FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Klepeis, VE
Deshpande, V
Sohani, AR
Ferry, JA
AF Klepeis, V. E.
Deshpande, V.
Sohani, A. R.
Ferry, J. A.
TI Sclerosing Inflammatory Pseudotumor of the Orbit: An IgG4-Related
Disease
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Klepeis, V. E.; Deshpande, V.; Sohani, A. R.; Ferry, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1371
BP 307A
EP 307A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301387
ER
PT J
AU Nardi, V
Abramson, JS
Hasserjian, RP
AF Nardi, V.
Abramson, J. S.
Hasserjian, R. P.
TI Morphologic Dysplasia in Staging Marrow from High-Grade Non-Hodgkin's
Lymphoma Patients: A Paraneoplastic Phenomenon Associated with Adverse
Clinical Outcome
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Nardi, V.; Abramson, J. S.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1403
BP 314A
EP 314A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301419
ER
PT J
AU Rodig, SJ
Kutok, JL
Paterson, JC
Zhang, W
Shipp, MA
Grogan, T
Pileri, SA
Montes-Moreno, S
Johnson, NA
Ben-Neriah, S
Farinha, P
Piris, MA
Gascoyne, R
Marafioti, T
AF Rodig, S. J.
Kutok, J. L.
Paterson, J. C.
Zhang, W.
Shipp, M. A.
Grogan, T.
Pileri, S. A.
Montes-Moreno, S.
Johnson, N. A.
Ben-Neriah, S.
Farinha, P.
Piris, M. A.
Gascoyne, R.
Marafioti, T.
TI VpreB3, a Pre-BCR Associated Protein, Is Expressed by a Subset of
Mature, Germinal Center B Cells and a Biomarker of Burkitt Lymphoma
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Univ Oxford, Oxford, England.
Ventana Med Syst, Tucson, AZ USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Arizona, Tucson, AZ USA.
Univ Bologna, Sch Med, Bologna, Italy.
Spanish Natl Canc Ctr CNIO, Madrid, Spain.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1424
BP 318A
EP 319A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301440
ER
PT J
AU Ryan, RJH
Zukerberg, L
Sloan, JM
Collins, B
Ferry, J
AF Ryan, R. J. H.
Zukerberg, L.
Sloan, J. M.
Collins, B.
Ferry, J.
TI MALT Lymphoma with Associated Amyloid Deposition - A
Clinico-Pathological Study of 18 Cases
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Boston Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1430
BP 320A
EP 320A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301446
ER
PT J
AU Wang, SA
Abruzzo, LV
Hasserjian, RP
Medeiros, LJ
Miranda, RN
AF Wang, S. A.
Abruzzo, L. V.
Hasserjian, R. P.
Medeiros, L. J.
Miranda, R. N.
TI Myelodysplastic Syndromes with Interstitial Deletions of 11q Lack
Cryptic 11q23 Translocations and Exhibit Characteristic
Clinicopathologic Features
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 UT MD Anderson, Houston, TX USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1460
BP 327A
EP 327A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301476
ER
PT J
AU Louissaint, A
Ferry, JA
Harris, NL
Zukerberg, LR
AF Louissaint, A.
Ferry, J. A.
Harris, N. L.
Zukerberg, L. R.
TI Morphology and Immunophenotype of Infectious Mononucleosis Presenting in
Axillary and Inguinal Lymph Nodes and Other Unusual Locations
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Louissaint, A.; Ferry, J. A.; Harris, N. L.; Zukerberg, L. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1491
BP 334A
EP 334A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301506
ER
PT J
AU Farris, AB
Taheri, D
Fazlollahi, L
Iafrate, AJ
Smith, RN
Collins, AB
Tolkoff-Rubin, N
Spitzer, TR
Kawai, T
Cosimi, AB
Sachs, DH
Colvin, RB
AF Farris, A. B.
Taheri, D.
Fazlollahi, L.
Iafrate, A. J.
Smith, R. N.
Collins, A. B.
Tolkoff-Rubin, N.
Spitzer, T. R.
Kawai, T.
Cosimi, A. B.
Sachs, D. H.
Colvin, R. B.
TI Distinctive Renal Biopsy Pathology in the Engraftment Syndrome: A
Response to Combined Kidney and Bone Marrow Transplantation
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Emory U, Atlanta, GA USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1512
BP 339A
EP 339A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301527
ER
PT J
AU Farris, AB
Coban, I
Klimstra, DS
Kim, G
Deshpande, V
Ohike, N
Adsay, N
AF Farris, A. B.
