, PAIN Grp, Boston, MA USA.
[Becerra, Lino; Borsook, David] Harvard Univ, Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Chizh, Boris] GSK Addenbrooks Hosp, Cambridge, England.
RP DaSilva, AF (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
EM adasilva@umich.edu
FU NINDS [R01 NS042721, 1K24NS064050]; GSK; NIDCR [K12-DE014528]
FX This work was primarily supported by NINDS R01 NS042721 and 1K24NS064050
(DB), as well as in part from an investigator initiated grant from GSK
(DB). Additional support was provided by NIDCR K12-DE014528 (AFMD).
NR 86
TC 65
Z9 67
U1 1
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 16
PY 2008
VL 3
IS 10
AR e3396
DI 10.1371/journal.pone.0003396
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432GT
UT WOS:000265122200001
PM 18923647
ER
PT J
AU Wyller, VB
Saul, JP
Barbieri, R
de Lange, C
Hopp, E
Norum, IB
Thaulow, E
AF Wyller, Vegard Bruun
Saul, J. Philip
Barbieri, Riccardo
de Lange, Charlotte
Hopp, Einar
Norum, Ingvild B.
Thaulow, Erik
TI Autonomic Heart Rate Control at Rest and During Unloading of the Right
Ventricle in Repaired Tetralogy of Fallot in Adolescents
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID BODY NEGATIVE-PRESSURE; RATE-VARIABILITY; NERVOUS ACTIVITY; SURGICAL
REPAIR; MODULATION; RESPONSES; OUTFLOW; TILT
AB Arrhythmias in patients with repaired tetralogy of Fallot (ToF) might be due in part to altered autonomic heart rate control caused by altered right ventricle hemodynamics. This study investigated autonomic heart rate control in adolescents with ToF at rest and during unloading of the right ventricle. A total of 17 patients with ToF and 56 healthy controls aged 12 to 18 years underwent orthostatic stress with lower body negative pressure of -20 mm Hg. Heart rate, blood pressure, and stroke volume were recorded noninvasively. Indices of heart rate variability were computed in time and frequency domains. All patients with ToF also underwent cardiac magnetic resonance imaging, demonstrating pulmonary regurgitation and right ventricular dilation. At rest, heart rate variability indices of vagal heart rate control were nonsignificantly lower in the patients with ToF compared with controls. During lower body negative pressure, heart rate increased more in controls than patients with ToF (p <= 0.001). Further, most heart rate variability indices decreased in controls, but increased in patients with ToF (p <= 0.01 or p <= 0.001 for all variables), suggesting vagal activation in the patients with ToF. In conclusion, adolescents after ToF repair have fairly normal heart rate control at rest despite altered right ventricular hemodynamics. During unloading of the right ventricle, however, vagal heart rate control increases in the patients with ToF and decreases in the controls. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1085-1089)
C1 [Wyller, Vegard Bruun; Norum, Ingvild B.; Thaulow, Erik] Univ Oslo, Rikshosp, Div Pediat, Univ Hosp, N-0027 Oslo, Norway.
[Saul, J. Philip] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA.
[Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA.
[de Lange, Charlotte; Hopp, Einar] Univ Oslo, Rikshosp, Univ Hosp, Dept Radiol, N-0027 Oslo, Norway.
RP Wyller, VB (reprint author), Univ Oslo, Rikshosp, Div Pediat, Univ Hosp, N-0027 Oslo, Norway.
EM brwylle@online.no
OI Barbieri, Riccardo/0000-0001-9381-3833
FU National Institutes of Health, Bethesda, Maryland [U01-HL068281-06,
R01-HL084502]
FX Dr. Saul was supported by Grant U01-HL068281-06 from the National
Institutes of Health, Bethesda, Maryland. Dr. Barbieri was supported by
Grant R01-HL084502 from the National Institutes of Health, Bethesda,
Maryland.
NR 21
TC 0
Z9 0
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 OCT 15
PY 2008
VL 102
IS 8
BP 1085
EP 1089
DI 10.1016/j.amjcard.2008.05.065
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YN
UT WOS:000260094800022
PM 18929714
ER
PT J
AU Kavvoura, FK
McQueen, MB
Khoury, MJ
Tanzi, RE
Bertram, L
Ioannidis, JPA
AF Kavvoura, Fotini K.
McQueen, Matthew B.
Khoury, Muin J.
Tanzi, Rudolph E.
Bertram, Lars
Ioannidis, John P. A.
TI Evaluation of the Potential Excess of Statistically Significant Findings
in Published Genetic Association Studies: Application to Alzheimer's
Disease
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Alzheimer disease; bias (epidemiology); genetic markers; genetics;
meta-analysis; publication bias
ID GENOME-WIDE ASSOCIATION; PUBLICATION BIAS; RANDOMIZED-TRIALS;
CLINICAL-TRIALS; METAANALYSIS; EPIDEMIOLOGY; REPLICATION; HETEROGENEITY;
LOCI; INCONSISTENCY
AB The authors evaluated whether there is an excess of statistically significant results in studies of genetic associations with Alzheimer's disease reflecting either between-study heterogeneity or bias. Among published articles on genetic associations entered into the comprehensive AlzGene database (www. alzgene. org) through January 31, 2007, 1,348 studies included in 175 meta-analyses with 3 or more studies each were analyzed. The number of observed studies (O) with statistically significant results (P = 0.05 threshold) was compared with the expected number (E) under different assumptions for the magnitude of the effect size. In the main analysis, the plausible effect size of each association was the summary effect presented in the respective meta-analysis. Overall, 19 meta-analyses (all with eventually nonsignificant summary effects) had a documented excess of O over E: Typically single studies had signi. cant effects pointing in opposite directions and early summary effects were dissipated over time. Across the whole domain, O was 235 (17.4%), while E was 164.8 (12.2%) (P < 10(-6)). The excess showed a predilection for meta-analyses with nonsignificant summary effects and between-study heterogeneity. The excess was seen for all levels of statistical significance and also for studies with borderline P values (P = 0.05 -0.10). The excess of signi. cant findings may represent significance-chasing biases in a setting of massive testing.
C1 [Kavvoura, Fotini K.; Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece.
[McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA.
[Tanzi, Rudolph E.; Bertram, Lars] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA USA.
[Ioannidis, John P. A.] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies,Dept Med, Boston, MA 02111 USA.
RP Ioannidis, JPA (reprint author), Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece.
EM jioannid@cc.uoi.gr
RI Ioannidis, John/G-9836-2011; Bertram, Lars/K-3889-2015
OI Bertram, Lars/0000-0002-0108-124X
FU European Union; European Social Fund; Greek Ministry of Development;
Cure Alzheimer Fund
FX Author affiliations: Clinical and Molecular Epidemiology Unit,
Department of Hygiene and Epidemiology, University of Ioannina School of
Medicine, Ioannina, Greece (Fotini K. Kavvoura, John P. A. Ioannidis);
Institute for Behavioral Genetics, University of Colorado, Boulder,
Colorado (Matthew B. McQueen); National Office of Public Health
Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia
(Muin J. Khoury); Genetics and Aging Research Unit, MassGeneral
Institute for Neurodegenerative Disease, Department of Neurology,
Massachusetts General Hospital, Charlestown, Massachusetts (Rudolph E.
Tanzi, Lars Bertram); Biomedical Research Institute, Foundation for
Research and Technology - Hellas, Ioannina, Greece (John P. A.
Ioannidis); Institute for Clinical Research and Health Policy Studies,
Department of Medicine, Tufts Medical Center, Tufts University School of
Medicine, Boston, Massachusetts (John P. A. Ioannidis).; Dr F. K.
Kavvoura was supported by a PENED (Programma Enisxusis Ereunitikou
Dunamikou) grant cofinanced by the European Union - European Social Fund
(75%) and the Greek Ministry of Development - General Secretariat of
Research and Technology (25%). The AlzGene database is sponsored by a
grant from the Cure Alzheimer Fund.
NR 50
TC 26
Z9 27
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 15
PY 2008
VL 168
IS 8
BP 855
EP 865
DI 10.1093/aje/kwn206
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 359DF
UT WOS:000259965800001
PM 18779388
ER
PT J
AU Janne, PA
AF Jaenne, Pasi A.
TI Gefitinib first or gefitinib second - Is timing everything in the
treatment of EGFR mutant non-small cell lung cancer?
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID RECEPTOR GENE-MUTATIONS; PROSPECTIVE PHASE-II
C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Jaenne, Pasi A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD OCT 15
PY 2008
VL 178
IS 8
BP 783
EP 785
DI 10.1164/rccm.200806-910ED
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 358QM
UT WOS:000259932600003
PM 18832554
ER
PT J
AU Liao, KP
Gaut, J
Huang, AJ
Cohen, G
AF Liao, Katherine P.
Gaut, Joseph
Huang, Ambrose J.
Cohen, George
TI A 20-Year-Old Man With Right Leg Pain Following Orofacial Surgery
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID COMPARTMENT SYNDROME; LITHOTOMY POSITION
C1 [Liao, Katherine P.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Gaut, Joseph; Huang, Ambrose J.; Cohen, George] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Liao, KP (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St,PBB-B3, Boston, MA 02115 USA.
EM kliao@partners.org
NR 12
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD OCT 15
PY 2008
VL 59
IS 10
BP 1527
EP 1532
DI 10.1002/art.24121
PG 6
WC Rheumatology
SC Rheumatology
GA 362RN
UT WOS:000260214900023
PM 18821652
ER
PT J
AU New, AS
Triebwasser, J
Charney, DS
AF New, Antonia S.
Triebwasser, Joseph
Charney, Dennis S.
TI The case for shifting borderline personality disorder to Axis I
SO BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Axis I; Axis II; borderline personality disorder; nosology; specificity;
validity
ID POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL-ABUSE; IMPULSIVE
AGGRESSIVE-BEHAVIOR; DEPRESSED-PATIENTS; PREFRONTAL CORTEX; BIPOLAR
DISORDER; RISK-FACTORS; FOLLOW-UP; ANTERIOR CINGULATE; LIFE EVENTS
AB Through reviewing what is known about the nature, course, and heritability of borderline personality disorder (BPD), we argue for a reconceptualization of this disorder that would lead to its placement on Axis I. Borderline personality disorder is a prevalent and disabling condition, and yet the empirical research into its nature and treatment has not been commensurate with the seriousness of the illness. We not only review empirical evidence about the etiology, phenomenology, and course of the disorder in BPD but we also address fundamental misconceptions about BPD that we believe have contributed to misunderstanding and stigmatization of the disease. Finally, we suggest future directions for research that might permit the identification of core features of this disorder, with a focus on the importance of naturalistic assessments and of assessments through the course of development.
C1 [New, Antonia S.; Triebwasser, Joseph; Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[New, Antonia S.; Triebwasser, Joseph] Bronx Vet Affairs Med Ctr, New York, NY USA.
RP New, AS (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1217, New York, NY 10029 USA.
EM antonia.new@mssm.edu
FU Veterans Administration (VA) [9001-03-0051]
FX Dr. New gratefully acknowledges the support of the Veterans
Administration (VA) for ber VA Merit Award (VA Project #: 9001-03-0051).
NR 100
TC 33
Z9 34
U1 2
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 OCT 15
PY 2008
VL 64
IS 8
BP 653
EP 659
DI 10.1016/j.biopsych.2008.04.020
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 357TE
UT WOS:000259868600003
PM 18550033
ER
PT J
AU Yanik, GA
Ho, VT
Levine, JE
White, ES
Braun, T
Antin, JH
Whitfield, J
Custer, J
Jones, D
Ferrara, JLM
Cooke, KR
AF Yanik, Gregory A.
Ho, Vincent T.
Levine, John E.
White, Eric S.
Braun, Thomas
Antin, Joseph H.
Whitfield, Joel
Custer, Joseph
Jones, Dawn
Ferrara, James L. M.
Cooke, Kenneth R.
TI The impact of soluble tumor necrosis factor receptor etanercept on the
treatment of idiopathic pneumonia syndrome after allogeneic
hematopoietic stem cell transplantation
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; DIFFUSE ALVEOLAR
HEMORRHAGE; RESPIRATORY-DISTRESS-SYNDROME; SEVERE APLASTIC-ANEMIA;
RHEUMATOID-ARTHRITIS; LUNG INJURY; INTERSTITIAL PNEUMONITIS;
MOLECULAR-CLONING; CONTROLLED-TRIAL
AB Idiopathic pneumonia syndrome (IPS) refers to a diffuse, noninfectious, acute lung injury after hematopoietic stem cell transplantation. Historically, IPS is associated with respiratory failure and mortality rates exceeding 50%. Preclinical studies have implicated tumor necrosis factor-alpha as an important effector molecule in the development of disease. We studied the tumor necrosis factor-alpha inhibitor, etanercept, combined with corticosteroids in treating 15 patients (median age, 18 years; range, 1-60 years) with IPS. Eight of 15 patients required mechanical ventilation at therapy onset. Etanercept was administered subcutaneously at a dose of 0.4 mg/kg (maximum 25 mg) twice weekly, for a maximum of 8 doses. Therapy was well tolerated with no infectious pulmonary complications noted. Ten of 15 patients had a complete response, defined as the ability to discontinue supplemental oxygen support during study therapy. The median time to complete response was 7 days (range, 3-18 days), with a day 28 survival of 73%. IPS onset was associated with elevations of several inflammatory proteins in the bronchoalveolar lavage fluid and plasma, and response to therapy correlated with reductions in pulmonary and systemic inflammation. The combination of etanercept and corticosteroids is safe and is associated with high response rates and improved survival in patients with IPS.
C1 [Yanik, Gregory A.] Univ Michigan, Med Ctr, Canc Ctr 5303, Blood & Marrow Transplantat Program,Dept Pediat, Ann Arbor, MI 48109 USA.
[Yanik, Gregory A.; Levine, John E.; Whitfield, Joel; Jones, Dawn; Ferrara, James L. M.; Cooke, Kenneth R.] Univ Michigan, Blood & Marrow Transplantat Program, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Ho, Vincent T.; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[White, Eric S.] Univ Michigan, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
[Braun, Thomas] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Custer, Joseph] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
RP Yanik, GA (reprint author), Univ Michigan, Med Ctr, Canc Ctr 5303, Blood & Marrow Transplantat Program,Dept Pediat, 1500 E Med Ctr Dr,SPC 5941, Ann Arbor, MI 48109 USA.
EM gyanik@umich.edu; kenneth.cooke@uhhospitals.org
OI Levine, John/0000-0002-9133-0800; White, Eric/0000-0003-4060-8443
FU Orphan Products Division of the Food and Drug Administration; Leukemia &
Lymphoma Society; Burroughs Wellcome Fund; Immunex Corporation, Seattle,
WA; Robert Wood Johnson Harold Amos Medical Faculty Development Program
FX This work was supported by grants from the Orphan Products Division of
the Food and Drug Administration, the Leukemia & Lymphoma Society, the
Burroughs Wellcome Fund, and Immunex Corporation, Seattle, WA(now Amgen,
Thousand Oaks, CA). K. R. C. is an Amy Strelzer-Manasevit Scholar of the
National Marrow Program, a Fellow of the Robert Wood Johnson Harold Amos
Medical Faculty Development Program, a Clinical Scholar of the Leukemia
& Lymphoma Society, and the recipient of a Clinical Scientist in
Translational Research Award from the Burroughs Wellcome Fund.
NR 48
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U2 0
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 OCT 15
PY 2008
VL 112
IS 8
BP 3073
EP 3081
DI 10.1182/blood-2008-03-143412
PG 9
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100019
PM 18664626
ER
PT J
AU Kindler, T
Cornejo, MG
Scholl, C
Liu, JN
Leeman, DS
Haydu, JE
Frohling, S
Lee, BH
Gilliland, DG
AF Kindler, Thomas
Cornejo, Melanie G.
Scholl, Claudia
Liu, Jianing
Leeman, Dena S.
Haydu, J. Erika
Froehling, Stefan
Lee, Benjamin H.
Gilliland, D. Gary
TI K-Ras(G12D)-induced T-cell lymphoblastic lymphoma/leukemias harbor
Notch1 mutations and are sensitive to gamma-secretase inhibitors
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; ONCOGENIC K-RAS; MOLECULAR-GENETICS; SIGNALING
PATHWAYS; SOMATIC ACTIVATION; HYPERACTIVE RAS; TRANSGENIC MICE;
DIFFERENTIATION; EXPRESSION; THYMOCYTE
AB To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-Ras(G12D) murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter. Transplantation of whole bone marrow cells that express oncogenic K-Ras into wild-type recipient mice resulted in a highly penetrant, aggressive T-cell leukemia/lymphoma. The lymphoblasts were composed of a CD4/CD8 double-positive population that aberrantly expressed CD44. Thymi of primary donor mice showed reduced cellularity, and immunophenotypic analysis demonstrated a block in differentiation at the double-negative 1 stage. With progression of disease, approximately 50% of mice acquired Notch1 mutations within the PEST domain. Of note, primary lymphoblasts were hypersensitive to gamma-secretase inhibitor treatment, which is known to impair Notch signaling. This inhibition was Notch-specific as assessed by down-regulation of Notch1 target genes and intracellular cleaved Notch. We also observed that the oncogenic K-Ras-induced T-cell disease was responsive to rapamycin and inhibitors of the RAS/MAPK pathway. These data indicate that patients with T-cell leukemia with K-Ras mutations may benefit from therapies that target the NOTCH pathway alone or in combination with inhibition of the PI3K/AKT/MTOR and RAS/MAPK pathways.
C1 [Kindler, Thomas; Cornejo, Melanie G.; Scholl, Claudia; Liu, Jianing; Leeman, Dena S.; Haydu, J. Erika; Froehling, Stefan; Lee, Benjamin H.; Gilliland, D. Gary] Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA.
[Lee, Benjamin H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Gilliland, D. Gary] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Kindler, T (reprint author), Johannes Gutenberg Univ Mainz, Dept Med 3, Langenbeckstr 1, D-55131 Mainz, Germany.
EM thomas.kindler@ukmainz.de
RI Kindler, Thomas/K-5995-2013
FU National Institutes of Health [CA66996, CA105423]; Leukemia & Lymphoma
Society; German Research Foundation
FX The authors thank members of the Gilliland laboratory for support and
helpful discussions, and Drs David A. Tuveson and Tyler E. Jacks for
providing us with the conditional murine K-RasG12D model.; This work was
supported by National Institutes of Health grants CA66996 and CA105423
(D.G.G.) and the Leukemia & Lymphoma Society (D.G.G.). T.K. is a fellow
of the German Research Foundation. D.G.G. is a Doris Duke Charitable
Foundation Distinguished Clinical Scientist and an Investigator of the
Howard Hughes Medical Institute.
NR 55
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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 OCT 15
PY 2008
VL 112
IS 8
BP 3373
EP 3382
DI 10.1182/blood-2008-03-147587
PG 10
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100054
PM 18663146
ER
PT J
AU Lee, SJ
Kukreja, M
Wang, T
Giralt, SA
Szer, J
Arora, M
Woolfrey, AE
Cervantes, F
Champlin, RE
Gale, RP
Halter, J
Keating, A
Marks, DI
McCarthy, PL
Olavarria, E
Stadtmauer, EA
Abecasis, M
Gupta, V
Khoury, HJ
George, B
Hale, GA
Liesveld, JL
Rizzieri, DA
Antin, JH
Bolwell, BJ
Carabasi, MH
Copelan, E
Ilhan, O
Litzow, MR
Schouten, HC
Zander, AR
Horowitz, MM
Maziarz, RT
AF Lee, Stephanie J.
Kukreja, Manisha
Wang, Tao
Giralt, Sergio A.
Szer, Jeffrey
Arora, Mukta
Woolfrey, Ann E.
Cervantes, Francisco
Champlin, Richard E.
Gale, Robert Peter
Halter, Joerg
Keating, Armand
Marks, David I.
McCarthy, Philip L.
Olavarria, Eduardo
Stadtmauer, Edward A.
Abecasis, Manuel
Gupta, Vikas
Khoury, H. Jean
George, Biju
Hale, Gregory A.
Liesveld, Jane L.
Rizzieri, David A.
Antin, Joseph H.
Bolwell, Brian J.
Carabasi, Matthew H.
Copelan, Edward
Ilhan, Osman
Litzow, Mark R.
Schouten, Harold C.
Zander, Axel R.
Horowitz, Mary M.
Maziarz, Richard T.
TI Impact of prior imatinib mesylate on the outcome of hematopoietic cell
transplantation for chronic myeloid leukemia
SO BLOOD
LA English
DT Article
ID CHRONIC MYELOGENOUS LEUKEMIA; MARROW TRANSPLANTATION; CHRONIC-PHASE;
BONE-MARROW; FOLLOW-UP; THERAPY; ERA; MULTICENTER; INTERFERON; FAILURE
AB Imatinib mesylate (IM, Gleevec) has largely supplanted allogeneic hematopoietic cell transplantation (HCT) as first line therapy for chronic myeloid leukemia (CML). Nevertheless, many people with CML eventually undergo HCT, raising the question of whether prior IM therapy impacts HCT success. Data from the Center for International Blood and Marrow Transplant Research on 409 subjects treated with IM before HCT (IM+) and 900 subjects who did not receive IM before HCT (IM-) were analyzed. Among patients in first chronic phase, IM therapy before HCT was associated with better survival but no statistically significant differences in treatment-related mortality, relapse, and leukemia-free survival. Better HLA-matched donors, use of bone marrow, and transplantation within one year of diagnosis were also associated with better survival. A matched-pairs analysis was performed and confirmed a higher survival rate among first chronic phase patients receiving IM. Among patients transplanted with advanced CML, use of IM before HCT was not associated with treatment-related mortality, relapse, leukemia-free survival, or survival. Acute graft-versus-host disease rates were similar between IM+ and IM- groups regardless of leukemia phase. These results should be reassuring to patients receiving IM before HCT.
C1 [Lee, Stephanie J.; Woolfrey, Ann E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Kukreja, Manisha; Wang, Tao; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Giralt, Sergio A.; Champlin, Richard E.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Szer, Jeffrey] Royal Melbourne Hosp, Parkville, Vic 3050, Australia.
[Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Cervantes, Francisco] Hosp Clin Barcelona, Barcelona, Spain.
[Gale, Robert Peter] Ctr Adv Studies Leukemia, Los Angeles, CA USA.
[Halter, Joerg] Univ Basel Hosp, CH-4031 Basel, Switzerland.
[Keating, Armand; Gupta, Vikas] Princess Margaret Hosp Children, Toronto, ON, Canada.
[Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England.
[McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Olavarria, Eduardo] Hammersmith Hosp, London, England.
[Stadtmauer, Edward A.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Abecasis, Manuel] Inst Portugues Oncol Francisco Gentil, Lisbon, Portugal.
[Khoury, H. Jean] Emory Univ, Sch Med, Atlanta, GA USA.
[George, Biju] Christian Med Coll & Hosp, Vellore 632004, Tamil Nadu, India.
[Hale, Gregory A.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Liesveld, Jane L.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA.
[Rizzieri, David A.] Duke Univ, Med Ctr, Durham, NC USA.
[Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bolwell, Brian J.; Copelan, Edward] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Carabasi, Matthew H.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Ilhan, Osman] Ibni Sinai Hosp, Ankara, Turkey.
[Litzow, Mark R.] Mayo Clin, Rochester, MN USA.
[Schouten, Harold C.] Univ Hosp Maastricht, Maastricht, Netherlands.
[Zander, Axel R.] Univ Hosp Eppendorf, Hamburg, Germany.
[Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA.
EM sjlee@fhcrc.org
RI Halter, Joerg/C-9487-2012;
OI Szer, Jeff/0000-0001-6783-2301
FU Novartis; National Cancer Institute [U24CA76518]; National Institute of
Allergy and Infectious Diseases; National Heart, Lung, and Blood
Institute; Office of Naval Research; Health Resources and Services
Administration; AABB; Aetna; American International Group; American
Society for Blood and Marrow Transplantation; Amgen; Anonymous donation
to the Medical College of Wisconsin; Astellas Pharma US; Baxter
International; Bayer HealthCare Pharmaceuticals; BioOne Corporation;
BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone
Marrow Foundation; Bristol-Myers Squibb Company; Cangene Corporation;
Celgene Corporation; CellGenix; Cerus Corporation; Cubist
Pharmaceuticals; Cylex; CytoTherm; DOR BioPharma; Dynal Biotech, an
Invitrogen company; EKR Therapeutics; Enzon Pharmaceuticals; Gambro BCT;
Gamida Cell; Genzyme Corporation; Gift of Life Bone Marrow Foundation;
GlaxoSmithKline; Histogenetics; HKS Medical Information Systems;
Hospira; Infectious Diseases Society of America; Kiadis Pharma; Kirin
Brewery; Merck Company; Medical College of Wisconsin; MGI Pharma;
Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA;
Miltenyi Biotec; MultiPlan; National Marrow Donor Program; Nature
Publishing Group; Oncology Nursing Society; Osiris Therapeutics; Pall
Life Sciences; PDL BioPharma; Pfizer; Pharmion Corporation; Roche
Laboratories; Schering Plough Corporation; Society for Healthcare
Epidemiology of America; StemCyte; StemSoft Software; SuperGen; Sysmex;
Teva Pharmaceutical Industries; Marrow Foundation; THERAKOS; University
of Colorado Cord Blood Bank; ViaCell; Vidacare Corporation; ViraCor
Laboratories; ViroPharma; Wellpoint
FX This work was supported by Novartis (research grant). The CIBMTR is
supported by Public Health Service Grant U24CA76518 from the National
Cancer Institute, the National Institute of Allergy and Infectious
Diseases, and the National Heart, Lung, and Blood Institute; Office of
Naval Research; Health Resources and Services Administration; and grants
from the following: AABB; Aetna; American International Group; American
Society for Blood and Marrow Transplantation; Amgen; Anonymous donation
to the Medical College of Wisconsin; Astellas Pharma US; Baxter
International; Bayer HealthCare Pharmaceuticals; BioOne Corporation;
BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone
Marrow Foundation; Bristol-Myers Squibb Company; Cangene Corporation;
Celgene Corporation; CellGenix; Cerus Corporation; Cubist
Pharmaceuticals; Cylex; CytoTherm; DOR BioPharma; Dynal Biotech, an
Invitrogen company; EKR Therapeutics; Enzon Pharmaceuticals; Gambro BCT;
Gamida Cell; Genzyme Corporation; Gift of Life Bone Marrow Foundation;
GlaxoSmithKline; Histogenetics; HKS Medical Information Systems;
Hospira; Infectious Diseases Society of America; Kiadis Pharma; Kirin
Brewery; Merck & Company; Medical College of Wisconsin; MGI Pharma;
Millennium Pharmaceuticals; Miller Pharmacal Group; Milliman USA;
Miltenyi Biotec; MultiPlan; National Marrow Donor Program; Nature
Publishing Group; Oncology Nursing Society; Osiris Therapeutics; Pall
Life Sciences; PDL BioPharma; Pfizer; Pharmion Corporation; Roche
Laboratories; Schering Plough Corporation; Society for Healthcare
Epidemiology of America; StemCyte; StemSoft Software; SuperGen; Sysmex;
Teva Pharmaceutical Industries; Marrow Foundation; THERAKOS; University
of Colorado Cord Blood Bank; ViaCell; Vidacare Corporation; ViraCor
Laboratories; ViroPharma; and Wellpoint.; The views expressed in this
article do not reflect the official policy or position of the National
Institutes of Health, the Department of the Navy, the Department of
Defense, or any other agency of the U. S. Government.
NR 24
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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 OCT 15
PY 2008
VL 112
IS 8
BP 3500
EP 3507
DI 10.1182/blood-2008-02-141689
PG 8
WC Hematology
SC Hematology
GA 357SH
UT WOS:000259866100067
PM 18664621
ER
PT J
AU Ford, JM
Roach, BJ
Hoffman, RS
Mathalon, DH
AF Ford, Judith M.
Roach, Brian J.
Hoffman, Ralph S.
Mathalon, Daniel H.
TI The dependence of P300 amplitude on gamma synchrony breaks down in
schizophrenia
SO BRAIN RESEARCH
LA English
DT Article
DE Schizophrenia; EEG; Phase synchrony; Power
ID SINGLE-TRIAL ANALYSIS; AUDITORY ODDBALL PARADIGM; EVOKED-RESPONSES;
WAVELET ANALYSIS; EEG ACTIVITY; METAANALYSIS; VARIABILITY; STIMULI;
HUMANS
AB Introduction: Auditory P300 amplitude reduction in schizophrenia is canonical and may be explained by poor synchronization or reduced power of the underlying neural activity. We asked if patients have reduced synchrony and power, and whether together with P300 amplitude, they make unique or overlapping contributions to the discrimination between patients and controls. We also asked whether people who have large P300s have higher power and greater synchrony of neural activity, and if the relationships between P300 and power and synchrony are different in patients and healthy controls. Methods: We recorded EEG data from 22 controls and 21 patients with schizophrenia (DSM-IV) while they performed an auditory target detection task. We used wavelet analyses of the single trial data to estimate total power and synchrony of delta, theta, alpha, beta, and gamma activity in a 50ms window around the peak of the P300 to the target. We measured P300 amplitude from the average of the single trials, in a 50ms window around its peak. Results and conclusions: P300 amplitude and delta and theta synchrony were reduced in patients; delta power and synchrony better distinguished between groups than P300 amplitude. In healthy controls, but not patients, gamma synchrony predicted P300 amplitude. In patients, P300 and gamma synchrony are affected by independent factors; the relationship between them is attenuated by an additional pathophysiological process. (c) Published by Elsevier B.V.
C1 [Ford, Judith M.; Roach, Brian J.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Ford, Judith M.; Roach, Brian J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA.
[Hoffman, Ralph S.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
RP Ford, JM (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St, San Francisco, CA 94121 USA.
EM judith.ford@ucsf.edu
OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974
FU VA Schizophrenia Biological Research Center; National Institute of
Mental Health [MH40052, MH S8262, MH067967]; National Alliance for
Research in Schizophrenia and Affective Disorders (NARSAD)
FX This work was supported by the VA Schizophrenia Biological Research
Center and grants from National Institute of Mental Health (MH40052, MH
S8262, MH067967), and the National Alliance for Research in
Schizophrenia and Affective Disorders (NARSAD).
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U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD OCT 15
PY 2008
VL 1235
SI SI
BP 133
EP 142
DI 10.1016/j.brainres.2008.06.048
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 371UZ
UT WOS:000260858400014
PM 18621027
ER
PT J
AU Saad, AG
Yeap, BY
Thunnissen, FBJM
Pinkus, GS
Pinkus, JL
Loda, M
Sugarbaker, DJ
Johnson, BE
Chirieac, LR
AF Saad, Ali G.
Yeap, Beow Y.
Thunnissen, Frederik B. J. M.
Pinkus, Geraldine S.
Pinkus, Jack L.
Loda, Massimo
Sugarbaker, David J.
Johnson, Bruce E.
Chirieac, Lucian R.
TI Immunohistochemical Markers Associated With Brain Metastases in Patients
With Nonsmall Cell Lung Carcinoma
SO CANCER
LA English
DT Article
DE epidermal growth factor receptor; Ki-67 labeling index; overall
survival; tumor markers; vascular endothelial growth factor
ID ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR; COMPUTED-TOMOGRAPHY;
ONCOLOGY-GROUP; TUMOR-GROWTH; CANCER; EXPRESSION; ANGIOGENESIS;
PROLIFERATION; CHEMOTHERAPY
AB BACKGROUND. To the authors' knowledge, there are no reliable markers able to identify patients with nonsmall cell lung cancer (NSCLC) that will develop metastases to the brain. The authors investigated associations between immunohistochemical markers and the development of brain metastases in patients with NSCLC.
METHODS. This was a hospital-based, case-control Study of patients who were newly diagnosed with NSCLC between 1989 and 2003, developed brain metastases, and had pathology material available from both the primary NSCLC and the brain metastases. These patients were compared with a control group of patients who had NSCLC and no evidence of brain metastases. NSCLC was examined for expression levels of Ki-67, caspase-3, vascular endothelial growth factor A (VEGF-A), VEGF-C, E-cadherin, and epidermal growth factor receptor (EGFR) in 54 surgical pathology specimens using immunohistochemistry, and associations were evaluated between those markers and the development of brain metastases.
RESULTS. Brain metastases developed after a median of 12.5 months (range, 1.7-89.4 months) after the diagnosis of NSCLC. A significantly increased risk of developing brain metastases was associated with patients with NSCLC who had primary tumors with high Ki-67 levels (adjusted odds ratio [OR] of 12.2; 95% confidence interval [95% CI], 2.4-70.4 [P < .001]), low caspase-3 expression (adjusted OR of 43; 95% CI, 5.3 to > 100 [P < .001]), high VEGF-C expression (adjusted OR of 14.6; 95% Cl, 2.0 to > 100 [P < .001]), and low E-cadherin (adjusted OR of 3.6; 95% Cl, 0.9-16.4 [P = .05]). No significant risk was associated with VEGF-A or EGFR expression. High Ki-67 expression also was associated with a shorter overall survival (P = .04).
CONCLUSIONS. The results of the current study indicated that patients with NSCLC who had high Ki-67 expression, low caspase-3 expression, high VEGF-C expression, and low E-cadherin expression in their tumors may benefit from close surveillance because they may have an increased risk of developing brain metastases. Cancer 2008; 113:2129-38. (C) 2008 American Cancer Society.
C1 [Saad, Ali G.; Pinkus, Geraldine S.; Pinkus, Jack L.; Loda, Massimo; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Saad, Ali G.; Yeap, Beow Y.; Pinkus, Geraldine S.; Pinkus, Jack L.; Loda, Massimo; Sugarbaker, David J.; Johnson, Bruce E.; Chirieac, Lucian R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Thunnissen, Frederik B. J. M.] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands.
[Sugarbaker, David J.] Brigham & Womens Hosp, Dept Gen Thorac Surg, Boston, MA 02115 USA.
[Johnson, Bruce E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Chirieac, LR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM lchirieac@partners.org
OI Thunnissen, Erik/0000-0001-5355-8508
FU National Institutes of Health [CA90578, CA074386, CA092824]; Brigham and
Women's Hospital
FX Supported by CA90578, CA074386, and CA092824 from the National
Institutes of Health and by the International Mesothelioma Program from
Brigham and Women's Hospital.
NR 55
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U1 1
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 15
PY 2008
VL 113
IS 8
BP 2129
EP 2138
DI 10.1002/cncr.23826
PG 10
WC Oncology
SC Oncology
GA 362LA
UT WOS:000260198000018
PM 18720359
ER
PT J
AU Haas, JS
Earle, CC
Orav, JE
Brawarsky, P
Keohane, M
Neville, BA
Williams, DR
AF Haas, Jennifer S.
Earle, Craig C.
Orav, John E.
Brawarsky, Phyllis
Keohane, Marie
Neville, Bridget A.
Williams, David R.
TI Racial Segregation and Disparities in Breast Cancer Care and Mortality
SO CANCER
LA English
DT Article
DE race; ethnicity; breast cancer; segregation
ID RESIDENTIAL SEGREGATION; CLAIMS DATA; LUNG-CANCER; OLDER WOMEN; MEDICARE
BENEFICIARIES; SOCIOECONOMIC-STATUS; GEOGRAPHIC-VARIATION; CARCINOMA
TREATMENT; CONSERVING SURGERY; ETHNIC DISPARITIES
AB BACKGROUND. Questions have existed as to whether residential segregation is a mediator of racial/ethnic disparities in breast cancer care and breast cancer mortality, or has a differential effect by race/ethnicity.
METHODS. Data from the Surveillance, Epidemiology, and End Results-Medicare database on white, black, and Hispanic women aged 66 to 85 years with breast cancer were examined for the receipt of adequate breast cancer care.
RESULTS. Blacks were less likely than whites to receive adequate breast cancer care (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.71-0.86). Individuals, both black and white, who lived in areas with greater black segregation were less likely to receive adequate breast cancer care (OR, 0.73; 95% CI, 0.64-0.82). Black segregation was a mediator of the black/white disparity in breast cancer care, explaining 8.9% of the difference. After adjustment, adequate care for Hispanics did not significantly differ from whites, but individuals, both Hispanic and white, who lived in areas with greater Hispanic segregation were less likely to receive adequate breast cancer care (OR, 0.73; 95% CI, 0.61-0.89). Although Blacks experienced greater breast cancer mortality than whites, black segregation did not substantially mediate the black-white disparity in survival, and was not significantly associated with mortality (hazards ratio, 1.03; 95% CI, 0.87-1.21). Breast cancer mortality did not differ between Hispanics and whites.
CONCLUSIONS. Among seniors, segregation mediates some of the black-white disparity in breast cancer care, but not mortality. Individuals who live in more segregated areas are less likely to receive adequate breast cancer care. Cancer 2008; 113:2166-72. (C) 2008 American Cancer Society.
C1 [Haas, Jennifer S.; Orav, John E.; Brawarsky, Phyllis; Keohane, Marie] Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, Boston, MA 02120 USA.
[Haas, Jennifer S.; Orav, John E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Earle, Craig C.; Neville, Bridget A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Williams, David R.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, 1620 Tremont St, Boston, MA 02120 USA.
EM jhaas@partners.org
FU National Cancer Institute [R01 CA112451]
FX Supported by the National Cancer Institute (R01 CA112451).; We thank
Joan Warren, PhD for her helpful comments on an earlier version of this
article. We thank Philip J. Ethington, PhD for sharing methods for
creating measures of residential segregation in municipal areas.
NR 46
TC 37
Z9 37
U1 2
U2 9
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 15
PY 2008
VL 113
IS 8
BP 2166
EP 2172
DI 10.1002/cncr.23828
PG 7
WC Oncology
SC Oncology
GA 362LA
UT WOS:000260198000023
PM 18798230
ER
PT J
AU Spain, P
Carpenter, WR
Talcott, JA
Clark, JA
Do, YK
Hamilton, RJ
Galanko, JA
Jackman, A
Godley, PA
AF Spain, Pamela
Carpenter, William R.
Talcott, James A.
Clark, Jack A.
Do, Young Kyung
Hamilton, Robert J.
Galanko, Joseph A.
Jackman, Anne
Godley, Paul A.
TI Perceived Family History Risk and Symptomatic Diagnosis of Prostate
Cancer The North Carolina Prostate Cancer Outcomes Study
SO CANCER
LA English
DT Article
DE prostatic neoplasms; diagnosis; treatment; African Americans/psychology;
European continental ancestry group/psychology; attitude to health;
socioeconomic factors; access to healthcare
ID AFRICAN-AMERICAN MEN; COMMON OUTCOMES; RELATIVE RISK; OLDER MEN;
KNOWLEDGE; SURVIVAL; ANTIGEN; SERVICES; BEHAVIOR; BELIEFS
AB BACKGROUND. Prostate cancer (PrCA) is the most common cancer and the second leading cause of cancer death among US men. African American (AA) men remain at significantly greater risk of PrCA diagnosis and mortality than other men. Many factors contribute to the experienced disparities.
METHODS. Guided by the Health Belief Model, the authors surveyed a population of AA and Caucasian men newly diagnosed with PrCA to describe racial differences in perceived risk of PrCA and to examine whether 1) perceived high risk predicts greater personal responsibility for prostate care; and 2) greater personal responsibility for prostate care predicts earlier, presymptomatic diagnosis. Multivariate general linear modeling was performed.
RESULTS. The authors found that men with a PrCA family history appreciated their increased risk, but AA men with a family history were less likely to appreciate their increased risk. Nevertheless, neither reporting a PrCA family history nor perceived increased risk significantly predicted screening and preventive behaviors. Furthermore, higher physician trust predicted increased likelihood to have regular prostate exams and screening, indicating that the racial differences in seeking prostate care may be mediated through physician trust. Expressed personal responsibility for screening and more frequent preventive behaviors were associated with more frequent screening diagnoses, fewer symptomatic diagnoses, and less frequent advanced cancers.
CONCLUSIONS. Together, these results indicate that appreciating greater risk for PrCA is not sufficient to ensure that men will intend, or be able, to act. Increased trust in physicians may be a useful, central marker that efforts to reduce disparities in access to medical care are succeeding. Cancer 2008;113:2180-7. (C) 2008 American Cancer Society.
C1 [Spain, Pamela] RTI Int, Hlth & Social Org Res, Res Triangle Pk, NC 27709 USA.
[Spain, Pamela; Jackman, Anne; Godley, Paul A.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA.
[Carpenter, William R.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Carpenter, William R.; Do, Young Kyung] Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC 27599 USA.
[Talcott, James A.] Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA USA.
[Talcott, James A.] Harvard Univ, Sch Med, Boston, MA USA.
[Clark, Jack A.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Clark, Jack A.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Hamilton, Robert J.] Univ Toronto, Dept Urol Surg, Toronto, ON, Canada.
[Galanko, Joseph A.; Godley, Paul A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Godley, Paul A.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
RP Spain, P (reprint author), RTI Int, Hlth & Social Org Res, POB 12194, Res Triangle Pk, NC 27709 USA.
EM pspain@rti.org
RI Carpenter, William/E-5125-2013;
OI Clark, Jack/0000-0002-7424-1670; Hamilton, Robert/0000-0002-6715-5934
FU Agency for Healthcare Research and Quality [5-P01-HS010861]; National
Center on Minority Health and Health Disparities [1 P60 MD0024-01];
National Cancer Institute [1 U01 CA114629-01, R25T CA 57726]; NIH [P30
DK 034987]; Department of Defense [PC040795]
FX Supported by Agency for Healthcare Research and Quality Grant
5-P01-HS010861, National Center on Minority Health and Health
Disparities Grant 1 P60 MD0024-01, and National Cancer Institute Grant 1
U01 CA114629-01.; Dr. Carpenter is supported by a training grant from
the National Cancer Institute (R25T CA 57726). Dr. Galanko is supported
by NIH Grant P30 DK 034987.; Dr. Godley is supported by Department of
Defense Grant PC040795.
NR 30
TC 11
Z9 11
U1 2
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 15
PY 2008
VL 113
IS 8
BP 2180
EP 2187
DI 10.1002/cncr.23801
PG 8
WC Oncology
SC Oncology
GA 362LA
UT WOS:000260198000025
PM 18798229
ER
PT J
AU Krull, KR
Gioia, G
Ness, KK
Ellenberg, L
Recklitis, C
Leisenring, W
Huang, S
Stovall, M
Robison, LL
Zeltzer, L
AF Krull, Kevin R.
Gioia, Gerard
Ness, Kirsten K.
Ellenberg, Leah
Recklitis, Christopher
Leisenring, Wendy
Huang, Sujuan
Stovall, Marilyn
Robison, Leslie L.
Zeltzer, Lonnie
TI Reliability and Validity of the Childhood Cancer Survivor Study
Neurocognitive Questionnaire
SO CANCER
LA English
DT Article
DE Childhood Cancer Survivor Study; neurocognitive; questionnaire; late
effects
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; QUALITY-OF-LIFE; TEMPORAL-LOBE EPILEPSY;
FRONTAL-LOBE; NEUROPSYCHOLOGICAL PERFORMANCE; CHILDREN; MEMORY;
DEPRESSION; ONCOLOGY; SEQUELAE
AB BACKGROUND. Up to 40% of childhood cancer survivors may experience neurocognitive impairment in I or more specific domains. As such, regular monitoring has been recommended for patients exposed to cranial irradiation and/or antimetabolite chemotherapy. This study reports the results of a questionnaire developed to identify those survivors who may be experiencing neurocognitive problems.
METHODS. Participants for this study were 7121 members of the Childhood Cancer Survivor Study cohort (6739 survivors and 382 siblings). These participants completed a new neurocognitive questionnaire designed to assess functions commonly affected by cancer therapy, as well as a standard measure of emotional functioning. A measure of cognitive and emotional functioning was also completed on a subset of the patients roughly 7 years before the current questionnaire. Responses to the questionnaires among subgroups of survivors were then analyzed to examine the reliability and validity of the new neurocognitive questionnaire.
RESULTS. Four reliable factors were identified that assessed task efficiency, emotional regulation, organization, and memory skills. These neurocognitive factors accurately discriminated survivors who were at "high risk" for neurocognitive dysfunction, because of neurologic abnormalities or a history of intensive focal cranial irradiation, from healthy "low-risk" survivors and siblings.
CONCLUSIONS. The questionnaire demonstrated excellent reliability, as well as construct and discriminative validity. It appears to be a practical and efficient tool for monitoring neurocognitive outcomes in adult survivors of pediatric cancer. Cancer 2008; 113:2188-97. (C) 2008 American Cancer Society.
C1 [Krull, Kevin R.; Ness, Kirsten K.; Huang, Sujuan; Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA.
[Gioia, Gerard] Childrens Natl Med Ctr, Dept Psychiat, Washington, DC 20010 USA.
[Ellenberg, Leah] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Recklitis, Christopher] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA.
[Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Dept Biostat, Seattle, WA 98104 USA.
[Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Zeltzer, Lonnie] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
RP Krull, KR (reprint author), St Jude Childrens Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St,MS 735, Memphis, TN 38105 USA.
EM kevin.krull@stjude.org
OI Zeltzer, Lonnie/0000-0001-9306-9450
FU NCI NIH HHS [U24 CA055727, U24 CA055727-14, U24-CA55727]
NR 56
TC 30
Z9 30
U1 1
U2 1
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 OCT 15
PY 2008
VL 113
IS 8
BP 2188
EP 2197
DI 10.1002/cncr.23809
PG 10
WC Oncology
SC Oncology
GA 362LA
UT WOS:000260198000026
PM 18792068
ER
PT J
AU Wang, JH
Cai, Y
Yu, WD
Ren, CX
Spencer, DM
Ittmann, M
AF Wang, Jianghua
Cai, Yi
Yu, Wendong
Ren, Chengxi
Spencer, David M.
Ittmann, Michael
TI Pleiotropic Biological Activities of Alternatively Spliced TMPRSS2/ERG
Fusion Gene Transcripts
SO CANCER RESEARCH
LA English
DT Article
ID HUMAN PROSTATE-CANCER; TMPRSS2-ERG FUSION; EXPRESSION; ERG;
TUMORIGENESIS; ANGIOGENESIS; ABERRATIONS; PROGRESSION; METASTASIS;
EPITHELIUM
AB TMPRSS2/ERG gene fusions are found in the majority of prostate cancers; however, there is significant heterogeneity in the 5' region of the alternatively spliced fusion gene transcripts. We have found that there is also significant heterogeneity within the coding exons as well. There is variable inclusion of a 72-bp exon and other novel alternatively spliced isoforms. To assess the biological significance of these alternatively spliced transcripts, we expressed various transcripts in primary prostatic epithelial cells (PrEC) and in an immortalized PrEC line, PNT1a. The fusion gene transcripts promoted proliferation, invasion, and motility with variable activities that depended on the structure of the 5' region encoding the TMPRSS2/ERG fusion and the presence of the 72-bp exon. Cotransfection of different isoforms further enhanced biological activity, mimicking the situation in vivo, in which multiple isoforms are expressed. Finally, knockdown of the fusion gene in VCaP cells resulted in inhibition of proliferation in vitro and tumor progression in an in vivo orthotopic mice model. Our results indicate that TMPRSS2/ERG fusion isoforms have variable biological activities promoting tumor initiation and progression and are consistent with our previous clinical observations indicating that certain TMPRSS2/ERG fusion isoforms are significantly correlated with more aggressive disease. [Cancer Res 2008; 68(20):8516-24]
C1 [Wang, Jianghua; Cai, Yi; Yu, Wendong; Ren, Chengxi; Ittmann, Michael] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
[Spencer, David M.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA.
[Wang, Jianghua; Cai, Yi; Yu, Wendong; Ren, Chengxi; Ittmann, Michael] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA.
RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA.
EM mittmann@bcm.tmc.edu
FU Department of Defense Prostate Cancer Research [DAMD W81XWH-08-1-0055];
National Cancer Institute [P50CA058204]; Department of Veterans Affairs;
Michael E. DeBakey Veterans Affairs Medical Center
FX Grant support: This work was supported by grants from the Department of
Defense Prostate Cancer Research program (DAMD W81XWH-08-1-0055), the
National Cancer Institute to the Baylor Prostate Cancer Specialized
Program of Research Excellence (P50CA058204), and the Department of
Veterans Affairs Merit Review program (M. Ittmann) and by the use of the
facilities of the Michael E. DeBakey Veterans Affairs Medical Center.
NR 35
TC 87
Z9 93
U1 0
U2 0
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 OCT 15
PY 2008
VL 68
IS 20
BP 8516
EP 8524
DI 10.1158/0008-5472.CAN-08-1147
PG 9
WC Oncology
SC Oncology
GA 364GE
UT WOS:000260323400038
PM 18922926
ER
PT J
AU Chin, LJ
Ratner, E
Leng, SG
Zhai, RH
Nallur, S
Babar, I
Muller, RU
Straka, E
Su, L
Burki, EA
Crowell, RE
Patel, R
Kulkarni, T
Homer, R
Zelterman, D
Kidd, KK
Zhu, Y
Christiani, DC
Belinsky, SA
Slack, FJ
Weidhaas, JB
AF Chin, Lena J.
Ratner, Elena
Leng, Shuguang
Zhai, Rihong
Nallur, Sunitha
Babar, Imran
Muller, Roman-Ulrich
Straka, Eva
Su, Li
Burki, Elizabeth A.
Crowell, Richard E.
Patel, Rajeshvari
Kulkarni, Trupti
Homer, Robert
Zelterman, Daniel
Kidd, Kenneth K.
Zhu, Yong
Christiani, David C.
Belinsky, Steven A.
Slack, Frank J.
Weidhaas, Joanne B.
TI A SNP in a let-7 microRNA Complementary Site in the KRAS 3 '
Untranslated Region Increases Non-Small Cell Lung Cancer Risk
SO CANCER RESEARCH
LA English
DT Article
ID TARGET SITES; POLYMORPHISMS; EXPRESSION; GENES; ASSOCIATION;
SUPPRESSION; HAPLOTYPES; GENOTYPES; MIR-125A; SURVIVAL
AB Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3' untrauslated regions of their target mRNAs. The purpose of this study was to identify single nucleotide polymorphisms (SNP) that could modify let-7 binding and to assess the effect of such SNPs on target gene regulation and risk for non-small cell lung cancer (NSCLC). let-7 complementary sites (LCS) were sequenced in the KRAS 3' untranslated region from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously unidentified SNP at LCS6 was characterized in 2,433 people (representing 46 human populations). The frequency of the variant allele is 18.1% to 20.3% in NSCLC patients and 5.8% in world populations. The association between the SNP and the risk for NSCLC was defined in two independent case-control studies. A case-control study of lung cancer from New Mexico showed a 2.3-fold increased risk (confidence interval, 1.1-4.6; P = 0.02) for NSCLC cancer in patients who smoked <40 pack-years. This association was validated in a second independent case-control study. Functionally, the variant allele results in KRAS overexpression in vitro. The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility. [Cancer Res 2008;68(20):8535-40]
C1 [Ratner, Elena; Nallur, Sunitha; Muller, Roman-Ulrich; Patel, Rajeshvari; Kulkarni, Trupti; Weidhaas, Joanne B.] Yale Univ, Dept Therapeut Radiol, New Haven, CT 06520 USA.
[Chin, Lena J.; Babar, Imran; Slack, Frank J.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
[Straka, Eva; Kidd, Kenneth K.] Yale Univ, Dept Genet, New Haven, CT 06520 USA.
[Homer, Robert] Yale Univ, Dept Pathol, New Haven, CT 06520 USA.
[Zelterman, Daniel; Zhu, Yong] Yale Univ, Dept Epidemiol, New Haven, CT 06520 USA.
[Zhai, Rihong; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulmonary & Crit Care Unit,Dept Med, Boston, MA USA.
[Crowell, Richard E.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Leng, Shuguang; Burki, Elizabeth A.; Belinsky, Steven A.] Lovelace Resp Res Inst, Lung Canc Program, Albuquerque, NM USA.
RP Weidhaas, JB (reprint author), Yale Univ, Dept Therapeut Radiol, 333 Cedar St, New Haven, CT 06520 USA.
EM frank.slack@yale.edu; joanne.weidhaas@yale.edu
RI Paranjape, Trupti/E-4338-2012;
OI Weidhaas, Joanne/0000-0002-5096-3281; Slack, Frank/0000-0001-8263-0409
FU Connecticut Department of Public Health; Shannon Foundation; Flight
Attendant Medical Research Institute [R01 CA122676, U01 CA097356,
CA074386, CA090578, CA092824, ES00002]
FX Grant support: Connecticut Department of Public Health (FJ. Slack and
J.B. Weidhaas), Shannon Foundation funds (J.B. Weidhaas), grant R01
CA122676 (Y. Zhu), grant U01 CA097356 (S. Belinsky), grants CA074386,
CA090578, CA092824, and ES00002 (D. Christiani), and a grant from the
Flight Attendant Medical Research Institute (R. Zhai).
NR 36
TC 366
Z9 401
U1 3
U2 30
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 OCT 15
PY 2008
VL 68
IS 20
BP 8535
EP 8540
DI 10.1158/0008-5472.CAN-08-2129
PG 6
WC Oncology
SC Oncology
GA 364GE
UT WOS:000260323400040
PM 18922928
ER
PT J
AU Chen, YM
Chen, PL
Chen, CF
Jiang, XZ
Riley, DJ
AF Chen, Yumay
Chen, Phang-Lang
Chen, Chi-Fen
Jiang, Xianzhi
Riley, Daniel J.
TI Never-in-mitosis related kinase 1 functions in DNA damage response and
checkpoint control
SO CELL CYCLE
LA English
DT Article
DE checkpoint control; radiation; S-phase; mitosis; chromosome breaks
ID POLYCYSTIC KIDNEY-DISEASE; NIMA-RELATED KINASES; PROTEIN-KINASE;
ASPERGILLUS-NIDULANS; FAMILY KINASE; CHROMATIN CONDENSATION;
ATAXIA-TELANGIECTASIA; MITOTIC PROGRESSION; MURINE MODELS; NEK2 KINASE
AB Nek1, the first mammalian ortholog of the fungal protein kinase never in mitosis A, is involved early in the DNA damage sensing/repair pathway after ionizing radiation. Here we extend this finding by showing that Nek1 localizes to nuclear foci of DNA damage in response to many different types of damage in addition to IR. Untransformed cells established from kat2J/Nek1(-/-) mice fail to arrest properly at G(1)/S and M-phase checkpoints in response to DNA damage. G(1)-S-phase checkpoint control can be rescued by ectopically overexpressing wild-type Nek1. In Nek1(-/-) murine cells and in human cells with Nek1 expression silenced by siRNA, the checkpoint kinases Chk1 and Chk2 fail to be activated properly in response to ionizing or UV radiation. In cells without functional Nek1, DNA is not repaired properly, double-stranded DNA breaks persist long after low dose IR, and excessive numbers of chromosome breaks are observed. These data show that Nek1 is important for efficient DNA damage checkpoint control and for proper DNA damage repair.
C1 [Chen, Yumay; Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA.
[Chen, Phang-Lang; Chen, Chi-Fen; Jiang, Xianzhi] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA.
[Riley, Daniel J.] S Texas Vet Hlth Care Syst, Renal Res Div, Audie L Murphy Div, San Antonio, TX USA.
RP Chen, YM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM cheny@uthscsa.edu
RI Jiang, Xianzhi/A-5427-2013
OI Jiang, Xianzhi/0000-0002-4645-154X
FU PKD foundation; American Society of Nephrology; National Kidney
Foundation; NIH [R01-DK067339, P50-DK061597, R01-DK61626]; George M.
O'Brien Kidney Research Center; Veterans Administration Renal Research
FX This work was supported by grants from the PKD foundation, the American
Society of Nephrology, the National Kidney Foundation, and the NIH
(R01-DK067339) to Y. C.; a George M. O'Brien Kidney Research Center
grant from the NIH to Y. C. (P50-DK061597), Hanna E. Abboud, Program
Director); and a grant from the NIH to D. J. R. (R01-DK61626). We thank
Huai-Chin Chiang and Sergio Garcia for technical support, and a Veterans
Administration Renal Research Excellence Award to the South Texas
Veterans Health Care System, Audie L. Murphy Division, for help with
core services, equipment, and institutional
NR 42
TC 34
Z9 34
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD OCT 15
PY 2008
VL 7
IS 20
BP 3194
EP 3201
DI 10.4161/cc.7.20.6815
PG 8
WC Cell Biology
SC Cell Biology
GA 363JI
UT WOS:000260263200015
PM 18843199
ER
PT J
AU Coleman, RE
Guise, TA
Lipton, A
Roodman, GD
Berenson, JR
Body, JJ
Boyce, BF
Calvi, LM
Hadji, P
McCloskey, EV
Saad, F
Smith, MR
Suva, LJ
Taichman, RS
Vessella, RL
Weilbaecher, KN
AF Coleman, Robert E.
Guise, Theresa A.
Lipton, Allan
Roodman, G. David
Berenson, James R.
Body, Jean-Jacques
Boyce, Brendan F.
Calvi, Laura M.
Hadji, Peyman
McCloskey, Eugene V.
Saad, Fred
Smith, Matthew R.
Suva, Larry J.
Taichman, Russell S.
Vessella, Robert L.
Weilbaecher, Katherine N.
TI Advancing Treatment for Metastatic Bone Cancer: Consensus
Recommendations from the Second Cambridge Conference
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID KAPPA-B LIGAND; BREAST-CANCER; PROSTATE-CANCER; ZOLEDRONIC ACID;
SKELETAL COMPLICATIONS; RECEPTOR ACTIVATOR; MULTIPLE-MYELOMA; TUMOR
BURDEN; SOLID TUMORS; LUNG-CANCER
AB Purpose: Summarize current knowledge, critical gaps in knowledge, and recommendations to advance the field of metastatic bone cancer.
Experimental Design: A multidisciplinary consensus conference was convened to review recent progress in basic and clinical research, assess critical gaps in current knowledge, and prioritize recommendations to advance research in the next 5 years. The program addressed three principal topics: biology of metastasis, preserving normal bone health, and optimizing bone-targeted therapies.
Results: A variety of specific recommendations were identified as important to advance research and clinical care over the next 5 years.
Conclusions: Priorities for research in bone biology include characterizing components of the stem cell niche in bone, developing oncogenic immunocompetent animal models of bone metastasis, and investigating the unique contribution of the bone microenvironment to tumor growth and dormancy. Priorities for research in preserving normal bone health include developing methods to measure and characterize disseminating tumor cells, assessing outcomes from the major prevention trials currently in progress, and improving methodologies to assess risks and benefits of treatment. Priorities for optimizing bone-targeted therapies include advancing studies of serum proteomics and genomics to reliably identify patients who will develop bone metastases, enhancing imaging for early detection of bone metastases and early response evaluation, and developing new tests to evaluate response to bone-directed treatments.
C1 [Coleman, Robert E.] Univ Sheffield, Canc Res Ctr, Weston Pk Hosp, Acad Unit Clin Oncol, Sheffield S10 2SJ, S Yorkshire, England.
[McCloskey, Eugene V.] Univ Sheffield, Metab Bone Ctr, Sheffield S10 2SJ, S Yorkshire, England.
[Guise, Theresa A.] Univ Virginia, Dept Internal Med, Div Endocrinol, Charlottesville, VA USA.
[Lipton, Allan] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Med & Oncol, Hershey, PA 17033 USA.
[Roodman, G. David] Vet Adm Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA.
[Berenson, James R.] Inst Myeloma & Bone Canc Res, West Hollywood, CA USA.
[Body, Jean-Jacques] Univ Libre Bruxelles, CHU Brugmann, Brussels, Belgium.
[Boyce, Brendan F.; Calvi, Laura M.] Univ Rochester, Sch Med & Dent, Div Endocrinol Metab, New York, NY USA.
[Hadji, Peyman] Univ Hosp Giessen & Marburg GmbH, Dept Endocrinol, Marburg, Germany.
[Saad, Fred] Univ Montreal, Hop Notre Dame, Ctr Hosp, Dept Urol Oncol, Montreal, PQ, Canada.
[Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Dept Genitourinary Med Oncol, Boston, MA USA.
[Suva, Larry J.] Univ Arkansas Med Sci, Ctr Orthopaed Res, Little Rock, AR 72205 USA.
[Taichman, Russell S.] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA.
[Vessella, Robert L.] Univ Washington, Seattle, WA 98195 USA.
[Weilbaecher, Katherine N.] Washington Univ, Sch Med, Div Mol Oncol, St Louis, MO USA.
RP Coleman, RE (reprint author), Univ Sheffield, Canc Res Ctr, Weston Pk Hosp, Acad Unit Clin Oncol, Whitham Rd, Sheffield S10 2SJ, S Yorkshire, England.
EM r.e.coleman@sheffield.ac.uk
OI Taichman, Russell S./0000-0002-7890-0020; Calvi, Laura
Maria/0000-0001-6969-239X
FU Novartis Pharmaceuticals; Amgen
FX The consensus conference was supported by educational grants provided by
Novartis Pharmaceuticals, Amgen, Inc., and Merck & Co. Editorial
assistance was provided by InforMEDical Communications, Inc., Carlisle,
MA.
NR 50
TC 35
Z9 36
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 OCT 15
PY 2008
VL 14
IS 20
BP 6387
EP 6395
DI 10.1158/1078-0432.CCR-08-1572
PG 9
WC Oncology
SC Oncology
GA 364TZ
UT WOS:000260359600006
PM 18927277
ER
PT J
AU Sabo, E
Meitner, PA
Tavares, R
Corless, CL
Lauwers, GY
Moss, SF
Resnick, MB
AF Sabo, Edmond
Meitner, Patricia A.
Tavares, Rosemarie
Corless, Christopher L.
Lauwers, Gregory Y.
Moss, Steven F.
Resnick, Murray B.
TI Expression Analysis of Barrett's Esophagus - Associated High-Grade
Dysplasia in Laser Capture Microdissected Archival Tissue
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GELATINASE-ASSOCIATED LIPOCALIN; SQUAMOUS-CELL CARCINOMA; BREAST-CANCER
PATIENTS; GENE-EXPRESSION; EPIDERMAL DIFFERENTIATION; NEOPLASTIC
PROGRESSION; TOPOISOMERASE-I; GASTRIC-CANCER; UP-REGULATION;
ADENOCARCINOMA
AB Purpose: Identifying genes differentially expressed in nonclysplastic BE (NDBE) from those expressed in high-grade clysplasia (HGD) should be of value in improving our understanding of this transition and may yield new diagnostic and/or prognostic markers. The aim of this study was to determine the differential transcriptome of HGD compared with NDBE through gene microarray analysis of epithelial cells microdissected from archival tissue specimens.
Experimental Design: Laser capture microdissection was used to isolate epithelial cells from adjacent inflammatory and stromal cells. Epithelial mRNA was extracted from areas of NDBE and HGD in matched biopsies from 11 patients. mRNA was reverse transcribed and applied on Affymetrix cDNA microarray chips customized for formalin-exposed tissue. For a subset of these genes, differential gene expression was confirmed by real-time PCR and immunohistochemistry.
Results: There were 131 genes overexpressed by at least 2.5-fold in HGD versus NDBE and 16 genes that were underexpressed by at least 2.5-fold. Among the overexpressed genes are several previously shown to be increased in the neoplastic progression of BE, as well as novel genes such as lipocalin-2, S100A9, matrix metallopeptidase 12, secernin 1, and topoisomerase II alpha. Genes decreased in dysplastic epithelium include MUC5AC, trefoil factor 1 (TFF1), meprin A, and CD13. Real-time PCR validated the changes in expression in 24 of 28 selected genes. Immunohistochemistry confirmed increased protein expression for topoisomerase II alpha, S100A9, and lipocalin-2 and decreased expression of TFF1 across the spectrum of BE-associated clysplasia from NDBE through adenocarcinoma.
Conclusions: This is the first study to identify epithelial genes differentially expressed in HGD versus NDBE in matched patient samples. The genes identified include several previously implicated in the pathogenesis of BE-associated dysplasia and new candidates for further investigation.
C1 [Sabo, Edmond; Meitner, Patricia A.; Tavares, Rosemarie; Resnick, Murray B.] Brown Univ, Rhode Isl Hosp, Dept Pathol, Providence, RI 02903 USA.
[Moss, Steven F.] Brown Univ, Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA.
[Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA.
[Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Resnick, MB (reprint author), Brown Univ, Rhode Isl Hosp, Dept Pathol, APC12,593 Eddy St, Providence, RI 02903 USA.
EM mresnick@lifespan.org
FU NIH [P20 RR17695]
FX Molecular Pathology Core of the COBRE Center for Cancer Research
Development and NIH grant P20 RR17695, awarded by the National Center
for Research Resources, Institutional Development Award Program.
NR 54
TC 25
Z9 26
U1 0
U2 0
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 OCT 15
PY 2008
VL 14
IS 20
BP 6440
EP 6448
DI 10.1158/1078-0432.CCR-08-0302
PG 9
WC Oncology
SC Oncology
GA 364TZ
UT WOS:000260359600012
PM 18927283
ER
PT J
AU Girnun, GD
Chen, L
Silvaggi, J
Drapkin, R
Chirieac, LR
Padera, RF
Upadhyay, R
Vafai, SB
Weissleder, R
Mahmood, U
Naseri, E
Buckley, S
Li, D
Force, J
McNamara, K
Demetri, G
Spiegelman, BM
Wong, KK
AF Girnun, Geoffrey D.
Chen, Liang
Silvaggi, Jessica
Drapkin, Ronny
Chirieac, Lucian R.
Padera, Robert F.
Upadhyay, Rabi
Vafai, Scott B.
Weissleder, Ralph
Mahmood, Umar
Naseri, Elnaz
Buckley, Stephanie
Li, Danan
Force, Jeremy
McNamara, Kate
Demetri, George
Spiegelman, Bruce M.
Wong, Kwok-Kin
TI Regression of Drug-Resistant Lung Cancer by the Combination of
Rosiglitazone and Carboplatin
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; GAMMA LIGAND TROGLITAZONE; HUMAN BREAST-CANCER;
PPAR-GAMMA; K-RAS; PHASE-II; SOLID TUMORS; COLON-CANCER; MUTATIONS; EGFR
AB Purpose: Current therapy for lung cancer involves multimodality therapies. However, many patients are either refractory to therapy or develop drug resistance. KRAS and epidermal growth factor receptor (EGFR) mutations represent some of the most common mutations in lung cancer, and many studies have shown the importance of these mutations in both carcinogenesis and chemoresistance. Genetically engineered murine models of mutant EGFR and KRAS have been developed that more accurately recapitulate human lung cancer, Recently, using cell-based experiments, we showed that platinum-based drugs and the anticliabetic drug rosiglitazone (PPAR gamma ligand) interact synergistically to reduce cancer cell and tumor growth. Here, we directly determined the efficacy of the PPAR gamma/carboplatin combination in these more relevant models of drug resistant non-small cell lung cancer.
Experimental Design: Tumorigenesis was induced by activation of either mutant KRAS or EGFR. Mice then received either rosiglitazone or carboplatin monotherapy, or a combination of both drugs. Change in tumor burden, pathology, and evidence of apoptosis and cell growth were assessed.
Results: Tumor burden remained unchanged or increased in the mice after monotherapy with either rosiglitazone or carboplatin. In striking contrast, we observed significant tumor shrinkage in mice treated with these drugs in combination. Immunohistochemical analyses showed that this synergy was mediated via both increased apoptosis and decreased proliferation. Importantly, this synergy between carboplatin and rosiglitazone did not increase systemic toxicity.
Conclusions: These data show that the PPAR gamma ligand/carboplatin combination is a new therapy worthy of clinical investigation in lung cancers, including those cancers that show primary resistance to platinum therapy or acquired resistance to targeted therapy.
C1 [Girnun, Geoffrey D.; Buckley, Stephanie] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Girnun, Geoffrey D.; Silvaggi, Jessica; Vafai, Scott B.; Naseri, Elnaz; Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA.
[Upadhyay, Rabi; Weissleder, Ralph; Mahmood, Umar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA.
[Chen, Liang; Drapkin, Ronny; Li, Danan; Force, Jeremy; McNamara, Kate; Demetri, George; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chen, Liang; Li, Danan; Force, Jeremy; McNamara, Kate; Demetri, George] Dana Farber Harvard Ctr Canc, Ludwig Ctr, Boston, MA USA.
[Drapkin, Ronny; Chirieac, Lucian R.; Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Demetri, George; Wong, Kwok-Kin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
RP Girnun, GD (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Off Bressler Res Bldg 10-039,Lab Bressler Res Bld, Baltimore, MD 21201 USA.
EM ggirnun@som.umaryland.edu; kwong1@partners.org
RI Drapkin, Ronny/E-9944-2016;
OI Drapkin, Ronny/0000-0002-6912-6977; wong, kwok kin/0000-0001-6323-235X
FU NIH [K08 AG024004, R01 CA122794, R01 AG2400401, K01 DK064685,
R37DK31405]; Sidney Kimmel Foundation; Joan Scarangello Foundation;
Cecily and Robert Harris Foundation; University of Maryland/Greenebaum
Cancer Center CRF
FX NIH grant K08 AG024004, R01 CA122794, R01 AG2400401, the Sidney Kimmel
Foundation for Cancer Research, the Joan Scarangello Foundation to
Conquer Lung Cancer, the Cecily and Robert Harris Foundation, and the
Flight Attendant Medical Research Institute (K.K. Wong); NIH grant K01
DK064685, and the University of Maryland/Greenebaum Cancer Center CRF
(G,D. Girnun); NIH MERIT award (B.M. Spiegelman); and R37DK31405 (J.
Silvaggi).
NR 52
TC 48
Z9 48
U1 1
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2008
VL 14
IS 20
BP 6478
EP 6486
DI 10.1158/1078-0432.CCR-08-1128
PG 9
WC Oncology
SC Oncology
GA 364TZ
UT WOS:000260359600016
PM 18927287
ER
PT J
AU Kondo, E
Maecker, B
Weihrauch, MR
Wickenhauser, C
Zeng, WY
Nadler, LM
Schultze, JL
von Bergwelt-Baildon, MS
AF Kondo, Eisei
Maecker, Britta
Weihrauch, Martin R.
Wickenhauser, Claudia
Zeng, WanYong
Nadler, Lee M.
Schultze, Joachim L.
von Bergwelt-Baildon, Michael S.
TI Cyclin D1-Specific Cytotoxic T Lymphocytes Are Present in the Repertoire
of Cancer Patients: Implications for Cancer Immunotherapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CD40-ACTIVATED B-CELLS; INDEPENDENT BINDING; EPITHELIAL-CELLS;
IMMUNE-RESPONSE; SELF-TOLERANCE; TUMOR-ANTIGENS; PROTEIN;
IDENTIFICATION; EXPRESSION; SELECTION
AB Purpose: Cyclin D1, a key cell cycle regulator, is overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for cancer immunotherapy. Nevertheless, it had previously been suggested that efficient T cells recognizing cyclin D1 derived epitopes are absent from the repertoire because of thymic deletion. We attempted to induce autologous CTL from healthy donors and patients with cyclin D1-overexpressing tumors using a highly efficient T-cell expansion system based on CD40-activated B cells as antigen-presenting cells.
Experimental Design: Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used for T-cell stimulation. The generated CTL lines and clones were analyzed by IFN-gamma enzyme-linked immunosorbent spot assay or cytolysis assay.
Results: After screening, at least two naturally processed and presented HLA-A*0201 - binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2(+) donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201 - matched, primary cyclin D1(+) tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1(+) colon cancer.
Conclusions: These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy.
C1 [Kondo, Eisei; Weihrauch, Martin R.; von Bergwelt-Baildon, Michael S.] Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany.
[Kondo, Eisei; Weihrauch, Martin R.; von Bergwelt-Baildon, Michael S.] Univ Hosp Cologne, Max Eder Nachwuchsgrp Deutschen Krebshilfe, D-50924 Cologne, Germany.
[Wickenhauser, Claudia] Univ Hosp Cologne, Inst Pathol, D-50924 Cologne, Germany.
[Maecker, Britta] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany.
[Zeng, WanYong; Nadler, Lee M.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Nadler, Lee M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Nadler, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Schultze, Joachim L.] Univ Bonn, Lab Genom & Immunoregulat, D-5300 Bonn, Germany.
RP von Bergwelt-Baildon, MS (reprint author), Univ Hosp Cologne, Max Eder Nachwuchsgrp, Joseph Stelzmann Str 9,Haus 16, D-50924 Cologne, Germany.
EM michael.bergwelt@uk-koeln.de
RI Kondo, Eisei/F-2791-2010; Schultze, Joachim/D-7794-2011
OI Kondo, Eisei/0000-0003-0995-9405; Schultze, Joachim/0000-0003-2812-9853
FU Deutsche Krebshilfe; Alexander von Humboldt Stiftung; Kanae Foundation;
Deutsche Forschungsgemeinschaft; Multiple Myeloma Research Foundation;
NIH [P01-CA-66996, P01-CA-78378]; Leukemia and Lymphoma Society
FX The Mildred Scheel Scholarship and Max-Eder Young Investigator Award
from Deutsche Krebshilfe (M.S. von Bergwelt-Baildon), the Alexander von
Humboldt Stiftung and Kanae Foundation for Life and Socio-Medical
Science (E Kondo), the Deutsche Forschungsgemeinschaft and Multiple
Myeloma Research Foundation (B. Maecker), NIH grants P01-CA-66996 and
P01-CA-78378 (L.M. Nadler), and a Sofja Kovalevskaja Award by the
Alexander von Humboldt Foundation and a Translational Research Award by
the Leukemia and Lymphoma Society (J.L. Schultze).
NR 40
TC 12
Z9 12
U1 0
U2 1
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 OCT 15
PY 2008
VL 14
IS 20
BP 6574
EP 6579
DI 10.1158/1078-0432.CCR-08-0825
PG 6
WC Oncology
SC Oncology
GA 364TZ
UT WOS:000260359600027
PM 18927298
ER
PT J
AU Mudumana, SP
Hentschel, D
Liu, Y
Vasilyev, A
Drummond, IA
AF Mudumana, Sudha P.
Hentschel, Dirk
Liu, Yan
Vasilyev, Aleksandr
Drummond, Iain A.
TI odd skipped related1 reveals a novel role for endoderm in regulating
kidney versus vascular cell fate
SO DEVELOPMENT
LA English
DT Article
DE odd-skipped related; endoderm; pronephros; vasculature; glomerulus;
kidney development; zebrafish
ID ZEBRAFISH PRONEPHROS; POSTERIOR MESODERM; XENOPUS-LAEVIS; EXPRESSION
ANALYSIS; ENDOTHELIAL-CELLS; GENE; DIFFERENTIATION; BMP; HEART;
VASCULOGENESIS
AB The kidney and vasculature are intimately linked both functionally and during development, when nephric and blood/vascular progenitor cells occupy adjacent bands of mesoderm in zebrafish and frog embryos. Developmental mechanisms that underlie the differentiation of kidney versus blood/vascular lineages remain unknown. The odd skipped related1 (osr1) gene encodes a zinc-finger transcription factor that is expressed in the germ ring mesendoderm and subsequently in the endoderm and intermediate mesoderm, prior to the expression of definitive kidney or blood/vascular markers. Knockdown of osr1 in zebrafish embryos resulted in a complete, segment-specific loss of anterior kidney progenitors and a compensatory increase in the number of angioblast cells in the same trunk region. Histology revealed a subsequent absence of kidney tubules, an enlarged cardinal vein and expansion of the posterior venous plexus. Altered kidney versus vascular development correlated with expanded endoderm development in osr1 knockdowns. Combined osr1 loss of function and blockade of endoderm development by knockdown of sox32/casanova rescued anterior kidney development. The results indicate that osr1 activity is required to limit endoderm differentiation from mesendoderm; in the absence of osr1, excess endoderm alters mesoderm differentiation, shifting the balance from kidney towards vascular development.
C1 [Mudumana, Sudha P.; Liu, Yan; Vasilyev, Aleksandr; Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA.
[Hentschel, Dirk] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA.
RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA.
EM idrummon@receptor.mgh.harvard.edu
FU National Institute of Health [DK071041]; American Heart Association
[0625923T]
FX We thank personnel in the Fish facility at MGH for help with fish
husbandry, Dr Alan Davidson for the swirl mutant and for comments on
this work, Dr Jing Wei Xiong for bonnie and clyde mutants and
blood/vascular lineage markers, Randy Peterson and Chetana Sachidanandan
for endoderm markers, Sasha Petrova for editing this manuscript, and Dr
Tom Schultheiss for critical review of the data. This work was funded by
a National Institute of Health grant (DK071041) to I.A.D. and by a
postdoctoral fellowship from American Heart Association (0625923T) to S.
P. M.
NR 79
TC 31
Z9 32
U1 0
U2 0
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 OCT 15
PY 2008
VL 135
IS 20
BP 3355
EP 3367
DI 10.1242/dev.022830
PG 13
WC Developmental Biology
SC Developmental Biology
GA 353LH
UT WOS:000259568600005
PM 18787069
ER
PT J
AU Wang, LB
Sewell, WF
Kim, SD
Shin, JT
MacRae, CA
Zon, LI
Seidman, JG
Seidman, CE
AF Wang, Libin
Sewell, William F.
Kim, Sang D.
Shin, Jordan T.
MacRae, Calum A.
Zon, Leonard I.
Seidman, J. G.
Seidman, Christine E.
TI Eya4 regulation of Na(+)/K(+)-ATPase is required for sensory system
development in zebrafish
SO DEVELOPMENT
LA English
DT Article
DE eya4; Na(+)/K(+)-ATPase; hair cells; myocardium; neuromast; otic vesicle
ID SENSORINEURAL HEARING-LOSS; BETA-SUBUNIT GENES; INNER-EAR; EYES ABSENT;
ALPHA-SUBUNIT; DILATED CARDIOMYOPATHY; TRANSCRIPTION FACTORS;
LATERAL-LINE; K-ATPASE; NA,K-ATPASE
AB To investigate the mechanisms by which mutations in the human transcriptional co-activator EYA4 gene cause sensorineural hearing loss that can occur in association with dilated cardiomyopathy, we studied eya4 expression during zebrafish development and characterized eya4 deficiency. eya4 morphant fish embryos had reduced numbers of hair cells in the otic vesicle and lateral line neuromasts with impaired sensory responses. Analyses of candidate genes that are known to be expressed in a temporal and spatial pattern comparable to eya4 focused our analyses on atp1b2b, which encodes the beta 2b subunit of the zebrafish Na(+)/K(+)-ATPase. We demonstrate atp1b2b levels are reduced in eya4 morphant fish and that morpholino oligonucleotides targeting the atp1b2b gene recapitulated the eya4 deficiency phenotypes, including heart failure, decreased sensory hair cell numbers in the otic vesicle and neuromasts, and abnormal sensory responses. Furthermore, atp1b2b overexpression rescued these phenotypes in eya4 morphant fish. We conclude that eya4 regulation of Na(+)/K(+)-ATPase is crucial for the development of mechanosensory cells and the maintenance of cardiac function in zebrafish.
C1 [Wang, Libin; Kim, Sang D.; Seidman, J. G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Wang, Libin; Zon, Leonard I.; Seidman, J. G.; Seidman, Christine E.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Sewell, William F.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA.
[Sewell, William F.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA.
[Sewell, William F.] MEEI, Boston, MA 02114 USA.
[Shin, Jordan T.; MacRae, Calum A.] Massachusetts Gen Hosp, Dev Biol Lab, Boston, MA 02129 USA.
[Shin, Jordan T.; MacRae, Calum A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA.
[Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
[Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Seidman, CE (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM cseidman@genetics.med.harvard.edu
FU Howard Hughes Medical Institute; National Institutes of Health
FX We greatly appreciate the scientific comments from David A. Conner and
his critical reading of the manuscript. We are grateful to Jost
Schonberger for his valuable discussions. We thank Jose
Rivera-Feliciano, Jenna Galloway, Sarah Keller, Haobing Wang, Yariv
Houvras, Bruce Barut and Susanne Bartlett for their technical
assistance. This work was supported by grants from the Howard Hughes
Medical Institute (C.E.S.) and the National Institutes of Health (J.G.S.
and C.E.S.).
NR 46
TC 23
Z9 25
U1 0
U2 3
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 OCT 15
PY 2008
VL 135
IS 20
BP 3425
EP 3434
DI 10.1242/dev.012237
PG 10
WC Developmental Biology
SC Developmental Biology
GA 353LH
UT WOS:000259568600011
PM 18799547
ER
PT J
AU Khatri, R
Schipani, E
AF Khatri, Richa
Schipani, Ernestina
TI About the importance of being desulfated
SO GENES & DEVELOPMENT
LA English
DT Article
DE Proteoglycan; desulfation; FGF; chondrocytes
ID MULTIPLE SULFATASE DEFICIENCY; ENDOPLASMIC-RETICULUM STRESS;
FIBROBLAST-GROWTH-FACTOR; MOLECULAR-MECHANISMS; BONE-DEVELOPMENT;
GENETIC-BASIS; AUTOPHAGY; HYPOXIA; BNIP3; CELLS
AB Sulfated proteoglycans have important structural and signaling functions in the growth plate. In the October 1, 2008, issue of Genes & Development, Settembre and colleagues (pp. 2645 - 2650) report that lack of SUMF1, a crucial enzyme in the activation of sulfatases, causes a severe chondrodysplasia by augmenting fibroblast growth factor signaling and by hampering the autophagic process, which the investigators show is constitutively on in chondrocytes. The findings highlight the essential role of desulfation in cartilage biology and organogenesis.
C1 [Khatri, Richa; Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
RP Schipani, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
EM schipani@helix.mgh.harvard.edu
FU NIH [RO1 AR048191-06]
FX This work was supported by NIH Grant RO1 AR048191-06 to E. S.
NR 37
TC 5
Z9 6
U1 0
U2 0
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD OCT 15
PY 2008
VL 22
IS 20
BP 2750
EP 2754
DI 10.1101/gad.1735508
PG 5
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 360QT
UT WOS:000260073200003
PM 18923073
ER
PT J
AU de Bakker, PIW
Ferreira, MAR
Jia, XM
Neale, BM
Raychaudhuri, S
Voight, BF
AF de Bakker, Paul I. W.
Ferreira, Manuel A. R.
Jia, Xiaoming
Neale, Benjamin M.
Raychaudhuri, Soumya
Voight, Benjamin F.
TI Practical aspects of imputation-driven meta-analysis of genome-wide
association studies
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENETIC-ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; LARGE-SCALE;
POPULATION; STRATIFICATION; POWER; REPLICATION; COVERAGE; DISEASE
AB Motivated by the overwhelming success of genome-wide association studies, droves of researchers are working vigorously to exchange and to combine genetic data to expediently discover genetic risk factors for common human traits. The primary tools that fuel these new efforts are imputation, allowing researchers who have collected data on a diversity of genotype platforms to share data in a uniformly exchangeable format, and meta-analysis for pooling statistical support for a genotype-phenotype association. As many groups are forming collaborations to engage in these efforts, this review collects a series of guidelines, practical detail and learned experiences from a variety of individuals who have contributed to the subject.
C1 [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Partners Healthcare Syst Ctr Genet & Genom, Div Genet,Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA.
[de Bakker, Paul I. W.; Ferreira, Manuel A. R.; Neale, Benjamin M.; Raychaudhuri, Soumya; Voight, Benjamin F.] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Ferreira, Manuel A. R.; Neale, Benjamin M.; Raychaudhuri, Soumya; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Jia, Xiaoming] Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
RP de Bakker, PIW (reprint author), Brigham & Womens Hosp, New Res Bldg,Suite 168,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM pdebakker@rics.bwh.harvard.edu
RI Voight, Benjamin/F-1775-2011; de Bakker, Paul/B-8730-2009; Ferreira,
Manuel/D-3609-2013
OI de Bakker, Paul/0000-0001-7735-7858;
FU NIH [AR007530-23, KAR055688A]
FX S.R. is Supported by a T32 NIH training grant (AR007530-23), an NIH K08
grant (KAR055688A), and through the BWH Rheumatology Fellowship program.
NR 42
TC 294
Z9 300
U1 0
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2008
VL 17
BP R122
EP R128
DI 10.1093/hmg/ddn288
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 398XG
UT WOS:000262764200006
PM 18852200
ER
PT J
AU McCarroll, SA
AF McCarroll, Steven A.
TI Extending genome-wide association studies to copy-number variation
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID STRUCTURAL VARIATION; LINKAGE DISEQUILIBRIUM; LARGE-SCALE; FINE-SCALE;
DISEASE; SUSCEPTIBILITY; POLYMORPHISM; MULTIPLE; SCHIZOPHRENIA;
CONTRIBUTE
AB Appreciating the contribution of human genome copy-number variation (CNV) to clinical phenotypes is one of the compelling genetics challenges of the coming years. It is increasingly possible to pursue such investigations as an extension of genome-wide association studies (GWAS), enabled by innovations in the design and analysis of SNP (single nucleotide polymorphism) arrays and by progress in determining the genomic locations and population-genetic properties of the CNVs that segregate in the human population. Extensions of GWAS to CNV have already resulted in discoveries of both de novo and inherited CNV that are associated with risk of common disease. This review will discuss new approaches, recent findings and the analytical challenges involved in expanding GWAS to appreciate the contribution of CNV to human phenotypes.
C1 [McCarroll, Steven A.] MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[McCarroll, Steven A.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[McCarroll, Steven A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[McCarroll, Steven A.] Harvard Univ, Sch Med, Boston, MA USA.
RP McCarroll, SA (reprint author), MIT & Harvard, Broad Inst, Program Med & Populat Genet, 7 Cambridge Ctr,Room 6145, Cambridge, MA 02142 USA.
EM smccarro@broad.mit.edu
RI McCarroll, Steven/A-8433-2009
FU Lilly Life Sciences Research Fellowship
FX The author Would like to acknowledge support from a Lilly Life Sciences
Research Fellowship.
NR 37
TC 99
Z9 106
U1 1
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 15
PY 2008
VL 17
BP R135
EP R142
DI 10.1093/hmg/ddn282
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 398XG
UT WOS:000262764200008
PM 18852202
ER
PT J
AU Nery, FC
Zeng, J
Niland, BP
Hewett, J
Farley, J
Irimia, D
Li, YQ
Wiche, G
Sonnenberg, A
Breakefield, XO
AF Nery, Flavia C.
Zeng, Juan
Niland, Brian P.
Hewett, Jeffrey
Farley, Jonathan
Irimia, Daniel
Li, Yuqing
Wiche, Gerhard
Sonnenberg, Arnoud
Breakefield, Xandra O.
TI TorsinA binds the KASH domain of nesprins and participates in linkage
between nuclear envelope and cytoskeleton
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Nesprin; Dystonia; Cell migration; Nuclear polarization; DYT1; Vimentin;
Actin
ID DYSTONIA PROTEIN TORSINA; EARLY-ONSET DYSTONIA; INTERMEDIATE-FILAMENTS;
DYT1 DYSTONIA; ENDOPLASMIC-RETICULUM; IDIOPATHIC DYSTONIA; SECRETORY
PATHWAY; MEMBRANE PROTEIN; CULTURED-CELLS; MOTOR DEFICITS
AB A specific mutation(Delta E) in torsinA underlies most cases of the dominantly inherited movement disorder, early-onset torsion dystonia (DYT1). TorsinA, a member of the AAA+ ATPase superfamily, is located within the lumen of the nuclear envelope ( NE) and endoplasmic reticulum ( ER). We investigated an association between torsinA and nesprin-3, which spans the outer nuclear membrane (ONM) of the NE and links it to vimentin via plectin in fibroblasts. Mouse nesprin-3 alpha co-immunoprecipitated with torsinA and this involved the C-terminal region of torsinA and the KASH domain of nesprin-3 alpha. This association with human nesprin-3 appeared to be stronger for torsinA Delta E than for torsinA. TorsinA also associated with the KASH domains of nesprin-1 and -2 (SYNE1 and 2), which link to actin. In the absence of torsinA, in knockout mouse embryonic fibroblasts (MEFs), nesprin-3 alpha was localized predominantly in the ER. Enrichment of yellow fluorescent protein ( YFP)-nesprin-3 in the ER was also seen in the fibroblasts of DYT1 patients, with formation of YFP-positive globular structures enriched in torsinA, vimentin and actin. TorsinA-null MEFs had normal NE structure, but nuclear polarization and cell migration were delayed in a wound-healing assay, as compared with wild-type MEFs. These studies support a role for torsinA in dynamic interactions between the KASH domains of nesprins and their protein partners in the lumen of the NE, with torsinA influencing the localization of nesprins and associated cytoskeletal elements and affecting their role in nuclear and cell movement.
C1 [Nery, Flavia C.; Zeng, Juan; Niland, Brian P.; Hewett, Jeffrey; Farley, Jonathan; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02114 USA.
[Nery, Flavia C.; Zeng, Juan; Niland, Brian P.; Hewett, Jeffrey; Farley, Jonathan; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Dept Radiol, Boston, MA 02114 USA.
[Nery, Flavia C.; Zeng, Juan; Niland, Brian P.; Hewett, Jeffrey; Farley, Jonathan; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA.
[Irimia, Daniel] Massachusetts Gen Hosp, Dept Surg & Bioengn, BioMEMS Resource Ctr, Boston, MA 02114 USA.
[Li, Yuqing] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA.
[Li, Yuqing] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA.
[Wiche, Gerhard] Univ Vienna, Dept Mol Cell Biol, Max F Perutz Labs, A-1030 Vienna, Austria.
[Sonnenberg, Arnoud] Netherlands Canc Inst, Dept Cell Biol, NL-1066 CX Amsterdam, Netherlands.
RP Breakefield, XO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02114 USA.
EM breakefield@hms.harvard.edu
RI Li, Yuqing/G-1596-2011;
OI Li, Yuqing/0000-0003-1211-5529; Irimia, Daniel/0000-0001-7347-2082
FU Bachmann-Strauss Foundation; Jack Fasciana Fund for Support of Dystonia
Research; NINDS [NS037409]; Fondazione Telethon
FX We thank Phyllis Hanson for advice and help with electron microscopy
analysis; Brian Burke for advice and for the GFP-KASH constructs for
nesprin-1 and -2; John Heuser for electron microscopy; Igor Bagayev,
Thomas Wurdinger, Johan Skog and Bakhos Tannous for help with image
analysis; D. Cristopher Bragg for advice; Miguel Sena-Esteves for vector
generation; Pradeep Bhide and Deirdre McCarthy for help with timed
pregnancies and for advice; Ashira Gendelman, Lisa Pike and John Kuster
for data analysis; David Corey for his generosity in allowing us to use
his confocal microscope; and Suzanne McDavitt for skilled editorial
assistance. Funding was provided by the Bachmann-Strauss Foundation, the
Jack Fasciana Fund for Support of Dystonia Research and NINDS NS037409.
NR 68
TC 98
Z9 106
U1 0
U2 9
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD OCT 15
PY 2008
VL 121
IS 20
BP 3476
EP 3486
DI 10.1242/jcs.029454
PG 11
WC Cell Biology
SC Cell Biology
GA 358JD
UT WOS:000259912100020
PM 18827015
ER
PT J
AU Kaunitz, JD
Yamaguchi, DT
AF Kaunitz, Jonathan D.
Yamaguchi, Dean T.
TI TNAP, TrAP, Ecto-Purinergic Signaling, and Bone Remodeling
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE OSTEOBLAST: OSTEOCLAST; P2Y RECEPTORS; BONE REMODELING COMPARTMENT; BONE
LINING CELLS; BICARBONATE; EXTRACELLULAR pH
ID RESISTANT ACID-PHOSPHATASE; OSTEOBLAST-LIKE CELLS; UTERINE BICARBONATE
SECRETION; STIMULATED ATPASE ACTIVITY; ALKALINE-PHOSPHATASE;
CYSTIC-FIBROSIS; CARBONIC-ANHYDRASES; EPITHELIAL-CELLS; EXTRACELLULAR
PH; DEFICIENT MICE
AB Bone remodeling is a process of continuous resorption and formation/mineralization carried out by osteoclasts and osteoblasts, which, along with osteocytes, comprise the bone multicellular unit (BMU). A key component of the BMU is the bone remodeling compartment (BRC), isolated from the marrow by a canopy of osteoblast-like lining cells. Although much progress has been made regarding the cytokine-dependent and hormonal regulation of bone remodeling, less attention has been placed on the role of extracellular pH (pH(e)). Osteoclastic bone resorption occurs at acidic pH(e). Furthermore, osteoclasts can be regarded as epithelial-like cells, due to their polarized structure and ability to form a seal against bone, isolating the lacunar space. The major ecto-phosphatases of osteoclasts and osteoblasts, acid and alkaline phosphatases, both have ATPase activity with pH optima several units different from neutrality. Furthermore, osteoclasts and osteoblasts express plasma membrane purinergic P2 receptors that, upon activation by ATP, accelerate bone osteoclast resorption and impair osteoblast mineralization. We hypothesize that these ecto-phosphatases help regulate [ATP](e) and localized pH(e) at the sites of bone resorption and mineralization by pH-dependent ATP hydrolysis coupled with P2Y-dependent regulation of osteoclast and osteoblast function. Furthermore, osteoclast cellular HCO(3)(-), formed as a product of lacunar V-ATPase H(+) secretion, is secreted into the BRC, which could elevate BRC pH(e), in turn affecting osteoblast function. We will review the existing data addressing regulation of BRC pH(e), present a hypothesis regarding its regulation, and discuss the hypothesis in the context of the function of proteins that regulate pH(e). J. Cell. Biochem. 105: 655-662, 2008. (c) 2008 Wiley-Liss, Inc.
C1 [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Div Gastroenterol, Dept Med, Los Angeles, CA 90073 USA.
[Kaunitz, Jonathan D.; Yamaguchi, Dean T.] Univ Calif Los Angeles, Sch Med, Greater Los Angeles Vet Affairs Hlth Syst, Res Serv, Los Angeles, CA 90073 USA.
[Kaunitz, Jonathan D.; Yamaguchi, Dean T.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA.
RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM jake@ucla.edu
FU Medical Service, West Los Angeles Veterans Affairs Medical Center
FX We thank Dr. Baruch Frenkel and Dr. Yasutada Akiba for their kind,
informed, and helpful advice, the Medical Service, West Los Angeles
Veterans Affairs Medical Center for its support, and Jenifer Kugler for
her editorial assistance.
NR 75
TC 51
Z9 54
U1 0
U2 11
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD OCT 15
PY 2008
VL 105
IS 3
BP 655
EP 662
DI 10.1002/jcb.21885
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 388MH
UT WOS:000262023400005
PM 18773425
ER
PT J
AU Zhang, XY
Yu, SB
Galson, DL
Luo, M
Fan, J
Zhang, J
Guan, YF
Xiao, GZ
AF Zhang, Xiaoyan
Yu, Shibing
Galson, Deborah L.
Luo, Min
Fan, Jie
Zhang, Jian
Guan, Youfei
Xiao, Guozhi
TI Activating Transcription Factor 4 Is Critical for Proliferation and
Survival in Primary Bone Marrow Stromal Cells and Calvarial Osteoblasts
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE ATF4; OSTEOBLASTS; PROLIFERATION; APOPTOSIS; CELL CYCLE; CYCLIN D1
ID OSTEOCALCIN GENE-EXPRESSION; DNA-BINDING PROTEINS; CYCLIN D1 PROMOTER;
RESPONSE ELEMENT; LEUCINE-ZIPPER; TARGETED DISRUPTION;
PARATHYROID-HORMONE; ANABOLIC ACTIONS; IN-VITRO; ATF4
AB Activating transcription factor 4 (ATF4) is essential for bone formation. However, the mechanism of its actions in bone is poorly understood. The present study examined the role for ATF4 in the regulation of proliferation and survival of primary mouse bone marrow stromal cells (BMSCs) and osteoblasts. Results showed that Atf4(-/-) cells display a severe proliferative defect as measured by multiple cell proliferation assays. Cell cycle progression of Atf4(-/-) BMSCs was largely delayed with significant G1 arrest. Expression of cyclin D1 was decreased both at the mRNA and protein level. A similar proliferation defect was observed in Atf4(-/-) calvarial periosteal osteoblasts when compared with wt control. Knocking down Atf4 mRNA by small interfering RNA in MC3T3-E1 subclone 4 preosteoblasts markedly reduced expression of cyclin D1 and cell proliferation. In contrast, overexpression of ATF4 increased cyclin D1 expression as well as cell proliferation in AV4(-/-) BMSCs. In addition, apoptosis was significantly increased in Atf4(-/-) BMSCs and calvarial periosteal osteoblasts relative to wt controls. Taken together, these results for the first time demonstrate that ATF4 is a critical regulator of proliferation and survival in BMSCs and osteoblasts in vitro and in vivo. J. Cell. Biochem. 105: 885-895, 2008. (C) 2008 Wiley-Liss, Inc.
C1 [Zhang, Xiaoyan; Yu, Shibing; Galson, Deborah L.; Luo, Min; Zhang, Jian; Xiao, Guozhi] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15240 USA.
[Zhang, Xiaoyan; Guan, Youfei] Peking Beijing Univ Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100083, Peoples R China.
[Fan, Jie] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15240 USA.
RP Xiao, GZ (reprint author), VA Pittsburgh Healthcare Syst, Rm 2E-109,151-U, Pittsburgh, PA 15240 USA.
EM xiaog@upmc.edu
RI Perez , Claudio Alejandro/F-8310-2010; YU, SHIBING/B-7648-2012; Galson,
Deborah/E-9370-2010
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Galson,
Deborah/0000-0002-2045-8807
FU NIH [DK072230]; Department of Defense [W81XWH-07-1-0160]; China National
Natural Science Foundation [NNSF 30530340, NNSF 30725033]
FX Thanks to Diane George and Dr. Scott Kulich ofthe VA Pittsburgh
Healthcare System for assistance in bone histology and the Nucleofector
electroporation transfection, respectively. This work was supported by
an NIH Grant DK072230 and a Department of Defense Grant W81XWH-07-1-0160
(to GX) and two China National Natural Science Foundation grants NNSF
30530340 and NNSF 30725033 (to Y.G).
NR 54
TC 16
Z9 17
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD OCT 15
PY 2008
VL 105
IS 3
BP 885
EP 895
DI 10.1002/jcb.21888
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 388MH
UT WOS:000262023400028
PM 18729081
ER
PT J
AU Stevceva, L
Yoon, V
Carville, A
Pacheco, B
Santosuosso, M
Korioth-Schmitz, B
Mansfield, K
Poznansky, MC
AF Stevceva, Liljana
Yoon, Victor
Carville, Angela
Pacheco, Beatriz
Santosuosso, Michael
Korioth-Schmitz, Birgit
Mansfield, Keith
Poznansky, Mark C.