Coban, I.
Klimstra, D. S.
Kim, G.
Deshpande, V.
Ohike, N.
Adsay, N.
TI Necrotizing Arteritis Presenting as a Pancreatic Mass: A New Addition to
the Immune-Related Tumoral Pancreatitides
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Emory U, Atlanta, GA USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
UCSF, San Francisco, CA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1576
BP 354A
EP 355A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301591
ER
PT J
AU Gupta, RK
Genevay, M
Johnson, NB
Lauwers, GY
Deshpande, V
AF Gupta, R. K.
Genevay, M.
Johnson, N. B.
Lauwers, G. Y.
Deshpande, V.
TI Is Autoimmune Pancreatitis Associated with an Increased Risk of
Malignancy? A Retrospective and Comparative Study
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Univ Geneva, Geneva, Switzerland.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Beth Israel Deaconess Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1584
BP 356A
EP 357A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301599
ER
PT J
AU Lennerz, JK
Chapman, WC
Brunt, EM
AF Lennerz, J. K.
Chapman, W. C.
Brunt, E. M.
TI Epithelial-Mesenchymal Transition (EMT) of K19 Structures within the
Stromal Compartment of HCV Cirrhosis Parallels Hepatocarcinogenesis
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Washington Univ, St Louis, MO 63130 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1604
BP 361A
EP 361A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301619
ER
PT J
AU Lisovsky, M
Dresser, K
Woda, B
Mino-Kenudson, M
AF Lisovsky, M.
Dresser, K.
Woda, B.
Mino-Kenudson, M.
TI Differentiation of Pancreatic Intraepithelial Neoplasia-3 (PanIN-3) and
Ductal Adenocarcinoma of the Pancreas from Lower Grade PanINs Utilizing
Immunohistochemistry for Cell Polarity Protein Lethal Giant Larva 2
(Igl2)
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
UMassMem Med Ctr, Worcester, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1615
BP 363A
EP 363A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301630
ER
PT J
AU Nagata, K
Lauwers, GY
Murata, S
Shimizu, M
AF Nagata, K.
Lauwers, G. Y.
Murata, S.
Shimizu, M.
TI Gallbladder Intramural Papillary Mucinous Neoplasm: A New Entity Similar
to IPMN of the Pancreas
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Saitama Med Univ, Saitama Int Med Ctr, Hidaka, Saitama, Japan.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1628
BP 366A
EP 366A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301643
ER
PT J
AU Shen, J
Konstantinidis, I
Ferrone, CR
Deshpande, V
AF Shen, J.
Konstantinidis, I.
Ferrone, C. R.
Deshpande, V.
TI Intrapancreatic Cholangiocarcinomas: A Clinicopathological and
Immunohistochemical Analysis
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Shen, J.; Konstantinidis, I.; Ferrone, C. R.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1651
BP 371A
EP 371A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301666
ER
PT J
AU Xiao, HD
Yamaguchi, H
Dias-Santagata, D
Kuboki, Y
Akhavanfard, S
Hatori, T
Yamamoto, M
Shiratori, K
Kobayashi, M
Shimizu, M
Mino-Kenudson, M
Furukawa, T
AF Xiao, H. D.
Yamaguchi, H.
Dias-Santagata, D.
Kuboki, Y.
Akhavanfard, S.
Hatori, T.
Yamamoto, M.
Shiratori, K.
Kobayashi, M.
Shimizu, M.
Mino-Kenudson, M.
Furukawa, T.
TI Molecular Characteristics and Biological Behavior of Intraductal
Papillary-Mucinous Neoplasm, Oncocytic Type (IPMN-O)
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Saitama Med Univ, Saitama, Japan.
Int Res & Educ Inst Integrated Med Sci, Tokyo, Japan.
Tokyo Womens Med Univ, Tokyo, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1667
BP 374A
EP 375A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301682
ER
PT J
AU Laury, AR
Hornick, JL
Piao, H
Perets, R
Barletta, J
Chirieac, LR
Krane, JF
Lis, R
Loda, M
Drapkin, R
Hirsch, MS
AF Laury, A. R.
Hornick, J. L.
Piao, H.
Perets, R.
Barletta, J.
Chirieac, L. R.
Krane, J. F.
Lis, R.
Loda, M.
Drapkin, R.
Hirsch, M. S.
TI PAX8 Is Highly Sensitive and Specific for Mullerian, Renal and Thyroid
Neoplasms: A Study of 1500 Epithelial Tumors
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RI Drapkin, Ronny/E-9944-2016
OI Drapkin, Ronny/0000-0002-6912-6977
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1730
BP 388A
EP 388A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301745
ER
PT J
AU Cheng, L
Janne, PA
Jackman, DM
Johnson, BE
Joshi, VA
Lindeman, NI
AF Cheng, L.
Janne, P. A.
Jackman, D. M.
Johnson, B. E.
Joshi, V. A.
Lindeman, N. I.
TI Mutational Analysis of EGFR, KRAS, BRAF, PIK3CA, and ERBB2 in
Non-Small-Cell Lung Carcinomas (NSCLC)
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Mol Med Lab, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1783
BP 399A
EP 399A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301798
ER
PT J
AU Klepeis, VE
Mark, EG
Dias-Santagata, D
Iafrate, AJ
Minto-Kenudson, M
AF Klepeis, V. E.
Mark, E. G.
Dias-Santagata, D.
Iafrate, A. J.
Minto-Kenudson, M.
TI Genotype-Phenotype Correlation in Lung Adenocarcinoma
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
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 NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1812
BP 406A
EP 406A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301827
ER
PT J
AU Hunt, JL
Smith, MT
Black-Schaffer, WS
AF Hunt, J. L.
Smith, M. T.
Black-Schaffer, W. S.
TI Joint Commission Standards for Ongoing and Focused Performance
Evaluation in Anatomic Pathology: Current Trends in Practice
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Med Univ S Carolina, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1870
BP 418A
EP 418A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301885
ER
PT J
AU Morgan, EA
Oh, KY
Waghorne, CG
Neuberg, D
Stevenson, K
Kutok, JL
AF Morgan, E. A.
Oh, K. Y.
Waghorne, C. G.
Neuberg, D.
Stevenson, K.
Kutok, J. L.
TI Flow Cytometry Underestimates the Bone Marrow CD34-Positive Blast
Population Compared to Immunohistochemical and Morphologic Assessments
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1874
BP 419A
EP 419A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301889
ER
PT J
AU Ryan, RJH
Snuderl, M
Black-Schaffer, WS
Hunt, J
AF Ryan, R. J. H.
Snuderl, M.
Black-Schaffer, W. S.
Hunt, J.
TI Improvements in Training and Credentialing of Residents for Independent
Frozen Section Sign-Out Responsibility
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Ryan, R. J. H.; Snuderl, M.; Black-Schaffer, W. S.; Hunt, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2010
VL 90
SU 1
MA 1880
BP 421A
EP 421A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 553AR
UT WOS:000274337301895
ER
PT J
AU Corrales-Medina, VF
Madjid, M
Musher, DM
AF Corrales-Medina, Vicente F.
Madjid, Mohammad
Musher, Daniel M.
TI Role of acute infection in triggering acute coronary syndromes
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; RESPIRATORY-TRACT
INFECTIONS; COMMUNITY-ACQUIRED PNEUMONIA; AMERICAN-HEART-ASSOCIATION;
HEAVY PHYSICAL EXERTION; CARDIOVASCULAR-DISEASE; INFLUENZA VACCINATION;
UNSTABLE ANGINA; ARTERY-DISEASE
AB Acute coronary syndromes are a leading cause of morbidity and mortality worldwide. The mechanisms underlying the triggering of these events are diverse and include increased coronary and systemic inflammatory activity dominant prothrombotic conditions, increased biomechanical stress on coronary arteries, variations in the coronary arterial tone, disturbed haemodynamic homoeostasis, and altered myocardial metabolic balance. There is experimental evidence that acute infections can promote the development of acute coronary syndromes, and clinical data strongly support a role for acute infections in triggering these events. In our Review, we summarise the pathogenesis of coronary artery disease and present the evidence linking acute infections with the development of acute coronary syndromes. Greater awareness of this association is likely to encourage research into ways of protecting patients who are at high risk.
C1 [Corrales-Medina, Vicente F.] Univ Ottawa, Dept Med, Div Infect Dis, Ottawa, ON K1N 6N5, Canada.
[Madjid, Mohammad; 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.
[Musher, Daniel M.] Baylor Coll Med, Infect Dis Sect, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Madjid, Mohammad] Univ Texas Hlth Sci Ctr Houston, Dept Med, Houston, TX USA.
[Madjid, Mohammad] St Lukes Episcopal Hosp, Texas Heart Inst, Atherosclerosis Res Lab, Houston, TX USA.