TI The efficacy of T cell-mediated immune responses is reduced by the
envelope protein of the chimeric HIV-1/SIV-KB9 virus in vivo
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; HUMAN
MONOCLONAL-ANTIBODIES; RHESUS-MONKEYS; HIV-1 GP120; MULTIDRUG-RESISTANT;
DISEASE PROGRESSION; LYMPHOCYTE RESPONSE; RAPID PROGRESSION; SYNTHETIC
PEPTIDE
AB Gp120 is a critical component of the envelope of HIV-1. Its role in viral entry is well described. In view of its position on the viral envelope, gp120 is a part of the retrovirus that immune cells encounter first and has the potential to influence antiretroviral immune responses. We propose that high levels of gp120 are present in tissues and may contribute to the failure of the immune system to fully control and ultimately clear the virus. Herein, we show for the first time that lymphoid tissues from acutely HIV-1/SIV (SHIV)-KB9-infected macaques contain deposits of gp120 at concentrations that are high enough to induce suppressive effects on T cells, thus negatively regulating the antiviral CTL response and contributing to virus survival and persistence. We also demonstrate that SHIV-KB9 gp120 influences functional T cell responses during SHIV infection in a manner that suppresses degranulation and cytokine secretion by CTLs. Finally, we show that regulatory T cells accumulate in lymphoid tissues during acute infection and that they respond to gp120 by producing TGF beta, a known suppressant of cytotoxic T cell activity. These findings have significant implications for our understanding of the contribution of non-entry-related functions of HIV-1 gp120 to the pathogenesis of HIV/AIDS.
C1 [Stevceva, Liljana; Yoon, Victor; Santosuosso, Michael; Poznansky, Mark C.] Massachusetts Gen Hosp East, Partners AIDS Res Ctr & Infect Dis Med, Boston, MA 02129 USA.
[Carville, Angela; Mansfield, Keith] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA.
[Pacheco, Beatriz] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Korioth-Schmitz, Birgit] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
RP Stevceva, L (reprint author), Massachusetts Gen Hosp East, Partners AIDS Res Ctr & Infect Dis Med, Bldg 149,Room 5234, Boston, MA 02129 USA.
EM lstevceva@hotmail.com; mpoznansky@partners.org
RI Korioth-Schmitz, Birgit/M-7816-2015
OI Korioth-Schmitz, Birgit/0000-0002-5271-9223
FU Public Health Service [R01 AI49757, T32A1007387]
FX M.C.P. and L.S. were supported by Public Health Service Grants R01
AI49757 and T32A1007387, respectively.
NR 87
TC 11
Z9 11
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2008
VL 181
IS 8
BP 5510
EP 5521
PG 12
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300043
PM 18832708
ER
PT J
AU Gelati, M
Aplin, AC
Fogel, E
Smith, KD
Nicosia, RF
AF Gelati, Maurizio
Aplin, Alfred C.
Fogel, Eric
Smith, Kelly D.
Nicosia, Roberto F.
TI The angiogenic response of the aorta to injury and inflammatory
cytokines requires macrophages
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-ASSOCIATED MACROPHAGES;
LIPOSOME-MEDIATED DEPLETION; STIMULATING FACTOR-I; RAT AORTA;
GENE-THERAPY; CXCR2; MODEL; VIVO; NEOVASCULARIZATION
AB The purpose of this study was to define early events during the angiogenic response of the aortic wall to injury. Rat aortic rings produced neovessels in collagen culture but lost this capacity over time. These quiescent rings responded to vascular endothelial growth factor but not to a mixture of macrophage-stimulatory cytokines and chemokines that was angiogenically active on fresh rings. Analysis of cytokine receptor expression revealed selective loss in quiescent rings of the proangiogenic chemokine receptor CXCR2, which was expressed predominantly in aortic macrophages. Pharmacologic inhibition of CXCR2 impaired angiogenesis from fresh rings but had no effect on vascular endothelial growth factor-induced angiogenesis from quiescent explants. Angiogenesis was also impaired in cultures of aortic rings from CXCR2-deficient mice. Reduced CXCR2 expression in quiescent rat aortic rings correlated with marked macrophage depletion. Pharmacologic ablation of macrophages from aortic explants blocked formation of neovessels in vitro and reduced aortic ring-induced angiogenesis in vivo. The angiogenic response of macrophage-depleted rings was completely restored by adding exogenous macrophages. Moreover, angiogenesis from fresh rings was promoted by macrophage CSF (CSF-1) and inhibited with anti-CSF-1 Ab. Thus, aortic angiogenic sprouting following injury is strongly influenced by conditions that modulate resident macrophage numbers and function.
C1 [Gelati, Maurizio] Carlo Besta Inst, Lab Neurobiol & Neuroregenerat Med, Milan, Italy.
[Aplin, Alfred C.; Smith, Kelly D.; Nicosia, Roberto F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Fogel, Eric; Nicosia, Roberto F.] Vet Adm Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Seattle, WA 98108 USA.
RP Nicosia, RF (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Pathol & Lab Med S Lab 113, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM roberto.nicosia@va.gov
RI Gelati, Maurizio/H-2110-2016
OI Gelati, Maurizio/0000-0002-4828-9849
FU National Heart, Lung, and Blood Institute [HL52585]; Department of
Veterans Affairs Medical Research Service
FX Supported by National Heart, Lung, and Blood Institute Grant HL52585 and
by a Merit Review Grant from the Department of Veterans Affairs Medical
Research Service.
NR 48
TC 24
Z9 25
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2008
VL 181
IS 8
BP 5711
EP 5719
PG 9
WC Immunology
SC Immunology
GA 359YX
UT WOS:000260025300065
PM 18832730
ER
PT J
AU Benn, CL
Sun, T
Sadri-Vakili, G
McFarland, KN
DiRocco, DP
Yohrling, GJ
Clark, TW
Bouzou, B
Cha, JHJ
AF Benn, Caroline L.
Sun, Tingting
Sadri-Vakili, Ghazaleh
McFarland, Karen N.
DiRocco, Derek P.
Yohrling, George J.
Clark, Timothy W.
Bouzou, Berengere
Cha, Jang-Ho J.
TI Huntingtin Modulates Transcription, Occupies Gene Promoters In Vivo, and
Binds Directly to DNA in a Polyglutamine-Dependent Manner
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE transcription factor; chromatin immunoprecipitation; DNA microarrays;
polyglutamine; gene expression; DNA conformation
ID DISEASE TRANSGENIC MICE; INTRANUCLEAR INCLUSIONS; REPRESSES
TRANSCRIPTION; MEDIATED TRANSCRIPTION; NUCLEAR-LOCALIZATION; STRIATAL
CELLS; PROTEIN; EXPRESSION; COMPLEXES; INTERACTS
AB Transcriptional dysregulation is a central pathogenic mechanism in Huntington's disease, a fatal neurodegenerative disorder associated with polyglutamine ( polyQ) expansion in the huntingtin (Htt) protein. In this study, we show that mutant Htt alters the normal expression of specific mRNA species at least partly by disrupting the binding activities of many transcription factors which govern the expression of the dysregulated mRNA species. Chromatin immunoprecipitation (ChIP) demonstrates Htt occupation of gene promoters in vivo in a polyQ-dependent manner, and furthermore, ChIP-on-chip and ChIP subcloning reveal that wild-type and mutant Htt exhibit differential genomic distributions. Exon 1 Htt binds DNA directly in the absence of other proteins and alters DNA conformation. PolyQ expansion increases Htt-DNA interactions, with binding to recognition elements of transcription factors whose function is altered in HD. Together, these findings suggest mutant Htt modulates gene expression through abnormal interactions with genomic DNA, altering DNA conformation and transcription factor binding.
C1 [Benn, Caroline L.; Sun, Tingting; Sadri-Vakili, Ghazaleh; McFarland, Karen N.; DiRocco, Derek P.; Yohrling, George J.; Cha, Jang-Ho J.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA.
[Clark, Timothy W.; Bouzou, Berengere] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Ctr Interdisciplinary Informat, Charlestown, MA 02129 USA.
[Yohrling, George J.] Galleon Pharmaceut, Horsham, PA 19044 USA.
RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA.
EM cha@helix.mgh.harvard.edu
RI McFarland, Karen/H-1890-2011;
OI Clark, Timothy/0000-0003-4060-7360
FU National Institutes of Health [NS38106, NS45242]
FX This work was supported by the Huntington's Disease Society of America
Coalition for the Cure Program, the Glendorn Foundation, National
Institutes of Health Grants NS38106 and NS45242, and the Massachusetts
General Hospital Fund for Medical Discovery (C. L. B.). Wewould like to
acknowledge the expert and generous guidance of Erik Nelson and David
Frank (Dana Farber Cancer Institute, Boston, MA) with ChIP subcloning.
Human brain samples were generously provided by the Alzheimer's Research
Disease Center at Massachusetts General Hospital. We thank Marcy E.
MacDonald (Massachusetts General Hospital, Boston, MA) for generously
sharing the STHdh striatal cell lines. We are grateful to Eileen M.
Denovan-Wright and Geraldine Gomez (Dalhousie University, Halifax,
Canada) for help with DNase footprinting assays and helpful discussions.
We thank Prianka Chawla, Kelly E. Glajch, Ryan P. Overland, Arjun Vasan,
and Samuel Bitoun for technical assistance. We are indebted to Weiguo
Zhai and Robert Tjian for helpful discussions regarding the RAP30 and
RAP74 chromatin immunoprecipitations. Finally, we especially thank
Gillian P. Bates for her insightful comments, constructive discussions,
and help with Southern blotting.
NR 60
TC 90
Z9 92
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 OCT 15
PY 2008
VL 28
IS 42
BP 10720
EP 10733
DI 10.1523/JNEUROSCI.2126-08.2008
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 360MC
UT WOS:000260060600026
PM 18923047
ER
PT J
AU Razansky, D
Vinegoni, C
Ntziachristos, V
AF Razansky, Daniel
Vinegoni, Claudio
Ntziachristos, Vasilis
TI Polarization-sensitive optoacoustic tomography of optically diffuse
tissues
SO OPTICS LETTERS
LA English
DT Article
ID PHOTOACOUSTIC TOMOGRAPHY; IN-VIVO; MICROSCOPY; DICHROISM; LIGHT
AB Polarization is indicative of material anisotropy, a property that reveals structural orientation information of molecules inside the material. Herein we investigate whether polarization can be detected optoacoustically in scattering and absorbing tissues. Using a laboratory prototype of polarization-sensitive optoacoustic tomography, we demonstrate high-resolution reconstructions of dichroism. contrast deep in optically diffusive tissue-mimicking phantoms. The technique is expected to enable highly accurate imaging of polarization contrast in tissues, far beyond the current capabilities of pure optical polarization-imaging approaches. (C) 2008 Optical Society of America
C1 [Razansky, Daniel; Ntziachristos, Vasilis] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany.
[Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, Sch Med, D-81675 Munich, Germany.
[Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, Sch Elect Engn, D-81675 Munich, Germany.
[Razansky, Daniel; Vinegoni, Claudio; Ntziachristos, Vasilis] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Boston, MA 02129 USA.
[Razansky, Daniel; Vinegoni, Claudio; Ntziachristos, Vasilis] Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Razansky, D (reprint author), Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
EM daniel.razansky@helmholtz-muenchen.de
OI Razansky, Daniel/0000-0001-8676-0964
FU National Institutes of Health (NIH) [R01 EB00438201]
FX This study was supported in part by the National Institutes of Health
(NIH) grant R01 EB00438201.
NR 15
TC 0
Z9 0
U1 0
U2 1
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 0146-9592
J9 OPT LETT
JI Opt. Lett.
PD OCT 15
PY 2008
VL 33
IS 20
BP 2308
EP 2310
DI 10.1364/OL.33.002308
PG 3
WC Optics
SC Optics
GA 373KP
UT WOS:000260970800009
PM 18923605
ER
PT J
AU Oaklander, AL
AF Oaklander, Anne Louise
TI RSD/CRPS: The end of the beginning
SO PAIN
LA English
DT Editorial Material
ID REGIONAL-PAIN-SYNDROME; REFLEX SYMPATHETIC DYSTROPHY; SYNDROME TYPE-I;
SYNDROME TYPE-1; CYTOKINES
C1 [Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Oaklander, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 275 Charles St,Warren 310 Mailbox, Boston, MA 02114 USA.
EM aoaklander@partners.org
FU NINDS NIH HHS [K24 NS059892, R01 NS042866, K24 NS059892-01A1,
R01NS42866, K24NS059892, R01 NS042866-04]
NR 17
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD OCT 15
PY 2008
VL 139
IS 2
BP 239
EP 240
DI 10.1016/j.pain.2008.08.006
PG 2
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 368UT
UT WOS:000260648900001
PM 18790569
ER
PT J
AU Kim, S
Mohapatra, G
Haber, DA
AF Kim, S.
Mohapatra, G.
Haber, D. A.
TI In vitro phosphorylation of BRCA2 by the checkpoint kinase CHEK2
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE BRCA1 or 2 (breast cancer gene 1 or 2); CHK2 or CHEK2 (checkpoint kinase
2); IR (ionising radiation); GTG banding (G-bands after trypsin and
giemsa); NLS (nuclear localisation signal)
ID DNA-DAMAGE CHECKPOINT; CHK2 PROTEIN-KINASE; BREAST-CANCER;
PROSTATE-CANCER; MUTATIONS; ATM; P53; SUSCEPTIBILITY; FAMILIES; PATHWAY
AB Germline mutations in both BRCA2 and CHEK2 are associated with an increased risk for male breast cancer. To search for potential interactions between the products of these breast cancer susceptibility genes, we undertook systematic mapping of BRCA2 for potential phosphorylation sites by CHEK2. In vitro kinase assays and mass spectrometric analysis identified a 50 amino-acid fragment within the N-terminus of BRCA2 potentially targeted by CHEK2, containing two major phosphopeptides. Inducible overexpression of this peptide, but not a derivative with mutated phosphorylation sites, leads to increased chromosome fragmentation and suppression of cellular proliferation. These results suggest a link between CHEK2 and BRCA2 pathways, which may contribute to the spectrum of cancers associated with germline CHEK2 mutations.
C1 [Kim, S.; Haber, D. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Mohapatra, G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA.
RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,CNY-7,13 St, Charlestown, MA 02129 USA.
EM Haber@helix.mgh.harvard.edu
FU NIH [CA84066]; NIH SPORE
FX This study was supported in part by NIH CA84066 (DAH) and the NIH SPORE
on breast cancer at Massachusetts General Hospital (DAH).
NR 32
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD OCT 14
PY 2008
VL 99
IS 8
BP 1302
EP 1306
DI 10.1038/sj.bjc.6604644
PG 5
WC Oncology
SC Oncology
GA 360BB
UT WOS:000260030900018
PM 18797466
ER
PT J
AU Wiviott, SD
Braunwald, E
Angiolillo, DJ
Meisel, S
Dalby, AJ
Verheugt, FWA
Goodman, SG
Corbalan, R
Purdy, DA
Murphy, SA
McCabe, CH
Antman, EM
AF Wiviott, Stephen D.
Braunwald, Eugene
Angiolillo, Dominick J.
Meisel, Simha
Dalby, Anthony J.
Verheugt, Freek W. A.
Goodman, Shaun G.
Corbalan, Ramon
Purdy, Drew A.
Murphy, Sabina A.
McCabe, Carolyn H.
Antman, Elliott M.
CA Triton-Timi 38 Invest
TI Greater clinical benefit of more intensive oral antiplatelet therapy
with prasugrel in patients with diabetes mellitus in the Trial to Assess
Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition
With Prasugrel-Thrombolysis in Myocardial Infarction 38
SO CIRCULATION
LA English
DT Article
DE angioplasty; anticoagulants; myocardial infarction; platelets; diabetes
mellitus
ID ACUTE CORONARY SYNDROMES; ST-SEGMENT-ELEVATION; MYOCARDIAL-INFARCTION;
ARTERY-DISEASE; CARDIOVASCULAR OUTCOMES; STENT THROMBOSIS; CLOPIDOGREL;
INSULIN; MORTALITY; ASPIRIN
AB Background-Patients with diabetes mellitus (DM) are at high risk for recurrent cardiovascular events after acute coronary syndromes, in part because of increased platelet reactivity. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) showed an overall reduction in ischemic events with more intensive antiplatelet therapy with prasugrel than with clopidogrel but with more bleeding. We compared prasugrel with clopidogrel among subjects with DM in TRITON-TIMI 38.
Methods and Results-We classified 13 608 subjects on the basis of preexisting history of DM and further according to insulin use. Prespecified analyses of the primary (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and key secondary end points, including net clinical benefit (death, nonfatal myocardial infarction, nonfatal stroke, and nonfatal TIMI major bleeding) were compared by use of the log-rank test. We found that 3146 subjects had a preexisting history of DM, including 776 receiving insulin. The primary end point was reduced significantly with prasugrel among subjects without DM (9.2% versus 10.6%; hazard ratio [HR], 0.86; P=0.02) and with DM (12.2% versus 17.0%; HR, 0.70; P<0.001, P(interaction)=0.09). A benefit for prasugrel was observed among DM subjects on insulin (14.3% versus 22.2%; HR, 0.63; P=0.009) and those not on insulin (11.5% versus 15.3%; HR, 0.74; P=0.009). Myocardial infarction was reduced with prasugrel by 18% among subjects without DM (7.2% versus 8.7%; HR, 0.82; P=0.006) and by 40% among subjects with DM (8.2% versus 13.2%; HR, 0.60; P<0.001, P(interaction)=0.02). Although TIMI major hemorrhage was increased among subjects without DM on prasugrel (1.6% versus 2.4%; HR, 1.43; P=0.02), the rates were similar among subjects with DM for clopidogrel and prasugrel (2.6% versus 2.5%; HR, 1.06; P=0.81, P(interaction)=0.29). Net clinical benefit with prasugrel was greater for subjects with DM (14.6% versus 19.2%; HR, 0.74; P=0.001) than for subjects without DM (11.5% versus 12.3%; HR, 0.92; P=0.16, P(interaction)=0.05).
Conclusions-Subjects with DM tended to have a greater reduction in ischemic events without an observed increase in TIMI major bleeding and therefore a greater net treatment benefit with prasugrel compared with clopidogrel. These data demonstrate that the more intensive oral antiplatelet therapy provided with prasugrel is of particular benefit to patients with DM.
C1 [Wiviott, Stephen D.; Braunwald, Eugene; Murphy, Sabina A.; McCabe, Carolyn H.; Antman, Elliott M.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA.
[Wiviott, Stephen D.; Braunwald, Eugene; Murphy, Sabina A.; McCabe, Carolyn H.; Antman, Elliott M.] Harvard Univ, Sch Med, Boston, MA USA.
[Angiolillo, Dominick J.] Univ Florida, Coll Med, Jacksonville, FL USA.
[Meisel, Simha] Hillel Yaffe Med Ctr, Hadera, Israel.
[Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Goodman, Shaun G.] Canadian Heart Res Ctr, Toronto, ON, Canada.
[Dalby, Anthony J.] Millpk Hosp, Johannesburg, South Africa.
[Verheugt, Freek W. A.] Univ Nijmegen Hosp, Dept Cardiol, NL-6500 HB Nijmegen, Netherlands.
[Corbalan, Ramon] Catholic Univ, Sch Med, Dept Cardiol, Santiago, Chile.
[Purdy, Drew A.] Black Hills Cardiovasc Res Grp, Black Hills, SD USA.
RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM swiviott@partners.org
RI Verheugt, F.W.A./H-8105-2014
FU Daiichi Sankyo Co, Ltd; Eli Lilly and Co; Sanofi-Aventis; Glaxo Smith
Kline; Bristol-Myers Squibb; Novartis; Portola; AstraZeneca; Schering
Plough; The Medicines Co
FX The TRITON-TIMI 38 trial was supported by Daiichi Sankyo Co, Ltd, and
Eli Lilly and Co. Dr Wiviott, Dr Braunwald, C.H. McCabe, S.A. Murphy,
and Dr Antman report receiving research grants from Daiichi Sankyo, Eli
Lilly, and Sanofi-Aventis. In addition, Dr Wiviott reports receiving
consulting or advisory board fees from Sanofi-Aventis and lecture fees
from Eli Lilly and Daiichi Sankyo; Dr Braunwald reports receiving
consulting or paid advisory board fees from Daiichi Sankyo and
Sanofi-Aventis and lecture fees from Eli Lilly and Sanofi-Aventis; Dr
Antman reports receiving consulting or advisory board fees from
Sanofi-Aventis and lecture fees from Eli Lilly and Sanofi-Aventis. Dr
Angiolillo reports research grant support from Glaxo Smith Kline and
consulting, speakers bureau, or advisory board fees from Daiichi Sankyo,
Eli Lilly, Bristol-Myers Squibb, Sanofi-Aventis, Novartis, and Portola.
Dr Goodman reports receiving research grant support, speaker honoraria,
or consulting income from AstraZeneca, Bristol-Myers Squibb, Daiichi
Sankyo, Eli Lilly, Schering Plough, and The Medicines Co. The other
authors report no conflicts.
NR 38
TC 384
Z9 401
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 14
PY 2008
VL 118
IS 16
BP 1626
EP 1636
DI 10.1161/CIRCULATIONAHA.108.791061
PG 11
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 359KX
UT WOS:000259986700005
PM 18757948
ER
PT J
AU Baggish, AL
Boucher, CA
AF Baggish, Aaron L.
Boucher, Charles A.
TI Radiopharmaceutical agents for myocardial perfusion imaging
SO CIRCULATION
LA English
DT Review
DE isotopes; radioisotopes; myocardial ischemia; nuclear medicine;
radiopharmaceuticals
ID EMISSION COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; ATTENUATION
CORRECTION; PROGNOSTIC VALUE; HUMAN BIODISTRIBUTION; CLINICAL
VALIDATION; VASCULAR-SURGERY; CARDIAC RISK; CHEST PAIN; SPECT
C1 [Baggish, Aaron L.; Boucher, Charles A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Boucher, CA (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA.
EM cboucher@partners.org
NR 49
TC 22
Z9 24
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 14
PY 2008
VL 118
IS 16
BP 1668
EP 1674
DI 10.1161/CIRCULATIONAHA.108.778860
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 359KX
UT WOS:000259986700010
PM 18852377
ER
PT J
AU Ho, PM
Peterson, PN
Masoudi, FA
AF Ho, P. Michael
Peterson, Pamela N.
Masoudi, Frederick A.
TI Evaluating the evidence - Is there a rigid hierarchy?
SO CIRCULATION
LA English
DT Article
DE cardiovascular diseases; epidemiology; research design
ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; VENTRICULAR
SYSTOLIC DYSFUNCTION; TO-BALLOON TIME; ESTROGEN PLUS PROGESTIN;
BETA-BLOCKER THERAPY; HEART-FAILURE; CLINICAL-TRIALS; POSTMENOPAUSAL
ESTROGEN; CARDIOVASCULAR-DISEASE
C1 [Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO 80202 USA.
[Ho, P. Michael; Peterson, Pamela N.; Masoudi, Frederick A.] Univ Colorado, Denver, CO 80202 USA.
[Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA.
RP Masoudi, FA (reprint author), MC 0960,777 Bannock St, Denver, CO 80204 USA.
EM fred.masoudi@uchsc.edu
FU Amgen; Oklahoma Foundation for Medical Quality; Colorado Foundation for
Medical Care
FX Dr Masoudi has served on advisory boards for Takeda, NA; Amgen; and
United Healthcare. Dr Masoudi has also received research support from
Amgen, has contracts with the Oklahoma Foundation for Medical Quality
and the Colorado Foundation for Medical Care, and is an Associate Editor
for Journal Watch Cardiology of the Massachusetts Medical Society. The
other authors report no conflicts.
NR 75
TC 57
Z9 57
U1 2
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 14
PY 2008
VL 118
IS 16
BP 1675
EP 1684
DI 10.1161/CIRCULATIONAHA.107.721357
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 359KX
UT WOS:000259986700011
PM 18852378
ER
PT J
AU Hu, P
Geles, KG
Paik, JH
DePinho, RA
Tjian, R
AF Hu, Ping
Geles, Kenneth G.
Paik, Ji-Hye
DePinho, Ronald A.
Tjian, Robert
TI Codependent Activators Direct Myoblast-Specific MyoD Transcription
SO DEVELOPMENTAL CELL
LA English
DT Article
ID MUSCLE PROGENITOR CELLS; SKELETAL-MUSCLE; INSULIN-RECEPTOR; SATELLITE
CELLS; SMOOTH-MUSCLE; MYOGENIC DIFFERENTIATION; GENE-TRANSCRIPTION;
MAMMALIAN-CELLS; FACTOR FOXO3A; PAX GENES
AB Although FoxO and Pax proteins represent two important families of transcription factors in determining cell fate, they had not been functionally or physically linked together in mediating regulation of a common target gene during normal cellular transcription programs. Here, we identify MyoD, a key regulator of myogenesis, as a direct target of FoxO3 and Pax3/7 in myoblasts. Our cell-based assays and in vitro studies reveal a tight codependent partnership between FoxO3 and Pax3/7 to coordinately recruit RNA polymerase II and form a preinitiation complex (PIC) to activate MyoD transcription in myoblasts. The role of FoxO3 in regulating muscle differentiation is confirmed in vivo by observed defects in muscle regeneration caused by MyoD downregulation in FoxO3 null mice. These data establish a mutual interdependence and functional link between two families of transcription activators serving as potential signaling sensors and regulators of cell fate commitment in directing tissue specific MyoD transcription.
C1 [Hu, Ping; Geles, Kenneth G.; Tjian, Robert] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Inst Innovat Canc Sci, Dept Med Oncol,Dana Farber Canc Inst,Belfer Fdn, Boston, MA 02115 USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Inst Innovat Canc Sci, Dept Med,Dana Farber Canc Inst,Belfer Fdn, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Inst Innovat Canc Sci, Dept Genet,Dana Farber Canc Inst,Belfer Fdn, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Ctr Appl Canc Sci,Inst Innovat Canc Sci, Dana Farber Canc Inst,Belfer Fdn, Boston, MA 02115 USA.
RP Tjian, R (reprint author), Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
EM jmlim@berkeley.edu
RI Hu, Ping/G-2384-2015
FU Damon Runyon Cancer Research Foundation
FX We thank M. Haggart for technical assistance, A. Fisher for assistance
in large scale cell culture, D. Schichnes for help on microscope usage,
and D. King and L. Kohlstaedt for help on peptide synthesis and mass
spec. We thank 1. Conboy and M. Carlson for help on satellite cell
isolation, M. Marr for help on in vitro transcription assays. and B. Gan
for help on isolation of primary myoblasts from knockout mice. We also
thank M. Deato, K. Wright, Y. Fong, W. Liu, R. Colemen, F. Herrera, B.
Guglielmi, E. Olson, M.E. Buckingham, and M. Rudnicki for critical
reading of the manuscript. We thank members of the Tjian laboratory for
valuable suggestions and discussions. J.-H.P. is Damon Runyon Fellows
supported by the Damon Runyon Cancer Research Foundation. R.T. is an
investigator of the Howard Hughes Medical Institute and Director of the
Li Ka-Shing Center for Biomedical and Health Sciences.
NR 74
TC 70
Z9 73
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD OCT 14
PY 2008
VL 15
IS 4
BP 534
EP 546
DI 10.1016/j.devcel.2008.08.018
PG 13
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 363BP
UT WOS:000260241200009
PM 18854138
ER
PT J
AU Villasenor, J
Besse, W
Benoist, C
Mathis, D
AF Villasenor, Jennifer
Besse, Whitney
Benoist, Christophe
Mathis, Diane
TI Ectopic expression of peripheral-tissue antigens in the thymic
epithelium: Probabilistic, monoallelic, misinitiated
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE AIRE; autoimmunity; gene expression; immunological tolerance; T cell
tolerance
ID PROMISCUOUS GENE-EXPRESSION; ALLELE-SPECIFIC EXPRESSION; CD4(+) T-CELLS;
TRANSCRIPTION FACTOR; TH2 CELLS; AIRE; DIFFERENTIATION; SELF; MICE;
STOCHASTICITY
AB Thymic medullary epithelial cells (MECs) express a broad repertoire of peripheral-tissue antigens (PTAs), many of which depend on the transcriptional regulatory factor Aire. Although Aire is known to be critically important for shaping a self-tolerant T cell repertoire, its role in MEC maturation and function remains poorly understood. Using a highly sensitive and reproducible single-cell PCR assay, we demonstrate that individual Aire-expressing MECs transcribe a subset of PTA genes in a probabilistic fashion, with no signs of preferential coexpression of genes characteristic of particular extrathymic epithelial cell lineages. In addition, Aire-dependent PTA genes in MECs are transcribed morloallelically or biallelically in a stochastic pattern, in contrast to the usually biallelic transcription of these same genes in the relevant peripheral cells or of Aire-independent genes in MECs. Expression of PTA genes in MECs depends on transcriptional regulators and uses transcriptional start sites different from those used in peripheral cells. These findings support the "terminal differentiation" model of Aire function: as MECs mature, they transcribe more and more PTA genes, culminating in a cell population that is both capable of presenting antigens (MHCIIhi, CD80(hi)) and can draw on a large repertoire of antigens to present.
C1 Harvard Univ, Sch Med, Boston, MA 02215 USA.
Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA.
RP Mathis, D (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl,Room 478, Boston, MA 02214 USA.
EM cbdm@joslin.harvard.edu
FU National Institutes of Health [R01 DK60027, T32 DK07260]; Young Chair
funds; Joslin's National Institutes of Diabetes and Digestive and Kidney
Diseases
FX We thank Jasmine Perez for excellent technical support. This work was
supported by National Institutes of Health Grant R01 DK60027 and Young
Chair funds (to D.M, and C.B.), and by Joslin's National Institutes of
Diabetes and Digestive and Kidney Diseases-funded Diabetes and
Endocrinology Research Center core facilities. J.V. and W.B. received
support from National Institutes of Health Training Grant T32 DK07260.
NR 45
TC 74
Z9 74
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2008
VL 105
IS 41
BP 15854
EP 15859
DI 10.1073/pnas.0808069105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900040
PM 18836079
ER
PT J
AU Venanzi, ES
Melamed, R
Mathis, D
Benoist, C
AF Venanzi, Emily S.
Melamed, Rachel
Mathis, Diane
Benoist, Christophe
TI The variable immunological self: Genetic variation and nongenetic noise
in Aire-regulated transcription
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE gene expression; immunological tolerance; microarray; thymus; autoimmune
regulator
ID THYMIC EPITHELIAL-CELLS; CANDIDIASIS-ECTODERMAL DYSTROPHY; AUTOIMMUNE
REGULATOR; INSULIN EXPRESSION; IDDM2 LOCUS; NOD MICE; TOLERANCE;
ANTIGEN; PROTEIN; SUSCEPTIBILITY
AB The Aire transcription factor plays an important role in immunological self-tolerance by mediating the ectopic expression of peripheral self-antigens by thymic medullary epithelial cells (MECs), and the deletion of thymocytes that recognize them. In Aire-deficient humans or mice, central tolerance is incomplete and multiorgan autoimmune disease results. We examined the variability of Aire's effects on ectopic transcription among individual mice of three different inbred strains. Aire's function was, overall, quite similar in the three backgrounds, although generally stronger in C57BL/6 than in BALB/c or NOD mice, and a minority of Aire-regulated genes did show clear differences. Gene expression profiling of wild-type MECs from single mice, or from the two thymic lobes of the same mouse, revealed significantly greater variability in Aire-controlled ectopic gene expression than in Aire-independent transcripts. This "noisy" ectopic expression did not result from parental or early developmental imprinting, but from programming occurring after the formation of the thymic anlage, resulting from epigenetic effects or from the stochastic nature of Aire activity. Together, genetic and nongenetic variability in ectopic expression of peripheral antigens in the thymus make for differences in the portion of self determinants presented for tolerance induction. This variable self may be beneficial in preventing uniform holes in the T-cell repertoire in individuals of a species, but at the cost of variable susceptibility to autoimmunity.
C1 [Mathis, Diane; Benoist, Christophe] Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Mathis, D (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA.
EM cbdm@joslin.harvaid.edu
OI Melamed, Rachel/0000-0003-3089-9806
FU National Institutes of Health [R01 DK60027, T32 DK07260]; Young Chair
funds; Joslin Diabetes Center's NIDDK
FX We thank Vincent Auyeung for the splenic Treg microarray data and Dr.
Hamish Scott for the anti-Aire antibody. This work was supported by a
National Institutes of Health Grant R01 DK60027, Young Chair funds (to
D.M. and C.B.), Joslin Diabetes Center's NIDDK-funded DERC core
facilities, and National Institutes of Health Training Grant T32 DK07260
(to E.V.).
NR 30
TC 38
Z9 38
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2008
VL 105
IS 41
BP 15860
EP 15865
DI 10.1073/pnas.0808070105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900041
PM 18838677
ER
PT J
AU Koh, AS
Kuo, AJ
Park, SY
Cheung, P
Abramson, J
Bua, D
Carney, D
Shoelson, SE
Gozani, O
Kingston, RE
Benoist, C
Mathis, D
AF Koh, Andrew S.
Kuo, Alex J.
Park, Sang Youn
Cheung, Peggie
Abramson, Jakub
Bua, Dennis
Carney, Dylan
Shoelson, Steven E.
Gozani, Or
Kingston, Robert E.
Benoist, Christophe
Mathis, Diane
TI Aire employs a histone-binding module to mediate immunological
tolerance, linking chromatin regulation with organ-specific autoimmunity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE T cell tolerance; plant homeodomain finger; thymus APS-1; APECED
ID THYMIC EPITHELIAL-CELLS; PROMISCUOUS GENE-EXPRESSION; PHD FINGER; H3;
PROTEIN; LYSINE-4; METHYLATION; DISEASE; DNA; MECHANISMS
AB Aire induces ectopic expression of peripheral tissue antigens WAS) in thymic medullary epithelial cells, which promotes immunological tolerance. Beginning with a broad screen of histone peptides, we demonstrate that the mechanism by which this single factor controls the transcription of thousands of genes involves recognition of the amino-terminal tail of histone H3, but not of other histones, by one of Aire's plant homeodomain (PHD) fingers. Certain posttranslational modifications of H3 tails, notably dimethylation or trimethylation at H3K4, abrogated binding by Aire, whereas others were tolerated. Similar PHD finger-H3 tail-binding properties were recently reported for BRAF-histone deacetylase complex 80 and DNA methyltransferase 3L; sequence alignment, molecular modeling, and biochemical analyses showed these factors and Aire to have structure-function relationships in common. In addition, certain PHD1 mutations underlying the polyendocrine disorder autoimmune polyendocrinopathy-candidiases-ectodermaldystrophy compromised Aire recognition of H3. In vitro binding assays demonstrated direct physical interaction between Aire and nucleosomes, which was in part buttressed by its affinity to DNA. In vivo Aire interactions with chromosomal regions depleted of H3K4me3 were dependent on its H3 tail-binding activity, and this binding was necessary but not sufficient for the up-regulation of genes encoding PTAs. Thus, Aire's activity as a histone-binding module mediates the thymic display of PTAs that promotes self-tolerance and prevents organ-specific autoimmunity.
C1 [Koh, Andrew S.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Koh, Andrew S.; Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Koh, Andrew S.; Park, Sang Youn; Abramson, Jakub; Shoelson, Steven E.; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA.
[Koh, Andrew S.; Park, Sang Youn; Abramson, Jakub; Shoelson, Steven E.; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Kuo, Alex J.; Cheung, Peggie; Bua, Dennis; Carney, Dylan; Gozani, Or] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM kingston@moibio.mgh.harvard.edu; cbdm@joslin.harvard.edu
RI ABRAMSON, JAKUB/K-1348-2012
FU National Institutes of Health (NIH) [P30 DK36836, R01 DK60027, R01
GM48405, R01 GM079641, T32 DK07260]; Genentech; National Research
Service [F32 DK774852]; Juvenile Diabetes Research Foundation
FX We thank Dr. A. G. W. Matthews for critical suggestions, and the Aire
group and Kingston lab for inspiration and helpful discussions. This
work was supported by National Institutes of Health (NIH) Grant P30
DK36836 to the Joslin Diabetes Center's Diabetes and Endocrinology
Research Center core facilities; NIH Grant R01 DK60027 and Young Chair
funds to D.M. and C.B.; NIH Grant R01 GM48405 to R.E.K.; and NIH Grant
R01 GM079641 and a Searle Scholar Award to O.G. A.S.K. was supported by
NIH Grant T32 DK07260, A.J.K. by a precloctoral fellowship from
Genentech, S.Y.P. by National Research Service Award F32 DK774852, and
J.A. by a Juvenile Diabetes Research Foundation Advanced Postdoctotal
Fellowship.
NR 47
TC 99
Z9 104
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2008
VL 105
IS 41
BP 15878
EP 15883
DI 10.1073/pnas.0808470105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900044
PM 18840680
ER
PT J
AU Diao, HY
Iwabuchi, K
Li, LJ
Onoe, K
Van Kaer, L
Kon, S
Saito, Y
Morimoto, J
Denhardt, DT
Rittling, S
Uede, T
AF Diao, Hongyan
Iwabuchi, Kazuya
Li, Lanjuan
Onoe, Kazunori
Van Kaer, Luc
Kon, Shigeyuki
Saito, Yoshinari
Morimoto, Junko
Denhardt, David T.
Rittling, Susan
Uede, Toshimitsu
TI Osteopontin regulates development and function of invariant natural
killer T cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE nuclear factor of activated T cells (NFAT); GATA-3; Fas ligand (FasL)
ID V-ALPHA-14I NKT CELLS; A-INDUCED HEPATITIS; DENDRITIC CELLS;
CONCANAVALIN-A; EXPRESSION; MICE; ACTIVATION; GATA-3; BET; CONTRIBUTES
AB Invariant natural killer T (iNKT) cells belong to a subset of lymphocytes bridging innate and acquired immunity. We demonstrated that osteopontin (OPN) is involved in the activation of iNKT cells. In the present work, we examined whether OPN affects development and function of iNKT cells. We found that the number of peripheral iNKT cells was significantly reduced in OPN-deficient mice compared with wild-type mice. Although the number of thymic iNKT cells was not different between WT and OPN-deficient mice, intrathymic iNKT cell maturation was impaired in OPN-deficient mice. iNKT cell function was also significantly altered in OPN-deficient mice, as evidenced by (i) deficient down-regulation of iNKT cell receptor, (h) reduction of IL-4 production while preserving production of IFN-gamma, and (iii) reduction of Fas ligand (FasL) expression, leading to reduced Fas/FasL-dependent cytotoxicity against hepatocytes. Importantly, activation of the transcription factors NFAT2 (nuclear factor of activated T cells 2) and GATA-3 was impaired, whereas activation of T-bet was preserved in iNKT cells of OPN-deficient mice. These data collectively indicate that OPN plays a pivotal role not only in the development, but also in the function of iNKT cells.
C1 [Diao, Hongyan; Li, Lanjuan] Hokkaido Univ, Inst Med Genet, Dept Matrix Med, Kita Ku, Sapporo, Hokkaido 0600815, Japan.
[Iwabuchi, Kazuya; Onoe, Kazunori] Hokkaido Univ, Inst Med Genet, Div Immunobiol, Sapporo, Hokkaido 0600815, Japan.
[Diao, Hongyan] Zhejiang Univ, State Key Lab Diag & Treatment Infect Dis, Affiliated Hosp 1, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China.
[Van Kaer, Luc] Vanderbilt Univ, Dept Microbiol & Immunol, Sch Med, Nashville, TN 37232 USA.
[Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA.
[Rittling, Susan] Forsyth Inst, Boston, MA 02115 USA.
RP Diao, HY (reprint author), Hokkaido Univ, Inst Med Genet, Dept Matrix Med, Kita Ku, Kita 15,Nishi 7, Sapporo, Hokkaido 0600815, Japan.
EM diao.hy@163.com; toshi@igm.hokudai.ac.jp
RI Kon, Shigeyuki/A-3809-2012; uede, toshimitsu/A-4273-2012; Van Kaer,
Luc/H-1033-2015
OI Van Kaer, Luc/0000-0001-5275-2309
FU Japan Society for the Promotion of Science [17790315]
FX We thank Drs. M. Taniguchi and K. Seino (Research Center for Allergy and
Immunology, institute of Physical and Chemical Research, Yokohama,
Japan) for TLR2 cells. This work was supported by Japan Society for the
Promotion of Science Grant 17790315 (to H.D.).
NR 30
TC 19
Z9 22
U1 1
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2008
VL 105
IS 41
BP 15884
EP 15889
DI 10.1073/pnas.0806089105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900045
PM 18836077
ER
PT J
AU Lin, B
Koizumi, A
Tanaka, N
Panda, S
Masland, RH
AF Lin, Bin
Koizumi, Amane
Tanaka, Nobushige
Panda, Satchidananda
Masland, Richard H.
TI Restoration of visual function in retinal degeneration mice by ectopic
expression of melanopsin
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID GANGLION-CELLS; MOUSE RETINA; RESPONSES; LIGHT; PHOTOPIGMENT;
PHOTOTRANSDUCTION; PHOTOSENSITIVITY; PERSISTENCE; DIVERSITY
AB The rod and cone cells of the mammalian retina are the principal photoreceptors for image-forming vision. They transmit information by means of a chain of intermediate cells to the retinal ganglion cells, which in turn send signals from the retina to the brain. Loss of photoreceptor cells, as happens in a number of human diseases, leads to irreversible blindness. in a mouse model (rd/rd) of photoreceptor degeneration, we used a viral vector to express in a large number of retinal ganglion cells the light sensitive protein melanopsin, normally present in only a specialized subset of the cells. Whole-cell patch-clamp recording showed photoresponses in these cells even after degeneration of the photoreceptors and additional pharmacological or Cd2+ block of synaptic function. Interestingly, similar responses were observed across a wide variety of diverse types of ganglion cell of the retina. The newly melanopsin-expressing ganglion cells provided an enhancement of visual function in rd/rd mice: the pupillary light reflex (PLR) returned almost to normal; the mice showed behavioral avoidance of light in an open-field test, and they could discriminate a light stimulus from a dark one in a two-choice visual discrimination alley. Recovery of the PLR was stable for at least 11 months. It has recently been shown that ectopic retinal expression of a light sensitive bacterial protein, channelrhodopsin-2, can restore neuronal responsiveness and simple visual abilities in rd/rd mice. For therapy in human photodegenerations, channelrhodopsin-2 and melanopsin have different advantages and disadvantages; both proteins (or modifications of them) should be candidates.
C1 [Lin, Bin; Koizumi, Amane; Masland, Richard H.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tanaka, Nobushige; Panda, Satchidananda] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Thier 429,50 Blossom St, Boston, MA 02114 USA.
EM richard_masland@hms.harvard.edu
RI Lin, Bin/E-9871-2010; Koizumi, Amane/E-7771-2011; Panda,
Satchidananda/J-6891-2012
FU National Institutes of Health [EY 017169, EY016807]; Pew Scholars award
FX We thank Aimee Wong and Richard Brown for advice on the testing of mouse
visual discriminations and Jeng-Shin Lee and the Harvard vector core for
providing the AAV constructs. This work was supported by National
Institutes of Health Grants EY 017169 (to R.H.M.) and EY016807 (to
S.P.). S.P. was supported by a Pew Scholars award. R.H.M. is a Senior
Investigator of Research to Prevent Blindness.
NR 28
TC 124
Z9 130
U1 0
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2008
VL 105
IS 41
BP 16009
EP 16014
DI 10.1073/pnas.0806114105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 363BM
UT WOS:000260240900066
PM 18836071
ER
PT J
AU Qiu, L
Larson, TA
Smith, D
Vitkin, E
Modell, MD
Korgel, BA
Sokolov, KV
Hanlon, EB
Itzkan, I
Perelman, LT
AF Qiu, Le
Larson, Timothy A.
Smith, Danielle
Vitkin, Edward
Modell, Mark D.
Korgel, Brian A.
Sokolov, Konstantin V.
Hanlon, Eugene B.
Itzkan, Irving
Perelman, Lev T.
TI Observation of plasmon line broadening in single gold nanorods
SO APPLIED PHYSICS LETTERS
LA English
DT Article
ID LIGHT-SCATTERING; PARTICLES; NANOPARTICLES; SPECTROSCOPY; CELLS; SHAPE
AB Attempts to realize the important potential of gold nanorods as extremely bright molecular markers have been limited by the broad spectroscopic linewidths usually observed. We identify the origin of this broadening as inhomogeneous broadening due to the extreme sensitivity of the surface plasmon resonance to the nanorod aspect ratio. Using confocal light scattering spectroscopic microscopy, we observed the narrow homogeneously broadened plasmon lines of single gold nanorods and obtained the first quantitative measurements of this homogeneous broadening. We show that homogeneous broadening can be predicted from first principals. (C) 2008 American Institute of Physics. [DOI: 10.1063/1.2995982]
C1 [Qiu, Le; Vitkin, Edward; Modell, Mark D.; Hanlon, Eugene B.; Itzkan, Irving; Perelman, Lev T.] Harvard Univ, Biomed Imaging & Spect Lab, BIDMC, Boston, MA 02215 USA.
[Larson, Timothy A.; Smith, Danielle; Korgel, Brian A.; Sokolov, Konstantin V.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
[Larson, Timothy A.; Smith, Danielle; Korgel, Brian A.; Sokolov, Konstantin V.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.
[Sokolov, Konstantin V.] Univ Texas MD Anderson Canc Ctr, Dept Biomed Engn, Houston, TX 77030 USA.
[Sokolov, Konstantin V.] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA.
[Hanlon, Eugene B.] Dept Vet Affairs, Med Res Serv, Bedford, MA 01730 USA.
RP Qiu, L (reprint author), Harvard Univ, Biomed Imaging & Spect Lab, BIDMC, Boston, MA 02215 USA.
EM ltperel@bidmc.harvard.edu
RI Korgel, Brian/I-5771-2013;
OI Sokolov, Konstantin/0000-0002-0198-2005
FU National Science Foundation [BES0116833]; National Institutes of Health
[RR017361, CA103830]; Department of Veterans Affairs; Office of Research
and Development
FX This work was supported by the National Science Foundation (Grant No.
BES0116833), National Institutes of Health (Grant Nos. RR017361 and
CA103830), and in part by the Department of Veterans Affairs, Office of
Research and Development. We thank K. Travis for helpful comments. The
electron microscopy studies were conducted at the electron microscope
facilities at the Institute of Cellular and Molecular Biology,
University of Texas at Austin.
NR 20
TC 17
Z9 17
U1 0
U2 11
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0003-6951
EI 1077-3118
J9 APPL PHYS LETT
JI Appl. Phys. Lett.
PD OCT 13
PY 2008
VL 93
IS 15
AR 153106
DI 10.1063/1.2995982
PG 3
WC Physics, Applied
SC Physics
GA 361JY
UT WOS:000260125100077
ER
PT J
AU Rigotti, NA
Munafo, MR
Stead, LF
AF Rigotti, Nancy A.
Munafo, Marcus R.
Stead, Lindsay F.
TI Smoking cessation interventions for hospitalized smokers - A systematic
review
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 9th Annual Meeting of the Society-for-Research-in-Nicotine-and-Tobacco
Europe
CY OCT 05, 2007
CL Madrid, SPAIN
SP Soc Res Nicotine & Tobacco Europe
ID RANDOMIZED CONTROLLED-TRIAL; TRANSDERMAL NICOTINE REPLACEMENT; ACUTE
MYOCARDIAL-INFARCTION; CLINICAL-TRIAL; CARDIOVASCULAR-DISEASE; EFFICACY;
SURGERY; INPATIENTS; ADMISSION
AB Background: A hospital admission provides an opportunity to help people stop smoking. Providing smoking cessation advice, counseling, or medication is now a quality-of-care measure for US hospitals. We assessed the effectiveness of smoking cessation interventions initiated during a hospital stay.
Methods: We searched the Cochrane Tobacco Addiction Review Group's register for randomized and quasi-randomized controlled trials of smoking cessation interventions (behavioral counseling and/or pharmacotherapy) that began during hospitalization and had a minimum of 6 months of follow-up. Two authors independently extracted data from each article, with disagreements resolved by consensus.
Results: Thirty-three trials met inclusion criteria. Smoking counseling that began during hospitalization and included supportive contacts for more than 1 month after discharge increased smoking cessation rates at 6 to 12 months (pooled odds ratio [OR], 1.65; 95% confidence interval [CI], 1.44-1.90). No benefit was found for interventions with less postdischarge contact. Counseling was effective when offered to all hospitalized smokers and to the subset admitted for cardiovascular disease. Adding nicotine replacement therapy to counseling produced a trend toward efficacy over counseling alone (OR, 1.47; 95% CI, 0.92-2.35). One study added bupropion hydrochloride to counseling, which had a nonsignificant result (OR, 1.56; 95% CI, 0.79-3.06).
Conclusions: Offering smoking cessation counseling to all hospitalized smokers is effective as long as supportive contacts continue for more than 1 month after discharge. Adding nicotine replacement therapy to counseling may further increase smoking cessation rates and should be offered when clinically indicated, especially to hospitalized smokers with nicotine withdrawal symptoms.
C1 [Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Munafo, Marcus R.] Univ Bristol, Dept Expt Psychol, Bristol, Avon, England.
[Stead, Lindsay F.] Univ Oxford, Oxford, England.
[Stead, Lindsay F.] Cochrane Tobacco Addict Review Grp, Oxford, England.
RP Rigotti, NA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, 50 Staniford St,Room 914, Boston, MA 02114 USA.
EM nrigotti@partners.org
OI Munafo, Marcus/0000-0002-4049-993X
FU NHLBI NIH HHS [2 K24 HL04440, K24 HL004440, K24 HL004440-10]
NR 44
TC 136
Z9 142
U1 1
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD OCT 13
PY 2008
VL 168
IS 18
BP 1950
EP 1960
DI 10.1001/archinte.168.18.1950
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 359KA
UT WOS:000259984400003
PM 18852395
ER
PT J
AU Alelu-Paz, R
Iturrieta-Zuazo, I
Byne, W
Haroutunian, V
Garcia-Villanueva, M
Rabano, A
Garcia-Amado, M
Prensa, L
Gimenez-Amaya, JM
AF Alelu-Paz, Raul
Iturrieta-Zuazo, Ignacio
Byne, William
Haroutunian, Vahram
Garcia-Villanueva, Mercedes
Rabano, Alberto
Garcia-Amado, Maria
Prensa, Lucia
Manuel Gimenez-Amaya, Jose
TI A New Antigen Retrieval Technique for Human Brain Tissue
SO PLOS ONE
LA English
DT Article
AB Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times.
C1 [Alelu-Paz, Raul; Iturrieta-Zuazo, Ignacio; Garcia-Amado, Maria; Prensa, Lucia; Manuel Gimenez-Amaya, Jose] Univ Autonoma Madrid, Fac Med, Dept Anat Histol & Neurociencia, Madrid, Spain.
[Iturrieta-Zuazo, Ignacio; Garcia-Amado, Maria] Univ Navarra, Clin Univ, Lab Neuromorfol Funcion, E-31080 Pamplona, Spain.
[Byne, William; Haroutunian, Vahram] Mount Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Byne, William; Haroutunian, Vahram] Bronx Vet Affairs Med Ctr, Bronx, NY USA.
[Garcia-Villanueva, Mercedes] Hosp Ramon & Cajal, Dept Anat Patol, Madrid, Spain.
[Rabano, Alberto] Hosp Alcorcon, Lab Neuropatol, Madrid, Spain.
RP Alelu-Paz, R (reprint author), Univ Autonoma Madrid, Fac Med, Dept Anat Histol & Neurociencia, Madrid, Spain.
EM josemanuel.gimenezamaya@uam.es
RI Garcia-Amado, Maria/K-2705-2014
OI Garcia-Amado, Maria/0000-0001-6778-5680
FU Spanish Ministerio de Educacion y Ciencia [BFU2006-01189]
FX This study was supported by a grant from the Spanish Ministerio de
Educacion y Ciencia (BFU2006-01189). The funder had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 46
TC 8
Z9 9
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 OCT 13
PY 2008
VL 3
IS 10
AR e3378
DI 10.1371/journal.pone.0003378
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432GN
UT WOS:000265121600004
PM 18852880
ER
PT J
AU Kuballa, P
Huett, A
Rioux, JD
Daly, MJ
Xavier, RJ
AF Kuballa, Petric
Huett, Alan
Rioux, John D.
Daly, Mark J.
Xavier, Ramnik J.
TI Impaired Autophagy of an Intracellular Pathogen Induced by a Crohn's
Disease Associated ATG16L1 Variant
SO PLOS ONE
LA English
DT Article
AB The genetic risk factors predisposing individuals to the development of inflammatory bowel disease are beginning to be deciphered by genome-wide association studies. Surprisingly, these new data point towards a critical role of autophagy in the pathogenesis of Crohn's disease. A single common coding variant in the autophagy protein ATG16L1 predisposes individuals to the development of Crohn's disease: while ATG16L1 encoding threonine at amino acid position 300 (ATG16L1*300T) confers protection, ATG16L1 encoding for alanine instead of threonine (ATG16L1*300A, also known as T300A) mediates risk towards the development of Crohn's disease. Here we report that, in human epithelial cells, the Crohn's disease-associated ATG16L1 coding variant shows impairment in the capture of internalized Salmonella within autophagosomes. Thus, we propose that the association of ATG16L1*300A with increased risk of Crohn's disease is due to impaired bacterial handling and lowered rates of bacterial capture by autophagy.
C1 [Kuballa, Petric; Huett, Alan; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA.
[Rioux, John D.; Daly, Mark J.] Harvard Univ, Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA.
[Rioux, John D.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
[Daly, Mark J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA.
RP Kuballa, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA.
EM xavier@molbio.mgh.harvard.edu
RI Rioux, John/A-9599-2015
OI Rioux, John/0000-0001-7560-8326
FU Deutsche Forschungsgemeinschaft [KU2511/1-1]; CCIB; National Institutes
of Allergy and Infectious Diseases [AI065687, AI067152]; National
Institute of Diabetes and Digestive and Kidney Diseases [DK064869,
DK062432]; Crohn's and Colitis Foundation of America [SRA512];
[AI062773]; [HL88297]
FX PK is supported by a fellowship award from the Deutsche
Forschungsgemeinschaft (KU2511/1-1). RJX is supported by the following
grants: AI062773, HL88297 and CCIB development funds. JDR is funded by
grants from the National Institutes of Allergy and Infectious Diseases
(AI065687; AI067152) from the National Institute of Diabetes and
Digestive and Kidney Diseases (DK064869; DK062432) and the Crohn's and
Colitis Foundation of America (SRA512). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 21
TC 184
Z9 194
U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 13
PY 2008
VL 3
IS 10
AR e3391
DI 10.1371/journal.pone.0003391
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432GN
UT WOS:000265121600014
PM 18852889
ER
PT J
AU Yan, BP
Kiernan, TJ
Clark, DJ
Jaff, MR
Schainfeld, RM
Rosenfield, K
AF Yan, Bryan P.
Kiernan, Thomas J.
Clark, David J.
Jaff, Michael R.
Schainfeld, Robert M.
Rosenfield, Kenneth
TI Carotid Duplex Ultrasound Velocity Measurements Versus Intravascular
Ultrasound in Detecting Carotid In-Stent Restenosis
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Yan, Bryan P.; Kiernan, Thomas J.; Jaff, Michael R.; Schainfeld, Robert M.; Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Clark, David J.] Austin Hosp, Melbourne, Vic 3084, Australia.
RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015
NR 0
TC 0
Z9 0
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 OCT 12
PY 2008
VL 102
IS 8A
BP 18I
EP 18I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700035
ER
PT J
AU Meliga, E
Valgimigli, M
Chieffo, A
Maree, AO
Cook, S
Garcia-Garcia, HM
D'Amico, M
Lombardi, P
De Servi, S
Marra, S
Palacios, I
Windecker, S
Colombo, A
Sheiban, I
Serruys, PW
AF Meliga, Emanuele
Valgimigli, Marco
Chieffo, Alaide
Maree, Andrew O.
Cook, Stephan
Garcia-Garcia, Hector M.
D'Amico, Maurizio
Lombardi, Primiano
De Servi, Stefano
Marra, Sebastiano
Palacios, Igor
Windecker, Stephane
Colombo, Antonio
Sheiban, Imad
Serruys, Patrick W.
TI Gender Differences In Short And Long Term Clinical Outcomes After
Percutaneous Coronary Interventions For Unprotected Left Main Coronary
Artery Disease With Drug Eluting Stents Implantation
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Meliga, Emanuele; D'Amico, Maurizio; Lombardi, Primiano; Marra, Sebastiano] San Giovanni Battista Hosp, Intervent Cardiol Dept, Turin, Italy.
[Meliga, Emanuele; Garcia-Garcia, Hector M.; Serruys, Patrick W.] Erasmus Univ, Intervent Cardiol Dept, Erasmus MC, Rotterdam, Netherlands.
Univ Ferrara, Inst Cardiol, I-44100 Ferrara, Italy.
[Chieffo, Alaide; Colombo, Antonio] Ist Sci San Raffaele, Intervent Cardiol Dept, Milan, Italy.
[Maree, Andrew O.; Palacios, Igor] Massachusetts Gen Hosp, Intervent Cardiol Dept, Boston, MA 02114 USA.
[Maree, Andrew O.; Windecker, Stephane] Univ Hosp Bern, Dept Cardiol, CH-3010 Bern, Switzerland.
[De Servi, Stefano] Osped Civile Legnano, Intervent Cardiol Dept, Legnaro, Italy.
[Sheiban, Imad] Univ Turin, San Giovanni Battista Hosp, Univ Intervent Cardiol Dept, Turin, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 85I
EP 85I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700192
ER
PT J
AU Meliga, E
Valgimigli, M
Chieffo, A
Maree, AO
Cook, S
Garcia-Garcia, HM
D'Amico, M
Lombardi, P
De Servi, S
Marra, S
Palacios, I
Windecker, S
Colombo, A
Sheiban, I
Serruys, PW
AF Meliga, Emanuele
Valgimigli, Marco
Chieffo, Alaide
Maree, Andrew O.
Cook, Stephan
Garcia-Garcia, Hector M.
D'Amico, Maurizio
Lombardi, Primiano
De Servi, Stefano
Marra, Sebastiano
Palacios, Igor
Windecker, Stephan
Colombo, Antonio
Sheiban, Imad
Serruys, Patrick W.
TI Very Long Term Clinical Outcomes After DES Implantation For Unprotected
Left Main Coronary Artery Disease In Very High Risk Patients
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Meliga, Emanuele; D'Amico, Maurizio; Lombardi, Primiano; Marra, Sebastiano; Sheiban, Imad] San Giovanni Battista Hosp, Intervent Cardiol Dept, Turin, Italy.
[Meliga, Emanuele; Garcia-Garcia, Hector M.; Serruys, Patrick W.] ERASMUS MC, Intervent Cardiol Dept, Thoraxctr, Rotterdam, Netherlands.
[Valgimigli, Marco] Univ Ferrara, Inst Cardiol, I-44100 Ferrara, Italy.
[Chieffo, Alaide; Colombo, Antonio] Ist Sci San Raffaele, Intervent Cardiol Dept, Milan, Italy.
[Maree, Andrew O.; Palacios, Igor] Massachusetts Gen Hosp, Intervent Cardiol Dept, Boston, MA 02114 USA.
[Cook, Stephan] Univ Hosp, Dept Cardiol 1, Bern, Switzerland.
[De Servi, Stefano] Osped Civile Legnano, Intervent Cardiol Dept, Legnano, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 86I
EP 86I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700193
ER
PT J
AU Azmoon, S
Lepor, NE
Ebrahimi, R
Madyoon, H
AF Azmoon, Shah
Lepor, Norman E.
Ebrahimi, Ramin
Madyoon, Hooman
TI Interpretation of Symptoms in addition to the predictive Value of
Coronary Artery Calcium Scores in Assessing Coronary Obstructive Risk
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Azmoon, Shah] NYMC, Valhalla, NY USA.
[Lepor, Norman E.; Madyoon, Hooman] Westside Med Imaging, Beverly Hills, CA USA.
[Ebrahimi, Ramin] W Los Angeles Vet Affairs Hosp, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 95I
EP 95I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700216
ER
PT J
AU Azmoon, S
Madyoon, H
Ebrahimi, R
Lepor, NE
AF Azmoon, Shah
Madyoon, Hooman
Ebrahimi, Ramin
Lepor, Norman E.
TI Gender Differences in the Assessment of Coronary Artery Stenosis in
Patients with Abnormal Coronary Calcium Scores Undergoing 64 Slice CT
Angiography
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Azmoon, Shah] NYMC, Valhalla, NY USA.
[Madyoon, Hooman; Lepor, Norman E.] Westside Med Coll, Beverly Hills, CA USA.
[Ebrahimi, Ramin] W Los Angeles Vet Affairs Hosp, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 98I
EP 98I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700227
ER
PT J
AU Pop, A
Ansel, G
Jaff, M
Bresnahan, J
Safian, R
AF Pop, Andrei
Ansel, Gary
Jaff, Michael
Bresnahan, John
Safian, Robert
TI Neurologic Outcome of Stroke After Carotid Stenting
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Pop, Andrei; Safian, Robert] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Ansel, Gary] MidWest Cardiol Res Fdn, Columbus, OH USA.
[Jaff, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bresnahan, John] Mayo Clin, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 101I
EP 102I
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700234
ER
PT J
AU Kiernan, TJ
Yan, BP
Cubeddu, RJ
Rengifo-Moreno, P
Gupta, V
Inglessis, I
Jaff, MR
Schainfeld, RM
Palacios, IF
AF Kiernan, Thomas J.
Yan, Bryan P.
Cubeddu, Roberto J.
Rengifo-Moreno, Pablo
Gupta, Vishal
Inglessis, Ignacio
Jaff, Michael R.
Schainfeld, Robert M.
Palacios, Igor F.
TI Patent Foramen Ovate, Cryptogenic Stroke and May-Thurner Syndrome : a
Retrospective Analysis
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Kiernan, Thomas J.; Yan, Bryan P.; Cubeddu, Roberto J.; Rengifo-Moreno, Pablo; Gupta, Vishal; Inglessis, Ignacio; Jaff, Michael R.; Schainfeld, Robert M.; Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 112I
EP 112I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700263
ER
PT J
AU Finn, AV
John, MC
Nakazawa, G
Raghunathan, C
Ezell, T
Lajoie, S
Xu, X
Cheng, Q
Kolodgie, F
Virmani, R
Gold, HK
AF Finn, Aloke V.
John, Michael C.
Nakazawa, Gaku
Raghunathan, Chitra
Ezell, Tucker
Lajoie, Scott
Xu, Xin
Cheng, Qi
Kolodgie, Frank
Virmani, Renu
Gold, Herman K.
TI Differential Healing in Paclitaxel and Sirolimus-Eluting Stents in
Combination with Oral PPAR Gamma Agents: The Importance of Drug
Interaction in Delayed Healing
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Finn, Aloke V.; Raghunathan, Chitra; Ezell, Tucker] Emory Univ, Atlanta, GA 30322 USA.
[John, Michael C.; Lajoie, Scott; Gold, Herman K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nakazawa, Gaku; Xu, Xin; Cheng, Qi; Kolodgie, Frank; Virmani, Renu] CVPath, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 128I
EP 128I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700303
ER
PT J
AU Kiernan, TJ
Yan, BP
Cubeddu, RJ
Cruz-Gonzalez, I
Rosenfield, K
Palacios, I
AF Kiernan, Thomas J.
Yan, Bryan P.
Cubeddu, Roberto J.
Cruz-Gonzalez, Ignacio
Rosenfield, Kenneth
Palacios, Igor
TI Coronary Artery Perforations in the Current Era of Percutaneous Coronary
Intervention
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Kiernan, Thomas J.; Yan, Bryan P.; Cubeddu, Roberto J.; Cruz-Gonzalez, Ignacio; Rosenfield, Kenneth; Palacios, Igor] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015
NR 0
TC 0
Z9 0
U1 0
U2 2
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 OCT 12
PY 2008
VL 102
IS 8A
BP 212I
EP 212I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700526
ER
PT J
AU Movahed, MR
Ebrahimi, R
Jamal, MM
Hashemzadeh, M
AF Movahed, Mohammad Reza
Ebrahimi, Ramin
Jamal, M. Mazen
Hashemzadeh, Mehrtash
TI Significant Decline in the Nationwide Trends in the Mortality in
Patients undergoing Percutaneous Coronary Intervention
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Movahed, Mohammad Reza] Univ Arizona, Med Ctr, Tucson, AZ USA.
[Movahed, Mohammad Reza] So Arizona VA Hlth Care Syst, Tucson, AZ USA.
[Ebrahimi, Ramin] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA.
[Jamal, M. Mazen] VA Long Beach Hlth Care Syst, Long Beach, CA USA.
[Hashemzadeh, Mehrtash] VA Long Beach Healthcare Syst, Long Beach, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 216I
EP 217I
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700540
ER
PT J
AU Movahed, MR
Hashemzadeh, MH
Jamal, MM
Ebrahimi, R
AF Movahed, Mohammad Reza
Hashemzadeh, Mehrtash Hashmezadeh
Jamal, M. Mazen
Ebrahimi, Ramin
TI Significant Decline in the Nationwide Trends in the Mortality in
Patients undergoing Multi Vessel Percutaneous Coronary Intervention
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 20th Annual Transcatheter Cardiovascular Therapeutics Conference
CY OCT 12-17, 2008
CL Washington, CA
SP Cardiovasc Res Fdn
C1 [Movahed, Mohammad Reza] So Arizona VA Hlth Care Syst, Tucson, AZ USA.
[Movahed, Mohammad Reza] Univ Arizona, Med Ctr, Tucson, AZ USA.
[Hashemzadeh, Mehrtash Hashmezadeh; Jamal, M. Mazen] VA Long Beach Hlth Care Syst, California, CA USA.
[Ebrahimi, Ramin] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD OCT 12
PY 2008
VL 102
IS 8A
BP 217I
EP 217I
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 360YM
UT WOS:000260094700541
ER
PT J
AU Hill, DR
Ryan, ET
AF Hill, David R.
Ryan, Edward T.
TI Management of travellers' diarrhoea
SO BRITISH MEDICAL JOURNAL
LA English
DT Review
ID NORTH-AMERICAN TRAVELERS; IRRITABLE-BOWEL-SYNDROME; DOUBLE-BLIND;
BISMUTH SUBSALICYLATE; ESCHERICHIA-COLI; PLUS LOPERAMIDE; MEXICO; TRIAL;
RIFAXIMIN; PLACEBO
C1 [Hill, David R.] Hosp Trop Dis, Natl Travel Hlth Network & Ctr, London WC1E 6JB, England.
[Hill, David R.] Hosp Trop Dis, London Sch Hyg & Trop Med, London WC1E 6JB, England.
[Ryan, Edward T.] Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, Boston, MA 02114 USA.
[Ryan, Edward T.] Massachusetts Gen Hosp, Trop & Geog Med Ctr, Boston, MA 02114 USA.
RP Hill, DR (reprint author), Hosp Trop Dis, Natl Travel Hlth Network & Ctr, London WC1E 6JB, England.
EM david.hill@uclh.org
NR 34
TC 11
Z9 11
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD OCT 11
PY 2008
VL 337
IS 7674
AR a1746
DI 10.1136/bmj.a1746
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 358FU
UT WOS:000259903300036
PM 18838421
ER
PT J
AU Shipman, C
Gysels, M
White, P
Worth, A
Murray, SA
Barclay, S
Forrest, S
Shepherd, J
Dale, J
Dewar, S
Peters, M
White, S
Richardson, A
Lorenz, K
Koffman, J
Higginson, IJ
AF Shipman, Cathy
Gysels, Marjolein
White, Patrick
Worth, Allison
Murray, Scott A.
Barclay, Stephen
Forrest, Sarah
Shepherd, Jonathan
Dale, Jeremy
Dewar, Steve
Peters, Marilyn
White, Suzanne
Richardson, Alison
Lorenz, Karl
Koffman, Jonathan
Higginson, Irene J.
TI Improving generalist end of life care: national consultation with
practitioners, commissioners, academics, and service user groups
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID PRIMARY PALLIATIVE CARE; GOLD-STANDARDS-FRAMEWORK; CANCER; DEATH;
COMMUNICATION; COUNTRIES; TRENDS; FAMILY; PLACE; DIE
AB Objective To identify major concerns of national and local importance in the provision, commissioning, research, and use of generalist end of life care.
Design A national consultation and prioritising exercise using a modified form of the nominal group technique.
Participants Healthcare practitioners, commissioners, academics, and representatives of user and voluntary groups.
Setting Primary and secondary care, specialist palliative care, and academic and voluntary sectors in England and Scotland.
Results 74% of those invited ( 210/ 285) participated. The stage of life to which "end of life care" referred was not understood in a uniform way. Perceptions ranged from a period of more than a year to the last few days of life. Prominent concerns included difficulties in prognosis and the availability of adequate support for patients with advanced non- malignant disease. Generalists in both primary and secondary care were usually caring for only a few patients approaching the end of life at any one time at a point in time. It was therefore challenging to maintain skills and expertise particularly as educational opportunities were often limited. End of life care took place among many other competing and incentivised activities for general practitioners in the community. More needs to be known about models of end of life care and how these can be integrated in a generalist's workload. A greater evidence base is needed about the effectiveness and application of current tools such as the gold standards framework and Liverpool care pathway and about models of palliation in patients with diseases other than cancer.
Conclusions Definitions of end of life care need clarification and standardisation. A greater evidence base is needed to define models of good practice together with a commitment to provide education and training and adequate resources for service provision. More needs to be known about the context of provision and the influence of competing priorities and incentives.
C1 [Shipman, Cathy; Gysels, Marjolein; Koffman, Jonathan; Higginson, Irene J.] Kings Coll London, Dept Palliat Care Policy & Rehabil, Weston Educ Ctr, London SE5 9RJ, England.
[Shipman, Cathy; White, Patrick; Peters, Marilyn; White, Suzanne] Kings Coll London, Dept Gen Practice & Primary Care, London SE11 6SP, England.
[Worth, Allison; Murray, Scott A.] Univ Edinburgh, Primary Palliat Care Res Grp, Edinburgh EH8 9DX, Midlothian, Scotland.
[Barclay, Stephen; Forrest, Sarah] Univ Cambridge, Gen Practice & Primary Care Res Unit, Dept Publ Hlth & Primary Care, Cambridge CB2 2SR, England.
[Shepherd, Jonathan; Dale, Jeremy] Univ Warwick, Ctr Primary Hlth Care Studies, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Dewar, Steve] Kings Fund, London W1G 0AN, England.
[Richardson, Alison] Kings Coll London, Florence Nightingale Sch Nursing & Midwifery, London SE1 8WA, England.
[Lorenz, Karl] Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
RP Shipman, C (reprint author), Kings Coll London, Dept Palliat Care Policy & Rehabil, Weston Educ Ctr, London SE5 9RJ, England.
EM Catherine.shipman@kcl.ac.uk
RI green, sam/C-2608-2008;
OI Barclay, Stephen/0000-0002-4505-7743; White,
Patrick/0000-0002-2047-8787; Dale, Jeremy/0000-0001-9256-3553
FU National Institute of Health Research Service Development and
Organisation research and development programme
FX National Institute of Health Research Service Development and
Organisation research and development programme.
NR 42
TC 67
Z9 67
U1 2
U2 12
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD OCT 11
PY 2008
VL 337
IS 7674
AR a1720
DI 10.1136/bmj.a1720
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 358FU
UT WOS:000259903300032
PM 18829640
ER
PT J
AU Sugiana, C
Pagliarini, DJ
McKenzie, M
Kirby, DM
Salemi, R
Abu-Amero, KK
Dahl, HHM
Hutchison, WM
Vascotto, KA
Smith, SM
Newbold, RF
Christodoulou, J
Calvo, S
Mootha, VK
Ryan, MT
Thorburn, DR
AF Sugiana, Canny
Pagliarini, David J.
McKenzie, Matthew
Kirby, Denise M.
Salemi, Renato
Abu-Amero, Khaled K.
Dahl, Hans-Henrik M.
Hutchison, Wendy M.
Vascotto, Katherine A.
Smith, Stacey M.
Newbold, Robert F.
Christodoulou, John
Calvo, Sarah
Mootha, Vamsi K.
Ryan, Michael T.
Thorburn, David R.
TI Mutation of C20orf7 Disrupts Complex I Assembly and Causes Lethal
Neonatal Mitochondrial Disease
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID RESPIRATORY-CHAIN DISORDERS; CYTOCHROME-C-OXIDASE; LEIGH-SYNDROME;
ENCODED SUBUNITS; DEFICIENCY; GENE; PROTEIN; ENCEPHALOMYOPATHY;
SUPERCOMPLEXES; ENCEPHALOPATHY
AB Complex I (NADH:ubiquinone oxidoreductase) is the first and largest multimeric complex of the mitochondrial respiratory chain. Human complex I comprises seven Subunits encoded by mitochondrial DNA and 38 nuclear-encoded subunits that are assembled together in a process that is only partially understood. To date, Mutations causing complex I deficiency have been described in all 14 core subunits, five supernumerary Subunits, and four assembly factors. We describe complex I deficiency caused by mutation of the putative complex I assembly factor C20orf7. A candidate region for a lethal neonatal form of complex I deficiency was identified by homozygosity mapping of an Egyptian family with one affected child and two affected pregnancies predicted by enzyme-based prenatal diagnosis. The region was confirmed by microcell-mediated chromosome transfer, and 11 candidate genes encoding potential mitochondrial proteins were sequenced. A homozygous missense mutation in C20orf7 segregated with disease in the family. We show that C20orf7 is peripherally associated with the matrix face of the mitochondrial inner membrane and that silencing its expression with RNAi decreases complex I activity. C20orf7 patient fibroblasts showed an almost cornplete absence of complex I holoenzyme and were defective at all early stage of complex I assembly, but in a manner distinct from the assembly defects caused by mutations in the assembly factor NDUFAF1. Our results indicate that C20orf7 is crucial in the assembly of complex I and that mutations in C20orf7 cause mitochondrial disease.
C1 [Sugiana, Canny; Kirby, Denise M.; Salemi, Renato; Vascotto, Katherine A.; Smith, Stacey M.; Thorburn, David R.] Royal Childrens Hosp, Mitochondrial & Metab Res Grp, Parkville, Vic 3052, Australia.
[Dahl, Hans-Henrik M.; Hutchison, Wendy M.] Royal Childrens Hosp, Murdoch Childresn Res Inst, Genet Hearing Res Grp, Parkville, Vic 3052, Australia.
[Sugiana, Canny; Thorburn, David R.] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia.
[Pagliarini, David J.; Calvo, Sarah; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Pagliarini, David J.; Calvo, Sarah; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA.
[Pagliarini, David J.; Calvo, Sarah; Mootha, Vamsi K.] MIT, Broad Inst, Cambridge, MA 02142 USA.
[Pagliarini, David J.; Calvo, Sarah; Mootha, Vamsi K.] Harvard Univ, Cambridge, MA 02142 USA.
[McKenzie, Matthew; Ryan, Michael T.] La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia.
[Kirby, Denise M.; Thorburn, David R.] Royal Childrens Hosp, Genet Hlth Serv Victoria, Melbourne, Vic 3052, Australia.
[Abu-Amero, Khaled K.] King Saud Univ, Coll Med, Mol Genet Lab, Riyadh 11461, Saudi Arabia.
[Newbold, Robert F.] Brunel Univ, Inst Cancer Genet & Pharmacogenom, Uxbridge UB8 3PH, Middx, England.
[Christodoulou, John] Childrens Hosp, Western Sydney Genet Program, Westmead, NSW 2145, Australia.
[Christodoulou, John] Univ Sydney, Discipline Paediat, Westmead, NSW 2145, Australia.
[Christodoulou, John] Univ Sydney, Discipline Child Hlth & Genet Med, Westmead, NSW 2145, Australia.
RP Thorburn, DR (reprint author), Royal Childrens Hosp, Mitochondrial & Metab Res Grp, Flemington Rd, Parkville, Vic 3052, Australia.
EM david.thorburn@mcri.edu.au
RI Ryan, Michael/C-6673-2011; Thorburn, David/G-6266-2013; Christodoulou,
John/E-5866-2015;
OI Ryan, Michael/0000-0003-2586-8829; thorburn, david/0000-0002-7725-9470;
Christodoulou, John/0000-0002-8431-0641; McKenzie,
Matthew/0000-0001-7508-1800; Pagliarini, Dave/0000-0002-0001-0087
FU Australian National Health; Medical Research Council; Australian
Research Council; University of Melbourne; Muscular Dystrophy
Association; Ramaciotti Foundation; National Institutes of Health
[GM077465]
FX We thank Andrew Cuthbert for advice on monochromosomal transfer. This
work was supported by grants (D.R.T. and M.T.R.), postdoctoral
fellowships (M.McK. and D.M.K.), and a principal research fellowship
(D.R.T.) from the Australian National Health and Medical Research
Council and a grant from the Australian Research Council (M.T.R.). C.S.
was supported by a University of Melbourne postgraduate research
scholarship. Grant funding was also received from the Muscular Dystrophy
Association (D.R.T.), the Ramaciotti Foundation (M.McK.), and the
National Institutes of Health (GM077465) (V.K.M.).
NR 58
TC 104
Z9 107
U1 0
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD OCT 10
PY 2008
VL 83
IS 4
BP 468
EP 478
DI 10.1016/j.ajhg.2008.09.009
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 363AV
UT WOS:000260239200004
PM 18940309
ER
PT J
AU Kim, HG
Kurth, I
Lan, F
Meliciani, I
Wenzel, W
Eom, SH
Kang, GB
Rosenberger, G
Tekin, M
Ozata, M
Bick, DP
Sherins, RJ
Walker, SL
Shi, Y
Gusella, JF
Layman, LC
AF Kim, Hyung-Goo
Kurth, Ingo
Lan, Fei
Meliciani, Irene
Wenzel, Wolfgang
Eom, Soo Hyun
Kang, Gil Bu
Rosenberger, Georg
Tekin, Mustafa
Ozata, Metin
Bick, David P.
Sherins, Richard J.
Walker, Steven L.
Shi, Yang
Gusella, James F.
Layman, Lawrence C.
TI Mutations in CHD7, Encoding a Chromatin-Remodeling Protein, Cause
Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID CHARGE-SYNDROME; HORMONE RECEPTOR; HISTONE H3; GENE; CHROMODOMAINS;
FAMILY; PREVALENCE; MOLECULES; ADHESION; NEURONS
AB CHARGE syndrome and Kallmann syndrome (KS) are two distinct developmental disorders sharing overlapping features of impaired olfaction and hypogonadism. KS is a genetically heterogeneous disorder consisting of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia, and is most commonly due to KAL1 or FGFR1 mutations. CHARGE syndrome, a multisystem autosomal-dominant disorder, is caused by CHD7 mutations. We hypothesized that CHD7 would be involved in the pathogenesis of IHH and KS (IHH/KS) without the CHARGE phenotype and that IHH/KS represents a milder allelic variant of CHARGE syndrome. Mutation screening of the 37 protein-coding exons of CHD7 was performed in 101 IHH/KS patients without a CHARGE phenotype. In an additional 96 IHH/KS patients, exons 6-10, encoding the conserved chromodomains, were sequenced. RT-PCR, SIFT, protein-structure analysis, and in situ hybridization were performed for additional supportive evidence. Seven heterozygous mutations, two splice and five missense, which were absent in >= 180 controls, were identified in three sporadic KS and four sporadic normosmic IHH patients. Three mutations affect chromodomains critical for proper CHD7 function in chromatin remodeling and transcriptional regulation, whereas the other four affect conserved residues, suggesting that they are deleterious. CHD7's role is further corroborated by specific expression in IHH/KS-relevant tissues and appropriate developmental expression. Sporadic CHD7 mutations occur in 6% of IHH/KS patients. CHD7 represents the first identified chromatin-remodeling protein with a role in human puberty and the second gene to cause both normosmic IHH and KS in humans. Our findings indicate that both normosmic IHH and KS are mild allelic variants of CHARGE syndrome and are caused by CHD7 mutations.
C1 [Walker, Steven L.; Layman, Lawrence C.] Med Coll Georgia, Dept Obstet & Gynecol, Sect Reprod Endocrinol Infertil & Genet, Augusta, GA 30912 USA.
[Walker, Steven L.; Layman, Lawrence C.] Med Coll Georgia, Inst Mol Med & Genet, Reprod Med Program, Augusta, GA 30912 USA.
[Walker, Steven L.; Layman, Lawrence C.] Med Coll Georgia, Inst Mol Med & Genet, Dev Neuobiol Program, Augusta, GA 30912 USA.
[Kim, Hyung-Goo; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA.
[Kim, Hyung-Goo; Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Kurth, Ingo; Rosenberger, Georg] Univ Klinikum Hamburg Eppendorf, Inst Human Genet, D-20246 Hamburg, Germany.
[Lan, Fei; Shi, Yang] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Meliciani, Irene] Univ Roma La Sapienza, Fac Sci, I-00185 Rome, Italy.
[Wenzel, Wolfgang] Forschungszentrum Karlsruhe, Inst Nanotechnol, D-76021 Karlsruhe, Germany.
[Eom, Soo Hyun; Kang, Gil Bu] Gwangju Inst Sci & Technol, Cell Dynam Res Ctr, Dept Life Sci, Kwangju 500712, South Korea.
[Tekin, Mustafa] Ankara Univ, Sch Med, Dept Pediat, Div Clin Mol Pathol & Genet, TR-06100 Ankara, Turkey.
[Ozata, Metin] GATA Haydarpasa Training Hosp, Dept Endocrinol, TR-34660 Istanbul, Turkey.
[Bick, David P.] Med Coll Wisconsin, Dept Pediat, Div Med Genet, Milwaukee, WI 53226 USA.
[Bick, David P.] Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA.
[Sherins, Richard J.] Columbia Fertil Associates, Washington, DC 20037 USA.
[Walker, Steven L.; Layman, Lawrence C.] Med Coll Georgia, Neurosci Program, Augusta, GA 30912 USA.
RP Layman, LC (reprint author), Med Coll Georgia, Dept Obstet & Gynecol, Sect Reprod Endocrinol Infertil & Genet, 1120 15th st, Augusta, GA 30912 USA.
EM Ilayman@mcg.edu
RI Wenzel, Wolfgang/B-3207-2009;
OI Wenzel, Wolfgang/0000-0001-9487-4689; Kurth, Ingo/0000-0002-5642-8378
FU National Institutes of Health (NIH) [HD33004, HD040287]; Medical College
of Georgia Research Institute (MCGRI); NIH [GM061354]; Deutsche
Forschungsgemeinschaft (DFG) [WE1863/10-2]; DFG Center for Functional
Nanostructures; EU Leonardo program "Unipharm Graduates
FX We thank all affected individuals and their families for their
cooperation. The authors also thank I. Hermans-Borgmeyer for
unrestricted support with the in situ hybridizations and interpretation
of the data; B. Dierkes for excellent technical assistance; G.
Schnitzler for helpful discussions; E. Moutevelis for
leucine-zipper-domain structure analysis; the Computational Science
Center, KIST (Seoul, Korea), and the volunteers from POEM@HOME for
computational resources; Y. Shen for RT-MLPA; S. West for zinc-finger
prediction analysis; L. Chorich for her efforts in supervising and
running the laboratory; and E. Shah for RT-PCR analysis.; We also
acknowledge support to L.C.L. from National Institutes of Health (NIH)
grants HD33004 and HD040287, as well as the Medical College of Georgia
Research Institute (MCGRI), Dean D.D. Miller, Institute of Molecular
Medicine and Genetics (IM-MAG) director R. Yu, and ob/gyn chair A.A.
Murphy at MCG. J.F.G. has support from NIH grant GM061354, W.W. from
Deutsche Forschungsgemeinschaft (DFG) grant WE1863/10-2 and the DFG
Center for Functional Nanostructures, and I.M. from the EU Leonardo
program "Unipharm Graduates."
NR 42
TC 134
Z9 138
U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD OCT 10
PY 2008
VL 83
IS 4
BP 511
EP 519
DI 10.1016/j.ajhg.2008.09.005
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 363AV
UT WOS:000260239200009
PM 18834967
ER
PT J
AU Marban, E
Braunwald, E
AF Marban, Eduardo
Braunwald, Eugene
TI Training the clinician investigator
SO CIRCULATION RESEARCH
LA English
DT Editorial Material
C1 [Marban, Eduardo] Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA.
[Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA.
RP Marban, E (reprint author), Cedars Sinai Heart Inst, 8700 Beverly Blvd, Los Angeles, CA 90048 USA.
EM eduardo.marban@csmc.edu
NR 0
TC 2
Z9 2
U1 0
U2 2
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 OCT 10
PY 2008
VL 103
IS 8
BP 771
EP 772
DI 10.1161/CIRCRESAHA.108.186791
PG 2
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 358NX
UT WOS:000259925900001
PM 18845813
ER
PT J
AU Mack, JW
Joffe, S
Hilden, JM
Watterson, J
Moore, C
Weeks, JC
Wolfe, J
AF Mack, Jennifer W.
Joffe, Steven
Hilden, Joanne M.
Watterson, Jan
Moore, Caron
Weeks, Jane C.
Wolfe, Joanne
TI Parents' views of cancer-directed therapy for children with no realistic
chance for cure
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ORAL ETOPOSIDE; PHASE-I; TREATMENT PREFERENCES; CHEMOTHERAPY USE;
NURSING RESEARCH; OVARIAN-CANCER; LIFE; END; CARE; AGGRESSIVENESS
AB Purpose Previous literature suggests that parents often wish to continue cancer-directed therapy for their children with incurable cancer. We assessed parents' experiences with treatment for their children with cancer and no realistic chance of cure. Patients and Methods We administered questionnaires to 141 parents of children with cancer who died after receiving care at one of two cancer centers. Parents were asked whether the child benefited and suffered from treatment administered after the parent recognized that cure was not a realistic expectation, and whether they would recommend cancer-directed therapy to other families of children with advanced cancer. Results Fifty-three (38%) of 141 children received cancer-directed therapy after the parent recognized that the child had no realistic chance for cure. Most of these parents felt that their child had experienced at least some suffering resulting from the therapy (61%, 31 of 51) and little to no benefit (57%, 29 of 51). Fifty-one (38%) of 135 parents overall would recommend standard chemotherapy and 46 (33%) of 140 would recommend experimental chemotherapy to families of children with advanced cancer. Even parents who would not recommend standard chemotherapy generally felt the physician should offer it (91%, 88 of 97). Parents who reported that their children experienced suffering resulting from cancer-directed therapy ( odds ratio = 0.46; P = .02) were less likely to recommend standard chemotherapy to other families. Conclusion Although many parents choose treatment for their children with incurable cancer, bereaved parents often would not recommend such therapy. Parents who felt their children suffered as a result of cancer treatment were particularly unlikely to recommend it.
C1 [Mack, Jennifer W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
Childrens Hosp, Dept Med, Boston, MA 02115 USA.
Peyton Manning Childrens Hosp St Vincent, Dept Pediat, Indianapolis, IN USA.
Childrens Hosp & Clin, Dept Pediat Hematol Oncol, St Paul, MN USA.
RP Mack, JW (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA.
EM Jennifer_mack@dfci.harvard.edu
OI Joffe, Steven/0000-0002-0667-7384
FU National Cancer Institute [NCI 5 K07 CA 096746]; American Society of
Clinical Oncology
FX Supported by Grant No. NCI 5 K07 CA 096746 from the National Cancer
Institute (J.W) and a Career Development Award from the American Society
of Clinical Oncology (J.W.M.).
NR 32
TC 38
Z9 38
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 OCT 10
PY 2008
VL 26
IS 29
BP 4759
EP 4764
DI 10.1200/JCO.2007.15.6059
PG 6
WC Oncology
SC Oncology
GA 358FP
UT WOS:000259902800012
PM 18779605
ER
PT J
AU Chanan-Khan, A
Sonneveld, P
Schuster, MW
Stadtmauer, EA
Facon, T
Harousseau, JL
Ben-Yehuda, D
Lonial, S
Goldschmidt, H
Reece, D
Neuwirth, R
Anderson, KC
Richardson, PG
AF Chanan-Khan, Asher
Sonneveld, Pieter
Schuster, Michael W.
Stadtmauer, Edward A.
Facon, Thierry
Harousseau, Jean-Luc
Ben-Yehuda, Dina
Lonial, Sagar
Goldschmidt, Hartmut
Reece, Donna
Neuwirth, Rachel
Anderson, Kenneth C.
Richardson, Paul G.
TI Analysis of herpes zoster events among bortezomib-treated patients in
the phase III APEX study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 48th Annual Meeting of the American-Society-of-Hematology
CY DEC 09-12, 2006
CL Orlando, FL
SP Amer Soc Hematol
ID PROTEASOME INHIBITOR BORTEZOMIB; RELAPSED MULTIPLE-MYELOMA; REFRACTORY
MYELOMA; VIRUS-INFECTION; CELLS; APOPTOSIS; DISEASE
AB Purpose The aim of this subset analysis was to determine if bortezomib treatment is associated with increased incidence of varicella-zoster virus (VZV) reactivation in patients with relapsed multiple myeloma (MM). Patients and Methods Incidence of herpes zoster was evaluated in 663 patients with relapsed MM from the phase III APEX trial comparing single-agent bortezomib with high-dose dexamethasone. Results Bortezomib was associated with a significantly higher incidence of herpes zoster compared with dexamethasone treatment (13%, 42 of 331 v 5%, 15 of 332; P = .0002). Most herpes zoster infections were grade 1/2; incidences of grade 3/4 events (1.8% v 1.5%) and infections considered serious adverse events (1.5% v 0.9%) were similar between treatment arms, and no herpes zoster-related deaths occurred. Neither the time to onset of the herpes event nor the patients' absolute lymphocyte counts at baseline differed significantly between arms. VZV reactivation was the only herpes viral event noted to be significantly elevated in the bortezomib treatment group compared with the dexamethasone treatment group (P = 0002). The incidence of non-VZV-related herpes viral infections was comparable between arms. No additional risk factors for herpes zoster reactivation were identified. Conclusion Further studies are needed to explain these observations and their implications; however, for patients treated with bortezomib or bortezomib-containing regimens, the risk of VZV reactivation should be monitored and routine use of antiviral prophylaxis considered.
C1 [Chanan-Khan, Asher] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
New York Presbyterian Hosp, New York, NY USA.
Alta Bates Canc Ctr, Berkeley, CA USA.
Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA.
Emory Univ, Atlanta, GA 30322 USA.
Millennium Pharmaceut Inc, Cambridge, MA USA.
Dana Farber Canc Inst, Boston, MA USA.
Univ Rotterdam Hosp, Rotterdam, Netherlands.
Hosp Claude Huriez, Lille, France.
Hop Hotel Dieu, Nantes, France.
Hadassah Univ Hosp, IL-91120 Jerusalem, Israel.
Univ Klinikum Heidelberg, Heidelberg, Germany.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
RP Chanan-Khan, A (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA.
EM asher.chanan-khan@roswellpark.org
RI FACON, THIERRY/M-9736-2014
OI FACON, THIERRY/0000-0001-7705-8460
NR 26
TC 130
Z9 133
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 10
PY 2008
VL 26
IS 29
BP 4784
EP 4790
DI 10.1200/JCO.2007.14.9641
PG 7
WC Oncology
SC Oncology
GA 358FP
UT WOS:000259902800016
PM 18711175
ER
PT J
AU Bracht, LK
Wen, P
Meyerhardt, JA
Kulke, MH
Hornick, JL
Redston, M
LaFrankie, DC
Black, PM
Kesari, S
Norden, A
Drappatz, J
AF Bracht, Lynn-Kristin
Wen, Patrick
Meyerhardt, Jeffrey A.
Kulke, Matthew H.
Hornick, Jason L.
Redston, Mark
LaFrankie, Debra Conrad
Black, Peter M.
Kesari, Santosh
Norden, Andrew
Drappatz, Jan
TI DNA repair enzyme expression and differential response to temozolomide
in a patient with both glioblastoma and metastatic pancreatic
neuroendocrine tumor
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID MGMT
C1 [Bracht, Lynn-Kristin] Ctr Neurooncol, Boston, MA USA.
[Bracht, Lynn-Kristin] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Dana Farber Brigham & Womens Canc Ctr,Ctr Neuroon, Boston, MA 02115 USA.
[Bracht, Lynn-Kristin] Univ Gottingen, Univ Klinikum, Fak Med, Gottingen, Germany.
[Meyerhardt, Jeffrey A.; Kulke, Matthew H.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA USA.
[Hornick, Jason L.; Redston, Mark] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Redston, Mark] AmeriPath Inc, Palm Beach Gardens, FL USA.
[Black, Peter M.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
RP Bracht, LK (reprint author), Ctr Neurooncol, Boston, MA USA.
RI Kesari, Santosh/E-8461-2013
NR 7
TC 2
Z9 2
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 10
PY 2008
VL 26
IS 29
BP 4843
EP 4844
DI 10.1200/JCO.2008.18.1776
PG 2
WC Oncology
SC Oncology
GA 358FP
UT WOS:000259902800024
PM 18779600
ER
PT J
AU Gazzin, S
Strazielle, N
Schmitt, C
Fevre-Montange, M
Ostrow, JD
Tiribelli, C
Ghersi-Egea, JF
AF Gazzin, Silvia
Strazielle, Nathalie
Schmitt, Charlotte
Fevre-Montange, Michelle
Ostrow, J. Donald
Tiribelli, Claudio
Ghersi-Egea, Jean-Francois
TI Differential expression of the multidrug resistance-related proteins
ABCb1 and ABCc1 between blood-brain interfaces
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE blood-brain barrier; choroid plexus; postnatal development;
neuroprotection
ID P-GLYCOPROTEIN EXPRESSION; CHOROID-PLEXUS; ENDOTHELIAL-CELLS; RAT-BRAIN;
POSTNATAL MATURATION; BARRIER; TRANSPORT; MRP1; EFFLUX; DRUGS
AB Cerebral homeostasis results from the presence of the protective blood-brain and blood-cerebrospinal fluid barriers located respectively at the brain capillary endothelium and the choroid plexus epithelium. ABCb1. (Pgp) and ABCc1 (Mrp1) transporters are two major proteins of neuroprotection whose localization and functional significance at both barriers remain partly unsettled. We conducted a comparative analysis of their relative protein content between the two blood-brain interfaces. Microvessels and choroid plexuses located in the fourth and lateral ventricles were isolated from developing and adult rat brains, and whole homogenates were submitted to quantitative Western blot analysis by using standard curves generated from one of the samples. In adult, choroid plexus-associated Pgp content was less than 0.5% of the level in microvessels, whereas Mrp1 content in microvessels was 4% of that in the fourth ventricle choroid plexus. Pgp but not Mrp1 was enriched in microvessels over parenchyma. In choroid plexuses, Mrp1 displayed a basolateral epithelial localization, and reached its high adult protein level, early during postnatal development. In postnatal as in adult microvessels, Pgp localization appeared luminal. However, by contrast to Mrp1, the level of this transporter increased 4.6-fold between 9-day-old and adult animals. Western blot analysis of human samples confirmed the mirror image of Pgp and Mrp1. expression between the two barriers. We conclude that there are major differences in the mechanisms by which blood-brain interfaces fulfill their neuroprotective functions. The data also highlight the significance of the neuroprotective function of the choroid plexus during brain maturation, when the microvasculature is still developing.
C1 [Gazzin, Silvia; Strazielle, Nathalie; Schmitt, Charlotte; Fevre-Montange, Michelle; Ghersi-Egea, Jean-Francois] Univ Lyon, INSERM, U842, Fac Med Laennec, F-69372 Lyon, France.
[Gazzin, Silvia; Tiribelli, Claudio] Univ Trieste, Ctr Fegato, Basovizza & Dept Life Sci, I-34012 Trieste, Italy.
[Strazielle, Nathalie] Brain i, F-69008 Lyon, France.
[Ostrow, J. Donald] Univ Washington, Sch Med, Div Gastroenterol Hepatol, Seattle, WA 98195 USA.
[Ostrow, J. Donald] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98195 USA.
RP Ghersi-Egea, JF (reprint author), Univ Lyon, INSERM, U842, Fac Med RTH Laennec, Rue Guillaume Paradin, F-69372 Lyon 08, France.
EM jean-francois.ghersi-egea@inserm.fr
OI Ghersi-Egea, Jean-Francois/0000-0002-0181-4909
FU ANR [ANR-06-SEST-38-03]; Amelie la vie-ANOCEF; Telethon (Italy) [GGP
05062]
FX Grant sponsor ANR; Grant number: ANR-06-SEST-38-03; Grant sponsor:
Amelie la vie-ANOCEF; (to J.F.G.E.); Grant sponsor: Telethon (Italy):
Grant number: GGP 05062 (to C.T.).
NR 47
TC 72
Z9 73
U1 1
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD OCT 10
PY 2008
VL 510
IS 5
BP 497
EP 507
DI 10.1002/cne.21808
PG 11
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 347ES
UT WOS:000259124000004
PM 18680196
ER
PT J
AU Imamura, S
Uchiyama, J
Koshimizu, E
Hanai, JI
Raftopoulou, C
Murphey, RD
Bayliss, PE
Imai, Y
Burns, CE
Masutomi, K
Gagos, S
Zon, LI
Roberts, TM
Kishi, S
AF Imamura, Shintaro
Uchiyama, Junzo
Koshimizu, Eriko
Hanai, Jun-ichi
Raftopoulou, Christina
Murphey, Ryan D.
Bayliss, Peter E.
Imai, Yoichi
Burns, Caroline Erter
Masutomi, Kenkichi
Gagos, Sarantis
Zon, Leonard I.
Roberts, Thomas M.