RP Musher, DM (reprint author), Baylor Coll Med, Infect Dis Sect, Michael E DeBakey Vet Affairs Med Ctr, Room 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM Daniel.Musher@va.gov
FU Department of Veterans Affairs; VFC-M
FX We thank Karla Absi-Delgado for her invaluable contribution to the
creation of the figures and the Medical Media Department of the Michael
E DeBakey VA Medical Center for assisting with their preparation. This
work was partly funded by the Department of Veterans Affairs through the
Merit Review Program for DMM. Funds from this source were used for
financial support of VFC-M in his role as Research Fellow at Baylor
College of Medicine under the direction of DMM.
NR 120
TC 88
Z9 95
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD FEB
PY 2010
VL 10
IS 2
BP 83
EP 92
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA 558DS
UT WOS:000274721600014
PM 20113977
ER
PT J
AU Je, YJ
Schutz, FAB
Choueiri, TK
AF Je, Youjin
Schutz, Fabio A. B.
Choueiri, Toni K.
TI Risk of bleeding not increased by sorafenib or sunitinib Reply
SO LANCET ONCOLOGY
LA English
DT Editorial Material
C1 [Je, Youjin] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Schutz, Fabio A. B.; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Je, YJ (reprint author), Harvard Univ, Sch Publ Hlth, Huntington Ave, Boston, MA 02215 USA.
EM toni_choueiri@dfci.harvard.edu
NR 1
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD FEB
PY 2010
VL 11
IS 2
BP 113
EP 113
PG 1
WC Oncology
SC Oncology
GA 563SC
UT WOS:000275152900011
ER
PT J
AU Goguen, LA
Norris, CM
Jaklitsch, MT
Sullivan, CA
Posner, MR
Haddad, RI
Tishler, RB
Burke, E
Annino, DJ
AF Goguen, Laura A.
Norris, Charles M.
Jaklitsch, Michael T.
Sullivan, Christopher A.
Posner, Marshall R.
Haddad, Robert I.
Tishler, Roy B.
Burke, Elaine
Annino, Donald J., Jr.
TI Combined Antegrade and Retrograde Esophageal Dilation for Head and Neck
Cancer-Related Complete Esophageal Stenosis
SO LARYNGOSCOPE
LA English
DT Article; Proceedings Paper
CT 112th Annual Meeting of the Triological-Society/Combined Otolaryngology
Spring Meeting
CY MAY 28-31, 2009
CL Phoenix, AZ
SP Triol Soc
DE Esophageal stenosis; pharyngo esophageal stenosis; dysphagia; head and
neck cancer; antegrade esophageal dilation; retrograde esophageal
dilation; CARD
ID SQUAMOUS-CELL CARCINOMA; ADVANCED LARYNGEAL-CANCER; LOCALLY ADVANCED
HEAD; QUALITY-OF-LIFE; RADIATION-THERAPY; CONCURRENT CHEMORADIATION;
ENDOSCOPIC MANAGEMENT; ORGAN PRESERVATION; CHEMOTHERAPY; DYSPHAGIA
AB Objectives/Hypothesis: Assess the safety and efficacy of combined antegrade and retrograde esophageal dilation (CARD) for complete esopbageal stenosis following head and neck cancer (HNC) treatment. Review HNC dysphagia management.
Study Design: Retrospective review of all patients undergoing CARD following HNC treatment between May 2001 and September 2008.
Methods: Forty-five patients were identified for review. Parameters assessed included: ability to obtain intraoperative esophageal patency, complications, number of dilations required, diet, and gastric tube (GT) status. Factors associated with dilation failure were analyzed.
Results: Intraoperative esophageal patency was obtained in 91% of patients. Median number of all dilations per patient was three. Median number of CARDs per patient was one. Resumption of oral intake occurred in 36/45 (80%). Diet results included: regular or soft diet 32/45 (71%), GT removal 27/45 (60%), and GT dependence with nothing by mouth 9/45 (20%). Laryngeal and pharyngeal stenosis, radionecrosis, tracheotomy dependence, and elongated stenosis were associated with dilation failure. Complications occurred in 18/63 (29%) CARD procedures: eight pneumomediastinum, seven GT site problems, two esophageal perforations, and one pharyngeal infection. All complications resolved spontaneously or with. minimal interventions.