Kishi, Shuji
TI A Non-Canonical Function of Zebrafish Telomerase Reverse Transcriptase
Is Required for Developmental Hematopoiesis
SO PLOS ONE
LA English
DT Article
AB Although it is clear that telomerase expression is crucial for the maintenance of telomere homeostasis, there is increasing evidence that the TERT protein can have physiological roles that are independent of this central function. To further examine the role of telomerase during vertebrate development, the zebrafish telomerase reverse transcriptase (zTERT) was functionally characterized. Upon zTERT knockdown, zebrafish embryos show reduced telomerase activity and are viable, but develop pancytopenia resulting from aberrant hematopoiesis. The blood cell counts in TERT-depleted zebrafish embryos are markedly decreased and hematopoietic cell differentiation is impaired, whereas other somatic lineages remain morphologically unaffected. Although both primitive and definitive hematopoiesis is disrupted by zTERT knockdown, the telomere lengths are not significantly altered throughout early development. Induced p53 deficiency, as well as overexpression of the anti-apoptotic proteins Bcl-2 and E1B-19K, significantly relieves the decreased blood cells numbers caused by zTERT knockdown, but not the impaired blood cell differentiation. Surprisingly, only the reverse transcriptase motifs of zTERT are crucial, but the telomerase RNA-binding domain of zTERT is not required, for rescuing complete hematopoiesis. This is therefore the first demonstration of a non-canonical catalytic activity of TERT, which is different from 'authentic'' telomerase activity, is required for during vertebrate hematopoiesis. On the other hand, zTERT deficiency induced a defect in hematopoiesis through a potent and specific effect on the gene expression of key regulators in the absence of telomere dysfunction. These results suggest that TERT non-canonically functions in hematopoietic cell differentiation and survival in vertebrates, independently of its role in telomere homeostasis. The data also provide insights into a non-canonical pathway by which TERT functions to modulate specification of hematopoietic stem/progenitor cells during vertebrate development. (276 words)
C1 [Imamura, Shintaro; Koshimizu, Eriko; Kishi, Shuji] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02115 USA.
[Uchiyama, Junzo; Bayliss, Peter E.; Roberts, Thomas M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA.
[Hanai, Jun-ichi] Beth Israel Deaconess Med Ctr, Dept Med, Renal Div, Boston, MA USA.
[Murphey, Ryan D.; Burns, Caroline Erter; Zon, Leonard I.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp Boston,Div Hematol Oncol, Boston, MA USA.
[Raftopoulou, Christina; Gagos, Sarantis] Biomed Res Fdn Acad Athens Greece, Lab Genet, Athens, Greece.
[Imai, Yoichi] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA.
[Masutomi, Kenkichi] Natl Canc Ctr, Canc Stem Cell Project, Tokyo, Japan.
RP Imamura, S (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02115 USA.
EM s.kishi@mac.com
FU A-T Childrens Project; Ellison Medical Foundation; NIA/NIH
FX This work is funded by research grants from the A-T Childrens Project,
the Ellison Medical Foundation and NIA/NIH to S.K..
NR 110
TC 28
Z9 28
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 OCT 10
PY 2008
VL 3
IS 10
AR e3364
DI 10.1371/journal.pone.0003364
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 432DU
UT WOS:000265114500005
PM 18846223
ER
PT J
AU Casali, M
Zambonelli, C
Goldwasser, J
Vu, HN
Yarmush, ML
AF Casali, Monica
Zambonelli, Carlo
Goldwasser, Jonathan
Vu, Halong N.
Yarmush, Martin L.
TI Moloney murine leukemia virus decay mediated by retroviral reverse
transcriptase degradation of genomic RNA
SO VIROLOGY
LA English
DT Article
DE gamma-retrovirus; moloney murine leukemia virus; virus decay; RNA and
protein stability; viral reverse transcriptase
ID RESPIRATORY SYNCYTIAL VIRUS; GENE-THERAPY; HUMAN SERUM; INFLUENZA-VIRUS;
VIRAL VECTORS; RECOMBINANT RETROVIRUSES; LIPID-PEROXIDATION; CELL-LINES;
TRANSDUCTION; MATURATION
AB Retroviral vectors are powerful tools for the introduction of transgenes into mammalian cells and for long-term gene expression. However, their application is often limited by a rapid loss of bioactivity: retroviruses spontaneously loose activity at 37 degrees C, with a half-life of 4 to 9 h depending on the retrovirus type. We sought to determine which components of the retrovirus are responsible for this loss in bioactivity and to obtain a quantitative characterization of their stability. To this end, we focused on RNA and viral proteins, two major components that we hypothesized may undergo degradation and negatively influence viral infectivity. Reverse transcription PCR (RT-PCR) targeting RNA encoding portions of the viral genome clearly demonstrated time-dependent degradation of RNA which correlated with the loss in viral bioactivity. Circular dichroism spectroscopy, SDS-PAGE and two-dimensional SDS-PAGE analyses of viral proteins did not show any change in secondary structure or evidence of proteolysis. The mechanism underlying the degradation of viral RNA was investigated by site-directed mutagenesis of proteins encoded by the viral genome. Reverse transcriptase and protease mutants exhibited enhanced RNA stability in comparison to wild type recombinant virus, suggesting that the degradation of RNA, and the corresponding virus loss of activity, is mediated by the reverse transcriptase enzyme. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Casali, Monica; Goldwasser, Jonathan; Vu, Halong N.; Yarmush, Martin L.] Harvard Univ, Sch Med, Shriners Burn Hosp,Ctr Engn Med, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA.
[Zambonelli, Carlo] Harvard Univ, Mol & Cellular Biol Dept, Cambridge, MA 02138 USA.
[Casali, Monica; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Mscataway, NJ 08854 USA.
RP Casali, M (reprint author), 51 Blossom St,Room 417, Boston, MA 02114 USA.
EM mcasali@hms.harvard.edu; ireis@sbi.org
FU National Science Foundation [CBET-0828244]
FX We would like to thank Dr. Zaki Megeed for useful discussions, Z. L.
Kelley for the excellent technical assistance and Dr. Xumbao Duan for
his help with the two-dimensional electrophoresis gel analysis. The
authors would like to thank also Professor Mary Roberts, Boston College
Chemistry Department, for the use of the CD instrument.; This work was
supported by National Science Foundation Grant CBET-0828244.
NR 57
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 0042-6822
J9 VIROLOGY
JI Virology
PD OCT 10
PY 2008
VL 380
IS 1
BP 91
EP 98
DI 10.1016/j.virol.2008.07.011
PG 8
WC Virology
SC Virology
GA 356TM
UT WOS:000259800500012
PM 18706668
ER
PT J
AU Wang, X
Qin, ZH
Shi, H
Savitz, SI
Qin, AP
Jiang, Y
Zhang, HL
AF Wang, Xuan
Qin, Zheng-Hong
Shi, Hong
Savitz, Sean Isaac
Qin, Ai-Ping
Jiang, Yan
Zhang, Hui-Ling
TI Protective effect of Ginkgolids (A plus B) is associated with inhibition
of NIK/IKK/I kappa B/NF-kappa B signaling pathway in a rat model of
permanent focal cerebral ischemia
SO BRAIN RESEARCH
LA English
DT Article
DE Ginkgolids (A plus B); Ischemia; Neuroprotection; NF-kappa B; NIK-IKK
ID CELL-DEATH; ACTIVATION; EXPRESSION; IKK; KINASE; ALPHA; PHOSPHORYLATION;
JNK
AB Background and purpose: We have previously reported that Ginkgolids which contain Ginkgolids A and B (Ginkgolids (A+B), GKAB) reduce infarct size in a rat model of focal ischemia. NF-kappa B-inducing kinase (NIK)I kappa B alpha kinase (IKK) pathway plays an important role in activation of nuclear factor kappaB (NF-kappa B). A previous study demonstrated that Ginkgolid B inhibited lipopolysaccharide (LPS)- and platelet activating factor (PAF)induced NF-kappa B activation in rat pleural polymorphonuclear granulocytes. However, little is known about the inhibitory mechanisms of Ginkgolids on the activation of NF-kappa B. The present study evaluated the effects of GKAB on NIK/IKK/I kappa B/NF-kappa B signaling pathway in a rat model of permanent focal cerebral ischemia.Methods: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by intraluminal suture blockade. GKAB was injected intravenously (iv) immediately after ischemic onset. Western blot analysis was employed to determine alterations in I kappa B alpha, phosphorylated NIK (p-NIK) and phosphorylated IKK alpha (p-IKK alpha). Immunohistochemistry was used to confirm the nuclear translocation of NF-kappa B p65. RT-PCR was used to detect induction of NF-kappa B target gene c-Myc mRNA. Results: The results showed a brief increase in p-NIK levels after ischemia. GKAB blocked ischemia-induced increases in p-NIK and p-IKK alpha levels, and reversed the decline in I kappa B alpha levels. Ischemia-induced nuclear translocation of NF-kappa B p65 was attenuated by GKAB. GKAB also repressed the ischemia-induced increase in expression of NF-KB target gene c-Myc mRNA. Conclusions: These findings suggest that
C1 [Wang, Xuan; Qin, Zheng-Hong; Qin, Ai-Ping; Zhang, Hui-Ling] Soochow Univ, Dept Pharmacol, Sch Med, Suzhou 215123, Peoples R China.
[Wang, Xuan; Qin, Zheng-Hong; Qin, Ai-Ping; Zhang, Hui-Ling] Soochow Univ, Dept Pharmacol, Lab Aging & Nervous Dis, Suzhou 215123, Peoples R China.
[Savitz, Sean Isaac; Jiang, Yan; Zhang, Hui-Ling] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
[Shi, Hong] Zhejiang Acad Med Sci, Dept Pharmacol, Hangzhou, Zhejiang, Peoples R China.
[Wang, Xuan] Shanghai Putuo Dist Peoples Hosp, Dept Pharm, Shanghai, Peoples R China.
RP Zhang, HL (reprint author), Soochow Univ, Dept Pharmacol, Sch Med, 199 Ren Ai Rd, Suzhou 215123, Peoples R China.
EM huilingzhang07@hotmail.com
FU Department of Education of Jinagsu Province [03KJB310123]; Natural
Science Foundation of Jiangsu Province [BK2004037]; Zhejiang Province
[Y205708]; Natural Science Foundation of China [30470587]
FX This work was supported by grants from the Department of Education of
Jinagsu Province (03KJB310123); The Natural Science Foundation of
Jiangsu Province (BK2004037) and Zhejiang Province (Y205708); and The
Natural Science Foundation of China (30470587).
NR 32
TC 11
Z9 15
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD OCT 9
PY 2008
VL 1234
BP 8
EP 15
DI 10.1016/j.brainres.2008.07.102
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 363RZ
UT WOS:000260285700002
PM 18722355
ER
PT J
AU Holschneider, DP
Yang, J
Sadler, TR
Galifianakis, NB
Bozorgzadeh, MH
Bading, JR
Conti, PS
Maarek, JMI
AF Holschneider, D. P.
Yang, J.
Sadler, T. R.
Galifianakis, N. B.
Bozorgzadeh, M. H.
Bading, J. R.
Conti, P. S.
Maarek, J. -M. I.
TI Changes in regional brain perfusion during functional brain activation:
Comparison of [Cu-64]-PTSM with [C-14]-Iodoantipyrine
SO BRAIN RESEARCH
LA English
DT Article
DE Brain mapping; Motor activity; Cerebral blood flow; Copper radioisotope
ID CEREBRAL-BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; GLUCOSE-METABOLISM;
PET; TRACER; COPPER-62-PTSM; RADIOPHARMACEUTICALS; EXTRACTION; WALKING;
MODEL
AB A dilemma in behavioral brain mapping is that conventional techniques immobilize the subject, extinguishing all but the simplest behaviors. This is avoided if brain activation is imaged after completion of the behavior and tissue capture of the tracer. A single-pass flow tracer proposed for positron emission tomography (PET) is a radiolabeled copper(II) complex of pyruvaldehyde bis(N-4-methylthiosemicarbazone), [Cu-64]-PTSM. [Cu-64]-PTSM reaches steady-state cerebral distribution more rapidly than the metabolic tracer [F-18]fluorodeoxyglucose, allowing imaging with substantially greater temporal resolution. Using dual-label autoradiography, this study compares the relative regional cerebral blood flow tracer distribution (CBF-TR) of [Cu-64]-PTSM to that of the classic perfusion tracer [C-14]-iodoantipyrine in a rat model during treadmill walking. Rats were exposed to continuous walking on a treadmill and compared to quiescent controls. [Cu-64]-PTSM was bolus injected (iv) after 1 min, followed by a 5-minute uptake and subsequent bolus injection of [C-14]-iodoantipyrine. CBF-TR was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping, as well as by region-of-interest analysis. A high homology was found between the [Cu-64] -PTSM and [C-14]-iodoantipyrine patterns of cerebral activation in cortical and subcortical regions. For white matter, however, [Cu-64] -PTSM showed lower perfusion than [Cu-14] -iodoantipyrine. [Cu-64]-PTSM is a useful tracer for functional brain mapping in freely-moving subjects. Its application in conjunction with PET promises to increase our understanding of the neural circuitry of behaviors dependent on locomotion. (c) 2008 Elsevier B.V. All rights reserved.
C1 [Holschneider, D. P.] Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, Los Angeles, CA 90089 USA.
[Holschneider, D. P.; Yang, J.] Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, Los Angeles, CA 90089 USA.
[Holschneider, D. P.; Galifianakis, N. B.] Univ So Calif, Dept Neurol, Keck Sch Med, Los Angeles, CA 90089 USA.
[Sadler, T. R.] Univ So Calif, Dept Pathol, Keck Sch Med, Los Angeles, CA 90089 USA.
[Bozorgzadeh, M. H.; Bading, J. R.; Conti, P. S.] Univ So Calif, Dept Radiol, Keck Sch Med, PET Imaging Sci Ctr, Los Angeles, CA 90089 USA.
[Holschneider, D. P.; Conti, P. S.; Maarek, J. -M. I.] Univ So Calif, Dept Biomed Engn, Viterbi Sch Engn, Los Angeles, CA 90089 USA.
[Holschneider, D. P.; Yang, J.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA.
RP Holschneider, DP (reprint author), Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, 1333 San Pablo St,BMT 403,MC 9112, Los Angeles, CA 90089 USA.
EM holschne@usc.edu
FU Mallinckrodt Institute at Washington University; NCI [5R24CA086307-03];
NIMH [R21 MH073000]; NCRR [S10 RR15703]
FX We would like to acknowledge Dr. X. Chen, Michel Tohme and Ryan Park,
for their technical help in conducting the dynamic PET study, Pooja
Sharma for her help with the selection of the regions of interest, and
Dr. Oscar U. Scremin for his comments AA regarding the manuscript.
[64CU] was obtained through the Research Resource in
Radionuclide Research at the Mallinckrodt Institute at Washington
University, St. Louis (NCI grant 5R24CA086307-03). Supported by grants
from NIMH #R21 MH073000 (DH) and NCRR S10 RR15703 (PC).
NR 35
TC 6
Z9 6
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD OCT 9
PY 2008
VL 1234
BP 32
EP 43
DI 10.1016/j.brainres.2008.07.038
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 363RZ
UT WOS:000260285700005
PM 18687316
ER
PT J
AU Ay, I
Francis, JW
Brown, RH
AF Ay, Ilknur
Francis, Jonathan W.
Brown, Robert H., Jr.
TI VEGF increases blood-brain barrier permeability to Evans blue dye and
tetanus toxin fragment C but not adeno-associated virus in ALS mice
SO BRAIN RESEARCH
LA English
DT Article
DE BBB; VEGF; Evans blue dye; Tetanus toxin fragment C; AAV2/5; SOD1(G93A)
mice
ID ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; CEREBRAL-ISCHEMIA;
VIRAL VECTORS; NITRIC-OXIDE; DELIVERY; ANGIOGENESIS; DISRUPTION;
CHEMOTHERAPY; EXPRESSION
AB Entry of most compounds into the CNS is impeded by the blood-brain barrier (BBB). Because vascular endothelial growth factor (VEGF) is important in the formation and maintenance of the BBB and is known to modulate BBB permeability in newborn rodents, we tested the hypothesis that VEGF may enhance BBB permeability in adult mice. We examined the effect of VEGF on the CNS distribution of three different agents: a small molecule (Evans blue dye) that is known to bind plasma proteins, an exogenous protein (tetanus toxin fragment C; TTC), and a viral vector (recombinant adeno-associated virus serotype 2/5 marked with lacZ; rAAV2/S-lacZ). Pretreatment with VEGF (20 mu g; i.v.) increased permeability of the BBB to Evans blue dye and TTC as detected by augmented concentrations of these substances in the cerebrum, brainstem, and spinal cord. By contrast, VEGF did not alter BBB permeability to AAV2/S-lacZ, as defined by beta-galactosidase activity assay. These data demonstrate the potential utility of VEGF for pharmacological modulation of the BBB, and indicate that increase in BBB permeability mediated by VEGF is limited by the size of the delivered substance. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Ay, Ilknur; Francis, Jonathan W.; Brown, Robert H., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Day Neuromuscular Res Lab, Charlestown, MA USA.
RP Ay, I (reprint author), Massachusetts Gen Hosp East, AA Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Boston, MA 02129 USA.
EM iay@partners.org
FU NIA; NINDS; ALS Association; Angel Fund; Al-Athel ALS Research
Foundation; ALS Research Foundation; Muscular Dystrophy Association
FX We thank Drs. Michele M. Maxwell and Zhanyun Fan for their assistance
with these experiments. Robert H. Brown, Jr receives support from the
NIA and NINDS, Project ALS, the ALS Association, the Angel Fund, the
Al-Athel ALS Research Foundation, and the Pierre L. deBourghknect ALS
Research Foundation. Jonathan W. Francis is supported by NINDS and the
Muscular Dystrophy Association.
NR 32
TC 26
Z9 26
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD OCT 9
PY 2008
VL 1234
BP 198
EP 205
DI 10.1016/j.brainres.2008.07.121
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 363RZ
UT WOS:000260285700021
PM 18725212
ER
PT J
AU Viatour, P
Somervaille, TC
Venkatasubrahmanyam, S
Kogan, S
McLaughlin, ME
Weissman, IL
Butte, AJ
Passegue, E
Sage, J
AF Viatour, Patrick
Somervaille, Tim C.
Venkatasubrahmanyam, Shivkumar
Kogan, Scott
McLaughlin, Margaret E.
Weissman, Irving L.
Butte, Atul J.
Passegue, Emmanuelle
Sage, Julien
TI Hematopoietic Stem Cell Quiescence Is Maintained by Compound
Contributions of the Retinoblastoma Gene Family
SO CELL STEM CELL
LA English
DT Article
ID BONE-MARROW MICROENVIRONMENT; SELF-RENEWAL; TUMOR-SUPPRESSOR; CYCLE; RB;
MICE; STRESS; ERYTHROPOIESIS; LEUKEMIA; BMI-1
AB Individual members of the retinoblastoma (Rb) tumor suppressor gene family serve critical roles in the control of cellular proliferation and differentiation, but the extent of their contributions is masked by redundant and compensatory mechanisms. Here we employed a conditional knockout strategy to simultaneously inactivate all three members, Rb, p107, and p130, in adult hematopoietic stem cells (HSCs). Rb family triple knockout (TKO) mice develop a cell-intrinsic myeloproliferation that originates from hyperproliferative early hematopoietic progenitors and is accompanied by increased apoptosis in lymphoid progenitor populations. Loss of quiescence in the TKO HSC pool is associated with an expansion of these mutant stem cells but also with an enhanced mobilization and an impaired reconstitution potential upon transplantation. The presence of a single p107 allele Is sufficient to largely rescue these defects. Thus, Rb family members collectively maintain HSC quiescence and the balance between lymphoid and myeloid cell fates in the hematopoietic system.
C1 [Viatour, Patrick; Venkatasubrahmanyam, Shivkumar; Butte, Atul J.; Sage, Julien] Stanford Med Sch, Dept Pediat, Stanford, CA 94305 USA.
[Viatour, Patrick; Sage, Julien] Stanford Med Sch, Dept Genet, Stanford, CA 94305 USA.
[Somervaille, Tim C.; Weissman, Irving L.] Stanford Med Sch, Dept Pathol, Stanford, CA 94305 USA.
[Venkatasubrahmanyam, Shivkumar; Butte, Atul J.] Stanford Med Sch, Dept Med, Stanford, CA 94305 USA.
[McLaughlin, Margaret E.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Kogan, Scott] Univ Calif San Francisco, Ctr Comprehens Canc, Dept Lab Med, San Francisco, CA 94143 USA.
[Passegue, Emmanuelle] Univ Calif San Francisco, Ctr Comprehens Canc, Inst Regenerat Med, San Francisco, CA 94143 USA.
[Viatour, Patrick] Univ Liege, Dept Med Chem, B-4000 Liege, Belgium.
RP Sage, J (reprint author), Stanford Med Sch, Dept Pediat, Stanford, CA 94305 USA.
EM julsage@stanford.edu
OI Somervaille, Tim/0000-0002-9188-4379
FU Lucile Packard Foundation for Children's Health; Damon Runyon Cancer
Research Foundation; NIH-NCI [RO1 CA114102, PO1 CA049605]; Human
Frontier Science Program; European Molecular Biology Organization; Fonds
de la Recherche Scientifique; Leon Fredericq Foundation; California
Institute for Regenerative Medicine; Leukemia and Lymphoma Society
FX The authors thank Tom Serwold, Anne Brunet, and Steven Artandi for
critical reading of the manuscript; Jinkuk Choi for his help with the
initial microarray analysis; Michael Cleary for his support and helpful
discussions; and Tyler Jacks for the generous provision of mutant mice
generated in his laboratory. This work was supported by the Lucile
Packard Foundation for Children's Health (J.S. and A.J.B.); the Damon
Runyon Cancer Research Foundation and NIH-NCI RO1 CA114102 (J.S.);
fellowships from the Human Frontier Science Program, the European
Molecular Biology Organization, the Fonds de la Recherche Scientifique,
and the Leon Fredericq Foundation (P.V.); and the California Institute
for Regenerative Medicine and NIH-NCI PO1 CA049605 (A.J.B.). S.K. is a
Leukemia and Lymphoma Society scholar.
NR 44
TC 90
Z9 91
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD OCT 9
PY 2008
VL 3
IS 4
BP 416
EP 428
DI 10.1016/j.stem.2008.07.009
PG 13
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 361TK
UT WOS:000260149800012
PM 18940733
ER
PT J
AU Makris, N
Gasic, GP
Kennedy, DN
Hodge, SM
Kaiser, JR
Lee, MJ
Kim, YW
Blood, AJ
Evins, AE
Seidman, LJ
Iosifescu, DV
Lee, S
Baxter, C
Perlis, RH
Smoller, JW
Fava, M
Breiter, HC
AF Makris, Nikos
Gasic, Gregory P.
Kennedy, David N.
Hodge, Steven M.
Kaiser, Jonathan R.
Lee, Myung Joo
Kim, Byoung Woo
Blood, Anne J.
Evins, A. Eden
Seidman, Larry J.
Iosifescu, Dan V.
Lee, Sang
Baxter, Claudia
Perlis, Roy H.
Smoller, Jordan W.
Fava, Maurizio
Breiter, Hans C.
TI Cortical Thickness Abnormalities in Cocaine Addiction-A Reflection of
Both Drug Use and a Pre-existing Disposition to Drug Abuse?
SO NEURON
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; VERBAL WORKING-MEMORY; HUMAN CEREBRAL-CORTEX;
HEART-RATE-VARIABILITY; LEFT-RIGHT ASYMMETRY; DECISION-MAKING;
ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; HUMAN BRAIN; NONPSYCHOTIC
RELATIVES
AB The structural effects of cocaine on neural systems mediating cognition and motivation are not well known. By comparing the thickness of neocortical and paralimbic brain regions between cocaine-dependent and matched control subjects, we found that four of 18 a priori regions involved with executive regulation of reward and attention were significantly thinner in addicts. Correlations were significant between thinner prefrontal cortex and reduced key-presses during judgment and decision making of relative preference in addicts, suggesting one basis for restricted behavioral repertoires in drug dependence. Reduced effortful attention performance in addicts also correlated with thinner paralimbic cortices. Some thickness differences in addicts were correlated with cocaine use independent of nicotine and alcohol, but addicts also showed diminished thickness heterogeneity and altered hemispheric thickness asymmetry. These observations suggest that brain structure abnormalities in addicts are related in part to drug use and in part to predisposition toward addiction.
C1 [Makris, Nikos; Blood, Anne J.; Evins, A. Eden; Seidman, Larry J.; Iosifescu, Dan V.; Lee, Sang; Perlis, Roy H.; Smoller, Jordan W.; Fava, Maurizio; Breiter, Hans C.] Massachusetts Gen Hosp, Addict Res Program, Depress Clin & Res Program, Boston, MA 02114 USA.
[Makris, Nikos; Blood, Anne J.; Evins, A. Eden; Seidman, Larry J.; Iosifescu, Dan V.; Lee, Sang; Perlis, Roy H.; Smoller, Jordan W.; Fava, Maurizio; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Makris, Nikos; Blood, Anne J.; Evins, A. Eden; Seidman, Larry J.; Iosifescu, Dan V.; Lee, Sang; Perlis, Roy H.; Smoller, Jordan W.; Fava, Maurizio; Breiter, Hans C.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Gasic, Gregory P.; Kennedy, David N.; Lee, Myung Joo; Kim, Byoung Woo; Seidman, Larry J.; Lee, Sang; Baxter, Claudia; Breiter, Hans C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MENC, Charlestown, MA 02129 USA.
[Gasic, Gregory P.; Kennedy, David N.; Lee, Myung Joo; Kim, Byoung Woo; Seidman, Larry J.; Lee, Sang; Baxter, Claudia; Breiter, Hans C.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA.
[Makris, Nikos; Gasic, Gregory P.; Kennedy, David N.; Hodge, Steven M.; Kaiser, Jonathan R.; Lee, Myung Joo; Kim, Byoung Woo; Seidman, Larry J.; Lee, Sang; Baxter, Claudia; Breiter, Hans C.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Makris, Nikos; Kennedy, David N.; Hodge, Steven M.; Kaiser, Jonathan R.] Massachusetts Gen Hosp, Ctr Integrat Informat, Ctr Morphometr Anal, Charlestown, MA 02129 USA.
[Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA.
[Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
EM hbreiter@partners.org
RI Kennedy, David/H-3627-2012;
OI Lee, Sang Han/0000-0001-9760-393X
FU NCCIH NIH HHS [P01 AT002048]; NCRR NIH HHS [P41 RR014075, M01 RR001066,
P41RR14075]; NIDA NIH HHS [K23 DA000510]; PHS HHS [14118, 34189]
NR 91
TC 62
Z9 62
U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD OCT 9
PY 2008
VL 60
IS 1
BP 174
EP 188
DI 10.1016/j.neuron.2008.08.011
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 363AC
UT WOS:000260237300017
PM 18940597
ER
PT J
AU Merkel, PA
McCarty, D
Sharma, A
Stone, JR
Rosenberg, ES
Seton, M
AF Merkel, Peter A.
McCarty, David
Sharma, Amita
Stone, James R.
Rosenberg, Eric S.
Seton, Margaret
TI A man with chest pain, arthralgias, and a mediastinal mass - Wegener's
granulomatosis involving the mediastinum, heart, and pulmonary artery
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; ANTIMYELOPEROXIDASE ANTIBODIES;
VASCULITIS; PREVALENCE; COHORT
C1 [Merkel, Peter A.] Boston Univ, Sch Med, Ctr Arthritis, Boston Med Ctr, Boston, MA 02118 USA.
[Merkel, Peter A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[McCarty, David] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[McCarty, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Sharma, Amita] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Stone, James R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Merkel, PA (reprint author), Boston Univ, Sch Med, Ctr Arthritis, Boston Med Ctr, Boston, MA 02118 USA.
FU Merck; Muscle Tech; GlaxoSmithKline; Proteon Therapeutics; Genzyme;
Bristol-Myers Squibb; Genentech
FX Dr. Stone reports receiving consulting fees from Merck, Muscle Tech,
GlaxoSmithKline, and Proteon Therapeutics. Dr. Merkel reports receiving
research support from Genzyme (to Boston University) and from
Bristol-Myers Squibb and Genentech (for research also sponsored by the
National Institutes of Health).
NR 16
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 9
PY 2008
VL 359
IS 15
BP 1603
EP 1614
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 358FS
UT WOS:000259903100011
PM 18843125
ER
PT J
AU Nandakumar, V
Singh, T
Katiyar, SK
AF Nandakumar, Vijayalakshmi
Singh, Tripti
Katiyar, Santosh K.
TI Multi-targeted prevention and therapy of cancer by proanthocyanidins
SO CANCER LETTERS
LA English
DT Review
DE Proanthocyanidins; Cancer prevention; Interleukin; Matrix
metalloproteinases; Ultraviolet radiation
ID GRAPE SEED PROANTHOCYANIDINS; NF-KAPPA-B; INDUCED OXIDATIVE STRESS;
PROSTATE TUMOR-GROWTH; SKH-1 HAIRLESS MICE; IN-VITRO; CARCINOMA-CELLS;
INDUCE APOPTOSIS; PHENOLIC-ACIDS; DIETARY AGENTS
AB In recent years, a considerable emphasis has been focused on the importance of the naturally available botanicals that can be consumed in an individual's everyday diet and that can also be useful as a chemopreventive or chemotherapeutic agent for certain diseases, including cancers. A wide variety of botanicals, mostly dietary flavonoids or polyphenolic substances, have been reported to possess substantial anti-carcinogenic and antimutagenic activities because of their antioxidant and anti-inflammatory properties. Proanthocyanidins are considered as one of them, and are abundantly available in various parts of the plants, such as fruits, berries, bark and seeds. Their modes of action were evaluated through a number of in vitro and in vivo studies which showed their potential role as anti-carcinogenic agent. We summarize and highlight the latest developments on anti-carcinogenic activities of proanthocyanidins from different sources, specifically from grape seeds, and their molecular targets, such as NF-kappa B, mitogen-activated protein kinases, PI3K/Akt, caspases, cytokines, angiogenesis and cell cycle regulatory proteins and other check points, etc. Although the bioavailability and metabolism data on proanthocyanidins is still largely unavailable, certain reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed in the gut. The modulation of various molecular targets by proanthocyanidins in vitro and in vivo tumor models suggests their importance, contribution and mechanism of action to the prevention of cancers of different organs. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Nandakumar, Vijayalakshmi; Singh, Tripti; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA.
RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA.
EM skatiyar@uab.edu
FU National Cancer Institute/NIH [CA104428]; Veterans Affairs Merit Review
Award
FX The work reported from the author's laboratory was supported by the
funds from National Cancer Institute/NIH (CA104428) and Veterans Affairs
Merit Review Award (S.K.K.). The content of this article does not
necessarily reflect the views or policies of the funding sources. The
authors apologize for not discussing and citing several valuable
publications because of the limitations of space and the number of
references.
NR 58
TC 138
Z9 142
U1 5
U2 34
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD OCT 8
PY 2008
VL 269
IS 2
BP 378
EP 387
DI 10.1016/j.canlet.2008.03.049
PG 10
WC Oncology
SC Oncology
GA 361QZ
UT WOS:000260143500017
PM 18457915
ER
PT J
AU Liu, LB
Brown, D
Mckee, M
LeBrasseur, NK
Yang, D
Albrecht, KH
Ravid, K
Pilch, PF
AF Liu, Libin
Brown, Dennis
McKee, Mary
LeBrasseur, Nathan K.
Yang, Dan
Albrecht, Kenneth H.
Ravid, Katya
Pilch, Paul F.
TI Deletion of Cavin/PTRF Causes Global Loss of Caveolae, Dyslipidemia, and
Glucose Intolerance
SO CELL METABOLISM
LA English
DT Article
ID TRANSCRIPT RELEASE FACTOR; RIPPLING MUSCLE DISEASE; INSULIN-RESISTANCE;
LIPID DROPLETS; MUSCULAR-DYSTROPHY; ADIPOCYTE CAVEOLAE; SKELETAL-MUSCLE;
KNOCKOUT MICE; POLYMERASE-I; GENE FAMILY
AB Caveolae are specialized invaginations of the plasma membrane found in numerous cell types. They have been implicated as playing a role in a variety of physiological processes and are typically characterized by their association with the caveolin family of proteins. We show here by means of targeted gene disruption in mice that a distinct caveolae-associated protein, Cavin/PTRF, is an essential component of caveolae. Animals lacking Cavin have no morphologically detectable caveolae in any cell type examined and have markedly diminished protein expression of all three caveolin isoforms while retaining normal or above normal caveolin mRNA expression. Cavin-knockout mice are viable and of normal weight but have higher circulating triglyceride levels, significantly reduced adipose tissue mass, glucose intolerance, and hyperinsulinemia-characteristics that constitute a lipodystrophic phenotype. Our results underscore the multiorgan role of caveolae in metabolic regulation and the obligate presence of Cavin for caveolae formation.
C1 [Liu, Libin; Yang, Dan; Ravid, Katya; Pilch, Paul F.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
[Brown, Dennis; McKee, Mary] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
[Brown, Dennis; McKee, Mary] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Brown, Dennis; McKee, Mary] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[LeBrasseur, Nathan K.] Boston Univ, Sch Med, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
[Albrecht, Kenneth H.] Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA.
[Albrecht, Kenneth H.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA.
RP Pilch, PF (reprint author), Boston Univ, Sch Med, Dept Biochem, 715 Albany St, Boston, MA 02118 USA.
EM ppilch@bu.edu
OI Albrecht, Kenneth/0000-0002-9769-3362; Ravid, Katya/0000-0002-9918-3024;
Pilch, Paul/0000-0003-1997-0499; LeBrasseur, Nathan/0000-0002-2002-0418
FU National Institutes of Health [DK38452, DK42596, AG031154, NH13262,
HD42779, DK30425, DK56935]; Microscopy Core Facility; Boston Area
Diabetes and Endocrinology Research Center [DK 57521]
FX We thank Greg Martin from the Boston University School of Medicine
Transgenic Core, Michelle Ganno from the Metabolic Phenotypic Core, and
Maria Makitalo for assistance in producing targeted ES cells. Mouse BAC
clones were kindly provided by The Wellcome Trust Sanger Institute
(Cambridge, UK), This work was supported by National Institutes of
Health grants DK38452 and DK42596 to D.B., AG031154 to N.K.L., NH13262
to K.R., HD42779 to K.H.A., and DK30425 and DK56935 to P.F.P. D.B. is
also supported by the Microscopy Core Facility of the MGH Program in
Membrane Biology and by the Boston Area Diabetes and Endocrinology
Research Center grant, DK 57521.
NR 44
TC 154
Z9 157
U1 1
U2 12
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 OCT 8
PY 2008
VL 8
IS 4
BP 310
EP 317
DI 10.1016/j.cmet.2008.07.008
PG 8
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 358DP
UT WOS:000259897200007
PM 18840361
ER
PT J
AU Wright, AA
Zhang, BH
Ray, A
Mack, JW
Trice, E
Balboni, T
Mitchell, SL
Jackson, VA
Block, SD
Maciejewski, PK
Prigerson, HG
AF Wright, Alexi A.
Zhang, Baohui
Ray, Alaka
Mack, Jennifer W.
Trice, Elizabeth
Balboni, Tracy
Mitchell, Susan L.
Jackson, Vicki A.
Block, Susan D.
Maciejewski, Paul K.
Prigerson, Holly G.
TI Associations between end-of-life discussions, patient mental health,
medical care near death, and caregiver bereavement adjustment
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ADVANCED CANCER-PATIENTS; TREATMENT PREFERENCES; FAMILY CAREGIVERS;
IMMINENT DEATH; SERIOUSLY ILL; BAD-NEWS; COMMUNICATION; PROGNOSIS;
PHYSICIANS; ILLNESS
AB Context Talking about death can be difficult. Without evidence that end- of- life discussions improve patient outcomes, physicians must balance their desire to honor patient autonomy against a concern of inflicting psychological harm.
Objective To determine whether end- of- life discussions with physicians are associated with fewer aggressive interventions.
Design, Setting, and Participants A US multisite, prospective, longitudinal cohort study of patients with advanced cancer and their informal caregivers ( n= 332 dy-ads), September 2002- February 2008. Patients were followed up from enrollment to death, a median of 4.4 months later. Bereaved caregivers' psychiatric illness and quality of life was assessed a median of 6.5 months later.
Main Outcome Measures Aggressive medical care ( eg, ventilation, resuscitation) and hospice in the final week of life. Secondary outcomes included patients' mental health and caregivers' bereavement adjustment.
Results One hundred twenty- three of 332 ( 37.0%) patients reported having end-of-life discussions before baseline. Such discussions were not associated with higher rates of major depressive disorder ( 8.3% vs 5.8%; adjusted odds ratio [ OR], 1.33; 95% confidence interval [ CI], 0.54- 3.32), or more worry ( mean McGill score, 6.5 vs 7.0; P=. 19). After propensity- score weighted adjustment, end- of- life discussions were associated with lower rates of ventilation ( 1.6% vs 11.0%; adjusted OR, 0.26; 95% CI, 0.08- 0.83), resuscitation ( 0.8% vs 6.7%; adjusted OR, 0.16; 95% CI, 0.03- 0.80), ICU admission ( 4.1% vs 12.4%; adjusted OR, 0.35; 95% CI, 0.14- 0.90), and earlier hospice enrollment ( 65.6% vs 44.5%; adjusted OR, 1.65; 95% CI, 1.04- 2.63). In adjusted analyses, more aggressive medical care was associated with worse patient quality of life ( 6.4 vs 4.6; F= 3.61, P=. 01) and higher risk of major depressive disorder in bereaved caregivers ( adjusted OR, 3.37; 95% CI, 1.12- 10.13), whereas longer hospice stays were associated with better patient quality of life ( mean score, 5.6 vs 6.9; F= 3.70, P=. 01). Better patient quality of life was associated with better caregiver quality of life at follow- up (beta=. 20; P=. 001).
Conclusions End- of- life discussions are associated with less aggressive medical care near death and earlier hospice referrals. Aggressive care is associated with worse patient quality of life and worse bereavement adjustment.
C1 [Wright, Alexi A.; Trice, Elizabeth] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wright, Alexi A.; Zhang, Baohui; Ray, Alaka; Trice, Elizabeth; Balboni, Tracy; Block, Susan D.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA.
[Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Ray, Alaka; Jackson, Vicki A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Balboni, Tracy] Harvard Univ, Harvard Radiat Oncol Program, Boston, MA USA.
[Jackson, Vicki A.; Block, Susan D.; Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA.
[Mitchell, Susan L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Block, Susan D.; Maciejewski, Paul K.; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
RP Wright, AA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 550 Shields Warren,44 Binney St, Boston, MA 02115 USA.
EM awright2@partners.org
FU National Cancer Institute [CA 106370]; National Institute of Mental
Health [MH63892]; National Cancer Institute's "Program in Cancer
Outcomes Research Training" [CA 92044343]; Dana-Farber Cancer
Institute's Friends Fellowship
FX This study was supported by grants CA 106370 from the National Cancer
Institute and MH63892 from the National Institute of Mental Health. Dr
Wright was supported, in part, by grant CA 92044343, which is part of
the National Cancer Institute's "Program in Cancer Outcomes Research
Training" and by the Dana-Farber Cancer Institute's Friends Fellowship.
NR 50
TC 729
Z9 732
U1 16
U2 84
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 OCT 8
PY 2008
VL 300
IS 14
BP 1665
EP 1673
DI 10.1001/jama.300.14.1665
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 356YF
UT WOS:000259812800028
PM 18840840
ER
PT J
AU Chung, DC
AF Chung, Daniel C.
TI Stool DNA testing and colon cancer prevention: Another step forward
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID FECAL OCCULT-BLOOD; COLORECTAL-CANCER; TASK-FORCE; NEOPLASIA;
METHYLATION; MUTATIONS
C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,50 Blossom St, Boston, MA 02114 USA.
EM dchung@partners.org
NR 14
TC 9
Z9 9
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD OCT 7
PY 2008
VL 149
IS 7
BP 509
EP 510
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 359QY
UT WOS:000260004400008
PM 18838731
ER
PT J
AU Kalaitzidis, D
Gilliland, DG
AF Kalaitzidis, Demetrios
Gilliland, D. Gary
TI Going with the flow: JAK-STAT signaling in JMML
SO CANCER CELL
LA English
DT Editorial Material
ID JUVENILE MYELOMONOCYTIC LEUKEMIA; COLONY-STIMULATING FACTOR; MICE;
DISEASE; CANCER; CELLS
AB Knowledge of the distinctive cellular and genetic traits of a cancer aids in diagnosis, prognosis, and potentially treatment. In this issue of Cancer Cell, Kotecha et al. (2008) demonstrate using a sophisticated flow cytometry approach that signal transduction responses to exogenous stimulation can inform diagnosis and pathobiology of myeloproliferative neoplasms.
C1 Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA.
Harvard Univ, Howard Hughes Med Inst, Broad Inst MIT, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA.
Harvard Stem Cell Inst, Boston, MA 02115 USA.
RP Kalaitzidis, D (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, 75 Francis St, Boston, MA 02115 USA.
EM ggilliland@rics.bwh.harvard.edu; dkalaitzidis@partners.org
FU Howard Hughes Medical Institute
NR 10
TC 6
Z9 7
U1 0
U2 5
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 OCT 7
PY 2008
VL 14
IS 4
BP 279
EP 280
DI 10.1016/j.ccr.2008.09.006
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 358DI
UT WOS:000259896500001
PM 18835028
ER
PT J
AU Antman, EM
AF Antman, Elliott M.
TI Time is muscle - Translation into practice
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE ST-segment elevation myocardial infarction; reperfusion; guidelines
ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION;
ST-SEGMENT-ELEVATION; PRIMARY ANGIOPLASTY; FIBRINOLYTIC THERAPY;
PREHOSPITAL FIBRINOLYSIS; REPERFUSION STRATEGY; THROMBOLYTIC THERAPY;
RANDOMIZED-TRIALS; CARE
AB In the future, advances in the care of patients with ST-segment elevation myocardial infarction (STEMI) will not come from the analysis of trials that do not reflect current practice in an effort to rationalize extending the percutaneous coronary intervention (PCI)-related delay time. We must move beyond such arguments and find ways to shorten total ischemic time. With the launching of the American College of Cardiology's D2B Alliance and the American Heart Association's Mission: Lifeline programs, the focus is now on systems improvement for reperfusion in patients with STEMI. The D2B Alliance was developed to focus on improvement in door-to-balloon times for patients with STEMI who are undergoing primary PCI. The American Heart Association Mission: Lifeline program is a broad, comprehensive national initiative to improve the quality of care and outcomes of patients with STEMI by improving health care system readiness and response to STEMI. Improvements in access to timely care for patients with STEMI will require a multifaceted approach involving patient education, improvements in the Emergency Medical Services and emergency department components of care, the establishment of networks of STEMI-referral hospitals (not PCI capable) and STEMI-receiving hospitals (PCI capable), as well as coordinated advocacy efforts to work with payers and policy makers to implement a much-needed health care system redesign. By focusing now on system efforts for improvements in timely care for STEMI, we will complete the cycle of research initiated by Reimer and Jennings 30 years ago. Time is muscle... we must translate that into practice.
C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
RP Antman, EM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
EM eantman@rics.bwh.harvard.edu
NR 37
TC 53
Z9 56
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 7
PY 2008
VL 52
IS 15
BP 1216
EP 1221
DI 10.1016/j.jacc.2008.07.011
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 355RY
UT WOS:000259727200003
PM 18926324
ER
PT J
AU Upadhyay, GA
Choudhry, NK
Auricchio, A
Ruskin, J
Singh, JP
AF Upadhyay, Gaurav A.
Choudhry, Niteesh K.
Auricchio, Angelo
Ruskin, Jeremy
Singh, Jagmeet P.
TI Cardiac resynchronization in patients with atrial fibrillation - A
meta-analysis of prospective cohort studies
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE atrial fibrillation; biventricular pacemaker; cardiac resynchronization;
congestive heart failure treatment
ID CHRONIC HEART-FAILURE; ATRIOVENTRICULAR JUNCTION ABLATION; RANDOMIZED
CONTROLLED-TRIALS; SINUS RHYTHM; PERMANENT PACEMAKER; CONDUCTION DELAY;
THERAPY; SURVIVAL; TRENDS; IMPLANTATION
AB Objectives This study is a meta-analysis of prospective cohort studies comparing the impact of cardiac resynchronization therapy (CRT) for patients in atrial fibrillation (AF) and sinus rhythm (SR).
Background Although close to one-third of advanced heart failure patients exhibit AF, the impact of CRT in this group remains unclear.
Methods Prospective cohort studies comparing patients in normal SR and chronic AF treated with CRT were included. All studies reported death, New York Heart Association functional class, rejection fraction, 6-min walk test, and the Minnesota score or its equivalent as outcomes. Data sources included Ovid MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Central Register of Controlled Trials, the Database of Abstracts of Reviews of Effects, and the American College of Physicians Journal Club.
Results Of 2,487 reports identified, 5 studies following a total of 1,164 patients were included. Both AF and SR patients benefited significantly from CRT. Mortality was not significantly different at 1 year (relative risk ratio: 1.57, 95% confidence interval [ CI]: 0.87 to 2.81). The New York Heart Association functional class improved similarly for both groups (-0.90 for SR patients,-0.84 for AF patients). SR patients showed greater relative improvement in the 6-min walk test (11.6 m greater, 95% CI: 10.4 to 12.8 m) and the Minnesota score (3.9 points less, 95% CI: 3.4 to 4.5 points) than AF patients. AF patients, however, achieved a small but statistically significant greater change in ejection fraction (0.39% greater change in ejection fraction, 95% CI: 0.22% to 0.55%).
Conclusions Patients in AF show significant improvement after CRT, with similar or improved ejection fraction as SR patients, but smaller benefits in regard to functional outcomes.
C1 [Singh, Jagmeet P.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Div Cardiol, Boston, MA 02114 USA.
[Upadhyay, Gaurav A.; Ruskin, Jeremy; Singh, Jagmeet P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Choudhry, Niteesh K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Auricchio, Angelo] Fdn Cardioctr Ticino, Div Cardiol, Lugano, Switzerland.
RP Singh, JP (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Div Cardiol, Gray Bldg 109,55 Fruit St, Boston, MA 02114 USA.
EM jsingh@partners.org
FU Boston Scientific; Medtronic; St. Jude Medical; Biotronik
FX Dr. Auricchio is a consultant to Medtronic and the Sorin Group; has
received research grants from Boston Scientific, Medtronic, St. Jude
Medical and Biotronik; and has lectured for Boston Scientific,
Medtronic, St. Jude Medical, Sorin, and Biotronik. Dr. Ruskin is a
consultant to Medtronic; is a part of the Fellows programs for St. Jude
Medical and Boston Scientific; and has received research support from
St. Jude Medical. Dr. Singh is a consultant to Biotronik, Boston
Scientific, Medtronic, and St. Jude Medical; has lectured for Biotronik,
Boston Scientific, Medtronic, St. Jude Medical, and the Sorin Group; and
has received research grants from Biotronik, Boston Scientific,
Medtronic, and St. Jude Medical.
NR 34
TC 93
Z9 97
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD OCT 7
PY 2008
VL 52
IS 15
BP 1239
EP 1246
DI 10.1016/j.jacc.2008.06.043
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 355RY
UT WOS:000259727200006
PM 18926327
ER
PT J
AU Li, ZJ
Lu, J
Sun, M
Mi, SL
Zhang, H
Luo, RT
Chen, P
Wang, YG
Yan, M
Qian, ZJ
Neilly, MB
Jin, J
Zhang, YM
Bohlander, SK
Zhang, DE
Larson, RA
Le Beau, MM
Thirman, MJ
Golub, TR
Rowley, JD
Chen, JJ
AF Li, Zejuan
Lu, Jun
Sun, Miao
Mi, Shuangli
Zhang, Hao
Luo, Roger T.
Chen, Ping
Wang, Yungui
Yan, Ming
Qian, Zhijian
Neilly, Mary Beth
Jin, Jie
Zhang, Yanming
Bohlander, Stefan K.
Zhang, Dong-Er
Larson, Richard A.
Le Beau, Michelle M.
Thirman, Michael J.
Golub, Todd R.
Rowley, Janet D.
Chen, Jianjun
TI Distinct microRNA expression profiles in acute myeloid leukemia with
common translocations
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE apoptosis and cell viability and proliferation; core binding factor
(CBF); microRNA expression profiling; miR-126; PLK2
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION; CANCER; TARGET; CELLS;
DIFFERENTIATION; POLO-LIKE-KINASE-2; IDENTIFICATION; ORGANIZATION;
MALIGNANCIES
AB MicroRNAs (miRNAs) are postulated to be important regulators in cancers. Here, we report a genome-wide miRNA expression analysis in 52 acute myeloid leukemia (AML) samples with common translocations, including t(8;21)/AML1(RUNX1)-ETO(RUNX1T1), inv(16)/CBFB-MYH11, t(15;17)/PML-RARA, and MLL rearrangements. Distinct miRNA expression patterns were observed for t(15;17), MLL rearrangements, and core-binding factor (CBF) AMLs including both t(8;21) and inv(16) samples. Expression signatures of a minimum of two (i.e., miR-126/126*), three (i.e., miR-224, miR-368, and miR-382), and seven (miR-17-5p and miR-20a, plus the aforementioned five) miRNAs could accurately discriminate CBF, t(15;17), and MLL-rearrangement AMLs, respectively, from each other. We further showed that the elevated expression of miR-126/126* in CBF AMLs was associated with promoter demethylation but not with amplification or mutation of the genomic locus. Our gain- and loss-of-function experiments showed that miR-126/ 126* inhibited apoptosis and increased the viability of AML cells and enhanced the colony-forming ability of mouse normal bone marrow progenitor cells alone and particularly, in cooperation with AML1-ETO, likely through targeting Polo-like kinase 2 (PLK2), a tumor suppressor. Our results demonstrate that specific alterations in miRNA expression distinguish AMLs with common translocations and imply that the deregulation of specific Ill may play a role in the development of leukemia with these associated genetic rearrangements.
C1 [Lu, Jun; Zhang, Hao; Golub, Todd R.] Broad Inst, Cambridge, MA 02141 USA.
[Li, Zejuan; Sun, Miao; Mi, Shuangli; Luo, Roger T.; Chen, Ping; Qian, Zhijian; Neilly, Mary Beth; Zhang, Yanming; Larson, Richard A.; Le Beau, Michelle M.; Thirman, Michael J.; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Lu, Jun; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Wang, Yungui; Jin, Jie] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Inst Hematol, Hangzhou 310003, Zhejiang, Peoples R China.
[Yan, Ming; Zhang, Dong-Er] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Zhang, Dong-Er] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
[Zhang, Dong-Er] Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA.
[Bohlander, Stefan K.] Univ Munich, Hosp Grosshadern, Dept Med 3, D-81377 Munich, Germany.
[Bohlander, Stefan K.] Natl Res Ctr Environm & Hlth, Clin Cooperat Grp Leukemia, D-81377 Munich, Germany.
[Golub, Todd R.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Golub, TR (reprint author), Broad Inst, Cambridge, MA 02141 USA.
EM golub@broad.mit.edu; jrowley@medicine.bsd.uchicago.edu;
jchen@medicine.bsd.uchicago.edu
OI Bohlander, Stefan/0000-0002-2202-9088; Larson,
Richard/0000-0001-9168-3203
FU National Institutes of Health (NIH) [CA127277, CA40046, CA104509,
CA014599]; Cancer Research Foundation; Leukemia and Lymphoma Society;
Spastic Paralysis Foundation of the Illinois; Eastern Iowa Branch of
Kiwanis International
FX We thank Drs. G. J. Hannon, S. M. Hammond, and L. He at Cold Spring
Harbor Laboratory for providing MSCVpuro-PlG vector, Dr. P. P. Liu at
National Human Genome Research Institute for providing the ME-1 cell
line, and Drs. Y. Sato and K. Sugita at Yamanashi University for
providing the KOCL-48 cell line. We also thank Dr. L. Pelloso at the
University of Chicago for helpful discussion and Drs. J. Xu and Y. Chen
at the University of Chicago for technical help with the methylation
analysis. This work was supported in part by National Institutes of
Health (NIH) Grant CA127277 (to J.C.), the G. Harold and Leila Y.
Mathers Charitable Foundation (J.C.), a Cancer Research Foundation Young
Investigator Award (to (J.C.), a Leukemia and Lymphoma Society
Translational Research Grant (to J.D.R.), the Spastic Paralysis
Foundation of the Illinois, the Eastern Iowa Branch of Kiwanis
International (J.D.R.), NIH Grants CA40046 (to M.M.L.B. and R.A.L) and
CA104509 (to D.-E.Z.). T.R.G. is an Investigator of the Howard Hughes
Medical Institute. The sequencing was done by the Cancer Research Center
DNA Sequencing Facility with the support of NIH Cancer Center Support
Grant CA014599.
NR 57
TC 256
Z9 277
U1 1
U2 22
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 OCT 7
PY 2008
VL 105
IS 40
BP 15535
EP 15540
DI 10.1073/pnas.0808266105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 364UI
UT WOS:000260360500058
PM 18832181
ER
PT J
AU Oral, E
Beckos, CG
Muratoglu, OK
AF Oral, Ebru
Beckos, Christine Godleski
Muratoglu, Orhun K.
TI Free radical elimination in irradiated UHMWPE through crystal mobility
in phase transition to the hexagonal phase
SO POLYMER
LA English
DT Article
DE Free radicals; Crystal mobility; Cross-linking
ID MOLECULAR-WEIGHT POLYETHYLENE; HIGH-PRESSURE PHASE; PROPAGATION
RESISTANCE; CRYSTALLIZATION; OXIDATION; WEAR; GROWTH; MELT
AB Ultra-high molecular weight polyethylene (UHMWPE) is radiation cross-linked to decrease wear in total joint applications. Irradiation decreases the strength of UHMWPE and introduces residual free radicals, which can cause oxidation in the long-term. We advanced a method eliminating the free radicals without a reduction in strength. UHMWPE exhibits a hexagonal phase at high pressure and temperature, where chain mobility in the crystalline phase is increased, leading to the formation of extended chain crystals. We hypothesized that the increased chain mobility during transformation from the orthorhombic to hexagonal phase could be used to eliminate the residual free radicals in irradiated UHMWPE. We eliminated the free radicals in 25-, 65- and 100-kGy irradiated UHMWPEs and these materials did not show oxidation after accelerated aging. The ultimate tensile strength and work-to-failure of 25 and 65-kGy irradiated UHMWPEs were improved significantly while that of 100-kGy irradiated UHMWPE was lower compared to irradiated UHMWPE melted at ambient pressure. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Oral, Ebru; Beckos, Christine Godleski; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, 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, Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA.
EM omuratoglu@partners.org
FU National Institutes of Health [AR110542]; Zimmer, Inc.
FX This study was funded by a grant from the National Institutes of Health
(AR110542) and a research grant from Zimmer, Inc. The authors would also
like to thank Prof. M. Shah Jahan and his group at the University of
Memphis for their help with the ESR experiments.
NR 21
TC 12
Z9 15
U1 0
U2 12
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0032-3861
J9 POLYMER
JI Polymer
PD OCT 6
PY 2008
VL 49
IS 21
BP 4733
EP 4739
DI 10.1016/j.polymer.2008.07.049
PG 7
WC Polymer Science
SC Polymer Science
GA 360MZ
UT WOS:000260062900033
PM 18985170
ER
PT J
AU Mick, E
Kim, JW
Biederman, J
Wozniak, J
Wilens, T
Spencer, T
Smoller, JW
Faraone, SV
AF Mick, Eric
Kim, Jang Woo
Biederman, Joseph
Wozniak, Janet
Wilens, Timothy
Spencer, Thomas
Smoller, Jordan W.
Faraone, Stephen V.
TI Family Based Association Study of Pediatric Bipolar Disorder and the
Dopamine Transporter Gene (SLC6A3)
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE bipolar disorder; dopamine transporter; pediatric
ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER; EARLY ADOLESCENT BIPOLARITY; LINKAGE DISEQUILIBRIUM;
TRANSMISSION DISEQUILIBRIUM; ONSET; POLYMORPHISMS; EXPRESSION;
HAPLOTYPE; DAT1
AB The dopamine transporter gene (SLC6A3) is a compelling candidate for pediatric bipolar disorder because (a) it has been associated with ADHD, (b) bipolar comorbidity with ADHD has been hypothesized to be an etiologically distinct familial subtype (c) blockade of the dopamine transporter with psychostimulants can induce mania in susceptible individuals and (d) previous studies have implicated the gene in bipolar disorder in adults. We conducted a family-based association study of SLC6A3 in 170 affected offspring trios defined by a child (12.9 +/- 5.3 years of age)with DSM-IV Bipolar-I disorder. Twenty-eight tag SNPs were chosen from the CEU (European) population of the International HapMap project (www.hapmap.org). Results indicated nominally positive association for 4 SNPs (rs40184, rs11133767, rs3776512, and rs464049), but only rs40184 survived correction for multiple statistical comparisons (P = 0.038). This is the first examination of the association with SLC6A3 and bipolar disorder in children and, like previous findings in adults with bipolar disorder, we found evidence of association with SNPs in the 3' region of the gene. These data provide suggestive evidence supporting a role for SLC6A3 in the etiology of pediatric bipolar disorder. (C) 2008 Wiley-Liss, Inc.
C1 [Mick, Eric; Biederman, Joseph; Wozniak, Janet; Wilens, Timothy; Spencer, Thomas; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Mick, Eric; Biederman, Joseph; Wozniak, Janet; Wilens, Timothy; Spencer, Thomas; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA USA.
[Kim, Jang Woo; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 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 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
FU NIH [K08MH001503, R01MH066237, R01MH050657, R01HD036317, R01DA012945,
K01MH065523]; Heinz C. Prechter Bipolar Research Fund
FX Grant sponsor: NIH; Grant numbers: K08MH001503, R01MH066237,
R01MH050657, R01HD036317, R01DA012945, K01MH065523; Grant sponsor: Heinz
C. Prechter Bipolar Research Fund.
NR 43
TC 25
Z9 27
U1 2
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD OCT 5
PY 2008
VL 147B
IS 7
BP 1182
EP 1185
DI 10.1002/ajmg.b.30745
PG 4
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 359IK
UT WOS:000259979500024
PM 18361424
ER
PT J
AU Kay, DM
Factor, SA
Samii, A
Higgins, DS
Griffith, A
Roberts, JW
Leis, BC
Nutt, JG
Montimurro, JS
Keefe, RG
Atkins, AJ
Yearout, D
Zabetian, CP
Payami, H
AF Kay, Denise M.
Factor, Stewart A.
Samii, Ali
Higgins, Donald S.
Griffith, Alida
Roberts, John W.
Leis, Berta C.
Nutt, John G.
Montimurro, Jennifer S.
Keefe, Robert G.
Atkins, April J.
Yearout, Dora
Zabetian, Cyrus P.
Payami, Haydeh
TI Genetic Association Between alpha-Synuclein and Idiopathic Parkinson's
Disease
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE REP1; risk; age at onset; relative predispositional effects; mode of
inheritance
ID LOCUS TRIPLICATION; ALLELIC VARIATION; NACP-REP1; SUSCEPTIBILITY; SNCA;
RELIABILITY; DUPLICATION; ONSET; RISK
AB Point mutations and copy number variations in SNCA, the gene encoding a-synuclein, cause familial Parkinson's disease (PD). A dinucleotide polymorphism. (REPI.) in the SNCA promoter may be a risk factor for common forms of PD. We studied 1,802 PD patients and 2,129 controls from the NeuroGenetics Research Consortium, using uniform, standardized protocols for diagnosis, subject recruitment, data collection, genotyping, and data analysis. Three common REP1 alleles (257, 259, and 261 bp, with control frequencies of 0.28, 0.65, and 0.06) and several rare alleles (combined frequency <0.01) were detected. We confirmed association of REP1 with PD risk [odds ratio (OR)=0.86, P=0.006 for 257-carriers; OR=1.25, P=0.022 for 261-carriers]. Using a normalization procedure, we showed that the 257 and 261 alleles are both independently associated with PD risk (for 257, P=0.002 in overall data, 0.003 in non-familial PD, 0.001 in early-onset PD; for 261, P=0.056 in overall data, 0.024 in non-familial PD, 0.052 in early-onset PD). The 257-associated risk was consistent with a dominant model [hazard ratio (HR)=0.99, P=0.91 for 257/257 vs. 257/X where X denotes all other common alleles; HR=1.16, P=0.004 for X/X vs. 257/X]. The 261-associated risk was consistent with a recessive model (HR=1.89, P=0.026 for 261/261 vs. 261/X; HR=0.95, P=0.42 for X/X vs. 261/X). Genotype-specific mean onset ages (+/- SD) ranged from 54.8 +/- 12.1 for 261/261 to 59.4 +/- 11.5 for 257/257, displaying a trend of decreasing onset age with increasing allele size (P=0.055). Genetic variation in SNCA and its regulatory regions play an important role in both familial and sporadic PD. (C) 2008 Wiley-Liss, Inc.
C1 [Kay, Denise M.; Montimurro, Jennifer S.; Keefe, Robert G.; Atkins, April J.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Div Genet Disorders, Albany, NY 12208 USA.
[Factor, Stewart A.; Higgins, Donald S.] Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA.
[Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Samii, Ali; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA.
[Samii, Ali; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA.
[Griffith, Alida; Leis, Berta C.] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA.
[Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Yearout, Dora; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Genet Disorders, POB 22002, Albany, NY 12208 USA.
EM hpayami@wadsworth.org
OI Kay, Denise/0000-0002-9928-2698
FU Michael J. Fox Foundation; National Institutes of Health (NIH) [NS
R01-36960, K08-NS044138, AG 08017]; VA Merit Award; Mental Health and
Geriatric Research Education and Clinical Centers; Genomics Institute of
the New York State Department of Health Wadsworth Center
FX Grant sponsor: Michael J. Fox Foundation Edmond J. Safra Global Genetics
Consortia Grant-Grant sponsor: National Institutes of Health (NIH)
National Institute for Neurological Disorders and Stroke grants; Grant
numbers: NS R01-36960, K08-NS044138; Grant sponsor: VA Merit Award;
Grant sponsor: NIH National Institutes of Aging grant; Grant number: AG
08017; Grant sponsor: Mental Health and Geriatric Research Education and
Clinical Centers at the VA Puget Sound Health Care System; Grant
sponsor: Genomics Institute of the New York State Department of Health
Wadsworth Center.
NR 26
TC 35
Z9 36
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD OCT 5
PY 2008
VL 147B
IS 7
BP 1222
EP 1230
DI 10.1002/ajmg.b.30758
PG 9
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 359IK
UT WOS:000259979500029
PM 18404644
ER
PT J
AU Platko, JV
Wood, FB
Pelser, I
Meyer, M
Gericke, GS
O'Rourke, J
Birns, J
Purcell, S
Pauls, DL
AF Platko, Jill V.
Wood, Frank B.
Pelser, Izelda
Meyer, Marianne
Gericke, George S.
O'Rourke, Julia
Birns, Julie
Purcell, Shaun
Pauls, David L.
TI Association of Reading Disability on Chromosome 6p22 in the Afrikaner
Population
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE dyslexia; Afrikaner; reading disability; association
ID QUANTITATIVE-TRAIT LOCUS; DEVELOPMENTAL DYSLEXIA; LINKAGE
DISEQUILIBRIUM; LEARNING-DISABILITIES; SUSCEPTIBILITY LOCUS; SPELLING
DISABILITY; CANADIAN FAMILIES; GENETIC ETIOLOGY; MAPPING PROVIDES;
CONFIRMATION
AB The genetic basis of reading disability (RD) has long been established through family and twin studies. More recently genetic linkage studies have identified genomic regions that appear to harbor susceptibility genes for RD. Association studies have been shown to have greater power for detecting genes of modest effect, particularly in genetically isolated populations. Hence, a case control study of RD was undertaken in the Afrikaner population in South Africa. Sixty-eight microsatellite markers in regions where linkages had been reported in previous studies were genotyped on 122 children with reading disability and 112 typically reading controls drawn from the same school population. A single allele of marker D6S299 showed a highly significant association with the RD phenotype (D6S299[229], P-value 0.000014). Other markers on other chromosomes also showed suggestive associations. Of particular interest were markers on chromosomes 1 and 15. These two regions have been implicated in studies of populations that formed the founding population in the Afrikaner population. (C) 2008 Wiley-Liss, Inc.
C1 [Platko, Jill V.; O'Rourke, Julia; Birns, Julie; Purcell, Shaun; Pauls, David L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
[Wood, Frank B.; Meyer, Marianne] Wake Forest Univ, Bowman Gray Sch Med, Sect Neuropsychol, Winston Salem, NC 27109 USA.
[Pelser, Izelda] Univ Limpopo, Ga Rankuwa, South Africa.
[Gericke, George S.] Tshwane Univ Technol Pretoria, Brain Behav Res Programme, Pretoria, South Africa.
RP Pauls, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St,6th Floor, Boston, MA 02114 USA.
EM dpauls@pngu.mgh.harvard.edu
NR 73
TC 6
Z9 6
U1 3
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD OCT 5
PY 2008
VL 147B
IS 7
BP 1278
EP 1287
DI 10.1002/ajmg.b.30774
PG 10
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 359IK
UT WOS:000259979500036
PM 18452150
ER
PT J
AU Neale, BM
Purcell, S
AF Neale, Benjamin M.
Purcell, Shaun
TI The Positives, Protocols, and Perils of Genome-Wide Association
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Review
DE genome-wide association; linkage disequilibrium; review; SNP chip
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; COMMON GENETIC VARIANT; FACTOR-H
POLYMORPHISM; MACULAR DEGENERATION; CARDIAC REPOLARIZATION;
LINKAGE-DISEQUILIBRIUM; SUSCEPTIBILITY LOCI; NICOTINE DEPENDENCE;
CROHNS-DISEASE; RISK LOCUS
AB Genome-wide association aims to comprehensively survey genetic variation for the purposes of disease and trait mapping. We provide a brief history of the development of genetic technology necessary to realize genome-wide association. From there we identify and review the publicly available resources for conducting such work including the molecular technologies, genomic databases, and analytic tools. Following on from the analytic tools, we highlight common analytic considerations, ranging from study design, quality control, and data cleaning to association analysis and replication. We conclude with a look toward future developments such as the analysis of copy number variation and integration of expression and epigenetic phenomenon into genome-wide association. (C) 2008 Wiley-Liss, Inc.
C1 [Neale, Benjamin M.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England.
[Neale, Benjamin M.; Purcell, Shaun] Broad Inst Harvard, Cambridge, MA USA.
[Neale, Benjamin M.; Purcell, Shaun] MIT, Cambridge, MA 02139 USA.
[Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodevelopmental Genet Unit, Boston, MA 02114 USA.
[Purcell, Shaun] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Neale, Benjamin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boson, MA USA.
RP Neale, BM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA.
EM b.neale@iop.kcl.ac.uk
NR 78
TC 26
Z9 27
U1 2
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD OCT 5
PY 2008
VL 147B
IS 7
BP 1288
EP 1294
DI 10.1002/ajmg.b.30747
PG 7
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 359IK
UT WOS:000259979500037
PM 18500721
ER
PT J
AU Blackwell, TK
Walker, AK
AF Blackwell, T. Keith
Walker, Amy K.
TI OMA-gosh, where's that TAF?
SO CELL
LA English
DT Editorial Material
ID OOCYTE MATURATION; C-ELEGANS; TRANSCRIPTION; ELONGATION; PROTEINS; PIE-1
AB How transcription is silenced in early embryos has long been a mystery. In this issue, Guven-Ozkan et al. (2008) report that transcriptional repression during worm embryogenesis is mediated through sequestration of the general transcription factor TAF-4 and is regulated by mechanisms that orchestrate the transition between maternal and zygotic gene expression.
C1 [Blackwell, T. Keith] Harvard Univ, Sch Med,Harvard Stem Cell Inst, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr,Dept Pathol, Boston, MA 02215 USA.
[Walker, Amy K.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
RP Blackwell, TK (reprint author), Harvard Univ, Sch Med,Harvard Stem Cell Inst, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr,Dept Pathol, Boston, MA 02215 USA.
EM keith.blackwell@joslin.harvard.edu; awalker6@partners.org
NR 8
TC 0
Z9 1
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 3
PY 2008
VL 135
IS 1
BP 18
EP 20
DI 10.1016/j.cell.2008.09.021
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 355SH
UT WOS:000259728100004
PM 18854150
ER
PT J
AU Yu, HY
Braun, P
Yildirim, MA
Lemmens, I
Venkatesan, K
Sahalie, J
Hirozane-Kishikawa, T
Gebreab, F
Li, N
Simonis, N
Hao, T
Rual, JF
Dricot, A
Vazquez, A
Murray, RR
Simon, C
Tardivo, L
Tam, S
Svrzikapa, N
Fan, CY
de Smet, AS
Motyl, A
Hudson, ME
Park, J
Xin, XF
Cusick, ME
Moore, T
Boone, C
Snyder, M
Roth, FP
Barabasi, AL
Tavernier, J
Hill, DE
Vidal, M
AF Yu, Haiyuan
Braun, Pascal
Yildirim, Muhammed A.
Lemmens, Irma
Venkatesan, Kavitha
Sahalie, Julie
Hirozane-Kishikawa, Tomoko
Gebreab, Fana
Li, Na
Simonis, Nicolas
Hao, Tong
Rual, Jean-Francois
Dricot, Amelie
Vazquez, Alexei
Murray, Ryan R.
Simon, Christophe
Tardivo, Leah
Tam, Stanley
Svrzikapa, Nenad
Fan, Changyu
de Smet, Anne-Sophie
Motyl, Adriana
Hudson, Michael E.
Park, Juyong
Xin, Xiaofeng
Cusick, Michael E.
Moore, Troy
Boone, Charlie
Snyder, Michael
Roth, Frederick P.
Barabasi, Albert-Laszlo
Tavernier, Jan
Hill, David E.
Vidal, Marc
TI High-quality binary protein interaction map of the yeast interactome
network
SO SCIENCE
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; REGULATORY NETWORKS; MASS-SPECTROMETRY;
ESCHERICHIA-COLI; 2-HYBRID SCREENS; GENOMIC ANALYSIS; C-ELEGANS; SCALE;
COMPLEXES; ANNOTATION
AB Current yeast interactome network maps contain several hundred molecular complexes with limited and somewhat controversial representation of direct binary interactions. We carried out a comparative quality assessment of current yeast interactome data sets, demonstrating that high- throughput yeast two- hybrid ( Y2H) screening provides high- quality binary interaction information. Because a large fraction of the yeast binary interactome remains to be mapped, we developed an empirically controlled mapping framework to produce a "second- generation" high- quality, high- throughput Y2H data set covering similar to 20% of all yeast binary interactions. Both Y2H and affinity purification followed by mass spectrometry ( AP/ MS) data are of equally high quality but of a fundamentally different and complementary nature, resulting in networks with different topological and biological properties. Compared to co- complex interactome models, this binary map is enriched for transient signaling interactions and intercomplex connections with a highly significant clustering between essential proteins. Rather than correlating with essentiality, protein connectivity correlates with genetic pleiotropy.
C1 [Yu, Haiyuan; Braun, Pascal; Yildirim, Muhammed A.; Venkatesan, Kavitha; Sahalie, Julie; Hirozane-Kishikawa, Tomoko; Gebreab, Fana; Li, Na; Simonis, Nicolas; Hao, Tong; Rual, Jean-Francois; Dricot, Amelie; Murray, Ryan R.; Simon, Christophe; Tardivo, Leah; Tam, Stanley; Svrzikapa, Nenad; Fan, Changyu; Park, Juyong; Cusick, Michael E.; Roth, Frederick P.; Barabasi, Albert-Laszlo; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.
[Yu, Haiyuan; Braun, Pascal; Yildirim, Muhammed A.; Venkatesan, Kavitha; Sahalie, Julie; Hirozane-Kishikawa, Tomoko; Gebreab, Fana; Li, Na; Simonis, Nicolas; Hao, Tong; Rual, Jean-Francois; Dricot, Amelie; Murray, Ryan R.; Simon, Christophe; Tardivo, Leah; Tam, Stanley; Svrzikapa, Nenad; Fan, Changyu; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Yu, Haiyuan; Braun, Pascal; Yildirim, Muhammed A.; Venkatesan, Kavitha; Sahalie, Julie; Hirozane-Kishikawa, Tomoko; Gebreab, Fana; Li, Na; Simonis, Nicolas; Hao, Tong; Rual, Jean-Francois; Dricot, Amelie; Murray, Ryan R.; Simon, Christophe; Tardivo, Leah; Tam, Stanley; Svrzikapa, Nenad; Fan, Changyu; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Yildirim, Muhammed A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Lemmens, Irma; de Smet, Anne-Sophie; Tavernier, Jan] Univ Ghent VIB, Dept Med Prot Res, Fac Med & Hlth Sci, B-9000 Ghent, Belgium.
[Lemmens, Irma; de Smet, Anne-Sophie; Tavernier, Jan] Univ Ghent, Dept Biochem, Fac Med & Hlth Sci, B-9000 Ghent, Belgium.
[Vazquez, Alexei] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA.
[Motyl, Adriana; Hudson, Michael E.; Snyder, Michael] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06620 USA.
[Park, Juyong; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
[Park, Juyong; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Park, Juyong; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Biol, Boston, MA 02115 USA.
[Park, Juyong; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA.
[Xin, Xiaofeng; Boone, Charlie] Univ Toronto, Banting & Best Dept Med Res, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
[Xin, Xiaofeng; Boone, Charlie] Univ Toronto, Dept Med Genet & Microbiol, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
[Moore, Troy] Open Biosyst, Huntsville, AL 35806 USA.
[Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Vidal, M (reprint author), Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.
EM marc_vidal@dfci.harvard.edu
RI Roth, Frederick/H-6308-2011; Yildirim, Muhammed/J-3695-2014; Braun,
Pascal/B-9669-2013; Xin, Xiaofeng/G-7736-2016; Simonis,
Nicolas/E-5124-2010; Hill, David/B-6617-2011; Park, Juyong/I-2290-2012;
OI Yildirim, Muhammed/0000-0003-2826-1766; Braun,
Pascal/0000-0003-2012-6746; Xin, Xiaofeng/0000-0002-2439-7183; Rual,
Jean-Francois/0000-0003-4465-8819; Roth, Frederick/0000-0002-6628-649X
FU W. M. Keck Foundation; Institute Sponsored Research funds from the
Dana-Farber Cancer Institute Strategic Initiative; NIH [R01-HG001715,
U01-A1070499-01, U56- CA113004, HG003224]; University of Ghent
[GOA12051401]; Fund for Scientific Research Flanders [FWO-V G. 0031.06];
National Cancer Institute of Canada
FX Supported by funds from the W. M. Keck Foundation (M.V. and F. P. R.);
by Institute Sponsored Research funds from the Dana-Farber Cancer
Institute Strategic Initiative (M.V. and CCSB); by NIH grant R01-
HG001715 (M.V. and F.P.R.); by NIH grants U01-A1070499- 01 and
U56-CA113004 (A.-L.B.); by grant GOA12051401 from the University of
Ghent and grant FWO-VG. 0031.06 from the Fund for Scientific Research
Flanders (J.T.); by a grant from the National Cancer Institute of Canada
(C.B.); and by NIH grant HG003224 (F.P.R.). I.L. is a postdoctoral
fellow with the Fonds Wetenschappelijk Onderzoek-Vlanderen. M.V. is a
"Chercheur Qualifi, Honoraire" from the Fonds de la Recherche
Scientifique (FRS-FNRS, French Community of Belgium). We thank members
of our laboratories for helpful discussions and Agencourt Biosciences
for sequencing assistance. All data sets can be downloaded from our Web
site (http://interactome.dfci.harvard.edu/S_cerevisiae).
NR 45
TC 716
Z9 733
U1 11
U2 108
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 OCT 3
PY 2008
VL 322
IS 5898
BP 104
EP 110
DI 10.1126/science.1158684
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 355AE
UT WOS:000259680200048
PM 18719252
ER
PT J
AU Tamborlane, WV
Beck, RW
Bode, BW
Buckingham, B
Chase, HP
Clemons, R
Fiallo-Scharer, R
Fox, LA
Gilliam, LK
Hirsch, IB
Huang, ES
Kollman, C
Kowalski, AJ
Laffel, L
Lawrence, JM
Lee, J
Mauras, N
O'Grady, M
Ruedy, KJ
Tansey, M
Tsalikian, E
Weinzimer, S
Wilson, DM
Wolpert, H
Wysocki, T
Xing, DY
AF Tamborlane, William V.
Beck, Roy W.
Bode, Bruce W.
Buckingham, Bruce
Chase, H. Peter
Clemons, Robert
Fiallo-Scharer, Rosanna
Fox, Larry A.
Gilliam, Lisa K.
Hirsch, Irl B.
Huang, Elbert S.
Kollman, Craig
Kowalski, Aaron J.
Laffel, Lori
Lawrence, Jean M.
Lee, Joyce
Mauras, Nelly
O'Grady, Michael
Ruedy, Katrina J.
Tansey, Michael
Tsalikian, Eva
Weinzimer, Stuart
Wilson, Darrell M.
Wolpert, Howard
Wysocki, Tim
Xing, Dongyuan
CA Juvenile Diabet Res Fdn Continuous
TI Continuous glucose monitoring and intensive treatment of type 1 diabetes
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GLYCEMIC CONTROL; PEDIATRIC-PATIENTS; PILOT TRIAL; YOUTH; SYSTEM;
COMPLICATIONS; ACCURACY; CHILDREN; MELLITUS; IMPACT
AB Background The value of continuous glucose monitoring in the management of type 1 diabetes mellitus has not been determined.
Methods In a multicenter clinical trial, we randomly assigned 322 adults and children who were already receiving intensive therapy for type 1 diabetes to a group with continuous glucose monitoring or to a control group performing home monitoring with a blood glucose meter. All the patients were stratified into three groups according to age and had a glycated hemoglobin level of 7.0 to 10.0%. The primary outcome was the change in the glycated hemoglobin level at 26 weeks.
Results The changes in glycated hemoglobin levels in the two study groups varied markedly according to age group ( P = 0.003), with a significant difference among patients 25 years of age or older that favored the continuous- monitoring group ( mean difference in change, - 0.53%; 95% confidence interval [ CI], - 0.71 to - 0.35; P< 0.001). The between- group difference was not significant among those who were 15 to 24 years of age ( mean difference, 0.08; 95% CI, - 0.17 to 0.33; P = 0.52) or among those who were 8 to 14 years of age ( mean difference, - 0.13; 95% CI, - 0.38 to 0.11; P = 0.29). Secondary glycated hemoglobin outcomes were better in the continuous- monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the two study groups; however, the trial was not powered to detect such a difference.
Conclusions Continuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes. Further work is needed to identify barriers to effectiveness of continuous monitoring in children and adolescents. ( ClinicalTrials. gov number, NCT00406133.).
C1 [Beck, Roy W.; Kollman, Craig; Ruedy, Katrina J.; Xing, Dongyuan] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
[Chase, H. Peter; Fiallo-Scharer, Rosanna] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Denver, CO 80202 USA.
[Laffel, Lori] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA.
[Buckingham, Bruce; Wilson, Darrell M.] Stanford Univ, Stanford, CA 94305 USA.
[Tansey, Michael; Tsalikian, Eva] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Wolpert, Howard] Joslin Diabet Ctr, Adult Sect, Boston, MA 02215 USA.
[Gilliam, Lisa K.; Hirsch, Irl B.] Univ Washington, Seattle, WA 98195 USA.
[Fox, Larry A.; Mauras, Nelly; Wysocki, Tim] Nemours Childrens Clin, Jacksonville, FL USA.
[Bode, Bruce W.] Atlanta Diabet Assoc, Atlanta, GA USA.
[Clemons, Robert; Lawrence, Jean M.] Kaiser Permanente, San Diego, CA USA.
[Weinzimer, Stuart] Yale Univ, Sch Med, New Haven, CT USA.
[Huang, Elbert S.; O'Grady, Michael] Univ Chicago, Natl Opin Res Ctr, Chicago, IL 60637 USA.
[Lee, Joyce] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Beck, RW (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr 350, Tampa, FL 33647 USA.
EM rbeck@jaeb.org
RI Meltzer, David/C-2926-2009
OI Meltzer, David/0000-0003-2790-7393
FU Juvenile Diabetes Research Foundation [22-2006-1107, 22-2006-1117,
22-20061112, 22-2006-1123, 01-2006-8031]; Abbott Diabetes Care;
Lifescan; Medtronic; DexCom; Novo Nordisk; Sanofi-Aventis; Symlin;
Roche; Charles Hood Foundation; AstraZeneca
FX Supported by grants (22-2006-1107, 22-2006-1117, 22-20061112,
22-2006-1123, and 01-2006-8031) from the Juvenile Diabetes Research
Foundation.; Dr. Tamborlane reports receiving consulting fees from
Abbott Diabetes Care and Lifescan and consulting and lecture fees and
grant support from Medtronic; Dr. Bode, receiving consulting and lecture
fees, travel reimbursement, and grant support from Abbott Diabetes Care
and Medtronic and grant support from DexCom; Dr. Buckingham, receiving
lecture fees and grant support from Abbott Diabetes Care, lecture and
consulting fees and grant support from Medtronic, and consulting fees
from Novo Nordisk and serving on an advisory board for Lifescan; Dr.
Chase, receiving lecture fees from Abbott Diabetes Care and
Sanofi-Aventis and grant support from Symlin; Dr. Fiallo-Scharer,
receiving supplies for research from Abbott Diabetes Care and Medtronic;
Dr. Fox, receiving supplies for research from Abbott Diabetes Care; Dr.
Hirsch, receiving consulting fees and travel reimbursement from Abbott
Diabetes Care and grant support from Medtronic; Dr. Laffel, receiving
consulting fees from Lifescan and Roche, consulting and lecture fees
from Abbott Diabetes Care, consulting fees and grant support from
Medtronic, and grant support from the Charles Hood Foundation; Dr.
Mauras, receiving grant support from AstraZeneca; Dr. Weinzimer,
receiving lecture fees and travel reimbursement from Medtronic; Dr.
Wilson, receiving equipment and software from Abbott Diabetes Care and
Medtronic and grant support from Medtronic; and Dr. Wolpert, receiving
consulting fees from Abbott Diabetes Care and grant support from
Medtronic. No other potential conflict of interest relevant to this
article was reported.
NR 31
TC 519
Z9 529
U1 6
U2 55
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 OCT 2
PY 2008
VL 359
IS 14
BP 1464
EP U65
PG 21
WC Medicine, General & Internal
SC General & Internal Medicine
GA 354ID
UT WOS:000259631700007
ER
PT J
AU Dienstag, JL
AF Dienstag, Jules L.
TI Drug therapy - Hepatitis B virus infection
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID SEVERELY DECOMPENSATED CIRRHOSIS; AWAITING LIVER-TRANSPLANTATION;
EXTENDED LAMIVUDINE TREATMENT; ALPHA-INTERFERON TREATMENT; CHRONIC
ACTIVE HEPATITIS; ADEFOVIR DIPIVOXIL ADV; LONG-TERM THERAPY; TENOFOVIR
DF TDF; E-ANTIGEN; VIRAL SUPPRESSION
C1 [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Off Dean Med Educ, Boston, MA USA.
RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Jackson 7,55 Fruit St, Boston, MA 02114 USA.
EM jdienstag@partners.org
NR 123
TC 482
Z9 525
U1 1
U2 31
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 OCT 2
PY 2008
VL 359
IS 14
BP 1486
EP 1500
DI 10.1056/NEJMra0801644
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA 354ID
UT WOS:000259631700009
PM 18832247
ER
PT J
AU Goldberger, ZD
Weinberger, SE
Nicosia, RF
Saint, S
Young, BA
AF Goldberger, Zachary D.
Weinberger, Steven E.
Nicosia, Roberto F.
Saint, Sanjay
Young, Bessie A.
TI Variations on a theme
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID GLOMERULAR BASEMENT-MEMBRANE; GOODPASTURES-SYNDROME; ALVEOLAR
HEMORRHAGE; ANTIBODY DISEASE; GLOMERULONEPHRITIS; EXPOSURE
C1 [Goldberger, Zachary D.; Saint, Sanjay] Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiovasc Med, CVC Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Saint, Sanjay] Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI 48109 USA.
[Saint, Sanjay] Univ Michigan Hlth Syst, Patient Safety Enhancement Program, Ann Arbor, MI 48109 USA.
[Goldberger, Zachary D.; Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA.
[Nicosia, Roberto F.] Vet Affairs Puget Sound Hlth Care Syst, Pathol Serv, Seattle, WA USA.
[Nicosia, Roberto F.] Vet Affairs Puget Sound Hlth Care Syst, Lab Serv, Seattle, WA USA.
[Nicosia, Roberto F.] Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA USA.
[Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA USA.
Univ Washington, Sch Med, Seattle, WA USA.
[Weinberger, Steven E.] Amer Coll Physicians, Philadelphia, PA USA.
RP Goldberger, ZD (reprint author), Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiovasc Med, CVC Cardiovasc Med, 1500 E Med Ctr Dr,SPC 5853, Ann Arbor, MI 48109 USA.
EM zgoldber@med.umich.edu
FU Advanced Career Development Award; Health Services Research and
Development Program of the Department of Veterans Affairs; National
Institutes of Health [RO1 DK079745-01]
FX We thank Drs. David Au, Vijay Reddy, and Heather Davidson for their care
of the patient.
NR 15
TC 2
Z9 3
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 2
PY 2008
VL 359
IS 14
BP 1502
EP 1507
DI 10.1056/NEJMcps0708762
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 354ID
UT WOS:000259631700012
PM 18832249
ER
PT J
AU Upadhyay, G
Goessling, W
North, TE
Xavier, R
Zon, LI
Yajnik, V
AF Upadhyay, G.
Goessling, W.
North, T. E.
Xavier, R.
Zon, L. I.
Yajnik, V.
TI Molecular association between beta-catenin degradation complex and Rac
guanine exchange factor DOCK4 is essential for Wnt/beta-catenin
signaling
SO ONCOGENE
LA English
DT Article
DE Wnt/beta-catenin; Rac; GSK3 beta; Axin; APC; DOCK4
ID GLYCOGEN-SYNTHASE KINASE-3; DESTRUCTION COMPLEX; NUCLEOTIDE EXCHANGE;
PHOSPHORYLATION; ZEBRAFISH; PATHWAY; GTPASE; ACTIVATION; MECHANISM;
PROTEINS
AB The canonical Wnt/beta-catenin pathway is a highly conserved signaling cascade that is involved in development and stem cell renewal. The deregulation of this pathway is often associated with increased cell growth and neoplasia. The small GTPase Rac has been shown to influence canonical Wnt signaling by regulating beta-catenin stability through an unknown mechanism. We report that DOCK4, a guanine nucleotide exchange factor (GEF) for Rac and a member of the CDM family of unconventional GEFs, mediates Wnt-induced Rac activation in the canonical Wnt/beta-catenin pathway. DOCK4 expression regulates cellular beta-catenin levels in response to the Wnt signal, in vitro. Biochemical studies demonstrate that DOCK4 interacts with the beta-catenin degradation complex, consisting of the proteins adenomatosis polyposis coli, Axin and glycogen synthase kinase 3 beta (GSK3 beta). This molecular interaction enhances beta-catenin stability and Axin degradation. Furthermore, we observe that DOCK4 is phosphorylated by GSK3 beta, which enhances Wnt-induced Rac activation. Using a T-cell factor reporter zebrafish we confirm that DOCK4 is required for Wnt/beta-catenin activity, in vivo. These results elucidate a novel intracellular signaling mechanism in which a Rac GEF, DOCK4 acts as a scaffold protein in the Wnt/beta-catenin pathway.
C1 [Upadhyay, G.; Goessling, W.; Xavier, R.; Yajnik, V.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA.
[Goessling, W.; North, T. E.; Zon, L. I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02114 USA.
RP Yajnik, V (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, 55 Fruit St,GRJ-825, Boston, MA 02114 USA.
EM gu6@georgetown.edu; vyajnik@partners.org
OI Goessling, Wolfram/0000-0001-9972-1569
FU NIH [DK 63933]; MGH GI unit
FX We thank Lars von Buchholtz (NIH, MD, USA), Parool Meelu (MGH, MA, USA),
Tiffany M Blake (Georgetown University, DC, USA) and Denver Matthew
Lough (Georgetown University, DC, USA) for the help in the preparation
of the paper. This study was supported by grant NIH DK 63933 (VY) and
MGH GI unit startup funds (VY).
NR 44
TC 33
Z9 34
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 2
PY 2008
VL 27
IS 44
BP 5845
EP 5855
DI 10.1038/onc.2008.202
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 355QC
UT WOS:000259722400008
PM 18641688
ER
PT J
AU Loerch, PM
Lu, T
Dakin, KA
Vann, JM
Isaacs, A
Geula, C
Wang, J
Pan, Y
Gabuzda, DH
Li, C
Prolla, TA
Yankner, BA
AF Loerch, Patrick M.
Lu, Tao
Dakin, Kelly A.
Vann, James M.
Isaacs, Adrian
Geula, Chengiz
Wang, Jianbin
Pan, Ying
Gabuzda, Dana H.
Li, Cheng
Prolla, Tomas A.
Yankner, Bruce A.
TI Evolution of the Aging Brain Transcriptome and Synaptic Regulation
SO PLOS ONE
LA English
DT Article
AB Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.
C1 [Loerch, Patrick M.; Lu, Tao; Dakin, Kelly A.; Isaacs, Adrian; Pan, Ying; Yankner, Bruce A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Vann, James M.; Prolla, Tomas A.] Univ Wisconsin, Dept Genet & Med Genet, Madison, WI 53706 USA.
[Geula, Chengiz] Northwestern Univ, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL USA.
[Wang, Jianbin; Gabuzda, Dana H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Loerch, Patrick M.; Li, Cheng] Harvard Uni, Harvard Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA USA.
RP Loerch, PM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM bruce_yankner@hms.harvard.edu
FU National Institute on Aging [AG26651, AG27040, AG27916]; Ellison Medical
Foundation Senior Scholar award; NIH [T32GM074897]
FX This work was supported by grants from the National Institute on Aging
(grant numbers AG26651, AG27040, AG27916), and an Ellison Medical
Foundation Senior Scholar award to B.A.Y.. P.L. was supported by NIH
training grant T32GM074897.
NR 37
TC 128
Z9 131
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 2
PY 2008
VL 3
IS 10
AR e3329
DI 10.1371/journal.pone.0003329
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RV
UT WOS:000264797300013
PM 18830410
ER
PT J
AU Damore, D
Mansbach, JM
Clark, S
Ramundo, M
Camargo, CA
AF Damore, Dorothy
Mansbach, Jonathan M.
Clark, Sunday
Ramundo, Maria
Camargo, Carlos A., Jr.
TI Prospective Multicenter Bronchiolitis Study: Predicting Intensive Care
Unit Admissions
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
Pediatric-Academic-Societies/Academic-Pediatric-Association/Society-for-
Pediatric-Research National Conference
CY MAY 02-06, 2008
CL Honolulu, HI
SP Pediat Acad Soc, Acad Pediat Assoc, Soc Pediat Res
DE bronchiolitis; risk factors; multivariate predictors; ICU admission
ID RESPIRATORY SYNCYTIAL VIRUS; RISK-FACTORS; YOUNG-CHILDREN;
EMERGENCY-DEPARTMENTS; CANADIAN CHILDREN; US CHILDREN; INFECTION;
INFANTS; HOSPITALIZATION; MANAGEMENT
AB Objectives: The authors sought to identify predictors of intensive care unit (ICU) admission among children hospitalized with bronchiolitis for 24 hours.
Methods: The authors conducted a prospective cohort study during two consecutive bronchiolitis seasons, 2004 through 2006, in 30 U.S. emergency departments (EDs). All included patients were aged <2 years and had a final diagnosis of bronchiolitis. Regular floor versus ICU admissions were compared.
Results: Of 1,456 enrolled patients, 533 (37%) were admitted to the regular floor and 50 (3%) to the ICU. Comparing floor and ICU admissions, multivariate ED predictors of ICU admission were age <2 months (26% vs. 53%; odds ratio [OR] = 4.1; 95% confidence interval [CI] = 2.1 to 8.3), an ED visit the past week (25% vs. 40%; OR = 2.2; 95% CI = 1.1 to 4.4), moderate/severe retractions (31% vs. 48%; OR = 2.6; 95%, CI = 1.3 to 5.2), and inadequate oral intake (31% vs. 53%; OR = 3.3; 95% CI = 1.6 to 7.1). Unlike previous studies, no association with male gender, socioeconomic factors, insurance status, breast-feeding, or parental asthma was found with ICU admission.
Conclusions: In this prospective multicenter ED-based study of children admitted for bronchiolitis, four independent predictors of ICU admission were identified. The authors did not confirm many putative risk factors, but cannot rule out modest associations. ACADEMIC EMERGENCY MEDICINE 2008; 15:887-894 (C) 2008 by the Society for Academic Emergency Medicine
C1 [Damore, Dorothy; Clark, Sunday] New York Presbyterian Hosp, Weill Cornell Medial Ctr, Dept Emergency Med, New York, NY USA.
[Mansbach, Jonathan M.] Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Ramundo, Maria] Northeastern Ohio Univ Coll Med & Pharm, Akron Childrens Hosp, Dept Emergency Med, Akron, OH USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
RP Damore, D (reprint author), New York Presbyterian Hosp, Weill Cornell Medial Ctr, Dept Emergency Med, New York, NY USA.
EM djt2001@med.cornell.edu
NR 43
TC 30
Z9 30
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD OCT
PY 2008
VL 15
IS 10
BP 887
EP 894
DI 10.1111/j.1553-2712.2008.00245.x
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 359FO
UT WOS:000259972000002
PM 18795902
ER
PT J
AU Huddle, TS
Heudebert, GR
AF Huddle, Thomas S.
Heudebert, Gustavo R.
TI Internal Medicine Training in the 21st Century
SO ACADEMIC MEDICINE
LA English
DT Article
ID RECOMMENDATIONS
AB Many are calling for changes for internal medicine training, arguing that changes in the practice environment mandate changes in how the internal medicine residency is structured. Residency could be shorter, more conducive to role differentiation among general internists, and more supportive of subspecialization. Training could provide more experience in ambulatory care, multidisciplinary team-based care, chronic disease management, and quality improvement.
The authors contend that the claim that internal medicine training ought to mirror internal medicine practice is mistaken. Many changes now proposed would likely damage if not destroy the consultant-generalist ideal of traditional internal medicine training which remains critical to effective medical care in the 21st century. The authors propose a model for training similar in structure but different in spirit from contending models. This model, like others, would involve a core experience in the first two years with tracking in the final year; unlike others, it would provide a conceptually coherent experience based on internal medicine's traditional ideal. Outpatient experience would be subsidiary to a predominantly inpatient experience, and it would be structured in blocks rather than continuity clinics. Twenty-first-century internists will continue to face what has always been the internist's task: the resolution of complex and ill-defined patient problems into proper diagnoses and therapeutic options. Contemporary internal medicine training must fit trainees for that task and must, thus, continue to offer the training experience necessary for the realization of the Oslerian ideal: a substantial apprenticeship taking care of inpatients with a wide range of medical illnesses.
C1 [Huddle, Thomas S.] UAB, Sch Med, Div Gen Internal Med, Birmingham, AL 35294 USA.
[Huddle, Thomas S.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Heudebert, Gustavo R.] Univ Alabama, Sch Med, Dept Med, Birmingham, AL 35294 USA.
RP Huddle, TS (reprint author), UAB, Sch Med, Div Gen Internal Med, 1530 3rd Ave S,FOT 720, Birmingham, AL 35294 USA.
EM thuddle@uab.edu
NR 14
TC 19
Z9 19
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD OCT
PY 2008
VL 83
IS 10
BP 910
EP 915
DI 10.1097/ACM.0b013e3181850a92
PG 6
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 466IJ
UT WOS:000267654500006
PM 18820519
ER
PT J
AU Bagic, A
Theodore, WH
Boudreau, EA
Bonwetsch, R
Greenfield, J
Elkins, W
Sato, S
AF Bagic, A.
Theodore, W. H.
Boudreau, E. A.
Bonwetsch, R.
Greenfield, J.
Elkins, W.
Sato, S.
TI Towards a non-invasive interictal application of hypothermia for
treating seizures: a feasibility and pilot study
SO ACTA NEUROLOGICA SCANDINAVICA
LA English
DT Article
DE brain; core temperature; cortical excitability; epilepsy; non-invasive
hypothermia; interictal cooling; seizures; treatment
ID EXPERIMENTAL NEOCORTICAL SEIZURES; TEMPERATURE-MEASUREMENT; FOCAL
SEIZURES; TECHNICAL NOTE; CRITICAL-CARE; EPILEPSY; BRAIN; PLACEBO;
CORTEX; TERMINATION
AB Objectives - To evaluate the feasibility and safety of head-neck cooling in conscious normal volunteers (10) and patients with medically refractory epilepsy (5) without causing shivering. Patients and methods - We used a non-invasive head-neck cooling system (CoolSystems Inc., Lincoln, CA, USA). The tympanic temperature (TT) and intestinal temperature (IT) were measured as two measurements of 'core temperature' (CT), and multi-site external temperatures, several physiologic variables and EEG were monitored. Seizure counts over 4-week precooling, treatment and follow-up phases were compared. Results - All 15 participants completed all the cooling sessions without significant complaints. At the end of 60 min of cooling, scalp temperature fell on average by 12.2 degrees C (P < 0.001), TT by 1.67 degrees C (P < 0.001), and IT by 0.12 degrees C (P = NS). Average weekly seizure frequency decreased from 2.7 to 1.7 events per patient per week (MANOVA: P < 0.05). Conclusions - Non-invasive head-neck cooling is safe and well-tolerated. Initial pilot data in patients suggest that additional therapeutic studies are warranted.
C1 [Bagic, A.] Univ Pittsburgh, Sch Med, CABMSI, Pittsburgh, PA 15213 USA.
[Bagic, A.; Bonwetsch, R.; Greenfield, J.; Sato, S.] NINDS, NIH, EEG Sect, Bethesda, MD 20892 USA.
[Bagic, A.; Theodore, W. H.] NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA.
[Boudreau, E. A.] Portland VA Med Ctr, Portland, OR USA.
[Elkins, W.] CoolSyst Inc, Lincoln, CA USA.
BioCool Technol, Lincoln, CA USA.
RP Bagic, A (reprint author), Univ Pittsburgh, Sch Med, CABMSI, Suite 811,Kaufmann Med Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM bagica@upmc.edu
FU Intramural NIH HHS [Z01 NS002236-33]
NR 38
TC 9
Z9 9
U1 0
U2 1
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 OCT
PY 2008
VL 118
IS 4
BP 240
EP 244
DI 10.1111/j.1600-0404.2008.01008.x
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 345BC
UT WOS:000258970000005
PM 18355392
ER
PT J
AU Kiernan, TJ
Yan, BP
Jaff, MR
AF Kiernan, Thomas J.
Yan, Bryan P.
Jaff, Michael R.
TI Renal Artery Revascularization: Collaborative Approaches for Specialists
SO ADVANCES IN CHRONIC KIDNEY DISEASE
LA English
DT Article
DE Renal artery stenosis; Stent angioplasty; Renal artery surgery; Embolic
protection device; Restenosis
ID ATHEROSCLEROTIC RENOVASCULAR DISEASE; BLOOD-PRESSURE CONTROL;
TERM-FOLLOW-UP; STENT REVASCULARIZATION; BALLOON ANGIOPLASTY;
HYPERTENSIVE PATIENTS; EMBOLIC PROTECTION; RANDOMIZED-TRIAL; MEDICAL
THERAPY; STENOSIS
AB Endovascular revascularization for atherosclerotic renal artery stenosis (RAS) is the revascularization strategy of choice for patients with hemodynamically and clinically significant renal artery stenosis. Surgical revascularization is reserved for failed endovascular therapy or concomitant abdominal aortic surgery. Endovascular renal artery stenting is associated with excellent technical success, low complication rates, and acceptable long-term patency. This technique has been proven to be beneficial for preserving kidney function and stabilizing or improving blood pressure control in selected patients. Nevertheless, deterioration in kidney function after the procedure in 10% to 20% of cases may limit the immediate benefits of this technique. Atheroembolism appears to play an important role in the cause of kidney dysfunction after renal revascularization. Renal revascularization with a distal embolic protection device is a promising strategy in reducing the risk of atheroembolism and deterioration in kidney function. (C) 2008 by the National Kidney Foundation, Inc. All rights reserved.
C1 [Kiernan, Thomas J.; Yan, Bryan P.; Jaff, Michael R.] Massachusetts Gen Hosp, Dept Vasc Med & Intervent, Boston, MA 02114 USA.
RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Dept Vasc Med & Intervent, 55 Fruit St, Boston, MA 02114 USA.
EM mjaff@partners.org
RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015
NR 43
TC 1
Z9 1
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1548-5595
J9 ADV CHRONIC KIDNEY D
JI Adv. Chronic Kidney Dis.
PD OCT
PY 2008
VL 15
IS 4
BP 363
EP 369
DI 10.1053/j.ackd.2008.07.005
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 360YH
UT WOS:000260094200006
PM 18805382
ER
PT J
AU Casserly, IP
AF Casserly, Ivan P.
TI Interventional Management of Critical Limb Ischemia in Renal Patients
SO ADVANCES IN CHRONIC KIDNEY DISEASE
LA English
DT Article
DE Kidney insufficiency; End-stage renal disease; Critical limb ischemia;
Revascularization; Endovascular therapy; Limb salvage
ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; PERIPHERAL ARTERIAL-DISEASE;
SURGICAL REVASCULARIZATION; BYPASS-SURGERY; INSUFFICIENCY; MORTALITY;
FIBROSIS; DIALYSIS; OUTCOMES; SALVAGE
AB Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease (PAD), defined as the presence of chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease. The occurrence of CLI in patients with kidney insufficiency portends a strikingly high rate of subsequent morbidity and mortality. Generally, the primary therapy for CLI is revascularization of the affected limb. However, patients with CLI and kidney insufficiency represent a unique and challenging patient subset, and data from surgical series suggest reduced rates of limb salvage and higher medium and long-term mortality rates for patients with kidney insufficiency compared with those with normal kidney function. In contemporary practice, endovascular techniques are fast replacing surgical bypass as the first-line revascularization strategy for CLI, based on high technical success rates and low rates of procedure-related morbidity and mortality. However, a large series on endovascular outcomes for the treatment of CLI in patients with kidney insufficiency is lacking. Based on the severely reduced long-term survival rates of patients with CLI and kidney insufficiency, future efforts should focus on early detection of PAD in patients with kidney insufficiency and institution of aggressive medical therapy to prevent progression in the global burden of atherosclerosis in this patient population. Published by Elsevier Inc.
C1 Denver VA Med Ctr, Denver, CO USA.
Univ Colorado Hlth Sci Aurora, Aurora, CO USA.
RP Casserly, IP (reprint author), Univ Colorado Hosp, Cardiac & Vasc Ctr, Mail Stop B-132,Anschutz Med Campus,Leprino Bldg,, Aurora, CO 80045 USA.
EM ivan.casserly@uchsc.edu
NR 27
TC 13
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 1548-5595
J9 ADV CHRONIC KIDNEY D
JI Adv. Chronic Kidney Dis.
PD OCT
PY 2008
VL 15
IS 4
BP 384
EP 395
DI 10.1053/j.ackd.2008.07.008
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 360YH
UT WOS:000260094200009
PM 18805385
ER
PT J
AU Selesniemi, K
Lee, HJ
Tilly, JL
AF Selesniemi, Kaisa
Lee, Ho-Joon
Tilly, Jonathan L.
TI Moderate caloric restriction initiated in rodents during adulthood
sustains function of the female reproductive axis into advanced
chronological age
SO AGING CELL
LA English
DT Article
DE aging; caloric restriction; fecundity; fertility; menopause; oocyte;
ovary; reproduction
ID NONGROWING FOLLICLE NUMBER; AGING C57BL/6J MICE; DIETARY RESTRICTION;
OOCYTE QUALITY; RHESUS-MONKEYS; BONE-MARROW; FOOD-INTAKE; FERTILITY;
MENOPAUSE; MIMETICS
AB Age-related ovarian failure in women heralds the transition into postmenopausal life, which is characterized by a loss of fertility and increased risk for cardiovascular disease, osteoporosis and cognitive dysfunction. Unfortunately, there are no options available for delaying loss of ovarian function with age in humans. Rodent studies have shown that caloric restriction (CR) can extend female fertile lifespan; however, much of this work initiated CR at weaning, which causes stunted adolescent growth and a delayed onset of sexual maturation. Herein we tested in mice if CR initiated in adulthood could delay reproductive aging. After 4 months of CR, the ovarian follicle reserve was doubled compared to ad libitum (AL)-fed age-matched controls, which in mating trials exhibited a loss of fertility by 15.5 months of age. In CR females returned to AL feeding at 15.5 months of age, approximately one-half remained fertile for 6 additional months and one-third continued to deliver offspring through 23 months of age. Notably, fecundity of CR-then-AL-fed females and postnatal offspring survival rates were dramatically improved compared with aging AL-fed controls. For example, between 10 and 23 months of age, only 22% of the 54 offspring delivered by AL-fed females survived. In contrast, over 73% of the 94 pups delivered by 15.5- to 23-month-old CR-then-AL-fed mice survived without any overt complications. These data indicate that in mice adult-onset CR maintains function of the female reproductive axis into advanced age and dramatically improves postnatal survival of offspring delivered by aged females.
C1 [Selesniemi, Kaisa; Lee, Ho-Joon; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent OB GYN Serv, Boston, MA 02114 USA.
RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent OB GYN Serv, THR 901B,55 Fruit St, Boston, MA 02114 USA.
EM jtilly@partners.org
FU National Institute on Aging [R37-AG012279]; Rubin Shulsky Philanthropic
Fund; Henry and Vivian Rosenberg Philanthropic Fund; Sea Breeze
Foundation; JM Foundation; Vincent Memorial Research Funds
FX This work was supported by a MERIT Award from the National Institute on
Aging (R37-AG012279), the Rubin Shulsky Philanthropic Fund, the Henry
and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation, the
JM Foundation, and Vincent Memorial Research Funds.
NR 49
TC 55
Z9 58
U1 4
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD OCT
PY 2008
VL 7
IS 5
BP 622
EP 629
DI 10.1111/j.1474-9726.2008.00409.x
PG 8
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 349TU
UT WOS:000259307000003
PM 18549458
ER
PT J
AU Strong, R
Miller, RA
Astle, CM
Floyd, RA
Flurkey, K
Hensley, KL
Javors, MA
Leeuwenburgh, C
Nelson, JF
Ongini, E
Nadon, NL
Warner, HR
Harrison, DE
AF Strong, Randy
Miller, Richard A.
Astle, Clinton M.
Floyd, Robert A.
Flurkey, Kevin
Hensley, Kenneth L.
Javors, Martin A.
Leeuwenburgh, Christiaan
Nelson, James F.
Ongini, Ennio
Nadon, Nancy L.
Warner, Huber R.
Harrison, David E.
TI Nordihydroguaiaretic acid and aspirin increase lifespan of genetically
heterogeneous male mice
SO AGING CELL
LA English
DT Article
DE aging; aspirin; longevity; mice; nordihydroguaiaretic acid
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TERT-BUTYL NITRONE;
COLORECTAL-CANCER; BREAST-CANCER; RATS; 5-LIPOXYGENASE; ACTIVATION;
GROWTH; CELLS; MODEL
AB The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex, with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p = 0.0006) and aspirin (p = 0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan; neither NDGA (p = 0.12) nor aspirin (p = 0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age-related outcomes reproducibly in mice.
C1 [Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA.
[Miller, Richard A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA.
[Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
[Miller, Richard A.] Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA.
[Astle, Clinton M.; Flurkey, Kevin; Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Floyd, Robert A.; Hensley, Kenneth L.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
[Floyd, Robert A.] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA.
[Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Leeuwenburgh, Christiaan] Univ Florida, Dept Aging & Geriatr, Gainesville, FL 32610 USA.
[Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Ongini, Ennio] Nicox Res Inst, Milan, Italy.
[Nadon, Nancy L.] NIA, Biol Aging Program, Bethesda, MD 20892 USA.
[Warner, Huber R.] Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA.
RP Strong, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 15355 Lambda Dr, San Antonio, TX 78245 USA.
EM strong@uthscsa.edu
FU National Institute on Aging [AG022303, AG025707, AG022308, AG022307,
AG13319]; Department of Veterans Affairs
FX This work was supported by National Institute on Aging grants AG022303
(R.A.M.), AG025707 and AG022308 (D.E.H.), and AG022307 and AG13319
(R.S.), and the Department of Veterans Affairs (R.M. and R.S.). We wish
to thank Vivian Diaz, Elizabeth Fernandez, Greg Friesenhahn, Melissa
Han, Patricia Harrison, Roni Kobrosly, Bill Kohler, Pam Krason, Jessica
Sewald, and Maggie Lauderdale for technical support. We thank Scott
Pletcher and Andrzej Galecki for assistance in power analysis and study
design.
NR 51
TC 103
Z9 106
U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD OCT
PY 2008
VL 7
IS 5
BP 641
EP 650
DI 10.1111/j.1474-9726.2008.00414.x
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 349TU
UT WOS:000259307000005
PM 18631321
ER
PT J
AU Sands, LP
Xu, H
Craig, BA
Eng, C
Covinsky, KE
AF Sands, Laura P.
Xu, Huiping
Craig, Bruce A.
Eng, Catherine
Covinsky, Kenneth E.
TI Predicting change in functional status over quarterly intervals for
older adults enrolled in the PACE community-based long-term care program
SO AGING CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE ADL status; change in functioning; long-term care
ID PHYSICAL PERFORMANCE; UNITED-STATES; RISK-FACTORS; HOME HEALTH; UNMET
NEED; DISABILITY; DEPENDENCE; DECLINE; SERVICES; RECOVERY
AB Background and aims: Many frail older adults experience multiple changes in activities of daily living (ADL) functioning over the course of a year. Accurate predictions of ADL status over quarterly intervals may improve the precision of care planning for older adults who seek long-term care in the community. The study sought to develop and validate a model that predicts older adults' ADL status over quarterly intervals. Methods: The study included 3127 enrollees from 11 Program of All Inclusive Care for the Elderly (PACE) sites. Nurses assessed ADL status quarterly. Potential predictors included baseline assessment of age, sex, race, and living situation and quarterly assessments of prior functioning, co-morbidities, prior hospitalizations, and mental status. Results: Change in level of functioning occurred for 30% of quarterly observations. Predictors of functioning at the end of a quarter were prior ADL change, prior hospitalization, living with others, impaired mental status., cancer, dementia, coronary artery disease, congestive heart failure and chronic obstructive pulmonary disease. When the model was applied to the validation observations, 93% of predictions were within one level and 72% of the predictions were the same level of ADL functioning observed at the end of the quarter. Conclusions: In a sample of community-living ADL-disabled older adults, changes in functional status over a quarter were common and associated with functional and health status at the beginning of the quarter. Further validation of the model may result in an index that helps clinicians better predict future ADL needs of community-living older adults who need long-term care. (Aging Clin Exp Res 2008; 20: 419-427) (c) 2008, Editrice Kurtis.
C1 [Sands, Laura P.] Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA.
[Sands, Laura P.; Craig, Bruce A.] Purdue Univ, Ctr Aging & Life Course, W Lafayette, IN 47907 USA.
[Eng, Catherine] OnLok Senior Hlth Serv, San Francisco, CA USA.
[Eng, Catherine; Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.
[Covinsky, Kenneth E.] Univ Calif San Francisco, MT Z Ctr Aging, San Francisco, CA 94143 USA.
[Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Sands, LP (reprint author), Purdue Univ, Sch Nursing, 502 N Univ St, W Lafayette, IN 47907 USA.
EM lsands@nursing.purdue.edu
RI Craig, Bruce/D-5797-2017; Sands, Laura/E-8919-2015
OI Craig, Bruce/0000-0001-9346-467X; Sands, Laura/0000-0003-2446-4486
FU NIH [R01AG-022090, R01AG023626]
FX This work was supported by NIH grants R01AG-022090 and R01AGO23626 to L.
Sands and K. Covinsky, respectively. A portion of this paper was
presented at the 58th Annual Scientific meeting of the Gerontological
Society of America, Washington DC.
NR 36
TC 5
Z9 5
U1 0
U2 4
PU EDITRICE KURTIS S R L
PI MILAN
PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY
SN 1594-0667
J9 AGING CLIN EXP RES
JI Aging Clin. Exp. Res.
PD OCT
PY 2008
VL 20
IS 5
BP 419
EP 427
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 381BR
UT WOS:000261510300006
PM 19039283
ER
PT J
AU Schackman, BR
Scott, CA
Walensky, RP
Losina, E
Freedberg, KA
Sax, PE
AF Schackman, Bruce R.
Scott, Callie A.
Walensky, Rochelle P.
Losina, Elena
Freedberg, Kenneth A.
Sax, Paul E.
TI The cost-effectiveness of HLA-B*5701 genetic screening to guide initial
antiretroviral therapy for HIV
SO AIDS
LA English
DT Article
DE abacavir; antiretroviral therapy; cost-effectiveness; genetic testing;
HIV
ID ABACAVIR HYPERSENSITIVITY REACTION; NAIVE PATIENTS; TENOFOVIR DF;
COMBINATION; PHARMACOGENOMICS; EMTRICITABINE; EFAVIRENZ; SAFETY; COHORT;
CARE
AB Objective: To evaluate the clinical impact and cost-effectiveness of HLA-B*5701 testing to guide selection of first-line HIV regimens in the United States.
Design: Cost-effectiveness analysis using a simulation model of HIV disease. The prevalence of HLA-B*5701 and the probabilities of confirmed and unconfirmed severe systemic hypersensitivity reaction among patients taking abacavir testing HLA-B*5701 positive and negative were from the Prospective Randomized Evaluation of DNA Screening in a Clinical Trial study. The monthly costs of abacavir-based and tenofovir-based regimens were $1135 and $1139, respectively; similar virologic efficacy was assumed and this assumption was varied in sensitivity analysis.
Patients: Simulated cohort of patients initiating HIV therapy.
Interventions: The interventions are first-line abacavir, lamivudine, and efavirenz without pretreatment HLA-B*5701 testing; the same regimen with HLA-B*5701 testing; and first-line tenofovir, emtricitabine, and efavirenz.
Main outcome measures: Quality-adjusted life years and lifetime medical costs discounted at 3% per annum, cost-effectiveness ratios ($/QALY).
Results: Abacavir-based treatment without HLA-B*5701 testing resulted in a projected 30.93 years life expectancy, 16.23 discounted quality-adjusted life years, and $472 200 discounted lifetime cost per person. HLA-B*5701 testing added 0.04 quality-adjusted months at all incremental cost of $110, resulting in a cost-effectiveness ratio of $36 700/ QALY compared with no testing. Initiating treatment with a tenofovir-based regimen increased costs without improving quality-adjusted life expectancy. HLA-B*5701 testing remained the preferred strategy only if abacavir-based treatment had equal efficacy and cost less per month than tenofovir-based treatment. Results were also sensitive to the cost of HLA-B*5701 testing and the prevalence of HLA-B*5701.
Conclusion: Pharmacogenetic testing for HLA-B*5701 is cost-effective only if abacavir-based treatment is as effective and costs less than tenofovir-based treatment. (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10021 USA.
[Scott, Callie A.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Scott, Callie A.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Scott, Callie A.; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
[Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.; Sax, Paul E.] Harvard Univ, Sch Med, Div AIDS, Boston, MA USA.
[Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.; Sax, Paul E.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA.
[Walensky, Rochelle P.; Sax, Paul E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, 411 E 69th St, New York, NY 10021 USA.
EM brs2006@med.cornell.edu
OI Walensky, Rochelle P./0000-0002-8795-379X
FU National Institute of Allergy and Infectious Diseases [K24 AI062476, K25
AI50436, R37 AI42006]; National Institute on Drug Abuse [K01 DA017179]
FX Financial Support: National Institute of Allergy and Infectious Diseases
(K24 AI062476, K25 AI50436 and R37 AI42006), National Institute on Drug
Abuse (K01 DA017179).
NR 34
TC 79
Z9 84
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD OCT 1
PY 2008
VL 22
IS 15
BP 2025
EP 2033
DI 10.1097/QAD.0b013e3283103ce6
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 355AD
UT WOS:000259680100015
PM 18784465
ER
PT J
AU Pyne, JM
Asch, SM
Lincourt, K
Kilbourne, AM
Bowman, C
Atkinson, H
Gifford, A
AF Pyne, Jeffrey M.
Asch, Steven M.
Lincourt, Katherine
Kilbourne, Amy M.
Bowman, Candice
Atkinson, Hamp
Gifford, Allen
TI Quality indicators for depression care in HIV patients
SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
LA English
DT Article
DE depression; expert panel; HIV; quality of care
ID MULTICENTER AIDS COHORT; ANTIRETROVIRAL THERAPY; HEALTH-CARE;
PSYCHIATRIC COMORBIDITY; INFECTED PATIENTS; RISK-FACTORS; DRUG-USERS;
ADHERENCE; SYMPTOMS; DISORDERS
AB HIV patients are at increased risk for depression. However, a comprehensive set of quality of care indicators for depression in the context of HIV does not exist. We report the results of a recent expert panel convened to develop a comprehensive set of HIV depression quality indicators. We systematically reviewed the depression and HIV depression literature to provide the evidence for the quality indicators. The HIV depression quality indicators were divided into six chapters: general, bereavement, substance abuse, viral hepatitis, cognitive impairment and drug interactions. A modified Delphi expert panel method was used to evaluate the validity and feasibility of the candidate quality indicators. The expert panel included HIV physicians, psychiatrists and a pharmacist, all with experience with HIV depression. The in-person eleven-member panel rated 80 candidate HIV-depression quality indicators. Indicators were evaluated using main and sensitivity analysis criteria for validity and feasibility. Seventy-four percent (59/80) of the quality indicators met a priori main analysis criteria for validity and feasibility and 61% met sensitivity analysis criteria. Approved indicators that are more specific to HIV depression include: depression screening frequency; depression screening and treatment in the context of hepatitis C optimizing depression and HIV treatment in the context of cognitive impairment;, and starting antidepressants at lower doses but advancing to doses typical for the general population. Most adverse medication interaction indicators did not meet main analysis validity criteria. The quality indicators identified in this study provide a useful tool for measuring and informing the quality of HIV-depression care.
C1 [Pyne, Jeffrey M.; Lincourt, Katherine] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA.
[Asch, Steven M.] GLAHS, Dept Vet Affairs, Los Angeles, CA USA.
[Kilbourne, Amy M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Kilbourne, Amy M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Kilbourne, Amy M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Bowman, Candice] VA San Diego Healthcare Syst, QUERI HIV, Hlth Serv Res & Dev, San Diego, CA USA.
[Atkinson, Hamp] San Diego Vet Healthcare Syst, Psychiat Serv, San Diego, CA USA.
[Atkinson, Hamp] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Gifford, Allen] VA Bedford Ctr Hlth Qual, Ctr Hlth Qual Outcomes & Econ Res, Boston, MA USA.
EM jmpyne@uams.edu
NR 44
TC 9
Z9 9
U1 5
U2 7
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0954-0121
J9 AIDS CARE
JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv
PD OCT
PY 2008
VL 20
IS 9
BP 1075
EP 1083
DI 10.1080/09540120701796884
PG 9
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychology, Multidisciplinary; Respiratory System; Social Sciences,
Biomedical
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychology; Respiratory System; Biomedical Social Sciences
GA 363WN
UT WOS:000260298300007
PM 18825515
ER
PT J
AU Pereyra, F
Heckerman, D
Rothchild, A
Brian, B
Baker, B
Walker, BD
AF Pereyra, F.
Heckerman, D.
Rothchild, A.
Brian, B.
Baker, B.
Walker, B. D.
TI Epitope Specific CD8+T-Cell Responses Predict Spontaneous HIV Virus
Replication
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Pereyra, F.; Heckerman, D.; Rothchild, A.; Brian, B.; Baker, B.; Walker, B. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 19
EP 20
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800045
ER
PT J
AU Schneidewind, A
Tang, Y
Ryland, E
Dunkley-Thompson, J
Steel-Duncan, J
Singh-Minott, I
John, AS
Kalams, S
Conrad, J
Christie, CD
Walker, BD
Allen, TM
Feeney, ME
AF Schneidewind, A.
Tang, Y.
Ryland, E.
Dunkley-Thompson, J.
Steel-Duncan, J.
Singh-Minott, I.
John, A. St.
Kalams, S.
Conrad, J.
Christie, C. D.
Walker, B. D.
Allen, T. M.
Feeney, M. E.
TI Control of Viremia in B57+Infants is Mediated by Fitness-Attenuating
Mutations
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Schneidewind, A.; Tang, Y.; Ryland, E.; Dunkley-Thompson, J.; Steel-Duncan, J.; Singh-Minott, I.; Christie, C. D.; Allen, T. M.] Univ Hosp W Indies, Kingston, Mona, Jamaica.
[John, A. St.] Queen Elizabeth Hosp, Bridgetown, Barbados.
[Kalams, S.; Conrad, J.] Vanderbilt Univ, Nashville, TN USA.
[Walker, B. D.; Feeney, M. E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 20
EP 20
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800047
ER
PT J
AU Wang, YE
Li, B
Carlson, JM
Streeck, H
Gladden, AD
Schneidewind, A
Power, KA
Toth, I
Frahm, N
Alter, G
Brander, C
Carrington, M
Walker, BD
Altfeld, M
Heckerman, D
Allen, T
AF Wang, Y. E.
Li, B.
Carlson, J. M.
Streeck, H.
Gladden, A. D.
Schneidewind, A.
Power, K. A.
Toth, I.
Frahm, N.
Alter, G.
Brander, C.
Carrington, M.
Walker, B. D.
Altfeld, M.
Heckerman, D.
Allen, T.
TI Protective HLA Class I Alleles Restrict Acute-Phase CD8 Responses that
Select for Viral Escape in Highly Conserved Regions of HIV
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Wang, Y. E.; Li, B.; Streeck, H.; Gladden, A. D.; Schneidewind, A.; Power, K. A.; Toth, I.; Frahm, N.; Alter, G.; Brander, C.; Altfeld, M.; Allen, T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
[Heckerman, D.] Microsoft Res, Redmond, WA USA.
[Carrington, M.] NCI, Lab Genom Div, Frederick, MD 21701 USA.
[Walker, B. D.] Howard Hughes Med Inst, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 21
EP 22
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800050
ER
PT J
AU Alter, G
Rihn, S
Kavanagh, D
Altfeld, M
AF Alter, G.
Rihn, S.
Kavanagh, D.
Altfeld, M.
TI NK Cell Mediated Deletion of Dendritic Cell Populations
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Alter, G.; Rihn, S.; Kavanagh, D.; Altfeld, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 29
EP 29
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800070
ER
PT J
AU Carr, WH
Naranbhai, V
Arase, H
Lanier, LL
Cavrois, M
Neidleman, JA
Greene, WC
AF Carr, W. H.
Naranbhai, V.
Arase, H.
Lanier, L. L.
Cavrois, M.
Neidleman, J. A.
Greene, W. C.
TI KIR2DS1, an HLA-Cw4 Specific Stimulatory NK Cell Receptor,
Preferentially Binds to HIV-1 Infected Cells Presenting
HLA-Cw4-Restricted HIV-1 Epitopes
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Carr, W. H.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Naranbhai, V.] Univ KwaZulu Natal, Sch Med, HPP, Durban, Kwazulu Natal, South Africa.
[Naranbhai, V.] Univ KwaZulu Natal, Sch Med, CAPRISA, Durban, Kwazulu Natal, South Africa.
[Arase, H.] Osaka Univ, Inst Microbial Dis, Osaka, Japan.
[Lanier, L. L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Cavrois, M.; Neidleman, J. A.; Greene, W. C.] Gladstone Inst Virol & Immunol, San Francisco, CA USA.
[Carr, W. H.] Univ KwaZulu Natal, Nelson Mandela Sch Med, Doris Duke Med Res Ctr, HIV Pathogenesis Programme, Durban, South Africa.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 30
EP 30
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800072
ER
PT J
AU Brumme, ZL
John, M
Brumme, CJ
Carlson, JM
Haubrich, R
Riddler, S
Swenson, L
Tao, I
Szeto, S
Chan, D
Kadie, C
Frahm, N
Brander, C
Walker, BD
Heckerman, D
Harrigan, P
Mallal, S
AF Brumme, Z. L.
John, M.
Brumme, C. J.
Carlson, J. M.
Haubrich, R.
Riddler, S.
Swenson, L.
Tao, I.
Szeto, S.
Chan, D.
Kadie, C.
Frahm, N.
Brander, C.
Walker, B. D.
Heckerman, D.
Harrigan, P.
Mallal, S.
TI Relationship between HLA Class I-driven Evolution in Gag, Pol and Nef
and Clinical Markers of HIV Disease: A Multicenter Collaborative Study
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Brumme, Z. L.; Brumme, C. J.; Frahm, N.; Brander, C.; Walker, B. D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
[John, M.; Mallal, S.] Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia.
[Carlson, J. M.; Kadie, C.; Heckerman, D.] Microsoft Res, Redmond, WA USA.
[Haubrich, R.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Riddler, S.] Univ Pittsburgh, Pittsburgh, PA USA.
[Swenson, L.; Tao, I.; Szeto, S.; Chan, D.; Harrigan, P.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
RI Grandhi, Manasa/A-7711-2008
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 75
EP 75
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800186
ER
PT J
AU Matthews, PC
Leslie, A
Katzourakis, A
Power, K
Kelleher, AD
Allen, T
Pybus, OG
Goulder, PJ
AF Matthews, P. C.
Leslie, A.
Katzourakis, A.
Power, K.
Kelleher, A. D.
Allen, T.
Pybus, O. G.
Goulder, P. J.
TI HLA Footprints in HIV-1 Drive Phylogenetic Clustering and Inter-Clade
Variation
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Power, K.; Allen, T.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
[Kelleher, A. D.] St Vincent Hosp, Ctr Immunol, Sydney, NSW, Australia.
[Leslie, A.; Goulder, P. J.] Univ Oxford, Dept Paediat, Oxford, Oxon, England.
[Katzourakis, A.; Pybus, O. G.] Univ Oxford, Dept Zool, Oxford, Oxon, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 75
EP 75
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800187
ER
PT J
AU Brumme, CJ
Brumme, ZL
Carlson, J
Markowitz, M
Jessen, H
Kelleher, A
John, M
Mallal, S
Allen, T
Heckerman, D
Walker, BD
AF Brumme, C. J.
Brumme, Z. L.
Carlson, J.
Markowitz, M.
Jessen, H.
Kelleher, A.
John, M.
Mallal, S.
Allen, T.
Heckerman, D.
Walker, B. D.
TI Reversion of HLA-Associated Polymorphisms in Gag, Pol and Nef during the
First Year of HIV Infection: Sites, Rates and pVL Correlations
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Brumme, Z. L.; Walker, B. D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
[Carlson, J.; Heckerman, D.] Microsoft Res, Redmond, WA USA.
[Markowitz, M.] Aaron Diamond AIDS Res Ctr, New York, NY USA.
[Jessen, H.] Jessen Praxis, Berlin, Germany.
[Kelleher, A.] Univ New S Wales, Sydney, NSW, Australia.
[John, M.; Mallal, S.] Murdoch Univ, Perth, WA, Australia.
RI Grandhi, Manasa/A-7711-2008
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 76
EP 77
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800190
ER
PT J
AU Miura, T
Brumme, C
Brockman, MA
Pereyra, F
Block, B
Trocha, A
Brumme, Z
John, M
Mallal, S
Harrigan, R
Walker, B
AF Miura, T.
Brumme, C.
Brockman, M. A.
Pereyra, F.
Block, B.
Trocha, A.
Brumme, Z.
John, M.
Mallal, S.
Harrigan, R.
Walker, B.
TI HLA-Associated Mutations Occur Less Frequently in HIV Elite Controllers
than in Chronically Infected Individuals
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Brockman, M. A.; Pereyra, F.; Block, B.; Trocha, A.; Brumme, Z.; Walker, B.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Miura, T.; Brumme, C.; John, M.; Mallal, S.] Murdoch Univ, Perth, WA, Australia.
[Miura, T.; Brumme, C.; John, M.; Mallal, S.] Royal Perth Hosp, Perth, WA, Australia.
[Harrigan, R.] St Pauls Hosp, BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 77
EP 78
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800193
ER
PT J
AU Hempel, U
Buranapraditkun, S
Chatkulkawin, P
Allgaier, RL
Thantivorasit, P
Pitakpolrat, P
Lorenzen, S
Sirivichayakul, S
Hildebrand, WH
Brander, C
Walker, BD
Phanuphak, P
Allen, TM
Ruxrungtham, K
AF Hempel, U.
Buranapraditkun, S.
Chatkulkawin, P.
Allgaier, R. L.
Thantivorasit, P.
Pitakpolrat, P.
Lorenzen, S.
Sirivichayakul, S.
Hildebrand, W. H.
Brander, C.
Walker, B. D.
Phanuphak, P.
Allen, T. M.
Ruxrungtham, K.
TI Viral Escape from a Dominant HLA-Cw01-Restricted Gag Epitope in HIV-1
Clade A/E Infection
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Hempel, U.; Allgaier, R. L.; Brander, C.; Walker, B. D.; Allen, T. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Buranapraditkun, S.; Chatkulkawin, P.; Thantivorasit, P.; Pitakpolrat, P.; Lorenzen, S.; Sirivichayakul, S.; Phanuphak, P.; Ruxrungtham, K.] Chulalongkorn Univ, Vaccine & Cellular Immunol Lab, Bangkok, Thailand.
[Hildebrand, W. H.] Univ Oklahoma, Dept Microbiol & Immunol, Oklahoma City, OK USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 78
EP 78
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800194
ER
PT J
AU Schneidewind, A
Brumme, ZL
Brume, CJ
Power, KA
Reyor, LL
O'Sullivan, K
Jessen, H
Markowitz, M
Rosenberg, ES
Sekaly, R
Kelleher, AD
Walker, BD
Allen, TM
AF Schneidewind, A.
Brumme, Z. L.
Brume, C. J.
Power, K. A.
Reyor, L. L.
O'Sullivan, K.
Jessen, H.
Markowitz, M.
Rosenberg, E. S.
Sekaly, R.
Kelleher, A. D.
Walker, B. D.
Allen, T. M.
TI Long-term Stability of Compensated CTL Escape Mutations following Acute
HIV Infection
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Schneidewind, A.; Brumme, Z. L.; Brume, C. J.; Power, K. A.; Reyor, L. L.; O'Sullivan, K.; Rosenberg, E. S.; Walker, B. D.; Allen, T. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA.
[Jessen, H.] Jessen Praxis, Berlin, Germany.
[Markowitz, M.] Aaron Diamond AIDS Res Ctr, New York, NY USA.
[Markowitz, M.] Univ Montreal, Motnreal, PQ, Canada.
[Kelleher, A. D.] Univ New S Wales, Sydney, NSW, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 78
EP 78
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800195
ER
PT J
AU Liu, Q
Sun, Y
Rihn, S
Pereyra, F
Walker, B
Alter, G
AF Liu, Q.
Sun, Y.
Rihn, S.
Pereyra, F.
Walker, B.
Alter, G.
TI Protective Antibody Dependent Cellular Cytotoxicity Depends on the
Coordinated Presence of Both Highly Functional NK Cells and HIV-Specific
Antibodies
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Liu, Q.; Rihn, S.; Pereyra, F.; Walker, B.; Alter, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sun, Y.] Fourth Mil Med Univ, Tangdu Hosp, Xian 710032, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 81
EP 82
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800203
ER
PT J
AU Wong, AH
Williams, K
Reddy, S
Van Der Stok, M
Giddy, J
Wilson, D
Alter, G
Ghebremichael, MS
Carrington, M
Ndung'u, T
Walker, B
Altfeld, M
Carr, WH
AF Wong, A. H.
Williams, K.
Reddy, S.
Van der Stok, M.
Giddy, J.
Wilson, D.
Alter, G.
Ghebremichael, M. S.
Carrington, M.
Ndung'u, T.
Walker, B.
Altfeld, M.
Carr, W. H.
TI Alterations in Natural Killer Cell Receptor Profiles during HIV-1
Disease Progression among Chronically Infected South African Adults
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Wong, A. H.; Williams, K.; Reddy, S.; Van der Stok, M.; Alter, G.; Ndung'u, T.; Walker, B.; Altfeld, M.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA.
[Giddy, J.] MCcord Hosp, Durban, Kwazulu Natal, South Africa.
[Wilson, D.] Edendale Hosp, Dept Med, Edendale, Kwazulu Natal, South Africa.
[Ghebremichael, M. S.] Harvard Univ, Boston, MA 02115 USA.
[Ghebremichael, M. S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Carrington, M.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Carr, W. H.] Univ Kwazulu Natal, Doris Duke Med Res Ctr, Durban, Kwazulu Natal, South Africa.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 83
EP 84
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800208
ER
PT J
AU Brumme, Z
Nair, K
Wang, B
van der Stok, M
Brumme, C
Bishop, K
Reddy, S
Mncube, Z
Chonco, F
Frahm, N
Goulder, P
Ndung'u, T
Freedberg, K
Losina, E
Walker, B
AF Brumme, Z.
Nair, K.
Wang, B.
van der Stok, M.
Brumme, C.
Bishop, K.
Reddy, S.
Mncube, Z.
Chonco, F.
Frahm, N.
Goulder, P.
Ndung'u, T.
Freedberg, K.
Losina, E.
Walker, B.
TI Combined Clinical and Immunological Biomarkers Predict Rates of CD4
Decline in Chronic Untreated HIV Infection
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Brumme, Z.; Brumme, C.; Frahm, N.; Walker, B.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
[Nair, K.; van der Stok, M.; Bishop, K.; Reddy, S.; Mncube, Z.; Chonco, F.; Ndung'u, T.] Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, Kwazulu Natal, South Africa.
[Wang, B.; Freedberg, K.; Losina, E.] Massachusetts Gen Hosp, Program HIV Outcomes Res, Boston, MA 02114 USA.
[Goulder, P.] Nuffield Dept Med, Dept Pediat, Oxford, England.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 122
EP 122
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800312
ER
PT J
AU Kwon, DS
Brockman, MA
Tighe, DP
Pavlik, DF
Addo, MM
Kavanagh, DG
Waring, M
Walker, BD
Kaufmann, DE
AF Kwon, D. S.
Brockman, M. A.
Tighe, D. P.
Pavlik, D. F.
Addo, M. M.
Kavanagh, D. G.
Waring, M.
Walker, B. D.
Kaufmann, D. E.
TI Role of CD4+CD25+Regulatory T Cells in IL-10 Mediated T Cell Impairment
in Chronic HIV Infection
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Kwon, D. S.; Brockman, M. A.; Tighe, D. P.; Pavlik, D. F.; Addo, M. M.; Kavanagh, D. G.; Waring, M.; Walker, B. D.; Kaufmann, D. E.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 2
U2 9
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 128
EP 128
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800327
ER
PT J
AU Juelg, B
Pereyra, F
Piechocka-Trocha, A
Rothchild, A
Baker, B
Walker, BD
AF Juelg, B.
Pereyra, F.
Piechocka-Trocha, A.
Rothchild, A.
Baker, B.
Walker, B. D.
TI Defining the Correlates of Immune Protection Using the Viral Inhibition
Assay: Does Immunodominance Correlate with Antiviral Suppressive
Capacity?
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Juelg, B.; Pereyra, F.; Piechocka-Trocha, A.; Rothchild, A.; Baker, B.; Walker, B. D.] Massachusetts Gen Hosp, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 129
EP 129
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800330
ER
PT J
AU Frahm, N
Price, DA
Hartman, K
Pereyra, F
Walker, BD
Douek, DC
Brander, C
AF Frahm, N.
Price, D. A.
Hartman, K. L.
Pereyra, F.
Walker, B. D.
Douek, D. C.
Brander, C.
TI The Functional Avidity of HIV-Specific CTL Responses is Associated with
Control of Viral Replication In Vivo
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT AIDS Vaccine 2008 Conference
CY OCT 13-16, 2008
CL Cape Town, SOUTH AFRICA
SP NIAID, Div AIDS, NIH, Div AIDS
C1 [Frahm, N.] Fred Hutchinson Canc Res Ctr, HVTN, Seattle, WA 98104 USA.
[Price, D. A.; Douek, D. C.] NIAID, Human Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hartman, K. L.; Pereyra, F.; Walker, B. D.; Brander, C.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA.
[Hartman, K. L.; Pereyra, F.; Walker, B. D.; Brander, C.] HMS, Charlestown, MA USA.
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2008
VL 24
BP 131
EP 131
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 367CT
UT WOS:000260530800335
ER
PT J
AU Al-Khatib, SM
Sanders, GD
Carlson, M
Cicic, A
Curtis, A
Fonarow, GC
Groeneveld, PW
Hayes, D
Heidenreich, P
Mark, D
Peterson, E
Prystowsky, EN
Sager, P
Salive, ME
Thomas, K
Yancy, CW
Zareba, W
Zipes, D
AF Al-Khatib, Sana M.
Sanders, Gillian D.
Carlson, Mark
Cicic, Aida
Curtis, Anne
Fonarow, Gregg C.
Groeneveld, Peter W.
Hayes, David
Heidenreich, Paul
Mark, Daniel
Peterson, Eric
Prystowsky, Eric N.
Sager, Philip
Salive, Marcel E.
Thomas, Kevin
Yancy, Clyde W.
Zareba, Wojciech
Zipes, Douglas
TI Preventing tomorrow's sudden cardiac death today: Dissemination of
effective therapies for sudden cardiac death prevention
SO AMERICAN HEART JOURNAL
LA English
DT Editorial Material
ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ACUTE MYOCARDIAL-INFARCTION;
CONGESTIVE-HEART-FAILURE; INITIATE LIFESAVING TREATMENT;
LEFT-VENTRICULAR DYSFUNCTION; QUALITY-OF-CARE; TRIAL SCD-HEFT;
COST-EFFECTIVENESS; RACIAL DISPARITY; ELDERLY-PATIENTS
AB Because the burden of sudden cardiac death (SCD) is substantial, it is important to use all guideline-driven therapies to prevent SCD. Among those therapies is the implantable cardioverter defibrillator (ICD). When indicated, ICD use is beneficial and cost-effective. Unfortunately, studies suggest that most patients who have indications for this therapy for primary or secondary prevention of SCD ore not receiving it. To explore potential reasons for this underuse and to propose potential facilitators for ICD dissemination, the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute (Durham, NC) organized a think tank meeting of experts on this issue. The meeting took place on December 12 and 13, 2007, and it included representatives of clinical cardiology, cardiac electrophysiology, general internal medicine, economics, health policy, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health care Research and Quality, and the device and pharmaceutical industry. Although the meeting was funded by industry participants, this article summarizing the presentations and discussions that occurred of the meeting presents the expert opinion of the authors.
C1 [Al-Khatib, Sana M.; Sanders, Gillian D.; Mark, Daniel; Peterson, Eric; Thomas, Kevin] Duke Clin Res Inst, Durham, NC 27715 USA.
[Carlson, Mark] St Jude Med, Sylmar, CA USA.
[Cicic, Aida] Medtronic Inc, Mounds View, MN USA.
[Curtis, Anne] Univ S Florida, Tampa, FL USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Groeneveld, Peter W.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Hayes, David] Mayo Clin, Rochester, MN USA.
[Heidenreich, Paul] Palo Alto Vet Affairs Hlth Care Syst, Palo Alto, CA USA.
[Prystowsky, Eric N.] St Vincents Hosp, Indianapolis, IN USA.
[Sager, Philip] CardioDx Inc, Palo Alto, CA USA.
[Salive, Marcel E.] Ctr Medicare, Baltimore, MD USA.
[Salive, Marcel E.] Ctr Medicaid Serv, Baltimore, MD USA.
[Yancy, Clyde W.] Baylor Univ, Med Ctr, Dallas, TX USA.
[Zareba, Wojciech] Univ Rochester, Rochester, NY USA.
[Zipes, Douglas] Indiana Univ, Indianapolis, IN 46204 USA.
RP Al-Khatib, SM (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
EM alkha001@mc.duke.edu
OI Mark, Daniel/0000-0001-6340-8087; Zipes, Douglas/0000-0001-7141-6829;
Heidenreich, Paul/0000-0001-7730-8490
NR 60
TC 30
Z9 32
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2008
VL 156
IS 4
BP 613
EP 622
DI 10.1016/j.ahj.2008.05.027
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 359CH
UT WOS:000259963300001
PM 18926144
ER
PT J
AU Steinberg, BA
Bhatt, DL
Mehta, S
Poole-Wilson, PA
O'Hagan, P
Montalescot, G
Ballantyne, CM
Cannon, CP
AF Steinberg, Benjamin A.
Bhatt, Deepalk L.
Mehta, Shamir
Poole-Wilson, Philip A.
O'Hagan, Philip
Montalescot, Gilles
Ballantyne, Christie M.
Cannon, Christopher P.
TI Diabetes and metabolism - Nine-year trends in achievement of risk factor
goals in the US and European outpatients with cardiovascular disease
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; BLOOD-GLUCOSE CONTROL; HEART SURVEY; STABLE
ANGINA; SECONDARY PREVENTION; MYOCARDIAL-INFARCTION; LOWERING TREATMENT;
EUROASPIRE-II; GUIDELINES; MANAGEMENT
AB Background Although control of major cardiovascular risk factors (hypertension, hyperlipidemia, diabetes) has been the centerpiece of guidelines for the prevention of cardiovascular disease, periodic surveys suggest adherence to recommendations and achievement of goals is poor. Few data are available in outpatients, and no studies describe trends in meeting clinical targets.
Methods A survey of outpatients with cardiovascular disease or risk factors was conducted annually, with a unique cohort each year, and included medical history, clinical data, and pharmacologic therapies. Data from 1998 to 2006 in the United States, United Kingdom, France, Italy, Spain, and Germany were analyzed for achievement of evidenced-based goals for hypertension, hyperlipidemia, and diabetes.
Results Over 9 years, 102,318 patients were entered, with a mean age of 60 years, half were male, and each had at least one cardiovascular disease risk factor. In 1998, nearly half of patients in the United States were not at their target for blood pressure or low-density lipoprotein cholesterol. In Europe, < 1 in 3 was at blood pressure goal, and a minority had low-density lipoprotein recorded. Only modest improvements were observed by 2006. Hemoglobin A(1c) levels improved from 2005 to 2006 in the United States and Europe, indicating improving glycemic control in these cohorts.
Conclusions Adherence to guidelines in these outpatients was suboptimal and lower in Europe than in the United States. Increases adherence to evidence-based targets for the treatment of hypertension, hyperlipidemia, and diabetes is needed to achieve ideal cardiovascular prevention.
C1 [Steinberg, Benjamin A.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Bhatt, Deepalk L.] Cleveland Clin, Cleveland, OH 44106 USA.
[Mehta, Shamir] McMaster Univ, Hamilton, ON, Canada.
[Poole-Wilson, Philip A.] Univ London Imperial Coll Sci Technol & Med, London, England.
[O'Hagan, Philip] Taylor Nelson Sofres Healthcare, Epsom, Surrey, England.
[Montalescot, Gilles] Pitie Salpetriere Univ Hosp, Inst Cardiol, Paris, France.
[Ballantyne, Christie M.] Baylor Coll Med, Houston, TX USA.
[Ballantyne, Christie M.] Methodist DeBakey Heart Ctr, Houston, TX USA.
[Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA.
EM cpcannon@partners.org
NR 39
TC 59
Z9 60
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2008
VL 156
IS 4
BP 719
EP 727
DI 10.1016/j.ahj.2008.05.020
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 359CH
UT WOS:000259963300014
PM 18926153
ER
PT J
AU Maddox, TM
Ross, C
Ho, PM
Masoudi, FA
Magid, D
Daugherty, SL
Peterson, P
Rumsfeld, JS
AF Maddox, Thomas M.
Ross, Colleen
Ho, P. Michael
Masoudi, Frederick A.
Magid, David
Daugherty, Stacie L.
Peterson, Pam
Rumsfeld, John S.
TI Imaging and diagnostic testing - The prognostic importance of abnormal
heart rate recovery and chronotropic response among exercise treadmill
test patients
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CORONARY-ARTERY DISEASE; BAROREFLEX SENSITIVITY; MYOCARDIAL-INFARCTION;
RATE-VARIABILITY; MORTALITY; PREDICTOR; SCORE; INCOMPETENCE;
ELECTROCARDIOGRAM; FAILURE
AB Background Heart rate recovery (HRR) and chronotropic response to exercise (CR) each have prognostic value among patients undergoing exercise treadmill testing (ETT). However, little is known about their prognostic use in combination and in addition to the Duke Treadmill Score (DTS).
Methods We studied 9,519 outpatients undergoing ETT between 2001 and 2004. Patients were categorized by HRR and CR. The primary outcome was all-cause mortality or nonfatal myocardial infarction (MI). Cox proportional hazards modeling was used to control for demographics, clinical history, and DTS.
Results After multivariable adjustment for DTS and other demographic and clinical variables, patients with abnormal HRR and CR had higher rates of all-cause mortality or nonfatal MI, as compared to patients with normal HRR and CR (hazard ratio [HR] = 1.90, 95% CI 1.35-2.69). Addition of the HRR and CR to the DTS improved outcome prediction (c-statistic improved from 0.61 to 0.68). Low-risk DTS patients with abnormal HRR and CR had significantly higher rates of all-cause mortality or nonfatal MI (HR 2.59, 95% CI 1.55-4.32), compared to low-risk DTS patients with normal HRR and CR.
Conclusions Abnormal HRR and CR identified ETT patients with higher rates of all-cause mortality or nonfatal MI and provided additional risk stratification among low-risk DTS patients. These results support the routine incorporation of HRR and CR in ETT reporting and suggest the need to evaluate whether further testing and/or more intensive treatment of these higher risk patients can improve outcomes.
C1 [Maddox, Thomas M.; Ho, P. Michael; Rumsfeld, John S.] Univ Colorado, Denver VAMC, Cardiol Sect 111B, Denver, CO 80209 USA.
[Ross, Colleen; Magid, David] Kaiser Permanente, Inst Hlth Res, Denver, CO USA.
[Masoudi, Frederick A.; Peterson, Pam] Univ Colorado, Denver Hlth, Denver, CO 80209 USA.
RP Maddox, TM (reprint author), Univ Colorado, Denver VAMC, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80209 USA.
EM thomas.maddox@va.gov
NR 29
TC 26
Z9 28
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD OCT
PY 2008
VL 156
IS 4
BP 736
EP 744
DI 10.1016/j.ahj.2008.05.025
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 359CH
UT WOS:000259963300016
PM 18926155
ER
PT J
AU Garcia, S
Moritz, TE
Ward, HB
Pierpont, G
Goldman, S
Larsen, GC
Littooy, F
Krupski, W
Thottapurathu, L
Reda, DJ
McFalls, EO
AF Garcia, Santiago
Moritz, Thomas E.
Ward, Herbert B.
Pierpont, Gordon
Goldman, Steve
Larsen, Greg C.
Littooy, Fred
Krupski, William
Thottapurathu, Lizy
Reda, Domenic J.
McFalls, Edward O.
TI Usefulness of revascularization of patients with multivessel coronary
artery disease before elective vascular surgery for abdominal aortic and
peripheral occlusive disease
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LONG-TERM SURVIVAL; NONCARDIAC SURGERY; CARDIAC RISK; CARP TRIAL;
MORTALITY; OUTCOMES
AB The Coronary Artery Revascularization Prophylaxis (CARP) study showed no survival benefit with preoperative coronary artery revascularization before elective vascular surgery. The generalizability of the trial results to all patients with multivessel. coronary artery disease (CAD) has been questioned. The objective of this study was to determine the impact of prophylactic coronary revascularization on long-term survival in patients with multivessel CAD. Over a 4-year period, 1,048 patients underwent coronary angiography before vascular surgery during screening into the CARP trial. The cohort was composed of registry (n = 586) and randomized (n = 462) patients, and their survival was determined at 2.5 years after vascular surgery. High-risk coronary anatomy without previous bypass surgery included 2-vessel disease (n = 204 [19.5%]), 3-vessel disease (n = 130 [12.4%]), and left main coronary artery stenosis >= 50% (n = 48 [4.6%]). By log-rank test, preoperative revascularization was associated with improved survival in patients with a left main coronary artery stenoses (0.84 vs 0.52, p <0.01) but not those with either 2-vessel (0.80 vs 0.79, p = 0.83) or 3-vessel (0.79 vs 0.71, p = 0.15) disease. In conclusion, unprotected left main coronary artery disease was present in 4.6% of patients who underwent coronary angiography before vascular surgery, and this was the only subset of patients showing a benefit with preoperative coronary artery revascularization. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Garcia, Santiago; Ward, Herbert B.; Pierpont, Gordon; McFalls, Edward O.] Univ Minnesota, Vet Affairs Med Ctr, Cardiol Sect, Minneapolis, MN 55455 USA.
[Littooy, Fred] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA.
[Goldman, Steve] Univ Arizona, So Arizona Vet Affairs Hlth Care Ctr, Tucson, AZ USA.
[Larsen, Greg C.] Portland VA Med Ctr, Portland, OR USA.
[Larsen, Greg C.] Oregon Hlth & Sci Univ, Portland, OR USA.
[Krupski, William] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA.
RP McFalls, EO (reprint author), Univ Minnesota, Vet Affairs Med Ctr, Cardiol Sect, Minneapolis, MN 55455 USA.
EM mcfal001@umn.edu
FU United States Department of Veterans Affairs, Office of Research and
Development, Washington, District of Columbia
FX This study was supported by the Cooperative Studies Program of the
United States Department of Veterans Affairs, Office of Research and
Development, Washington, District of Columbia.
NR 16
TC 31
Z9 31
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 OCT 1
PY 2008
VL 102
IS 7
BP 809
EP 813
DI 10.1016/j.amjcard.2008.05.022
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 354CI
UT WOS:000259616100003
PM 18805102
ER
PT J
AU Sorgente, A
Truong, QA
Conca, C
Singh, JP
Hoffmann, U
Faletra, FF
Klersy, C
Bhatia, R
Pedrazzini, GB
Pasotti, E
Moccetti, T
Auricchio, A
AF Sorgente, Antonio
Truong, Quynh A.
Conca, Cristina
Singh, Jagmeet P.
Hoffmann, Udo
Faletra, Francesco F.
Klersy, Catherine
Bhatia, Rinky
Pedrazzini, Giovanni B.
Pasotti, Elena
Moccetti, Tiziano
Auricchio, Angelo
TI Influence of left atrial and ventricular volumes on the relation between
mitral valve annulus and coronary sinus
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CARDIAC RESYNCHRONIZATION THERAPY; VENOUS ANATOMY; COMPUTED-TOMOGRAPHY;
ANNULOPLASTY; REGURGITATION; ECHOCARDIOGRAPHY; VISUALIZATION;
TACHYCARDIA; VENOGRAPHY; ABLATION
AB The aim of this study was to evaluate the anatomic relation between the coronary sinus (CS), mitral annulus, and coronary arteries using 64-multislice computed tomography (MSCT) in patients presenting with a wide range of atrial volumes and left ventricular functions to determine the potential clinical use for percutaneous mitral annuloplasty (PMA). The MSCT data of 165 patients (age 63.65 +/- 12.89 years, 67.3% men) were evaluated. The following variables were measured: CS length, CS ostium area, area of the section of CS when it becomes great cardiac vein, area between CS and atrioventricular groove assessed in volume-rendered 3-dimensional images, axial angle measured as the angle between CS and mitral annulus assessed in axial section, mitral valve annulus (MVA) area, left atrium volume, and left circumflex artery/marginal branch-CS relation referring to mitral annulus. The correlation was inversed between the reduction of the axial angle and all following variables: enlargement of both left ventricular end-systolic (r = -0.429, p <0.001) and end-diastolic (r = -0.428, p <0.001) volumes, left atrial volume (r = -0.361, p <0.001), and MVA (r = -0.324, p <0.001). Similarly, there was inverse correlation between the reduction of the area between CS and atrioventricular groove, and enlargement of both left ventricular end-systolic (r = -0.376, p <0.001) and end-diastolic (r = -0.291, p <0.001) volumes, left atrial volume (r = -0.221, p = 0.001), and MVA (r = -0.155, p = 0.019). Of note, circumflex artery was located between CS and MVA in 77% of the patients, but in patients with severe mitral regurgitation CS crossed circumflex/marginal branch artery more frequently (97% of cases). In conclusion, a close proximity of the CS to the mitral annulus but also to circumflex artery is more likely to occur with left atrial and ventricular enlargement. Thus, MSCT should be considered as part of the selection process of potential candidate to PMA to avoid external compression of circumflex artery/marginal branch by the device. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Sorgente, Antonio; Conca, Cristina; Faletra, Francesco F.; Pedrazzini, Giovanni B.; Pasotti, Elena; Moccetti, Tiziano; Auricchio, Angelo] Fondaz Cardioctr Ticino, Dept Cardiol, Lugano, Switzerland.
[Truong, Quynh A.; Hoffmann, Udo; Bhatia, Rinky] Harvard Univ, Sch Med, Cardiac MR PET CT Program, Dept Radiol, Cambridge, MA 02138 USA.
[Truong, Quynh A.; Hoffmann, Udo; Bhatia, Rinky] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CIMIT, Cambridge, MA 02138 USA.
[Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cambridge, MA 02138 USA.
[Singh, Jagmeet P.] Harvard Univ, Sch Med, Cardiac Resynchronizat Therapy Program, MGH Heart Ctr, Cambridge, MA 02138 USA.
[Klersy, Catherine] Policlin San Matteo, Fondaz IRCCS, Res Dept, Biometry & Clin Epidemiol Serv, I-27100 Pavia, Italy.
RP Auricchio, A (reprint author), Fondaz Cardioctr Ticino, Dept Cardiol, Lugano, Switzerland.
EM angelo.auricchio@cardiocentro.org
OI Klersy, Catherine/0000-0003-0314-8548
FU NHLBI NIH HHS [T32 HL076136, T32 HL076136-05]
NR 19
TC 4
Z9 4
U1 0
U2 3
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 OCT 1
PY 2008
VL 102
IS 7
BP 890
EP 896
DI 10.1016/j.amjcard.2008.05.044
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 354CI
UT WOS:000259616100018
PM 18805117
ER
PT J
AU Martinez-Rumayor, A
Camargo, CA
Green, SM
Baggish, AL
O'Donoghue, M
Januzzi, JL
AF Martinez-Rumayor, Abelardo
Camargo, Carlos A., Jr.
Green, Sandy M.
Baggish, Aaron L.
O'Donoghue, Michelle
Januzzi, James L., Jr.
TI Soluble ST2 plasma concentrations predict 1-year mortality in acutely
dyspneic emergency department patients with pulmonary disease
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE interleukin-1 receptor; ST2; dyspnea; pulmonary disease; mortality
ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE CORONARY SYNDROMES; RECEPTOR
FAMILY-MEMBER; RISK STRATIFICATION; NATRIURETIC PEPTIDE; ACUTE
EXACERBATION; IL-1 RECEPTOR; HEART-FAILURE; TH2 CELLS; EXPRESSION
AB We evaluated the association between ST2 concentrations and mortality at 1 year in 231 acutely, dyspneic patients with pulmonary diseases seen in the emergency, department. Blood concentrations of ST2 were ascertained: using 1-year survival as the reference standard, receiver operating characteristic re curves with resultant area under the curve (AUC) were measured Cox proportional hazards models identified independent predictors of 1-year death. Hazard curves compared rates of death as a function of ST2 concentration.
Concentrations of ST2 were siganificantly higher in patients with pulmonary diseases compared with 153 subjects without cardiopulmonary disease (0.23 vs 0.11 ng/mL: P =.01). Among patients with pulmonary diseases, concentrations of ST2 were higher among decedents compared with survivors (1.14 ng/mL vs 0.19 ng/mL P < .001). ST2 had an AUC of 0.72 as a predictor of death (P < .0001). An ST2 of 0.20 ng/mL had a hazard ratio for death of 6.1 (95% confidence interval, 1.8-21.0; P = .004). Compared with patients with lower ST2 concentrations, mortality rates for patients with an enrollment ST2 of 0.20 ng/mL or more diverged early, and rose progressively in 1 year (P < .001).
ST2 concentrations are frequently elevated in acute pulmonary diseases and are markedly prognostic for death by 1 year.
C1 [Baggish, Aaron L.; O'Donoghue, Michelle; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Martinez-Rumayor, Abelardo; Green, Sandy M.; Baggish, Aaron L.; O'Donoghue, Michelle; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Yawkey 5984, Boston, MA 02114 USA.
NR 39
TC 33
Z9 35
U1 0
U2 1
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD OCT
PY 2008
VL 130
IS 4
BP 578
EP 584
DI 10.1309/WMG2BFRC97MKKQKP
PG 7
WC Pathology
SC Pathology
GA 349ZY
UT WOS:000259323400011
PM 18794051
ER
PT J
AU Roehrl, MHA
Rho, J
Wang, JY
AF Roehrl, Michael H. A.
Rho, Jung-hyun
Wang, Julia Y.
TI Glycoproteomic analysis of human lung adenocarcinomas using glycoarrays
and tandem mass spectrometry: Differential expression and glycosylation
patterns of vimentin and fetuin a isoforms
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Pathology
CY OCT 16-19, 2008
CL Baltimore, MD
SP Amer Soc Clin Pathol
C1 [Roehrl, Michael H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rho, Jung-hyun; Wang, Julia Y.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wang, Julia Y.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD OCT
PY 2008
VL 130
IS 4
MA 7
BP 650
EP 650
PG 1
WC Pathology
SC Pathology
GA 349ZY
UT WOS:000259323400030
ER
PT J
AU Ahmed, AAR
Garcia-Godoy, F
Kunzelmann, KH
AF Rashid Ahmed, Aya Abdulla
Garcia-Godoy, Franklin
Kunzelmann, Karl-Heinz
TI Self-limiting caries therapy with proteolytic agents
SO AMERICAN JOURNAL OF DENTISTRY
LA English
DT Article
ID ELECTRON-MICROSCOPIC OBSERVATIONS; ORGANIC MATRIX COMPONENTS; BOVINE
INCISOR ROOTS; DENTIN IN-VITRO; CARIOUS DENTIN; CHEMOMECHANICAL REMOVAL;
DEMINERALIZED DENTIN; COLLAGENOUS MATRIX; LESION FORMATION; DECIDUOUS
TEETH
AB Purpose: To determine the extent to which artificial carious dentin can be removed by agents that do not seem to attack sound dentin such as pepsin, trypsin, collagenase and NaOCl, and to evaluate the effect of the enzyme pepsin and a new enzymatic solution SFC-V (pepsin in mild acidic buffer) as a self-limiting caries therapy in deep dentin carious lesions using our new model for artificial dentin caries. Methods: Artificial dentin caries was used to investigate different proteolytic agents which have the potential to remove carious tissue. 408 slices of coronal dentin were subjected to a demineralization regime which produces dentin caries very similar to natural lesions: acetic acid (pH 5) or lactic acid (pH 4) were used (7 days). Subsequently, sodium hypochlorite, collagenase, trypsin and pepsin were dissolved each in a suitable buffer and the demineralized dentin was treated for 10 minutes or 24 hours with these solutions. To differentiate the influence of the acidic buffer in case of pepsin, a second experiment was performed. 192 slices were exposed to lactic acid for 1 week. Subsequently the demineralized dentin surfaces were treated with either the enzyme pepsin in its acidic buffer, the acidic buffer alone, and in addition a neutral buffer as a control. In addition a fourth group was added where a new enzyme-based solution SFC-V was used. This second experiment differentiated further the influence of "diffusion enhanced by agitation" versus "diffusion" alone. The application time of the solutions was 3 minutes with and without agitation using a stiff nylon brush. To obtain information on the morphology of the pre- and post-treatment dentin surfaces, high resolution FE-SEM was used. Descriptive statistics were used based on cross tabulation of the morphological criteria. Results: Lactic acid produced demineralized dentin covered with a surface layer removable by proteolytic enzymes while acetic acid produced only demineralized dentin. The amount of tissue removed with the current proteolytic agents ranked as follows: trypsin 50% from WT values (P < 0.05) and were accompanied by a twofold higher collagen content (P < 0.05). Persistent myocardial EMMPRINexp in aging mice caused increased levels of both soluble and membrane type MMPs, fibrosis, and was associated with adverse LV remodeling. These findings suggest that EMMPRIN is an upstream signaling pathway that can play a mechanistic role in adverse remodeling within the myocardium.
C1 Med Univ S Carolina, Charleston, SC 29425 USA.
Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Spinale, FG (reprint author), Rm 625,770 MUSC Complex,114 Doughty St, Charleston, SC 29425 USA.
EM wilburnm@musc.edu
OI Chang, Eileen/0000-0002-3444-7260
FU Veterans Affairs Health Administration
FX This study was supported by a merit award from the Veterans Affairs
Health Administration (to F. G. Spinale).
NR 53
TC 23
Z9 27
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD OCT
PY 2008
VL 295
IS 4
BP H1394
EP H1402
DI 10.1152/ajpheart.00346.2008
PG 9
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 357PB
UT WOS:000259857500006
PM 18689500
ER
PT J
AU Albers, AB
Biener, L
Siegel, M
Cheng, DM
Rigotti, N
AF Albers, Alison B.
Biener, Lois
Siegel, Michael
Cheng, Debbie M.
Rigotti, Nancy
TI Household smoking bans and adolescent antismoking attitudes and smoking
initiation: Findings from a longitudinal study of a Massachusetts youth
cohort
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID ENVIRONMENTAL TOBACCO-SMOKE; ESTABLISHED SMOKING; SOCIAL ACCEPTABILITY;
UNITED-STATES; RESTRICTIONS; REGULATIONS; PROGRESSION; RESTAURANT;
EXPOSURE; SOCIALIZATION
AB Objectives. We sought to determine whether adolescents living in households in which smoking was banned were more likely to develop antismoking attitudes and less likely to progress to smoking compared with those living in households in which smoking was not banned.
Methods. We completed a longitudinal 4-year, 3-wave study of a representative sample of 3834 Massachusetts youths aged 12 to 17 years at baseline; 2791 (72.8%) were reinterviewed after 2 years, and 2217 (57.8%) were reinterviewed after 4 years. We used a 3-level hierarchical linear model to analyze the effect of a household ban on antismoking attitudes and smoking behaviors.
Results. The absence of a household smoking ban increased the odds that youths perceived a high prevalence of adult smoking, among both youths living with a smoker (odds ratio [OR]=1.56; 95% confidence interval [CI]=1.15, 2.13) and those living with nonsmokers (OR=1.75; 95% CI=1.29, 2.37). Among youths who lived with nonsmokers, those with no home ban were more likely to transition from nonsmoking to early experimentation (OR=1.89; 95% CI=1.30, 2.74) than were those with a ban.
Conclusions. Home smoking bans may promote antismoking attitudes among youths and reduce progression to smoking experimentation among youths who live with nonsmokers.
C1 [Albers, Alison B.; Siegel, Michael] Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02118 USA.
[Biener, Lois] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA.
[Cheng, Debbie M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Rigotti, Nancy] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rigotti, Nancy] Harvard Univ, Sch Med, Boston, MA USA.
RP Albers, AB (reprint author), Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, 801 Massachusetts Ave,Crosstown Ctr 4th Moor, Boston, MA 02118 USA.
EM aalbers@bu.edu
OI Biener, Lois/0000-0002-4130-8138
FU Flight Attendant Medical Research Institute; National Cancer Institute's
State and Community Tobacco Control Interventions Research [21301
CA86257]
FX This work was supported by the Flight Attendant Medical Research
Institute and the National Cancer Institute's State and Community
Tobacco Control Interventions Research Grant Program (grant 21301
CA86257).
NR 31
TC 36
Z9 36
U1 0
U2 1
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD OCT
PY 2008
VL 98
IS 10
BP 1886
EP 1893
DI 10.2105/AJPH.2007.129320
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 354HT
UT WOS:000259630400030
PM 18703438
ER
PT J
AU Chang, DW
Hayashi, S
Gharib, SA
Vaisar, T
King, ST
Tsuchiya, M
Ruzinski, JT
Park, DR
Matute-Bello, G
Wurfel, MM
Bumgarner, R
Heinecke, JW
Martin, TR
AF Chang, Dong W.
Hayashi, Shinichi
Gharib, Sina A.
Vaisar, Tomas
King, S. Trevor
Tsuchiya, Mitsuhiro
Ruzinski, John T.
Park, David R.
Matute-Bello, Gustavo
Wurfel, Mark M.
Bumgarner, Roger
Heinecke, Jay W.
Martin, Thomas R.
TI Proteomic and computational analysis of bronchoalveolar proteins during
the course of the acute respiratory distress syndrome
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE acute respiratory distress syndrome; acute lung injury; proteomic
analysis; bronchoalveolar lavage; 2D gel electrophoresis
ID ACUTE LUNG INJURY; POSTTRAUMATIC CYTOKINE RELEASE; STIMULATED
WHOLE-BLOOD; GENDER-DIFFERENCES; TRAUMA-HEMORRHAGE; SEX-DIFFERENCES;
SEVERE SEPSIS; EDEMA FLUID; P38 MAPK; ARDS
AB Rationale: Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment.
Objectives: The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS).
Methods: Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis.
Measurements and Main Results: An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks.
Conclusions: Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.
C1 [Martin, Thomas R.] VA Puget Sound Hlth Care Syst, Pulm Res Labs, Med Res Serv, Seattle, WA 98108 USA.
[Chang, Dong W.; Hayashi, Shinichi; Gharib, Sina A.; Ruzinski, John T.; Park, David R.; Matute-Bello, Gustavo; Wurfel, Mark M.; Martin, Thomas R.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[Vaisar, Tomas; Heinecke, Jay W.] Univ Washington, Div Endocrinol & Metab, Dept Med, Seattle, WA 98195 USA.
[King, S. Trevor; Tsuchiya, Mitsuhiro; Bumgarner, Roger] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Gharib, Sina A.] Univ Washington, Ctr Lung Biol, Seattle, WA 98195 USA.
[Gharib, Sina A.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
RP Martin, TR (reprint author), VA Puget Sound Hlth Care Syst, Pulm Res Labs, Med Res Serv, 1660 S Columbian Way,151L, Seattle, WA 98108 USA.
EM trmartin@u.washington.edu
RI Bumgarner, Roger/K-3531-2015
OI Bumgarner, Roger/0000-0002-8168-6985
FU NIH/NHLBI [HL073996, HL090298]
FX Funding: NIH/NHLBI HL073996, NIH/NHBLI HL090298.
NR 35
TC 41
Z9 41
U1 0
U2 1
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD OCT 1
PY 2008
VL 178
IS 7
BP 701
EP 709
DI 10.1164/rccm.200712-1895OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 353RJ
UT WOS:000259585600010
PM 18658106
ER
PT J
AU Kleweno, CP
Brynat, WK
Jacir, AM
Levine, WN
Ahmad, CS
AF Kleweno, Conor P.
Brynat, Whitney K.
Jacir, Albert M.
Levine, William N.
Ahmad, Christopher S.
TI Discrepancies and rates of publication in orthopaedic sports medicine
abstracts
SO AMERICAN JOURNAL OF SPORTS MEDICINE
LA English
DT Article
DE abstract; publication; sports medicine; AOSSM
ID SOCIETY MEETINGS; PRESENTATIONS; SURGEONS; ACADEMY
AB Background: Presentations of clinically relevant data at AOSSM national meetings are presented yearly and may influence clinical decision making.
Hypothesis: The incidence of presentations that do not subsequently get published is high, and the numbers of major and minor inconsistencies, once published, are also high.
Study Design: Systematic review.
Methods: A database was created of all abstracts presented at AOSSM meetings from 1999 to 2001 from official program books. To assess whether each abstract had been followed by publication in a peer-reviewed journal, a PubMed search was conducted to include a 5-year follow-up for each conference. Minor inconsistencies included differences in title, authors, presentation of all outcomes, and authors' interpretation of data. Major inconsistencies included discrepancies in study objective and/or hypothesis, study design, primary and secondary outcome measures, sample size, statistical analysis, results, and standard deviations/confidence intervals.
Results: Overall, 98 of the 165 abstracts presented at AOSSM national meetings from 1999 to 2001 were published in a peer-reviewed journal within 5 years, a publication rate of 59.4%. The median time to publication for all articles was 21 (range, 1-60) months. The majority of articles (61) were published in the American Journal of Sports Medicine (62.2%). The median number of major and minor inconsistencies from abstract to publication was 1 (range, 0-5) and 1 (range, 0-4), respectively. Sixty-two of the 98 published abstracts (63%) had at least 1 major inconsistency, while 79 (81%) had at least 1 minor inconsistency. In 5 manuscripts (5%), the authors' interpretation of the data had changed, and in 2 (2%), the change essentially invalidated the abstract.
Conclusion: A large number of scientific presentations do not get published in a peer-reviewed journal. In addition, those published have a significant number of changes that, in a small percentage of cases, alter the validity of the original presentation.
Clinical Relevance: Orthopaedic surgeons and other attendees as well as nonattendees who reference conference abstracts need to exercise good judgment when considering the implications of oral presentations of unpublished materials. When reviewing meeting presentation abstracts, readers should remember that the material being presented is often not in its definitive or ultimate form.
C1 [Ahmad, Christopher S.] Columbia Univ, Dept Orthopaed Surg, Ctr Shoulder Elbow & Sports Med, New York, NY 10032 USA.
[Kleweno, Conor P.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA.
[Kleweno, Conor P.] Massachusetts Gen Hosp, Harvard Combined Orthopaed Surg Residency Program, Boston, MA 02114 USA.
[Brynat, Whitney K.] NYU, Bellevue Hosp Ctr, Dept Emergency Med, New York, NY 10016 USA.
[Jacir, Albert M.] St Johns Hosp, Dept Family Practice, Detroit, MI USA.
[Levine, William N.] Columbia Univ, New York Orthopaed Hosp, Dept Orthopaed Surg, New York, NY 10032 USA.
RP Ahmad, CS (reprint author), Columbia Univ, Dept Orthopaed Surg, Ctr Shoulder Elbow & Sports Med, 622 W 168th St,PH-11th Floor, New York, NY 10032 USA.
EM csa4@columbia.edu
NR 10
TC 24
Z9 25
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0363-5465
J9 AM J SPORT MED
JI Am. J. Sports Med.
PD OCT
PY 2008
VL 36
IS 10
BP 1875
EP 1879
DI 10.1177/0363546508319054
PG 5
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 354MA
UT WOS:000259642500002
PM 18667625
ER
PT J
AU Barkley, CR
Ligibel, JA
Wong, JS
Lipsitz, S
Smith, BL
Golshan, M
AF Barkley, Christina R.
Ligibel, Jennifer A.
Wong, Julia S.
Lipsitz, Stuart
Smith, Barbara L.
Golshan, Mehra
TI Mucinous breast carcinoma: a large contemporary series
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article; Proceedings Paper
CT 9th Annual Meeting of the American-Society-of-Breast-Surgeons
CY APR 30-MAY 04, 2008
CL New York, NY
SP Amer Soc Breast Surg
DE Breast cancer; Mucinous carcinoma; Sentinel lymph node
AB BACKGROUND: Mucinous breast cancer is typically associated with a favorable prognosis. This study aimed to assess recent trends and prognostic features in the treatment of mucinous breast carcinoma.
METHODS: A retrospective review of our database of patients who presented with mucinous breast cancer was performed. We evaluated patient and tumor characteristics and examined the relationships between these factors and risk for locoregional recurrence.
RESULTS: One hundred eleven patients with mucinous breast cancer were identified. Severity-one (64%) underwent lumpectomy with radiotherapy. Fourteen (13%) had lymph node metastasis, and node positivity was associated with larger tumor sized node-positive patients had a mean tumor size of 2.7 cm compared with 1.5 cm for node-negative patients (P = .0003). No patients with tumor size < 1 cm had lymph node metastasis. Five patients (5%) had local and/or distant recurrence.
CONCLUSIONS: Mucinous breast cancer is associated with a low recurrence rate as well as a low incidence of lymph node metastasis. In patients with small (< 1cm) tumors, consideration for deferring nodal evaluation may be made. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Barkley, Christina R.; Lipsitz, Stuart; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Ligibel, Jennifer A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Wong, Julia S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA.
[Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
EM mgolshan@partners.org
NR 7
TC 24
Z9 31
U1 1
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD OCT
PY 2008
VL 196
IS 4
BP 549
EP 551
DI 10.1016/j.amjsurg.2008.06.013
PG 3
WC Surgery
SC Surgery
GA 358IL
UT WOS:000259910300017
PM 18809061
ER
PT J
AU Murphy, CD
Jones, JL
Javid, SH
Michaelson, JS
Nolan, ME
Lipsitz, SR
Specht, MC
Lesnikoski, BA
Hughes, KS
Gadd, MA
Smith, BL
AF Murphy, Colleen D.
Jones, Julie L.
Javid, Sara Hughes
Michaelson, James S.
Nolan, Matthew E.
Lipsitz, Stuart R.
Specht, Michelle C.
Lesnikoski, Beth-Ann
Hughes, Kevin S.
Gadd, Michele A.
Smith, Barbara L.
TI Do sentinel node micrometastases predict recurrence risk in ductal
carcinoma in situ and ductal carcinoma in situ with microinvasion?
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article; Proceedings Paper
CT 9th Annual Meeting of the American-Society-of-Breast-Surgeons
CY APR 30-MAY 04, 2008
CL New York, NY
SP Amer Soc Breast Surg
DE Breast neoplasm; Ductal carcinoma in situ; Ductal carcinoma in situ with
microinvasion; Sentinel lymph node biopsy; Sentinel lymph node
micrometastases
ID BREAST-CANCER; BIOPSY; MASTECTOMY
AB BACKGROUND: Because the implications of micrometastases found on sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM)are largely unknown, we wished to determine if SNB pathology predicted recurrence risk in DCIS/DCISM.
METHODS: Retrospective chart review identified patients with DCIS/DCISM who underwent SNB. SNB findings and all local and distant recurrences were determined.
RESULTS: A total of 322 patients underwent SNB for DCIS/DCISM. There were 13 local recurrences (4.0%) and 1 (.03%) distant recurrence at a median follow-up of 47.9 months (range 0 to 110.6). 12 in patients with negative SNBs: 1 patient had a positive SNB. There were 4 recurrences after mastectomy and 9 after lumpectomy. In 29 patients with positive SNBs, there was only 1 recurrence (3.4%).
CONCLUSIONS: Positive SNBs in patients with DCIS or DCISM are not associated with higher risk of local or distant recurrence. Other features of DCIS and DCISM may be important in predicting recurrence risk. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Murphy, Colleen D.; Javid, Sara Hughes; Michaelson, James S.; Nolan, Matthew E.; Specht, Michelle C.; Hughes, Kevin S.; Gadd, Michele A.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA.
[Jones, Julie L.; Lesnikoski, Beth-Ann] Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA.
[Lipsitz, Stuart R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Lipsitz, Stuart R.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
RP Murphy, CD (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA.
EM blsmith@partners.org
OI Hughes, Kevin/0000-0003-4084-6484
NR 10
TC 13
Z9 19
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD OCT
PY 2008
VL 196
IS 4
BP 566
EP 568
DI 10.1016/j.amjsurg.2008.06.011
PG 3
WC Surgery
SC Surgery
GA 358IL
UT WOS:000259910300022
PM 18760400
ER
PT J
AU Vakiani, E
Young, RH
Carcangiu, ML
Klimstra, DS
AF Vakiani, Efsevia
Young, Robert H.
Carcangiu, Maria Luisa
Klimstra, David S.
TI Acinar cell carcinoma of the pancreas metastatic to the ovary - A report
of 4 cases
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE acinar cell carcinoma; pancreas; ovary; metastasis
ID ENDOCRINE TUMORS; MUCINOUS TUMORS; DIFFERENTIATION; NEOPLASMS;
KRUKENBERG; MARKERS; SERIES
AB We report 4 cases of acinar cell carcinoma of the pancreas, 3 presenting as metastases in the ovary, the first report of this circumstance, which may pose a broad differential diagnosis and caused significant diagnostic difficulty in all the cases. The average patient age was 57 (range: 28 to 81) years. In 3 cases, the ovarian tumors were detected before the pancreatic tumor; in I case, a large abdominal mass and ovarian tumors were discovered synchronously. The ovarian tumors were large, solid, white-tan on gross examination, and bilateral in 3 cases; the single case involving only 1 ovary had 2 discrete masses of tumor. Microscopic examination showed highly cellular neoplasms with a small amount of fibrous stroma. Two cases had a predominant acinar growth pattern of cells with brightly eosinophilic, granular cytoplasm. In 2 cases, the pattern was predominantly solid-cribriform with areas of comedolike necrosis, and the cells had pale eosinophilic, finely granular cytoplasm. Nuclei in all cases were uniform with prominent nucleoli. The main differential diagnostic consideration was well-differentiated neuroendocrine neoplasm (carcinoid tumor); positive immunostaining with antibodies against chymotrypsin and trypsin and negative immunostaining with antibodies against synaptophysin and chromogranin helped exclude this diagnosis. We observed focal a-inhibin immunostaining in 2 cases, which may represent a potential diagnostic pitfall, as a Sertoli cell tumor or unusual granulosa cell tumor may also enter the differential diagnosis. Inclusion of antibodies against the pancreatic enzymes chymotrypsin and trypsin in the immunohistochemical panel is critical in establishing the correct diagnosis and should be considered when evaluating ovarian tumors with architectural (mainly acinar) and cytologic (granular eosinophilic cytoplasm) characteristics that should bring a metastatic acinar cell carcinoma into consideration.
C1 [Vakiani, Efsevia; Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Lab, Boston, MA 02115 USA.
[Carcangiu, Maria Luisa] Natl Canc Inst, Dept Pathol, I-20133 Milan, Italy.
RP Klimstra, DS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA.
EM klimstrd@mskcc.org
NR 29
TC 9
Z9 9
U1 0
U2 0
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 OCT
PY 2008
VL 32
IS 10
BP 1540
EP 1545
DI 10.1097/PAS.0b013e31817a8ebb
PG 6
WC Pathology; Surgery
SC Pathology; Surgery
GA 355BQ
UT WOS:000259684300013
PM 18724247
ER
PT J
AU Koporc, Z
Pilat, N
Nierlich, P
Blaha, P
Bigenzahn, S
Pree, I
Selzer, E
Sykes, M
Muehlbacher, F
Wekerle, T
AF Koporc, Z.
Pilat, N.
Nierlich, P.
Blaha, P.
Bigenzahn, S.
Pree, I.
Selzer, E.
Sykes, M.
Muehlbacher, F.
Wekerle, T.
TI Murine mobilized peripheral blood stem cells have a lower capacity than
bone marrow to induce mixed chimerism and tolerance
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE costimulation blockade; mixed chimerism; PBSC; tolerance
ID COLONY-STIMULATING FACTOR; DONOR-SPECIFIC TOLERANCE; WHOLE-BODY
IRRADIATION; LARGE-ANIMAL-MODEL; COSTIMULATION BLOCKADE; HEMATOPOIETIC
CHIMERISM; TRANSPLANTATION TOLERANCE; ALLOGENEIC MARROW; IN-VIVO;
PREPARATIVE REGIMEN
AB Allogeneic bone marrow transplantation (BMT) under costimulation blockade allows induction of mixed chimerism and tolerance without global T-cell depletion (TCD). The mildest such protocols without recipient cytoreduction, however, require clinically impracticable bone marrow (BM) doses. The successful use of mobilized peripheral blood stem cells (PBSC) instead of BM in such regimens would provide a substantial advance, allowing transplantation of higher doses of hematopoietic donor cells. We thus transplanted fully allogeneic murine granulocyte colony-stimulating factor (G-CSF) mobilized PBSC under costimulation blockade (anti-CD40L and CTLA4Ig). Unexpectedly, PBSC did not engraft, even when very high cell doses together with nonmyeloablative total body irradiation (TBI) were used. We show that, paradoxically, T cells contained in the donor PBSC triggered rejection of the transplanted donor cells. Rejection of donor BM was also triggered by the cotransplantation of unmanipulated donor T cells isolated from naive (nonmobilized) donors. Donor-specific transfusion and transient immunosuppression prevented PBSC-triggered rejection and mixed chimerism and tolerance were achieved, but graft-versus-host disease (GVHD) occurred. The combination of in vivo TCD with costimulation blockade prevented rejection and GVHD. Thus, if allogeneic PBSC are transplanted instead of BM, costimulation blockade alone does not induce chimerism and tolerance without unacceptable GVHD-toxicity, and the addition of TCD is required for success.
C1 [Koporc, Z.; Pilat, N.; Nierlich, P.; Blaha, P.; Bigenzahn, S.; Pree, I.; Muehlbacher, F.; Wekerle, T.] Med Univ Vienna, Dept Surg, Div Transplantat, Vienna, Austria.
[Selzer, E.] Med Univ Vienna, Vienna Gen Hosp, Dept Radiotherapy & Radiobiol, Vienna, Austria.
[Sykes, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA.
RP Wekerle, T (reprint author), Med Univ Vienna, Dept Surg, Div Transplantat, Vienna, Austria.
EM Thomas.Wekerle@meduniwien.ac.at
RI Selzer, Edgar/K-7547-2015;
OI Wekerle, Thomas/0000-0001-5159-2796
FU Roche Organ Transplantation Research Foundation (ROTRF) [110578928];
Austrian National Bank [10809]; Austrian Science Fund [F2310]
FX We thank Maria Weiss, Helga Bergmeister; Martin Ploder and Franz
Winkler, for technical assistance, and Andreas Heitger for critical
review of the article. The authors declare no competing financial
interests. This work was supported by grants from the Roche Organ
Transplantation Research Foundation (ROTRF, # 110578928), from the
Jubilee Fund of the Austrian National Bank (# 10809), and from the
Austrian Science Fund (FWF, F2310).
NR 50
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U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD OCT
PY 2008
VL 8
IS 10
BP 2025
EP 2036
DI 10.1111/j.1600-6143.2008.02371.x
PG 12
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 349GS
UT WOS:000259269900010
PM 18828766
ER
PT J
AU Reese, PP
Feldman, HI
McBride, MA
Anderson, K
Asch, DA
Bloom, RD
AF Reese, P. P.
Feldman, H. I.
McBride, M. A.
Anderson, K.
Asch, D. A.
Bloom, R. D.
TI Substantial variation in the acceptance of medically complex live kidney
donors across US renal transplant centers
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE kidney transplantation; live donor; outcomes research
ID HYPERTENSIVE LIVING DONORS; GLOMERULAR-FILTRATION-RATE; BODY-MASS INDEX;
BLOOD-PRESSURE; FOLLOW-UP; ORGAN PROCUREMENT; DONATION; DISEASE; RISK;
ASSOCIATION
AB Concern exists about accepting live kidney donation from 'medically complex donors'-those with risk factors for future kidney disease. This study's aim was to examine variation in complex kidney donor use across US transplant centers. We conducted a retrospective cohort study of live kidney donors using organ procurement and transplantation network data. Donors with hypertension, obesity or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) were considered medically complex. Among 9319 donors, 2254 (24.2%) were complex: 1194 (12.8%) were obese, 956 (10.3%) hypertensive and 392 (4.2%) had low eGFR. The mean proportion of medically complex donors at a center was 24% (range 0-65%). In multivariate analysis, donor characteristics associated with medical complexity included spousal relationship to the recipient (OR 1.29, CI 1.06-1.56, p < 0.01), low education (OR 1.19, CI 1.04-1.37, p = 0.01), older age (OR 1.01 per year, CI 1.01-1.02, p < 0.01) and non-US citizenship (OR 0.70, CI 0.51-0.97, p = 0.03). Renal transplant centers with the highest transplant volume (OR 1.26, CI 1.02-1.57, p = 0.03), and with a higher proportion of (living donation)/(all kidney transplants) (OR 1.97, CI 1.23-3.16, p < 0.01) were more likely to use medically complex donors. Though controversial, the use of medically complex donors is widespread and varies widely across centers.
C1 [Reese, P. P.; Feldman, H. I.; Bloom, R. D.] Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA.
[McBride, M. A.; Anderson, K.] United Network Organ Sharing, Richmond, VA USA.
[Asch, D. A.] Univ Penn, Dept Med, Leonard Davis Inst, Philadelphia, PA 19104 USA.
[Asch, D. A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Reese, PP (reprint author), Univ Penn, Dept Med, Div Renal, Philadelphia, PA 19104 USA.
EM peter.reese@uphs.upenn.edu
OI Asch, David/0000-0002-7970-286X
FU NIH [K23 DK078688-01]
FX Dr. Reese is supported by NIH Career Development Award, K23 DK078688-01.
NR 50
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U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD OCT
PY 2008
VL 8
IS 10
BP 2062
EP 2070
DI 10.1111/j.1600-6143.2008.02361.x
PG 9
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 349GS
UT WOS:000259269900014
PM 18727695
ER
PT J
AU Sandberg, WS
AF Sandberg, Warren S.
TI Anesthesia information management systems: Almost there
SO ANESTHESIA AND ANALGESIA
LA English
DT Editorial Material
ID DOCUMENTATION; PERFORMANCE
C1 [Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Sandberg, Warren S.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 4, Boston, MA 02114 USA.
EM wsandberg@partners.org
OI Sandberg, Warren/0000-0002-9246-777X
NR 10
TC 9
Z9 9
U1 0
U2 1
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 OCT
PY 2008
VL 107
IS 4
BP 1100
EP 1102
DI 10.1213/ane.0b013e3181867fd0
PG 3
WC Anesthesiology
SC Anesthesiology
GA 352UE
UT WOS:000259522100004
PM 18806010
ER
PT J
AU Lee, IH
Culley, DJ
Baxter, MG
Xie, ZC
Tanzi, RE
Crosby, G
AF Lee, In Ho
Culley, Deborah J.
Baxter, Mark G.
Xie, Zhongcong
Tanzi, Rudolph E.
Crosby, Gregory
TI Spatial memory is intact in aged rats after propofol anesthesia
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID RADIAL-ARM MAZE; NITROUS OXIDE ANESTHESIA; LONG-TERM POTENTIATION;
METHYL-D-ASPARTATE; SYNAPTIC-TRANSMISSION; COGNITIVE DYSFUNCTION;
HIPPOCAMPAL-NEURONS; ISOFLURANE; DEFICITS; RECEPTOR
AB BACKGROUND: We have previously demonstrated that aged rats have persistent impairment of spatial memory after sedation with nitrous oxide or general anesthesia with isoflurane-nitrous oxide. Propofol has different receptor mechanisms of action and a favorable short-term recovery profile, and it has been proposed that propofol is devoid of enduring effects on cognitive performance. No studies have investigated this question in aged subjects, however, so we designed an experiment to examine the long-term effects of propofol anesthesia on spatial working memory.
METHODS: Eighteen-mo-old rats were randomized to 2h of 100% oxygen-propofol anesthesia (n = 11) or to a control group that breathed 100% oxygen (n = 10). Propofol was administered by continuous infusion via a tail vein catheter. Rats breathed spontaneously and rectal temperature was maintained. Mean arterial blood pressure was measured noninvasively and a venous blood gas was obtained just before discontinuation of propofol. After a 2-day recovery, spatial working memory was assessed for 14 days using a 12-arm radial maze. The number of total errors, number of correct choices to first error, and time to complete the maze was recorded and analyzed using a repeated measure analysis of variance (ANOVA), with P < 0.05 being considered statistically significant.
RESULTS: The average propofol infusion rate was 0.6 +/- 0.1 mg center dot kg(-1) center dot min(-1), a rate corresponding to a 50% effective concentration dose in adult rats. Mean arterial blood pressure during anesthesia was 1.00 +/- 2 mm Hg and venous blood gases remained in the normal range. There was no difference between the control and previously anesthetized rats on any measure of radial arm maze performance, indicating propofol anesthesia produces no lasting impairment in spatial working memory in aged rats.
CONCLUSIONS: In aged rats, propofol anesthesia is devoid of the persistent memory effects observed with other general anesthetics in this model. Thus, while it appears that the state of general anesthesia is neither necessary nor sufficient for development of postanesthetic memory impairment, the choice of anesthetics may play a role in late cognitive outcome in the aged.
C1 [Culley, Deborah J.; Crosby, Gregory] Harvard Univ, Sch Med, Dept Anesthesia, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lee, In Ho] Korea Univ, Guro Hosp, Dept Anesthesiol, Seoul, South Korea.
[Baxter, Mark G.] Univ Oxford, Oxford, England.
[Xie, Zhongcong] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Tanzi, Rudolph E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA USA.
RP Crosby, G (reprint author), Brigham & Womens Hosp, Dept Anesthesiol, Lab Aging Neurosci, 75 Francis St, Boston, MA 02115 USA.
EM gcrosby@zeus.bwh.harvard.edu
FU American Geriatrics Society Jahnigen Award [GM077057, AG20253,
NS048140]; Harvard University; Alzheimer's Association; Cure Alzheimer's
Fund [AG014713, MH60009]
FX This research was supported by GM077057, American Geriatrics Society
Jahnigen Award (DC); AG20253 (GC); NS048140, American Geriatrics Society
Jahnigen Award, William F. Milton Fund from Harvard University,
Investigator-Initiated Research Grant from Alzheimer's Association (ZX);
and AG014713, MH60009, Cure Alzheimer's Fund (RT).
NR 38
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Z9 32
U1 1
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 OCT
PY 2008
VL 107
IS 4
BP 1211
EP 1215
DI 10.1213/ane.0b013e31817ee879
PG 5
WC Anesthesiology
SC Anesthesiology
GA 352UE
UT WOS:000259522100023
PM 18806029
ER
PT J
AU Nagasaka, Y
Fernandez, BO
Garcia-Saura, MF
Petersen, B
Ichinose, F
Bloch, KD
Feelisch, M
Zapol, WM
AF Nagasaka, Yasuko
Fernandez, Bernadette O.
Garcia-Saura, Maria F.
Petersen, Bodil
Ichinose, Fumito
Bloch, Kenneth D.
Feelisch, Martin
Zapol, Warren M.
TI Brief periods of nitric oxide inhalation protect against myocardial
ischemia-reperfusion injury
SO ANESTHESIOLOGY
LA English
DT Article
ID DECREASES INFARCTION SIZE; ISCHEMIA/REPERFUSION INJURY; BIOLOGICAL
TISSUES; GUANYLATE-CYCLASE; CORONARY-ARTERY; S-NITROSYLATION; INHALED
NO; IN-VIVO; HEMOGLOBIN; BLOOD
AB Background: Prolonged breathing of nitric oxide reduces myocardial ischemia-reperfusion injury, but the precise mechanisms responsible for the cardioprotective effects of inhaled nitric oxide are incompletely understood.
Methods: The authors investigated die fate of inhaled nitric oxide (80 parts per million) in mice and quantified the formation of nitric oxide metabolites in blood and tissues. The authors tested whether the accumulation of nitric oxide metabolites correlated with the ability of inhaled nitric oxide to protect against cardiac ischemia-reperfusion injury.
Results: Mice absorbed nitric oxide in a nearly linear fashion (0.19 +/- 0.02 mu mol/g (.) h). Breathing nitric oxide rapidly increased a broad spectrum of nitric oxide metabolites. Levels of erythrocytic S-nitrosothiols, N-nitrosamines, and nitrosyl-hemes increased dramatically within 30 s of commencing nitric oxide inhalation. Marked increases of lung S-nitrosothiol and liver N-nitrosamine levels were measured, as, well as elevated cardiac and brain nitric oxide metabolite levels. Breathing low oxygen concentrations potentiated die ability of inhaled nitric oxide to increase cardiac nitric oxide metabolite levels. Concentrations of each nitric oxide metabolite, except nitrate, rapidly reached a plateau and were similar after 5 and 60 min. In a murine cardiac ischemia-reperfusion injury model, breathing nitric oxide for either 5 or 60 min before reperfusion decreased myocardial infarction size as a fraction of myocardial area at risk by 31% or 32%, respectively.
Conclusions: Breathing nitric oxide leads to the rapid accumulation of a variety of nitric oxide metabolites in blood and tissues, contributing to the ability of brief periods of nitric oxide inhalation to provide cardioprotection against ischemia-reperfusion injury. The nitric oxide metabolite concentrations achieved in a target tissue may be more important than the absolute amounts of nitric oxide absorbed.
C1 [Zapol, Warren M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Anesthesia Ctr Crit C, Boston, MA 02114 USA.
[Feelisch, Martin] Univ Warwick, Warwick Med Sch, Clin Sci Res Inst, Coventry CV4 7AL, W Midlands, England.
Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA.
RP Zapol, WM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Anesthesia Ctr Crit C, 55 Fruit St, Boston, MA 02114 USA.
EM wzapol@partners.org
RI Feelisch, Martin/C-3042-2008
OI Feelisch, Martin/0000-0003-2320-1158
FU National Institutes of Helath, Bethesda, Maryland [HL07224];
Massachusetts General Hospital, Boston, Massachusetts, and IKARIA,
Clinton, New Jersey; [HL42397]; [DA020644]; [HL70896]
FX Received from the Anesthesia Center for Critical Care Research,
Department of Anesthesia and Critical Care, Massachusetts General
Hospital and Harvard Medical School, Boston, Massachusetts; and the
Whitaker Cardiovascular Institute, Boston University School of Medicine.
Boston, Massachusetts. Submitted for publication February 1, 2008.
Accepted tor publication June 27, 2008. Supported in part by grant Nos.
HL42397 (to Dr. Zapol), DA020644 (to Dr. Feelisch), and HL70896 to (Dr.
Bloch) and multidisciplinary training in cardiovascular research grant
No. HL07224 (to Dr. Fernandez) from the National Institutes of Helath,
Bethesda, Maryland; and a sponsored research agreement between
Massachusetts General Hospital, Boston, Massachusetts, and IKARIA,
Clinton, New Jersey (to Dr. Bloch). Drs. Zapol and Bloch have obtained
patents relating to the use of inhaled nitric oxide. These patents are
assigned to Massachusetts General Hospital, which has licensed them to
IKARIA and Linde Gas Therapeutics, Lidingo, Sweden. Dr. Zapol receives
royalties and Dr. Bloch has received grants from IKARIA and Linde, which
helped the authors to study inhaled nitric oxide. Presented at the
Annual Meeting of the American Heart Association. Orlando, Florida,
November 7, 2007 (Abstract Oral Sessions, presentation No. 1484). The
first two authors (Drs. Nagasaka and Fernandez) contributed equally to
this work. The senior authors (Drs. Feelisch and Zapol) contributed
equally to this work.
NR 33
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U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD OCT
PY 2008
VL 109
IS 4
BP 675
EP 682
PG 8
WC Anesthesiology
SC Anesthesiology
GA 352TY
UT WOS:000259521500015
PM 18813047
ER
PT J
AU Antman, EM
AF Antman, Elliott M.
TI The specialty of emergency medicine: Needed now more than ever before
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Editorial Material
ID CARE
C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
RP Antman, EM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
NR 9
TC 1
Z9 1
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
BP 317
EP 319
DI 10.1016/j.annemergmed.2008.07.025
PG 3
WC Emergency Medicine
SC Emergency Medicine
GA 354PP
UT WOS:000259651800003
PM 18809101
ER
PT J
AU Pollack, CV
Antman, EM
Hollander, JE
AF Pollack, Charles V., Jr.
Antman, Elliott M.
Hollander, Judd E.
TI 2007 focused update to the ACC/AHA guidelines for the management of
patients with ST-segment elevation myocardial infarction: Implications
for emergency department practice
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID PERCUTANEOUS CORONARY INTERVENTION; ASSOCIATION TASK-FORCE; NONSTEROIDAL
ANTIINFLAMMATORY DRUGS; INTRAVENOUS THROMBOLYTIC THERAPY; RANDOMIZED
CLINICAL-TRIALS; PLACEBO-CONTROLLED TRIAL; TO-BALLOON TIME; PRIMARY
ANGIOPLASTY; FIBRINOLYTIC THERAPY; AMERICAN-COLLEGE
AB The American College of Cardiology and American Heart Association have issued a "focused update" of their 2004 guidelines for the management of ST-segment elevation myocardial infarction (STEMI). Several of the issues addressed involve new data and new recommendations on treatment decisions that may be made in the emergency department. In this review, we present the new recommendations that are pertinent to emergency medicine practice and comment on their potential implementation into an evidence-based, multidisciplinary approach to the timely care of the STEMI patient.
C1 [Pollack, Charles V., Jr.] Univ Penn, Dept Emergency Med, Penn Hosp, Philadelphia, PA 19107 USA.
[Antman, Elliott M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA.
[Hollander, Judd E.] Univ Penn, Hosp Univ Penn, Philadelphia, PA 19104 USA.
RP Pollack, CV (reprint author), Univ Penn, Dept Emergency Med, Penn Hosp, Philadelphia, PA 19107 USA.