Conclusions: CARD was safe and effective. Intraoperative patency was achieved in 91% of patients. Eighty percent resumed oral intake. The majority of patients had their GTs removed and resumed a soft or regular diet. Dilation failure was associated with laryngeal, pharyngeal, and excessively long esophageal stenosis, often resulting from radionecrosis. Complications were minor. CARD should be considered before relegating patients with complete esophageal stenosis to chronic GT dependence or subjecting them to laryngopharyngo esophagectomy.
C1 [Goguen, Laura A.; Norris, Charles M.; Sullivan, Christopher A.; Annino, Donald J., Jr.] Brigham & Womens Hosp, Div Otolaryngol, Dept Surg, Boston, MA 02115 USA.
[Jaklitsch, Michael T.] Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA.
[Posner, Marshall R.; Haddad, Robert I.] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA.
[Tishler, Roy B.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[Burke, Elaine] Brigham & Womens Hosp, Dept Rehabil Speech & Swallow Serv, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Goguen, LA (reprint author), Brigham & Womens Hosp, Div Otolaryngol, Dept Surg, 45 Francis St, Boston, MA 02115 USA.
EM lgoguen@partners.org
NR 43
TC 14
Z9 14
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD FEB
PY 2010
VL 120
IS 2
BP 261
EP 266
DI 10.1002/lary.20727
PG 6
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 556QA
UT WOS:000274605000009
PM 19998421
ER
PT J
AU Kumai, Y
Kobler, JB
Park, H
Galindo, M
Herrera, VLM
Zeitels, SM
AF Kumai, Yoshihiko
Kobler, James B.
Park, Hyoungshin
Galindo, Marilyn
Herrera, Victoria L. M.
Zeitels, Steven M.
TI Modulation of Vocal Fold Scar Fibroblasts By Adipose-Derived
Stem/Stromal Cells
SO LARYNGOSCOPE
LA English
DT Article; Proceedings Paper
CT 112th Annual Meeting of the Triological-Society/Combined Otolaryngology
Spring Meeting
CY MAY 28-31, 2009
CL Phoenix, AZ
SP Triol Soc
DE Adipose-derived stem cells; scar fibroblast; coculture; hepatocyte
growth factor; alpha-smooth muscle actin
ID HEPATOCYTE GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; STROMAL CELLS;
EXTRACELLULAR-MATRIX; EXPRESSION; INJECTION; ACTIVATION; PREVENTION;
MODEL
AB Objectives/Hypothesis: To explore whether adipose-derived stem/stromal cells (ASCs) have therapeutic potential for treating scarred superficial lamina propria through the effects of secreted hepatocyte growth factor (HGF) on scar fibroblasts.
Study Design: In vitro study using coculture system.
Methods: Scar fibroblasts (SFs) were isolated from ferret vocal folds electrocauterized 2 weeks previously. ASCs were isolated from ferret lipoaspirated subcutaneous abdominal fat. For coculture experiments, the two cell types were combined in Transwell plates for 6 days, followed by 1 or 3 days of monoculture after removing the upper chamber. Assays were then performed on cells and media from the bottom chamber. We measured: 1) the production of hyaluronic acid (RA), collagen and HGF via enzyme-linked immunosorbent assays, 2) the expression of alpha-smooth muscle actin (alpha-SMA), 3) cell proliferation, and 4) apoptosis of SFs (2, 3, and 4 via flow cytometry). Other experiments examined the effects of HGF on SFs and the effects of HGF neutralization in the coculture system.
Results: Coculture led to significant decreases in SF collagen production (P <.05), cell proliferation (P <.05), and a-SMA expression (P <.05), whereas HA production increased (P <.05). Coculture also increased HGF secretion from ASCs (P <.05). Neutralization of HGF abolished the inhibitory effects of ASCs on SF collagen synthesis (P <.05).
Conclusions: ASCs influence SFs to adopt a less fibrotic profile. It appears that HGF is at least one of the soluble factors responsible for this effect. Implanted ASCs could potentially ameliorate vocal fold scar by acting as long-term, intrinsic sources of HGF.
C1 [Kobler, James B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Surg, Ctr Laryngeal Surg & Voice Rehabil,Laryngeal Surg, Boston, MA 02114 USA.
[Herrera, Victoria L. M.] Boston Univ, Sch Med, Dept Med, Sect Mol Med, Boston, MA 02118 USA.
[Herrera, Victoria L. M.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
RP Kobler, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Surg, Ctr Laryngeal Surg & Voice Rehabil,Laryngeal Surg, 55 Fruit St,620 Their, Boston, MA 02114 USA.