EM pollackc@pahosp.com
OI Hollander, Judd/0000-0002-1318-2785
NR 66
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PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
BP 344
EP 355
DI 10.1016/j.annemergmed.2008.04.004
PG 12
WC Emergency Medicine
SC Emergency Medicine
GA 354PP
UT WOS:000259651800010
PM 18519158
ER
PT J
AU Camargo, CA
Ginde, AA
Blanc, PG
Tsai, C
AF Camargo, Jr C. A.
Ginde, A. A.
Blanc, P. G.
Tsai, C.
TI Improved Emergency Department Management of Acute Exacerbation of
Chronic Obstructive Pulmonary Disease
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Colorado, Denver Sch Med, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 15
BP S46
EP S46
DI 10.1016/j.annemergmed.2008.06.080
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900016
ER
PT J
AU Capp, R
Bosson, N
Noble, VE
Lamhaut, L
Marx, JS
Liteplo, A
Carli, P
AF Capp, R.
Bosson, N.
Noble, V. E.
Lamhaut, L.
Marx, J. S.
Liteplo, A.
Carli, P.
TI Can Physicians Who Work in the Out-of-Hospital System Accurately
Interpret Chest Ultrasound Images for Pneumothorax and Pulmonary Edema
Following Focused Training?
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
NYU Emergency Med, New York, NY USA.
SAMU Hop Necker, Paris, France.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 341
BP S145
EP S145
DI 10.1016/j.annemergmed.2008.06.367
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900342
ER
PT J
AU Capp, R
Murray, A
Noble, VE
Steele, D
Liteplo, A
AF Capp, R.
Murray, A.
Noble, V. E.
Steele, D.
Liteplo, A.
TI The Dynamics of B-lines: A Useful Tool in the Evaluation of Pulmonary
Fluid Status as Fluid Shifts Occur in the Body
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 [Capp, R.; Murray, A.; Noble, V. E.; Steele, D.; Liteplo, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 62
BP S61
EP S61
DI 10.1016/j.annemergmed.2008.06.128
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900063
ER
PT J
AU Ginde, AA
Espinola, JA
Sullivan, AF
Blurn, FC
Camargo, CA
AF Ginde, A. A.
Espinola, J. A.
Sullivan, A. F.
Blurn, F. C.
Camargo, Jr C. A.
TI Use of Physician Assistants and Nurse Practitioners in United States
Emergency Departments, 1993-2005: Implications for the Emergency
Physician Workforce
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Univ Colorado Denver, Sch Med, Aurora, CO USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
W Virginia Univ, Sch Med, Morgantown, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 145
BP S87
EP S87
DI 10.1016/j.annemergmed.2008.06.059
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900146
ER
PT J
AU Janishidi, S
Kandiah, P
Singhal, AB
Resnick, JB
Furie, KL
Botczuk, P
Parry, BA
Lev, M
Koroshetz, WJ
Nagurney, JT
AF Janishidi, S.
Kandiah, P.
Singhal, A. B.
Resnick, J. B.
Furie, K. L.
Botczuk, P.
Parry, B. A.
Lev, M.
Koroshetz, W. J.
Nagurney, J. T.
TI Clinical Predictors of Significant Findings on Head Computed Tomographic
Angiography
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 [Janishidi, S.; Kandiah, P.; Singhal, A. B.; Resnick, J. B.; Furie, K. L.; Botczuk, P.; Parry, B. A.; Lev, M.; Koroshetz, W. J.; Nagurney, J. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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U1 0
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PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 380
BP S158
EP S158
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900381
ER
PT J
AU Lozner, A
Connolly, J
Millen, J
Shaltis, P
Reisner, A
Thomas, SH
AF Lozner, A.
Connolly, J.
Millen, J.
Shaltis, P.
Reisner, A.
Thomas, S. H.
TI How Frequently Do Patients Want Their Pain Assessed?
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 [Lozner, A.; Connolly, J.; Millen, J.; Shaltis, P.; Reisner, A.; Thomas, S. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
BP S164
EP S165
DI 10.1016/j.annemergmed.2008.06.429
PG 2
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900402
ER
PT J
AU Millen, JC
Ginde, AA
Anderson, AT
Fang, P
Camargo, CA
AF Millen, J. C.
Ginde, A. A.
Anderson, A. T.
Fang, P.
Camargo, Jr C. A.
TI Multicenter Study of HPV Knowledge and Attitudes in Emergency Department
Patients
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Harvard Affiliated Emergency Med Residency, Boston, MA USA.
Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA.
Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 260
BP S121
EP S122
DI 10.1016/j.annemergmed.2008.06.279
PG 2
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900260
ER
PT J
AU Patel, SN
Kilgannon, H
Boudreaux, ED
Sullivan, AF
Blumenthal, D
Camargo, CA
AF Patel, S. N.
Kilgannon, H.
Boudreaux, E. D.
Sullivan, A. F.
Blumenthal, D.
Camargo, Jr C. A.
TI Multicenter Study of Cigarette Smoking Among Patients Presenting to the
Emergency Department With Acute Asthma
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 9
BP S44
EP S44
DI 10.1016/j.annemergmed.2008.06.074
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900010
ER
PT J
AU Richman, P
Kabrhel, C
Mandell, M
Beam, D
Courtney, D
Moore, C
Kline, JA
AF Richman, P.
Kabrhel, C.
Mandell, M.
Beam, D.
Courtney, D.
Moore, C.
Kline, J. A.
TI Age Differences in the Clinical Presentation of Department Patients With
Venous Thromboembolism
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Mayo Clin Hosp, Phoenix, AZ USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Morristown Mem Hosp, Morristown, NJ USA.
E Carolina Univ, Greenville, NC USA.
Northwestern Univ, Chicago, IL 60611 USA.
Yale Univ, New Haven, CT USA.
Carolinas Med Ctr, Charlotte, NC 28203 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 14
BP S45
EP S46
DI 10.1016/j.annemergmed.2008.06.079
PG 2
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900015
ER
PT J
AU Soremekun, OA
Noble, V
Litepio, A
Brown, D
AF Soremekun, O. A.
Noble, V
Litepio, A.
Brown, D.
TI Financial Impact of Emergency Department Ultrasound: Current and
Potential Revenue
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 [Soremekun, O. A.; Noble, V; Litepio, A.; Brown, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 127
BP S81
EP S81
DI 10.1016/j.annemergmed.2008.06.041
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900128
ER
PT J
AU Sullivan, AF
Kansagra, SM
Rao, SR
Gordon, JA
Kaushal, R
Magid, DJ
Camargo, CA
Blumenthal, D
AF Sullivan, A. F.
Kansagra, S. M.
Rao, S. R.
Gordon, J. A.
Kaushal, R.
Magid, D. J.
Camargo, C. A., Jr.
Blumenthal, D.
TI Personal Safety and Prevalence of Violence and Weapons in the Emergency
Department
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
New York Presbyterian Hosp, New York, NY USA.
Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 425
BP S171
EP S171
DI 10.1016/j.annemergmed.2008.06.453
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900425
ER
PT J
AU Temin, E
Harrington, L
Mitchell, P
Rebholz, C
Dyer, K
Doyle, J
Hughes, P
Moyer, P
AF Temin, E.
Harrington, L.
Mitchell, P.
Rebholz, C.
Dyer, K.
Doyle, J.
Hughes, P.
Moyer, P.
TI Success Rates in Out-of-Hospital Intubation
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Boston Med Ctr, Boston, MA USA.
Boston Emergency Med Serv, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 364
BP S153
EP S153
DI 10.1016/j.annemergmed.2008.06.391
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900365
ER
PT J
AU Waseem, M
Mansbach, JM
Clark, S
Camargo, CA
AF Waseem, M.
Mansbach, J. M.
Clark, S.
Camargo, Jr C. A.
TI Prospective Multicenter Study of Bronchiolitis: Predictors of Relapse
Following Treatment in the Emergency Department
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Lincoln Med & Mental Hlth Ctr, Bronx, NY 10451 USA.
Childrens Hosp Boston, Boston, MA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 4
BP S42
EP S42
DI 10.1016/j.annemergmed.2008.06.069
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900005
ER
PT J
AU Weed, S
Caterino, JM
Espinola, JA
Camargo, CA
AF Weed, S.
Caterino, J. M.
Espinola, J. A.
Camargo, Jr C. A.
TI National Patterns in Emergency Department Antibiotic Prescribing for
Elderly Patients With Urinary Tract Infections, 1996-2005
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Meeting Abstract
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
C1 Duke Univ, Coll Med, Raleigh, NC USA.
Ohio State Univ, Columbus, OH 43210 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD OCT
PY 2008
VL 52
IS 4
MA 370
BP S155
EP S155
DI 10.1016/j.annemergmed.2008.06.397
PG 1
WC Emergency Medicine
SC Emergency Medicine
GA 354PQ
UT WOS:000259651900371
ER
PT J
AU Sonnenberg, A
AF Sonnenberg, Amnon
TI Birth-Cohort Patterns of Mortality From Ulcerative Colitis and Peptic
Ulcer
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Birth Cohorts; Duodenal Ulcer; Enteric Infections; Etiology of
Ulcerative Colitis; Gastric Ulcer; Mortality; Time Trends
ID INFLAMMATORY-BOWEL-DISEASE; HELICOBACTER-PYLORI INFECTION; TIME TRENDS;
CROHNS-DISEASE; RISK-FACTORS; PREVALENCE; EPIDEMIOLOGY; ENGLAND; COUNTY;
PERIOD
AB PURPOSE: The aim was to follow the time trends of mortality from ulcerative colitis and compare them with those of gastric and duodenal ulcer.
METHODS: Mortality data from 21' different countries between 1941 and 2004 were analyzed. The age-specific death rates of each individual country, as well as the average age-specific rates of all countries, were plotted against the periods of birth and death.
RESULTS: The average trends of mortality from ulcerative colitis, gastric and duodenal ulcer reveal distinctive and unique birth-cohort patterns of all three diseases. Similar to both types of peptic ulcer, the risk of developing ulcerative colitis started to rise in successive generations born during the second half of the 19(th) century. It peaked shortly before the turn of the century and has continued to decline since then. The rise and fall in the occurrence of ulcerative colitis preceded those of both ulcer types.
CONCLUSION: The birth-cohort pattern indicates that exposure to the relevant risk factors of ulcerative colitis occurs during early life. As the model of H. pylori and its associated birth-cohort patterns of gastric and duodenal ulcer suggest, an enteric infection provides a possible explanation for such temporal trends of ulcerative colitis as well. Ann Epidemiol 2008;18:813-819. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA.
[Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-G1,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM sonnenbe@ohsu.edu
NR 18
TC 6
Z9 6
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD OCT
PY 2008
VL 18
IS 10
BP 813
EP 819
DI 10.1016/j.annepidem.2008.07.006
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 359XS
UT WOS:000260022200010
PM 18922397
ER
PT J
AU Hickey, M
Saunders, C
Partridge, A
Santoro, N
Joffe, H
Stearns, V
AF Hickey, M.
Saunders, C.
Partridge, A.
Santoro, N.
Joffe, H.
Stearns, V.
TI Practical clinical guidelines for assessing and managing menopausal
symptoms after breast cancer
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE atrophic vaginitis; breast cancer; hot flashes; nonhormonal treatment;
sexual dysfunction after breast cancer
ID RANDOMIZED CONTROLLED-TRIAL; HORMONE-REPLACEMENT THERAPY;
QUALITY-OF-LIFE; INDUCED HOT FLASHES; VAGINAL ESTROGEN THERAPY;
POSTMENOPAUSAL WOMEN; VASOMOTOR SYMPTOMS; DOUBLE-BLIND; CLIMACTERIC
SYMPTOMS; MAMMOGRAPHIC DENSITY
AB Background: The purpose of this study was to provide practical, evidence-based guidelines for evaluating and treating common menopausal symptoms following breast cancer.
Methods: Literature review of the causes, assessment and management of menopausal symptoms in breast cancer patients.
Results: A number of nonhormonal treatments are effective in treating hot flashes. Whether pharmacological treatment is given will depend on the severity of symptoms and on patient wishes. For severe and frequent hot flashes, the best data support the use of venlafaxine, paroxetine and gabapentin in women with breast cancer. Side-effects are relatively common with all these agents. For vaginal dryness, topical estrogen treatment is the most effective but the safety of estrogens following breast cancer is not established. There are limited data on effective treatments for sexual dysfunction during menopause.
Conclusion: Menopausal symptoms after breast cancer should be evaluated and managed as warranted using a systematic approach and may benefit from multidisciplinary input.
C1 [Hickey, M.] Univ Western Australia, Sch Womens & Infants Hlth, King Edward Mem Hosp, Perth, WA 6008, Australia.
[Saunders, C.] Univ Western Australia, Sch Surg & Pathol, Perth, WA 6008, Australia.
[Partridge, A.] Dana Farber Canc Inst, Dept Obstet Gynecol & Womens Hlth, Boston, MA 02115 USA.
[Santoro, N.] Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA.
[Joffe, H.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Joffe, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA USA.
[Stearns, V.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Hickey, M (reprint author), Univ Western Australia, Sch Womens & Infants Hlth, 374 Bagot Rd, Perth, WA 6008, Australia.
EM mhickey@meddent.uwa.edu.au
RI Saunders, Christobel/H-5779-2014;
OI Saunders, Christobel/0000-0003-2281-9829; Hickey,
Martha/0000-0002-3941-082X
NR 123
TC 55
Z9 56
U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD OCT
PY 2008
VL 19
IS 10
BP 1669
EP 1680
DI 10.1093/annonc/mdn353
PG 12
WC Oncology
SC Oncology
GA 353PT
UT WOS:000259581200002
PM 18522932
ER
PT J
AU Ng, AK
Li, S
Neuberg, D
Chi, R
Fisher, DC
Silver, B
Mauch, PM
AF Ng, A. K.
Li, S.
Neuberg, D.
Chi, R.
Fisher, D. C.
Silver, B.
Mauch, P. M.
TI A prospective study of pulmonary function in Hodgkin's lymphoma patients
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE bleomycin; hodgkin lymphoma; lung toxicity; radiation parameters
ID PREDICTING RADIATION PNEUMONITIS; VOLUME HISTOGRAM PARAMETERS;
MANTLE-FIELD IRRADIATION; LUNG-CANCER; MEDIASTINAL IRRADIATION; DISEASE;
BLEOMYCIN; RADIOTHERAPY; CHEMOTHERAPY; TOXICITY
AB Background: To prospectively study changes in lung function in Hodgkin's lymphoma (HL) patients and to explore predictors for these changes over time.
Methods: In all, 52 patients with HL receiving bleomycin-based chemotherapy with (n = 23) or without (n = 29) mediastinal radiotherapy were enrolled. Pretreatment pulmonary function tests were carried out. These were repeated at 1 month, 6 months, and 1 year after therapy.
Results: With chemotherapy alone, the median %DLCO declined significantly at 1 month but returned to baseline by 6 months. The median %DLCO did not further decrease with radiotherapy, but remained persistently reduced at 1 year. In patients who received radiotherapy, having > 33% of lung volume receive 20 Gy (V20) and a mean lung dose (MLD) of > 13 Gy significantly predicted for persistently reduced %DLCO at 6 months (P = 0.035). Smoking significantly predicted for a persistently reduced %DLCO at 1 year (P = 0.036). On multivariable analysis, significant predictors for decline in %DLCO at 1 year were higher baseline %DLCO (P = 0.01), higher MLD (P = 0.02), and a smoking history (P = 0.02).
Conclusions: Several factors contribute to decline in %DLCO in HL patients who received bleomycin-based computed tomography. The identification of threshold radiation dosimetric parameters for reduced lung function may provide guidance in the radiation planning of these patients.
C1 [Ng, A. K.; Chi, R.; Silver, B.; Mauch, P. M.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Li, S.; Neuberg, D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Fisher, D. C.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP Ng, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02114 USA.
EM ang@lroc.harvard.edu
FU American Society of Hematology Junior Faculty Clinical Research Award
FX American Society of Hematology Junior Faculty Clinical Research Award.
NR 26
TC 13
Z9 15
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD OCT
PY 2008
VL 19
IS 10
BP 1754
EP 1758
DI 10.1093/annonc/mdn284
PG 5
WC Oncology
SC Oncology
GA 353PT
UT WOS:000259581200013
PM 18467315
ER
PT J
AU Esnaola, NF
Hall, BL
Hosokawa, PW
Ayanian, JZ
Henderson, WG
Khuri, SE
Zinner, MJ
Rogers, SO
AF Esnaola, Nestor F.
Hall, Bruce L.
Hosokawa, Patrick W.
Ayanian, John Z.
Henderson, William G.
Khuri, Shukri E.
Zinner, Michael J.
Rogers, Selwyn O., Jr.
TI Race and Surgical Outcomes It Is Not All Black and White
SO ANNALS OF SURGERY
LA English
DT Article
ID QUALITY IMPROVEMENT PROGRAM; 30-DAY POSTOPERATIVE MORTALITY; UNIVERSITY
MEDICAL-CENTERS; VETERANS-AFFAIRS HOSPITALS; CLINICAL COMORBIDITY INDEX;
HIGH-VOLUME HOSPITALS; 8 COMMON OPERATIONS; RISK-ADJUSTMENT;
RACIAL-DIFFERENCES; COLORECTAL-CANCER
AB Background: Studies using Medicare data have suggested that African American race is an independent predictor of death after major surgery. We hypothesized that the apparent adverse effect of race on surgical outcomes is due to confounding by comorbidity, not race itself
Methods: We identified all non-Hispanic white and African American general surgery, private sector patients included in the National Surgery Quality Improvement Program (NSQIP) Patient Safety in Surgery Study (2001-2004). Patient characteristics, comorbidities, and postoperative outcomes were collected/analyzed using NSQIP methodology. Characteristics between races were compared using Student t and chi(2) tests. Odds ratios (OR) for 30-day morbidity and mortality were calculated using multivariable logistic regression.
Results: We identified 34,141 white and 5068 African American patients. African Americans were younger but more likely to undergo emergency surgery and present with hypertension, dyspnea, diabetes, renal failure, open wounds/infection, or advanced American Society of Anesthesiology class (all P < 0.001). African Americans underwent less complex procedures but had higher unadjusted 30-day morbidity (14.33% vs. 12.35%; P < 0.001) and mortality (2.09% vs. 1.65%; P = 0.02). After controlling for comorbidity, African American race had no independent effect on mortality (OR 0.95, (0.74-1.23)) but was associated with a higher risk of postoperative cardiac arrest (OR 2.49, (1.80-3.45)) and renal insufficiency/failure (OR 1.70 (1.32-2.18)).
Conclusion: African American race is associated with greater comorbidity and cardiac/renal complications but is not an independent predictor of perioperative mortality after general surgery. Efforts to improve postoperative outcomes in African Americans should focus on reducing the need for emergency surgery and improving perioperative management of comorbid conditions.
C1 [Esnaola, Nestor F.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA.
[Esnaola, Nestor F.] Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA.
[Hall, Bruce L.] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA.
[Hall, Bruce L.] Washington Univ, Barnes Jewish Hosp, Dept Surg, Sch Med, St Louis, MO USA.
[Hall, Bruce L.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA.
[Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO 63130 USA.
[Hosokawa, Patrick W.; Henderson, William G.] Colorado Hlth Outcomes Program, Aurora, CO USA.
[Ayanian, John Z.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Ayanian, John Z.; Zinner, Michael J.; Rogers, Selwyn O., Jr.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Khuri, Shukri E.] Vet Adm Med Ctr, Dept Surg, W Roxbury, MA USA.
[Zinner, Michael J.; Rogers, Selwyn O., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
RP Esnaola, NF (reprint author), Med Univ S Carolina, Dept Surg, 25 Courtenay Dr Suite 7018 MSC 295, Charleston, SC 29425 USA.
EM esnaolan@musc.edu
FU Agency for Healthcare Research and Quality [1U18HS11913-03]
FX Supported by Agency for Healthcare Research and Quality grant
1U18HS11913-03.
NR 53
TC 24
Z9 24
U1 1
U2 1
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 OCT
PY 2008
VL 248
IS 4
BP 647
EP 654
DI 10.1097/SLA.0b013e31818a159a
PG 8
WC Surgery
SC Surgery
GA 366LT
UT WOS:000260483700029
PM 18936578
ER
PT J
AU Smith, MJ
Culhane, AC
Killeen, S
Kelly, MA
Wang, JH
Cotter, TG
Redmond, HP
AF Smith, Myles J.
Culhane, Aedin C.
Killeen, Shane
Kelly, Maura A.
Wang, Jiang H.
Cotter, Thomas G.
Redmond, Henry P.
TI Mechanisms driving local breast cancer recurrence in a model of
breast-conserving surgery
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
DE breast cancer; local recurrence; animal model; microarray; vaccine
ID GENE-EXPRESSION SIGNATURE; SMALL-MOLECULE INHIBITOR; HEAT-SHOCK
PROTEINS; RANDOMIZED-TRIAL; SURVIVAL; AKT; METASTASIS; THERAPY; CELLS;
PCR
AB Objective: We aimed to identify mechanisms driving local recurrence in a model of breast-conserving surgery (BCS) for breast cancer.
Background: Breast cancer recurrence after BCS remains a clinically significant, but poorly understood problem. We have previously reported that recurrent colorectal tumours demonstrate altered growth dynamics, increased metastatic burden and resistance to apoptosis, mediated by upregulation of phosphoinositide-3-kinase/Akt (PI3K/Akt). We investigated whether similar characteristics were evident in a model of locally recurrent breast cancer.
Methods: Tumours were generated by orthotopic inoculation of 4T1 cells in two groups of female Balb/c mice and cytoreductive surgery performed when mean tumour size was above 150 mm(3). Local recurrence was observed and gene expression was examined using Affymetrix GeneChips in primary and recurrent tumours. Differential expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR). Phosphorylation of Akt was assessed using Western immunoblotting. An ex vivo heat shock protein (HSP)-loaded dendritic cell vaccine was administered in the perioperative period.
Results: We observed a significant difference in the recurrent 4T1 tumour volume and growth rate (p < 0.05). Gene expression studies suggested roles for the PI3K/Akt system and local immunosuppression driving the altered growth kinetics. We demonstrated that perioperative vaccination with an ex vivo HSP-loaded dendritic cell vaccine abrogated recurrent tumour growth in vivo (p = 0.003 at day 15).
Conclusion: Investigating therapies which target tumour survival pathways such as PI3K/Akt and boost immune surveillance in the perioperative period may be useful adjuncts to contemporary breast cancer treatment.
C1 [Smith, Myles J.; Killeen, Shane; Kelly, Maura A.; Wang, Jiang H.; Redmond, Henry P.] Cork Univ Hosp, Acad Dept Surg, Cork, Ireland.
[Smith, Myles J.; Cotter, Thomas G.] Natl Univ Ireland Univ Coll Cork, Cork Univ Hosp, Cork, Ireland.
[Culhane, Aedin C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Culhane, Aedin C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Smith, MJ (reprint author), Cork Univ Hosp, Acad Dept Surg, Cork, Ireland.
EM mylessmith@hotmail.com
RI Smith, Myles/B-7803-2009
OI Smith, Myles/0000-0002-3254-4817
NR 42
TC 7
Z9 7
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 OCT
PY 2008
VL 15
IS 10
BP 2954
EP 2964
DI 10.1245/s10434-008-0037-5
PG 11
WC Oncology; Surgery
SC Oncology; Surgery
GA 348BP
UT WOS:000259186300044
PM 18622646
ER
PT J
AU Roedl, JB
Harisinghani, MG
Colen, RR
Fischman, AJ
Blake, MA
Mathisen, DJ
Mueller, PR
AF Roedl, Johannes B.
Harisinghani, Mukesh G.
Colen, Rivka R.
Fischman, Alan J.
Blake, Michael A.
Mathisen, Douglas J.
Mueller, Peter R.
TI Assessment of treatment response and recurrence in esophageal carcinoma
based on tumor length and standardized uptake value on positron emission
tomography-computed tomography
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; NEOADJUVANT CHEMORADIOTHERAPY; ESOPHAGOGASTRIC
JUNCTION; FDG-PET; CANCER; SURVIVAL; TRIAL; CHEMOTHERAPY; SURGERY; CT
AB Background. Previous studies demonstrated that a decrease of the standardized uptake value between pretreatment and posttreatment positron emission tomography (PET) scans can predict histopathologic treatment response in patients with esophageal cancer.
Methods. Forty-seven patients who underwent PET computed tomography (CT) scans before (scan 1) and after (scan 2) neoadjuvant chemoradiotherapy and during the follow-up period after surgery (scan 3) were included in this study. It was evaluated whether decrease of metabolic tumor length between scan 1 and scan 2 can predict histopathologic response to treatment. Moreover, the value of PET-CT was compared with PET in the assessment of tumor recurrence based on a visual analysis of scan 3. Reference standards for treatment response and recurrence were histopathology results.
Results. The reduction of tumor length between before and after chemoradiotherapy scans (between scan 1 and scan 2) was a better predictor of histopathologic response and of time to recurrence than the decrease in standardized uptake value. The most accurate differentiation was achieved when using a cut-off value of 33% reduction of the initial tumor length. Using this threshold to define metabolic response, the sensitivity was 91% (19 of 21) and the specificity was 92% (24 of 26) for predicting histopathologic treatment response. Based on a visual analysis, PET-CT was more accurate than PET in the differentiation of tumor recurrence from posttreatment tissue changes. Integrated PET-CT achieved a sensitivity of 91% (48 of 53) and a specificity of 81% (30 of 37) in identifying sites of tumor recurrence, compared with 83% (44 of 53) and 65% (24 of 37) with PET.
Conclusions. Decrease of tumor length was shown to be a better predictor of treatment response and disease-free survival than decrease of standardized uptake value. Furthermore, PET-CT is more accurate in the evaluation of recurrence than PET.
C1 [Roedl, Johannes B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA.
RP Roedl, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Fruit St 55, Boston, MA 02114 USA.
EM johannes.roedl@gmail.com
NR 31
TC 24
Z9 28
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD OCT
PY 2008
VL 86
IS 4
BP 1131
EP 1138
DI 10.1016/j.athoracsur.2008.05.019
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 357LT
UT WOS:000259848000012
PM 18805147
ER
PT J
AU Chu, D
Bakaeen, FG
Wang, XL
Dao, TK
LeMaire, SA
Coselli, JS
Huh, J
AF Chu, Danny
Bakaeen, Faisal G.
Wang, Xing Li
Dao, Tam K.
LeMaire, Scott A.
Coselli, Joseph S.
Huh, Joseph
TI The impact of peripheral vascular disease on long-term survival after
coronary artery bypass graft surgery
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID INTERMITTENT CLAUDICATION; CARDIAC-SURGERY; RISK-FACTORS; MORTALITY;
REVASCULARIZATION; MORBIDITY; MODEL
AB Background. Although peripheral vascular disease is known to negatively affect overall survival, its effects on survival after surgical myocardial revascularization have not been well described. The objective of this study was to examine the impact of peripheral vascular disease on long-term survival after coronary artery bypass grafting.
Methods. We reviewed records of 1,164 consecutive patients (370 with peripheral vascular disease and 794 without it) who underwent primary isolated coronary artery bypass graft surgery between 1997 and 2007. Univariate and multivariate logistic regression methods were used to analyze variables associated with early outcomes. We assessed long-term survival by using Kaplan-Meier curves generated by log-rank tests, adjusting for confounding factors with Cox proportional hazards regression analysis.
Results. Patients with peripheral vascular disease were generally sicker and had more comorbidities than patients without peripheral vascular disease. The presence of peripheral vascular disease does not predict increased rates of 30- day mortality or major adverse cardiac events. However, after controlling for potential confounding factors, patients with peripheral vascular disease had a significantly worse 9- year survival rate than patients without peripheral vascular disease (72.9% +/- 4.1% versus 82.8% +/- 2.4%; adjusted hazard ratio, 1.7; 95% confidence interval: 1.2 to 2.4; p = 0.004).
Conclusions. Although peripheral vascular disease does not affect early outcomes in coronary artery bypass operations, it is an independent predictor of poor long-term survival among patients undergoing coronary artery bypass graft surgery. Identifying the mechanism that underlies this difference is important for improving survival in patients with peripheral vascular disease who undergo surgical myocardial revascularization.
C1 [Chu, Danny] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
St Lukes Episcopal Hosp, Texas Heart Inst, Sect Adult Cardiac Surg, Houston, TX USA.
RP Chu, D (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Dept Psychiat & Behav Sci, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA.
EM dchumd@gmail.com
NR 19
TC 9
Z9 9
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD OCT
PY 2008
VL 86
IS 4
BP 1175
EP 1180
DI 10.1016/j.athoracsur.2008.06.024
PG 6
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 357LT
UT WOS:000259848000018
PM 18805156
ER
PT J
AU Craig, WA
Andes, DR
AF Craig, W. A.
Andes, D. R.
TI In vivo pharmacodynamics of ceftobiprole against multiple bacterial
pathogens in murine thigh and lung infection models
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID METHICILLIN-RESISTANT STAPHYLOCOCCI; PARENTERAL CEPHALOSPORIN; SPECTRUM
CEPHALOSPORIN; BAL9141; PHARMACOKINETICS; VITRO; ANTIBIOTICS; PNEUMONIA;
EFFICACY; BAL5788
AB Ceftobiprole medocaril is the parenteral prodrug of ceftobiprole, a novel pyrrolidinone broad-spectrum cephalosporin with in vitro and in vivo bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). We have used murine thigh and lung infection models in neutropenic and normal mice to characterize the in vivo pharmacokinetic (PK)-pharmacodynamic (PD) activities of ceftobiprole against multiple strains of S. aureus (including MRSA), S. pneumoniae (including PRSP), and gram-negative bacilli. Serum levels of ceftobiprole following the administration of multiple doses were determined by a microbiological assay. In vivo bactericidal activities and postantibiotic effects (PAEs) of ceftobiprole against MRSA and PRSP strains were determined from serial CFU/thigh values following single doses of ceftobiprole (40 and 160 mg/kg of body weight). Dose fractionation studies were used to determine which PK-PD index correlated best with activity. Magnitudes of the PK-PD indices were calculated from MICs and PK parameters. A sigmoid dose-response model was used to estimate the dose (mg/kg/24 h) required to achieve a static and 2-log(10) kill effects over 24 h. PK results showed area under the concentration-time curve/dose values of 1.8 to 2.8 and half-lives of 0.29 to 0.51 h. MICs ranged from 0.015 to 2 mu g/ml. Ceftobiprole demonstrated time-dependent killing; its in vivo PAEs varied from 3.8 h to 4.8 h for MRSA and from 0 to 0.8 h for PRSP. The time above MIC (T > MIC) correlated best with efficacy for both MRSA and PRSP. The T > MIC values required for the static doses were significantly longer (P < 0.001) for Enterobacteriaceae (36 to 45%) than for S. aureus (14 to 28%) and S. pneumoniae (15 to 22%). The drug showed activities in the lung model similar to those in the thigh model. The presence of neutrophils significantly enhanced the activity of ceftobiprole against S. pneumoniae but only slightly against Klebsiella pneumoniae. Based on its PD profile, ceftobiprole is a promising new beta-lactam agent with activity against gram-negative and gram-positive organisms including MRSA and PRSP.
C1 [Craig, W. A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA.
[Craig, W. A.; Andes, D. R.] Univ Wisconsin, Dept Med, Infect Dis Sect, Sch Med & Publ Hlth, Madison, WI 53706 USA.
RP Craig, WA (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA.
EM wac@medicine.wisc.edu
NR 25
TC 45
Z9 46
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD OCT
PY 2008
VL 52
IS 10
BP 3492
EP 3496
DI 10.1128/AAC.01273-07
PG 5
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 352FJ
UT WOS:000259480800004
PM 18676887
ER
PT J
AU Forrest, GN
Roghmann, MC
Toombs, LS
Johnson, JK
Weekes, E
Lincalis, DP
Venezia, RA
AF Forrest, Graeme N.
Roghmann, Mary-Claire
Toombs, Latoya S.
Johnson, Jennifer K.
Weekes, Elizabeth
Lincalis, Durry P.
Venezia, Richard A.
TI Peptide nucleic acid fluorescent in situ hybridization for
hospital-acquired enterococcal bacteremia: Delivering earlier effective
antimicrobial therapy
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID VANCOMYCIN-RESISTANT ENTEROCOCCUS; BLOOD-STREAM INFECTIONS; STEM-CELL
TRANSPLANT; RISK-FACTORS; FAECIUM BACTEREMIA; STAPHYLOCOCCUS-AUREUS;
CANDIDA-ALBICANS; RAPID DETECTION; MORTALITY; IDENTIFICATION
AB Hospital-acquired vancomycin-resistant enterococcal bacteremia has been associated with increased hospital costs, length of stay, and mortality. The peptide nucleic acid fluorescent in situ hybridization (PNA FISH) test for Enterococcus faecalis and other enterococci (EFOE) is a multicolor probe that differentiates E. faecalis from other enterococcal species within 3 h directly from blood cultures demonstrating gram-positive cocci in pairs and chains (GPCPC). A quasiexperimental study was performed over two consecutive years beginning in 2005 that identified GPCPC by conventional microbiological methods, and in 2006 PNA FISH was added with a treatment algorithm developed by the antimicrobial team (AMT). The primary outcome assessed was the time from blood culture draw to the implementation of effective antimicrobial therapy before and after PNA FISH. The severity of illness, patient location, and empirical antimicrobial therapy were measured. A total of 224 patients with hospital-acquired enterococcal bacteremia were evaluated, with 129 in the preintervention period and 95 in the PNA FISH period. PNA FISH identified E. faecalis 3 days earlier than conventional cultures (1.1 versus 4.1 days; P < 0.001). PNA FISH identified Enterococcus faecium a median 2.3 days earlier (1.1 versus 3.4 days; P < 0.001) and was associated with statistically significant reductions in the time to initiating effective therapy (1.3 versus 3.1 days; P < 0.001) and decreased 30-day mortality (26% versus 45%; P = 0.04). The EFOE PNA FISH test in conjunction with an AMT treatment algorithm resulted in earlier initiation of appropriate empirical antimicrobial therapy for patients with hospital-acquired E. faecium bacteremia.
C1 [Forrest, Graeme N.] Univ Maryland, Sch Med, Div Infect Dis, Baltimore, MD 21201 USA.
[Roghmann, Mary-Claire] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Toombs, Latoya S.; Weekes, Elizabeth] Univ Maryland, Dept Pharm, Med Ctr, Baltimore, MD 21201 USA.
[Johnson, Jennifer K.; Lincalis, Durry P.; Venezia, Richard A.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
RP Forrest, GN (reprint author), Portland VA Med Ctr, 3701 SW US Vet Hosp Rd,P31D, Portland, OR 97239 USA.
EM forrestg@ohsu.edu
OI Roghmann, Mary-Claire/0000-0003-1063-9257
FU AdvanDx; Cubist Pharmaceuticals, Inc.; Pfizer Inc; 3M
FX Potential conflicts of interest: G.N.F. has received research funding
and speaking honoraria from AdvanDx, Cubist Pharmaceuticals, Inc., and
Pfizer Inc. M.-C.R. has received research funding from 3M and Merck.
R.A.V. and J.K.J. have received speaking honoraria from AdvanDx.
NR 40
TC 81
Z9 83
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD OCT
PY 2008
VL 52
IS 10
BP 3558
EP 3563
DI 10.1128/AAC.00283-08
PG 6
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 352FJ
UT WOS:000259480800013
PM 18663022
ER
PT J
AU Rodrigues, MS
Reddy, MM
Sattler, M
AF Rodrigues, Margret S.
Reddy, Mamatha M.
Sattler, Martin
TI Cell cycle regulation by oncogenic tyrosine kinases in myeloid
neoplasias: From molecular redox mechanisms to health implications
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID NF-KAPPA-B; CHRONIC MYELOGENOUS LEUKEMIA; HYPOXIA-INDUCIBLE FACTOR;
FORKHEAD TRANSCRIPTION FACTOR; ENDOTHELIAL GROWTH-FACTOR; P210 BCR-ABL;
GUANINE-NUCLEOTIDE EXCHANGE; TUMOR-SUPPRESSOR PTEN; UBIQUITIN-PROTEASOME
PATHWAY; ANTIOXIDANT GENE-EXPRESSION
AB Neoplastic expansion of myeloid cells is associated with specific genetic changes that lead to chronic activation of signaling pathways, as well as altered metabolism. It has become increasingly evident that transformation relies on the interdependency of both events. Among the various genetic changes, the oncogenic BCR-ABL tyrosine kinase in patients with Philadelphia chromosome positive chronic myeloid leukemia (CML) has been a focus of extensive research. Transformation by this oncogene is associated with elevated levels of intracellular reactive oxygen species (ROS). ROS have been implicated in processes that promote viability, cell growth, and regulation of other biological functions such as migration of cells or gene expression. Currently, the BCR-ABL inhibitor imatinib mesylate (Gleevec) is being used as a first-line therapy for the treatment of CML. However, BCR-ABL transformation is associated with genomic instability, and disease progression or resistance to imatinib can occur. Imatinib resistance is not known to cause or significantly alter signaling requirements in transformed cells. Elevated ROS are crucial for transformation, making them an ideal additional target for therapeutic intervention. The underlying mechanisms leading to elevated oxidative stress are reviewed, and signaling mechanisms that may serve as novel targeted approaches to overcome ROS-dependent cell growth are discussed.
C1 [Sattler, Martin] Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Sattler, M (reprint author), Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM martin_sattler@dfci.harvard.edu
FU American Cancer Society; United States Department of Defense; Adams Barr
Program in Innovative Cancer Research
FX This work was supported by grants from the American Cancer Society, the
United States Department of Defense, and the Adams Barr Program in
Innovative Cancer Research.
NR 416
TC 30
Z9 31
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD OCT
PY 2008
VL 10
IS 10
BP 1813
EP 1848
DI 10.1089/ars.2008.2071
PG 36
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 340DI
UT WOS:000258625900006
PM 18593226
ER
PT J
AU Marijon, E
Lung, B
Mocumbi, AO
Kamblock, J
Thanh, CV
Gamra, H
Esteves, C
Palacios, IF
Vahanian, A
AF Marijon, Eloi
Lung, Bernard
Mocumbi, Ana-Olga
Kamblock, Joel
Thanh, Chien Vo
Gamra, Habib
Esteves, Cesar
Palacios, Igor F.
Vahanian, Alec
TI What are the differences in presentation of candidates for percutaneous
mitral commissurotomy across the world and do they influence the results
of the procedure?
SO ARCHIVES OF CARDIOVASCULAR DISEASES
LA English
DT Article
DE Mitral stenosis; Rheumatic fever; Balloon mitral commissurotomy
ID RHEUMATIC HEART-DISEASE; TERM-FOLLOW-UP; BALLOON VALVULOPLASTY;
STENOSIS; VALVOTOMY; VARIABLES; PERIOD
AB Background. - Despite marked global differences in the prevalence of rheumatic heart disease, little is known about geographic variations in the characteristics of patients with severe mitral stenosis.
Aim. - To determine if differences in rheumatic fever epidemiology influence the characteristics of patients with mitral stenosis and the immediate results of percutaneous mitral commissurotomy (PMC).
Methods. - We compared 350 patients (mean age: 41 +/- 17 years, 81% women) scheduled for PMC in five non-Western and two Western countries. Fifty consecutive patients were included in each centre. All presented a mitral valve area less than 1.5 cm(2) and were in New York Heart Association (NYHA) functional class greater or equal to 11, with no contraindications to PMC.
Results. - The 250 patients from non-Western countries were younger than the 100 patients from Western countries (35 +/- 12 vs 57 +/- 15 years, p < 0.0001) and had more severe valve disease, assessed by indexed valve area (0.57 +/- 0.14 vs 0.62 +/- 0.14 cm(2)/m(2) body surface area, p = 0.006), mean gradient (15 +/- 6 vs 8 +/- 4 mmHg, p < 0.0001) and systolic pulmonary artery pressure (57 +/- 21 vs 42 +/- 14 mmHg, p < 0.0001). PMC complication rates did not differ significantly. Good immediate PMC results were observed in 225 patients (90%) in non-Western and 88 (88%) in Western centres (p = 0.58).
Conclusions. - Compared with Western countries, PMC candidates from non-Western countries are younger, with more severe valve stenosis. However, PMC achieves good immediate results in a similarly high proportion of patients, showing the wide applicability of this technique. (C) 2008 Elsevier Masson SAS. All rights reserved.
C1 [Marijon, Eloi; Lung, Bernard; Vahanian, Alec] Hop Xavier Bichat, Dept Cardiol, AP HP, F-75018 Paris, France.
[Mocumbi, Ana-Olga] Inst Coracao, Maputo, Mozambique.
[Kamblock, Joel] Taaone Hosp, Dept Cardiol, Papeete, Fr Polynesia.
[Thanh, Chien Vo] Cho Ray Hosp, Dept Cardiol, Ho Chi Minh City, Vietnam.
[Gamra, Habib] Fattouma Bourguiba Hosp, Dept Cardiol, Monastir, Tunisia.
[Esteves, Cesar] Dante Pazzanese Inst, Dept Cardiol, Sao Paulo, Brazil.
[Palacios, Igor F.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Marijon, E (reprint author), Hop Xavier Bichat, Dept Cardiol, AP HP, 46 Rue Henri Huchard, F-75018 Paris, France.
EM eloi_marijon@yahoo.fr
NR 24
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 1875-2136
EI 1875-2128
J9 ARCH CARDIOVASC DIS
JI Arch. Cardiovasc. Dis.
PD OCT
PY 2008
VL 101
IS 10
BP 611
EP 617
DI 10.1016/j.acvd.2008.09.012
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 386ZT
UT WOS:000261922200004
PM 19056067
ER
PT J
AU Schaffer, BAJ
Bertram, L
Miller, BL
Mullin, K
Weintraub, S
Johnson, N
Bigio, EH
Mesulam, M
Wiedau-Pazos, M
Jackson, GR
Cummings, JL
Cantor, RM
Levey, AI
Tanzi, RE
Geschwind, DH
AF Schaffer, Barbara A. J.
Bertram, Lars
Miller, Bruce L.
Mullin, Kristina
Weintraub, Sandra
Johnson, Nancy
Bigio, Eileen H.
Mesulam, Marsel
Wiedau-Pazos, Martina
Jackson, George R.
Cummings, Jeffrey L.
Cantor, Rita M.
Levey, Allan I.
Tanzi, Rudolph E.
Geschwind, Daniel H.
TI Association of GSK3B with Alzheimer disease and frontotemporal dementia
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; PRIMARY PROGRESSIVE APHASIA;
NEUROFIBRILLARY TANGLES; GENETIC ASSOCIATION; APOLIPOPROTEIN-E;
NEURODEGENERATION; POLYMORPHISMS; VARIANTS; ONSET; CDK5
AB Background: Deposits of abnormally hyperphosphorylated tau are a hallmark of several dementias, including Alzheimer disease ( AD), and about 10% of familial frontotemporal dementia (FTD) cases are caused by mutations in the tau gene. As a known tau kinase, GSK3B is a promising candidate gene in the remaining cases of FTD and in AD, for which tau mutations have not been found.
Objective: To examine the promoter of GSK3B and all 12 exons, including the surrounding intronic sequence, in patients with FTD, patients with AD, and aged healthy subjects to identify single-nucleotide polymorphisms associated with disease.
Design, Setting, and Participants: Single-nucleotide polymorphism frequency was examined in a case-control cohort of 48 patients with probable AD, 102 patients with FTD, 38 patients with primary progressive aphasia, and 85 aged healthy subjects. Results were followed up in 2 independent AD family samples consisting of 437 multiplex families with AD (National Institute of Mental Health Genetics Initiative AD Study) or 150 sibships discordant for AD (Consortium on Alzheimer's Genetics Study).
Results: Several rare sequence variants in GSK3B were identified in the case-control study. An intronic polymorphism (IVS2-68G > A) occurred at more than twice the frequency among patients with FTD (10.8%) and patients with AD (14.6%) than in aged healthy subjects (4.1%). The polymorphism showed association with disease in both follow-up samples independently, although only the Consortium on Alzheimer's Genetics sample showed the same direction of association as the case-control sample.
Conclusions: To our knowledge, this is the first evidence that a gene known to be involved in tau phosphorylation, GSK3B, is associated with risk for primary neurodegenerative dementias. This supports previous work in animal models suggesting that such genes are therapeutic targets.
C1 [Schaffer, Barbara A. J.; Wiedau-Pazos, Martina; Jackson, George R.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA.
[Cummings, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA.
[Bertram, Lars; Mullin, Kristina; Tanzi, Rudolph E.] Harvard Univ, MassGeneral Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Dept Neurol,Sch Med,Genet & Aging Res Unit, Charlestown, MA USA.
[Miller, Bruce L.] Univ Calif San Francisco, Dept Neurol, Ctr Memory & Aging, San Francisco, CA 94143 USA.
[Weintraub, Sandra; Johnson, Nancy; Mesulam, Marsel] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA.
[Bigio, Eileen H.] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA.
[Levey, Allan I.] Emory Univ, Alzheimers Dis Ctr, Atlanta, GA 30322 USA.
[Levey, Allan I.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
RP Geschwind, DH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, 2506 Gonda,695 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM dhg@ucla.edu
RI Bertram, Lars/K-3889-2015
OI Bertram, Lars/0000-0002-0108-124X
FU National Institute on Aging [AG16570, AG19724, AG13854, AG025688];
National Institute of Mental Health [MH60009]
FX This work was supported by grants AG16570 (Ms Schaffer and Dr
Geschwind), AG19724 (Dr Miller), AG13854 (Dr Mesulam), and AG025688 (Dr
Levey) from the National Institute on Aging, grant MH60009 from the
National Institute of Mental Health (Dr Tanzi), The John Douglas French
Alzheimer's Foundation (Drs Wiedau-Pazos and Geschwind), the Cure
Alzheimer's Fund (Dr Tanzi), and the Turken Family Scholarship Award
from the Alzheimer's Association of Los Angeles (Dr Geschwind). At the
time of this work, Dr Bertram was a fellow of the Harvard Center for
Neurodegeneration and Repair and was a fellow of the Deutsche
Forschungsgemeinschaft.
NR 32
TC 51
Z9 54
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD OCT
PY 2008
VL 65
IS 10
BP 1368
EP 1374
DI 10.1001/archneur.65.10.1368
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 359JY
UT WOS:000259984200016
PM 18852354
ER
PT J
AU Dighe, AS
Jones, JB
Parham, S
Lewandrowski, KB
AF Dighe, Anand S.
Jones, Jay B.
Parham, Sue
Lewandrowski, Kent B.
TI Survey of Critical Value Reporting and Reduction of False-Positive
Critical Value Results
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID LABORATORY CRITICAL-VALUES; NOTIFICATION; INSTITUTIONS; INFORMATION
AB Context.-Reporting of laboratory critical values has become an issue of national attention because of important regulatory, medicolegal, and clinical concerns.
Objective.-To survey aspects of the laboratory critical-value reporting process at a broad range of institutions.
Design.-A survey was developed regarding the operational and information-technology aspects of critical value reporting.
Results.-More than 730 responses were obtained from a broad distribution of hospitals. In addition, we analyzed more than 700 written responses from survey participants.
Conclusions.-The survey results provide insight into the standard of practice and level of compliance with current Joint Commission and College of American Pathologists requirements for critical values, demonstrate considerable heterogeneity, and suggest areas for improvement. A common issue raised during the survey and follow-up teleconference was the incidence of outpatient false-positive critical values. In this report, we also demonstrate that attention to preanalytic transport and processing issues can assist in minimizing this issue. (Arch Pathol Lab Med. 2008; 132: 1666-1671)
C1 [Dighe, Anand S.; Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Jones, Jay B.] Geisinger Med Labs, Danville, PA USA.
[Parham, Sue] Amer Assoc Clin Chem, Washington, DC USA.
RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bigelow 510,55 Fruit St, Boston, MA 02114 USA.
EM klewandrowski@partners.org
NR 16
TC 17
Z9 23
U1 2
U2 6
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD OCT
PY 2008
VL 132
IS 10
BP 1666
EP 1671
PG 6
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 358FT
UT WOS:000259903200027
PM 18834227
ER
PT J
AU Wilens, TE
Adamson, J
Monuteaux, MC
Faraone, SV
Schillinger, M
Westerberg, D
Biederman, J
AF Wilens, Timothy E.
Adamson, Joel
Monuteaux, Michael C.
Faraone, Stephen V.
Schillinger, Mary
Westerberg, Diana
Biederman, Joseph
TI Effect of prior stimulant treatment for attention-deficit/hyperactivity
disorder on subsequent risk for cigarette smoking and alcohol and drug
use disorders in adolescents
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; PSYCHIATRIC
COMORBIDITY; EARLY EXPOSURE; YOUNG-ADULTS; ADHD; CHILDREN; ABUSE;
METHYLPHENIDATE; PREVALENCE
AB Objective: To examine the effects of early stimulant treatment on subsequent risk for cigarette smoking and substance use disorders (SUDs) in adolescents with attentiondeficit/hyperactivity disorder (ADHD).
Design: Case-controlled, prospective, 5-year follow-up study.
Setting: Massachusetts General Hospital, Boston.
Participants: Adolescents with and without ADHD from psychiatric and pediatric sources. Blinded interviewers determined all diagnoses using structured interviews.
Intervention: Naturalistic treatment exposure with psychostimulants for ADHD.
Main Outcome Measures: We modeled time to onset of SUDs and smoking as a function of stimulant treatment.
Results: We ascertained 114 subjects with ADHD (mean age at follow-up, 16.2 years) having complete medication and SUD data; 94 of the subjects were treated with stimulants. There were no differences in SUD risk factors between naturalistically treated and untreated groups other than family history of ADHD. We found no increased risks for cigarette smoking or SUDs associated with stimulant therapy. We found significant protective effects of stimulant treatment on the development of any SUD (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.13-0.60; chi(2)(113) = 10.57, P =. 001) and cigarette smoking(HR, 0.28; 95% CI, 0.14-0.60; chi(2)(111) = 10.05, P=. 001) that were maintained when controlling for conduct disorder. We found no effects of time to onset or duration of stimulant therapy on subsequent SUDs or cigarette smoking in subjects with ADHD.
Conclusion: Stimulant therapy does not increase but rather reduces the risk for cigarette smoking and SUDs in adolescents with ADHD.
C1 [Wilens, Timothy E.; Adamson, Joel; Monuteaux, Michael C.; Schillinger, Mary; Westerberg, Diana; Biederman, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Boston, MA 02114 USA.
[Faraone, Stephen V.] NYU, Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Faraone, Stephen V.] NYU, Upstate Med Univ, Dept Neurosci, Syracuse, NY USA.
[Faraone, Stephen V.] NYU, Upstate Med Univ, Dept Physiol, Syracuse, NY USA.
RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Program, 55 Parkman St,Yawkey 6A, Boston, MA 02114 USA.
EM twilens@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU National Institutes of Health [DA R01 DA14419, K24 DA016264]; Lilly
Foundation
FX This study was supported by grants DA R01 DA14419 and K24 DA016264 from
the National Institutes of Health (Dr Wilens) and by the Lilly
Foundation.
NR 39
TC 54
Z9 54
U1 0
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD OCT
PY 2008
VL 162
IS 10
BP 916
EP 921
DI 10.1001/archpedi.162.10.916
PG 6
WC Pediatrics
SC Pediatrics
GA 356VY
UT WOS:000259806900003
PM 18838643
ER
PT J
AU Pagulayan, KF
Hoffman, JM
Temkin, NR
Machamer, JE
Dikmen, SS
AF Pagulayan, Kathleen Farrell
Hoffman, Jeanne M.
Temkin, Nancy R.
Machamer, Joan E.
Dikmen, Sureyya S.
TI Functional Limitations and Depression After Traumatic Brain Injury:
Examination of the Temporal Relationship
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Brain injuries; Depression; Longitudinal studies; Rehabilitation;
Sickness Impact Profile
ID MAJOR DEPRESSION; RANDOMIZED-TRIAL; PRIMARY-CARE; CHRONIC PAIN;
HEAD-INJURY; SCALE; RELIABILITY; DISORDER; VALIDITY; PREVALENCE
AB Objective: To examine the temporal relationship between self-reported injury-related functional limitations and depressive symptomatology after traumatic brain injury (TBI).
Design: A longitudinal cohort study with 3 evaluation points.
Setting: A level I trauma center.
Participants: Adolescents and adults (N=135) with complicated mild to severe TBI (72% had complicated mild injuries) who were recruited within 24 hours of injury and then completed the measure at all 3 time points.
Interventions: Not applicable.
Main Outcome Measures: Sickness Impact Profile and Center for Epidemiological Studies-Depression Scale.
Results: Individuals who reported more depressive symptomatology consistently endorsed more injury-related difficulties, showing the strong relationship between depression and perceived psychosocial functioning. Examination of these relationships over time revealed that increased depressive symptomatology follows higher levels of perceived injury-related changes but that reports of injury-related changes are not associated with earlier depression. These findings suggest a unidirectional temporal relationship between these variables.
Conclusions: Perceived changes in daily functioning appear to influence emotional well-being over time after TBI. However, depressive symptoms do not appear to negatively impact individuals' perception of later functioning. These results further our understanding of the complicated relationship between these variables and may have important implications for treatment of depression after TBI.
C1 [Pagulayan, Kathleen Farrell; Hoffman, Jeanne M.; Temkin, Nancy R.; Machamer, Joan E.; Dikmen, Sureyya S.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Temkin, Nancy R.; Dikmen, Sureyya S.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA.
[Temkin, Nancy R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Pagulayan, KF (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-116 MHC, Seattle, WA 98108 USA.
EM farkat@u.washington.edu
FU National Institute of Neurological Disorders and Stroke; National
Institutes of Health [RO1 NS19643, F32 HD048030]; National Center for
Medical Rehabilitation Research
FX Supported by the National Institute of Neurological Disorders and
Stroke, National Institutes of Health (grant no. RO1 NS19643) and the
National Center for Medical Rehabilitation Research, National Institutes
of Health (grant no. F32 HD048030).
NR 56
TC 45
Z9 45
U1 1
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 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD OCT
PY 2008
VL 89
IS 10
BP 1887
EP 1892
DI 10.1016/j.apmr.2008.03.019
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 366LY
UT WOS:000260484200006
PM 18929017
ER
PT J
AU Kaafarani, HMA
Atluri, PV
Thornby, J
Itani, KMF
AF Kaafarani, Haytham M. A.
Atluri, Prasad V.
Thornby, John
Itani, Kamal M. F.
TI beta-Blockade in Noncardiac Surgery Outcome at All Levels of Cardiac
Risk
SO ARCHIVES OF SURGERY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; VASCULAR-SURGERY; MYOCARDIAL-INFARCTION;
MORTALITY; METOPROLOL; ISCHEMIA
AB Hypothesis: We hypothesized that the relationship among beta-blocker use, heart rate control, and perioperative cardiovascular outcome would be similar in patients at all levels of cardiac risk.
Design: Retrospective cohort study.
Setting: Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
Patients: Among all patients who underwent various noncardiac surgical procedures in 2000, those who received perioperative beta-blockers were matched and compared with a control group from the same patient population.
Main Outcome Measures: Thirty-day stroke, cardiac arrest, myocardial infarction, and mortality, as well as mortality at 1 year.
Results: Patients at all levels of cardiac risk who received beta-blockers had lower preoperative and intraoperative heart rates. The beta-blocker group had higher rates of 30-day myocardial infarction (2.94% vs 0.74%, P=.03) and 30-day mortality (2.52% vs 0.25%, P=.007) compared with the control group. In the beta-blocker group, patients who died perioperatively had significantly higher preoperative heart rate (86 vs 70 beats/min, P=.03). None of the deaths occurred among the patients at high cardiac risk.
Conclusion: Among patients at all levels of cardiac risk undergoing noncardiac surgery, administration of beta-blockers should achieve adequate heart rate control and should be carefully monitored in patients who are not at high cardiac risk.
C1 [Kaafarani, Haytham M. A.] Univ S Florida, Dept Surg, Tampa, FL 33620 USA.
[Kaafarani, Haytham M. A.; Itani, Kamal M. F.] Vet Affairs Boston Hlth Care Syst, W Roxbury, MA USA.
[Kaafarani, Haytham M. A.; Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA.
[Kaafarani, Haytham M. A.; Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA.
[Atluri, Prasad V.] Baylor Coll Med, Dept Anesthesia, Houston, TX 77030 USA.
[Thornby, John] Michael E DeBakey Vet Affairs Med Ctr, Biostat Lab, Houston, TX USA.
RP Itani, KMF (reprint author), Vet Affairs Boston Healthcare Syst 112, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM kitani@med.va.gov
NR 14
TC 18
Z9 19
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD OCT
PY 2008
VL 143
IS 10
BP 940
EP 944
DI 10.1001/archsurg.143.10.940
PG 5
WC Surgery
SC Surgery
GA 360GG
UT WOS:000260045400005
PM 18936371
ER
PT J
AU Berger, DL
AF Berger, David L.
TI Pancreatogastrostomy as a Salvage Procedure to Treat Severe
Postoperative Pancreatic Fistula After Pancreatoduodenectomy INVITED
CRITIQUE
SO ARCHIVES OF SURGERY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang 465, Boston, MA 02114 USA.
EM dberger@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD OCT
PY 2008
VL 143
IS 10
BP 971
EP 971
DI 10.1001/archsurg.143.10.971
PG 1
WC Surgery
SC Surgery
GA 360GG
UT WOS:000260045400011
ER
PT J
AU Musunuru, K
Nasir, K
Pandey, S
Campbell, CC
Carvalho, JAM
Meneghello, R
Budoff, MJ
Blumenthal, RS
Santos, RD
AF Musunuru, Kiran
Nasir, Khurram
Pandey, Shivda
Campbell, Catherine C.
Carvalho, Jose A. M.
Meneghello, Romeu
Budoff, Matthew J.
Blumenthal, Roger S.
Santos, Raul D.
TI A synergistic relationship of elevated low-density lipoprotein
cholesterol levels and systolic blood pressure with coronary artery
calcification
SO ATHEROSCLEROSIS
LA English
DT Article
DE Coronary calcification; Systolic blood pressure; LDL-cholesterol;
Electron beam tomography; Risk factors; Subclinical atherosclerosis
ID BEAM COMPUTED-TOMOGRAPHY; INTIMA-MEDIA THICKNESS; PROGNOSTIC VALUE;
HEART-DISEASE; RISK-FACTORS; CALCIUM; ATHEROSCLEROSIS; QUANTIFICATION;
PATHOGENESIS; ASSOCIATION
AB We sought to evaluate this "response-to-injury" hypothesis of atherosclerosis by studying the interaction between systolic blood pressure (SBP) and LDL-cholesterol (LDL-C) in predicting the presence of coronary artery calcification (CAC) in asymptomatic men. We Studied 526 men (46 +/- 7 years of age) referred for electron-beam tomography (EBT) exam. The prevalence of CAC was determined across LDL-C tertiles (low: <115 mg/dl; middle: 115-139 mg/dl high: >= 140 mg/dl) within tertiles of SBP (low: <121 mmHg; middle: 121-130 mmHg; high: >= 131 mmHg). CAC was found in 220 (42%) men. There was no linear trend in the presence of CAC across LDL-C tertiles in the low (p = 0.6 for trend) and middle (p = 0.3 for trend) SBP tertile groups, respectively. In contrast, there was a significant trend for increasing CAC with increasing LDL-C (1st: 44%; 2nd: 49%; 3rd: 83%; p < 0.0001 for trend) in the high SBP tertile group. In multivariate logistic analyses (adjusting for age, smoking, triglyceride levels, HDL-cholesterol levels, body mass index, and fasting glucose levels), the odds ratio for any CAC associated with increasing LDL-C was significantly higher in those with highest SBP levels, whereas no such relationship was observed among men with SBP in the lower two tertiles. An interaction term (LDL-C x SBP) incorporated in the multivariate analyses was statistically significant (p = 0.038). The finding of an interaction between SBP and LDL-C relation to CAC in asymptomatic men support the response-to-injury model of atherogenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
C1 [Musunuru, Kiran; Campbell, Catherine C.; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA.
[Nasir, Khurram; Pandey, Shivda] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac PET CT MRI Program, Boston, MA USA.
[Carvalho, Jose A. M.; Meneghello, Romeu; Santos, Raul D.] Albert Einstein Hosp Sao Paulo, Prevent Med Ctr, Sao Paulo, Brazil.
[Budoff, Matthew J.] Harbor UCLA, Torrance, CA USA.
[Santos, Raul D.] Univ Sao Paulo, Lipid Clin Heart Inst InCor, Sch Med, Hosp Sao Paulo, BR-05508 Sao Paulo, Brazil.
RP Santos, RD (reprint author), Unidade Clin Lipides InCor HCFMUSP, Av Dr Eneas C Aguiar 44,Anexo 2 Sala 4, BR-05403900 Sao Paulo, Brazil.
EM rdsf@uol.com.br
RI Santos, Raul/A-1170-2010
OI Santos, Raul/0000-0002-9860-6582
NR 22
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD OCT
PY 2008
VL 200
IS 2
BP 368
EP 373
DI 10.1016/j.atherosclerosis.2007.12.015
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 368UJ
UT WOS:000260647700019
PM 18243213
ER
PT J
AU Swanlund, JM
Kregel, KC
Oberley, TD
AF Swanlund, Jamie M.
Kregel, Kevin C.
Oberley, Terry D.
TI Autophagy following heat stress - The role of aging and protein
nitration
SO AUTOPHAGY
LA English
DT Article
DE mitochondria; 3-nitrotyrosine; autophagy; heat stress; oxidative stress;
nitric oxide
ID OXIDATIVE STRESS; RAT HEPATOCYTES; CELLS; PEROXYNITRITE; SECTIONS
AB Stress can originate from a variety of sources (e.g., physical, chemical, etc.,) and cause protein denaturation, DNA damage and possibly death. In an effort to prevent such deleterious consequences, most organisms possess one or more ways to counteract or even prevent the harmful effect(s) from a given stressor. Such compensation by an organism is known as a stress response; this involves inhibition of housekeeping genes and subsequent activation of genes associated with the stress response.(1) One of the most widely studied groups of stress response genes Is a family of molecular chaperones known as heat shock proteins (HSPs). Work from our laboratory agrees with many other studies showing an age-related decline in stress-induced synthesis of HSPs.(2) A decline in the availability and/or function of HSPs with age can lead to accumulation of damaged proteins, which in turn damages cells. Recently, our laboratory found a significant increase in mitochondrial damage as well as evidence of increased autophagy in rat hepatocytes following heat stress.(3) These results, along with findings of increased protein nitration with age, suggest a major role for reactive nitrogen species (RNS) in both the decline in HSP induction and increased hepatocyte pathology observed in old rats following heat stress.
C1 [Swanlund, Jamie M.; Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Madison, WI 53705 USA.
[Oberley, Terry D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA.
[Kregel, Kevin C.] Univ Iowa, Dept Radiat Oncol, Dept Integrat Physiol, Iowa City, IA USA.
[Kregel, Kevin C.] Univ Iowa, Dept Radiat Oncol, Free Radical & Radiat Biol Program, Iowa City, IA USA.
RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Room A-35,2500 Overlook Terrace, Madison, WI 53705 USA.
EM toberley@wisc.edu
FU NIA NIH HHS [R01 AG012350-09A1]
NR 25
TC 19
Z9 19
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD OCT 1
PY 2008
VL 4
IS 7
BP 936
EP 939
PG 4
WC Cell Biology
SC Cell Biology
GA 357ES
UT WOS:000259829700016
PM 18758235
ER
PT J
AU Guichard, C
Moreau, R
Pessayre, D
Epperson, TK
Krause, KH
AF Guichard, Cecile
Moreau, Richard
Pessayre, Dominique
Epperson, Terry Kay
Krause, Karl-Heinz
TI NOX family NADPH oxidases in liver and in pancreatic islets: a role in
the metabolic syndrome and diabetes?
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article; Proceedings Paper
CT 3rd Intracellular Proteolysis Meeting
CY MAR 05-07, 2008
CL Canary Isl, SPAIN
SP Joint Biochem Soc, INPROTEOLYS Network
DE diabetes; liver; metabolic Syndrome; NADPH oxidase; NOX family;
pancreatic islet
ID HEPATIC STELLATE CELLS; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN
RESPONSE; ENZYME GENE-EXPRESSION; OXIDATIVE STRESS; BETA-CELL; NAD(P)H
OXIDASE; INSULIN-RESISTANCE; MITOCHONDRIAL DYSFUNCTION; HEPATOCYTE
APOPTOSIS
AB The incidence of obesity and non-esterified ('free') fatty acid-associated metabolic disorders such as the metabolic syndrome and diabetes is increasing dramatically in most countries. Although the pathogenesis of these metabolic disorders is complex, there is emerging evidence that ROS (reactive oxygen species) are critically involved in the aberrant signalling and tissue damage observed in this context. indeed, it is now widely accepted that ROS not only play an important role in physiology, but also contribute to cell and tissue dysfunction. inappropriate ROS generation may contribute to tissue dysfunction in two ways: (i) dysregulation of redox-sensitive signalling pathways, and (ii) oxidative damage to biological structures (DNA, proteins, lipids, etc.). An important source of ROS is the NOX family of NADPH oxidases. Several NOX isoforms are expressed in the liver and pancreatic beta-cells. There is now evidence that inappropriate activation of NOX enzymes may damage the liver and pancreatic beta-cells. in the context of the metabolic syndrome, the emerging epidemic of non-alcoholic steatohepatitis is thought to be NOX/ROS-dependent and of particular medical relevance. NOX/ROS-dependent beta-cell damage is thought to be involved in glucolipotoxicity and thereby leads to progression from the metabolic syndrome to Type 2 diabetes. Thus understanding the role of NOX enzymes in liver and beta-cell damage should lead to an increased understanding of pathomechanisms in the metabolic syndrome and diabetes and may identify useful targets for novel therapeutic strategies.
C1 [Guichard, Cecile; Pessayre, Dominique; Krause, Karl-Heinz] Geneva Med Fac, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland.
[Guichard, Cecile; Pessayre, Dominique; Krause, Karl-Heinz] Univ Hosp Geneva, CH-1211 Geneva, Switzerland.
[Guichard, Cecile; Pessayre, Dominique; Krause, Karl-Heinz] Geneva Med Fac, Dept Genet, CH-1211 Geneva 4, Switzerland.
[Guichard, Cecile; Pessayre, Dominique; Krause, Karl-Heinz] Geneva Med Fac, Lab Med, CH-1211 Geneva 4, Switzerland.
[Guichard, Cecile; Moreau, Richard] Ctr Rech Biomed Bichat Beaujon CRB3, U773, INSERM, F-75870 Paris, France.
[Pessayre, Dominique] Univ Beaujon, Grp Hosp, Serv Hepatol, F-92110 Clichy, France.
[Epperson, Terry Kay] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Epperson, Terry Kay] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA.
RP Krause, KH (reprint author), Geneva Med Fac, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland.
EM Karl-Heinz.Krause@medecine.unige.ch
RI Krause, Karl-Heinz/E-8030-2011;
OI Moreau, Richard /0000-0003-0862-403X
NR 86
TC 61
Z9 64
U1 0
U2 4
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0300-5127
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD OCT
PY 2008
VL 36
BP 920
EP 929
DI 10.1042/BST0360920
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 360RW
UT WOS:000260076300027
PM 18793162
ER
PT J
AU Gulbahce, N
Lehmann, S
AF Gulbahce, Natali
Lehmann, Sune
TI The art of community detection
SO BIOESSAYS
LA English
DT Article
ID PROTEIN INTERACTION NETWORK; COMPLEX NETWORKS; METABOLIC NETWORKS;
MODULARITY; GENOME
AB Networks in nature possess a remarkable amount of structure. Via a series of data-driven discoveries, the cutting edge of network science has recently progressed from positing that the random graphs of mathematical graph theory might accurately describe real networks to the current viewpoint that networks in nature are highly complex and structured entities. The identification of high order structures in networks unveils insights into their functional organization. Recently, Clauset, Moore, and Newman,((1)) introduced a new algorithm that identifies such heterogeneities in complex networks by utilizing the hierarchy that necessarily organizes the many levels of structure. Here, we anchor their algorithm in a general community detection framework and discuss the future of community detection. BioEssays 30:934-938, 2008. (C) 2008 Wiley Periodicals, Inc.
C1 [Gulbahce, Natali; Lehmann, Sune] NE Univ, Ctr Complex Networks Res, Boston, MA 02115 USA.
[Gulbahce, Natali; Lehmann, Sune] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
RP Gulbahce, N (reprint author), NE Univ, Ctr Complex Networks Res, 110 Forsyth St, Boston, MA 02115 USA.
EM natali.gulbahce@gmail.com
OI Lehmann, Sune/0000-0001-6099-2345
FU NHGRI NIH HHS [P50 HG004233]
NR 39
TC 26
Z9 32
U1 0
U2 7
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD OCT
PY 2008
VL 30
IS 10
BP 934
EP 938
DI 10.1002/bies.20820
PG 5
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 359AX
UT WOS:000259959700004
PM 18800363
ER
PT J
AU Berriz, GF
Roth, FP
AF Berriz, Gabriel F.
Roth, Frederick P.
TI The Synergizer service for translating gene, protein and other
biological identifiers
SO BIOINFORMATICS
LA English
DT Article
ID RESOURCES; DATABASES
AB The Synergizer is a database and web service that provides translations of biological database identifiers. It is accessible both programmatically and interactively.
C1 [Berriz, Gabriel F.; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Roth, Frederick P.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
RP Roth, FP (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA.
RI Roth, Frederick/H-6308-2011;
OI Roth, Frederick/0000-0002-6628-649X
FU National Institutes of Health [HG003224, HG0017115, HL081341]; Keck
Foundation
FX Funding: National Institutes of Health. (grants HG003224, HG0017115, and
HL081341), Keck Foundation.
NR 9
TC 23
Z9 24
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD OCT 1
PY 2008
VL 24
IS 19
BP 2272
EP 2273
DI 10.1093/bioinformatics/btn424
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 353PZ
UT WOS:000259581900028
PM 18697767
ER
PT J
AU Bashey, A
Perez, WS
Zhang, MJ
Anderson, KC
Ballen, K
Berenson, JR
To, LB
Fonseca, R
Freytes, CO
Gale, RP
Gibson, J
Giralt, SA
Kyle, RA
Lazarus, HM
Maharaj, D
McCarthy, PL
Milone, GA
Nimer, S
Pavlovsky, S
Reece, DE
Schiller, G
Vesole, DH
Hari, P
AF Bashey, Asad
Perez, Waleska S.
Zhang, Mei-jie
Anderson, Kenneth C.
Ballen, Karen
Berenson, James R.
To, L. Bik
Fonseca, Rafael
Freytes, Cesar O.
Gale, Robert Peter
Gibson, John
Giralt, Sergio A.
Kyle, Robert A.
Lazarus, Hillard M.
Maharaj, Dipnarine
McCarthy, Philip L.
Milone, Gustavo A.
Nimer, Stephen
Pavlovsky, Santiago
Reece, Donna E.
Schiller, Gary
Vesole, David H.
Hari, Parameswaran
CA Plasma Cell Disorders Working Comm
TI Comparison of twin and autologous transplants for multiple myeloma
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE twin; autotransplant; multiple myeloma; graft-versus-myeloma
ID STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY;
BONE-MARROW-TRANSPLANTATION; TUMOR CONTAMINATION; BLOOD; HARVESTS;
PREDICT; GRAFTS
AB Relapse is the overwhelming cause of treatment failure after autologous transplantation for multiple myeloma (MM). For patients with a syngeneic donor, twin transplants provide a healthy graft that is free of myeloma. The relative impact of the graft on posttransplant relapse can be estimated by comparing risk of relapse after hematopoietic cell transplantation from genetically identical twins versus autotransplants because confounding differences in minor or major histocompatibility antigens are absent in the syngeneic transplant setting. Outcomes of 43 subjects who received twin transplants for MM were compared to 170 matched autotransplant recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Multivariate analysis was performed by fitting a Cox model stratified on matched pairs. The matched transplant patients studied were similar with respect to subject-, disease-, and transplant-related characteristics. Cumulative incidence of relapse/progression was significantly lower, and progression free survival (PFS) was significantly higher following twin transplants. In multivariate analysis, the probability of relapse/progression was lower in twins (relative risk [RR] = 0.49, 95% confidence interval [CI] 0.28-0.86, P = .011). Twin transplants have a significantly lower relapse risk than autotransplants in MM, suggesting that graft composition may impact outcomes following high-dose chemotherapy.
C1 [Perez, Waleska S.; Zhang, Mei-jie; Hari, Parameswaran] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Bashey, Asad] BMT Grp Georgia, Atlanta, GA USA.
[Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Berenson, James R.] Inst Myeloma & Bone Canc Res, W Hollywood, CA USA.
[To, L. Bik] Inst Med & Vet Sci, Adelaide, SA 5000, Australia.
[Fonseca, Rafael] Mayo Clin Scottsdale, Scottsdale, AZ USA.
[Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Gale, Robert Peter] Celgene Corp, Summit, NJ USA.
[Gibson, John] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia.
[Giralt, Sergio A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Kyle, Robert A.] Mayo Clin Rochester, Rochester, MN USA.
[Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Cleveland, OH USA.
[Maharaj, Dipnarine] S Florida Bone Marrow Stem Cell Transplant Inst, Boynton Beach, FL USA.
[McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Milone, Gustavo A.; Pavlovsky, Santiago] FUNDALEU, Buenos Aires, DF, Argentina.
[Nimer, Stephen] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Schiller, Gary] Univ Calif Los Angeles, Los Angeles, CA USA.
[Vesole, David H.] St Vincents Comprehens Canc Ctr, New York, NY USA.
RP Hari, P (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suits C5500, Milwaukee, WI 53226 USA.
EM phari@mcw.edu
OI Fonseca, Rafael/0000-0002-5938-3769; Hari,
Parameswaran/0000-0002-8800-297X
FU National Cancer Institute [U24-CA76518]; National Institute of Allergy
and Infectious Diseases; National Heart, Lung and Blood Institute;
Office of Naval Research; Health Services Research Administration
(DHHS); AABB; Abbott Laboratories; Aetna; American International Group,
Inc; Amgen, Inc
FX The CIBMTR is supported by Public Health Service Grant U24-CA76518 from
the National Cancer Institute, the National Institute of Allergy and
Infectious Diseases, and the National Heart, Lung and Blood Institute;
Office of Naval Research; Health Services Research Administration
(DHHS); and grants from AABB; Abbott Laboratories; Aetna; American
International Group, Inc.; Amgen, Inc.; anonymous donation to the
Medical College of Wisconsin;, AnorNIED, Inc.; Astellas Pharma US, Inc.;
Baxter International, Inc., Berlex Laboratories, Inc.; Biogen IDEC,
Inc.; BioOne Corporation; Blood Center of Wisconsin;, Blue Cross and
Blue Shield Association; Bone Marrow Foundation; Bristol-Myers Squibb
Company; Cangene Corporation; Celgene Corporation; CellGenix, GrnbH;
Cerus Corporation; Cylex Inc.; CytoTherm; DOR BIoPharma, Inc.; Dynal
Biotech, an Invitrogen Company; EKR Therapeutics; Enzon Pharmaceuticals,
Inc.; Gambro BCT, Inc.; Gamida Cell, Ltd.; Genzyme Corporation; Gift of
Life Bone Marrow Foundation, GlaxoSmitliKline, Inc.; Histogenetics,
Inc.; HKS Medical Information Systems; Hospira, Inc.; Kiadis Pharma;
Kirin Brewery Co., Ltd.; Merck & Company; The Medical College of
Wisconsin; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group;
Millunan USA, Inc.; Miltenyi Biotec, Inc.; MultiPlan, Inc.; National
Marrow Donor Program; Nature Publishing Group; Oncology Nursing Society;
Osiris Therapeutics, Inc.; Pall Life Sciences; PDL BioPharma, Inc;,
Pfizer Inc; Pharmion Corporation; Roche Laboratories; Sanofi-aventis-
Schering Plough Corporation, StemCyte, Inc.; StemSoft Software, Inc.
SuperGen, Inc.; Sysmex; Teva Pharmaceutical Industries; The Marrow
Foundation; THERAKOS, Inc.; University of Colorado Cord Blood Bank;
ViaCell, Inc.; Vidocare Corporation; ViraCor Laboratories; ViroPharma,
Inc.; Wellpoint, Inc.; and Zelos Therapeutics, Inc. The views expressed
in this article do not reflect the official policy or position of the
National Institutes of Health, the Department of the Navy, the
NR 22
TC 13
Z9 13
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD OCT
PY 2008
VL 14
IS 10
BP 1118
EP 1124
DI 10.1016/j.bbmt.2008.07.007
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 354WF
UT WOS:000259669100005
PM 18804041
ER
PT J
AU Kumar, S
Perez, WS
Zhang, MJ
Ballen, K
Bashey, A
To, LB
Bredeson, CN
Cairo, MS
Elfenbein, GJ
Freytes, CO
Gale, RP
Gibson, J
Kyle, RA
Lacy, MQ
Lazarus, HM
McCarthy, PL
Milone, GA
Moreb, JS
Pavlovsky, S
Reece, DE
Vesole, DH
Wiernik, PH
Hari, P
AF Kumar, Shaji
Perez, Waleska S.
Zhang, Mei-Jie
Ballen, Karen
Bashey, Asad
To, L. Bik
Bredeson, Christopher N.
Cairo, Mitchell S.
Elfenbein, Gerald J.
Freytes, Cesar O.
Gale, Robert Peter
Gibson, John
Kyle, Robert A.
Lacy, Martha Q.
Lazarus, Hillard M.
McCarthy, Philip L.
Milone, Gustavo A.
Moreb, Jan S.
Pavlovsky, Santiago
Reece, Donna E.
Vesole, David H.
Wiernik, Peter H.
Hari, Parameswaran
TI Comparable outcomes in nonsecretory and secretory multiple myeloma after
autologous stem cell transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE nonsecretory myeloma; autologous hematopoietic stem cell transplantation
ID AMINO-ACID SUBSTITUTION; VARIABLE REGION; BENCE-JONES; CHAIN; SINGLE;
IMMUNOGLOBULIN; CHEMOTHERAPY; THERAPY; SURVIVAL; KAPPA
AB Nonsecretory myeloma (NSM) accounts for <5% of cases of multiple myeloma (MM). The outcome of these patients following autologous stem cell transplantation (ASCT) has not been evaluated in clinical trials. We compared the outcomes after ASCT for patients with NSM reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1989 and 2003, to a matched group of 438 patients (4 controls for each patient) with secretory myeloma (SM). The patients were matched using propensity scores calculated using age, Durie-Salmon stage, sensitivity to pretransplant therapy, time from diagnosis to transplant, and year of transplant. Disease characteristics were similar in both groups at diagnosis and at transplant except higher risk of anemia, hypoalbuminemia, and marrow plasmacytosis (in SM) and plasmacytoma (more in NSM). Cumulative incidence of treatment-related mortality (TRM), relapse, progression-free survival (PFS), and overall survival (OS) were similar between the groups. In multivariate analysis, based on a Cox model stratified on matched pairs and adjusted for covariates not considered in the propensity score, we found no difference in outcome between the NSM and SM groups. In this large cohort of patients undergoing ASCT we found no difference in outcomes of patients with NSM compared to those with SM.
C1 [Perez, Waleska S.; Zhang, Mei-Jie; Hari, Parameswaran] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Kumar, Shaji; Kyle, Robert A.; Lacy, Martha Q.] Mayo Clin, Rochester, MN USA.
[Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bashey, Asad] Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA.
[To, L. Bik] Inst Med & Vet Sci, Adelaide, SA 5000, Australia.
[Bredeson, Christopher N.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Cairo, Mitchell S.] New York Presbyterian Hosp, New York, NY USA.
[Elfenbein, Gerald J.] Boston Univ, Boston, MA 02215 USA.
[Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Gale, Robert Peter] Celgene Corp, Summit, NJ USA.
[Gibson, John] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia.
[Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Cleveland, OH USA.
[McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Milone, Gustavo A.; Pavlovsky, Santiago] Fundaleu, Buenos Aires, DF, Argentina.
[Moreb, Jan S.] Univ Florida, Gainesville, FL USA.
[Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Vesole, David H.] St Vincents Comprehens Canc, New York, NY USA.
[Wiernik, Peter H.] New York Med Coll, Our Lady Mercy Med Ctr, Bronx, NY USA.
RP Hari, P (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA.
EM phari@mcw.edu
RI Kumar, Shaji/A-9853-2008;
OI Kumar, Shaji/0000-0001-5392-9284; Hari, Parameswaran/0000-0002-8800-297X
FU National Cancer Institute [U24-CA76518]; National Institute of Allergy
and Infectious Diseases,; National Heart, Lung and Blood Institute;
Office of Naval Research; Health Resources and Services Administration
(DHHS); AABB; Aetna; American Soclety for Blood and Marrow
Transplantation; Amgen, Inc; Anonymous donation to the Medical College
of Wisconsin; Association of Medical Microbiology and Infectious Disease
Canada; Astellas Pharma US, Inc; Baxter International, Inc; Bayer
HealthCare Pharmaceuticals; BloodCenter of Wisconsin; Blue Cross and
Blue Shield Association; Bone Marrow Foundation; Canadian Blood and
Marrow Transplant Group; Celgene Corporation; CellGenix, GmbH; Centers
for Disease Control and Prevention; ClinImmune Labs; CTI Clinical Trial
and Consulting Services; Cubist Pharmaceuticals; Cylex Inc; Cylex Inc.;
CytoTherm; DOR BioPhama, Inc; Dynal Biotech, an Invitrogen Company;
Enzon Pharmaceuticals, Inc; European Group for Blood and Marrow
Transplantation; Garnbro BCT, Inc; Gamida Cell, Ltd; Genzyme
Corporation; Histogenetics, Inc; HKS Medical Information Systems;
Hospira, Inc; Infectious Diseases Society of America; Kiadis Pharma;
Kirin Brewery Co., Ltd; Merck Company; The Medical College of Wisconsin;
MGI Pharma, Inc
FX Financial disclosure: The CIBMTR is supported by Public Health Service
Grant U24-CA76518 from the National Cancer Institute, the National
Institute of Allergy and Infectious Diseases, and the National Heart,
Lung and Blood Institute; Office of Naval Research; Health Resources and
Services Administration (DHHS); and grants from AABB; Aetna; American
Soclety for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous
donation to the Medical College of Wisconsin; Association of Medical
Microbiology and Infectious Disease Canada; Astellas Pharma US, Inc.;
Baxter International, Inc.; Bayer HealthCare Pharmaceuticals;
BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone
Marrow Foundation; Canadian Blood and Marrow Transplant Group; Celgene
Corporation; CellGenix, GmbH; Centers for Disease Control and
Prevention; ClinImmune Labs; CTI Clinical Trial and Consulting Services;
Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPhama, Inc., Dynal
Biotech, an Invitrogen Company; Enzon Pharmaceuticals, Inc.; European
Group for Blood and Marrow Transplantation; Garnbro BCT, Inc.; Gamida
Cell, Ltd.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical
Information Systems; Hospira, Inc.; Infectious Diseases Society of
America; Kiadis Pharma; Kirin Brewery Co., Ltd.; Merck & Company; The
Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood
Centers; Millennium Pharmaceuticals, Inc.; Miller Pharniacal Group;
Milliman USA, Inc., Miltenyl Biotec, Inc., National Marrow Donor
Program; Nature Publishing Group; New York Blood Center; Novartis
Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka
Pharmaceutical Development & Commercialization, Inc.; Pall Life
Sciences; PDL BioPharma, Inc; Pfizer Inc, Pharmion Corporation; Saladax
Biomedical, Inc.; Schering Plough Corporation-, Society for Healthcare
Epidemiology of America; StemCyte, Inc.; StemSoft Software, Inc.;
Sysmex; Teva Pharmaceutical Industries; The Marrow Foundation; THERAKOS,
Inc.; Viclacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor
Laboratories-, ViroPharma, Inc.; and Wellpoint, Inc.
NR 25
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD OCT
PY 2008
VL 14
IS 10
BP 1134
EP 1140
DI 10.1016/j.bbmt.2008.07.011
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 354WF
UT WOS:000259669100007
PM 18804043
ER
PT J
AU Cho, CH
Berthiaume, F
Tilles, AW
Yarmush, ML
AF Cho, Chenl H.
Berthiaume, Francois
Tilles, Arno W.
Yarmush, Martin L.
TI A new technique for primary hepatocyte expansion in vitro
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE hepatocyte proliferation; coculture; DNA synthesis; cell patterning;
subculture
ID ADULT-RAT HEPATOCYTES; ACUTE LIVER-FAILURE; EMBRYONIC STEM-CELLS;
PRIMARY CULTURE; DIFFERENTIATED FUNCTIONS; NONPARENCHYMAL CELLS;
CONTROLLED-TRIAL; JUNCTIONAL COMMUNICATION; SANDWICH CONFIGURATION;
CELLULAR INTERACTIONS
AB The current application for many potential cell-based treatments for liver failure is limited by the low availability of mature functional hepatocytes. Although adult hepatocytes have a remarkable ability to proliferate in vivo, attempts to proliferate adult hepatocytes in vitro have been less successful. In this study, we investigated the effect of coculture cell type on the proliferative response and the functional activities of hepatocytes. We show, for the first time, a robust proliferative response of primary adult rat hepatocytes when cocultured with mouse 3T3-J2 fibroblasts. Hepatocytes cultured at low density on growth-arrested 3T3-J2 fibroblast feeder layers underwent significantly higher proliferation rates than when cultured on feeder layers made of four other cell types. Increasing colony size correlaled with an increase in hepatocellular functions. The proliferating hepatocytes retained their morphologic, phenotypic, and functional characteristics. Using a cell patterning technique, we found that 3T3-J2 fibroblasts stimulate DNA synthesis in hepatocytes by short-range heterotypic cell-cell interactions. When hepatocytes that proliferated in cocultures were harvested and further subcultured either on 3T3-J2 fibroblast feeders or in the collagen sandwich configuration, their behavior was similar to that of freshly isolated hepatocytes. We conclude that adult rat hepatocytes can proliferate in vitro in a coculture cell type-dependent manner, and can be serially propagated by coculturing with 3T3-J2 fibroblasts while maintaining their differentiated characteristics. Our results also suggest that one of the major reasons for the functional differences in hepatocyte cocultures may be due to the different proliferative responses of hepatocytes as a function of coculture cell type. This study provides new insights in the roles of coculture cell types and cell-cell interactions in the modulation of hepatic proliferation and function.
C1 [Yarmush, Martin L.] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA.
Shriners Hosp Children, Boston, MA 02114 USA.
RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA.
EM ireis@sbi.org
RI Yu, weiting/I-7417-2013
FU National Institutes of Health [R01 DK43371, K08 DK066040, K18 DK076819]
FX We thank Dr. Jaesung Park for providing PDMS stencils, and Dr. Yaakov
Nahmias and Dr. Laurent Bathe for their assistance with LSFC isolation.
This study was partially supported by the National Institutes of Health
(grain numbers R01 DK43371, K08 DK066040, and K18 DK076819) and the
Shriners Hospitals for Children.
NR 57
TC 31
Z9 31
U1 0
U2 9
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0006-3592
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD OCT 1
PY 2008
VL 101
IS 2
BP 345
EP 356
DI 10.1002/bit.21911
PG 12
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 352QS
UT WOS:000259512900013
PM 18465801
ER
PT J
AU Cao, HH
Ackerman, J
Ecklund, K
Steigman, S
Glimcher, M
Wu, YT
AF Cao, Haihui
Ackerman, Jerome
Ecklund, Kirsten
Steigman, Shaun
Glimcher, Melvin
Wu, Yaotang
TI Water and Fat Suppressed Proton Projection MRI (WASPI)/micro CT
measurements of bone mineralization
SO BONE
LA English
DT Meeting Abstract
CT International Conference on Osteoporosis and Bone Research
CY OCT 22-25, 2008
CL Beijing, PEOPLES R CHINA
SP Chinese Med Assoc, Int Bone & Mineral Soc, Int Chinese Hard Tissue Soc
C1 [Cao, Haihui; Glimcher, Melvin; Wu, Yaotang] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
[Cao, Haihui; Ackerman, Jerome; Ecklund, Kirsten; Steigman, Shaun; Glimcher, Melvin; Wu, Yaotang] Harvard Univ, Sch Med, Boston, MA USA.
[Ackerman, Jerome] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Ecklund, Kirsten] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Steigman, Shaun] Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD OCT
PY 2008
VL 43
SU 1
BP S95
EP S95
DI 10.1016/j.bone.2008.07.188
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360TT
UT WOS:000260081500223
ER
PT J
AU Hadjikhani, N
Hoge, R
Snyder, J
de Gelder, B
AF Hadjikhani, Nouchine
Hoge, Rick
Snyder, Josh
de Gelder, Beatrice
TI Pointing with the eyes: The role of gaze in communicating danger
SO BRAIN AND COGNITION
LA English
DT Article
DE Face processing; Gaze; Emotion; Fear recognition; Action representation
ID SUPERIOR TEMPORAL SULCUS; SURFACE-BASED ANALYSIS; HUMAN NEURAL SYSTEM;
FACIAL EXPRESSIONS; HUMAN AMYGDALA; FACE PERCEPTION; CEREBRAL-CORTEX;
FUSIFORM GYRUS; FEAR; BRAIN
AB Facial expression and direction of gaze are two important sources of social information, and what message each conveys may ultimately depend on how the respective information interacts in the eye of the perceiver. Direct gaze signals an interaction with the observer but averted gaze amounts to "pointing with the eyes", and in combination with a fearful facial expression may signal the presence of environmental danger. We used fMRI to examine how gaze direction influences brain processing of facial expression of fear. The combination of fearful faces and averted gazes activated areas related to gaze shifting (STS, IPS) and fear-processing (amygdala, hypothalamus, pallidum). Additional modulation of activation was observed in motion detection areas, in premotor areas and in the somatosensory cortex, bilaterally.
Our results indicate that the direction of gaze prompts a process whereby the brain combines the meaning of the facial expression with the information provided by gaze direction, and in the process computes the behavioral implications for the observer. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Hadjikhani, Nouchine; Hoge, Rick; Snyder, Josh; de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Hadjikhani, Nouchine; Hoge, Rick] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lausanne, Switzerland.
[de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
RP Hadjikhani, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA.
EM nouchine@nmr.mgh.harvard.edu
RI Hadjikhani, Nouchine/C-2018-2008
OI Hadjikhani, Nouchine/0000-0003-4075-3106
FU NIH [RO1 NS44824-01]; Swiss National Foundation [PPOOB-110741]
FX This research was supported by NIH Grant RO1 NS44824-01 and Swiss
National Foundation Grant PPOOB-110741 to Nouchine Hadjikhani. We thank
Reginald Adams and an anonymous reviewer for their comments on our
manuscript.
NR 57
TC 61
Z9 61
U1 4
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0278-2626
J9 BRAIN COGNITION
JI Brain Cogn.
PD OCT
PY 2008
VL 68
IS 1
BP 1
EP 8
DI 10.1016/j.bandc.2008.01.008
PG 8
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 360RD
UT WOS:000260074300001
PM 18586370
ER
PT J
AU Patil, S
Perry, A
MacCollin, M
Dong, S
Betensky, RA
Yeh, TH
Gutmann, DH
Stemmer-Rachamimov, AO
AF Patil, Sushama
Perry, Arie
MacCollin, Mia
Dong, Shumin
Betensky, Rebecca A.
Yeh, Tu-Hsueh
Gutmann, David H.
Stemmer-Rachamimov, Anat O.
TI Immunohistochemical analysis supports a role for INI1/SMARCB1 in
hereditary forms of schwannomas, but not in solitary, sporadic
schwannomas
SO BRAIN PATHOLOGY
LA English
DT Article
DE Schwannoma; NF2; Schwannomatosis; INI1; SMARCB1; expression
ID FAMILIAL SCHWANNOMATOSIS; RHABDOID TUMORS; EXPRESSION; MUTATION
AB The INI1/SMARCB1 protein product (INI1), a component of a transcription complex, was recently implicated in the pathogenesis of schwannomas in two members of a single family with familial schwannomatosis. Tumors were found to have both constitutional and somatic mutations of the SMARCB1 gene and showed a mosaic pattern of loss of INI1 expression by immunohistochemistry, suggesting a tumor composition of mixed null and haploinsufficient cells. To determine if this finding could be extended to all tumors arising in familial schwannomatosis, and how it compares with other multiple schwannoma syndromes [sporadic schwannomatosis and neurofibromatosis 2 (NF2)] as well as to sporadic, solitary schwannomas, we performed an immunohistochemistry analysis on 45 schwannomas from patients with multiple schwannoma syndromes and on 38 solitary, sporadic schwannomas from non-syndromic patients. A mosaic pattern of INI1 expression was seen in 93% of tumors from familial schwannomatosis patients, 55% of tumors from sporadic schwannomatosis, 83% of NF2-associated tumors and only 5% of solitary, sporadic schwannomas. These results confirm a role for INI1/SMARCB1 in multiple schwannoma syndromes and suggest that a different pathway of tumorigenesis occurs in solitary, sporadic tumors.
C1 [Patil, Sushama; Perry, Arie] Washington Univ, Sch Med, Div Neuropathol, St Louis, MO USA.
[Yeh, Tu-Hsueh; Gutmann, David H.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[MacCollin, Mia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA.
[Dong, Shumin; Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Mol Neuro Oncol Lab, Boston, MA 02114 USA.
[Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Yeh, Tu-Hsueh] Chang Gung Mem Hosp & Univ, Dept Neurol, Taipei, Taiwan.
RP Stemmer-Rachamimov, AO (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, MGH East,Bldg 149,13th St, Charlestown, MA 02129 USA.
EM astemmerrachamimov@partners.org
OI Perry, Arie/0000-0002-8300-7261
FU Children's Tumor Foundation (ASR); Congressionally Directed Medical
Research Program (MM)
FX This work was supported by grants from the Children's Tumor Foundation
(ASR) and from the Congressionally Directed Medical Research Program
(MM). The authors thank Drs Michael Lawlor and Pavan Auluck for their
help with the graph.
NR 10
TC 65
Z9 65
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1015-6305
J9 BRAIN PATHOL
JI Brain Pathol.
PD OCT
PY 2008
VL 18
IS 4
BP 517
EP 519
DI 10.1111/j.1750-3639.2008.00155.x
PG 3
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 347MW
UT WOS:000259146700006
PM 18422762
ER
PT J
AU O'Callaghan, P
Sandwall, E
Li, JP
Yu, H
Ravid, R
Guan, ZZ
van Kuppevelt, TH
Nilsson, LNG
Ingelsson, M
Hyman, BT
Kalimo, H
Lindahl, U
Lannfelt, L
Zhang, X
AF O'Callaghan, Paul
Sandwall, Elina
Li, Jin-Ping
Yu, Hong
Ravid, Rivka
Guan, Zhi-Zhong
van Kuppevelt, Toin H.
Nilsson, Lars N. G.
Ingelsson, Martin
Hyman, Bradley T.
Kalimo, Hannu
Lindahl, Ulf
Lannfelt, Lars
Zhang, Xiao
TI Heparan sulfate accumulation with A beta deposits in Alzheimer's disease
and Tg2576 mice is contributed by glial cells
SO BRAIN PATHOLOGY
LA English
DT Article
DE beta-Amyloid; glial cells; heparan sulfate
ID FIBROBLAST GROWTH FACTOR-2; CEREBRAL-CORTEX; SENILE PLAQUES;
DOWN-SYNDROME; PROTEOGLYCANS; BRAIN; EXPRESSION; GLYCOSAMINOGLYCANS;
A-BETA-40; PROTEINS
AB Amyloid beta-peptide (A beta) plaques, one of the major neuropathological lesions in Alzheimer's disease (AD), can be broadly subdivided into two morphological categories: neuritic and diffuse. Heparan sulfate (HS) and HS proteoglycans (HSPGs) are codeposits of multiple amyloidoses, including AD. Although HS has been considered a limiting factor in the initiation of amyloid deposition, the pathological implications of HS in A beta deposits of AD remain unclear. In this study, immunohistochemistry combined with fluorescence and confocal microscopy was employed to gain deeper insight into the accumulation of HS with A beta plaques in sporadic and familial AD. Here we demonstrate that HS preferentially accumulated around the A beta 40 dense cores of neuritic plaques, but was largely absent from diffuse A beta 42 plaques, suggesting that A beta 42 deposition may occur independently of HS. A codeposition pattern of HS with A beta deposits in Tg2576 mice was also examined. We identified the membrane-bound HSPGs, glypican-1 (GPC1) and syndecan-3 (SDC3), in glial cells associated with A beta deposits, proximal to sites of HS accumulation. In mouse primary glial cultures, we observed increased levels of GPC1 and SDC3 following A beta stimulation. These results suggest that HS codeposits with A beta 40 in neuritic plaques and is mainly derived from glial cells.
C1 [O'Callaghan, Paul; Nilsson, Lars N. G.; Ingelsson, Martin; Lannfelt, Lars; Zhang, Xiao] Uppsala Univ, Dept Publ Hlth & Caring Sci, Div Mol Geriatr, Rudbeck Lab, SE-75185 Uppsala, Sweden.
[Sandwall, Elina; Li, Jin-Ping; Lindahl, Ulf] Uppsala Univ, Biomed Ctr, Dept Med Biochem & Microbiol, SE-75185 Uppsala, Sweden.
[Yu, Hong] AstraZeneca R&D, CNS & Pain Control, Local Discovery Res Area, Dept Dis Biol, Sodertalje, Sweden.
[Guan, Zhi-Zhong] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
[Ravid, Rivka] Netherlands Brain Bank, Amsterdam, Netherlands.
[van Kuppevelt, Toin H.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Biochem, Nijmegen, Netherlands.
[Hyman, Bradley T.] Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA USA.
RP Zhang, X (reprint author), Uppsala Univ, Dept Publ Hlth & Caring Sci, Div Mol Geriatr, Rudbeck Lab, SE-75185 Uppsala, Sweden.
EM xiao.zhang@pubcare.uu.se
RI Kuppevelt, A.H.M.S.M./L-4463-2015;
OI O'Callaghan, Paul/0000-0003-3117-5367
FU The Swedish Research Council [2006-2822, 2006-2818, 32X-15023];
Landstinget i Uppsala lan; European Commission (EURAMY);
Polysackaridforskning AB Uppsala; Alzheimerfonden; Stohnes Stiftelse;
Stiftelsen for Gamla Tjanarinnor; Stiftelsen Demensfonden; Swedish Brain
Foundation; Bertil Hallstens Forskningsstiftelse; Massachusetts
Alzheimer Disease Research Center [PS0AG05134]
FX We would like to thank Guido David (University of Leuven), Lars-Ake
Fransson and Fang Cheng (Lund University) for contributing antibodies.;
Supported by The Swedish Research Council (2006-2822, 2006-2818,
32X-15023), Landstinget i Uppsala lan, European Commission (EURAMY),
Polysackaridforskning AB Uppsala, Alzheimerfonden, Stohnes Stiftelse,
Stiftelsen for Gamla Tjanarinnor, Stiftelsen Demensfonden, The Swedish
Brain Foundation, Bertil Hallstens Forskningsstiftelse and the
Massachusetts Alzheimer Disease Research Center PS0AG05134.
NR 42
TC 34
Z9 34
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1015-6305
J9 BRAIN PATHOL
JI Brain Pathol.
PD OCT
PY 2008
VL 18
IS 4
BP 548
EP 561
DI 10.1111/j.1750-3639.2008.00152.x
PG 14
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 347MW
UT WOS:000259146700009
PM 18422760
ER
PT J
AU Niesvizky, R
Richardson, PG
Rajkumar, SV
Coleman, M
Rosinol, L
Sonneveld, P
Schuster, MW
Irwin, D
Stadtmauer, EA
Facon, T
Harousseau, JL
Boral, AL
Esseltine, DL
Anderson, KC
Blade, J
AF Niesvizky, Ruben
Richardson, Paul G.
Rajkumar, S. Vincent
Coleman, Morton
Rosinol, Laura
Sonneveld, Pieter
Schuster, Michael W.
Irwin, David
Stadtmauer, Edward A.
Facon, Thierry
Harousseau, Jean-Luc
Boral, Anthony L.
Esseltine, Dixie-Lee
Anderson, Kenneth C.
Blade, Joan
TI The relationship between quality of response and clinical benefit for
patients treated on the bortezomib arm of the international, randomized,
phase 3 APEX trial in relapsed multiple myeloma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE multiple myeloma; bortezomib; complete response; clinical benefit;
minimal response
ID STEM-CELL TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; HIGH-DOSE THERAPY;
BONE-MARROW; AUTOLOGOUS TRANSPLANTATION; COMPLETE REMISSION; PROGNOSTIC
PARAMETER; MOLECULAR REMISSION; FREE SURVIVAL; CHEMOTHERAPY
AB Quality of response is associated with prolonged overall survival (OS) in newly diagnosed multiple myeloma patients. This cohort study within the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of bortezomib versus dexamethasone in relapsed myeloma assessed the relationship between quality of response to bortezomib (n = 315) and clinical benefit. Treatment-free interval (TFI), time to alternative therapy (TTAT), time to progression (TTP) and OS were assessed in response-evaluable patients in the bortezomib arm in cohorts defined by achievement of complete response (CR; n = 27), very good partial response (VGPR; n = 31), partial response (PR; n = 77), minimal response (MR; n = 21) or non-response (NR, including stable and progressive disease; n = 159). CR was associated with significantly longer median TFI (24.1 vs. 6.9/6.4 months) and TTAT (27.1 vs. 13.6/14 months) versus VGPR/PR. Median TTP was similar in CR, VGPR and PR cohorts; median OS was not reached. Patients achieving MR appeared to have prolonged median TFI (3.8 vs. 2.3 months), TTAT (8.7 vs. 6.2 months), TTP (4.9 vs. 2.8 months) and OS (24.9 vs. 18.7 months) versus NR. In conclusion, bortezomib had substantial activity in relapsed myeloma patients; CR may be a surrogate marker for significant clinical benefit with bortezomib. MR appeared to be valid as a separate response category in this setting.
C1 [Niesvizky, Ruben] Cornell Univ, Weill Med Coll, Ctr Excellence Lymphoma & Myeloma, New York Presbyterian Hosp, New York, NY 10021 USA.
[Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA.
[Rosinol, Laura; Blade, Joan] Hosp Clin Barcelona, IDIBAPS, Barcelona, Spain.
[Sonneveld, Pieter] Erasmus MC, Rotterdam, Netherlands.
[Irwin, David] Alta Bates Canc Ctr, Berkeley, CA USA.
[Stadtmauer, Edward A.] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA.
[Facon, Thierry] Hosp Claude Huriez, Lille, France.
[Harousseau, Jean-Luc] Hop Hotel Dieu, Nantes, France.
[Boral, Anthony L.; Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA.
RP Niesvizky, R (reprint author), Cornell Univ, Weill Med Coll, Ctr Excellence Lymphoma & Myeloma, New York Presbyterian Hosp, New York, NY 10021 USA.
EM run9001@med.cornell.edu
RI FACON, THIERRY/M-9736-2014;
OI FACON, THIERRY/0000-0001-7705-8460; Rajkumar, S.
Vincent/0000-0002-5862-1833
FU Millennium Pharmaceuticals, Inc; Johnson & Johnson Pharmaceutical
Research Development
FX The authors would like to thank Steve Hill and Rosemary Washbrook for
editorial assistance in the development of this manuscript. Steve Hill
is a medical writer and Rosemary Washbrook is a medical editor with
Gardiner-Caldwell London.; This research was supported by Millennium
Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research &
Development L. L. C.
NR 31
TC 71
Z9 73
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD OCT
PY 2008
VL 143
IS 1
BP 46
EP 53
DI 10.1111/j.1365-2141.2008.07303.x
PG 8
WC Hematology
SC Hematology
GA 345BH
UT WOS:000258970500005
PM 18673366
ER
PT J
AU Lonial, S
Richardson, PG
Miguel, JS
Sonneveld, P
Schuster, MW
Blade, J
Cavenagh, J
Rajkumar, SV
Jakubowiak, AJ
Esseltine, DL
Anderson, KC
Harousseau, JL
AF Lonial, Sagar
Richardson, Paul G.
Miguel, Jesus San
Sonneveld, Pieter
Schuster, Michael W.
Blade, Joan
Cavenagh, Jamie
Rajkumar, S. Vincent
Jakubowiak, Andrzej J.
Esseltine, Dixie-Lee
Anderson, Kenneth C.
Harousseau, Jean-Luc
TI Characterisation of haematological profiles and low risk of
thromboembolic events with bortezomib in patients with relapsed multiple
myeloma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE bortezomib; haematological toxicity; multiple myeloma; thromboembolic
event
ID LENALIDOMIDE PLUS DEXAMETHASONE; PEGYLATED LIPOSOMAL DOXORUBICIN;
INDUCTION TREATMENT PRIOR; NEWLY-DIAGNOSED MYELOMA; DEEP VENOUS
THROMBOSIS; TERM-FOLLOW-UP; FACTOR-KAPPA-B; PHASE-II;
THALIDOMIDE-DEXAMETHASONE; RECEIVING THALIDOMIDE
AB Haematological toxicities and thromboembolic (TE) events are common complications of myeloma therapy. TE risk may be elevated with combination regimens, notably thalidomide/lenalidomide plus high-dose dexamethasone; concomitant erythropoietin appears to further increase the risk with lenalidomide-dexamethasone. We characterised thrombocytopenia and neutropenia in the phase 3 APEX (Assessment of Proteasome Inhibition for Extending Remissions) study of bortezomib versus high-dose dexamethasone in relapsed myeloma, and calculated the incidences of deep-vein thrombosis (DVT)/pulmonary embolism (PE) with: bortezomib or dexamethasone +/- erythropoietin in APEX; bortezomib +/- dexamethasone +/- erythropoietin in two phase 2 studies of relapsed/refractory myeloma. Bortezomib-associated thrombocytopenia and neutropenia were transient, predictable and manageable; mean platelet and neutrophil counts followed a cyclical pattern, and improved over the treatment course. Grade 3/4 thrombocytopenia incidence was higher with bortezomib versus dexamethasone (26%/4% vs. 5%/1%), but significant bleeding events were comparable (4% vs. 5%). DVT/PE incidence was low (<= 3.1%) in all analyses; addition of dexamethasone/erythropoietin did not affect TE risk. In APEX, TE risk appeared lower with bortezomib versus dexamethasone. Bortezomib caused transient and cyclical thrombocytopenia and was not associated with elevated TE risk, alone or with dexamethasone +/- erythropoietin. Preliminary data suggest bortezomib may reduce the thrombogenic potential of combination regimens via inhibition of platelet function or other mechanism-specific effects on coagulation.
C1 [Lonial, Sagar] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA.
[Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Miguel, Jesus San] Hosp Univ Salamanca, CIC, IBMCC, USAL,CSIC, Salamanca, Spain.
[Sonneveld, Pieter] Univ Rotterdam Hosp, Rotterdam, Netherlands.
[Schuster, Michael W.] NY Presbyterian Hosp, New York, NY USA.
[Blade, Joan] Hosp Clin Barcelona, IDIBAPS, Dept Haematol, Barcelona, Spain.
[Cavenagh, Jamie] St Bartholomews Hosp, London, England.
[Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA.
[Jakubowiak, Andrzej J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA.
[Harousseau, Jean-Luc] Hop Hotel Dieu, Nantes, France.
RP Lonial, S (reprint author), Emory Univ, Winship Canc Ctr, Bldg C,1365 Clifton Rd, Atlanta, GA 30322 USA.
EM sloni01@emory.edu
RI 2008, Ibsal/A-1268-2012;
OI Rajkumar, S. Vincent/0000-0002-5862-1833; SAN MIGUEL,
JESUS/0000-0002-9183-4857
FU Millennium Pharmaceuticals, Inc; Johnson & Johnson Pharmaceutical
Research & Development L. L. C.
FX This research was supported by Millennium Pharmaceuticals, Inc. and
Johnson & Johnson Pharmaceutical Research & Development L. L. C.
Editorial assistance in preparation of this manuscript was provided by
Gardiner-Caldwell London.
NR 56
TC 54
Z9 55
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD OCT
PY 2008
VL 143
IS 2
BP 222
EP 229
DI 10.1111/j.1365-2141.2008.07321.x
PG 8
WC Hematology
SC Hematology
GA 352OF
UT WOS:000259505900007
PM 18713253
ER
PT J
AU Farwell, WR
Gaziano, JM
Norkus, EP
Sesso, HD
AF Farwell, Wildon R.
Gaziano, J. Michael
Norkus, Edward P.
Sesso, Howard D.
TI The relationship between total plasma carotenoids and risk factors for
chronic disease among middle-aged and older men
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Carotenoids; Risk factors; Chronic disease
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; ALPHA-TOCOPHEROL;
BETA-CAROTENE; CARDIOVASCULAR-DISEASE; SERUM CONCENTRATIONS; ENZYMATIC
DETERMINATION; LYCOPENE; RETINOL; ZEAXANTHIN
AB Individual plasma carotenoids have been associated with various chronic diseases but little is known about the relationship between total plasma carotenoids and risk-factors lot chronic diseases. In the Physicians' Health Study, we examined 492 men free of CVD and cancer for the relationship between total plasma carotenoids (the sum of alpha-carotene. beta-carotene, lycopene, zeaxanthin, lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic disease. Multivariate linear and logistic regression was performed to calculate parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In linear regression models, BMI, hypertension, alcohol intake and plasma levels of each lipid parameter and alpha-tocopherol significantly predicted levels of total plasma carotenoids. Upon adjustment for multiple chronic disease risk factors. the OR for levels of total plasma carotenoids greater than or equal to the median (>= 1.301 mu mol/l) was statistically significant for Current smoking. (OR 0.21; 95% CI 0.06; 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06; 4.99), daily alcohol ingestion (OR 2.46; 95 % CI 1.29; 467). each 100 mg/l increase in total cholesterol (OR 0.73; 95% CI 0.58; 0.91), HDL-cholesterol (OR 1.48; 95% CI 1.17; 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26; 1.99), each 100 mg/ml increase in intercellular adhesion molecule-l (OR 0.70; 95% CI 0.53; 0.93) and each 10 mu mol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12; 1.57), using logistic regression. Few lifestyle and clinical risk factors appear to be related to levels of total plasma carotenoid however, levels of biomarkers Such as plasma lipids and alpha-tocopheiol may he strongly related.
C1 [Farwell, Wildon R.; Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston Div 151 MAV, Boston, MA 02130 USA.
[Farwell, Wildon R.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Farwell, Wildon R.; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Norkus, Edward P.] New York Med Coll, Dept Med Res, Our Lady Mercy Med Ctr & Community & Prevent Med, Bronx, NY USA.
RP Farwell, WR (reprint author), VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston Div 151 MAV, 150 S Huntington Ave, Boston, MA 02130 USA.
EM Wildon.Farwell@va.gov
FU NIH [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; BASF AG; Roche
Vitamins, Inc; Cooperative Studies Program; Department of Veterans
Affairs Office of Research and Development; Roche Vitamins. Inc; PHS;
[29071]
FX The present study was funded by NIH CA 97193 and BASF AG, plus a grant
from Roche Vitamins, Inc. Approximately half of the participants in PHS
II also participated in PHS 1, which was established through NIH CA
34944. CA 40360, HL 26490 and HL 34595. Work on the present Study was
also supported by the Cooperative Studies Program of the Department of
Veterans Affairs Office of Research and Development.; This research was
supported in part by a grant from Roche Vitamins. Inc. The authors have
no other financial or personal interests related to this research. The
authors would like to acknowledge the crucial contributions of the
entire staff of the PHS. We are also indebted to the 29071 dedicated and
committed participants randomised into the PHS starting in either 1982
or 1995.
NR 24
TC 6
Z9 6
U1 0
U2 3
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD OCT
PY 2008
VL 100
IS 4
BP 883
EP 889
DI 10.1017/S0007114508944111
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 359QT
UT WOS:000260003900028
PM 18334043
ER
PT J
AU Miller, DD
Caroff, SN
Davis, SM
Rosenheck, RA
McEvoy, JP
Saltz, BL
Riggio, S
Chakos, MH
Swartz, MS
Keefe, RSE
Stroup, TS
Lieberman, JA
AF Miller, Del D.
Caroff, Stanley N.
Davis, Sonia M.
Rosenheck, Robert A.
McEvoy, Joseph P.
Saltz, Bruce L.
Riggio, Silvana
Chakos, Miranda H.
Swartz, Marvin S.
Keefe, Richard S. E.
Stroup, T. Scott
Lieberman, Jeffrey A.
CA CATIE Investigators
TI Extrapyramidal side-effects of antipsychotics in a randomised trial
SO BRITISH JOURNAL OF PSYCHIATRY
LA English
DT Article
ID TARDIVE-DYSKINESIA; CHRONIC-SCHIZOPHRENIA; ATYPICAL ANTIPSYCHOTICS;
2ND-GENERATION ANTIPSYCHOTICS; SCHIZOAFFECTIVE DISORDER; ACUTE
EXACERBATION; CLINICAL-TRIAL; RISPERIDONE; HALOPERIDOL; OLANZAPINE
AB Background
There are claims that second-generation antipsychotics produce fewer extrapyramidal side-effects (EPS) compared with first-generation drugs.
Aims
To compare the incidence of treatment-emergent EPS between second-generation antipsychotics and perphenazine in people with schizophrenia.
Method
Incidence analyses integrated data from standardised rating scales and documented use of concomitant medication or treatment discontinuation for EPS events. mixed model analyses of change in rating scales from baseline were also conducted.
Results
There were no significant differences in incidence or change in rating scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when comparing second-generation antipsychotics with perphenazine or comparing between second-generation antipsychotics. Secondary analyses revealed greater rates of concomitant antiparkinsonism medication among individuals on risperidone and lower rates among individuals on quetiapine, and lower rates of discontinuation because of parkinsonism among people on quetiapine and ziprasidone. There was a trend for a greater likelihood of concomitant medication for akathisia among individuals on risperidone and perphenazine.
Conclusions
The incidence of treatment-emergent EPS and change in EPS ratings indicated that there are no significant differences between second-generation antipsychotics and perphenazine or between second-generation antipsychotics in people with schizophrenia.
C1 [Miller, Del D.] Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USA.
[Caroff, Stanley N.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Caroff, Stanley N.] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Davis, Sonia M.] Quintiles Inc, Morrisville, NC USA.
[Rosenheck, Robert A.] Yale Univ, Sch Med, West Haven, CT 06516 USA.
[McEvoy, Joseph P.; Swartz, Marvin S.] Duke Univ, Med Ctr, Durham, NC USA.
[Saltz, Bruce L.] Mental Hlth Advocates Inc, Boca Raton, FL USA.
[Riggio, Silvana] Mt Sinai Sch Med James J Peter VAMC, Bronx, NY USA.
[Chakos, Miranda H.] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA.
[Stroup, T. Scott] Neurosci Hosp, N Carolina Sch Med, Chapel Hill, NC USA.
[Lieberman, Jeffrey A.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
RP Miller, DD (reprint author), Univ Iowa, Carver Coll Med, 2-105 MEB,500 Newton Rd, Iowa City, IA 52242 USA.
EM del-miller@uiowa.edu
RI Stroup, Thomas/F-9188-2014
OI Adler, Lawrence/0000-0002-6619-2493; Stroup, Thomas/0000-0002-3123-0672
FU NIMH NIH HHS [N01 MH90001, N01MH90001]
NR 51
TC 103
Z9 106
U1 2
U2 9
PU ROYAL COLLEGE OF PSYCHIATRISTS
PI LONDON
PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG,
ENGLAND
SN 0007-1250
EI 1472-1465
J9 BRIT J PSYCHIAT
JI Br. J. Psychiatry
PD OCT
PY 2008
VL 193
IS 4
BP 279
EP 288
DI 10.1192/bjp.bp.108.050088
PG 10
WC Psychiatry
SC Psychiatry
GA 363RS
UT WOS:000260285000004
PM 18827289
ER
PT J
AU Yu, EW
Blackwell, T
Ensrud, KE
Hillier, TA
Lane, NE
Orwoll, E
Bauer, DC
AF Yu, Elaine W.
Blackwell, Terri
Ensrud, Kristine E.
Hillier, Teresa A.
Lane, Nancy E.
Orwoll, Eric
Bauer, Douglas C.
TI Acid-Suppressive Medications and Risk of Bone Loss and Fracture in Older
Adults
SO CALCIFIED TISSUE INTERNATIONAL
LA English
DT Article
DE Bone density; Fracture; H2 receptor antagonist; Proton pump inhibitor
ID PROTON PUMP INHIBITORS; OSTEOPOROTIC FRACTURES; CALCIUM-ABSORPTION; HIP
FRACTURE; MINERAL DENSITY; K+-ATPASE; WOMEN; MEN; OMEPRAZOLE; AGE
AB Recent studies have suggested an increased fracture risk with acid-suppressive medication use. We studied two cohorts of men and women over age 65 who were enrolled in the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF), respectively. We used dual-energy X-ray absorptiometry and assessed baseline use of proton pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs) in 5,755 men and 5,339 women. Medication use and bone mineral density (BMD) were assessed, and hip and other nonspine fractures were documented. On multivariate analysis, men using either PPIs or H2RAs had lower cross-sectional bone mass. No significant BMD differences were observed among women. However, there was an increased risk of nonspine fracture among women using PPIs (relative hazard [RH] = 1.34, 95% confidence interval [CI] 1.10-1.64). PPI use was also associated with an increased risk of nonspine fracture in men but only among those who were not taking calcium supplements (RH = 1.49, 95% CI 1.04-2.14). H2RA use was not associated with nonspine fractures, and neither H2RA use nor PPI use was associated with incident hip fractures in men or women. The use of PPIs in older women, and perhaps older men with low calcium intake, may be associated with a modestly increased risk of nonspine fracture.
C1 [Yu, Elaine W.] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA.
[Blackwell, Terri] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Ensrud, Kristine E.] VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA.
[Ensrud, Kristine E.] Univ Minnesota, Dept Epidemiol & Community Hlth, Minneapolis, MN USA.
[Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res, NW & Hawaii, Portland, OR USA.
[Lane, Nancy E.] Univ Calif Davis, Davis, CA 95616 USA.
[Orwoll, Eric] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Yu, EW (reprint author), Massachusetts Gen Hosp, Div Endocrine, Thier 1101,50 Blossom St, Boston, MA 02114 USA.
EM ewyu@partners.org; TBlackwell@sfcc-cpmc.net; Ensru001@umn.edu;
Teresa.Hillier@kpchr.org; NeLane@ucdavis.edu; Orwoll@ohsu.edu;
DBauer@psg-ucsf.org
OI Orwoll, Eric/0000-0002-8520-7355
FU National Institutes of Health funding; National Institute of Arthritis
and Musculoskeletal and Skin Diseases (NIAMS); National Institute on
Aging (NIA) [AG05407, AR35582, AG05394, AR35584, AR35583, R01 AG005407,
R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG02757422A1]
FX The SOF is supported by National Institutes of Health funding. The
following institutes provide support: the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National
Institute on Aging (NIA) under grant numbers AG05407, AR35582, AG05394,
AR35584, AR35583, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1,
and 2 R01 AG02757422A1. The MrOS is supported by National Institutes of
Health (NIH) funding. The following institutes provide support: NIAMS,
NIA, the National Center for Research Resources, and the NIH Roadmap for
Medical Research under grant numbers U01 AR45580, U01 AR45614, U01
AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197,
U01-AG027810, and UL1 RR024140. Midcareer mentoring awards have been
given to D.C.B. and N.E.L. ( K24-AR-04884).
NR 29
TC 94
Z9 100
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0171-967X
J9 CALCIFIED TISSUE INT
JI Calcif. Tissue Int.
PD OCT
PY 2008
VL 83
IS 4
BP 251
EP 259
DI 10.1007/s00223-008-9170-1
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 363IO
UT WOS:000260261200002
PM 18813868
ER
PT J
AU Motzer, RJ
Bukowski, RM
Figlin, RA
Hutson, TE
Michaelson, MD
Kim, ST
Baum, CM
Kaftan, MW
AF Motzer, Robert J.
Bukowski, Ronald M.
Figlin, Robert A.
Hutson, Thomas E.
Michaelson, M. Dror
Kim, Sindy T.
Baum, Charles M.
Kaftan, Michael W.
TI Prognostic nomogram for sunitinib in patients with metastatic renal cell
carcinoma
SO CANCER
LA English
DT Article
DE sunitinib; nomogram; metastatic renal cell carcinoma; progression-free
survival
ID ENDOTHELIAL GROWTH-FACTOR; INTERFERON-ALPHA; FACTOR RECEPTOR; SURVIVAL;
EFFICACY; THERAPY; CANCER
AB BACKGROUND. in a randomized, phase 3 trial, sunitinib demonstrated superior efficacy over interferon-alfa as first-line therapy in patients with metastatic clear-cell renal cell carcinoma (RCC). On the basis Of outcome data from that trial, the authors developed a nomogram for predicting the probability of 12-month progression-free survival for patients who received sunitinib therapy.
METHODS. Three-hundred seventy-five patients who received sunitinib in the phase 3 trial were the Subject of the Current analysis. Nomogram pretreatment predictor variables included corrected serum calcium levels, the number of metastatic sites, hemoglobin levels, prior nephrectomy, the presence Of lung and liver metastases, thrombocytosis, Eastern Cooperative Oncology Group performance status, time from diagnosis to treatment, and serum levels of alkaline phosphatase and lactate dehydrogenase. Investigator-assessed progression-free survival was the predicted outcome endpoint. Internal validation of the nomogram consisted of quantification of the discrimination with the concordance index and assessment of calibration.
RESULTS. One-hundred seventy-four of 375 patients (46%) who received sunitinib achieved an objective response, and the median progression-free survival was 10.8 months (95% confidence interval, 10.6-12.6 months). A nomogram for predicting the probability of 12-month progression-free survival for patients who received sunitinib therapy was constructed on the basis of a Cox regression model from 11 parameters that were determined before treatment. The concordance index was 0.633.
CONCLUSIONS. A nomogram was developed from pretreatment clinical features to predict the probability of achieving 12-month progression-free survival with sunitinib therapy for metastatic clear-cell RCC. The authors concluded that independent validation of the nomogram and additional studies to identify tumor specific prognostic factors are warranted.
C1 [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Bukowski, Ronald M.] Cleveland Clin, Taussig Canc Ctr, Expt Therapeut Program, Cleveland, OH 44106 USA.
[Figlin, Robert A.] City Hope Natl Med Ctr, Div Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
[Hutson, Thomas E.] Baylor Sammons Canc Ctr Texas Oncol, Genitourinary Oncol Program, Dallas, TX USA.
[Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA.
[Kim, Sindy T.; Baum, Charles M.] Pfizer Global Res & Dev, Oncol Clin Dev, San Diego, CA USA.
RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
EM motzerr@mskcc.org
OI Michaelson, Dror/0000-0001-9249-6338
FU Pfizer [NCT00083889]
FX Supported by funding from Pfizer (clinicaltrials.gov no. NCT00083889).
NR 28
TC 109
Z9 119
U1 0
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 1
PY 2008
VL 113
IS 7
BP 1552
EP 1558
DI 10.1002/cncr.23776
PG 7
WC Oncology
SC Oncology
GA 354TK
UT WOS:000259661700010
PM 18720362
ER
PT J
AU Marsit, CJ
Posner, MR
McClean, MD
Kelsey, KI
AF Marsit, Carmen J.
Posner, Marshall R.
McClean, Michal D.
Kelsey, Karl T.
TI Hypermethylation of E-cadherin is an independent predictor of improved
survival in head and neck squamous cell carcinoma
SO CANCER
LA English
DT Article
DE hypermethylation; epigenetic; head and neck squamous cell carcinoma;
survival; E-cadherin
ID HUMAN-PAPILLOMAVIRUS; RISK-FACTORS; PROMOTER HYPERMETHYLATION;
EPIGENETIC INACTIVATION; SFRP GENES; CANCER; ALCOHOL; TOBACCO;
METHYLATION; EXPRESSION
AB BACKGROUND. The loss of E-cadherin (ECAD) protein expression has been linked to aggressive head and neck squamous cell carcinoma (HNSCC). Promoter hypermethylation of the cadherin 1, type 1 (CDH1) gene (encoding ECAD) is 1 mechanism by which this protein can be inactivated, although this epigenetic alteration of the gene has not been linked conclusively to poorer patient outcome and, in fact, may be associated with better patient prognosis.
METHODS. The authors investigated the prevalence of CDH1 promoter hypermethylation in a population-based case series of 340 primary HNSCC tumors using methylation-specific polymerase chain reaction. They also studied the association between CDH1 hypermethylation and patient demographic characteristics using multivariate analysis and examined the impact of CDH1 hypermethylation on patient survival using both univariate and multivariate methods.
RESULTS. Hypermethylation of CDH1 was significantly more prevalent (P <.03) among individuals with a low smoking history independent of whether they were seropositive for human papillomavirus type 16 (HPV-16). Patients who had tumors with CDH1 hypermethylation had significantly better overall survival compared with patients who had tumors without hypermethylation (P <.02; log-rank test). This effect was independent of HPV-16 status and demonstrated a significant hazard ratio of 0.5 (95% confidence interval, 0.3-0.9) in a model that controlled for HPV-16 serology, age, sex, and tumor stage.
CONCLUSIONS. The current results suggested that hypermethylation of CDH1 occurs more commonly in patients with HNSCC who are low smokers, suggesting that an additional factor may be driving this epigenetic alteration. Clinically, CDH1 hypermethylation may hold powerful prognostic potential in addition to that observed with HPV serology, and the authors concluded that it should be pursued in additional studies.
C1 [Marsit, Carmen J.; Kelsey, Karl T.] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA.
[Posner, Marshall R.] Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA.
[McClean, Michal D.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Kelsey, Karl T.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA.
RP Marsit, CJ (reprint author), Brown Univ, Dept Pathol & Lab Med, Box G-E537, Providence, RI 02912 USA.
EM carmen_marsit@brown.edu
RI McClean, Michael/J-2934-2015;
OI Marsit, Carmen/0000-0003-4566-150X
FU National Institutes of Health [R01CA078609, R01CA100679]; Friends of
Dana-Farber; Flight Attendants Medical Research Institute
FX Supported by National Institutes of Health grants R01CA078609 and
R01CA100679, by the Friends of Dana-Farber, and by the Flight Attendants
Medical Research Institute (C.J.M.).
NR 33
TC 32
Z9 33
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 1
PY 2008
VL 113
IS 7
BP 1566
EP 1571
DI 10.1002/cncr.23770
PG 6
WC Oncology
SC Oncology
GA 354TK
UT WOS:000259661700012
PM 18711702
ER
PT J
AU Tanabe, KK
AF Tanabe, Kenneth K.
TI The past 60 years in liver surgery
SO CANCER
LA English
DT Review
ID MAJOR HISTOCOMPATIBILITY COMPLEX; SEROLOGY PREDICTS TUMOR; HEPATIC
RESECTION; HEPATOCELLULAR-CARCINOMA; RADIOFREQUENCY ABLATION;
PORTAL-VEIN; DISEASE CHARACTERISTICS; COLORECTAL METASTASES; VASCULAR
ISOLATION; VENOUS BYPASS
AB The anniversary of the first publication of Cancer provides an opportunity to review the progress in liver cancer surgery in the past 60 years. Indeed, the past half century has been witness to remarkable advances in liver surgery that have provided benefit to so many patients afflicted with primary or secondary liver Minors. However, no matter now astounding these past achievements may be, it is clear that the future holds even greater promise.
C1 [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA.
[Tanabe, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA.
RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Yawkey 7-924,55 Fruit St, Boston, MA 02114 USA.
EM ktanabe@partners.org
FU National Institutes of Health [5R01CA076183, 5R21CA119600]; Tucker
Gosnell Gastrointestinal Cancer Center
FX Supported by grants 5R01CA076183 and 5R21CA119600 from the National
Institutes of Health and by and the Tucker Gosnell Gastrointestinal
Cancer Center.
NR 103
TC 5
Z9 7
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD OCT 1
PY 2008
VL 113
IS 7
SI SI
BP 1888
EP 1896
DI 10.1002/cncr.23652
PG 9
WC Oncology
SC Oncology
GA 354TL
UT WOS:000259661800015
PM 18798530
ER
PT J
AU Schemhammer, ES
Giovannuccci, E
Fuchs, CS
Ogino, S
AF Schemhammer, Eva S.
Giovannuccci, Edward
Fuchs, Charles S.
Ogino, Shuji
TI A prospective study of dietary folate and vitamin B and colon cancer
according to microsatellite instability and KRAS mutational status
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; MULTIVITAMIN USE;
COMPETING RISKS; NURSES HEALTH; LIFE-STYLE; K-RAS; WOMEN;
REPRODUCIBILITY; METHYLATION
AB Sporadic microsatellite instability (MSI)-high colon cancers are positively associated with MLH1 promoter methylation and inversely with KRAS mutation. One-carbon metabolism is critical for methylation reactions and nucleotide biosynthesis, but the influence of dietary one-carbon nutrients such as folate and B vitamins on molecular changes in colon cancer is not known. Using the database of two independent prospective cohort studies (88,691 women and 47,371 men), we examined the relation between dietary intake of one-carbon nutrients and the incidence of microsatellite instability and KRAS mutation in 669 incident colon cancers. The overall inverse association between folate and colon cancer did not differ significantly according to MSI status [relative ratio (RR), 0.79; 95% confidence interval (95% CI), 0.60-1.03 for microsatellite stable/MSI-low colon cancers; and RR, 0.61, 95% CI, 0.37-1.02 for MSI-high colon cancers; P-heterogeneity 0.53] or KRAS status (RR, 0.66; 95% CI, 0.49-0.87 for KRAS wild-type colon cancers; and RR, 1.05; 95% CI, 0.68-1.61 for KRAS mutated colon cancers; Pheterogeneity = 0.12), although our analyses had limited power to preclude an effect of folate on KRAS wild-type colon cancers. Similarly, high vitamin B-6 or B-12 intake was inversely associated with colon cancers, regardless of MSI or KRAS status. No significant effect of methionine intake or alcohol consumption was observed for colon cancers with MSI high or KRAS mutation. In conclusion, the influence of dietary one-carbon nutrient intake on colon cancer risk does not seem to differ according to MSI or KRAS mutational status.
C1 [Schemhammer, Eva S.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA.
[Schemhammer, Eva S.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA.
[Schemhammer, Eva S.; Giovannuccci, Edward; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA.
[Schemhammer, Eva S.] KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria.
[Schemhammer, Eva S.] Appl Canc Res Inst Translat Res Vienna, Vienna, Austria.
RP Schemhammer, ES (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02215 USA.
EM eva.schemhammer@channing.harvard.edu
FU NIH [CA70817, CA87969, CA55075, CA42812, CA58684, CA90598, CA122826];
Bennett Family Fund and Entertainment Industry Foundation; Entertainment
Industry Foundation National Colorectat Cancer Research Alliance
FX Grant support: NIH research grants CA70817, CA87969, CA55075, CA42812,
CA58684, CA90598, CA122826, the Bennett Family Fund and Entertainment
Industry Foundation, and the Entertainment Industry Foundation National
Colorectat Cancer Research Alliance.
NR 24
TC 27
Z9 28
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD OCT
PY 2008
VL 17
IS 10
BP 2895
EP 2898
DI 10.1158/1055-9965.EPI-08-0638
PG 4
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 360IK
UT WOS:000260051000049
PM 18843035
ER
PT J
AU Wirth, LJ
Krane, JF
Li, Y
Othus, M
Moran, AE
Dorfman, DM
Norris, CM
Goguen, L
Posner, MR
Haddad, RI
Bertagnolli, MM
AF Wirth, Lori J.
Krane, Jeffrey F.
Li, Yi
Othus, Megan
Moran, Amy E.
Dorfman, David M.
Norris, Charles M., Jr.
Goguen, Laura
Posner, Marshall R.
Haddad, Robert I.
Bertagnolli, Monica M.
TI A Pilot Surrogate Endpoint Biomarker Study of Celecoxib in Oral
Premalignant Lesions
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; PARTIAL HYDATIDIFORM MOLES; GROWTH-FACTOR
RECEPTOR; 2ND PRIMARY TUMORS; RANDOMIZED-TRIAL; NECK-CANCER;
MALIGNANT-TRANSFORMATION; COLORECTAL ADENOMAS; PROSTAGLANDIN E-2;
CYCLOOXYGENASE-2 EXPRESSION
AB This study evaluated changes in prostaglandin E(2) (PGE(2)) levels and related biomarkers in oral premalignant lesions (OPL) in response to celecoxib treatment. Twenty-two subjects were enrolled and treated with celecoxib. Pretreatment and 12-week biopsies were done. Subjects whose biopsy showed >= 30% decrease in PGE(2) remained on celecoxib for a total of 12 months when repeat biopsy was done. Biopsies were examined to assess degree of dysplasia, DNA ploidy, and immunohistochemical expression of BCL2, pAKT-Ser473, Ki-67, and CD31 (microvessel density). In 18 paired biopsies available at baseline and 12 weeks, mean normalized PGE(2) levels decreased by 38% (P = 0.002). After 12 months, PGE2 decreased by 31% (P = 0.340). Twelve biopsies (67%; P = 0.0129) showed improvement in degree of dysplasia after 12 weeks, and 8 of 11 biopsies (73%; P = 0.0703) continued to show an improvement in the degree of dysplasia after 12 months. Trends suggested down-modulation of cyclooxygenase-2 and Ki-67 in some tissues, increased pAKT-Ser473 expression, and an inverse relationship between PGE(2) and BCL2 expression. This study documents the feasibility of measuring potential surrogate endpoint biomarkers of chemopreventive agent response in OPLs. Treatment with celecoxib in subjects with OPLs favorably modulates the primary mediator of cyclooxygenase-2 activity, PGE(2), after 12 weeks.
C1 [Moran, Amy E.; Norris, Charles M., Jr.; Goguen, Laura; Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Wirth, Lori J.; Posner, Marshall R.; Haddad, Robert I.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Wirth, Lori J.; Posner, Marshall R.; Haddad, Robert I.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Krane, Jeffrey F.; Dorfman, David M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
EM mbertagnolli@partners.org
NR 48
TC 11
Z9 11
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD OCT
PY 2008
VL 1
IS 5
BP 339
EP 348
DI 10.1158/1940-6207.CAPR-07-0003
PG 10
WC Oncology
SC Oncology
GA 420MK
UT WOS:000264293700006
PM 19138978
ER
PT J
AU Nemenoff, R
Meyer, AM
Hudish, TM
Mozer, AB
Snee, A
Narumiya, S
Stearman, RS
Winn, RA
Weiser-Evans, M
Geraci, MW
Keith, RL
AF Nemenoff, Raphael
Meyer, Amy M.
Hudish, Tyler M.
Mozer, Anthony B.
Snee, Amy
Narumiya, Shuh
Stearman, Robert S.
Winn, Robert A.
Weiser-Evans, Mary
Geraci, Mark W.
Keith, Robert L.
TI Prostacyclin Prevents Murine Lung Cancer Independent of the Membrane
Receptor by Activation of Peroxisomal Proliferator-Activated Receptor
gamma
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PULMONARY PROSTACYCLIN; SYNTHASE
OVEREXPRESSION; PROSTANOID RECEPTORS; TRANSGENIC MICE; A/J MICE; CELL;
INHIBITION; TUMORIGENESIS; EXPRESSION
AB Overexpression of prostacyclin synthase (PGIS) decreases lung tumor multiplicity in chemical- and cigarette-smoke-induced murine lung cancer models. Prostacyclin signals through a single G-protein-coupled receptor (IP), which signals through cyclic AMP. To determine the role of this receptor in lung cancer chemoprevention by prostacyclin, PGIS-overexpressing mice were crossed to mice that lack the IP receptor [IP(-/-)]. Carcinogen-induced lung tumor incidence was similar in IP(+/+), IP(+/-), and IP(-/-) mice, and overexpression of PGIS gave equal protection in all three groups, indicating that the protective effects of prostacyclin are not mediated through activation of IP. Because prostacyclin can activate members of the peroxisomal proliferator-activated receptor (PPAR) family of nuclear receptors, we examined the role of PPAR. in the protection of prostacyclin against lung tumorigenesis. Iloprost, a stable prostacyclin analogue, activated PPAR. in nontransformed bronchial epithelial cells and in a subset of human non-small-cell lung cancer cell lines. Iloprost-impregnated chow fed to wild-type mice resulted in elevated lung macrophages and decreased lung tumor formation. Transgenic animals with lung-specific PPAR. overexpression also developed fewer lung tumors. This reduction was not enhanced by administration of supplemental iloprost. These studies indicate that PPAR. is a critical target for prostacyclin-mediated lung cancer chemoprevention and may also have therapeutic activity.
C1 [Hudish, Tyler M.; Mozer, Anthony B.; Keith, Robert L.] Denver VA Med Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80220 USA.
[Nemenoff, Raphael; Meyer, Amy M.; Snee, Amy; Weiser-Evans, Mary] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Renal Dis & Hypertens, Denver, CO 80262 USA.
[Stearman, Robert S.; Winn, Robert A.; Geraci, Mark W.; Keith, Robert L.] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA.
[Narumiya, Shuh] Kyoto Univ, Fac Med, Dept Pharmacol, Kyoto 606, Japan.
[Narumiya, Shuh] Kyoto Univ, Fac Pharmaceut Sci, Dept Physiol Chem, Kyoto 606, Japan.
RP Keith, RL (reprint author), Denver VA Med Ctr, Dept Med, Div Pulm Sci & Crit Care Med, 1055 Clermont St,Box 111A, Denver, CO 80220 USA.
EM Robert.Keith@UCHSC.edu
FU NIH [CA103618, CA108610, CA58187]; Department of Veterans Affairs
FX Grant support: NIH grants CA103618, CA108610, and CA58187. R.L. Keith
was supported by VA Advanced Career Development and Merit Review Awards
from the Department of Veterans Affairs.
NR 42
TC 36
Z9 36
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD OCT
PY 2008
VL 1
IS 5
BP 349
EP 356
DI 10.1158/1940-6207.CAPR-08-0145
PG 8
WC Oncology
SC Oncology
GA 420MK
UT WOS:000264293700007
PM 19138979
ER
PT J
AU Shen, CH
Chen, HY
Lin, MS
Li, FY
Chang, CC
Kuo, ML
Settleman, J
Chen, RH
AF Shen, Che-Hung
Chen, Hsin-Yi
Lin, Ming-Shien
Li, Fang-Yen
Chang, Cheng-Chi
Kuo, Min-Liang
Settleman, Jeffrey
Chen, Ruey-Hwa
TI Breast tumor kinase phosphorylates p190RhoGAP to regulate Rho and Ras
and promote breast carcinoma growth, migration, and invasion
SO CANCER RESEARCH
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; BRK TYROSINE KINASE; MAMMARY
EPITHELIAL-CELLS; C-SRC; DUCTAL MORPHOGENESIS; P190 RHOGAP; EXPRESSION;
CANCER; LOCALIZATION; INACTIVATION
AB Breast tumor kinase (Brk), an Src-like nonreceptor tyrosine kinase, is overexpressed in breast cancer and several other cancer types. Our previous study indicates that Brk promotes cell migration and tumor invasion by phosphorylating the focal adhesion protein paxillin. Here, we report the identification of p190RhoGAP-A (p190) as a Brk substrate. Brk phosphorylates p190 at the Y-1105 residue both in vitro and in vivo, thereby promoting the association of p190 with p120RasGAP (p120). As a consequence, Brk stimulates p190 and attenuates p120 functions, leading to RhoA inactivation and Ras activation, respectively. In carcinoma cells expressing high levels of Brk, endogenous Brk functions as a key contributor to epidermal growth factor-induced p190 tyrosine phosphorylation. We present evidence showing that p190 phosphorylation plays essential roles in both migratory and proliferative effects of Brk. Furthermore, disruption of p190 phosphorylation-induced p190/p120 complex in breast cancer cells abolishes not only the abilities of Brk to regulate RhoA and Ras but also the stimulatory effects of Brk on proliferation, migration, invasion, transformation, and tumorigenicity. Together, our findings reveal a previously unknown function of Brk in regulating both RhoA and Ras by phosphorylating p190 and provide evidence for the crucial roles of this Brk-elicited signaling pathway in promoting breast malignancy.
C1 [Chen, Hsin-Yi; Chen, Ruey-Hwa] Acad Sinica, Inst Biol Chem, Taipei, Taiwan.
[Shen, Che-Hung; Lin, Ming-Shien; Chen, Ruey-Hwa] Natl Taiwan Univ, Inst Mol Med, Taipei 10764, Taiwan.
[Chang, Cheng-Chi; Kuo, Min-Liang] Natl Taiwan Univ, Coll Med, Inst Toxicol, Taipei 10764, Taiwan.
[Li, Fang-Yen; Chen, Ruey-Hwa] Natl Taiwan Univ, Inst Biochem Sci, Taipei, Taiwan.
[Settleman, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Canc Ctr, Charlestown, MA USA.
RP Chen, RH (reprint author), Acad Sinica, Inst Biol Chem, Taipei, Taiwan.
EM rhchen@gate.sinica.edu.tw
RI Kuo , Min-Liang/C-4872-2009;
OI KUO, MIN-LIANG/0000-0002-7139-0144
FU National Health Research Institute [NHRI-EX97-9502BI]
FX Grant support: National Health Research Institute grant.
NHRI-EX97-9502BI. The costs of publication of this article were defrayed
in part by the payment of page charges. This article must therefore be
hereby marked advertisement in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
NR 38
TC 48
Z9 51
U1 1
U2 3
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 OCT 1
PY 2008
VL 68
IS 19
BP 7779
EP 7787
DI 10.1158/0008-5472.CAN-08-0997
PG 9
WC Oncology
SC Oncology
GA 360AR
UT WOS:000260029900012
PM 18829532
ER
PT J
AU Yi, CL
Wilker, EW
Yaffe, MB
Stemmer-Rachamimov, A
Kissil, JL
AF Yi, Chunling
Wilker, Erik W.
Yaffe, Michael B.
Stemmer-Rachamimov, Anat
Kissil, Joseph L.
TI Validation of the p21-activated kinases as targets for inhibition in
neurofibromatosis type
SO CANCER RESEARCH
LA English
DT Article
ID NF2 TUMOR-SUPPRESSOR; SCHWANNOMA CELLS; MERLIN; TRANSFORMATION; RAC;
PHOSPHORYLATION; ACTIVATION; EXPRESSION; GROWTH; GENE
AB Neurofibromatosis type 2 (NF2) is a dominantly inherited cancer disorder caused by mutations at the NF2 gene locus. Merlin, the protein product of the NF2 gene, has been shown to negatively regulate Rac1 signaling by inhibiting its downstream effector kinases, the p21-activated kinases (Pak). Given the implication of Paks in tumorigenesis, it Is plausible that merlin's tumor suppressive function might be mediated, at least in part, via inhibition of the Paks. We present data indicating this is indeed the case. First, analysis of primary schwannoma samples derived from NF2 patients showed that in a significant fraction of the tumors, the activity of Pak1 was highly elevated. Second, we used shRNAs to knockdown Pak1, 2, and 3 in NIH3T3 cells expressing a dominant-negative form of merlin, NF2(BBA) (NIH3T3/NF2(BBA)), and find that simultaneous knockdown of Pak1-3 in these cells significantly reduced their growth rates in vitro and inhibited their ability to form tumors in vivo. Finally, while attempting to silence Pak1 in rat schwannoma cells, we found that these cells were unable to tolerate long-term Pak1 inhibition and rapidly moved to restore Pak1 levels by shutting down Pak1 shRNA expression through a methylation-dependent mechanism. These data suggest that inhibiting Pak could be a beneficial approach for the development of therapeutics toward NF2. In addition, the finding that the shRNA-mediated Pak1 suppression was silenced rapidly by methylation raises questions about the future application of such technologies for the treatment of diseases such as cancer.
C1 [Kissil, Joseph L.] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA.
[Wilker, Erik W.; Yaffe, Michael B.] MIT, Ctr Canc Res, Cambridge, MA 02139 USA.
[Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Kissil, JL (reprint author), Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM jkissil@wistar.org
FU Department of Defense Neurofibromatosis Research Program; Ruth L.
Kirschstein NRSA fellowship
FX Department of Defense Neurofibromatosis Research Program. C. Yi is a
recipient of Ruth L. Kirschstein NRSA fellowship.
NR 20
TC 35
Z9 36
U1 0
U2 1
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 OCT 1
PY 2008
VL 68
IS 19
BP 7932
EP 7937
DI 10.1158/0008-5472.CAN-08-0866
PG 6
WC Oncology
SC Oncology
GA 360AR
UT WOS:000260029900030
PM 18829550
ER
PT J
AU Kutuk, O
Letai, A
AF Kutuk, Ozgur
Letai, Anthony
TI Alteration of the mitochondrial apoptotic pathway is key to acquired
paclitaxel resistance and can be reversed by ABT-737
SO CANCER RESEARCH
LA English
DT Article
ID BH3 MIMETIC ABT-737; BREAST-CANCER CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA;
DRUG-INDUCED APOPTOSIS; BCL-2 FAMILY PROTEINS; III BETA-TUBULIN;
LUNG-CANCER; CHEMOTHERAPY; BIM; INHIBITOR
AB Paclitaxel is a microtubule-targeting antineoplastic drug widely used in human cancers. Even when tumors are initially responsive, progression of disease despite continued taxane therapy is all too common in the treatment of many of the most common epithelial cancers, including breast cancer. However, the mechanisms underlying paclitaxel resistance in cancer cells are not completely understood. Our hypothesis is that changes in the intrinsic (or mitochondrial) cell death pathway controlled by the BCL-2 family are key to the development of acquired paclitaxel resistance. Here we show that paclitaxel activates the mitochondrial apoptosis pathway, which can be blocked by BCL-2 overexpression. Treatment with ABT-737, a small-molecule BCL-2 antagonist, restores sensitivity to paclitaxel in BCL-2-overexpressing cells. To investigate the importance of changes in the intrinsic apoptotic pathway in the absence of enforced BCL-2 expression, we generated two independent breast cancer cell lines with acquired resistance to apoptosis induced by paclitaxel. In these lines, acquired resistance to paclitaxel is mediated either by increased antiapoptotic BCL-2 proteins or decreased proapoptotic BCL-2 proteins. In both cases, ABT-737 can engage the mitochondrial apoptosis pathway to restore sensitivity to paclitaxel to cell lines with acquired paclitaxel resistance. In summary, these findings suggest that alterations in the intrinsic apoptotic pathway controlled by BCL-2 protein family members may be crucial to causing paclitaxel resistance. Furthermore, our results suggest that combining small-molecule BCL-2 antagonists with paclitaxel may offer benefit to patients with paclitaxel-resistant tumors, an oncologic problem of great prevalence.
C1 [Kutuk, Ozgur; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 530B,44 Binney St, Boston, MA 02115 USA.
EM anthony_letai@dfci.harvard.edu
FU National Cancer Institute [K08 CA 102548, R01 CA129974]
FX National Cancer Institute grants K08 CA 102548 and R01 CA129974.
NR 39
TC 73
Z9 82
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD OCT 1
PY 2008
VL 68
IS 19
BP 7985
EP 7994
DI 10.1158/0008-5472.CAN-08-1418
PG 10
WC Oncology
SC Oncology
GA 360AR
UT WOS:000260029900036
PM 18829556
ER
PT J
AU Aqel, R
Zoghbi, GJ
Hage, F
Dell'Italia, L
Iskandrian, AE
AF Aqel, Raed
Zoghbi, Gilbert J.
Hage, Fadi
Dell'Italia, Louis
Iskandrian, Ami E.
TI Hemodynamic Evaluation of Coronary Artery Bypass Graft Lesions Using
Fractional Flow Reserve
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE bypass grafts; coronary; coronary flow; hemodynamics; quantitative
coronary angiography
ID EMISSION COMPUTED-TOMOGRAPHY; MYOCARDIAL-PERFUSION; PRESSURE
MEASUREMENT; BLOOD-FLOW; FOLLOW-UP; ANGIOGRAPHY; STENOSIS; VELOCITY;
DISEASE; PREDICT
AB Background: Coronary angiography is limited by its inability to assess the hemodynamic significance of a coronary artery stenosis. The assessment of the physiological significance of saphenous vein graft (SVG) lesions with a pressure wire to determine the fractional flow reserve (FFR) is lacking. Methods: FFR was determined in 10 SVG lesions of 10 males who had stress myocardial perfusion imaging (MPI) prior to referral for percutaneous coronary intervention for clinical indications. Results: All SVGs had a diameter stenosis (DS) >50% and 30% had a DS >= 70%. A significant FFR was present in 30% of patients. Ischemia along the territory of the SVG was present in 20% of patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FFR <0.75 for the detection of ischemia on stress MPI were 50, 75, 33, 85, and 70%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FFR <0.75 for detecting >= 70% DS on angiography were 33, 71, 33, 71, and 60%, respectively. There was no significant correlation between FFR and % DS (R(2) = 0.1, P = 0.35). Conclusion: The use of FFR to assess the physiological significance of SVG lesions is feasible and provides an acceptable specificity and negative predictive value compared to stress MPI. (C) 2008 Wiley-Liss, Inc.
C1 [Aqel, Raed; Zoghbi, Gilbert J.; Hage, Fadi; Dell'Italia, Louis] Birmingham VA Med Ctr, Birmingham, VA USA.
[Aqel, Raed; Zoghbi, Gilbert J.; Hage, Fadi; Dell'Italia, Louis; Iskandrian, Ami E.] Univ Alabama, Birmingham, VA USA.
RP Aqel, R (reprint author), 1808 7th Ave S,BDB 383, Birmingham, AL 35294 USA.
EM raed.aqel@va.gov
OI Hage, Fadi/0000-0002-1397-4942
FU Radi Medical Systems, Inc
FX Dr. Aqel received a grant from Radi Medical Systems, Inc.
NR 19
TC 18
Z9 18
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1522-1946
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD OCT 1
PY 2008
VL 72
IS 4
BP 479
EP 485
DI 10.1002/ccd.21675
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 379JM
UT WOS:000261392500008
PM 18814221
ER
PT J
AU Adly, MA
Assaf, HA
Hussein, MRA
AF Adly, Mohamed A.
Assaf, Hanan A.
Hussein, Mahmoud Rezk A.
TI Heat shock protein 27 expression in the human testis showing normal and
abnormal spermatogenesis
SO CELL BIOLOGY INTERNATIONAL
LA English
DT Article
DE Testis; HSP27; Spermatogenesis
ID CUTANEOUS MALIGNANT MELANOMAS; MALE GERM-CELLS; IMMUNE-RESPONSE;
MICROSATELLITE INSTABILITY; TRANSCRIPTION FACTOR-1; DECREASED
EXPRESSION; MOLECULAR CHAPERONES; SERTOLI-CELLS; TUMOR-CELLS;
HEAT-SHOCK-PROTEIN-70
AB Heat shock proteins (HSPs) are molecular chaperones involved in protein folding, assembly and transport, and which play critical roles in the regulation of cell growth, survival and differentiation. We set out to test the hypothesis that HSP27 protein is expressed in the human testes and its expression varies with the state of spermatogenesis. HSP27 expression was examined in 30 human testicular biopsy specimens (normal spermatogenesis, maturation arrest and Sertoli cell only syndrome, 10 cases each) using immunofluorescent methods. The biopsies were obtained from patients undergoing investigations for infertility. The seminiferous epithelium of the human testes showing normal spermatogenesis had a cell type-specific expression of HSP27. HSP27 expression was strong in the cytoplasm of the Sertoli cells, spermatogonia, and Leydig cells. Alternatively, the expression was moderate in the spermatocytes, weak in the spermatids and absent in the spermatozoa. In testes showing maturation arrest, HSP27 expression was strong in the Sertoli cells, weak in the spermatogonia, and spermatocytes. It was absent in the spermatids and Leydig cells. In Sertoli cell only syndrome, HSP27 expression was strong in the Sertoli cells and absent in the Leydig cells. We report for the first time the expression patterns of HSP27 in the human testes and show differential expression during normal spermatogenesis, indicating a possible role in this process. The altered expression of this protein in testes showing abnormal spermatogenesis may be related to the pathogenesis of male infertility. (c) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
C1 [Hussein, Mahmoud Rezk A.] Assuit Univ Hosp, Fac Med, Dept Pathol, Assiut, Egypt.
[Adly, Mohamed A.] S Valley Univ, Sohag Fac Sci, Dept Zool, Kena, Egypt.
[Adly, Mohamed A.] King Khalid Univ, Fac Sci, Dept Life Sci, Abha, Saudi Arabia.
[Assaf, Hanan A.] S Valley Univ, Sohag Fac Med, Dept Dermatol & Venerol, Kena, Egypt.
[Hussein, Mahmoud Rezk A.] KKU, Assir Cent Hosp, Dept Pathol, Abha, Saudi Arabia.
[Hussein, Mahmoud Rezk A.] Univ Wisconsin, Sch Med, Madison, WI 53705 USA.
[Hussein, Mahmoud Rezk A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA.
RP Hussein, MRA (reprint author), Assuit Univ Hosp, Fac Med, Dept Pathol, Assiut, Egypt.
EM mrh17@gawab.com
NR 54
TC 13
Z9 14
U1 0
U2 1
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1065-6995
J9 CELL BIOL INT
JI Cell Biol. Int.
PD OCT
PY 2008
VL 32
IS 10
BP 1247
EP 1255
DI 10.1016/j.cellbi.2008.07.009
PG 9
WC Cell Biology
SC Cell Biology
GA 369CT
UT WOS:000260671800009
PM 18692580
ER
PT J
AU Qiao, M
Sheng, SJ
Pardee, AB
AF Qiao, Meng
Sheng, Shijie
Pardee, Arthur B.
TI Metastasis and AKT activation
SO CELL CYCLE
LA English
DT Review
DE cancer; metastasis; PI3K; PTEN; AKT activation; GSK-3 beta; SNAIL;
E-cadherin
ID EPITHELIAL-MESENCHYMAL TRANSITION; CELL-CELL ADHESION; PROTEIN-TYROSINE
PHOSPHATASES; GLYCOGEN-SYNTHASE KINASE-3; HUMAN BREAST-CANCER;
E-CADHERIN; TUMOR PROGRESSION; BETA-CATENIN; PHOSPHATIDYLINOSITOL-3
KINASE; SIGNALING CASCADES
AB Metastasis is responsible for 90% of cancer patient deaths. More information is needed about the molecular basis for its potential detection and treatment. The activated AKT kinase is necessary for many events of the metastatic pathway including escape of cells from the tumor's environment, into and then out of the circulation, activation of proliferation, blockage of apoptosis, and activation of angiogenesis. A series of steps leading to metastatic properties can be initiated upon activation of AKT by phosphorylation on Ser-473. These findings lead to the question of how this activation is connected to metastasis. Activated AKT phosphorylates GSK-3 beta causing its proteolytic removal. This increases stability of the negative transcription factor SNAIL, thereby decreasing transcription of the transmembrane protein E-cadherin that forms adhesions between adjacent cells, thereby permitting their detachment. How is AKT hyperactivated in metastatic cells? Increased PI3K or TORC2 kinase activity- or decreased PHLPP phosphatase could be responsible. Furthermore, a positive feedback mechanism is that the decrease of E-cadherin lowers PTEN and thereby increases PIP3, further activating AKT and metastasis.
C1 [Qiao, Meng; Pardee, Arthur B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Sheng, Shijie] Wayne State Univ, Sch Med, Detroit, MI USA.
[Sheng, Shijie] Barbara Ann Karmanos Canc Inst, Detroit, MI USA.
RP Qiao, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM meng_qiao@dfci.harvard.edu
NR 63
TC 126
Z9 133
U1 3
U2 8
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD OCT 1
PY 2008
VL 7
IS 19
BP 2991
EP 2996
DI 10.4161/cc.7.19.6784
PG 6
WC Cell Biology
SC Cell Biology
GA 363JG
UT WOS:000260263000011
PM 18818526
ER
PT J
AU Feng, P
Yee, KK
Rawson, NE
Feldman, LM
Feldman, RS
Breslin, PAS
AF Feng, Pu
Yee, Karen K.
Rawson, Nancy E.
Feldman, Lauren M.
Feldman, Roy S.
Breslin, Paul A. S.
TI Immune Cell Populations in Healthy Human Fungiform Papillae
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 15th International Symposium on Olfaction and Taste
CY JUL 21-26, 2008
CL San Francisco, CA
C1 [Feng, Pu; Yee, Karen K.; Rawson, Nancy E.; Feldman, Roy S.; Breslin, Paul A. S.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA.
[Feldman, Lauren M.] Barnard Coll, New York, NY USA.
[Feldman, Roy S.] Philadelphia Vet Affairs Med Ctr, Dent Serv, Philadelphia, PA USA.
[Feldman, Lauren M.] Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0379-864X
J9 CHEM SENSES
JI Chem. Senses
PD OCT
PY 2008
VL 33
IS 8
BP S73
EP S73
PG 1
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
Neurology; Physiology
GA 359GE
UT WOS:000259973600289
ER
PT J
AU Holbrook, EH
Schwob, JE
AF Holbrook, Eric H.
Schwob, James E.
TI An Integrated Immunohistochemical Analysis of Human Whole-Mount and
Cryosectioned Olfactory Tissue
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 15th International Symposium on Olfaction and Taste
CY JUL 21-26, 2008
CL San Francisco, CA
C1 [Holbrook, Eric H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA.
[Schwob, James E.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0379-864X
J9 CHEM SENSES
JI Chem. Senses
PD OCT
PY 2008
VL 33
IS 8
BP S78
EP S78
PG 1
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
Neurology; Physiology
GA 359GE
UT WOS:000259973600307
ER
PT J
AU Maurer, J
Rebbapragada, V
Borson, S
Goldstein, R
Kunik, ME
Yohannes, AM
Hanania, NA
AF Maurer, Janet
Rebbapragada, Venkata
Borson, Soo
Goldstein, Roger
Kunik, Mark E.
Yohannes, Abebaw M.
Hanania, Nicola A.
CA ACCP Workshop Panel Anxiety Depr
TI Anxiety and Depression in COPD Current Understanding, Unanswered
Questions, and Research Needs
SO CHEST
LA English
DT Review
DE anxiety; comorbidities; COPD; depression; mood disorders
ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; RANDOMIZED
CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; CHRONIC BREATHING
DISORDERS; AIR-FLOW LIMITATION; HEALTH-STATUS; PRIMARY-CARE;
MYOCARDIAL-INFARCTION; COLLABORATIVE CARE
AB Background: Approximately 60 million people in the United States live with one of four chronic conditions: heart disease, diabetes, chronic respiratory disease, anti major depression. Anxiety and depression are very common comorbidities in COPD and have significant impact on patients, their families, society, and the course of the disease.
Methods: We report the proceedings of a multidisciplinary, workshop on anxiety and depression in COPD that aimed to shed light on the current understanding of these comorbidities, and outline unanswered questions and areas of future research needs.
Results: Estimates of prevalence of anxiety and depression in COPD vary widely but are generally higher than those reported in sonic other advanced chronic diseases. Untreated and undetected anxiety and depressive symptoms may increase physical disability, morbidity, and health-care utilization. Several patient, physician, and system barriers contribute to the underdiagnosis of these disorders in patients with COPD. While few published studies demonstrate that these disorders associated with COPD respond well to appropriate pharmacologic and nonpharmacologic therapy, only a small proportion of COPD patients with these disorders receive effective treatment.
Conclusion: Future research is needed to address the impact, early detection, and management of anxiety and depression in COPD. (CHEST 2008; 134:43S-56S)
C1 [Rebbapragada, Venkata; Hanania, Nicola A.] Baylor Coll Med, Pulm & Crit Care Med Sect, Houston, TX 77030 USA.
[Maurer, Janet] Hlth Dialog Inc, Phoenix, AZ USA.
[Borson, Soo] Univ Washington, Sch Med, Seattle, WA USA.
[Goldstein, Roger] Univ Toronto, Toronto, ON, Canada.
[Kunik, Mark E.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[Yohannes, Abebaw M.] Manchester Metropolitan Univ, Manchester M15 6BH, Lancs, England.
RP Hanania, NA (reprint author), Baylor Coll Med, Pulm & Crit Care Med Sect, 1504 Taub Loop, Houston, TX 77030 USA.
EM Hanania@bcm.edu
FU National Institute of Mental Health and the Alpha-1 Foundation
[R13-MH07322S-01A1]
FX This workshop was supported by grant R13-MH07322S-01A1 from the National
Institute of Mental Health and the Alpha-1 Foundation.
NR 105
TC 180
Z9 185
U1 4
U2 28
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD OCT
PY 2008
VL 134
IS 4
SU S
BP 43S
EP 56S
DI 10.1378/chest.08-0342
PG 14
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 360ZQ
UT WOS:000260097700001
PM 18842932
ER
PT J
AU Vasan, RS
MacRae, CA
AF Vasan, Ramachandran S.
MacRae, Calum A.
TI A Dream, a Journey, and a Promise The Inauguration of Circulation:
Cardiovascular Genetics
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Editorial Material
C1 [Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01701 USA.
Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01701 USA.
EM vasan@bu.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD OCT
PY 2008
VL 1
IS 1
BP 1
EP 2
DI 10.1161/CIRCGENETICS.108.813352
PG 2
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA V11AF
UT WOS:000207503800001
PM 20031535
ER
PT J
AU Musunuru, K
Kathiresan, S
AF Musunuru, Kiran
Kathiresan, Sekar
TI HapMap and Mapping Genes for Cardiovascular Disease
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE cardiovascular diseases; genes; mapping
C1 [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Musunuru, Kiran; Kathiresan, Sekar] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Musunuru, Kiran; Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA.
RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA.
EM skathiresan@partners.org
FU NHLBI NIH HHS [K23 HL083102-02, K23 HL083102]
NR 32
TC 9
Z9 10
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD OCT
PY 2008
VL 1
IS 1
BP 66
EP 71
DI 10.1161/CIRCGENETICS.108.813675
PG 6
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA V11AF
UT WOS:000207503800011
PM 20031544
ER
PT J
AU Long, AA
Camargo, CA
AF Long, A. A.
Camargo, C. A., Jr.
TI Current practice of venom immunotherapy in the UK
SO CLINICAL AND EXPERIMENTAL ALLERGY
LA English
DT Editorial Material
ID STINGING INSECT HYPERSENSITIVITY; ANAPHYLAXIS; ALLERGY
C1 [Long, A. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
[Camargo, C. A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Long, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol, Cox 201,55 Fruit St, Boston, MA 02114 USA.
EM aalong@mgh.harvard.edu
NR 15
TC 0
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-7894
EI 1365-2222
J9 CLIN EXP ALLERGY
JI Clin. Exp. Allergy
PD OCT
PY 2008
VL 38
IS 10
BP 1576
EP 1578
DI 10.1111/j.1365-2222.2008.03077.x
PG 3
WC Allergy; Immunology
SC Allergy; Immunology
GA 356RS
UT WOS:000259795900003
PM 18665844
ER
PT J
AU Maine, GT
Edwards, M
Haverstick, DM
Sluss, P
Young, J
Schmidt, E
Kettlety, T
AF Maine, G. T.
Edwards, M.
Haverstick, D. M.
Sluss, P.
Young, J.
Schmidt, E.
Kettlety, T.
TI Analytical evaluation of the Abbott ARCHITECT cyclosporine assay in
comparison to LC/MS/MS and Abbott TDX/FLX
SO CLINICAL BIOCHEMISTRY
LA English
DT Meeting Abstract
C1 [Maine, G. T.] Abbott Diagnost, Abbott Pk, IL USA.
[Edwards, M.; Haverstick, D. M.] Univ Virginia Hlth Syst, Charlottesville, VA USA.
[Sluss, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Young, J.; Schmidt, E.; Kettlety, T.] Fujirebio Diagnost, Malvern, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0009-9120
J9 CLIN BIOCHEM
JI Clin. Biochem.
PD OCT
PY 2008
VL 41
IS 14-15
MA 129
BP 1274
EP 1274
DI 10.1016/j.clinbiochem.2008.08.031
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 366MT
UT WOS:000260486900053
ER
PT J
AU Goss, PE
Muss, HB
Ingle, JN
Whelan, TJ
Wu, M
AF Goss, Paul E.
Muss, Hyman B.
Ingle, James N.
Whelan, Timothy J.
Wu, Melinda
TI Extended Adjuvant Endocrine Therapy in Breast Cancer: Current Status and
Future Directions
SO CLINICAL BREAST CANCER
LA English
DT Review
DE Anastrozole; Aromatase inhibitors; Hormone receptor; Letrozole;
Tamoxifen
ID QUALITY-OF-LIFE; PLACEBO-CONTROLLED TRIAL; LETROZOLE VS. PLACEBO;
TO-TREAT ANALYSIS; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; NCICCTG
MA.17; HORMONAL-THERAPY; UPDATED FINDINGS; ATAC ARIMIDEX
AB Women with hormone receptor-positive breast cancer have traditionally been treated with 5 years of adjuvant tamoxifen to reduce their risk of subsequent recurrent disease. Among those who experience subsequent disease recurrence, the majority do so after 5 years, suggesting that longer durations of endocrine therapy might be beneficial. Two options tested include longer tamoxifen and, in postmenopausal women, a switch to an aromatase inhibitor (AI). In the National Cancer Institute of Canada Cooperative Trials Group MA.17 trial, we tested the Al letrozole given to postmenopausal women for 5 years after tamoxifen as extended adjuvant therapy because of its efficacy in patients with advanced breast cancer in progression on previous tamoxifen. The first interim analysis (median, 2.4 patient years) showed substantial benefits from letrozole, and all patients were unblinded and offered the option of letrozole. Despite two thirds of the patients crossing over to letrozole, an intent-to-treat analysis at 54 months' follow-up continued to demonstrate the strong beneficial effect of extended adjuvant letrozole. Furthermore, significant benefit was demonstrated among patients who had been randomized to placebo but elected to take letrozole after a prolonged washout from previous tamoxifen (late extended adjuvant therapy). A trial examining the merits of > 5 years of treatment with an Al, MA.17R, is ongoing, as are a number of other trials of duration of therapy. This article reviews results from MA.17 and the design of these trials of duration.
C1 [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Goss, Paul E.] Harvard Univ, Sch Med, Boston, MA USA.
[Muss, Hyman B.] Univ Vermont, Burlington, VT 05405 USA.
[Ingle, James N.] Mayo Clin, Div Med Oncol, Rochester, MN USA.
[Whelan, Timothy J.] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON L8S 4L8, Canada.
[Wu, Melinda] Univ Toronto, Toronto, ON M5S 1A1, Canada.
RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH-302, Boston, MA 02114 USA.
EM pgoss@partners.org
RI Whelan, Timothy/D-3185-2017
NR 49
TC 25
Z9 25
U1 0
U2 2
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1526-8209
J9 CLIN BREAST CANCER
JI Clin. Breast Cancer
PD OCT
PY 2008
VL 8
IS 5
BP 411
EP 417
DI 10.3816/CBC.2008.n.049
PG 7
WC Oncology
SC Oncology
GA 365KW
UT WOS:000260406300004
PM 18952554
ER
PT J
AU Toschi, L
Janne, PA
AF Toschi, Luca
Janne, Pasi A.
TI Single-Agent and Combination Therapeutic Strategies to Inhibit
Hepatocyte Growth Factor/MET Signaling in Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SMALL-MOLECULE INHIBITOR; CELL LUNG-CANCER; RECEPTOR TYROSINE KINASE;
SUPPRESSES TUMOR-GROWTH; FACTOR SCATTER FACTOR; C-MET INHIBITOR;
COLORECTAL-CANCER; GASTRIC-CANCER; OVARIAN-CANCER; IN-VIVO
AB Receptor tyrosine kinases are often aberrantly activated in human malignancies and contribute to cancer development and progression. Specific receptor tyrosine kinase inhibitors have been shown to be clinically effective therapies in subsets of cancer patients with either hematologic or solid tumors. Activation of the hepatocyte growth factor (HGF)/MET signaling pathway has been found to play a critical role in oncogenesis, cancer metastasis, and drug resistance. These observations have led to the development of agents that can effectively inhibit HGF/MET signaling through direct inhibition of the receptor (anti-MET antibodies), through inactivation of its ligand HGF (AMG102, L2G7), by interfering with HGF binding to MET (NK4), or by inhibiting MET kinase activity (PHA-665752 and SU11274). Moreover, the combination of anti-MET therapeutic agents with either signal transduction inhibitors (ERBB family or mTOR inhibitors) or with cytotoxic chemotherapy has been evaluated in preclinical models. These studies provide insight into the rational development of combination therapeutic strategies that can be evaluated in clinical trials. This review will discuss different strategies of MET inhibition with a specific focus on combination therapeutic approaches.
C1 [Toschi, Luca; Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Toschi, Luca; Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Janne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Janne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA.
[Toschi, Luca] Ist Ricovero & Cura Carattere Sci, Ist Clin Humanitas, Dept Hematol Oncol, Rozzano, Italy.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820,44 Binney St, Boston, MA 02115 USA.
EM pjanne@partners.org
FU American Cancer Society [RSG-06-102-01-CCE]; Hazel and Sam Bellin
Research Fund for Thoracic Oncology
FX American Cancer Society grant RSG-06-102-01-CCE (P.A. Janne) and the
Hazel and Sam Bellin Research Fund for Thoracic Oncology (P.A. Janne).
NR 71
TC 67
Z9 72
U1 0
U2 0
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 OCT 1
PY 2008
VL 14
IS 19
BP 5941
EP 5946
DI 10.1158/1078-0432.CCR-08-0071
PG 6
WC Oncology
SC Oncology
GA 361QP
UT WOS:000260142500002
PM 18829470
ER
PT J
AU Ansen, S
Butler, MO
Berezovskaya, A
Murray, AP
Stevenson, K
Nadler, LM
Hirano, N
AF Ansen, Sascha
Butler, Marcus O.
Berezovskaya, Alla
Murray, Andrew P.
Stevenson, Kristen
Nadler, Lee M.
Hirano, Naoto
TI Dissociation of Its Opposing Immunologic Effects Is Critical for the
Optimization of Antitumor CD8(+) T-Cell Responses Induced by Interleukin
21
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ANTIGEN-PRESENTING CELLS; TUMOR-ASSOCIATED ANTIGEN;
CANCER-IMMUNOTHERAPY; DENDRITIC CELL; REGULATORY CELLS; IL-21; THERAPY;
MEMORY; GENERATION; EXPANSION
AB Purpose: Interleukin 21 (IL-21) is a promising new cytokine, which is undergoing clinical testing as an anticancer agent. Although IL-21 provides potent stimulation of CD8(+) T cells, it has also been suggested that IL-21 is immunosuppressive by counteracting the maturation of dendritic cells. The dissociation of these two opposing effects may enhance the utility of IL-21 as an immunotherapeutic. In this study, we used a cell-based artificial antigen-presenting cell (aAPC) lacking a functional IL-21 receptor (IL-21R) to investigate the immunostimulatory properties of IL-21.
Experimental Design: The immunosuppressive activity of IL-21 was studied using human IL-21R(+) dendritic cells. Antigen-specific CD8(+) T cells stimulated with human cell - based IL-21R(-) aAPC were used to isolate the T-cell immunostimulatory effects of IL-21. The functional outcomes, including phenotype, cytokine production, proliferation, and cytotoxicity were evaluated.
Results: IL-21 limits the immune response by maintaining immunologically immature dendritic cells. However, stimulation of CD8(+) T cells with IL-21R- aAPC, which secrete IL-21, results in significant expansion. Although priming in the presence of IL-21 temporarily modulated the T-cell phenotype, chronic stimulation abrogated these differences. Importantly, exposure to IL-21 during restimulation promoted the enrichment and expansion of antigen-specific CD8(+) T cells that maintained IL-2 secretion and gained enhanced IFN-gamma secretion. Tumor antigen-specific CTL generated in the presence of IL-21 recognized tumor cells efficiently, demonstrating potent effector functions.
Conclusions: IL-21 induces opposing effects on antigen-presenting cells and CD8(+) T cells. Strategic application of IL-21 is required to induce optimal clinical effects and may enable the generation of large numbers of highly avid tumor-specific CTL for adoptive immunotherapy.
C1 [Ansen, Sascha; Butler, Marcus O.; Berezovskaya, Alla; Murray, Andrew P.; Nadler, Lee M.; Hirano, Naoto] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Stevenson, Kristen] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Ansen, Sascha; Butler, Marcus O.; Nadler, Lee M.; Hirano, Naoto] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Ansen, Sascha; Butler, Marcus O.; Stevenson, Kristen; Nadler, Lee M.; Hirano, Naoto] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Hirano, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM Naoto_-Hirano@dfci.harvard.edu
FU Dr. Mildred Scheel Stiftung der Deutschen Krebshilfe; NIH [CA87720,
CA92625, HL54785, CA129240]; Cancer Research Institute
FX Dr. Mildred Scheel Stiftung der Deutschen Krebshilfe (S. Ansen); NIH
grants CA87720 (M.D. Butler), CA92625 (L.M. Nadler), HL54785 (N.
Hirano), and CA129240 (N. Hirano); and Cancer Research Institute grant
(L.M. Nadler).
NR 48
TC 15
Z9 15
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 OCT 1
PY 2008
VL 14
IS 19
BP 6125
EP 6136
DI 10.1158/1078-0432.CCR-08-1146
PG 12
WC Oncology
SC Oncology
GA 361QP
UT WOS:000260142500024
PM 18829491
ER
PT J
AU Arteaga, CL
O'Neill, A
Moulder, SL
Pins, M
Sparano, JA
Sledge, GW
Davidson, NE
AF Arteaga, Carlos L.
O'Neill, Anne
Moulder, Stacy L.
Pins, Michael
Sparano, Joseph A.
Sledge, George W.
Davidson, Nancy E.
TI A Phase I-II Study of Combined Blockade of the ErbB Receptor Network
with Trastuzumab and Gefitinib in Patients with HER2
(ErbB2)-Overexpressing Metastatic Breast Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER;
DIMERIZATION INHIBITOR; ZD1839 IRESSA; MONOCLONAL-ANTIBODY; ADJUVANT
CHEMOTHERAPY; NEGATIVE PHENOTYPE; DOWN-REGULATION; SINGLE-AGENT
AB Purpose: To determine the safety, and efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in combination with trastuzumab in patients with metastatic HER2-positive metastatic breast cancer.
Experimental Design: Patients with HER2-overexpressing breast cancer were treated with trastuzumab 2 mg/kg/week and gefitinib 250 to 500 mg/day. The primary end point of the study was to increase the proportion progression-free from 50% to 65% at 6 months in chemotherapynaive patients and from 50% to 70% at 3 months in patients previously treated with chemotherapy in the metastatic setting. Results: In the phase I study, all patients treated with gefitinib 500 mg/day developed grade 3 diarrhea. The phase 11 study was conducted using trastuzumab and gefitinib 250 mg/day. One patient achieved a complete response, 2 had a partial response, and 6 had stable disease for an overall response rate of 9% and a clinical benefit rate of 28% (9 of 32). Median time to progression (TTP) was 3 months (95% confidence interval, 2.3-4.1) in patients with no prior systemic therapy in the metastatic setting (n = 23). In patients treated with prior systemic therapy (n = 9), the median TTP of 5.3 months (95% confidence interval, 2.8-8.1). Overall median survival was 27 months. TTP was similar in EGFR-positive compared with EGFR-negative patients.
Conclusions: Gefitinib 250 mg/day was the maximal dose that can be safely administered with weekly trastuzumab. Interim analysis of the efficacy suggested that the combination was unlikely to result in clinical benefit compared with trastuzumab alone. These results do not support the use of this combination in patients with HER2-positive breast cancer.
C1 [Arteaga, Carlos L.] Vanderbilt Univ, Div Oncol, Med Ctr, Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN 37232 USA.
[O'Neill, Anne] Dana Farber Canc Inst, Boston, MA 02115 USA.
[O'Neill, Anne] Eastern Cooperat Oncol Grp, Boston, MA USA.
[Moulder, Stacy L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Pins, Michael] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Sparano, Joseph A.] Albert Einstein Canc Ctr, Montefiore Med Ctr, New York, NY USA.
[Sledge, George W.] Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA.
[Davidson, Nancy E.] Johns Hopkins Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Arteaga, CL (reprint author), Vanderbilt Univ, Div Oncol, Med Ctr, Vanderbilt Ingram Comprehens Canc Ctr, 2200 Pierce Ave,777 PRB, Nashville, TN 37232 USA.
EM carlos.arteaga@vanderbilt.edu
FU NCI NIH HHS [CA 21115, CA 23318, CA 66636, P30 CA 68485, P30 CA068485,
P50 CA098131, R01 CA 80195, R01 CA080195, R01 CA080195-09, U10 CA021115,
U10 CA023318, U10 CA066636]
NR 55
TC 48
Z9 49
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 OCT 1
PY 2008
VL 14
IS 19
BP 6277
EP 6283
DI 10.1158/1078-0432.CCR-08-0482
PG 7
WC Oncology
SC Oncology
GA 361QP
UT WOS:000260142500043
PM 18829509
ER
PT J
AU Christo, K
Cord, J
Mendes, N
Miller, KK
Goldstein, MA
Klibanski, A
Misra, M
AF Christo, Karla
Cord, Jennalee
Mendes, Nara
Miller, Karen K.
Goldstein, Mark A.
Klibanski, Anne
Misra, Madhusmita
TI Acylated ghrelin and leptin in adolescent athletes with amenorrhea,
eumenorrheic athletes and controls: a cross-sectional study
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID BONE-DENSITY; LUTEINIZING-HORMONE; HEALTHY ADOLESCENTS; SECRETORY
DYNAMICS; PHYSICAL-ACTIVITY; ANOREXIA-NERVOSA; PLASMA GHRELIN; WOMEN;
GIRLS; EXERCISE
AB Objectives Neuroendocrine factors may predict which athletes develop amenorrhea and which athletes remain eugonadal. Specifically, ghrelin and leptin have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that adolescent athletes with amenorrhea (AA) would have higher ghrelin and lower leptin levels than eumenorrheic athletes (EA) and would predict levels of gonadal steroids.
Design Cross-sectional
Subjects and measurements We enrolled 58 girls, 21 AA, 19 EA and 18 nonathletic controls 12-18 years old. Fasting blood was drawn for active ghrelin, leptin, E(2) and testosterone. Athletes were > 85% of ideal body weight for age based on body mass index (BMI).
Results AA girls had lower BMI than EA and controls (P = 0.003). Log ghrelin was higher in AA than in EA and controls (P < 0.0001), and remained higher after controlling for BMI Z-scores. Leptin was lower in AA than in the other groups (P < 0.0001), however, the differences did not persist after controlling for BMI Z-scores. Testosterone was lower in AA than in EA and controls (P = 0.002) and log E(2) trended lower in AA (P = 0.07). We observed inverse associations of log active ghrelin with testosterone (P = 0.01), and positive associations of leptin with testosterone and log E(2) (P = 0.02 and 0.009).
Conclusion Higher ghrelin levels, even after controlling for BMI, and lower leptin in AA compared with EA and controls, and their inverse and positive associations, respectively, with gonadal steroids suggest endocrine perturbations that may explain why hypogonadism occurs in some but not all athletes.
C1 [Christo, Karla; Cord, Jennalee; Mendes, Nara; Miller, Karen K.; Klibanski, Anne; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Christo, Karla; Cord, Jennalee; Mendes, Nara; Miller, Karen K.; Klibanski, Anne; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA.
[Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA.
[Goldstein, Mark A.] Massachusetts Gen Hosp Children, Adolescent Med Unit, Boston, MA USA.
RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02114 USA.
EM mmisra@partners.org
RI Mendes Estella, Nara/E-4682-2013; Mendes Estella, Nara/A-1469-2015
FU NIH [R01 DK 062249, K23 RR018851, P30DK040561, M01-RR-01066]
FX We would like to thank the skilled nurses of the General Clinical
Research Center (GCRC) of Massachusetts General Hospital and Ellen
Anderson and the Bionutrition team for their help in carrying out this
study. We would also like to thank Jeff Breu at MIT for running our
assays. Finally, we would like to thank our subjects, without whom this
study would not have been possible. This work was supported in part by
NIH grants R01 DK 062249, K23 RR018851, P30DK040561 and M01-RR-01066.
NR 33
TC 32
Z9 33
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD OCT
PY 2008
VL 69
IS 4
BP 628
EP 633
DI 10.1111/j.1365-2265.2008.03237.x
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 347MX
UT WOS:000259146800018
PM 18331605
ER
PT J
AU Sonnenberg, A
Rodriguez, SA
Faigel, DO
AF Sonnenberg, Amnon
Rodriguez, Sarah A.
Faigel, Douglas O.
TI Diagnostic Ascertainment of Suspicious Pancreatic Mass: A Threshold
Analysis
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
ID FINE-NEEDLE-ASPIRATION; QUALITY-OF-LIFE; ENDOSCOPIC ULTRASOUND;
COST-EFFECTIVENESS; AUTOIMMUNE PANCREATITIS; COMPUTED-TOMOGRAPHY; CYSTIC
NEOPLASMS; CANCER; PANCREATICODUODENECTOMY; EUS
AB Background & Aims: it is frequently difficult to differentiate between a benign and malignant pancreatic mass. The aim of this study was to assess the parameters that affect the decision to perform surgery on a suspicious pancreatic head lesion. Methods : A cost-benefit analysis, using decision tree and threshold analysis, accumulates costs and quality-adjusted life years in patients undergoing pancreaticoduodenectomy or expectant management. The threshold value is defined as the diagnostic probability for pancreatic cancer when the cost-benefit relationships of pancreaticoduodenectomy or expectant management are equal. Results: For a localized pancreatic head lesion, the threshold probability of cancer is 43%. Any higher probability of pancreatic cancer makes pancreaticoduodenectomy the preferred treatment option. Within a range of $20,000 to $80,000 spent on surgery, the threshold in favor of Whipple procedure remains relatively low at 40% to 65%. A reduced quality of life after surgery weighs against surgery and raises its threshold. Varying quality of life between 100% and 80% changes the threshold between 31% and 67%. The threshold also is increased in younger patients because of the potentially more dire consequences of unnecessary surgery in instances of long life expectancy. Conclusion : Even if diagnostic certainty cannot be achieved, it frequently is beneficial to perform surgery despite the risk of subjecting the occasional patient with benign pancreatic head lesion to an unnecessary pancreaticoduodenectomy.
C1 Portland VA Med Ctr, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Div Gastroenterol, 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 36
TC 4
Z9 7
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD OCT
PY 2008
VL 6
IS 10
BP 1162
EP 1166
DI 10.1016/j.cgh.2008.05.015
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 360VS
UT WOS:000260086900020
PM 18928941
ER
PT J
AU Boyd, C
Smith, MJ
Kluwe, L
Balogh, A
MacCollin, M
Plotkin, SR
AF Boyd, C.
Smith, M. J.
Kluwe, L.
Balogh, A.
MacCollin, M.
Plotkin, S. R.
TI Alterations in the SMARCB1 (INI1) tumor suppressor gene in familial
schwannomatosis
SO CLINICAL GENETICS
LA English
DT Article
DE INI1; neurofibromatosis; schwannoma; schwannomatosis; SMARCB1; tumor
suppressor gene
ID ATYPICAL TERATOID/RHABDOID TUMORS; RHABDOID PREDISPOSITION SYNDROME;
HSNF5/INI1 GENE; BRAIN-TUMORS; NEUROFIBROMATOSIS TYPE-1; MOLECULAR
ANALYSIS; GERMLINE MUTATION; NF2; PHENOTYPE; FREQUENCY
AB Schwannomatosis is a third major form of neurofibromatosis that has recently been linked to mutations in the SMARCB1 (hSnf5/INI1) tumor suppressor gene. We analyzed the coding region of SMARCB1 by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) in genomic DNA from 19 schwannomatosis kindreds. Microsatellite markers in the SMARCB1 region were developed to determine loss of heterozygosity (LOH) in associated tumors. We detected four alterations in conserved splice acceptor or donor sequences of exons 3, 4 and 6. Two alterations that likely affect splicing were seen in introns 4 and 5. An additional four alterations of unclear pathogenicity were found to segregate on the affected allele in eight families including two non-conservative missense alterations in three families. No constitutional deletions or duplications were detected by MLPA. Nine of 13 tumors examined showed partial LOH of the SMARCB1 region consistent with 'second hits.' Alterations were detected in tumors both with and without somatic NF2 gene changes. These findings support the hypothesis that SMARCB1 is a tumor suppressor for schwannomas in the context of familial disease. Further work is needed to determine its role in other multiple and single tumor syndromes.
C1 [Plotkin, S. R.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Boyd, C.; Smith, M. J.; Balogh, A.; MacCollin, M.; Plotkin, S. R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Kluwe, L.] Univ Hosp Eppendorf, Dept Maxillofacial Surg, Hamburg, Germany.
RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA.
EM splotkin@partners.org
RI Smith, Miriam/J-4001-2015
OI Smith, Miriam/0000-0002-3184-0817
FU NF, Inc; Congressionally Directed Medical Research Fund
FX We thank many patients and families who have so generously contributed
to this study, the health care providers who have coordinated their
participation and Drs Anat Stemmer-Rachamimov and Charles Roberts for
their thoughtful reading of the manuscript. Expert chart review was
provided by Ms Melanie O'Leary who is supported by NF, Inc. through the
Harvard Center for Human Genetic Research. M. M. was supported by a
grant from the Congressionally Directed Medical Research Fund.
NR 38
TC 76
Z9 76
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD OCT
PY 2008
VL 74
IS 4
BP 358
EP 366
DI 10.1111/j.1399-0004.2008.01060.x
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 349GW
UT WOS:000259270300011
PM 18647326
ER
PT J
AU Bradshaw, EM
Kent, SC
Tripuraneni, V
Orban, T
Ploegh, HL
Hafler, DA
Love, JC
AF Bradshaw, Elizabeth M.
Kent, Sally C.
Tripuraneni, Vinay
Orban, Tiharner
Ploegh, Hidde L.
Hafler, David A.
Love, J. Christopher
TI Concurrent detection of secreted products from human lymphocytes by
microengraving: Cytokines and antigen-reactive antibodies
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE human; microengraving; type 1 diabetes; single cell analysis;
autoantibodies; cytokines; proinsulin
ID MEMORY B-CELLS; CD4(+) T-CELLS; PERIPHERAL-BLOOD; AUTOANTIBODIES;
INSULIN; AUTOANTIGEN; PROFILES; DISEASE; TYPE-1; FREQUENCY
AB Cell surface determinants, cytokines and antibodies secreted by hematopoietic cells are used to classify their lineage and function. Currently available techniques are unable to elucidate multiple secreted proteins white also assigning phenotypic surface-displayed markers to the individual living cells. Here, a soft lithographic method, microengraving, was adapted for the multiplexed interrogation of populations of individual human peripheral blood mononuclear cells for secreted cytokines (IFN-gamma and IL-6), antigen-specific antibodies, and lineage-specific surface-expressed markers. Application of the method to a clinical sample from a recent-onset Type 1 diabetic subject with a positive titer of anti-insulin antibodies showed that similar to 0.58% of circulating CD19(+) B cells secreted proinsulin-reactive antibodies of the IgG isotype and 2-3% of circulating cells secreted IL-6. These data demonstrate the utility of microengraving for interrogating multiple phenotypes of single human cells concurrently and for detecting rare populations of cells by their secreted products. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Bradshaw, Elizabeth M.; Kent, Sally C.; Hafler, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, NRB,Ctr Neurol Dis,Div Mol Immunol, Boston, MA 02115 USA.
[Tripuraneni, Vinay; Love, J. Christopher] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Orban, Tiharner] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA.
[Ploegh, Hidde L.] MIT, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA.
[Ploegh, Hidde L.; Hafler, David A.] MIT & Harvard, Broad Inst, Cambridge, MA 02139 USA.
RP Hafler, DA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, NRB,Ctr Neurol Dis,Div Mol Immunol, Room 641,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM dhafler@rics.bwh.harvard.edu; clove@mit.edu
FU NIH Autoimmunity Prevention Center; Broad Institute of MIT; Harvard;
Juvenile Diabetes Research Foundation International [NIH Al651003];
National Institutes of Health [R01 Al39229, R01 Al44447, P01 Al39671];
Jacob Javits Merit Award [NS2427]; National Institute of Neurological
Disorders and Stroke; National Multiple Sclerosis Society
FX Support for these studies was provided by grants from the NIH
Autoimmunity Prevention Center and the Broad Institute of MIT and
Harvard (H.L.P. and J.C.L.), S.C.K. (Juvenile Diabetes Research
Foundation International), E.M.B. (NIH Al651003), National Institutes of
Health Grants R01 Al39229, R01 Al44447, and P01 Al39671 (to D.A.H.); and
a Jacob Javits Merit Award (NS2427 to D.A.H.) from the National
Institute of Neurological Disorders and Stroke and a grant from the
National Multiple Sclerosis Society. The authors thank Khadir Raddassi
for helpful discussions.
NR 32
TC 38
Z9 38
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD OCT
PY 2008
VL 129
IS 1
BP 10
EP 18
DI 10.1016/j.clim.2008.06.009
PG 9
WC Immunology
SC Immunology
GA 351XM
UT WOS:000259459200003
PM 18675591
ER
PT J
AU Bradshaw, S
Zheng, WJ
Tsoi, LC
Gilkeson, G
Zhang, XK
AF Bradshaw, Sarah
Zheng, W. Jim
Tsoi, Lam C.
Gilkeson, Gary
Zhang, Xian K.
TI A role for Fli-1 in B cell proliferation: Implications for SLE
pathogenesis
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE B cell; BCR; Fli-1; IL12; NFAT; proliferation; SLE; TNF beta; TLR
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; BLOOD
MONONUCLEAR-CELLS; MRL/MP-LPR/LPR MICE; TOLL-LIKE RECEPTORS;
TRANSCRIPTION FACTOR; ETS FAMILY; PERIPHERAL-BLOOD; RENAL-DISEASE;
SOLUBLE CD23
AB Transgenic overexpression of Fli-1 in normal mice leads to SLE-like disease and increased expression was reported in SLE-affected human and murine lymphocytes. Reducing Fli-1 expression in MRL/lpr mice decreased antibody production, proteinuria, renal pathology, and mortality. Compared to those with wild-type expression of Fli-1, we report here that proliferative responses of Fli-1-deficient naive B cells to several mitogens were reduced in lupus-prone and control mice. Expression of mitogen receptors, including BCR, TLR4, and TLR9, was not significantly impacted in Fli-1-deficient naive B cells. IL12a transcripts were upregulated and NFAT transcripts were downregulated in Fli-1-deficient MRL/lpr B cells. These results demonstrate that Fli-1 deficiency affects B cell proliferative responses to mitogens, independent of BCR and TLR expression. IL12a and NFAT, known to influence proliferation, were identified as potential mediators of this effect. This may be a mechanism by which overexpression of Fli-1 contributes to B cell hyperactivity and subsequent SLE pathogenesis. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Bradshaw, Sarah; Gilkeson, Gary; Zhang, Xian K.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Zheng, W. Jim; Tsoi, Lam C.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA.
[Gilkeson, Gary] Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA.
RP Bradshaw, S (reprint author), 96 Jonathan Lucas St,Suite 912,MSC 637, Charleston, SC 29425 USA.
EM gallant@musc.edu
OI Tsoi, Lam Cheung/0000-0003-1627-5722
FU NIAMS NIH HHS [K01 AR051385, R03 AR054546, K01 AR051385-01A1, R03
AR054546-01]
NR 86
TC 15
Z9 16
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 1521-6616
EI 1521-7035
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD OCT
PY 2008
VL 129
IS 1
BP 19
EP 30
DI 10.1016/j.clim.2008.05.010
PG 12
WC Immunology
SC Immunology
GA 351XM
UT WOS:000259459200004
PM 18692443
ER
PT J
AU Musher, DM
AF Musher, Daniel M.
TI Neurosyphilis: Diagnosis and response to treatment
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CEREBROSPINAL-FLUID; SYPHILIS; PENICILLIN
C1 [Musher, Daniel M.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA.
[Musher, Daniel M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Musher, Daniel M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
RP Musher, DM (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, 2002 Holcombe Blvd,Rm 4B-370, Houston, TX 77030 USA.
EM daniel.musher@med.va.gov
NR 16
TC 3
Z9 5
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD OCT 1
PY 2008
VL 47
IS 7
BP 900
EP 902
DI 10.1086/591535
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 345ZO
UT WOS:000259038400006
PM 18715158
ER
PT J
AU Asmal, M
Factor, RE
Walensky, RP
AF Asmal, Mohammed
Factor, Rachel E.
Walensky, Rochelle P.
TI An HIV-infected man with an upset stomach
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID EXTRACEREBRAL TOXOPLASMOSIS; PATIENT; GONDII
C1 [Asmal, Mohammed; Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA.
[Factor, Rachel E.] Brigham & Womens Hosp, Div Anat Pathol, Boston, MA 02115 USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis & Gen Med, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA.
RP Asmal, M (reprint author), 41 Ave Louis Pasteur, Boston, MA 02115 USA.
EM masmal@partners.org
NR 7
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD OCT 1
PY 2008
VL 47
IS 7
BP 935
EP +
DI 10.1086/591694
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 345ZO
UT WOS:000259038400014
PM 18778229
ER
PT J
AU Souza, FF
Israel, DA
AF Souza, Frederico F.
Israel, David A.
TI PET/CT Appearance of Non-Hodgkin Lymphoma of the Vermiform Appendix
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Editorial Material
DE appendix; F-18FDG PET/CT; lymphoma
ID PATHOLOGICAL CORRELATION; MALIGNANT-LYMPHOMA; CT
AB We present a case of a 53-year-old man with large B-cell non-Hodgkin lymphoma that infiltrated the vermiform appendix. The patient underwent F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT scan) for staging, which demonstrated intense abnormal tracer uptake in the appendix. After 2 cycles of chemotherapy (R-CHOP), a follow-up PET/CT scan demonstrated complete resolution of the abnormal tracer uptake within the appendix. This case highlights the contribution of F-18 FDG PET/CT in the diagnosis and post-therapy evaluation of this involvement.
C1 [Souza, Frederico F.; Israel, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02215 USA.
RP Souza, FF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02215 USA.
EM ffsouza@partners.org
NR 9
TC 8
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-9762
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD OCT
PY 2008
VL 33
IS 10
BP 694
EP 696
DI 10.1097/RLU.0b013e318184c8dc
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 357UE
UT WOS:000259871300009
PM 18806571
ER
PT J
AU Sung, AD
Anderson, ME
Zurakowski, D
Hornicek, FJ
Gebhardt, MC
AF Sung, Anthony D.
Anderson, Megan E.
Zurakowski, David
Hornicek, Francis J.
Gebhardt, Mark C.
TI Unicameral bone cyst - A retrospective study of three surgical
treatments
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID LONG BONES; FOLLOW-UP; METHYLPREDNISOLONE ACETATE; SUBTOTAL RESECTION;
STEROID INJECTION; MARROW; PATHOGENESIS; MATRIX; ALLOGRAFT; CHILDREN
AB Between 1979 and 2004, 167 patients younger than 20 years were treated surgically for humeral or femoral unicameral bone cysts with either injection of corticosteroids (steroids), curettage plus bone grafting (curettage), or a combination injection of steroids, demineralized bone matrix, and bone marrow aspirate (SDB) at Children's Hospital of Boston and Massachusetts General Hospital (mean followup, 7.3 years; range, 1 month-27 years). Outcomes included treatment failure (defined clinically as subsequent pathologic fracture or need for retreatment to prevent pathologic fracture) and complications. Information was obtained from medical records and by telephone questionnaire. After one treatment, 84% of cysts treated with steroids experienced failed treatment versus 64% with curettage and 50% with SDB. For unicameral bone cysts requiring retreatment (regardless of first treatment), 76% retreated with steroids had failed treatment versus 63% with curettage and 71% with SDB. Curettage was associated with the lowest rate of posttreatment pathologic fractures and highest rate of pain and other complications. Multivariate logistic regression indicated treatment with steroids alone and younger age were independent predictors of failure. We believe SDB is a reasonable first treatment for unicameral bone cysts in the humerus and femur in patients younger than 20 years, being less invasive yet comparable to curettage in preventing recurrence.
C1 [Sung, Anthony D.] Harvard Univ, Sch Med, Boston, MA USA.
[Anderson, Megan E.; Zurakowski, David; Gebhardt, Mark C.] Childrens Hosp, Boston, MA 02115 USA.
[Hornicek, Francis J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Anderson, ME (reprint author), 330 Brookline Ave, Boston, MA 02215 USA.
EM manders6@bidmc.harvard.edu
NR 42
TC 30
Z9 32
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD OCT
PY 2008
VL 466
IS 10
BP 2519
EP 2526
DI 10.1007/s11999-008-0407-0
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 347KX
UT WOS:000259141600030
PM 18679761
ER
PT J
AU Spencer, TJ
AF Spencer, Thomas J.
TI ADULT ADHD: DIVERSION AND MISUSE OF MEDICATIONS
SO CNS SPECTRUMS
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; SUBSTANCE USE DISORDERS; COCAINE ABUSERS; PRESCRIPTION
STIMULANTS; CONDUCT DISORDER; PREVALENCE; ADOLESCENTS; METHYLPHENIDATE;
SMOKING
C1 [Spencer, Thomas J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Spencer, Thomas J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA.
RP Spencer, TJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
NR 28
TC 0
Z9 0
U1 0
U2 0
PU M B L COMMUNICATIONS, INC
PI NEW YORK
PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA
SN 1092-8529
J9 CNS SPECTRUMS
JI CNS Spectr.
PD OCT
PY 2008
VL 13
IS 10
SU 15
BP 9
EP 13
PG 5
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 371HD
UT WOS:000260821500003
PM 18955949
ER
PT J
AU Sano, M
AF Sano, Mary
TI NON-AMYLOID APPROACHES TO NEUROPROTECTION
SO CNS SPECTRUMS
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; MODERATE ALZHEIMERS-DISEASE; MILD COGNITIVE
IMPAIRMENT; GLOBAL FUNCTION; DOUBLE-BLIND; PLACEBO; ROFECOXIB;
ATORVASTATIN; INDIVIDUALS; DONEPEZIL
C1 [Sano, Mary] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA.
[Sano, Mary] James J Peters VAMC, Bronx, NY USA.
[Sano, Mary] Bristol Myers Squibb Co, New York, NY 10154 USA.
Eisai & Co Ltd, Teaneck, NJ 07666 USA.
[Sano, Mary] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA.
[Sano, Mary] Pfizer, New York, NY USA.
RP Sano, M (reprint author), Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA.
NR 17
TC 0
Z9 0
U1 0
U2 0
PU M B L COMMUNICATIONS, INC
PI NEW YORK
PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA
SN 1092-8529
J9 CNS SPECTRUMS
JI CNS Spectr.
PD OCT
PY 2008
VL 13
IS 10
SU 16
BP 42
EP 44
PG 3
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 364ZF
UT WOS:000260373900013
PM 18955963
ER
PT J
AU Linden, M
Golier, J
AF Linden, Maria
Golier, Julia
TI Challenges in the Implementation of Manualized Psychotherapy in
Combat-related PTSD
SO CNS SPECTRUMS
LA English
DT Article
C1 [Linden, Maria; Golier, Julia] Mt Sinai Sch Med, New York, NY 10029 USA.
[Golier, Julia] Bronx Vet Adm Med Ctr, PTSD Clin, Dept Psychiat, New York, NY USA.
RP Linden, M (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
EM maria.linden@mssm.edu
NR 4
TC 2
Z9 2
U1 0
U2 0
PU M B L COMMUNICATIONS, INC
PI NEW YORK
PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA
SN 1092-8529
J9 CNS SPECTRUMS
JI CNS Spectr.
PD OCT
PY 2008
VL 13
IS 10
BP 872
EP 877
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 363KT
UT WOS:000260266900008
PM 18955942
ER
PT J
AU Smith, FA
Wittmann, CW
Stern, TA
AF Smith, Felicia A.
Wittmann, Curtis W.
Stern, Theodore A.
TI Medical Complications of Psychiatric Treatment
SO CRITICAL CARE CLINICS
LA English
DT Article
ID SEROTONIN-REUPTAKE INHIBITORS; ATYPICAL ANTIPSYCHOTIC-DRUGS; NEUROLEPTIC
MALIGNANT SYNDROME; PLACEBO-CONTROLLED TRIALS; PULMONARY-EMBOLISM;
PSYCHOTROPIC-DRUGS; DIABETES-MELLITUS; CEREBRAL VASOCONSTRICTION;
SCHIZOPHRENIA-PATIENTS; PLACENTAL PASSAGE
AB Psychiatric medications are frequently an essential component of care for critically ill patients. Their use may lead to medical complications, however, as a result of (1) direct toxicity from psychotropic medications, (2) drug-drug interactions, or (3) intoxication or withdrawal states. These complications may be a nuisance (eg, dry mouth and nausea) or serious and life-threatening (eg, neuroleptic malignant syndrome and cardiac arrhythmias). This article addresses the most important medical complications (organized by organ systems) of psychiatric treatment.
C1 [Smith, Felicia A.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Avery D Weisman MD Psychiat Consultat Serv, Boston, MA 02114 USA.
[Smith, Felicia A.; Wittmann, Curtis W.; Stern, Theodore A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Smith, FA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Avery D Weisman MD Psychiat Consultat Serv, Warren 605,55 Fruit St, Boston, MA 02114 USA.
EM fsmith2@partners.org
NR 77
TC 5
Z9 5
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0749-0704
J9 CRIT CARE CLIN
JI Crit. Care Clin.
PD OCT
PY 2008
VL 24
IS 4
BP 635
EP +
DI 10.1016/j.ccc.2008.05.004
PG 23
WC Critical Care Medicine
SC General & Internal Medicine
GA 371WI
UT WOS:000260863000002
PM 18929938
ER
PT J
AU Robertson, TE
Mann, HJ
Hyzy, R
Rogers, A
Douglas, I
Waxman, AB
Weinert, C
Alapat, P
Guntupalli, KK
Buchman, TG
AF Robertson, T. Elizabeth
Mann, Henry J.
Hyzy, Robert
Rogers, Angela
Douglas, Ivor
Waxman, Aaron B.
Weinert, Craig
Alapat, Philip
Guntupalli, Kalpalatha K.
Buchman, Timothy G.
CA Partnership Excellence Critical Ca
TI Multicenter implementation of a consensus-developed, evidence-based,
spontaneous breathing trial protocol
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE respirator; acute respiratory distress syndrome artificial; ventilator
weaning; practice guideline; interdisciplinary communication;
professional practice; guideline adherence
ID INTENSIVE-CARE-UNIT; MANAGED CLINICAL NETWORK; CRITICALLY-ILL PATIENTS;
MECHANICAL VENTILATION; HEALTH-CARE; GUIDELINES; INTERVENTION; DURATION;
QUALITY; PNEUMONIA
AB Objective: Evidence-based practice recommendations abound, but implementation is often unstructured and poorly audited. We assessed the ability of a peer network to implement an evidence-based best practice protocol and to measure patient outcomes.
Design: Consensus definition of spontaneous breathing trial followed by implementation in eight academic medical centers.
Setting: Six medical, two surgical, and two combined medical/surgical adult intensive care units among eight academic medical centers.
Study Population: Patients initiating mechanical ventilation through an endotracheal tube during a 12-wk interval formed the study population.
Interventions: Adoption and implementation of a common spontaneous breathing trial protocol across multiple intensive care units.
Measurements and Main Results: Seven hundred five patients had 3,486 safety screens for conducting a spontaneous breathing trial; 2072 (59%) patients failed the safety screen. Another 379 (11%) patients failed a 2-min tolerance screen and 1,122 (34%) patients had a full 30-120 min spontaneous breathing trial performed. Seventy percent of eligible patients were enrolled. Only 55% of passing spontaneous breathing trials resulted in liberation from mechanical ventilatory support before another spontaneous breathing trial was performed.
Conclusions: Peer networks can be effective in promoting and implementing evidence-based best practices. Implementation of a best practice (spontaneous breathing trial) may be necessary for, but by itself insufficient to achieve, consistent and timely liberation from ventilator support.
C1 [Robertson, T. Elizabeth; Buchman, Timothy G.] Washington Univ, Dept Surg, St Louis, MO 63130 USA.
[Mann, Henry J.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA.
[Hyzy, Robert] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Rogers, Angela; Waxman, Aaron B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Douglas, Ivor] Denver Hlth Med Ctr, Denver, CO USA.
[Weinert, Craig] Univ Minnesota, Dept Med, Div Pulm Allergy & Crit Care, Minneapolis, MN USA.
[Alapat, Philip; Guntupalli, Kalpalatha K.] Baylor Coll Med, Dept Med, Div Pulm & Crit Care, Houston, TX 77030 USA.
RP Robertson, TE (reprint author), Washington Univ, Dept Surg, St Louis, MO 63130 USA.
EM robertsont@wudosis.wustl.edu
OI Douglas, Ivor/0000-0002-4541-1431; Buchman, Timothy/0000-0001-7350-5921
FU James S. McDonnell Foundation; NIGMS [GM008795]
FX Supported in part by a grant from the James S. McDonnell Foundation and
NIGMS postdoctoral fellowship, GM008795 (to TER).
NR 38
TC 16
Z9 16
U1 0
U2 0
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 OCT
PY 2008
VL 36
IS 10
BP 2753
EP 2762
DI 10.1097/CCM.0b013e3181872833
PG 10
WC Critical Care Medicine
SC General & Internal Medicine
GA 356GF
UT WOS:000259766000006
PM 18828193
ER
PT J
AU Hamdy, O
Carver, C
AF Hamdy, Osama
Carver, Catherine
TI The Why WAIT Program: Improving Clinical Outcomes Through Weight
Management in Type 2 Diabetes
SO CURRENT DIABETES REPORTS
LA English
DT Article
ID LIFE-STYLE MODIFICATION; INSULIN-RESISTANCE; GLYCEMIC CONTROL;
OBESE-PATIENTS; RENAL-FUNCTION; LIVER-DISEASE; HIGH-PROTEIN; FOLLOW-UP;
LOSS DIET; ADULTS
AB Targeting body weight, as an alternative model to targeting hemoglobin A(1c), is emerging as a viable and potentially cost-effective approach to diabetes management in clinical practice. Why WAIT (Weight Achievement and Intensive Treatment) is a 12-week multidisciplinary program for weight control and intensive diabetes management specifically designed for application in routine diabetes practice. The program, which is generally covered by insurance, is followed by continuous support aimed at long-term maintenance of weight loss and diabetes control. This model was effective in improving key metabolic abnormalities observed in diabetic patients. Eighty-two percent of participants achieved the target hemoglobin A(1c) of less than 7% on less diabetes medications. The achieved weight reduction after 12 weeks of intervention was maintained for an additional year. Future dissemination of this intervention model in routine clinical practice may require wider endorsement by third-party payers and support of governmental health care agencies to halt the progression of the epidemic of obesity and diabetes in the United States.
C1 [Hamdy, Osama] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Hamdy, O (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM Osama.Hamdy@joslin.harvard.edu
NR 32
TC 29
Z9 29
U1 0
U2 3
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 OCT
PY 2008
VL 8
IS 5
BP 413
EP 420
DI 10.1007/s11892-008-0071-5
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 375GH
UT WOS:000261101600011
PM 18778592
ER
PT J
AU Carman, CV
Springer, TA
AF Carman, Christopher V.
Springer, Timothy A.
TI Trans-cellular migration: cell-cell contacts get intimate
SO CURRENT OPINION IN CELL BIOLOGY
LA English
DT Article
ID ABSORBING LYMPHATIC VESSEL; BLOOD-BRAIN-BARRIER; ENDOTHELIAL-CELLS;
TRANSCELLULAR MIGRATION; PHENOTYPIC HETEROGENEITY; TRANSENDOTHELIAL
PASSAGE; INFLAMMATORY RESPONSE; VASCULAR ENDOTHELIUM; PEYERS-PATCHES;
TUMOR-CELL
AB Trans-cellular migration, the movement of one cell directly through another, seems an unlikely, counterintuitive, and even bizarre process. Trans-cellular migration has been reported for nearly half a century in leukocyte transendothelial migration in vivo, but is not well enough accepted to widely feature in textbook accounts of diapedesis. Recently, the first in vitro and additional in vivo observations of trans-cellular diapedesis have been reported. Mechanisms by which this occurs are just beginning to be elucidated and point to podosome-like protrusive activities in leukocytes and specific fusogenic functions in endothelial cells. Emerging evidence for a quantitatively significant contribution of trans-cellular migration to leukocyte trafficking in increasingly diverse settings suggests that this phenomenon represents an important and physiologic cell biological process.
C1 [Carman, Christopher V.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA.
RP Carman, CV (reprint author), Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
EM ccarman@bidmc.harvard.edu; springeroffice@idi.harvard.edu
RI Carman, Christopher/L-8108-2016
OI Carman, Christopher/0000-0001-7358-2548
FU Arthritis Foundation; NIH
FX We would like to thank Ann Dvorak for her comments and discussion and
both Ann Dvorak and Tracey Sciuto for providing electron micrographs for
Figure 1. This work was supported by grants from the Arthritis
Foundation (CVC) and the NIH (TAS).
NR 65
TC 104
Z9 107
U1 0
U2 11
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0955-0674
J9 CURR OPIN CELL BIOL
JI Curr. Opin. Cell Biol.
PD OCT
PY 2008
VL 20
IS 5
BP 533
EP 540
DI 10.1016/j.ceb.2008.05.007
PG 8
WC Cell Biology
SC Cell Biology
GA 358TJ
UT WOS:000259940100008
PM 18595683
ER
PT J
AU Traum, AZ
Ko, DSC
Kawai, T
AF Traum, Avram Z.
Ko, Dicken S. C.
Kawai, Tatsuo
TI The potential for tolerance in pediatric renal transplantation
SO CURRENT OPINION IN ORGAN TRANSPLANTATION
LA English
DT Review
DE adolescent; kidney transplantation; pediatric; tolerance
ID TOTAL-LYMPHOID IRRADIATION; DONOR BONE-MARROW; ALLOGRAFT TOLERANCE;
LYMPHOHEMATOPOIETIC CHIMERISM; KIDNEY-TRANSPLANTATION; CARDIOVASCULAR
RISK; STEROID WITHDRAWAL; MULTIPLE-MYELOMA; ACUTE REJECTION; RECIPIENTS
AB Purpose of review
Immune tolerance has remained the Holy Grail in transplantation since the first kidney transplantation was performed over 50 years ago. Children present unique challenges in renal transplantation because of increased infectious risks and adolescent nonadherence to the intensive medication regimen necessary for allograft function. The current review presents recent studies and approaches toward achieving tolerance in renal transplantation and the prospects for pediatric patients.
Recent findings
A number of approaches have been used toward minimization of immunosuppression in pediatric patients, but none has yet achieved true operational tolerance with maintenance of allograft function of all immunosuppression. Recent work in adult renal transplant recipients using combined kidney-bone marrow transplantation by the induction of transient mixed chimerism has allowed for full withdrawal of immunosuppression with stable long-term renal function.
Summary
On the basis of recent adult studies, the prospect of immune tolerance in pediatric renal transplantation remains hopeful and may be ready for extension to the adolescent population.
C1 [Kawai, Tatsuo] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Unit, Dept Surg,Transplant Ctr, Boston, MA 02114 USA.
[Traum, Avram Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Nephrol Unit, Boston, MA 02114 USA.
RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Unit, Dept Surg,Transplant Ctr, 55 Fruit St,White 510, Boston, MA 02114 USA.
EM tkawai@partners.org
FU National Institutes of Health [NO1-Al-15416]
FX This work was supported in part by grants from the Immune Tolerance
Network (NO1-Al-15416) of the National Institutes of Health.
NR 61
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1087-2418
J9 CURR OPIN ORGAN TRAN
JI Curr. Opin. Organ Transpl.
PD OCT
PY 2008
VL 13
IS 5
BP 489
EP 494
DI 10.1097/MOT.0b013e328310b0cd
PG 6
WC Transplantation
SC Transplantation
GA 363CN
UT WOS:000260243600003
PM 19060531
ER
PT J
AU Kotton, CN
AF Kotton, Camille Nelson
TI Update on infectious diseases in pediatric solid organ transplantation
SO CURRENT OPINION IN ORGAN TRANSPLANTATION
LA English
DT Review
DE BK virus; cytomegalovirus; infection; pediatric solid organ transplant;
vaccine/vaccination/immunization
ID ORTHOTOPIC LIVER-TRANSPLANTATION; URINARY-TRACT-INFECTION;
VARICELLA-ZOSTER-VIRUS; RENAL-TRANSPLANTATION; SINGLE-CENTER;
POLYOMAVIRUS BK; HEPATITIS-B; RECIPIENTS; CHILDREN; VACCINE
AB Purpose of review
Numerous recent advances have been made in the field of infectious diseases and pediatric solid organ transplant.
Recent findings
Although many studies contain somewhat small cohorts of individuals, when summarized together they contribute significantly to our knowledge about pediatric solid organ transplant, especially regarding risk factors for infection, management of BK virus nephropathy, the use of live viral vaccines, and consideration for rare infections as well as donor-derived infections.
Summary
In sum, these recent advances in infection in the field of pediatric solid organ transplant will help decrease infection, thus improving morbidity and mortality, as well as transplant outcomes, especially by decreasing direct (graft injury) and indirect (immune upregulation) effects on organ transplantation. This review will focus on recent advances in the field of infectious diseases in pediatric solid organ transplant by highlighting some of the most important and interesting articles in the field within the past few years.
C1 [Kotton, Camille Nelson] Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA.
[Kotton, Camille Nelson] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,Cox 5, Boston, MA 02114 USA.
EM ckotton@partners.org
NR 40
TC 4
Z9 4
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1087-2418
J9 CURR OPIN ORGAN TRAN
JI Curr. Opin. Organ Transpl.
PD OCT
PY 2008
VL 13
IS 5
BP 500
EP 505
DI 10.1097/MOT.0b013e328310b0a4
PG 6
WC Transplantation
SC Transplantation
GA 363CN
UT WOS:000260243600005
PM 19060533
ER
PT J
AU Liu, YL
Chacko, BK
Ricksecker, A
Shingarev, R
Andrews, E
Patel, RP
Lang, JD
AF Liu, Yuliang
Chacko, Balu K.
Ricksecker, Ana
Shingarev, Roman
Andrews, Eric
Patel, Rakesh P.
Lang, John D., Jr.
TI Modulatory effects of hypercapnia on in vitro and in vivo pulmonary
endothelial-neutrophil adhesive responses during inflammation
SO CYTOKINE
LA English
DT Article
DE Hypercapnia; Neutrophil; Endothelium; Adhesion molecule; Lung injury
ID RESPIRATORY-DISTRESS-SYNDROME; INDUCED LUNG INJURY; FACTOR-KAPPA-B;
MECHANICAL VENTILATION; ESCHERICHIA-COLI; GENE-EXPRESSION;
CELL-ADHESION; INTERLEUKIN-8; ACTIVATION; CYTOKINE
AB Reducing tidal volume as a part of a protective ventilation strategy may result in hypercapnia. In this study, we focused on the influence of hypercapnia on endothelial-neutrophil responses in models of inflammatory-stimulated human pulmonary microvascular endothelial cells (HMVEC) and in an animal model of lipopolysaccharide (LPS)-induced acute lung injury. Neutrophil adhesion and adhesion molecules expression and nuclear factor-kappa B (NF-kappa B) were analyzed in TNF-alpha and LPS-treated HMVEC exposed to either eucapnia or hypercapnia. In the in vivo limb, bronchoalveolar lavage fluid cell counts and differentials, adhesion molecule and chemokine expression were assessed in LPS-treated rabbits ventilated with either low tidal volume ventilation and eucapnia or hypercapnia. In both the in vitro and in vivo models, hypercapnia significantly increased neutrophil adhesion and adhesion molecule expression compared to eucapnia. Activity of NF-kappa B was significantly enhanced by hypercapnia in the in vitro experiments. IL-8 expression was greatest both in vitro and in vivo under conditions of hypercapnia and concomitant inflammation. CD11a expression was greatest in isolated human neutrophils exposed to hypercapnia + LPS. Our results demonstrate that endothelial-neutrophil responses per measurement of fundamental molecules of adhesion are significantly increased during hypercapnia and that hypercapnia mimics conditions of eucapnia + inflammation. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Liu, Yuliang; Lang, John D., Jr.] Univ Washington, Sch Med, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Ricksecker, Ana] Univ Alabama, Dept Anesthesiol, Birmingham, AL 35294 USA.
[Chacko, Balu K.; Patel, Rakesh P.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
[Shingarev, Roman; Andrews, Eric] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
RP Liu, YL (reprint author), Univ Washington, Sch Med, Dept Anesthesiol, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM yuliang6@u.washington.edu
OI Patel, Rakesh/0000-0002-1526-4303
FU National Institutes of Health [HL067982]
FX This work was supported by a National Institutes of Health Grant,
#HL067982 to John D. Lang, Jr., M.D.
NR 41
TC 14
Z9 16
U1 0
U2 0
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD OCT
PY 2008
VL 44
IS 1
BP 108
EP 117
DI 10.1016/j.cyto.2008.06.016
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 369NG
UT WOS:000260700600018
PM 18713668
ER
PT J
AU Beuling, E
Bosse, T
aan de Kerk, DJ
Piaseckyj, CM
Fujiwara, Y
Katz, SG
Orkin, SH
Grand, RJ
Krasinski, SD
AF Beuling, Eva
Bosse, Tjalling
aan de Kerk, Daniel J.
Piaseckyj, Christina M.
Fujiwara, Yuko
Katz, Samuel G.
Orkin, Stuart H.
Grand, Richard J.
Krasinski, Stephen D.
TI GATA4 mediates gene repression in the mature mouse small intestine
through interactions with friend of GATA (FOG) cofactors
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE GATA4; friend of GATA; FOG; intestinal differentiation; apical
sodium-dependent; bile acid transporter; ASBT
ID BILE-ACID TRANSPORTER; HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; TRANSCRIPTION
FACTOR GATA-1; BINDING PROTEIN GENE; ZINC-FINGER PROTEIN; PHLORHIZIN
HYDROLASE PROMOTER; HEART TUBE FORMATION; TRANSGENIC MICE; VENTRAL
MORPHOGENESIS; TARGETED MUTATION
AB GATA4, a transcription factor expressed in the proximal small intestine but not in the distal ileum, maintains proximal-distal distinctions by multiple processes involving gene repression, gene activation, and cell fate determination. Friend of GATA (FOG) is an evolutionarily conserved family of cofactors whose members physically associate with GATA factors and mediate GATA-regulated repression in multiple tissues. Using a novel, inducible, intestine-specific Gata4 knock-in model in mice, in which wild-type GATA4 is specifically inactivated in the small intestine, but a GATA4 mutant that does not bind FOG cofactors (GATA4ki) continues to be expressed, we found that ileal-specific genes were significantly induced in the proximal small intestine (P<0.01); in contrast, genes restricted to proximal small intestine and cell lineage markers were unaffected, indicating that GATA4-FOG interactions contribute specifically to the repression function of GATA4 within this organ. Fog1 mRNA displayed a proximal-distal pattern that parallels that of Gata4, and FOG1 protein was co-expressed with GATA4 in intestinal epithelia[ cells, implicating FOG] as the likely mediator of GATA4 function in the small intestine. Our data are the first to indicate FOG function and expression in the mammalian small intestine. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Piaseckyj, Christina M.; Grand, Richard J.; Krasinski, Stephen D.] Childrens Hosp, Div Gastroenterol & Nutr, Dept Med, Boston, MA 02115 USA.
[Beuling, Eva; Bosse, Tjalling] Erasmus Univ, Sch Med, NL-3000 DR Rotterdam, Netherlands.
[Bosse, Tjalling; aan de Kerk, Daniel J.] Univ Amsterdam, Sch Med, NL-1100 DD Amsterdam, Netherlands.
[Fujiwara, Yuko; Katz, Samuel G.; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Fujiwara, Yuko; Katz, Samuel G.; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA.
[Fujiwara, Yuko; Katz, Samuel G.; Orkin, Stuart H.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Krasinski, Stephen D.] Tufts Univ, Gerald J & Dorothy R Friedman Sch Nutr Sci & Poli, Boston, MA 02111 USA.
RP Krasinski, SD (reprint author), Childrens Hosp, Div Gastroenterol & Nutr, Dept Med, EN 720,300 Longwood Ave, Boston, MA 02115 USA.
EM stephen.krasinski@childrens.harvard.edu
OI Bosse, Tjalling/0000-0002-6881-8437
FU Children's Hospital Boston; National Institute of Diabetes and Digestive
and Kidney Diseases [R01 -DK-061382, R37-DK-32658]; Harvard Digestive
Disease Center [5P30-DK-34854]; Nutricia Research Foundation; De Drie
Lichten; Doctor Catharine van Tussenbroek
FX We thank Drs. W. T. Pu (Children's Hospital Boston, Boston, MA) for the
floxed Gata Mouse line, S. Robine (Institut Curie, Paris, France) for
the VillinCreERT2 transgenic mouse line, and P.A. Dawson
(Wake Forest School of Medicine, Winson-Salem, NC) for the ASBT
antibody. We also thank Lena Liu (Department of Pathology, Children's
Hospital Boston, Boston, MA) for the technical support.; This work was
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases Grants R01 -DK-061382 (SDK) and R37-DK-32658 (RJG), the Harvard
Digestive Disease Center (5P30-DK-34854), the Nutricia Research
Foundation (EB and TB), the Foundation De Drie Lichten (EB) and the
Foundation Doctor Catharine van Tussenbroek (EB) in The Netherlands.
NR 51
TC 21
Z9 21
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 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD OCT 1
PY 2008
VL 322
IS 1
BP 179
EP 189
DI 10.1016/j.ydbio.2008.07.022
PG 11
WC Developmental Biology
SC Developmental Biology
GA 356PL
UT WOS:000259790000017
PM 18692040
ER
PT J
AU Simone, S
Gorin, Y
Velagapudi, C
Abboud, HE
Habib, SL
AF Simone, Simona
Gorin, Yves
Velagapudi, Chakradhar
Abboud, Hanna E.
Habib, Samy L.
TI Mechanism of oxidative DNA damage in diabetes - tuberin inactivation and
downregulation of DNA repair enzyme
8-oxo-7,8-dihydro-2'-deoxyguanosine-DNA glycosylase
SO DIABETES
LA English
DT Article
ID RENAL EPITHELIAL-CELLS; AKT/PROTEIN KINASE-B; HIGH GLUCOSE;
PHOSPHOINOSITIDE 3-KINASE; PROTEIN-KINASE; SIGNALING PATHWAYS;
MITOCHONDRIAL-DNA; NAD(P)H OXIDASE; SKELETAL-MUSCLE; MESANGIAL CELLS
AB OBJECTIVE-To investigate potential mechanisms of oxidative DNA damage in a rat model of type 1 diabetes and in murine proximal tubular epithelial cells and primary culture of rat proximal tubular epithelial cells.
RESEARCH DESIGN AND METHODS-Phosphorylation of Akt and tuberin, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels, and 8-oxoG-DNA glycosylase (OGG1) expression were measured in kidney cortical tissue of control and type 1 diabetic animals and in proximal tubular cells incubated with normal or high glucose.
RESULTS-In the renal cortex of diabetic rats, the increase in Akt phosphorylation is associated with enhanced phosphorylation of tuberin, decreased OGG1 protein expression, and 8-oxodG accumulation. Exposure of proximal tubular epithelial cells to high glucose causes a rapid increase in reactive oxygen species (ROS) generation that correlates with the increase in Akt and tuberin phosphorylation. High glucose also resulted in downregulation of OGG1 protein expression, paralleling its effect on Akt and tuberin. Inhibition of phosphatidylinositol 3-kinase/Akt significantly reduced high glucose-induced tuberin phosphorylation and restored OGG1 expression. Hydrogen peroxide stimulates Akt and tuberin phosphorylation and decreases OGG1 protein expression. The antioxidant N-acetylcysteine significantly inhibited ROS generation, Akt/protein kinase B, and tuberin phosphorylation and resulted in deceased 8-oxodG accumulation and upregulation of OGG1 protein expression.
CONCLUSIONS-Hyperglycemia in type 1 diabetes and treatment of proximal tubular epithelial cells with high glucose leads to phosphorylation/inactivation of tuberin and downregulation of OGG1 via a redox-dependent activation of Akt in renal tubular epithelial cells. This signaling cascade provides a mechanism of oxidative stress-mediated DNA damage in diabetes.
C1 [Simone, Simona; Gorin, Yves; Velagapudi, Chakradhar; Abboud, Hanna E.; Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78284 USA.
[Simone, Simona] Univ Bari, Dept Emergency & Transplantat, Bari, Italy.
[Abboud, Hanna E.; Habib, Samy L.] S Texas Vet Healthcare Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA.
RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78284 USA.
EM habib@uthscsa.edu
RI Velagapudi, Chakradhar/F-9750-2015;
OI Gorin, Yves/0000-0003-4048-6925
FU NIDDK NIH HHS [R37 DK033665, R37-DK-33665]
NR 49
TC 43
Z9 44
U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD OCT
PY 2008
VL 57
IS 10
BP 2626
EP 2636
DI 10.2337/db07-1579
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360FT
UT WOS:000260043800012
PM 18599524
ER
PT J
AU Jiang, Y
Nishimura, W
Devor-Henneman, D
Kusewitt, D
Wang, H
Holloway, MP
Dohi, T
Sabo, E
Robinson, ML
Altieri, DC
Sharma, A
Altura, RA
AF Jiang, Yuying
Nishimura, Wataru
Devor-Henneman, Deborah
Kusewitt, Donna
Wang, Haijuan
Holloway, Michael P.
Dohi, Takehiko
Sabo, Edmond
Robinson, Michael L.
Altieri, Dario C.
Sharma, Arun
Altura, Rachel A.
TI Postnatal expansion of the pancreatic beta-cell mass is dependent on
survivin
SO DIABETES
LA English
DT Article
ID ANTI-APOPTOSIS GENE; EXPRESSION; GROWTH; PROLIFERATION; DEATH;
DIFFERENTIATION; REPLICATION; INHIBITOR; PROTEINS; CANCER
AB OBJECTIVE-Diabetes results from a deficiency of functional beta-cells due to both an increase in beta-cell death and an inhibition of beta-cell replication. The molecular mechanisms responsible for these effects in susceptible individuals are mostly unknown. The objective of this study was to determine whether a gene critical for cell division and cell survival in cancer cells, survivin, might also be important for beta-cells.
RESEARCH DESIGN AND METHODS-We generated mice harboring a conditional deletion of survivin in pancreatic endocrine cells using mice with a Pax-6-Cre transgene promoter construct driving tissue-specific expression of Cre-recombinase in these cells. We performed metabolic studies and immunohistochemical analyses to determine the effects of a mono- and biallelic deletion of survivin.
RESULTS-Selective deletion of survivin in pancreatic endocrine cells in the mouse had no discernible effects during embryogenesis but was associated with striking decreases in beta-cell number after birth, leading to hyperglycemia and early-onset diabetes by 4 weeks of age. Serum insulin levels were significantly decreased in animals lacking endocrine cell survivin, with relative stability of other hormones. Exogenous expression of survivin in mature beta-cells lacking endogenous survivin completely rescued the hyperglycemic phenotype and the decrease in P-cell mass, confirming the specificity of the survivin effect in these cells.
CONCLUSIONS-Our findings implicate survivin in the maintenance of beta-cell mass through both replication and antiapoptotic mechanisms. Given the widespread involvement of survivin in cancer, a novel role for survivin may well be exploited in beta-cell regulation in diseased states, such as diabetes.
C1 [Jiang, Yuying; Holloway, Michael P.; Altura, Rachel A.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
[Nishimura, Wataru; Sharma, Arun] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Devor-Henneman, Deborah; Kusewitt, Donna] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA.
[Wang, Haijuan; Holloway, Michael P.; Altura, Rachel A.] Brown Univ, Dept Pediat, Providence, RI 02912 USA.
[Dohi, Takehiko; Altieri, Dario C.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA.
[Sabo, Edmond] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA.
[Robinson, Michael L.] Miami Univ, Dept Zool, Oxford, OH 45056 USA.
RP Altura, RA (reprint author), Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
EM rachel_altura@brown.edu
RI Kusewitt, Donna/E-8107-2011;
OI Nishimura, Wataru/0000-0002-8068-1277
FU National Institutes of Health [CA-78810, CA-90917, HL-54131, DK-060127,
1R21-DK-078300-01]; Juvenile Diabetes Research Foundation
FX W.N. is a recipient of the Mary K. Iacocca Fellowship. D.C.A. has
received National Institutes of Health grants CA-78810, CA-90917, and
HL-54131. A.S. has received National Institutes of Health Grant
DK-060127. R.A.A. has received support from the Juvenile Diabetes
Research Foundation and National Institutes of Health Grant
1R21-DK-078300-01.
NR 56
TC 26
Z9 28
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD OCT
PY 2008
VL 57
IS 10
BP 2718
EP 2727
DI 10.2337/db08-0170
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360FT
UT WOS:000260043800023
PM 18599523
ER
PT J
AU Kawahara, S
Hata, Y
Kita, T
Arita, R
Miura, M
Nakao, S
Mochizuki, Y
Enaida, H
Kagimoto, T
Goto, Y
Hafezi-Moghadam, A
Ishibashi, T
AF Kawahara, Shuhei
Hata, Yasuaki
Kita, Takeshi
Arita, Ryoichi
Miura, Muneki
Nakao, Shintaro
Mochizuki, Yasutaka
Enaida, Hiroshi
Kagimoto, Tadahisa
Goto, Yoshinobu
Hafezi-Moghadam, Ali
Ishibashi, Tatsuro
TI Potent inhibition of cicatricial contraction in proliferative
vitreoretinal diseases by statins
SO DIABETES
LA English
DT Article
ID MASSIVE PERIRETINAL PROLIFERATION; PIGMENT EPITHELIAL-CELLS; COLLAGEN
GEL CONTRACTION; COA REDUCTASE INHIBITORS; TISSUE GROWTH-FACTOR;
RHO-KINASE; EPIRETINAL MEMBRANES; HYALOCYTES; INVOLVEMENT; SIMVASTATIN
AB OBJECTIVE-Despite tremendous progress in vitreoretinal surgery, certain postsurgical complications limit the success in the treatment of proliferative vitreoretinal diseases (PVDs), such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). One of the most significant complications is the cicatricial contraction of proliferative membranes, resulting in tractional retinal detachment and severe vision loss. Novel pharmaceutical approaches are thus urgently needed for the management of these vision-threatening diseases. In the current study, we investigated the inhibitory effects of statins on the progression of PVDs.
RESEARCH DESIGN AND METHODS-Human vitreous concentrations of transforming growth factor-beta 2 (TGF-beta 2) were measured by enzyme-linked immunosorbent assay. TGF-beta 2- and vitreous-dependent phosphorylation of myosin light chain (MLC), a downstream mediator of Rho-kinase pathway, and collagen gel contraction simulating cicatrical contraction were analyzed using cultured hyalocytes. Inhibitory effects of simvastatin on cicatrical contraction were assessed both in vitro and in vivo.
RESULTS-Human vitreous concentrations of TGF-beta 2 were significantly higher in the samples from patients with PVD compared with those without PVD. Simvastatin inhibited TGF beta 2-dependent MLC phosphorylation and gel contraction in a dose- and time-dependent manner and was capable of inhibiting translocation of Rho protein to the plasma membrane in the presence of TGF-beta 2. Vitreous samples from patients with PVD enhanced MLC phosphorylation and gel contraction, whereas simvastatin almost completely inhibited these phenomena. Finally, intravitreal injection of simvastatin dose-dependently prevented the progression of diseased states in an in vivo model of PVR.
CONCLUSIONS-Statins might have therapeutic potential in the prevention of PVDs.
C1 [Kawahara, Shuhei; Hata, Yasuaki; Kita, Takeshi; Arita, Ryoichi; Miura, Muneki; Mochizuki, Yasutaka; Enaida, Hiroshi; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka, Japan.
[Nakao, Shintaro; Hafezi-Moghadam, Ali] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Kagimoto, Tadahisa] Aqumen Biopharmaceut, Tenjin, Chuo Ku, Fukuoka, Japan.
[Goto, Yoshinobu] Int Univ Hlth & Welf Okawa, Fac Rehabil, Dept Occupat Therapy, Fukuoka, Japan.
RP Hata, Y (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka, Japan.
EM hatachan@med.kyushu-u.ac.jp
OI Hafezi-Moghadam, Ali/0000-0002-5336-0697
FU Bausch Lomb; Japan Eye Bank Association; National Institutes of Health
[AI050775, HL086933]; Ministry of Education, Science, Sports and
Culture, Japan [19592026, 18791283, 18591925]; National Eye Institute
Core [EY14104]; Massachusetts Lions Eye Research Fund; Edward F. Knight
Age-Related and Macular Degeneration Fund; Research to Prevent Blindness
FX S.N. has received a Research Fellowship Award from Bausch & Lomb and a
Fellowship Award from the Japan Eye Bank Association. A.H.-M. has
received National Institutes of Health Grants AI050775 and HL086933.
This study has received Grants-in-Aid for Scientific Research 19592026,
18791283, and 18591925 from the Ministry of Education, Science, Sports
and Culture, Japan; National Eye Institute Core Grant EY14104; and
support from the Massachusetts Lions Eye Research Fund, the Marion W.
and Edward F. Knight Age-Related and Macular Degeneration Fund, and
Research to Prevent Blindness.
NR 50
TC 31
Z9 37
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD OCT
PY 2008
VL 57
IS 10
BP 2784
EP 2793
DI 10.2337/db08-0302
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360FT
UT WOS:000260043800031
PM 18599521
ER
PT J
AU Musen, G
Jacobson, AM
Ryan, CM
Cleary, PA
Waberski, BH
Weinger, K
Dahms, W
Bayless, M
Silvers, N
Harth, J
White, N
AF Musen, Gail
Jacobson, Alan M.
Ryan, Christopher M.
Cleary, Patricia A.
Waberski, Barbara H.
Weinger, Katie
Dahms, William
Bayless, Meg
Silvers, Nancy
Harth, Judith
White, Neil
CA DCCT EDIC Res Grp
TI Impact of Diabetes and Its Treatment on Cognitive Function Among
Adolescents Who Participated in the Diabetes Control and Complications
Trial
SO DIABETES CARE
LA English
DT Article
ID SEVERE HYPOGLYCEMIA; CHILDREN; INTERVENTIONS; EPIDEMIOLOGY; MELLITUS;
ONSET
AB OBJECTIVE - The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13-19 years at entry in the Diabetes Control and Complications Trial (DCCT).
RESEARCH DESIGN AND METHODS - This was a longitudinal Study involving 249 patients with type I diabetes who were between 13 and 19 years old when they were randomly assigned in the DCCT. Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study, similar to 18 years later, were compared with baseline performance. We assessed the effects of the original DCCT treatment. group assignment, mean A1C values, and frequency of severe hypoglycemic events on eight domains of cognition.
RESULTS - There were a total of 294 reported episodes of coma or seizure. Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain. As in a previous analysis of the entire study cohort, higher A1C values were associated with declines in the psychomotor and mental efficiency domain (P < 0.01); however, the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis.
CONCLUSIONS - Despite relatively high rates of severe hypoglycemia, cognitive function did not decline over an extended period of time in the youngest cohort of patients with type I diabetes.
C1 [Musen, Gail; Jacobson, Alan M.; Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Ryan, Christopher M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Cleary, Patricia A.; Waberski, Barbara H.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Dahms, William] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Bayless, Meg] Univ Iowa, Coll Med, Iowa City, IA USA.
[Silvers, Nancy] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Harth, Judith] Univ Western Ontario, Schulich Sch Med, London, ON, Canada.
[White, Neil] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
RP Musen, G (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
EM gail.musen@joslin.harvard.edu
FU National Instiute of Diabetes and Digestive and Kidney Diseases [5 R01
DK062218-02]; General Clinical Research Centers Program; National Center
for Research Resources; Herbert Graetz Psychosocial Research Fund
FX Funding for this study was provided by grant 5 R01 DK062218-02 from the
National Instiute of Diabetes and Digestive and Kidney Diseases and by
contracts with the Division of Diabetes, Endocrinology and Metabolic
Diseases of the National Institute of Diabetes and Digestive and Kidney
Diseases, the General Clinical Research Centers Program, National Center
for Research Resources, and the Herbert Graetz Psychosocial Research
Fund.
NR 25
TC 51
Z9 53
U1 1
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD OCT
PY 2008
VL 31
IS 10
BP 1933
EP 1938
DI 10.2337/dc08-0607
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360FR
UT WOS:000260043600002
PM 18606979
ER
PT J
AU Pani, LN
Korenda, L
Meigs, JB
Driver, C
Chamany, S
Fox, CS
Sullivan, L
D'Agostino, RB
Nathan, DM
AF Pani, Lydir N.
Korenda, Leslie
Meigs, James B.
Driver, Cynthia
Chamany, Shadi
Fox, Caroline S.
Sullivan, Lisa
D'Agostino, Ralph B.
Nathan, David M.
TI Effect of Aging on A1C Levels in Individuals Without Diabetes
SO DIABETES CARE
LA English
DT Article
ID GLYCATED HEMOGLOBIN; GLYCOSYLATED HEMOGLOBIN; SEVERE HYPOGLYCEMIA;
HBA(1C); AGE; POPULATION; DIAGNOSIS; MELLITUS; GLYCOHEMOGLOBIN; DISEASE
AB OBJECTIVE - Although glycemic levels are known to rise with normal aging, the nondiabetic A1C range is not age specific. We examined whether A1C was associated with age in nondiabetic subjects and in subjects with normal glucose tolerance (NGT) in two population-based cohorts.
RESEARCH DESIGN AND METHODS - We performed cross-sectional analyses 01 A1C across age categories in 2,473 nondiabetic participants of the Framingham Offspring Study (FOS) and in 3,270 nondiabetic participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. In FOS, we examined A1C by age in a subset With NGT, i.e., after excluding those With impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Multivariate analyses were performed, adjusting for sex, BMI, fasting glucose, and 2-h postload glucose values.
RESULTS- In the FOS and NHANES cohorts, A1C levels were positively associated with age in nondiabetic subjects. Linear regression revealed 0.014- and 0.010-unit increases in A1C per year in the nondiabetic FOS and NHANES populations, respectively. The 97.5th percentiles for A1C were 6.0% and 5.6% for nondiabetic individuals aged < 40 years in FOS and NHANES, respectively, compared With 6.6% and 6.2% for individuals aged >= 70 years (P-trend < 0.001). The association of A1C With age was similar when restricted to the subset of FOS Subjects With NGT and after adjustments for sex, BMI, lasting glucose, and 2-h postload glucose values.
CONCLUSIONS- A1C levels are positively associated with age in nondiabetic populations even after exclusion of subjects With IFG and/or IGT. Further Studies are needed to determine whether age-specific diagnostic and treatment criteria would be appropriate.
C1 [Pani, Lydir N.; Meigs, James B.; Nathan, David M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Pani, Lydir N.; Meigs, James B.; Nathan, David M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Pani, Lydir N.; Meigs, James B.; Nathan, David M.] Harvard Univ, Sch Med, Boston, MA USA.
[Korenda, Leslie; Driver, Cynthia; Chamany, Shadi] Dept Hlth & Mental Hyg, New York, NY USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Metab & Hypertens, Boston, MA 02115 USA.
[Sullivan, Lisa; D'Agostino, Ralph B.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
RP Pani, LN (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
EM lpani@partners.org
FU National Heart, Lung and Blood Institute's Framingham Heart Study
(National Heart, Lung and Blood Institute/National Institutes of Health)
[N01-HC-25195]; Boston University School of Medicine; American Diabetes
Association Career Development Award; National Institute of Diabetes and
Digestive and Kidney Diseases [K24 DK080140]; Earl P. Charlton Fund for
Innovative Diabetes Research; National Research Service Award [T32]
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (National Heart, Lung and Blood
Institute/National Institutes of Health Contract N01-HC-25195) and
Boston University School of Medicine. J.B.M. is supported by an American
Diabetes Association Career Development Award and National Institute of
Diabetes and Digestive and Kidney Diseases Grant K24 DK080140D.M.N. is
supported in part by the Earl P. Charlton Fund for Innovative Diabetes
Research. L.P. is supported by an institutional National Research
Service Award (T32).; We thank Peter Shrader and Sharon Saydah for
assistance with Statistical analyses. For contribution to the study, we
thank Deborah Wexler, Diana Berger, Randie Little, Eran Bellin, and Curt
Rohlfing.
NR 33
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U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD OCT
PY 2008
VL 31
IS 10
BP 1991
EP 1996
DI 10.2337/dc08-0577
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360FR
UT WOS:000260043600013
PM 18628569
ER
PT J
AU Lopes-Virella, MF
Carter, RE
Gilbert, GE
Klein, RL
Jaffa, M
Jenkins, AJ
Lyons, TJ
Garvey, WT
Virella, G
AF Lopes-Virella, Maria F.
Carter, Rickey E.
Gilbert, Gregory E.
Klein, Richard L.
Jaffa, Miran
Jenkins, Alicia J.
Lyons, Timothy J.
Garvey, W. Timothy
Virella, Gabriel
CA DCCT EDIC Cohort Study Grp
TI Risk Factors Related to Inflammation and Endothelial Dysfunction in the
DCCT/EDIC Cohort and Their Relationship With Nephropathy and
Macrovascular Complications
SO DIABETES CARE
LA English
DT Article
ID TYPE-1 DIABETIC-PATIENTS; INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN;
LOW-GRADE INFLAMMATION; ADHESION MOLECULE-1; CLINICAL-EVIDENCE; PLASMA
MARKERS; MELLITUS; ASSOCIATION; PROGRESSION
AB OBJECTIVE - Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1 , and E-selectin, and fibrinolytic markers) in a subgroup) Of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology, of Diabetes Intervention and Complications (EDIC) Study cohort.
RESEARCH DESIGN AND METHODS - We determined which of these risk factors or clusters thereof -,ire associated with the presence of and Subsequent development of nephropathy and macrovascular complications (reflected by carotid intima-media thickness [IMT]).
RESULTS - After adjustment for conventional risk factors (age, sex, DCCT treatment group, diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, total and HDL cholesterol,a nd smoking status), fibrinogen remained strongly associated with progression of internal and common carotid IMT (P < 0.01) and soluble E-selectin had a strong association with nephropathy (P < 0.01).
CONCLUSIONS - The best predictor for IMT progression in the DCCT/EDIC cohort was plasma fibrinogen, and the levels of soluble E-selectin discriminate patients with albuminuria better than conventional risk factors.
C1 [Lopes-Virella, Maria F.; Klein, Richard L.; Jenkins, Alicia J.; Lyons, Timothy J.; Garvey, W. Timothy] Med Univ S Carolina, Dept Med & Lab Serv, Charleston, SC 29425 USA.
[Lopes-Virella, Maria F.; Klein, Richard L.; Jenkins, Alicia J.; Lyons, Timothy J.; Garvey, W. Timothy] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Carter, Rickey E.; Gilbert, Gregory E.; Jaffa, Miran] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA.
[Jenkins, Alicia J.; Lyons, Timothy J.] Univ Oklahoma, Hlth Sci Ctr, Endocrinol Sect, Oklahoma City, OK USA.
[Garvey, W. Timothy] Univ Alabama, Dept Nutr, Birmingham, AL USA.
[Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med & Lab Serv, Charleston, SC 29425 USA.
EM virellam@musc.edu
RI Gilbert, Gregory/C-7735-2016
OI Gilbert, Gregory/0000-0003-0879-5496
FU Merit Review Program of the Department of Veterans Affairs; National
Institutes of Health and Juvenile Diabetes Research Foundation [PO1
HL55782]; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institutes of Health
FX This research was supported by funding of the Merit Review Program of
the Department of Veterans Affairs and by joint funding of the National
Institutes of Health and Juvenile Diabetes Research Foundation (PO1
HL55782). The DCCT/EDIC Research Group is sponsored through research
contracts from the National Institute of Diabetes, Endocrinology and
Metabolic Diseases of the National Institute of Diabetes and Digestive
and Kidney Diseases and the National Institutes of Health.; The
technical assistance of Charlyne Chassereau, Andrea Semler, and Karma
Moller and efforts of stud), coordinators jenny Smith, Leslie Nicholson,
Marlene Brabham, and Erica Hood are gratefully acknowledged. Finally,
the authors are grateful to the patients in the DCCT/EDIC cohort for
their long-term participation in this important trial.
NR 25
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U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD OCT
PY 2008
VL 31
IS 10
BP 2006
EP 2012
DI 10.2337/dc08-0659
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 360FR
UT WOS:000260043600017
PM 18628568
ER
PT J
AU Huang, JM
Karakucuk, V
Levitsky, LL
Rhoads, DB
AF Huang, Jianmin
Karakucuk, Vildan
Levitsky, Lynne L.
Rhoads, David B.
TI Expression of HNF4 alpha variants in pancreatic islets and Ins-1 beta
cells
SO DIABETES-METABOLISM RESEARCH AND REVIEWS
LA English
DT Article
DE hormone nuclear receptor; alternative splicing; transcriptional activity
ID NUCLEAR FACTOR 4; TRANSCRIPTION FACTOR; GENE-EXPRESSION;
DIABETES-MELLITUS; MISSENSE MUTATION; INSULIN-RELEASE; FACTOR 4-ALPHA;
MESSENGER-RNA; MOUSE-LIVER; HNF-4 GENE
AB Background Hepatocyte nuclear factor (HNF4 alpha) is a nuclear receptor essential for endodermal differentiation and cell functions in the adult pancreas, liver, and other tissues. Mutations in the HNF4A gene cause MODY1. Up to nine protein variants arise from two developmentally regulated promoters. Because some variants lack the N-terminal activation function 1 (AF-1) and/or C-terminal inhibitory F domain, defining their tissue-specific regulation and function is important for understanding pancreatic cell behaviour.
Methods Expression of HNF4 alpha. variants in islets, rat Ins-1 insulinoma cells, and human Hep3B hepatocellular carcinoma cells was assessed using a long-range reverse transcription-polymerase chain reaction (RT-PCR) strategy capable of recognizing each combination of mRNA termini. Protein expression was verified by immuno-blotting with terminus-specific antibodies and DNA-binding assays.
Results Mouse islets and both cell lines express HNF4 alpha 9, which lacks both AF-1 and the F domain. Islets also expressed the HNF4 alpha PI promoter variants HNF4 alpha 1/alpha 2, and Hep3B cells expressed HNF4 alpha 3. When ectopically expressed in COS-7 cells, HNF4 alpha 1, alpha 3, alpha 7, and alpha 9 each stimulated an HNF4 alpha-dependent promoter. Variants containing exon 1B (HNF4 alpha 4 - alpha 6) were not detected. Lack of canonical splicing signals and species conservation argues against exon 1B usage.
Conclusions This is the first report of HNF4 alpha 9 expression in any tissue. Our findings extend our understanding of HNF4 alpha gene transcription and function. This knowledge may be useful in efforts to recover or establish regulated insulin secretion. Copyright (c) 2008 John Wiley & Sons, Ltd.
C1 [Rhoads, David B.] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Rhoads, DB (reprint author), MassGen Hosp Children, Pediat Endocrine Unit, 55 Fruit St,BHX410, Boston, MA 02114 USA.
EM rhoads@helix.mgh.harvard.edu
FU American Diabetes Association Research [7-0S-RA-121]; Diabetes Action
Research & Education Foundation [204]; Nicholas Dulong Diabetes Research
Fund (LLL)
FX We appreciate reagent gifts from FM Sladek, W Hwa ng-Verslues, R
Cortese, CB Wollheim, MK Thomas, and V Stanojevic. We thank D DuGuerre
and L Zhang for technical assistance, A Torjesen for assistance
constructing plasmids, AK Leonberg for a critical reading, and a peer
reviewer for very insightful and thorough comments. We are grateful to
the islet Cell Resource Centers of the University of Minnesota and the
University of Alabama for providing human islets.; This study was
supported by American Diabetes Association Research Grant 7-0S-RA-121
(DBR), Diabetes Action Research & Education Foundation Grant #204 (DBR),
and the Nicholas Dulong Diabetes Research Fund (LLL).
NR 50
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U1 0
U2 1
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1520-7552
J9 DIABETES-METAB RES
JI Diabetes-Metab. Res. Rev.
PD OCT
PY 2008
VL 24
IS 7
BP 533
EP 543
DI 10.1002/dmrr.870
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 364YM
UT WOS:000260371700003
PM 18561282
ER
PT J
AU Akashi, T
Shigematsu, H
Hamamoto, Y
Iwasaki, H
Yatoh, S
Bonner-Weir, S
Akashi, K
Weir, GC
AF Akashi, Tomoyuki
Shigematsu, Hirokazu
Hamamoto, Yoshiyuki
Iwasaki, Hiromi
Yatoh, Shigeru
Bonner-Weir, Susan
Akashi, Koichi
Weir, Gordon C.
TI Bone marrow or foetal liver cells fail to induce islet regeneration in
diabetic Akita mice
SO DIABETES-METABOLISM RESEARCH AND REVIEWS
LA English
DT Article
DE diabetes; islets; beta-cells; bone marrow; foetal liver; regeneration
ID PANCREATIC BETA-CELLS; INSULIN-PRODUCING CELLS; MESENCHYMAL STEM-CELLS;
IN-VIVO; TRANSCRIPTION FACTORS; PROGENITOR CELLS; GENE-EXPRESSION;
MUTANT MICE; REVERSAL; TRANSPLANTATION
AB Background In this study, we carried out bone marrow and foetal liver cell transplantation to determine if these cells could differentiate into pancreatic beta-cells or promote regeneration.
Methods To exclude an artificial or immunological influence for induction of diabetes to recipients, Akita mice, which develop diabetes spontaneously,were used. In addition, we used mice harbouring the transgenic green fluorescent protein (GFP) reporter for insulin I gene as donors to mark donor-derived beta-cells.
Results All transplanted Akita mice after intravenous injection showed full donor chimerism in peripheral blood analysis. Their diabetic state represented by blood glucose levels did not change after transplantation. In spite of examination of more than 200 islets in each group, we could not find GFP-positive cells in any of the recipients.
Conclusions Bone marrow cells or foetal liver cells do not differentiate to new pancreatic beta-cells or promote regeneration in Akita mice, a non-chemical or non-immune model of diabetes. Copyright (c) 2008 John Wiley & Sons, Ltd.
C1 [Akashi, Tomoyuki; Hamamoto, Yoshiyuki; Yatoh, Shigeru; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA.
[Shigematsu, Hirokazu; Iwasaki, Hiromi; Akashi, Koichi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA.
EM gordon.weir@joslin.harvard.edu
OI Bonner-Weir, Susan/0000-0003-4682-0656
FU National Institute of Health [U19DK6125]; Juvenile Diabetes Research
Foundation; Diabetes Research and Wellness Foundation; National
Institutes of Health [P30 DK36836]; Manpei Suzuki Diabetes Foundation
FX This study was supported by grants from the National Institute of Health
(U19DK6125), the Juvenile Diabetes Research Foundation, the Diabetes
Research and Wellness Foundation and an important group of private
donors. Help was also provided by the Advanced Microscopy Core of the
Diabetes Endocrinology Research Center (DERC) of Joslin supported by the
National Institutes of Health (P30 DK36836). S.Y. was the recipient of a
fellowship from Manpei Suzuki Diabetes Foundation.
NR 37
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U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1520-7552
J9 DIABETES-METAB RES
JI Diabetes-Metab. Res. Rev.
PD OCT
PY 2008
VL 24
IS 7
BP 585
EP 590
DI 10.1002/dmrr.884
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 364YM
UT WOS:000260371700010
PM 18727153
ER
PT J
AU Hirsch, IB
Abelseth, J
Bode, BW
Fischer, JS
Kaufman, FR
Mastrototaro, J
Parkin, CG
Wolpert, HA
Buckingham, BA
AF Hirsch, Irl B.
Abelseth, Jill
Bode, Bruce W.
Fischer, Jerome S.
Kaufman, Francine R.
Mastrototaro, John
Parkin, Christopher G.
Wolpert, Howard A.
Buckingham, Bruce A.
TI Sensor-augmented insulin pump therapy: Results of the first randomized
treat-to-target study
SO DIABETES TECHNOLOGY & THERAPEUTICS
LA English
DT Article
ID BLOOD-GLUCOSE; INFUSION; IMPROVEMENT; TRIAL
AB Background: The objective of the study was to evaluate the clinical effectiveness and safety of a device that combines an insulin pump with real-time continuous glucose monitoring (CGM), compared to using an insulin pump with standard blood glucose monitoring systems.
Methods: This 6-month, randomized, multicenter, treat-to-target study enrolled 146 subjects treated with continuous subcutaneous insulin infusion between the ages of 12 and 72 years with type 1 diabetes and initial A1C levels of >= 7.5%. Subjects were randomized to pump therapy with real-time CGM (sensor group [SG]) or to pump therapy and self-monitoring of blood glucose only (control group [CG]). Clinical effectiveness and safety were evaluated.
Results: A1C levels decreased (P < 0.001) from baseline (8.44 +/- 0.70%) in both groups (SG, -0.71 +/- 0.71%; CG, -0.56 +/- 0.072%); however, between-group differences did not achieve significance. SG subjects showed no change in mean hypoglycemia area under the curve (AUC), whereas CG subjects showed an increase (P = 0.001) in hypoglycemia AUC during the blinded periods of the study. The between-group difference in hypoglycemia AUC was significant (P < 0.0002). Greater than 60% sensor utilization was associated with A1C reduction (P = 0.0456). Fourteen severe hypoglycemic events occurred (11 in the SG group and three in the CG group, P = 0.04).
Conclusions: A1C reduction was no different between the two groups. Subjects in the CG group had increased hypoglycemia AUC and number of events during blinded CGM use; however, there was no increase in hypoglycemia AUC or number of events in the SG group. Subjects with greater sensor utilization showed a greater improvement in A1C levels.
C1 [Hirsch, Irl B.] Univ Washington, St Lukes Roosevelt Med Ctr, Seattle, WA 98105 USA.
[Abelseth, Jill] Endocrine Grp LLP, Albany, NY USA.
[Bode, Bruce W.] Atlanta Diabet Associates, Atlanta, GA USA.
[Fischer, Jerome S.] Diabet & Glandular Dis Clin San Antonio, San Antonio, TX USA.
[Kaufman, Francine R.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Mastrototaro, John] Medtron Minimed, Northridge, CA USA.
[Parkin, Christopher G.] CGParkin Commun Inc, Carmel, IN USA.
[Wolpert, Howard A.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Buckingham, Bruce A.] Stanford Univ, Dept Pediat Endocrinol, Stanford, CA 94305 USA.
RP Hirsch, IB (reprint author), Univ Washington, St Lukes Roosevelt Med Ctr, 4225 Roosevelt Way NE,Suite 101,Box 354691, Seattle, WA 98105 USA.
EM ihirsch@u.washington.edu
FU Medtronic, Inc
FX This research was supported by a grant from Medtronic, Inc.
NR 14
TC 133
Z9 135
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1520-9156
J9 DIABETES TECHNOL THE
JI Diabetes Technol. Ther.
PD OCT
PY 2008
VL 10
IS 5
BP 377
EP 383
DI 10.1089/dia.2008.0068
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 347YL
UT WOS:000259177600007
PM 18715214
ER
PT J
AU Frayling, TM
Colhoun, H
Florez, JC
AF Frayling, T. M.
Colhoun, H.
Florez, J. C.
TI A genetic link between type 2 diabetes and prostate cancer - Commentary
SO DIABETOLOGIA
LA English
DT Editorial Material
DE epidemiology; genes; genome-wide association study; pleiotropy; prostate
cancer; transcription factors; type 2 diabetes
ID GENOME-WIDE ASSOCIATION; METABOLIC SYNDROME; REDUCED RISK; US MEN;
VARIANTS; MELLITUS; MUTATIONS; MULTIPLE; LOCI; SUSCEPTIBILITY
AB Epidemiological studies suggest that men with type 2 diabetes are less likely than non-diabetic men to develop prostate cancer. The cause of this association is not known. Recent genetic studies have highlighted a potential genetic link between the two diseases. Two studies have identified a version (allele) of a variant in the HNF1B (also known as TCF2) gene that predisposes to type 2 diabetes, and one of them showed that the same allele protects men from prostate cancer. Other, separate, studies have identified different variants in the JAZF1 gene, one associated with type 2 diabetes, another associated with prostate cancer. These findings are unlikely to completely explain the epidemiological association between the two diseases but they provide new insight into a possible direct causal link, rather than one that is confounded or biased in some way.
C1 [Frayling, T. M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England.
[Colhoun, H.] Univ Dundee, Dundee, Scotland.
[Florez, J. C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Frayling, TM (reprint author), Univ Exeter, Peninsula Coll Med & Dent, Magdalen Rd, Exeter EX1 2LU, Devon, England.
EM Tim.frayling@pms.ac.uk
NR 29
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U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD OCT
PY 2008
VL 51
IS 10
BP 1757
EP 1760
DI 10.1007/s00125-008-1114-9
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 344WQ
UT WOS:000258958400001
PM 18696045
ER
PT J
AU Gonzalez, JS
Delahanty, LM
Safren, SA
Meigs, JB
Grant, RW
AF Gonzalez, J. S.
Delahanty, L. M.
Safren, S. A.
Meigs, J. B.
Grant, R. W.
TI Differentiating symptoms of depression from diabetes-specific distress:
relationships with self-care in type 2 diabetes
SO DIABETOLOGIA
LA English
DT Article
DE adherence; depression; diabetes-specific distress; self-care;
self-management; type 2 diabetes
AB Aims/hypothesis The aim of this study was to examine the relationship between depressive symptoms and diabetes-specific distress and the independent relationships of each of these factors with diabetes self-care. We expected that symptoms of depression would be associated with poorer diabetes self-care, independent of diabetes-specific distress.
Methods We surveyed 848 primary care patients with type 2 diabetes using the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS), Problem Areas in Diabetes scale (PAID), Summary of Diabetes Self-Care Activities, and self-reported medication adherence.
Results The PAID and HANDS scores were positively correlated in the overall sample (r=0.54, p < 0.0001), among those who did not meet diagnostic criteria for major depressive disorder (MDD) based on the HANDS screening result (n=685; r=0.36, p < 0.001) and in patients who did meet the screening criteria for MDD (n=163; r=0.36, p < 0.001). Higher PAID scores significantly predicted lower levels of diet, exercise and medication adherence (all p values < 0.05). However, once depression symptom scores were entered into these models, most relationships were reduced to non-significance, while the HANDS score retained significant relationships with most indices of diabetes self-care. The same pattern of results was found in the subset of patients who did not screen positive for MDD.
Conclusions/interpretation These results suggest that specific symptoms of depression have a greater negative relationship with diabetes self-care than diabetes-specific distress, even among those patients who do not meet screening criteria for MDD. Interventions that focus on improving the management of specific symptoms of depression may be more effective in improving self-care than those that focus on reducing distress.
C1 [Gonzalez, J. S.; Safren, S. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Gonzalez, J. S.; Delahanty, L. M.; Safren, S. A.; Meigs, J. B.; Grant, R. W.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Delahanty, L. M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Meigs, J. B.; Grant, R. W.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA.
RP Gonzalez, JS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM jsgonzalez@partners.org
OI Grant, Richard/0000-0002-6164-8025
FU National Institute of Mental Health [1R01MH078571]; American Diabetes
Association Career Development Award; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) [K24 DK080140, K23 DK067452];
GlaxoSmithKline
FX J. S. Gonzalez's and S. A. Safren's efforts on this manuscript were
supported by a grant from the National Institute of Mental Health (no.
1R01MH078571). J. B. Meigs was supported by an American Diabetes
Association Career Development Award and by National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) grant no. K24
DK080140. J. B. Meigs currently has research grants from GlaxoSmithKline
and sanofi-aventis, and consults for GlaxoSmithKline, sanofi-aventis,
Interleukin Genetics, Kalypsis and Outcomes Science. R. W. Grant is
supported by a Career Development Award (no. K23 DK067452) from the
NIDDK.
NR 9
TC 39
Z9 42
U1 4
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD OCT
PY 2008
VL 51
IS 10
BP 1822
EP 1825
DI 10.1007/s00125-008-1113-x
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 344WQ
UT WOS:000258958400011
PM 18690422
ER
PT J
AU Baddley, JW
Sankara, IR
Rodriquez, JM
Pappas, PG
Many, WJ
AF Baddley, John W.
Sankara, Ishwara R.
Rodriquez, J. Martin
Pappas, Peter G.
Many, Wickliffe J., Jr.
TI Histoplasmosis in HIV-infected patients in a Southern regional medical
center: poor prognosis in the era of highly active antiretroviral
therapy
SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
LA English
DT Article
DE Histoplasma capsulatum; HIV; histoplasmosis; mortality
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RISK-FACTORS; DIAGNOSIS; BRAZIL
AB Histoplasmosis is an important opportunistic infection among HIV-infected patients in endemic areas, and clinical outcomes are often poor. Additional data on factors associated with outcomes are needed to better identify patients who may require aggressive care. Using a cohort of 46 HIV-infected patients with histoplasmosis from an underserved city endemic for histoplasmosis, we explored epidemiology, outcomes, and prognostic factors. Histoplasmosis was the 1st recognized manifestation of HIV Infection in 12 (26.1%) of 46 patients. Death occurred in IS (39%) patients within 3 months of diagnosis of histoplasmosis. Fungemia (odds ratio [OR], 12. 1; 95% confidence interval [0], 1.9-76; P = 0.008), renal insufficiency (OR, 11.3; 95% Cl, 1.7-77.2; P = 0.01), and age (OR, 0.9; 95% CI, 0.8-0.98; P = 0.02) were independent predictors of poor prognosis. Histoplasmosis in HIV patients is associated with poor outcomes. Identification of prognostic factors may be helpful in identifying patients who require more aggressive care. Published by Elsevier Inc.
C1 [Baddley, John W.; Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
[Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35322 USA.
[Sankara, Ishwara R.; Rodriquez, J. Martin; Many, Wickliffe J., Jr.] UAB Hlth Ctr Montgomery, Dept Med, Montgomery, AL 36116 USA.
RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
EM jbaddley@uab.edu
NR 13
TC 24
Z9 30
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0732-8893
J9 DIAGN MICR INFEC DIS
JI Diagn. Microbiol. Infect. Dis.
PD OCT
PY 2008
VL 62
IS 2
BP 151
EP 156
DI 10.1016/j.diagmicrobio.2008.05.006
PG 6
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 356SG
UT WOS:000259797300005
PM 18597967
ER
PT J
AU Leung, FW
AF Leung, Felix W.
TI Risk factors for gastrointestinal complications in aspirin users: Review
of clinical and experimental data
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Review
DE aspirin; stomach; NSAID; smoking; alcohol; nitric oxide; nitroglycerin
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; PROTON PUMP
INHIBITORS; INDUCED GASTRIC-ULCERS; NITRIC-OXIDE-DONORS; MUCOSAL
BLOOD-FLOW; FIBROBLAST-GROWTH-FACTOR; TOBACCO CIGARETTE-SMOKE;
ACETIC-ACID ULCERS; PEPTIC-ULCER
AB This paper reviews recent clinical evidence that suggests that aspirin prophylaxis against cardiac and cerebral vascular ischemia is associated with significant gastrointestinal complications. The clinical and experimental evidence to confirm the role of risk factors of concomitant use of nonsteroidal anti-inflammatory drugs (NSAID), tobacco cigarette smoking, and alcohol consumption are discussed. The limitations of long-term acid suppression treatment for the prevention of these complications are considered. Future experimental studies to guide the clinical approach to develop novel and potentially cost-effective management strategies are discussed.
C1 [Leung, Felix W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Div Gastroenterol Res & Med Serv, Sepulveda, CA 91343 USA.
[Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
RP Leung, FW (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Div Gastroenterol Res & Med Serv, 111G,16111 Plummer St, Sepulveda, CA 91343 USA.
EM felix.leung@va.gov
FU VA Medical Research Funds
FX This work was supported in part by VA Medical Research Funds.
NR 102
TC 4
Z9 6
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 OCT
PY 2008
VL 53
IS 10
BP 2604
EP 2615
DI 10.1007/s10620-007-0178-6
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 343DV
UT WOS:000258833800003
PM 18306040
ER
PT J
AU Rosman, AS
Chaparala, G
Monga, A
Spungen, AM
Bauman, WA
Korsten, MA
AF Rosman, Alan S.
Chaparala, Geeta
Monga, Amit
Spungen, Ann M.
Bauman, William A.
Korsten, Mark A.
TI Intramuscular neostigmine and glycopyrrolate safely accelerated bowel
evacuation in patients with spinal cord injury and defecatory disorders
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE bowel care; difficulty with evacuation; glycopyrrolate; neostigmine;
spinal cord injury
ID ACUTE COLONIC PSEUDOOBSTRUCTION; INTRANASAL NEOSTIGMINE;
MYASTHENIA-GRAVIS; ATROPINE; CARE
AB Difficulty with evacuation after spinal cord injury (SCI) may be due to a lack of parasympathetic stimulation of the colon. Prior studies in persons with spinal cord injury have suggested that intravenous administration of neostigmine stimulates colonic motility while glycopyrrolate attenuates some of the cholinergic side effects of neostigmine. We thus performed a double-blind, cross-over study to evaluate the effect of neostigmine/glycopyrrolate injections in patients with SCI and defecatory difficulties. Seven subjects received active treatment (neostigmine 2 mg and glycopyrrolate 0.4 mg intramuscularly) during three consecutive bowel evacuation sessions and were crossed-over to placebo injections for three consecutive sessions. Compared with placebo, neostigmine/glycopyrrolate reduced the total bowel evacuation time from 98.1 +/- 7.2 to 74.8 min +/- 5.8 (p < 0.05). The lowest heart rate or blood pressure was not significantly different between the treatment and placebo groups. In conclusion, neostigmine/glycopyrrolate may improve bowel evacuation in patients with SCI-related defecatory disorders.
C1 [Rosman, Alan S.; Korsten, Mark A.] James J Peters VA Med Ctr, Gastroenterol Practice & Spinal Cord Ctr Excellen, Bronx, NY 10468 USA.
[Chaparala, Geeta; Monga, Amit; Spungen, Ann M.; Bauman, William A.] James J Peters VA Med Ctr, Spinal Cord Ctr Excellence, Bronx, NY 10468 USA.
[Rosman, Alan S.; Chaparala, Geeta; Monga, Amit; Spungen, Ann M.; Bauman, William A.; Korsten, Mark A.] NYU, Mt Sinai Sch Med, New York, NY USA.
RP Korsten, MA (reprint author), James J Peters VA Med Ctr, Gastroenterol Practice & Spinal Cord Ctr Excellen, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM Mark.Korsten@VA.gov
NR 18
TC 17
Z9 18
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD OCT
PY 2008
VL 53
IS 10
BP 2710
EP 2713
DI 10.1007/s10620-008-0216-z
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 343DV
UT WOS:000258833800018
PM 18338263
ER
PT J
AU Leung, FW
AF Leung, Felix W.
TI Unsedated colonoscopy introduced to ensure access is acceptable to a
subgroup of veterans
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE unsedated colonoscopy; access; trainee; nursing shortage
ID FLEXIBLE SIGMOIDOSCOPY; SEDATION; ENDOSCOPY; INTUBATION; SKILLS
AB Background Nurses for monitoring and recovery are required for sedated colonoscopy. A nursing shortage necessitated discontinuation of sedated colonoscopy at a VA academic training program. Aim Elements of a case series that documented acceptance of unsedated colonoscopy are reviewed to raise awareness of the feasibility of this option. Method The pros and cons of sedation and no sedation were summarized. After discussion, patients who chose the unsedated option were scheduled for examination locally while those who desired sedation were scheduled at another VA site. Colonoscopy was performed by supervised trainees. Results From September 2002 to June 2005 scheduled unsedated colonoscopy was accepted by 145 of 483 veterans. Cecal intubation was achieved in 81%. Thus, of the cohort 30% had local access to and 24% completed unsedated colonoscopy. Implementation of unsedated colonoscopy obviated the need for two registered nurses previously required for sedated colonoscopy. Conclusion Unsedated colonoscopy offered as an option to ensure access was acceptable to a subgroup of our veteran patients. Implementation required less nursing resources. Techniques to enhance the cecal intubation rate of unsedated colonoscopy performed by supervised trainees deserves to be assessed in future studies.
C1 [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, VAGLAHS, Sepulveda Ambulatory Care Ctr,Div Gastroenterol, Sepulveda, CA 91343 USA.
[Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Vet Affairs Med Ctr, Sepulveda Ambulatory Care Ctr, Res & Med Serv, Los Angeles, CA USA.
RP Leung, FW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VAGLAHS, Sepulveda Ambulatory Care Ctr,Div Gastroenterol, 111G,16111 Plummer St, Sepulveda, CA 91343 USA.
EM Felix.leung@va.gov
FU Veterans Affairs Medical Research Funds; ASGE Endoscopic Career
Development Award
FX This work was supported in part by the Veterans Affairs Medical Research
Funds and ASGE Endoscopic Career Development Award (FWL 1985). The
author has full access to all of the data in the study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis. The author has no conflict of interest to declare.
NR 25
TC 8
Z9 8
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD OCT
PY 2008
VL 53
IS 10
BP 2719
EP 2722
DI 10.1007/s10620-007-0192-8
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 343DV
UT WOS:000258833800020
PM 18274901
ER
PT J
AU Adla, M
Downey, KK
Ahmad, J
AF Adla, Mahathi
Downey, Kathy K.
Ahmad, Jawad
TI Hepatic sarcoidosis associated with pegylated interferon alfa therapy
for chronic hepatitis C: Case report and review of literature
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
ID OF-THE-LITERATURE; VIRUS-INFECTION; RIBAVIRIN THERAPY; PLUS RIBAVIRIN
C1 [Adla, Mahathi; Ahmad, Jawad] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA.
[Downey, Kathy K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA.
RP Ahmad, J (reprint author), Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA.
EM ahmadj@msx.upmc.edu
NR 17
TC 11
Z9 11
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD OCT
PY 2008
VL 53
IS 10
BP 2810
EP 2812
DI 10.1007/s10620-008-0209-y
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 343DV
UT WOS:000258833800035
PM 18320314
ER
PT J
AU Kwon, DS
Gandhi, RT
AF Kwon, Douglas S.
Gandhi, Rajesh T.
TI HIV vaccines: current approaches and new developments
SO DRUGS OF THE FUTURE
LA English
DT Review
ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; ANKARA BOOST
REGIMEN; CELL RESPONSES; TYPE-1 INFECTION; AIDS VACCINE; THERAPEUTIC
IMMUNIZATION; ANTIBODY NEUTRALIZATION; ANTIRETROVIRAL THERAPY;
MONOCLONAL-ANTIBODY
AB The challenge of developing an acquired immune deficiency syndrome (AIDS) vaccine continues to be paramount as the global AIDS epidemic progresses. Traditional vaccine strategies that induce broadly neutralizing antibodies have so far been ineffective, and focus is now turning toward more novel approaches that seek to elicit T-lymphocyte responses. Recent results from the STEP vaccine trial, a test-of-concept trial of an adenoviral serotype 5-based vaccine, failed to show a protective effect despite clear induction of human immunodeficiency virus (HIV) immunogenicity and early promising results in nonhuman primate studies. The results from the STEP trial demonstrate that innovative approaches and a better understanding of the immunopathogenesis of HIV disease are needed for the goal of a safe, globally effective HIV vaccine to be realized.
C1 [Kwon, Douglas S.; Gandhi, Rajesh T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02115 USA.
[Kwon, Douglas S.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Gandhi, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02115 USA.
EM rgandhi@partners.org
FU Harvard University [1 P30AI060354-02]; National Institutes of Health
(NIH) [1 R01 AI066992-01A1]; Howard Hughes Medical Institute
FX RTG would like to acknowledge grant support from the Harvard University
Center for AIDS Research (1 P30AI060354-02), a National Institutes of
Health (NIH) funded program, and the NIH (1 R01 AI066992-01A1). DSK
would like to acknowledge fellowship support from the Howard Hughes
Medical Institute.
NR 78
TC 0
Z9 0
U1 1
U2 4
PU PROUS SCIENCE, SA
PI BARCELONA
PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN
SN 0377-8282
J9 DRUG FUTURE
JI Drug Future
PD OCT
PY 2008
VL 33
IS 10
BP 861
EP 868
DI 10.1358/dof.2008.033.10.1253844
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 388JB
UT WOS:000262015000005
ER
PT J
AU Gallun, F
Souza, P
AF Gallun, Frederick
Souza, Pamela
TI Exploring the role of the modulation spectrum in phoneme recognition
SO EAR AND HEARING
LA English
DT Article
ID AMPLITUDE-MODULATION; FREQUENCY-SELECTIVITY; TEMPORAL INFORMATION;
RELATIVE IMPORTANCE; SPEECH RECOGNITION; INTELLIGIBILITY; RECEPTION;
MASKING; CUES
AB Objectives: The ability of human listeners to identify consonants (presented as nonsense syllables) on the basis of primarily temporal information was compared with the predictions of a simple model based on the amplitude modulation spectra of the stimuli calculated for six octave-spaced carrier frequencies (250 to 8000 Hz) and six octave-spaced amplitude modulation frequencies (1 to 32 Hz).
Design: The listeners and the model were presented with 16 phonemes each spoken by four different talkers processed so that one, two, four, or eight bands of spectral information remained. The average modulation spectrum of each of the processed phonemes was extracted and similarity across phonemes was calculated by the use of a spectral correlation index (SCI).
Results: The similarity of the modulation spectra across phonemes as assessed by the spectral correlation index was a strong predictor of the confusions made by human listeners.
Conclusions: This result suggests that a sparse set of time-averaged patterns of modulation energy can capture a meaningful aspect of the information listeners use to distinguish among speech signals.
C1 [Gallun, Frederick] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res, Portland, OR USA.
[Souza, Pamela] Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA.
RP Gallun, F (reprint author), VA NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM Frederick.Gallun@va.gov
OI Gallun, Frederick/0000-0002-4145-2199
FU Department of Veterans Affairs, Veterans Health Administration,
Rehabilitation Research and Development Service [DC006014]; National
Institute for Deaffness and Communication Disorders [DC04661]; Bloedel
Hearing Research Center
FX The research was supported by the Department of Veterans Affairs,
Veterans Health Administration, Rehabilitation Research and Development
Service (to F. G.), grants DC006014 and DC04661 from the National
Institute for Deaffness and Communication Disorders (to P. S.), and by
the Bloedel Hearing Research Center (to P. S.).
NR 39
TC 24
Z9 24
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0196-0202
J9 EAR HEARING
JI Ear Hear.
PD OCT
PY 2008
VL 29
IS 5
BP 800
EP 813
DI 10.1097/AUD.0b013e31817e73ef
PG 14
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 350FS
UT WOS:000259338700012
PM 18596640
ER
PT J
AU Khandaker, GM
Barnett, JH
Jones, PB
AF Khandaker, G. M.
Barnett, J. H.
Jones, P. B.
TI Systematic review and meta-analysis of population-based Studies of
premorbid intelligence and schizophrenia
SO EARLY INTERVENTION IN PSYCHIATRY
LA English
DT Meeting Abstract
C1 [Khandaker, G. M.] Cambridge & Peterborough Mental Hlth Partnership, Cambridge, England.
[Barnett, J. H.; Jones, P. B.] Univ Cambridge, Dept Psychiat, Cambridge, England.
[Barnett, J. H.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1751-7885
J9 EARLY INTERV PSYCHIA
JI Early Interv. Psychiatry
PD OCT
PY 2008
VL 2
BP A69
EP A69
PG 1
WC Psychiatry
SC Psychiatry
GA 449PB
UT WOS:000266341400256
ER
PT J
AU Tranulis, C
Park, L
Freudenreich, O
Goff, DC
Good, BJ
AF Tranulis, C.
Park, L.
Freudenreich, O.
Goff, D. C.
Good, B. J.
TI Early psychosis experiences - IPSOS report for the Boston site
SO EARLY INTERVENTION IN PSYCHIATRY
LA English
DT Meeting Abstract
C1 [Tranulis, C.; Good, B. J.] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA.
[Park, L.; Freudenreich, O.; Goff, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1751-7885
J9 EARLY INTERV PSYCHIA
JI Early Interv. Psychiatry
PD OCT
PY 2008
VL 2
BP A27
EP A27
PG 1
WC Psychiatry
SC Psychiatry
GA 449PB
UT WOS:000266341400104
ER
PT J
AU Chiu, Y
Rudin, CM
Shapiro, GI
Roberts, AW
Brown, JR
Wilson, W
O'Connor, O
Xiong, H
Enschede, S
Krivoshik, A
AF Chiu, Y.
Rudin, C. M.
Shapiro, G. I.
Roberts, A. W.
Brown, J. R.
Wilson, W.
O'Connor, O.
Xiong, H.
Enschede, S.
Krivoshik, A.
TI Advantages of a modified continual reassessment method (CRM) for dose
finding studies: experience in ongoing phase I trials with ABT-263
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Chiu, Y.] Abbott Labs, Clin Pharmacol & Pharmacometr, Abbott Pk, IL 60064 USA.
[Rudin, C. M.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Shapiro, G. I.; Brown, J. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Roberts, A. W.] Royal Melbourne Hosp, Dept Clin Haematol & Med Oncol, Parkville, Vic 3050, Australia.
[Wilson, W.] NCI, Canc Res Ctr, Bethesda, MD 20892 USA.
[O'Connor, O.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
[Xiong, H.; Enschede, S.; Krivoshik, A.] Abbott Labs, Abbott Oncol, Abbott Pk, IL 60064 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 14
EP 14
DI 10.1016/S1359-6349(08)71966-9
PG 1
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200032
ER
PT J
AU Anderson, K
AF Anderson, K.
TI Bortezomib therapy of multiple myeloma
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Anderson, K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 15
EP 16
DI 10.1016/S1359-6349(08)71970-0
PG 2
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200036
ER
PT J
AU Spratlin, J
Arkenau, HT
George, S
Serkova, NJ
Germuska, M
Brock, K
Gedrich, R
Scurr, M
Demetri, GD
Camidge, DR
AF Spratlin, J.
Arkenau, H. T.
George, S.
Serkova, N. J.
Germuska, M.
Brock, K.
Gedrich, R.
Scurr, M.
Demetri, G. D.
Camidge, D. R.
TI Analyses of pharmacodynamic (PD) assessments collected during expanded
cohorts (EC) of a phase I trial with OSI-930, a multi-targeted oral
tyrosine kinase inhibitor (TKI)
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Spratlin, J.; Serkova, N. J.; Camidge, D. R.] Univ Colorado, Ctr Canc, Dev Therapeut Program, Aurora, CO USA.
[Arkenau, H. T.; Germuska, M.; Scurr, M.] Royal Marsden Hosp, Drug Dev Unit, Sutton, Surrey, England.
[George, S.; Demetri, G. D.] Harvard Univ, Sch Med, Ludwig Ctr, Boston, MA USA.
[George, S.; Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Brock, K.] OSI Pharmaceut Inc, Oxford, England.
[Gedrich, R.] OSI Pharmaceut Inc, Boulder, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 19
EP 19
DI 10.1016/S1359-6349(08)71981-5
PG 1
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200047
ER
PT J
AU Besse, B
Eaton, KD
Soria, JC
Lynch, TJ
Miller, V
Wong, KK
Powell, C
Quinn, S
Zacharchuk, C
Sequist, LV
AF Besse, B.
Eaton, K. D.
Soria, J. C.
Lynch, T. J.
Miller, V.
Wong, K. K.
Powell, C.
Quinn, S.
Zacharchuk, C.
Sequist, L. V.
TI Neratinib (HKI-272), an irreversible pan-ErbB receptor tyrosine kinase
inhibitor: preliminary results of a phase 2 trial in patients with
advanced non-small cell lung cancer
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Sequist, L. V.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Lynch, T. J.; Sequist, L. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Besse, B.; Soria, J. C.] Inst Gustave Roussy, Dept Med, Serv Gard 7, Villejuif, France.
[Eaton, K. D.] Univ Washington, Dept Med, Seattle, WA USA.
[Lynch, T. J.] Harvard Univ, Sch Med, Div Hematol & Oncol, Boston, MA USA.
[Miller, V.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Quinn, S.; Zacharchuk, C.] Wyeth Ayerst Res, Oncol, Cambridge, MA USA.
[Powell, C.] Wyeth Ayerst Res, Global Biostat & Programming, Cambridge, MA USA.
[Wong, K. K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wong, K. K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
NR 0
TC 7
Z9 8
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 64
EP 64
DI 10.1016/S1359-6349(08)72135-9
PG 1
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200201
ER
PT J
AU Wagner, AJ
Yazji, S
Morgan, JA
Choy, E
George, S
Hohos, M
O'Mara, M
Demetri, GD
AF Wagner, A. J.
Yazji, S.
Morgan, J. A.
Choy, E.
George, S.
Hohos, M.
O'Mara, M.
Demetri, G. D.
TI A phase II study of the KIT inhibitor XL820 in patients with advanced
gastrointestinal stromal tumors (GIST) resistant to or intolerant of
imatinib and/or sunitinib
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Choy, E.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA.
[Yazji, S.] Exelixis Inc, Oncol Clin Dev, San Francisco, CA USA.
[Wagner, A. J.; Morgan, J. A.; George, S.; Hohos, M.; O'Mara, M.; Demetri, G. D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 67
EP 67
DI 10.1016/S1359-6349(08)72144-X
PG 1
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200210
ER
PT J
AU Calvo, E
Edelman, G
Baselga, J
Kwak, E
Scheffold, C
Nguyen, L
Shapiro, GI
AF Calvo, E.
Edelman, G.
Baselga, J.
Kwak, E.
Scheffold, C.
Nguyen, L.
Shapiro, G. I.
TI A phase I dose-escalation study of the safety, pharmacokinetics and
pharmacodynamics of XL147, a novel PI3K inhibitor administered orally to
patients with advanced solid tumors
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Calvo, E.; Baselga, J.] Hosp Univ Vall Hebron, Barcelona, Spain.
[Edelman, G.] Texas Onc, Med Oncol, Irving, TX USA.
[Kwak, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Scheffold, C.] Exelixis Inc, Clin Dev, San Francisco, CA USA.
[Nguyen, L.] Exelixis Inc, Nonclin Dev, San Francisco, CA USA.
[Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 5
Z9 5
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 69
EP 69
DI 10.1016/S1359-6349(08)72150-5
PG 1
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200216
ER
PT J
AU LoRusso, P
Sarker, D
Von Hoff, D
Tibes, R
Derynck, MK
Ware, JA
Yan, Y
Demetri, GD
de Bono, JS
Wagner, AJ
AF LoRusso, P.
Sarker, D.
Von Hoff, D.
Tibes, R.
Derynck, M. K.
Ware, J. A.
Yan, Y.
Demetri, G. D.
de Bono, J. S.
Wagner, A. J.
TI Pharmacokinetics and pharmacodynamic biomarkers for the pan-PI3K
inhibitor GDC-0941: Initial Phase I evaluation
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA.
[Sarker, D.; de Bono, J. S.] Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England.
[Von Hoff, D.; Tibes, R.] TGen Scottsdale Healthcare Oncol, Scottsdale, AZ USA.
[Derynck, M. K.; Ware, J. A.; Yan, Y.] Genentech Inc, Oncol, San Francisco, CA 94080 USA.
[Demetri, G. D.; Wagner, A. J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 3
Z9 3
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 70
EP 71
DI 10.1016/S1359-6349(08)72155-4
PG 2
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200221
ER
PT J
AU Pishvajan, MJ
Wagner, A
Deeken, J
He, AR
Hwang, J
Malik, S
Cotarla, I
Demetri, G
Marshall, JL
Wojtowicz-Praga, S
AF Pishvajan, M. J.
Wagner, A.
Deeken, J.
He, A. R.
Hwang, J.
Malik, S.
Cotarla, I.
Demetri, G.
Marshall, J. L.
Wojtowicz-Praga, S.
TI A Phase 1 clinical trial of the oral PPAR gamma agonist, CS-7017 in
patients with advanced malignancies
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Pishvajan, M. J.; Deeken, J.; He, A. R.; Hwang, J.; Malik, S.; Cotarla, I.; Marshall, J. L.] Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Wagner, A.; Demetri, G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wojtowicz-Praga, S.] Daiichi Sankyo Pharma Dev, Clin Dev Oncol, Edison, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 128
EP 129
DI 10.1016/S1359-6349(08)72343-7
PG 2
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200408
ER
PT J
AU Castaigne, JP
Elian, KM
Bouchard, D
Neale, A
Rosenfeld, S
Drappatz, J
Groves, M
Wen, P
Bento, P
Lawrence, B
AF Castaigne, J. P.
Elian, K. M.
Bouchard, D.
Neale, A.
Rosenfeld, S.
Drappatz, J.
Groves, M.
Wen, P.
Bento, P.
Lawrence, B.
TI ANG1005: Preliminary clinical safety and tolerability in patients with
recurrent malignant glioma
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Castaigne, J. P.; Elian, K. M.; Bouchard, D.; Bento, P.] Angiochem Inc, Clin Res, Montreal, PQ, Canada.
[Neale, A.] WinPharm Associates LLC, Clin Res, Danville, PA USA.
[Rosenfeld, S.] Columbia Univ, Med Ctr, Brain Tumor Ctr, New York, NY USA.
[Drappatz, J.; Wen, P.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA.
[Groves, M.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Lawrence, B.] Angiochem Inc, Drug Dev, Montreal, PQ, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 133
EP 134
DI 10.1016/S1359-6349(08)72359-0
PG 2
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200424
ER
PT J
AU Hurwitz, H
LoRusso, P
Shapiro, GI
Wolanksi, A
Chemidlin, J
Masson, E
Syed, S
Kollia, G
Conlon, K
AF Hurwitz, H.
LoRusso, P.
Shapiro, G. I.
Wolanksi, A.
Chemidlin, J.
Masson, E.
Syed, S.
Kollia, G.
Conlon, K.
TI Phase I study of food effects on pharmacokinetics of brivanib alaninate
in patients with advanced or metastatic solid tumors
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Hurwitz, H.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA.
[Shapiro, G. I.; Wolanksi, A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chemidlin, J.; Masson, E.; Syed, S.; Kollia, G.; Conlon, K.] Bristol Myers Squibb Co, Princeton, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 135
EP 135
DI 10.1016/S1359-6349(08)72363-2
PG 1
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200428
ER
PT J
AU Matthews, CM
Ho, SN
Barve, M
Bell-McGuinn, KM
Gilbert, L
Penson, RT
Lengyel, E
Weymer, S
Gilder, K
Schilder, RJ
AF Matthews, C. M.
Ho, S. N.
Barve, M.
Bell-McGuinn, K. M.
Gilbert, L.
Penson, R. T.
Lengyel, E.
Weymer, S.
Gilder, K.
Schilder, R. J.
TI A phase 2, single-arm study of volociximab (an anti-a5 beta 1 integrin
antibody) monotherapy in patients with platinum-resistant advanced
epithelial ovarian cancer or primary peritoneal cancer
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Matthews, C. M.] Mary Crowley Canc Res Ctr, Dallas, TX USA.
[Ho, S. N.] Biogen Idec, Translat Oncobiol, San Diego, CA USA.
[Barve, M.] Texas Oncol Presbyterian, Med Oncol, Dallas, TX USA.
[Bell-McGuinn, K. M.] Mem Sloan Kettering, Gynecol Med Oncol, New York, NY USA.
[Gilbert, L.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
[Penson, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lengyel, E.] Univ Chicago, Dept Obstet & Gynecol Gynecol Oncol, Chicago, IL 60637 USA.
[Weymer, S.] Biogen Idec, Clin Operat Oncol, San Diego, CA USA.
[Gilder, K.] Biogen Idec, Biostat, San Diego, CA USA.
[Schilder, R. J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
RI Lengyel, Ernst/D-9220-2014
OI Lengyel, Ernst/0000-0001-8624-1507
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 164
EP 165
DI 10.1016/S1359-6349(08)72453-4
PG 2
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200516
ER
PT J
AU Janne, PA
Wax, M
Leach, J
Engelman, J
AF Janne, P. A.
Wax, M.
Leach, J.
Engelman, J.
TI Targeting MET with XL184 to reverse EGFR tyrosine kinase inhibitor (TKI)
resistance in NSCLC: impact of preclinical studies on clinical trial
design
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Janne, P. A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Wax, M.] Summit Med Grp, Berkeley Hts, NJ USA.
[Leach, J.] Pk Nicollet Clin, St Louis, MN USA.
[Engelman, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
NR 0
TC 5
Z9 5
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 174
EP 174
DI 10.1016/S1359-6349(08)72486-8
PG 1
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200549
ER
PT J
AU Schellens, J
Guo, F
Janne, PA
Eckhardt, SG
Camidge, DR
Taylor, I
Lucca, J
Boss, DS
Wong, SG
Britten, CD
AF Schellens, J.
Guo, F.
Jaenne, P. A.
Eckhardt, S. G.
Camidge, D. R.
Taylor, I.
Lucca, J.
Boss, D. S.
Wong, S. G.
Britten, C. D.
TI First-in-human (FIH) study of PF-00299804 in advanced cancer patients:
correlation between pharmacokinetics (PK) and pharmacodynamics (PD)
SO EJC SUPPLEMENTS
LA English
DT Meeting Abstract
CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY OCT 21-24, 2008
CL Geneva, SWITZERLAND
SP EORTC, NCI, AACR
C1 [Schellens, J.; Boss, D. S.] Netherlands Canc Inst, Amsterdam, Netherlands.
[Guo, F.] Pfizer Global Res & Dev, Clin Pharmacol, New London, CT USA.
[Jaenne, P. A.; Lucca, J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Eckhardt, S. G.; Camidge, D. R.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA.
[Taylor, I.] Pfizer Global Res & Dev, Groton New London Labs, New London, CT USA.
[Britten, C. D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1359-6349
J9 EJC SUPPL
JI EJC Suppl.
PD OCT
PY 2008
VL 6
IS 12
BP 177
EP 178
DI 10.1016/S1359-6349(08)72498-4
PG 2
WC Oncology
SC Oncology
GA 376ZJ
UT WOS:000261221200561
ER
PT J
AU Bouillon, R
Carmeliet, G
Verlinden, L
van Etten, E
Verstuyf, A
Luderer, HF
Lieben, L
Mathieu, C
Demay, M
AF Bouillon, Roger
Carmeliet, Geert
Verlinden, Lieve
van Etten, Evelyne
Verstuyf, Annemieke
Luderer, Hilary F.
Lieben, Liesbet
Mathieu, Chantal
Demay, Marie
TI Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice
SO ENDOCRINE REVIEWS
LA English
DT Review
ID PROSTATE-CANCER RISK; NONOBESE DIABETIC MICE; EXPERIMENTAL AUTOIMMUNE
ENCEPHALOMYELITIS; MINERAL ION HOMEOSTASIS; D-DEFICIENCY RICKETS;
D-RESISTANT RICKETS; D-3 1-ALPHA-HYDROXYLASE GENE;
INFLAMMATORY-BOWEL-DISEASE; PARATHYROID-HORMONE GENE; DNA MICROARRAY
ANALYSIS
AB The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxy-vitamin D [1,25-(OH)(2)D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1 alpha-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype. The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)(2)D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1 alpha-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D- deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR- deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status. (Endocrine Reviews 29: 726-776, 2008)
C1 [Bouillon, Roger; Carmeliet, Geert; Verlinden, Lieve; van Etten, Evelyne; Verstuyf, Annemieke; Lieben, Liesbet; Mathieu, Chantal] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, B-3000 Louvain, Belgium.
[Luderer, Hilary F.; Demay, Marie] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
RP Bouillon, R (reprint author), Katholieke Univ Leuven, Lab Expt Med & Endocrinol, Herestr 49,O&N 1 Bus 902, B-3000 Louvain, Belgium.
EM Roger.Bouillon@med.kuleuven.be
RI Verlinden, Lieve/E-6517-2011
FU University of Leuven [GOA/04/10, EF/05/007]; Flanders Research
Foundation [G.0084.02, G.0233.04, G.0508.05, G.0552.06, G.0553.06,
G.0649.08]; Juvenile Diabetes Research Foundation (JDRF) [4-2005-1237,
3-2006-33]; Belgium Program on Interuniversity Poles of Attraction
initiated by the Belgian State [IUAP P5/17, P6/34]; Clinical Research
Fellowship (FWO, Belgium); National Institutes of Health [DK46974]
FX The work in the authors' laboratories was supported by the University of
Leuven (GOA/04/10, EF/05/007), Flanders Research Foundation [Fonds voor
Wetenschappelijk onderzoek Vlaanderen (FWO), Grants G.0084.02,
G.0233.04, G.0508.05, G.0552.06, G.0553.06, and G.0649.08], the Juvenile
Diabetes Research Foundation (JDRF; Grant 4-2005-1237), and the Belgium
Program on Interuniversity Poles of Attraction initiated by the Belgian
State (Grants IUAP P5/17 and P6/34). C.M. is holder of a Clinical
Research Fellowship (FWO, Belgium), E. v. E. holds a Post-doctoral
Fellowship (JDRF, 3-2006-33), and L.L. is a fellow of the IWT-Flanders.
The work in Boston was supported by National Institutes of Health Grant
DK46974.
NR 668
TC 640
Z9 673
U1 13
U2 62
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD OCT
PY 2008
VL 29
IS 6
BP 726
EP 776
DI 10.1210/er.2008-0004
PG 51
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 358CB
UT WOS:000259893000004
PM 18694980
ER
PT J
AU Knauf, C
Cani, PD
Ait-Belgnaoui, A
Benani, A
Dray, C
Cabou, C
Colom, A
Uldry, M
Rastrelli, S
Sabatier, E
Godet, N
Waget, A
Penicaud, L
Valet, P
Burcelin, R
AF Knauf, Claude
Cani, Patrice D.
Ait-Belgnaoui, Afifa
Benani, Alexandre
Dray, Cedric
Cabou, Cendrine
Colom, Andre
Uldry, Marc
Rastrelli, Sophie
Sabatier, Eric
Godet, Natacha
Waget, Aurelie
Penicaud, Luc
Valet, Philippe
Burcelin, Remy
TI Brain glucagon-like peptide 1 signaling controls the onset of high-fat
diet-induced insulin resistance and reduces energy expenditure
SO ENDOCRINOLOGY
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; MUSCLE GLYCOGEN-SYNTHESIS; ACTIVATED
RECEPTOR-ALPHA; GLUCOSE-HOMEOSTASIS; KNOCKOUT MOUSE; BINDING-SITES;
FOOD-INTAKE; RAT-BRAIN; NULL MICE; GLP-1
AB Glucagon-like peptide-1 (GLP-1) is a peptide released by the intestine and the brain. We previously demonstrated that brain GLP-1 increases glucose-dependent hyperinsulinemia and insulin resistance. These two features are major characteristics of the onset of type 2 diabetes. Therefore, we investigated whether blocking brain GLP-1 signaling would prevent high-fat diet (HFD)-induced diabetes in the mouse. Our data show that a 1-month chronic blockage of brain GLP-1 signaling by exendin-9 (Ex9), totally prevented hyperinsulinemia and insulin resistance in HFD mice. Furthermore, food intake was dramatically increased, but body weight gain was unchanged, showing that brain GLP-1 controlled energy expenditure. Thermogenesis, glucose utilization, oxygen consumption, carbon dioxide production, muscle glycolytic respiratory index, UCP2 expression in muscle, and basal ambulatory activity were all increased by the exendin-9 treatment. Thus, we have demonstrated that in response to a HFD, brain GLP-1 signaling induces hyperinsulinemia and insulin resistance and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity.
C1 [Knauf, Claude; Cani, Patrice D.; Dray, Cedric; Cabou, Cendrine; Colom, Andre; Rastrelli, Sophie; Sabatier, Eric; Godet, Natacha; Waget, Aurelie; Valet, Philippe; Burcelin, Remy] Univ Toulouse 3, CHU Rangueil, Inst Med Mol Rangueil 12MR, Unite 858,Inst Federatif Rech 31,Inst Natl Sante, F-31432 Toulouse 4, France.
[Cani, Patrice D.] Catholic Univ Louvain, Unit Pharmacokinet Metab Nutr & Toxicol, B-1200 Brussels, Belgium.
[Ait-Belgnaoui, Afifa] Inst Natl Rech Agron ESAP, Unite Mixte Rech 1054, Neurogastroenterol & Nutr Unit, F-31931 Toulouse, France.
[Benani, Alexandre; Penicaud, Luc] Univ Toulouse 3, Ctr Natl Rech Sci, Unite Mixte Rech 5241, Lab Metab Plasticite Mitochondrie, F-31432 Toulouse, France.
[Uldry, Marc] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Uldry, Marc] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Burcelin, R (reprint author), Univ Toulouse 3, CHU Rangueil, Inst Med Mol Rangueil 12MR, Unite 858,Inst Federatif Rech 31,Inst Natl Sante, BP84225, F-31432 Toulouse 4, France.
EM remy.burcelin@inserm.fr
RI burcelin, remy/M-6013-2014; Benani, Alexandre/F-4002-2012;
OI Benani, Alexandre/0000-0003-2046-0162; Cani, Patrice
D./0000-0003-2040-2448
FU CESNA (Club d'Etude du Systeme Nerveux Autonome)
FX We thank Prof. Louis Casteilla for helpful discussion. R.B., C.K., and
P.D.C. are members of CESNA (Club d'Etude du Systeme Nerveux Autonome)
and are grateful for its financial support. We fully acknowledge the
expertise of Laurent Montbrun and Sophie Le Gonidec from the functional
exploration platform, Toulouse-Midi-Pyrenees-Genopole concerning energy
expenditure measurements, and Daniele Daviaud for technical advice. We
also thank Dr. John Woodley for editing the English.
NR 47
TC 65
Z9 67
U1 0
U2 5
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 OCT
PY 2008
VL 149
IS 10
BP 4768
EP 4777
DI 10.1210/en.2008-0180
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 351BW
UT WOS:000259400300002
PM 18556349
ER
PT J
AU Sang, XP
Curran, MS
Wood, AW
AF Sang, Xianpeng
Curran, Matthew S.
Wood, Antony W.
TI Paracrine insulin-like growth factor signaling influences primordial
germ cell migration: In vivo evidence from the zebrafish model
SO ENDOCRINOLOGY
LA English
DT Article
ID ADHESION MOLECULES; EMBRYONIC GROWTH; STEM-CELLS; EXPRESSION; RECEPTOR;
CHEMOKINE; SURVIVAL; GENE; CANCER; CXCR4
AB IGF signaling has been shown to stimulate migration of multiple cell types in vitro, but few studies have confirmed an equivalent function for IGF signaling in vivo. We recently showed that suppression of IGF receptors in the zebrafish embryo disrupts primordial germ cell (PGC) migration, but the mechanism underlying these effects has not been elucidated. We hypothesized that PGCs are intrinsically dependent upon IGF signaling during the migratory phase of development. To test this hypothesis, we first examined the spatial expression patterns of IGF ligand genes (igf1, igf2a, and igf2b) in the zebrafish embryo. In situ analyses revealed distinct expression patterns for each IGF ligand gene, with igf2b mRNA expressed in a spatial pattern that correlates strongly with PGC migration. To determine whether PGC migration is responsive to IGF signaling in vivo, we synthesized gene hybrid expression constructs that permit conditional overexpression of IGF ligands by PGCs into the PGC microenvironment. Conditional overexpression of IGF ligands consistently disrupted PGC migration, confirming that PGC migration is sensitive to local aberrations in IGF signaling. Finally, we show that conditional suppression of IGF signaling, via PGC-specific overexpression of a mutant IGF-I receptor, disrupts PGC migration, confirming that zebrafish PGCs intrinsically require IGF signaling for directional migration in vivo. Collectively, these studies confirm an in vivo role for IGF signaling in cell migration and identify a candidate ligand gene (igf2b) regulating PGC migration in the zebrafish.
C1 Harvard Univ, Sch Med, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol,Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Wood, AW (reprint author), 55 Fruit St,THR 933, Boston, MA 02114 USA.
EM awwood@partners.org
FU Vincent Memorial Research Funds; Harvard University; Harvard
Undergraduate Research Program; Harvard Stem Cell Institute Summer
Undergraduate Research Program
FX The study was supported financially by Vincent Memorial Research Funds.
X. S. received a fellowship from the Program for Research in Science and
Engineering at Harvard University, and was supported by the Harvard
Undergraduate Research Program. X. S. and M. S. C. were further
supported by the Harvard Stem Cell Institute Summer Undergraduate
Research Program.
NR 41
TC 19
Z9 19
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 OCT
PY 2008
VL 149
IS 10
BP 5035
EP 5042
DI 10.1210/en.2008-0534
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 351BW
UT WOS:000259400300029
PM 18566124
ER
PT J
AU Lin, D
Bucci, MK
Eisele, DW
Wang, SJ
AF Lin, Doris
Bucci, M. Kara
Eisele, David W.
Wang, Steven J.
TI Squamous cell carcinoma of the buccal mucosa: A retrospective analysis
of 22 cases
SO ENT-EAR NOSE & THROAT JOURNAL
LA English
DT Article
AB We examined our institution's experience with 22 cases of previously untreated buccal squamous cell carcinoma via a retrospective chart review. Eleven of these patients had been treated with a combination of surgical excision and postoperative radiation therapy, 8 patients with surgical excision alone, and 3 patients with radiation therapy alone. The overall 3-year locoregional recurrence rate was 32% (n = 7). The 3-year survival rates were 82% after surgery plus radiation (9 of 11 patients), 63% after surgery alone (5 of 8), and 33% after radiation alone (1 of 3). Three-year T-category-specific survival rates were 100% for category T1 tumors (3 of 3 patients), 73% for T2 (8 of 11), 50% for T3 (3 of 6), and 50% for T4 (1 of 2). Although the small size of our study precluded any statistically significant conclusions, we believe that locoregional control and survival rates may be greater with surgical excision plus postoperative radiation than with treatment with either modality alone.
C1 [Lin, Doris; Eisele, David W.; Wang, Steven J.] Univ Calif San Francisco, Sch Med, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USA.
[Bucci, M. Kara] Univ Calif San Francisco, Sch Med, Dept Radiat Oncol, San Francisco, CA 94143 USA.
RP Wang, SJ (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111B, San Francisco, CA 94121 USA.
EM swang@ohns.ucsf.edu
NR 15
TC 3
Z9 3
U1 0
U2 0
PU VENDOME GROUP LLC
PI NEW YORK
PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA
SN 0145-5613
J9 ENT-EAR NOSE THROAT
JI ENT-Ear Nose Throat J.
PD OCT
PY 2008
VL 87
IS 10
BP 582
EP 586
PG 5
WC Otorhinolaryngology
SC Otorhinolaryngology
GA V10PD
UT WOS:000207475000012
PM 18833538
ER
PT J
AU Garshick, E
Laden, F
Hart, JE
Rosner, B
Davis, ME
Eisen, EA
Smith, TJ
AF Garshick, Eric
Laden, Francine
Hart, Jaime E.
Rosner, Bernard
Davis, Mary E.
Eisen, Ellen A.
Smith, Thomas J.
TI Lung cancer and vehicle exhaust in trucking industry workers
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE diesel exhaust; lung cancer; occupational exposure; particulate matter;
traffic
ID PARTICULATE AIR-POLLUTION; IN-USE DIESEL; SIZE DISTRIBUTION; RAILROAD
WORKERS; EMISSION RATES; FOLLOW-UP; EXPOSURE; MATTER; SMOKING; PARTICLES
AB BACKGROUND: An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties.
OBJECTIVES We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure.
METHODS: Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey.
RESULTS: Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk.
CONCLUSIONS: Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.
C1 [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA.
[Garshick, Eric; Laden, Francine; Hart, Jaime E.; Rosner, Bernard] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA.
[Laden, Francine; Hart, Jaime E.; Davis, Mary E.; Smith, Thomas J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA.
[Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Davis, Mary E.] Univ Maine, Sch Econ, Orono, ME USA.
[Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci Div, Berkeley, CA 94720 USA.
[Eisen, Ellen A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA.
RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, Boston, MA 02132 USA.
EM eric.garshick@va.gov
FU National Institutes of Health [R01 CA90792]; National Cancer Institute;
National Institute of Environmental Health Sciences [ES00002]
FX This work was supported by grant R01 CA90792 from the National
Institutes of Health/National Cancer Institute and grant ES00002 from
the National Institute of Environmental Health Sciences.
NR 52
TC 55
Z9 56
U1 3
U2 17
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD OCT
PY 2008
VL 116
IS 10
BP 1327
EP 1332
DI 10.1289/chp.11293
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 355TA
UT WOS:000259730100024
PM 18941573
ER
PT J
AU Borges, K
Gearing, M
Rittling, S
Sorensen, ES
Kotloski, R
Denhardt, DT
Dingledine, R
AF Borges, Karin
Gearing, Maria
Rittling, Susan
Sorensen, Esben S.
Kotloski, Robert
Denhardt, David T.
Dingledine, Raymond
TI Characterization of osteopontin expression and function after status
epilepticus
SO EPILEPSIA
LA English
DT Article
DE Seizure; Pilocarpine; Inflammation; Axonal degeneration; Neuronal
degeneration
ID AMYLOID PRECURSOR PROTEIN; UP-REGULATION; FOCAL STROKE;
PARKINSONS-DISEASE; FOREBRAIN ISCHEMIA; DEFICIENT MICE; MESSENGER-RNA;
AXONAL INJURY; BRAIN-DAMAGE; RAT-BRAIN
AB Purpose: Osteopontin is a cytokine found in many tissues and plays a role in tissue injury and repair. This study had two goals: to characterize osteopontin expression after status epilepticus (SE), and to test the hypotheses that osteopontin affects the susceptibility to seizures or alters cell death and inflammation after SE.
Methods: Pilocarpine was used to induce SE in OPN-/- and OPN+/+ mice to compare seizure susceptibility, neuropathological markers including real time PCR for inflammatory genes, and osteopontin immunohistochernistry. The effect of added osteopontin on excitotoxicity by N-methyl-D-aspartate in neuronal cultures of ONP-/- mice was determined.
Results: Neurons undergoing degeneration showed osteopontin immunoreactivity 2-3 days after SE. After 10 to 31 days degenerating axons in the thalamus were osteoponti n -positive. The susceptibility to seizures of OPN-/- and OPN+/+ mice in the pilocarpine, fluorothyl, and maximal electroshock models was similar. There were no significant differences in the extent of neuronal damage after pilocarpine-induced SE, the expression of several neuropathological markers or the RNA levels of selected inflammatory genes. Recombinant and natural bovine osteopontin did not affect the extent of NMDA-induced cell death in OPN-/- mouse neuronal cultures.
Conclusion: We demonstrated that osteopontin is up-regulated in response to SE in distinct temporal sequences in the hippocampus, specifically in degenerating neurons and axons. However, osteopontin did not appear to regulate neurodegeneration or inflammation within the first 3 days after SE.
C1 [Borges, Karin] Texas Tech Hlth Sci Ctr, Dept Pharmaceut Sci, Amarillo, TX USA.
[Borges, Karin; Dingledine, Raymond] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA.
[Gearing, Maria] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Rittling, Susan] Forsyth Inst, Dept Cell Biol & Neurosci, Boston, MA USA.
[Sorensen, Esben S.] Univ Aarhus, Prot Chem Lab, Dept Mol Biol, Aarhus, Denmark.
[Kotloski, Robert] Duke Univ, Dept Neurobiol, Durham, NC USA.
[Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA.
RP Borges, K (reprint author), Texas Tech Univ Hlth Sci, Dept Pharmaceut Sci, 1300 S Coulter, Amarillo, TX 79106 USA.
EM karin.borges@ttuhsc.edu
RI Borges, Karin/B-4276-2011; dingledine, Ray/F-5173-2011
OI Borges, Karin/0000-0001-7448-0770;
FU Epilepsy Foundation; National Institutes of Health [5U54-HG003918]
FX We are grateful to the Epilepsy Foundation for funding (KB) and National
Institutes of Health Grant 5U54-HG003918 (R.D.). We thank Lucy Liaw for
providing OPN-/- and OPN+/+ mice, Aaron Kowalski
and Larry Fisher for osteopontin antibodies. James McNamara for help
with the electroshock tests, Kroshona Tabb for help with the fluorothyl
test. Valerie Boss and James P. O'Callaghan for sharing real time primer
sequences, Dayna McDermott for help with the immunohistochemistry and
Renee Shaw for help with RNA isolations and real-time PCR.
NR 41
TC 13
Z9 13
U1 0
U2 3
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD OCT
PY 2008
VL 49
IS 10
BP 1675
EP 1685
DI 10.1111/j.1528-1167.2008.01613.x
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 362AQ
UT WOS:000260171000003
PM 18522644
ER
PT J
AU Kopp, CMC
Muzykewicz, DDA
Staley, BA
Thiele, EA
Pulsifer, MB
AF Kopp, Claudine M. C.
Muzykewicz, Davi D. A.
Staley, Brigid A.
Thiele, Elizabeth A.
Pulsifer, Margaret B.
TI Behavior problems in children with tuberous sclerosis complex and
parental stress
SO EPILEPSY & BEHAVIOR
LA English
DT Article
DE tuberous sclerosis complex; epilepsy; behavioral problems; mental
retardation; autism spectrum disorder; attention; hyperactivity; seizure
frequency; mixed seizure disorder; parenting stress
ID DIAGNOSTIC-CRITERIA; INFANTILE SPASMS; POPULATION; DISORDERS; AUTISM;
CANCER; TSC1; METHYLPHENIDATE; ADOLESCENTS; FAMILIES
AB Behavioral problems are common in children with tuberous sclerosis complex (TSC) and can be challenging to manage at home. Standardized measures were used to assess behavior in 99 pediatric patients with TSC and to evaluate parenting stress in their parents. About 40% of the pediatric patients presented clinically significant behavioral problems, most frequently involving symptoms of autism spectrum disorder, inattention, and hyperactivity. Higher seizure frequency, mixed seizure disorder, and low intellectual functioning placed the patient at significant risk for behavior problems. Almost 50% of participating parents reported experiencing clinically significant parenting stress, which was associated with specific characteristics of the child, including the presence of current seizures, a history of psychiatric diagnosis, low intelligence, and behavioral problems. Clinicians should be aware that behavioral problems are prominent in children with TSC. Referrals for behavioral intervention and monitoring of parental stress should be included in the medical management of children with TSC. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA.
[Kopp, Claudine M. C.; Muzykewicz, Davi D. A.; Staley, Brigid A.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Pulsifer, MB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, 1 Bldg Sq,7th Floor, Boston, MA 02114 USA.
EM mpulsifer@partners.org
FU Carol and James Herscot Center
FX This study was supported by the Carol and James Herscot Center for
Tuberous Sclerosis Complex at the Massachusetts General Hospital.
NR 51
TC 20
Z9 21
U1 1
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1525-5050
J9 EPILEPSY BEHAV
JI Epilepsy Behav.
PD OCT
PY 2008
VL 13
IS 3
BP 505
EP 510
DI 10.1016/j.yebeh.2008.05.010
PG 6
WC Behavioral Sciences; Clinical Neurology; Psychiatry
SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry
GA 350DC
UT WOS:000259331800015
PM 18602868
ER
PT J
AU Major, P
Greenberg, E
Khan, A
Thiele, EA
AF Major, Philippe
Greenberg, Erica
Khan, Alisa
Thiele, Elizabeth A.
TI Pyridoxine supplementation for the treatment of levetiracetam-induced
behavior side effects in children: Preliminary results
SO EPILEPSY & BEHAVIOR
LA English
DT Article
DE pyridoxine; vitamin B6; levetiracetam; behavior; irritability
ID VITAMIN-B-6; SAFETY
AB Behavioral side effects related to the use of levetiracetam (LEV) in epilepsy are increasingly being recognized. Patients followed in our center have reported improvement of these side effects after starting pyridoxine (vitamin B-6) supplements. Using mailed questionnaires, retrospective chart reviews, and phone call follow-ups, we analyzed 42 pediatric patients who had been treated with LEV and pyridoxine. Twenty-two patients started pyridoxine after being on LEV, and significant behavioral improvement was observed in nine (41%), no effect in eight (36%), deterioration in four (18%), and an uncertain effect in one. The effects of pyridoxine supplementation were observed during the first week. The remaining patients (20) were already on pyridoxine before LEV was started, started pyridoxine and LEV at the same time, or took pyridoxine intermittently. Pyridoxine is an easily available, inexpensive, and safe therapeutic option. Given these preliminary results, we plan to conduct a placebo-controlled cross-over study to better characterize these observations. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Major, Philippe; Greenberg, Erica; Khan, Alisa; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Thiele, EA (reprint author), Pediatr Epilepsy Program, Herscot Ctr Tuberous Sclerosis Complex,175 Cambri, Boston, MA 02114 USA.
EM ethiele@partners.org
NR 12
TC 20
Z9 21
U1 5
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1525-5050
J9 EPILEPSY BEHAV
JI Epilepsy Behav.
PD OCT
PY 2008
VL 13
IS 3
BP 557
EP 559
DI 10.1016/j.yebeh.2008.07.004
PG 3
WC Behavioral Sciences; Clinical Neurology; Psychiatry
SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry
GA 350DC
UT WOS:000259331800025
PM 18647662
ER
PT J
AU Michaelides, C
Thibert, RL
Shapiro, MJ
Kinirons, P
John, T
Manchharam, D
Thiele, EA
AF Michaelides, Costas
Thibert, Ronald L.
Shapiro, Michelle J.
Kinirons, Peter
John, Tanya
Manchharam, Dipti
Thiele, Elizabeth A.
TI Tolerability and dosing experience of intravenous levetiracetam in
children and infants
SO EPILEPSY RESEARCH
LA English
DT Article
DE Levetiracetam; Intravenous; Dosing; Tolerability; Children; Infants
ID REFRACTORY PARTIAL SEIZURES; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND;
EPILEPSY; SAFETY; MULTICENTER; INFUSION; EFFICACY; THERAPY
AB Objective: To evaluate the use and tolerability of intravenous (IV) levetiracetam (LEV) in a pediatric cohort under 14 years of age.
Methods: A retrospective analysis of the use of the IV formulation of LEV was performed for the first 9 months that it was available in our institution.
Results: Overall, 118 infusions in 15 patients were performed during the period assessed. No adverse reactions were observed during the infusion phase of the IV formulation. Nine minor adverse reactions were observed during the rest of the hospitalization that were potentially related to the IV formulation. Three of these were decreases in the white cell. counts, white the majority of the rest were behavioral adverse effects. The median starting dose in LEV naive patients was 8.8 mg/kg (range = 5.0-50), with a median maintenance dose of 30.4 mg/kg/day for all patients (range = 5.0-92). The majority of these infusions (82/118) were in a subgroup of children under 4 years of age where the median maintenance dose was 28 mg/kg/day.
Conclusion: IV LEV was very well tolerated in this cohort of pediatric patients including a subgroup of children under the age of 4 years. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Michaelides, Costas; Thibert, Ronald L.; Shapiro, Michelle J.; Kinirons, Peter; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[John, Tanya; Manchharam, Dipti] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA.
RP Michaelides, C (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA.
EM cmichaelides@partners.org
NR 17
TC 14
Z9 14
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-1211
J9 EPILEPSY RES
JI Epilepsy Res.
PD OCT
PY 2008
VL 81
IS 2-3
BP 143
EP 147
DI 10.1016/j.eplepsyres.2008.05.004
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 374CW
UT WOS:000261021000007
PM 18571898
ER
PT J
AU Murphy, SA
Antman, EM
Wiviott, SD
Weerakkody, G
Morocutti, G
Huber, K
Lopez-Sendon, J
McCabe, CH
Braunwald, E
AF Murphy, Sabina A.
Antman, Elliott M.
Wiviott, Stephen D.
Weerakkody, Govinda
Morocutti, Giorgio
Huber, Kurt
Lopez-Sendon, Jose
McCabe, Carolyn H.
Braunwald, Eugene
CA TRITON-TIMI 38 Investigators
TI Reduction in recurrent cardiovascular events with prasugrel compared
with clopidogrel in patients with acute coronary syndromes from the
TRITON-TIMI 38 trial
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Acute coronary syndrome; Percutaneous coronary intervention; Prasugrel;
Clopidogrel
ID ELEVATION MYOCARDIAL-INFARCTION; PLATELET INHIBITION; STENT THROMBOSIS;
RISK SCORE; THROMBOLYSIS; REACTIVITY; PREDICTORS; MORTALITY
AB Aims In the TRITON-TIMI 38 trial, greater platelet inhibition with prasugrel reduced the first occurrence of the primary end-point (cardiovascular death, MI, or stroke) compared with clopidogrel in patients with an acute coronary syndrome (ACS) undergoing planned percutaneous coronary intervention. We hypothesized that prasugrel would reduce not only first events but also recurrent primary endpoint events and therefore total events compared with clopidogrel.
Methods and results Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between prasugrel and clopidogrel. in TRITON-TIMI 38. Landmark analytic methods were used to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4%, HR 0.65, 95% CI 0.46-0.92; P = 0.016), as was CV death following the non-fatal event (3.7 vs. 7.1%, HR 0.46, 95% CI 0.25-0.82; P = 0.008). Overall there was a reduction of 195 total primary efficacy events with prasugrel vs. clopidogrel (rate ratio 0.79, 95% CI 0.71-0.87; P < 0.001). Recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). Study drug discontinuation was frequent following the initial major bleeding event (42% of patients discontinued study drug).
Conclusion While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with dopidogrel in patients with ACS.
C1 [Murphy, Sabina A.; Antman, Elliott M.; Wiviott, Stephen D.; McCabe, Carolyn H.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA.
[Weerakkody, Govinda] Eli Lilly Res Labs, Indianapolis, IN USA.
[Morocutti, Giorgio] Osped S Maria Misericordia, Udine, Italy.
[Huber, Kurt] Wilhelminenhosp, Dept Med 3, Vienna, Austria.
[Lopez-Sendon, Jose] Hosp Univ La Paz, Dept Cardiol, Madrid, Spain.
RP Antman, EM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA.
EM eantman@partners.org
FU Daiichi Sankyo; Eli Lilly
FX TRITON-TIMI 38 was supported by research grants from Daiichi Sankyo and
Eli Lilly. Funding to pay the Open Access publication charges for this
article was provided by Eli Lilly.
NR 19
TC 90
Z9 95
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD OCT
PY 2008
VL 29
IS 20
BP 2473
EP 2479
DI 10.1093/eurheartj/ehn362
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 366ZZ
UT WOS:000260523600005
PM 18682445
ER
PT J
AU Poh, KK
Levine, RA
Solis, J
Shen, L
Flaherty, M
Kang, YJ
Guerrero, JL
Hung, J
AF Poh, Kian Keong
Levine, Robert A.
Solis, Jorge
Shen, Liang
Flaherty, Mary
Kang, Yue-Jian
Guerrero, J. Luis
Hung, Judy
TI Assessing aortic valve area in aortic stenosis by continuity equation: a
novel approach using real-time three-dimensional echocardiography
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Aortic stenosis; Real-time three-dimensional echocardiography; Colour
Doppler; Valvular heart disease; Continuity equation
ID COLOR DOPPLER-ECHOCARDIOGRAPHY; EFFECTIVE ORIFICE AREA; STROKE VOLUME;
CARDIAC-OUTPUT; QUANTIFICATION
AB Aims Two-dimensional echocardiographic (2DE) continuity-equation derived aortic valve area (AVA) in aortic stenosis (AS) relies on non-simultaneous measurement of left ventricular outflow tract (LVOT) velocity and geometric assumptions of LVOT area, which can amplify error, especially in upper septal hypertrophy (USH). We hypothesized that real-time three-dimensional echocardiography (RT3DE) can improve accuracy of AVA by directly measuring LVOT stroke volume (SV) in one window.
Methods and results RT3DE colour Doppler and 2DE were acquired in 68 AS patients (74 +/- 12 yrs) prospectively. SV was derived from flow obtained from a sampling curve placed orthogonal to LVOT (Tomtec Imaging). Agreement between continuity-equation derived AVA by RT3DE (AVA(3D-SV)) and 2DE (AVA(2D)) and predictors of discrepancies were analysed. Validation of LVOT SV was performed by aortic flow probe in a sheep model with balloon inflation of septum to mimic USH. There was only modest correlation between AVA(2D) and AVA(3D-SV) (r = 0.71, difference 0.11 +/- 0.23 cm(2)). The degree of USH was significantly associated with difference in AVA calculation (r = 0.4, P = 0.005). In experimentally distorted LVOT geometry in sheep, RT3DE correlated better with flow probe assessment (r = 0.96, P < 0.001) than 2DE (r = 0.71, P = 0.006).
Conclusion RT3DE colour Doppler-derived LVOT SV in the calculation of AVA by continuity equation is more accurate than 2D, including in situations such as USH, common in the elderly, which modify LVOT geometry.
C1 [Poh, Kian Keong; Levine, Robert A.; Solis, Jorge; Flaherty, Mary; Kang, Yue-Jian; Hung, Judy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Div Cardiol, Boston, MA 02114 USA.
[Poh, Kian Keong] Natl Univ Singapore Hosp, Dept Cardiac, Singapore 117548, Singapore.
[Shen, Liang] Natl Univ Singapore, Yong Loo Lin Sch Med, Biostat Unit, Singapore 117595, Singapore.
RP Hung, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Div Cardiol, Blake 256,55 Fruit St, Boston, MA 02114 USA.
EM jhung@partners.org
FU NIH NIBIB [R21 EB005294, R01 038176]; National Medical Research Council,
Singapore
FX This work was supported in part by NIH NIBIB R21 EB005294 (J.H.) and NIH
NHLBI R01 038176 (R.A.L.) and a fellowship award from the National
Medical Research Council, Singapore (K.K.P.).
NR 32
TC 68
Z9 68
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD OCT
PY 2008
VL 29
IS 20
BP 2526
EP 2535
DI 10.1093/eurheartj/ehn022
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 366ZZ
UT WOS:000260523600013
PM 18263866
ER
PT J
AU Alsayed, Y
Leleu, X
Leontovich, A
Oton, AB
Melhem, M
George, D
Ghobrial, IM
AF Alsayed, Yazan
Leleu, Xavier
Leontovich, Alexey
Oton, Ana B.
Melhem, Mona
George, Diane
Ghobrial, Irene M.
TI Proteomics analysis in post-transplant lymphoproliferative disorders
SO EUROPEAN JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE post-transplant lymphoproliferative disorders; proteomic analysis;
targeted therapy
ID ORGAN TRANSPLANT RECIPIENTS; WALDENSTROM MACROGLOBULINEMIA;
MULTIPLE-MYELOMA; IN-VITRO; B-CELLS; IDENTIFICATION; SURVIVAL
AB Little is known about the biology of post-transplant lymphoproliferative disorders (PTLDs). The objective of this study was to determine the molecular alterations that occur at the protein level in patients with PTLDs. Six tumor samples from adult patients with PTLD and four benign lymph nodes were studied using protein microrarray technique. Proteins that were dysregulated included proteins in the PI3K/mTOR, NFkB and HSP90 pathways. Inhibitors of these proteins induced cytotoxicity and apoptosis in EBV+ve and -ve cell lines. These results provide insight into pathways that are dysregulated in PTLD and can be targeted in future clinical trials.
C1 [Leleu, Xavier; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Leleu, Xavier; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA.
[Alsayed, Yazan; Oton, Ana B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Leleu, Xavier] CHRU, Serv Malad Sang, Lille, France.
[Leleu, Xavier] CHRU, Immunol Lab, Lille, France.
[Leontovich, Alexey] Mayo Clin, Coll Med, Rochester, MN USA.
[Melhem, Mona; George, Diane] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 548A, Boston, MA 02115 USA.
EM irene_ghobrial@dfci.harvard.edu
FU Franco-American Fulbright Foundation
FX This work was supported in part by the Leukemia and Lymphoma Society. XL
is supported by a grant from the Franco-American Fulbright Foundation.
NR 18
TC 8
Z9 8
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0902-4441
J9 EUR J HAEMATOL
JI Eur. J. Haematol.
PD OCT
PY 2008
VL 81
IS 4
BP 298
EP 303
DI 10.1111/j.1600-0609.2008.01106.x
PG 6
WC Hematology
SC Hematology
GA 348QH
UT WOS:000259224500008
PM 18573174
ER
PT J
AU Gohler, A
Conrads-Frank, A
Worrell, SS
Geisler, BP
Halpern, EF
Dietz, R
Anker, SD
Gazelle, GS
Siebert, U
AF Goehler, Alexander
Conrads-Frank, Annette
Worrell, Stewart S.
Geisler, Benjamin P.
Halpern, Elkan F.
Dietz, Rainer
Anker, Stefan D.
Gazelle, G. Scott
Siebert, Uwe
TI Decision-analytic evaluation of the clinical effectiveness and
cost-effectiveness of management programmes in chronic heart failure
SO EUROPEAN JOURNAL OF HEART FAILURE
LA English
DT Article
DE Hearth failure; Management programme; Cost-effectiveness analysis;
Markov model
ID HEALTH-CARE COSTS; QUALITY-OF-CARE; DISEASE MANAGEMENT; INTERVENTION;
METAANALYSIS; STANDARD; EUROPE; TRIALS; RISK
AB Background and aims: While management programmes (MPs) for chronic heart failure (CHF) are clinically effective, their cost-effectiveness remains uncertain. Thus, this study sought to determine the cost-effectiveness of MPs.
Methods and results: We developed a Markov model to estimate life expectancy, quality-adjusted life expectancy, lifetime costs, and the incremental cost-effectiveness of MPs as compared to standard care. Standard care was defined by the EuroHeart Failure Survey for Germany, MP efficacy was derived from our recent meta-analysis and cost estimates were based on the German healthcare system. For a population with a mean age 67 years (35% female) at onset of CHF, our model predicted an average quality-adjusted life expectancy of 2.64 years for standard care and 2.83 years for MP. MP yielded additional lifetime costs of C 1700 resulting in an incremental cost-utility ratio (ICUR) of is an element of 8900 (95% CI: dominant to 177,100) per quality-adjusted life year (QALY) gained. Sensitivity analyses demonstrated that the ICUR was sensitive to age and sex.
Conclusion: MPs increase life expectancy in patients with CHF by an average of 84 days and increase lifetime cost of care by approximately is an element of 1700. MPs improve outcomes in a cost-effective manner, although they are not cost-saving on a lifetime horizon. (c) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
C1 [Goehler, Alexander; Conrads-Frank, Annette; Worrell, Stewart S.; Geisler, Benjamin P.; Halpern, Elkan F.; Gazelle, G. Scott; Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA.
[Goehler, Alexander; Conrads-Frank, Annette; Worrell, Stewart S.; Geisler, Benjamin P.; Halpern, Elkan F.; Gazelle, G. Scott; Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Goehler, Alexander; Dietz, Rainer; Anker, Stefan D.] Charite Campus Virchow Klinikum, Div Cardiol, Berlin, Germany.
[Gazelle, G. Scott; Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Siebert, U (reprint author), Harvard Univ, Sch Med, MGH Inst Technol Assessment, Cardiovasc Res Program, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM usiebert@hsph.harvard.edu
OI Geisler, Benjamin/0000-0003-1704-6067
FU German Cardiac Society
FX Dr. Gohler was supported by the "Boston-Scientific-Scholarship" of the
German Cardiac Society. We thank Dr. Dieter Gohler for his help in
conducting the survey to estimate outpatient costs. We thank all
colleagues who participated in the survey. We also thank Jennifer Manne
for her critical input on this manuscript as well as two anonymous
reviewers for their very helpful comments on an earlier version of this
manuscript.
NR 27
TC 17
Z9 17
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-9842
J9 EUR J HEART FAIL
JI Eur. J. Heart Fail.
PD OCT
PY 2008
VL 10
IS 10
BP 1026
EP 1032
DI 10.1016/j.ejheart.2008.07.018
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 370FZ
UT WOS:000260749400008
PM 18760666
ER
PT J
AU Badgaiyan, RD
Alpert, NM
Spencer, TJ
Fischman, AJ
AF Badgaiyan, R. D.
Alpert, N. M.
Spencer, T. J.
Fischman, A. J.
TI Molecular imaging, response inhibition and ADHD
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD OCT
PY 2008
VL 35
SU 2
BP S150
EP S150
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA V28OS
UT WOS:000208690700107
ER
PT J
AU Fischman, AJ
Spencr, TJ
Biederman, J
Badgaiyan, RD
Meltzer, P
Livni, E
Bonab, AA
AF Fischman, A. J.
Spencr, T. J.
Biederman, J.
Badgaiyan, R. D.
Meltzer, P.
Livni, E.
Bonab, A. A.
TI Evaluation of the time course of dopamine transporter (DAT) occupancy by
a long-acting formulation of dexmethylphenidate by PET imaging with C-11
Altropane.
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Meeting Abstract
C1 [Fischman, A. J.; Spencr, T. J.; Biederman, J.; Badgaiyan, R. D.; Livni, E.; Bonab, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Meltzer, P.] Organix Inc, Woburn, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD OCT
PY 2008
VL 35
SU 2
BP S216
EP S216
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA V28OS
UT WOS:000208690701003
ER
PT J
AU Becerra, L
Borsook, D
AF Becerra, Lino
Borsook, David
TI Signal valence in the nucleus accumbens to pain onset and offset
SO EUROPEAN JOURNAL OF PAIN
LA English
DT Article
DE fMRI; nucleus accumbens; pain; analgesia; reward; aversion
ID NEURAL RESPONSES; FUNCTIONAL MRI; REWARD; FMRI; ACTIVATION; DOPAMINE;
BRAIN; EXPECTATIONS; EXPERIENCE; RECEPTORS
AB Pain and relief are at opposite ends of the reward-aversion continuum. Studying them provides an opportunity to evaluate dynamic changes in brain activity in reward-aversion pathways as measured by functional magnetic resonance imaging (fMRI). Of particular interest is the nucleus accumbens (NAc), a brain substrate known to be involved in reward-aversion processing, whose activation valence has been observed to be opposite in response to reward or aversive stimuli. Here we have used pain onset (aversive) and pain offset (rewarding) involving a prolonged stimulus applied to the dorsum of the hand in 10 male subjects over 120 s to study the NAc fMRI response. The results show a negative signal change with pain onset and a positive signal change with pain offset in the NAc contralateral to the stimulus. The study supports the idea that the NAc fMRI signal may provide a useful marker for the effects of pain and analgesia in healthy volunteers. (C) 2007 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.
C1 [Becerra, Lino; Borsook, David] McLean Hosp, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02178 USA.
[Borsook, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Engn, Cambridge, MA 02138 USA.
RP Becerra, L (reprint author), McLean Hosp, Brain Imaging Ctr, PAIN Grp, 115 Mill St, Belmont, MA 02178 USA.
EM lbecerra@mclean.harvard.edu
FU NINDS [NS 042721]
FX This work was supported by a grant from NINDS to DB (NS 042721).
NR 30
TC 48
Z9 48
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1090-3801
J9 EUR J PAIN
JI Eur. J. Pain
PD OCT
PY 2008
VL 12
IS 7
BP 866
EP 869
DI 10.1016/j.ejpain.2007.12.007
PG 4
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 350TL
UT WOS:000259375900006
PM 18226937
ER
PT J
AU Ballantyne, JC
AF Ballantyne, Jane C.
TI Medical use of opioids: what drives the debate? A brief commentary
SO EUROPEAN JOURNAL OF PAIN
LA English
DT Article
CT 1st San Matteo International Meeting on Pain Research
CY OCT 03-04, 2008
CL Pavia, ITALY
DE Opioid; Opioid History; Addiction
ID ANTAGONISTS; PAIN
AB Medical advances have not obviated the need for opioids to relieve pain and suffering. There are no better analgesics. Pain and suffering have not abated. Scientific endeavor has helped unravel some of the mechanisms of pain and addiction; yet the compelling and addictive properties of opioids continue to plague their use. This article explores the factors that drive the current debate about the use of opioids to relieve the suffering of patients with chronic intractable pain. (C) 2008 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.
C1 [Ballantyne, Jane C.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, MGH Pain Ctr, Boston, MA 02114 USA.
[Ballantyne, Jane C.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Pain Ctr, Div Pain Med, 15 Parkman St,WACC 333, Boston, MA 02114 USA.
EM jballantyne@partners.org
NR 16
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1090-3801
J9 EUR J PAIN
JI Eur. J. Pain
PD OCT
PY 2008
BP 67
EP 68
PG 2
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 463GU
UT WOS:000267419900013
ER
PT J
AU Diehm, N
Pattynama, PM
Jaff, MR
Cremonesi, A
Becker, GJ
Hopkins, LN
Mahler, F
Talen, A
Cardella, JF
Ramee, S
van Sambeek, M
Vermassen, F
Biamino, G
AF Diehm, N.
Pattynama, P. M.
Jaff, M. R.
Cremonesi, A.
Becker, G. J.
Hopkins, L. N.
Mahler, F.
Talen, A.
Cardella, J. F.
Ramee, S.
van Sambeek, M.
Vermassen, F.
Biamino, G.
TI Clinical Endpoints in Peripheral Endovascular Revascularization Trials:
a Case for Standardized Definitions
SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY
LA English
DT Article
DE Reporting standards; Outcome analysis; Clinical improvement; Angiography
ID FEMORAL-ARTERY DISEASE; LOWER-EXTREMITY; ANGIOGRAPHY; PREDICTION;
GUIDELINES; ISCHEMIA; STENT; COLOR
AB Background: Endovascular therapy is a rapidly expanding option for the treatment of patients with peripheral arterial disease (PAD), leading to a myriad of published studies reporting on various revascularization strategies. However, these reports are often difficult to interpret and compare because they do not utilize uniform clinical endpoint definitions. Moreover, few of these studies describe clinical outcomes from a patients' perspective.
Methods and results: The DEFINE Group is a collaborative effort of an ad-hoc multidisciplinary team from various specialties involved in peripheral arterial disease therapy in Europe and the United States. DEFINE's goat was to arrive at a broad based consensus for baseline and endpoint definitions in peripheral endovascular revascularization trials for chronic tower limb ischemia. In this project, which started in 2006, the individual team members reviewed the existing pertinent literature. Following this, a series of telephone conferences and face-to-face meetings were held to agree upon definitions. Input was also obtained from regulatory (United States Food and Drug Administration) and industry (device manufacturers with an interest in peripheral endovascular revascularization) stakeholders, respectively. The efforts resulted in the current document containing proposed baseline and endpoint definitions in chronic tower limb PAD. Although the consensus has inevitably included certain arbitrary choices and compromises, adherence to these proposed standard definitions would provide consistency across future trials, thereby facilitating evaluation of clinical effectiveness and safety of various endovascular revascularization techniques.
Conclusion: This current document is based on a broad based consensus involving relevant stakeholders from the medical community, industry and regulatory bodies. It is proposed that the consensus document may have value for study design of future clinical trials in chronic tower limb ischemia as well as for regulatory purposes. (C) 2008 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
C1 [Diehm, N.; Mahler, F.] Univ Bern, Inselspital, Div Clin & Intervent Angiol, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland.
[Pattynama, P. M.] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Jaff, M. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, Boston, MA USA.
[Cremonesi, A.; Biamino, G.] Villa Maria Cecilia Hosp, Grp Villa Maria Endovasc, Cotignola, Italy.
[Becker, G. J.] Univ Arizona, Coll Med, Sarver Heart Ctr, Tucson, AZ 85721 USA.
[Becker, G. J.] Univ Arizona, Coll Med, Dept Radiol, Vasc & Intervent Sect, Tucson, AZ 85721 USA.
[Hopkins, L. N.] Sch Med & Biomed Sci, Dept Neurosurg, Buffalo, NY USA.
[Talen, A.] Genae Associates Nv, Antwerp, Belgium.
[Cardella, J. F.] Tufts Univ, Sch Med, Dept Radiol, Springfield, MA 01199 USA.
[Ramee, S.] Ochsner Heart & Vasc Inst, New Orleans, LA USA.
[van Sambeek, M.] Catharina Hosp, Dept Surg, Eindhoven, Netherlands.
[Vermassen, F.] Univ Hosp, Dept Vasc Surg, Ghent, Belgium.
RP Diehm, N (reprint author), Univ Bern, Inselspital, Div Clin & Intervent Angiol, Swiss Cardiovasc Ctr, Freiburgstr, CH-3010 Bern, Switzerland.
EM diehm@gmx.ch
FU Abbott Vascular; Biotronik GmbH; Boston Scientific; Cook Corporation;
Cordis (a Johnson Et Johnson company); Datascope Corporation; Edwards
Lifesciences; Ev3 GmbH; Invatec srl; Medtronic Europe
FX Unrestricted grants were provided to the DEFINE to cover costs of
travel, meeting rooms, and lodging for academic attendees at the
Washington, DC, and New York, NY, meetings by Abbott Vascular, Biotronik
GmbH, Boston Scientific, Cook Corporation, Cordis (a Johnson Et Johnson
company), Datascope Corporation, Edwards Lifesciences, Ev3 GmbH, Invatec
srl, Medtronic Europe. Contributing physicians did not receive honoraria
for participation in the DEFINE project.
NR 30
TC 62
Z9 62
U1 1
U2 4
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1078-5884
J9 EUR J VASC ENDOVASC
JI Eur. J. Vasc. Endovasc. Surg.
PD OCT
PY 2008
VL 36
IS 4
BP 409
EP 419
DI 10.1016/j.ejvs.2008.06.020
PG 11
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 363BX
UT WOS:000260242000009
PM 18692415
ER
PT J
AU Efstathiou, JA
Bae, K
Shipley, WU
Hanks, GE
Pilepich, MV
Sandler, HM
Smith, MR
AF Efstathiou, Jason A.
Bae, Kyounghwa
Shipley, William U.
Hanks, Gerald E.
Pilepich, Miljenko V.
Sandler, Howard M.
Smith, Matthew R.
TI Cardiovascular Mortality and Duration of Androgen Deprivation for
Locally Advanced Prostate Cancer: Analysis of RTOG 92-02
SO EUROPEAN UROLOGY
LA English
DT Article
DE Cardiovascular mortality; Gonadotropin-releasing hormone agonist;
Hormonal therapy; Prostate cancer; Radiation therapy
ID BONE-MINERAL DENSITY; HORMONE AGONISTS; BODY-COMPOSITION; THERAPY; MEN;
TRIAL; RADIOTHERAPY; SUPPRESSION; IMMEDIATE; CARCINOMA
AB Objectives: Gonadotropin-releasing hormone agonists (GnRHa) are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about their potential effects on cardiovascular mortality. We assessed the relationship between duration of GnRHa therapy and cardiovascular mortality in a large randomized trial of men treated with short-term versus longer-term adjuvant goserelin and radiation therapy (RT) for locally advanced prostate cancer.
Methods: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-4, prostate-specific antigen [PSA] < 150 ng/ml) received RT and 4mo of goserelin and then were randomized to no additional therapy (arm 1) or 24 mo adjuvant goserelin (arm 2) in a phase 3 trial (Radiation Therapy Oncology Group [RTOG] 92-02). Cox regression analyses were performed to evaluate the relationship between treatment arm and cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes (DM), race, PSA, Gleason score, and stage.
Results: After median follow-up of 8.1 yr, 185 cardiovascular-related deaths had occurred. No increase in cardiovascular mortality occurred for men receiving a longer duration of goserelin. At 5 yr, cardiovascular mortality for men receiving longer-term adjuvant goserelin was 5.9% versus 4.8% with short-term goserelin (Gray's p = 0.16). In multivariate analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.81-1.47; p = 0.58; when censoring at time of salvage goserelin, HR = 1.02, 95%CI, 0.73-1.43; p = 0.9). Traditional cardiac risk factors, including age, prevalent CVD, and DM, were significantly associated with greater cardiovascular mortality.
Conclusions: Longer duration of adjuvant GnRHa therapy does not appear to increase cardiovascular mortality in men with locally advanced prostate cancer. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Efstathiou, Jason A.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Bae, Kyounghwa] Radiat Therapy Oncol Grp, Dept Stat, Philadelphia, PA USA.
[Hanks, Gerald E.] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA.
[Pilepich, Miljenko V.] Univ Calif Los Angeles, Sch Med, Dept Radiat Oncol, Los Angeles, CA USA.
[Sandler, Howard M.] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI USA.
[Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA.
EM jefstathiou@partners.org
FU Radiation Therapy Oncology Group [U10 CA21661]; Community Clinical
Oncology Program [U10 CA37422]; National Cancer Institute [Stat U10
CA32115]
FX Supported by Radiation Therapy Oncology Group U10 CA21661, Community
Clinical Oncology Program U10 CA37422, and Stat U10 CA32115 grants from
the National Cancer Institute.
NR 32
TC 115
Z9 117
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD OCT
PY 2008
VL 54
IS 4
BP 816
EP 824
DI 10.1016/j.eururo.2008.01.021
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 361LG
UT WOS:000260128600015
PM 18243498
ER
PT J
AU Zdychova, J
Kazdova, L
Pelikanova, T
Lindsley, JN
Anderson, S
Komers, R
AF Zdychova, Jana
Kazdova, Ludmila
Pelikanova, Terezie
Lindsley, Jessie N.
Anderson, Sharon
Komers, Radko
TI Renal activity of Akt kinase in obese Zucker rats
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Akt kinase; phosphatidylinositol 3-kinase; Zucker rat; mammalian target
of rapamycin; mTOR; endothelial nitric oxide synthase
ID MESSENGER-RNA TRANSLATION; DIABETIC KIDNEY-DISEASE; NITRIC-OXIDE
SYNTHASE; PROTEIN-KINASE; EPITHELIAL-CELLS; HIGH GLUCOSE;
PHOSPHOINOSITIDE 3-KINASE; SIGNAL-TRANSDUCTION; MAMMALIAN TARGET;
SKELETAL-MUSCLE
AB Insulin resistance (IR) and consequent hyperinsulinemia are hallmarks of Type 2 diabetes (DM2). Akt kinase (Akt) is an important molecule in insulin signaling, implicated in regulation of glucose uptake, cell growth, cell survival, protein synthesis, and endothelial nitric oxide (NO) production. Impaired Akt activation in insulin-sensitive tissues contributes to IR. However, Akt activity in other tissues, particularly those affected by complications of DM2, has been less studied. We hypothesized that hyperinsulinemia could have an impact on activity of Akt and its effectors involved in regulation of renal morphology and function in DM2. To address this issue, renal cortical Akt was determined in obese Zucker rats (ZO), a model of DM2, and lean controls (ZL). We also studied expression and phosphorylation of the mammalian target of rapamycin (mTOR) and endothelial NO synthase (eNOS), molecules downstream of Akt in the insulin signaling cascade, and documented modulators of renal injury. Akt activity was measured by a kinase assay with GSK-3 as a substrate. Expression of phosphorylated (active) and total proteins was measured by immunoblotting and immunohistochemistry. Renal Akt activity was increased in ZO as compared to ZL rats, in parallel with progressive hyperinsulinemia. No differences in Akt were observed in the skeletal muscle. Corresponding to increases in Akt activity, ZO rats demonstrated enhanced phosphorylation of renal mTOR. Acute PI3K inhibition with wortmannin (100 mu g/kg) attenuated renal Akt and mTOR activities in ZO, but not in ZL rats. In contrast to mTOR, eNOS phosphorylation was similar in ZO and ZL rats, despite higher total eNOS expression. In conclusion, ZO rats demonstrated increases in renal Akt and mTOR activity and expression. However, eNOS phosphorylation did not follow this pattern. These data suggest that DM2 is associated with selective IR in the kidney, allowing pro-growth signaling via mTOR, whereas potentially protective effects mediated by eNOS are blunted.
C1 [Lindsley, Jessie N.; Anderson, Sharon; Komers, Radko] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97239 USA.
[Zdychova, Jana; Kazdova, Ludmila; Pelikanova, Terezie; Komers, Radko] Inst Clin & Expt Med, Ctr Diabet, Prague, Czech Republic.
[Anderson, Sharon] Portland VA Med Ctr, Portland, OR 97329 USA.
RP Komers, R (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM komersr@ohsu.edu
FU Czech Ministry of Health Care [MZO 00023001]; NIH [DK 63231]
FX These studies were supported by the institutional Grant # MZO 00023001
of the Czech Ministry of Health Care (RK), and by DK 63231 from the NIH
(SA).
NR 50
TC 14
Z9 17
U1 0
U2 2
PU SOC EXPERIMENTAL BIOLOGY MEDICINE
PI MAYWOOD
PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA
SN 1535-3702
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD OCT
PY 2008
VL 233
IS 10
BP 1231
EP 1241
DI 10.3181/0801-RM-29
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 355SU
UT WOS:000259729500005
PM 18641049
ER
PT J
AU Katsuta, Y
Ogura, Y
Iriyama, S
Goetinck, PF
Klement, JF
Uitto, J
Amano, S
AF Katsuta, Yuji
Ogura, Yuki
Iriyama, Shunsuke
Goetinck, Paul F.
Klement, John F.
Uitto, Jouni
Amano, Satoshi
TI Fibulin-5 accelerates elastic fibre assembly in human skin fibroblasts
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Article
DE elastic fibre; fibulin-5; tropoelastin
ID EXTRACELLULAR-MATRIX PROTEIN-1; IN-VIVO; ELASTOTIC MATERIAL;
MOLECULAR-CLONING; CUTIS LAXA; MICROFIBRILS; EXPRESSION; HETEROGENEITY;
GLYCOPROTEIN; MECHANISMS
AB Fibulin-5 null mice display abnormalities in the elastic fibres in the dermis. We postulated, therefore, that fibulin-5 might be a regulator of elastic fibre assembly and stability. To clarify the role of fibulin-5 in elastic fibre formation, we employed in vitro systems that allowed increasing expression of elastic fibre components by gene transduction using retroviral vector constructs. First, the human tropoelastin gene (ELN) was transduced into human dermal fibroblasts, which resulted in elevated gene expression. These cells were then cultured in monolayer, but the overexpression of ELN in this system did not alter the assembly of elastic fibres. However, incubation of fibroblasts with TGF-beta 1 resulted in elastic fibre accumulation, and the expression of fibulin-5 was enhanced by TGF-beta 1. Thus, we overexpressed human fibulin-5 cDNA in dermal fibroblasts using a retroviral vector containing a cytomegalovirus (CMV) promoter. These cells deposited elastic fibres. These results suggest that fibulin-5 is a critical component in the control of elastic fibre assembly by dermal fibroblasts.
C1 [Katsuta, Yuji; Ogura, Yuki; Iriyama, Shunsuke; Amano, Satoshi] Shiseido Life Sci Res Ctr, Yokohama, Kanagawa, Japan.
[Katsuta, Yuji; Klement, John F.; Uitto, Jouni] Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA.
[Katsuta, Yuji; Goetinck, Paul F.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
RP Katsuta, Y (reprint author), Shiseido Life Sci Res Ctr, Yokohama, Kanagawa, Japan.
EM yuji.katsuta@to.shiseido.co.jp
NR 37
TC 16
Z9 20
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD OCT
PY 2008
VL 17
IS 10
BP 837
EP 842
DI 10.1111/j.1600-0625.2008.00709.x
PG 6
WC Dermatology
SC Dermatology
GA 348KX
UT WOS:000259210500006
PM 18341572
ER
PT J
AU Mollenhauer, B
Cullen, V
Kahn, I
Krastins, B
Outeiro, TF
Pepivani, I
Ng, J
Schulz-Schaeffer, W
Kretzschmar, HA
McLean, PJ
Trenkwalder, C
Sarracino, DA
VonSattel, JP
Locascio, JJ
El-Agnaf, OMA
Schlossmacher, MG
AF Mollenhauer, Brit
Cullen, Valerie
Kahn, Ilana
Krastins, Bryan
Outeiro, Tiago F.
Pepivani, Imelda
Ng, Juliana
Schulz-Schaeffer, Walter
Kretzschmar, Hans A.
McLean, Pamela J.
Trenkwalder, Claudia
Sarracino, David A.
VonSattel, Jean-Paul
Locascio, Joseph J.
El-Agnaf, Omar M. A.
Schlossmacher, Michael G.
TI Direct quantification of CSF alpha-synuclein by ELISA and first
cross-sectional study in patients with neurodegeneration
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE alpha-synuclein; parkinsonism; dementia; cerebrospinal fluid; mass
spectrometry; ELISA; biomarker
ID PARKINSONS-DISEASE DEMENTIA; CREUTZFELDT-JAKOB-DISEASE;
AMYLOID-BETA-PEPTIDES; CEREBROSPINAL-FLUID; LEWY BODIES;
ALZHEIMERS-DISEASE; TAU-PROTEIN; HUMAN PLASMA; WILD-TYPE;
CLINICAL-DIAGNOSIS
AB Because accumulation of alpha-synuclein (alpha S) in the brain is a hallmark of Parkinson disease (PD) and related disorders, we examined its Occurrence in human cerebrospinal fluid (CSF). Following affinity enrichment and trypsin digestion of CSF collected from a neurologically healthy donor, we identified several alpha S-derived peptides by mass spectrometry. The concentration of us amounted to < 0.001% of the CSF proteome. We then built, validated and optimized a sandwich-type, enzyme-linked immunoadsorbent assay (ELISA) to measure total alpha S levels in unconcentrated CSF. In a cross-sectional study of 100 living donors, we examined cell-free CSF samples from subjects clinically diagnosed with advanced PD, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and a group of non-neurodegenerative disease controls (NCO). In these four groups the CSF alpha S concentrations ranged from 0.8 to 16.2 pg/mu l. Mean CSF aS values were lower in donors with a primary synucleinopathy (PD, DLB: n=57) than in the other two groups (AD, NCO: n=35; p=0.025). By contrast, living Creutzfeldt-Jakob disease patients showed markedly elevated CSF alpha S levels (n=8; mean, 300 pg/mu l; p < 0.001). Our results unequivocally confirm the presence of aS in adult human CSF. In a first feasibility study employing a novel ELISA, we found relatively low CSF alpha S concentrations in subjects with parkinsonism linked to synucleinopathy, PD and DLB. In definite prion disease cases, we recorded a marked rise in total CSF alpha S resulting from rapid cell death. Our results will likely aid future biomarker explorations in neurodegenerative conditions and facilitate target validation studies. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Ng, Juliana; Schlossmacher, Michael G.] Univ Ottawa, Ottawa Hlth Res Inst, Div Neurosci, Ottawa, ON K1H 8M5, Canada.
[Mollenhauer, Brit; Cullen, Valerie; Kahn, Ilana; Pepivani, Imelda; Schlossmacher, Michael G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Neurol Dis, Boston, MA USA.
[Krastins, Bryan; Sarracino, David A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Proteom Core Facil, Cambridge, MA 02138 USA.
[Outeiro, Tiago F.; McLean, Pamela J.; Locascio, Joseph J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
[Schulz-Schaeffer, Walter] Univ Gottingen, Dept Neuropathol, Gottingen, Germany.
[Kretzschmar, Hans A.] Univ Munich, Dept Pathol, D-80539 Munich, Germany.
[Trenkwalder, Claudia] Univ Gottingen, Paracelsus Elena Klin, Kassel, Germany.
[VonSattel, Jean-Paul] Columbia Univ, Inst Pathol, New York, NY USA.
[El-Agnaf, Omar M. A.] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Biochem, Al Ain, U Arab Emirates.
RP Schlossmacher, MG (reprint author), Univ Ottawa, Ottawa Hlth Res Inst, Div Neurosci, 451 Smyth Rd 1462, Ottawa, ON K1H 8M5, Canada.
EM mschlossmacher@ohri.ca
FU Dr. W. Jackstaedt Fellowship des Stifterverbandes fuer die Deutsche
Wissenschaft; American Parkinson Disease Association; Michael J Fox
Foundation; NIH/NINDS [5P50-NS038375]; Parkinson Research Consortium at
the University of Ottawa
FX We are grateful to the CSF donors for their participation and to the
family members for tissue donation. We thank P.T. Lansbury for his gifts
of recombinant proteins and encouragement; H. Zetterberg for sharing his
mass spectrometry results; A. Ivinson, D. Grimes and D. Park for the
critical reading of earlier versions of this manuscript. This work was
supported by a "Dr. W. Jackstaedt Fellowship des Stifterverbandes fuer
die Deutsche Wissenschaft" and the American Parkinson Disease
Association (to B.M.), Michael J Fox Foundation (to O.M.A.E., M.G.S.),
M.S.A. Fund at BWH, NIH/NINDS 5P50-NS038375, and the Parkinson Research
Consortium at the University of Ottawa (to M.G.S.).
NR 70
TC 186
Z9 190
U1 0
U2 14
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 OCT
PY 2008
VL 213
IS 2
BP 315
EP 325
DI 10.1016/j.expneurol.2008.06.004
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 351ZG
UT WOS:000259464200008
PM 18625222
ER
PT J
AU Brown, JR
AF Brown, Jennifer R.
TI Inherited predisposition to chronic lymphocytic leukemia
SO EXPERT REVIEW OF HEMATOLOGY
LA English
DT Review
DE association; familial chronic lymphocytic leukemia; linkage;
lymphocytosis; monoclonal B cell
AB Inherited susceptibility to chronic lymphocytic leukemia (CLL) has been recognized for decades Approximately 10% of individuals with CLL report a family history of CLL or a related lymphoproliferative disorder and genetic predisposition is the best understood risk factor for CLL Studies of familial CLL have suggested that the disease features are largely similar to sporadic CLL, although recent data suggest that familial CLL may more commonly show somatic hypermutation of the immunoglobulin heavy-chain variable region suggesting a more indolent disease course Monoclonal B-cell lymphocytosis (MBL) has been identified recently as a likely precursor to CLL, it is found in the general population with increasing age and enriched in unaffected relatives of individuals with familial CLL Studies of MBL as well as mouse models of CLL may lead to better understanding of early CLL pathogenesis that is relevant to familial predisposition To date the identification of genes that predispose to familial CLL has been slow primarily due to the relatively few families available for study the small size of those families and disease causation most likely by multiple genes that each confer smaller risks In the coming years the application of systematic genomics approaches to familial CLL should hopefully lead to the identification of novel loci involved in the disease
C1 [Brown, Jennifer R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Brown, JR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 44 Binney St, Boston, MA 02115 USA.
FU NCI NIH HHS [K23 CA115682-01, K23 CA115682-03, K23 CA115682, K23
CA115682-02, K23 CA115682-04]
NR 122
TC 6
Z9 6
U1 0
U2 0
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1747-4086
J9 EXPERT REV HEMATOL
JI Expert Rev. Hematol.
PD OCT
PY 2008
VL 1
IS 1
BP 51
EP 61
DI 10.1586/17474086.1.1.51
PG 11
WC Hematology
SC Hematology
GA V14KV
UT WOS:000207734200013
PM 19802369
ER
PT J
AU Koreth, J
Antin, JH
AF Koreth, John
Antin, Joseph H.
TI Current and future approaches for control of graft-versus-host disease
SO EXPERT REVIEW OF HEMATOLOGY
LA English
DT Review
DE allogeneic stem cell transplantation; graft versus host disease
AB Graft-versus-host disease (GVHD) both acute and chronic remains one of the major barriers to improving outcomes after allogeneic stem cell transplantation The pathophysiology of GVHD is complex and incompletely understood GVHD is believed to arise from the interaction of tissue damage and proinflammatory cytokines causing activation of antigen-presenting cells (APCs, donor T-cell activation by APCs and cytokines and host tissue injury by effector T lymphocytes and proinflammatory cytokines There is also a role for additional lymphocyte subtypes (naive and memory T cells regulatory T cells, natural killer T cells and B cells) in GVHD pathogenesis Strategies to improve donor recipient HLA match and to minimize conditioning toxicity cytokine release and ARC and effector T-lymphocyte activation will likely improve prophylaxis of acute (and possibly chronic) GVHD Therapy of established acute and chronic GVHD is still heavily dependent on corticosteroids despite their limited efficacy and considerable toxicity Novel agents (and/or combinations of agents) comprising pharmacologic biologic and cellular therapies targeting specific steps or subsets involved in immune activation will likely comprise future advances in GVHD control This article reviews the current state of knowledge regarding the prevention and treatment of acute and chronic GVHD Novel approaches currently undergoing evaluation are also highlighted
C1 [Koreth, John; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA.
FU NHLBI NIH HHS [P01 HL070149, P01 HL070149-05]
NR 245
TC 15
Z9 18
U1 0
U2 3
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1747-4086
J9 EXPERT REV HEMATOL
JI Expert Rev. Hematol.
PD OCT
PY 2008
VL 1
IS 1
BP 111
EP 128
DI 10.1586/17474086.1.1.111
PG 18
WC Hematology
SC Hematology
GA V14KV
UT WOS:000207734200018
PM 20151032
ER
PT J
AU Traum, AZ
AF Traum, Avram Z.
TI Urine proteomic profiling to identify biomarkers of steroid resistance
in pediatric nephrotic syndrome
SO EXPERT REVIEW OF PROTEOMICS
LA English
DT Review
DE focal segmental glomerulosclerosis; high-abundance protein; nephrotic
syndrome; normal urine proteome; pediatric; urine proteomics
ID AMINO-ACID OXIDATION; MASS-SPECTROMETRY; PRIMARY CULTURES; PROTEINS;
AMMONIA; PHOSPHORYLATION; ASTROCYTES; NEURONS; SERUM; UREA
AB Long-term prognosis for children with nephrotic syndrome (NS) is directly related to steroid responsiveness. There are currently no diagnostic tests that accurately predict steroid responsiveness in pediatric NS. The initial prolonged course of daily, high-dose corticosteroid therapy thus serves both as a diagnostic and therapeutic maneuver. Urine proteomics is emerging as a potentially rich source of noninvasive biomarkers of drug responsiveness in NS. In this article, we discuss some of the initial studies of the urinary proteome in NS as well as ongoing and future challenges, define the normal urinary proteome and address the overwhelming abundance of urinary albumin and its impact on biomarker discovery.
C1 [Traum, Avram Z.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA.
[Traum, Avram Z.] Harvard Univ, Sch Med, Boston, MA USA.
RP Traum, AZ (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, 55 Fruit St, Boston, MA 02114 USA.
EM atraum@partners.org
FU National Kidney Foundation of MA/RI/ VT/NH
FX This work was supported by the National Kidney Foundation of MA/RI/
VT/NH. The author has no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in
the manuscript apart from those disclosed.
NR 29
TC 8
Z9 10
U1 0
U2 7
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1478-9450
J9 EXPERT REV PROTEOMIC
JI Expert Rev. Proteomics
PD OCT
PY 2008
VL 5
IS 5
BP 715
EP 719
DI 10.1586/14789450.5.5.715
PG 5
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 369NK
UT WOS:000260701000012
PM 18937561
ER
PT J
AU Kim, DH
Daskalakis, C
Plumb, JD
Adams, S
Brawer, R
Orr, N
Hawtborne, K
Toto, EC
Whellan, DJ
AF Kim, Dae Hyun
Daskalakis, Constantine
Plumb, James D.
Adams, Suzanne
Brawer, Rickie
Orr, Nicole
Hawtborne, Katie
Toto, Erin Cunningham
Whellan, David J.
TI Modifiable cardiovascular risk factors among individuals in low
socioeconomic communities and homeless shelters
SO FAMILY & COMMUNITY HEALTH
LA English
DT Article
DE cardiovascular disease; borneless persons; risk factors; socioeconomic
factors
ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; MANAGEMENT;
NEIGHBORHOOD; ATHEROSCLEROSIS; ENVIRONMENTS; DISPARITIES
AB To understand cardiovascular health in low socioeconomic populations, we analyzed the data from 426 low socioeconomic community-dwelling males and females and 287 homeless males in Philadelphia. Despite higher prevalence of smoking and hypertension, the proportion of homeless participants at increased risk for coronary heart disease was comparable with that of low socioeconomic community-dwelling participants. Among various characteristics, emotional stress was significantly associated with coronary heart disease risk in low socioeconomic community-dwelling participants only, suggestive of a differential psychosocial effect of stress. Our findings suggest that low socioeconomic populations are heterogeneous with respect to their risk factors and needs for interventions.
C1 [Kim, Dae Hyun; Adams, Suzanne; Orr, Nicole] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Daskalakis, Constantine] Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA.
[Plumb, James D.] Massachusetts Gen Hosp, Dept Family & Community Med, Boston, MA 02114 USA.
[Brawer, Rickie] Massachusetts Gen Hosp, Off Adv Populat Hlth, Boston, MA 02114 USA.
[Hawtborne, Katie] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
[Toto, Erin Cunningham] NW Mem Hosp, Chicago, IL 60611 USA.
[Whellan, David J.] Thomas Jefferson Univ, Div Cardiol, Philadelphia, PA 19107 USA.
RP Whellan, DJ (reprint author), 925 Chestnut St,Mezzanine Level, Philadelphia, PA 19107 USA.
EM david.whellan@jefferson.edu
NR 24
TC 12
Z9 12
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0160-6379
J9 FAM COMMUNITY HEALTH
JI Fam. Community Health
PD OCT-DEC
PY 2008
VL 31
IS 4
BP 269
EP 280
PG 12
WC Family Studies; Public, Environmental & Occupational Health
SC Family Studies; Public, Environmental & Occupational Health
GA 350LQ
UT WOS:000259354400004
PM 18794634
ER
PT J
AU Venkatesan, B
Ghosh-Choudhury, N
Das, F
Mahimainathan, L
Kamat, A
Kasinath, BS
Abboud, HE
Choudhury, GG
AF Venkatesan, Balachandar
Ghosh-Choudhury, Nandini
Das, Falguni
Mahimainathan, Lenin
Kamat, Amrita
Kasinath, Balakuntalam S.
Abboud, Hanna E.
Choudhury, Goutam Ghosh
TI Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial
cells: role of PTP1B
SO FASEB JOURNAL
LA English
DT Article
DE SIRT1; Akt kinase; CDK2
ID PROTEIN-TYROSINE PHOSPHATASE-1B; INDUCED DNA-SYNTHESIS; CARCINOMA A431
CELLS; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR; INSULIN SENSITIVITY; SIRT1
DEACETYLASE; IN-VIVO; C-FOS; PROLIFERATIVE GLOMERULONEPHRITIS
AB Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells with an IC50 of 10 mu M without inducing apoptosis. Remarkably, the increased SIRT1 deacetylase activity induced by resveratrol was not necessary for this inhibitory effect. Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Furthermore, resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. This deficiency in PDGFR phosphorylation resulted in significant inhibition of PI 3 kinase and Erk1/2 MAPK activity. Interestingly, resveratrol increased the activity of protein tyrosine phosphatase PTP1B, which dephosphorylates PDGF-stimulated phosphorylation at tyrosine-751 and tyrosine-716 on PDGFR with concomitant reduction in Akt and Erk1/2 kinase activity. PTP1B significantly inhibited PDGF-induced DNA synthesis without inducing apoptosis. These results for the first time provide evidence that the stilbene resveratrol targets PTP1B to inhibit PDGFR mitogenic signaling.
C1 [Venkatesan, Balachandar; Das, Falguni; Mahimainathan, Lenin; Kamat, Amrita; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, OBrien Kidney Res Ctr, Dept Med, San Antonio, TX 78229 USA.
[Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, OBrien Kidney Res Ctr, Dept Pathol, San Antonio, TX 78229 USA.
[Kamat, Amrita; Choudhury, Goutam Ghosh] Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA.
[Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, OBrien Kidney Res Ctr, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM choudhuryg@uthscsa.edu
OI /0000-0001-5077-3552
FU National Institutes of Health (NIH) [RO1 DK 50190]; Juvenile Diabetes
Research Foundation; NIH [RO1 AR52425, RO1 DK 33665]; VA Merit Review
and Morrison Trust; VA VISN; American Diabetes Association [077295]; VA
Research Service Merit
FX We thank Dr. Brent Wagner for critically reading the manuscript. This
work was supported by National Institutes of Health (NIH) grant RO1 DK
50190, the Juvenile Diabetes Research Foundation, and a VA Merit Review
grant to G.G.C., who is a research career scientist in the Department of
Veterans Affairs. N.G.C. is supported by NIH RO1 AR52425 and VA Merit
Review and Morrison Trust grants. A.K. is a recipient of a VA VISN
grant. B.S.K. is supported by grants from the NIH O'Brien Kidney Center,
NIH RO1 DK 077295, the American Diabetes Association, and a VA Research
Service Merit. Review grant. H.E.A. is supported by NIH RO1 DK 33665 and
VA Merit Review grants.
NR 95
TC 26
Z9 26
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 OCT
PY 2008
VL 22
IS 10
BP 3469
EP 3482
DI 10.1096/fj.08-109488
PG 14
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 354MB
UT WOS:000259642600009
PM 18567737
ER
PT J
AU Ng, AKL
Zhang, HM
Tan, KM
Li, ZL
Liu, JH
Chan, PKS
Li, SM
Chan, WY
Au, SWN
Joachimiak, A
Walz, T
Wang, JH
Shaw, PC
AF Ng, Andy Ka-Leung
Zhang, Hongmin
Tan, Kemin
Li, Zongli
Liu, Jin-Huan
Chan, Paul Kay-Sheung
Li, Sui-Mui
Chan, Wood-Yee
Au, Shannon Wing-Ngor
Joachimiak, Andrzej
Walz, Thomas
Wang, Jia-Huai
Shaw, Pang-Chui
TI Structure of the influenza virus A H5N1 nucleoprotein: implications for
RNA binding, oligomerization, and vaccine design
SO FASEB JOURNAL
LA English
DT Article
DE protein-RNA interaction; crystal structure; trimerization
ID CYTOTOXIC T-LYMPHOCYTES; LIMIT ESCAPE; POLYMERASE; COMPLEX;
IDENTIFICATION; TRANSCRIPTION; PROTEINS; ROLES; MODEL; NP
AB The threat of a pandemic outbreak of influenza virus A H5N1 has become a major concern worldwide. The nucleoprotein (NP) of the virus binds the RNA genome and acts as a key adaptor between the virus and the host cell. It, therefore, plays an important structural and functional role and represents an attractive drug target. Here, we report the 3.3-angstrom crystal structure of H5N1 NP, which is composed of a head domain, a body domain, and a tail loop. Our structure resolves the important linker segments (residues 397401, 429-437) that connect the tail loop with the remainder of the molecule and a flexible, basic loop (residues 73-91) located in an arginine-rich groove surrounding Arg150. Using surface plasmon resonance, we found the basic loop and arginine-rich groove, but mostly a protruding element containing Arg174 and Arg175, to be important in RNA binding by NP. We also used our crystal structure to build a ring-shaped assembly of nine NP subunits to model the miniribonucleo-protein particle previously visualized by electron microscopy. Our study of H5N1 NP provides insight into the oligomerization interface and the RNA-binding groove, which are attractive drug targets, and it identifies the epitopes that might be used for universal vaccine development.
C1 [Ng, Andy Ka-Leung; Li, Sui-Mui; Au, Shannon Wing-Ngor; Shaw, Pang-Chui] Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China.
[Ng, Andy Ka-Leung; Shaw, Pang-Chui] Chinese Univ Hong Kong, Mol Biotechnol Program, Shatin, Hong Kong, Peoples R China.
[Ng, Andy Ka-Leung; Li, Sui-Mui; Au, Shannon Wing-Ngor; Shaw, Pang-Chui] Chinese Univ Hong Kong, Ctr Prot Sci & Crystallog, Shatin, Hong Kong, Peoples R China.
[Chan, Paul Kay-Sheung] Chinese Univ Hong Kong, Dept Microbiol, Shatin, Hong Kong, Peoples R China.
[Chan, Wood-Yee] Chinese Univ Hong Kong, Dept Anat, Shatin, Hong Kong, Peoples R China.
[Li, Zongli; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Tan, Kemin; Joachimiak, Andrzej] Argonne Natl Lab, Midwest Ctr Struct Genom, Argonne, IL 60439 USA.
[Tan, Kemin; Joachimiak, Andrzej] Argonne Natl Lab, Struct Biol Ctr, Argonne, IL 60439 USA.
[Zhang, Hongmin; Liu, Jin-Huan; Wang, Jia-Huai] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med,Dept Pediat,Dept Biol Chem & Mol Pharmaco, Boston, MA 02115 USA.
RP Shaw, PC (reprint author), Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China.
EM pcshaw@cuhk.edu.hk
RI Zhang, Hongmin/C-4503-2009; Chan, Paul/J-9360-2013
OI Zhang, Hongmin/0000-0001-6357-4106;
FU Chinese University [CUHK 472808]; HK-SAR; National Institutes of Health
(NIH); Giovanni Armenise Harvard Center for Strucutural Biology
FX This work was supported by a Direct Research grant from the Chinese
University and a General Research Fund grant (CUHK 472808) from the
Research Grants Council of HK-SAR (P.-C.S.), a subcontracted National
Institutes of Health (NIH) grant, and the Claudia Adams Barr Program in
Cancer Research (J.-H.W.). The molecular EM facility at Harvard Medical
School was established with it generous donation from the Giovanni
Armenise Harvard Center for Strucutural Biology and is maintained with
funds from NIH (T.W.), The authors (flank Professor Ming Luo for advice
on the manuscript.
NR 40
TC 125
Z9 132
U1 1
U2 17
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 OCT
PY 2008
VL 22
IS 10
BP 3638
EP 3647
DI 10.1096/fj.08-112110
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 354MB
UT WOS:000259642600025
PM 18614582
ER
PT J
AU Chen, XZ
Li, Q
Wu, YL
Liang, GQ
Lara, CJ
Cantiello, HF
AF Chen, Xing-Zhen
Li, Qiang
Wu, Yuliang
Liang, Genqing
Lara, Carlos J.
Cantiello, Horacio F.
TI Submembraneous microtubule cytoskeleton: interaction of TRPP2 with the
cell cytoskeleton
SO FEBS JOURNAL
LA English
DT Review
DE actin filament; autosomal dominant polycystic kidney disease; cellular
sensor; fibrocystin; interacting partner; ion channel; kinesin-2;
microtubule; polycystin; transient receptor potential
ID POLYCYSTIC KIDNEY-DISEASE; CATION CHANNEL FUNCTION; ACTIN CYTOSKELETON;
ALPHA-ACTININ; HUMAN SYNCYTIOTROPHOBLAST; CD2-ASSOCIATED PROTEIN;
EPITHELIAL-CELLS; PKD2 INTERACTS; NMDA RECEPTOR; PRIMARY CILIA
AB TRPP2, also called polycystin-2, the gene product of PKD2, is a membrane protein defective in 10-15% of cases of autosomal dominant polycystic kidney disease. Mutations in PKD2 are also associated with extrarenal disorders, such as hepatic cystogenesis and cardiovascular abnormalities. TRPP2 is a Ca-permeable nonselective cation channel present in the endoplasmic reticulum and plasma membrane, as well as in cilia of renal epithelial and embryonic nodal cells, in which it likely forms part of a flow sensor. Recent studies have identified a number of TRPP2-interacting proteins, of which many are cytoskeletal components. Work from our and other laboratories indicates that cytoskeletal partner proteins seem to play important, albeit highly complex, roles in the regulation of TRPP2 expression, localization and channel function. This minireview covers current knowledge about cytoskeletal interactions with TRPP2, and suggests that mutations in proteins of the TRPP2-cytoskeleton complex may be implicated in the pathogenesis of autosomal dominant polycystic kidney disease.
C1 [Chen, Xing-Zhen; Li, Qiang; Wu, Yuliang; Liang, Genqing; Lara, Carlos J.] Univ Alberta, Dept Physiol, Membrane Prot Res Grp, Edmonton, AB T6G 2H7, Canada.
[Cantiello, Horacio F.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Cantiello, Horacio F.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA.
RP Chen, XZ (reprint author), Univ Alberta, Dept Physiol, Membrane Prot Res Grp, 7-29 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada.
EM xzchen@ualberta.ca
RI Liang, Genqing/B-7180-2011
FU Canadian Institutes of Health Research and the Kidney Foundation of
Canada; Alberta Heritage Foundation for Medical Research Senior
Scholarship
FX This work was supported by the Canadian Institutes of Health Research
and the Kidney Foundation of Canada. X. Z. C. is a recipient of the
Alberta Heritage Foundation for Medical Research Senior Scholarship.
NR 59
TC 23
Z9 23
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD OCT
PY 2008
VL 275
IS 19
BP 4675
EP 4683
DI 10.1111/j.1742-4658.2008.06616.x
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 348KO
UT WOS:000259209600004
PM 18754774
ER
PT J
AU Grady, WM
Carethers, JM
AF Grady, William M.
Carethers, John M.
TI Genomic and epigenetic instability in colorectal cancer pathogenesis
SO GASTROENTEROLOGY
LA English
DT Review
ID DNA MISMATCH REPAIR; ISLAND METHYLATOR PHENOTYPE; NONPOLYPOSIS
COLON-CANCER; TUMOR MICROSATELLITE-INSTABILITY; HMLH1 PROMOTER
HYPERMETHYLATION; CAUSE CHROMOSOMAL INSTABILITY; REPLICATION PROTEIN-A;
BASE-EXCISION-REPAIR; CELL NUCLEAR ANTIGEN; ABERRANT CRYPT FOCI
AB Colorectal cancer arises as a consequence of the accumulation of genetic alterations (gene mutations, gene amplification, and so on) and epigenetic alterations (aberrant DNA methylation, chromatin modifications, and so on) that transform colonic epithelial cells into colon adenocarcinoma cells. The loss of genomic stability and resulting gene alterations are key molecular pathogenic steps that occur early in tumorigenesis; they permit the acquisition of a sufficient number of alterations in tumor suppressor genes and oncogenes that transform cells and promote tumor progression. Two predominant forms of genomic instability that have been identified in colon cancer are microsatellite instability and chromosome instability. Substantial progress has been made to identify causes of chromosomal instability in colorectal cells and to determine the effects of the different forms of genomic instability on the biological and clinical behavior of colon tumors. In addition to genomic instability, epigenetic instability results in the aberrant methylation of tumor suppressor genes. Determining the causes and roles of genomic and epigenomic instability in colon tumor formation has the potential to yield more effective prevention strategies and therapeutics for patients with colorectal cancer.
C1 [Carethers, John M.] Univ Calif San Diego, Dept Med, Div Gastroenterol, La Jolla, CA 92093 USA.
[Carethers, John M.] Univ Calif San Diego, Rebecca & John Moores Comprehens Canc Ctr, La Jolla, CA 92093 USA.
[Carethers, John M.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Grady, William M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Grady, William M.] VA Puget Sound Healthcare Syst, Seattle, WA USA.
RP Carethers, JM (reprint author), Univ Calif San Diego, Dept Med, Div Gastroenterol, UC303,MC 0063,9500 Gilman Dr, La Jolla, CA 92093 USA.
EM jcarethers@ucsd.edu
FU US Public Health Service [CA11518, DK067287, DK080506]; VA Research
Service
FX Supported by the US Public Health Service (CA11518 to W.M.G. and
DK067287 and DK080506 to J.M.C.) and the VA Research Service (W.M.G. and
J.M.C.).
NR 215
TC 345
Z9 357
U1 3
U2 29
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 OCT
PY 2008
VL 135
IS 4
BP 1079
EP 1099
DI 10.1053/j.gastro.2008.07.076
PG 21
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 359JM
UT WOS:000259982800015
PM 18773902
ER
PT J
AU Lieberman, D
Moravec, M
Holub, J
Michaels, L
Eisen, G
AF Lieberman, David
Moravec, Matthew
Holub, Jennifer
Michaels, Leann
Eisen, Glenn
TI Polyp size and advanced histology in patients undergoing colonoscopy
screening: Implications for CT colonography
SO GASTROENTEROLOGY
LA English
DT Article
ID AMERICAN-CANCER-SOCIETY; COLORECTAL-CANCER; ASYMPTOMATIC ADULTS;
ADVANCED NEOPLASIA; TASK-FORCE; SURVEILLANCE; ADENOMAS; POLYPECTOMY;
GUIDELINES; UPDATE
AB Background & Aims: Colorectal cancer screening with diagnostic imaging can detect polyps. The management of patients whose largest polyp is less than 10 mm is uncertain. The primary aim of this study was to determine rates of advanced histology in patients undergoing colorectal cancer screening whose largest polyp is 9 mm or less. Methods: Subjects include all asymptomatic adults receiving colonoscopy for screening during 2005 from 17 practice sites, which provide both colonoscopy and pathology reports to the Clinical Outcomes Research Initiative repository. Patients were classified by size of largest polyp. Advanced histology was defined as an adenoma. with villous or serrated histology, highgrade dysplasia, or an invasive cancer. Risk factors for advanced histology were determined using Pearson X-2 and Fisher exact tests. Results: Among 13,992 asymptomatic patients who had screening colonoscopy, 6360 patients (45%) had polyps, with complete histology available in 5977 (94%) patients. The proportion with advanced histology was 1.7% in the 1- to 5-mm group, 6.6% in the 6- to 9-mm group, 30.6% in the greater than 10-mm group, and 72.1% in the tumor group. Distal location was associated with advanced histology in the 6- to 9-mm group (P = .04) and in the greater than 10-mm group (P = .002). Conclusions: One in 15 asymptomatic patients whose largest polyp is 6 to 9 nun will have advanced histology and would undergo surveillance at 3 years based on current guidelines. Because histology is necessary for this decision, most of these patients should be offered colonoscopy. Further study should determine whether patients whose largest polyp is 1-5 mm. can be safely followed without polypectomy.
C1 [Lieberman, David; Moravec, Matthew; Holub, Jennifer; Michaels, Leann; Eisen, Glenn] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97239 USA.
RP Lieberman, D (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, Portland VA Med Ctr, P3-GI,1037 SW Vet Hosp Rd, Portland, OR 97239 USA.
EM lieberma@ohsu.edu
FU NIDDK [U01 DK57132, R33-DK6177801]; AstraZeneca; Bard International;
Pentax USA; ProVation; Endosoft; GIVEN Imaging; Ethicon; federal and
industry sources
FX Supported with funding from NIDDK U01 DK57132 and R33-DK6177801, and, in
addition, the practice network (Clinical Outcomes Research Ini tiative)
has received support from the following entities to support the
infrastructure of the practice-based network: AstraZeneca, Bard
International, Pentax USA, ProVation, Endosoft, GIVEN Imaging, and
Ethicon; however, the commercial entities had no involvement in this
research.; Financial disclosure and conflicts of interest: Dr Lieberman
is the executive director of the Clinical Outcomes Research Initiative
(CORI), a nonprofit organization that receives funding from federal and
industry sources. The CORI database is used in this study. This
relationship has been reviewed and managed by the OHSU and Portland VAMC
Conflict of Interest in Research Committee.
NR 21
TC 198
Z9 203
U1 2
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD OCT
PY 2008
VL 135
IS 4
BP 1100
EP 1105
DI 10.1053/j.gastro.2008.06.083
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 359JM
UT WOS:000259982800016
PM 18691580
ER
PT J
AU Suter, MJ
Vakoc, BJ
Yachimski, PS
Shishkov, M
Lauwers, GY
Mino-Kenudson, M
Bouma, BE
Nishioka, NS
Tearney, GJ
AF Suter, Melissa J.
Vakoc, Benjamin J.
Yachimski, Patrick S.
Shishkov, Milen
Lauwers, Gregory Y.
Mino-Kenudson, Mari
Bouma, Brett E.
Nishioka, Norman S.
Tearney, Guillermo J.
TI Comprehensive microscopy of the esophagus in human patients with optical
frequency domain imaging
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article
ID HIGH-GRADE DYSPLASIA; COHERENCE TOMOGRAPHY; BARRETTS-ESOPHAGUS; IN-VIVO;
INTESTINAL METAPLASIA; ULTRAHIGH-RESOLUTION; GI TRACT; SURVEILLANCE;
ADENOCARCINOMA; DIAGNOSIS
AB Background: Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas.
Objective: The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (similar to 6.0 cm) in patients.
Design: A pilot feasibility study.
Setting: Massachusetts General Hospital.
Patients: Twelve patients undergoing routine EGD.
Results: Comprehensive microscopy of the distal esophagus was successfully performed in 10 patient with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion.
Limitations: Inability to obtain direct correlation of OFDI data and histopathologic diagnoses.
Conclusions: Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses.
C1 [Lauwers, Gregory Y.; Mino-Kenudson, Mari; Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Suter, Melissa J.; Vakoc, Benjamin J.; Shishkov, Milen; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Suter, Melissa J.; Vakoc, Benjamin J.; Shishkov, Milen; Bouma, Brett E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA.
[Yachimski, Patrick S.; Nishioka, Norman S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Tearney, GJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 40 Blossom St,BAR 703, Boston, MA 02114 USA.
FU National Institutes of Health [R01CA103769]; Center for Integration of
Medicine and Innovative Technology (development of the imaging platform)
FX The authors report that there are no disclosures relevant to this
publication. This work was supported by National Institutes of Health
grant No. R01CA103769 and by the Center for Integration of Medicine and
Innovative Technology (development of the imaging platform).
NR 27
TC 89
Z9 90
U1 2
U2 11
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD OCT
PY 2008
VL 68
IS 4
BP 745
EP 753
DI 10.1016/j.gie.2008.05.014
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 355NQ
UT WOS:000259716000023
PM 18926183
ER
PT J
AU Labbe, C
Goyette, P
Lefebvre, C
Stevens, C
Green, T
Tello-Ruiz, MK
Cao, Z
Landry, AL
Stempak, J
Annese, V
Latiano, A
Brant, SR
Duerr, RH
Taylor, KD
Cho, JH
Steinhart, AH
Daly, MJ
Silverberg, MS
Xavier, RJ
Rioux, JD
AF Labbe, C.
Goyette, P.
Lefebvre, C.
Stevens, C.
Green, T.
Tello-Ruiz, M. K.
Cao, Z.
Landry, A. L.
Stempak, J.
Annese, V.
Latiano, A.
Brant, S. R.
Duerr, R. H.
Taylor, K. D.
Cho, J. H.
Steinhart, A. H.
Daly, M. J.
Silverberg, M. S.
Xavier, R. J.
Rioux, J. D.
TI MAST3: a novel IBD risk factor that modulates TLR4 signaling
SO GENES AND IMMUNITY
LA English
DT Article
DE MAST3; inflammatory bowel disease; TLR4; NF-kappa B
ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; KAPPA-B ACTIVATION;
CROHNS-DISEASE; SUSCEPTIBILITY LOCI; SERINE/THREONINE KINASES;
ULCERATIVE-COLITIS; GENETIC-VARIATION; PATHOGENESIS; EXPRESSION
AB Inflammatory bowel disease (IBD) is a chronic disorder caused by multiple factors in a genetically susceptible host. Significant advances in the study of genetic susceptibility have highlighted the importance of the innate immune system in this disease. We previously completed a genome-wide linkage study and found a significant locus (IBD6) on chromosome 19p. We were interested in identifying the causal variant in IBD6. We performed a two-stage association mapping study. In stage 1, 1530 single-nucleotide polymorphisms (SNPs) were selected from the HapMap database and genotyped in 761 patients with IBD. Among the SNPs that passed the threshold for replication, 26 were successfully genotyped in 754 additional patients (stage 2). One intronic variant, rs273506, located in the microtubule-associated serine/threonine- protein kinase gene-3 (MAST3), was found to be associated in both stages (pooled P = 1.8 x 10(-4)). We identified four MAST3 coding variants, including a nonsynonymous SNP rs8108738, correlated to rs273506 and associated with IBD. To test whether MAST3 was expressed in cells of interest, we performed expression assays, which showed abundant expression of MAST3 in antigen-presenting cells and in lymphocytes. The knockdown of MAST3 specifically decreased Toll-like receptor-4-dependent NF-kappa B activity. Our findings are additional proofs of the pivotal role played by modulators of NF-kappa B activity in IBD pathogenesis.
C1 [Rioux, J. D.] Univ Montreal, Montreal Heart Inst, Res Ctr, Dept Med, Montreal, PQ H1T 1C8, Canada.
[Labbe, C.; Goyette, P.; Lefebvre, C.; Rioux, J. D.] Inst Cardiol Montreal, Montreal, PQ, Canada.
[Stevens, C.; Green, T.; Tello-Ruiz, M. K.; Daly, M. J.; Rioux, J. D.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Cao, Z.; Landry, A. L.; Daly, M. J.; Xavier, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA.
[Cao, Z.; Landry, A. L.; Daly, M. J.; Xavier, R. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA.
[Stempak, J.; Steinhart, A. H.; Silverberg, M. S.] Univ Toronto, Mt Sinai Hosp, IBD Ctr, Toronto, ON M5G 1X5, Canada.
[Annese, V.; Latiano, A.] IRCCS Hosp, Gastrointestinal & Endoscopy Units, San Giovanni Rotondo, Italy.
[Brant, S. R.] Johns Hopkins Univ, Sch Med, Meyerhoff Inflammatory Bowel Dis Ctr, Baltimore, MD USA.
[Duerr, R. H.] Univ Pittsburgh, Sch Med, Inflammatory Bowel Dis Genet Program, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Taylor, K. D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Taylor, K. D.] Cedars Sinai Med Ctr, IBD Ctr, Los Angeles, CA 90048 USA.
[Cho, J. H.] Yale Univ, Dept Med, IBD Ctr, Div Gastroenterol, New Haven, CT 06520 USA.
RP Rioux, JD (reprint author), Univ Montreal, Montreal Heart Inst, Res Ctr, Dept Med, 5000 Belanger St,Rm S-6200, Montreal, PQ H1T 1C8, Canada.
EM John.David.Rioux@umontreal.ca
RI Silverberg, Mark/B-4183-2008; Rioux, John/A-9599-2015; Latiano,
Anna/R-1965-2016;
OI Rioux, John/0000-0001-7560-8326; Latiano, Anna/0000-0003-3719-2061;
Duerr, Richard/0000-0001-6586-3905
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK062432, AI062773]; Broad Institute Center for Genotyping and Analysis
[U54 RR020278]; National Center for Research Resources
FX This project was funded by grants from the National Institute of
Diabetes and Digestive and Kidney Diseases DK062432 to JDR and AI062773
to RJX. The Broad Institute Center for Genotyping and Analysis is
supported by Grant U54 RR020278 from the National Center for Research
Resources. C Labbe is the recipient of a Fond de Recherche en Sante du
Quebec studentship award. We thank Marcia Budarf, Marie- Pierre Levesque
and Jing Lian for their help in the review of the paper.
NR 35
TC 11
Z9 12
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
J9 GENES IMMUN
JI Genes Immun.
PD OCT
PY 2008
VL 9
IS 7
BP 602
EP 612
DI 10.1038/gene.2008.57
PG 11
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 362WS
UT WOS:000260228500004
PM 18650832
ER
PT J
AU Poitras, JL
Dal Cin, P
Aster, JC
DeAngelo, DJ
Morton, CC
AF Poitras, Jennifer L.
Dal Cin, Paola
Aster, Jon C.
DeAngelo, Daniel J.
Morton, Cynthia C.
TI Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in
pre-B acute lymphocytic leukemia
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE
DISORDERS; POLYCYTHEMIA-VERA; PCM1-JAK2 FUSION; T(8/9) TRANSLOCATION;
BINDING PROTEIN; LIM-DOMAIN; MUTATION; PATIENT
AB Activating mutations in JAK2 are found in virtually all patients with polycythemia vera, and about half of those with essential thrombocythemia and primary myelofibrosis. In addition, less common aberrations (particularly gene fusions) involving JAK2 have been described in acute leukemias. With the advent of JAK2 inhibitor trials in myeloproliferative disorders, tumors with JAK2 mutations or rearrangements have become candidates for targeted therapy. In this report, we identify SSBP2 as a new JAK2 fusion partner in a patient with pi cell acute lymphocytic leukemia. This finding adds to the expanding compendium of JAK2 aberrations found in various hematopoietic malignancies, as well as the potential need for a diagnostic FISH analysis in the appropriate clinical setting. (C) 2008 Wiley-Liss, Inc.
C1 [Poitras, Jennifer L.; Dal Cin, Paola; Aster, Jon C.; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Dal Cin, Paola; Aster, Jon C.; DeAngelo, Daniel J.; Morton, Cynthia C.] Harvard Univ, Sch Med, Boston, MA USA.
[DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Ob Gyn, 77 Ave Louis Pasteur,NRB 160, Boston, MA 02115 USA.
EM cmorton@partners.org
FU Department of Pathology at Brigham; Women's Hospital; Dana-Farber Cancer
Institute [P01CA066996-11A1]
FX We thank the Department of Pathology at Brigham and Women's Hospital for
support of this investigation. Harvard Partners Center for Genetics and
Genomics for kindly providing BAC clones, the Dana-Farber/I larvard
Cancer Center DNA Resource Core for the automated DNA sequence analysis
(P30CA006516), the Molecular Diagnostics Laboratory at Brigham and
Women's Hospital for performing JAK2 V617F screening, and Ilene
Galinsky, RN for assistance in sample collection. Samples were stored in
the Connell O'Reily Cell Manipulation Core Facility, at the Dana-Farber
Cancer Institute, supported by P01CA066996-11A1.
NR 28
TC 30
Z9 30
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD OCT
PY 2008
VL 47
IS 10
BP 884
EP 889
DI 10.1002/gcc.20585
PG 6
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 340ZM
UT WOS:000258683500007
PM 18618714
ER
PT J
AU Kharchenko, PV
Woo, CJ
Tolstorukov, MY
Kingston, RE
Park, PJ
AF Kharchenko, Peter V.
Woo, Caroline J.
Tolstorukov, Michael Y.
Kingston, Robert E.
Park, Peter J.
TI Nucleosome positioning in human HOX gene clusters
SO GENOME RESEARCH
LA English
DT Article
ID MICROCOCCAL NUCLEASE; PROMOTER ELEMENTS; CHROMATIN DNA; SEQUENCE; YEAST;
TRANSCRIPTION; GENOME; RESOLUTION; OCCUPANCY; STABILITY
AB The distribution of nucleosomes along the genome is a significant aspect of chromatin structure and is thought to influence gene regulation through modulation of DNA accessibility. However, properties of nucleosome organization remain poorly understood, particularly in mammalian genomes. Toward this goal we used tiled microarrays to identify stable nucleosome positions along the HOX gene clusters in human cell lines. We show that nucleosome positions exhibit sequence properties and long-range organization that are different from those characterized in other organisms. Despite overall variability of internucleosome distances, specific loci contain regular nucleosomal arrays with 195-bp periodicity. Moreover, such arrays tend to occur preferentially toward the 3' ends of genes. Through comparison of different cell lines, we find that active transcription is correlated with increased positioning of nucleosomes, suggesting an unexpected role for transcription in the establishment of well-positioned nucleosomes.
C1 [Woo, Caroline J.; Kingston, Robert E.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Kharchenko, Peter V.; Tolstorukov, Michael Y.; Park, Peter J.] Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA.
[Kharchenko, Peter V.; Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM kingston@molbio.mgh.harvard.edu; peter_park@harvard.edu
FU NLM [T15LM007092]; NSRA [F32 GM062265]; NIH [R01 GM082798, GM49301]
FX We thank John Rinn for sharing the design of the tiling microarray. This
research was supported by NLM training fellowship T15LM007092 (P. V.
K.), NSRA fellowship F32 GM062265 (C. J. W.), NIH R01 GM082798 (P. J.
P.), and NIH grant GM49301 (R. E. K.).
NR 41
TC 30
Z9 30
U1 0
U2 2
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD OCT
PY 2008
VL 18
IS 10
BP 1554
EP 1561
DI 10.1101/gr.075952.107
PG 8
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 355HU
UT WOS:000259700800002
PM 18723689
ER
PT J
AU Karel, M
AF Karel, M.
TI GEROPSYCHOLOGY INTERNSHIP TRAINING: EVALUATING COMPETENCIES AND FINDING
A GOOD FIT
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Karel, M.] VA Boston Healthcare Syst, Brockton, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD OCT
PY 2008
VL 48
SI 3
BP 7
EP 7
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 399PA
UT WOS:000262810600027
ER
PT J
AU Roberge, B
Mahoney, E
Minaker, K
Chuang, S
AF Roberge, B.
Mahoney, E.
Minaker, K.
Chuang, S.
TI IDENTIFICATION OF NURSES' CONCERNS: THE BASIS FOR IMPROVING GERIATRIC
SENSITIVE QUALITY INDICATORS FOR VULNERABLE HOSPITALIZED OLDER ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Roberge, B.; Minaker, K.; Chuang, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mahoney, E.] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD OCT
PY 2008
VL 48
SI 3
BP 31
EP 32
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA 399PA
UT WOS:000262810600109
ER
PT J
AU Mroczek, D
Turiano, N
Spiro, A
AF Mroczek, D.
Turiano, N.
Spiro, A., III
TI EFFECTS OF NEUROTICISM CHANGE AND WIDOWHOOD ON MORTALITY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Mroczek, D.; Turiano, N.] Purdue Univ, W Lafayette, IN 47907 USA.
[Spiro, A., III] VA Boston Healthcare Syst, Boston, MA 02215 USA.
[Spiro, A., III] Boston Univ, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD OCT
PY 2008
VL 48
SI 3
BP 135
EP 135
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 399PA
UT WOS:000262810600465
ER
EF