EM jkobler@partners.org
NR 28
TC 22
Z9 24
U1 1
U2 10
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD FEB
PY 2010
VL 120
IS 2
BP 330
EP 337
DI 10.1002/lary.20753
PG 8
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 556QA
UT WOS:000274605000022
PM 20013848
ER
PT J
AU Jia, WC
Sun, V
Tran, N
Choi, B
Liu, SW
Mihm, MC
Phung, TL
Nelson, JS
AF Jia, Wangcun
Sun, Victor
Tran, Nadia
Choi, Bernard
Liu, Shaiw-wen
Mihm, Martin C., Jr.
Phung, Thuy L.
Nelson, J. Stuart
TI Long-Term Blood Vessel Removal With Combined Laser and Topical Rapamycin
Antiangiogenic Therapy: Implications for Effective Port Wine Stain
Treatment
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE laser dermatologic surgery; port wine stain; rapamycin; angiogenesis;
laser speckle imaging; dorsal window chamber
ID PULSED DYE-LASER; ENDOTHELIAL GROWTH-FACTOR; DORSAL SKIN FOLD; 577 NM
TREATMENT; MICROVASCULAR RESPONSE; FLOW DYNAMICS; IN-VITRO;
ANGIOGENESIS; SPECKLE; NEOVASCULARIZATION
AB Background and Objectives: Complete blanching of port wine stain (PWS) birthmarks after laser therapy is rarely achieved for most patients. We postulate that the low therapeutic efficacy or treatment failure is caused by regeneration and revascularization of photocoagulated blood vessels due to angiogenesis associated with the skin's normal wound healing response. Rapamycin (RPM), an antiangiogenic agent, has been demonstrated to inhibit growth of pathological blood vessels. Our objectives were to (1) investigate whether topical RPM can inhibit reperfusion of photocoagulated blood vessels in an animal model and (2) determine the effective RPM concentration required to achieve this objective.
Study Design/Materials and Methods: For both laser-only and combined laser and RPM treated animals, blood vessels in the dorsal window chambers implanted on golden Syrian banisters were photocoagulated with laser pulses. Structural and flow dynamics of blood vessels were documented with color digital photography and laser speckle imaging to evaluate photocoagulation and reperfusion. For the combined treatment group, topical RPM was applied to the epidermal side of the window daily for 14 days after laser exposure.
Results: In the laser-only group, 23 out of 24 photocoagulated blood vessels reperfused within 5-14 days. In the combined treatment group with different RPM formulae and concentrations, the overall reperfusion rate of 36% was much lower as compared to the laser-only group. We also found that the reperfusion rate was not linearly proportional to the RPM concentration.
Conclusions: With topical RPM application, the frequency of vessel reperfusion was considerably reduced, which implies that combined light and topical antiangiogenic therapy might be a promising approach to improve the treatment efficacy of PWS birthmarks. Lasers Surg. Med. 42:105-112, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Jia, Wangcun; Sun, Victor; Tran, Nadia; Choi, Bernard; Nelson, J. Stuart] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92617 USA.
[Choi, Bernard; Nelson, J. Stuart] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92617 USA.
[Choi, Bernard] Univ Calif Irvine, Edwards Lifesci Ctr Adv Cardiovasc Technol, Irvine, CA 92617 USA.
[Liu, Shaiw-wen] Conrex Pharmaceut, Newtown Sq, PA 19073 USA.
[Mihm, Martin C., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02215 USA.
[Phung, Thuy L.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
RP Jia, WC (reprint author), Univ Calif Irvine, Beckman Laser Inst, 1002 Hlth Sci Rd E, Irvine, CA 92617 USA.
EM wjia@uci.edu
RI Jia, Wangcun/A-9935-2011
FU National Institutes of Health [AR47551, EB002495, AR056147,
P41-RR001192]; American Society for Laser Medicine and Surgery; Sturge
Weber Foundation; Arnold and Mabel Beckman Foundation
FX Contract grant sponsor National Institutes of Health; Contract grant
numbers: AR47551, EB002495, AR056147; Contract grant sponsor National
Institutes of Health Laser Microbeam and Medical Program; Contract grant
number P41-RR001192; Contract grant sponsor: American Society for Laser
Medicine and Surgery; Contract grant sponsor: Sturge Weber Foundation;
Contract grant sponsor: Arnold and Mabel Beckman Foundation.
NR 42
TC 35
Z9 35
U1 1
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD FEB
PY 2010
VL 42
IS 2
SI SI
BP 105
EP 112
DI 10.1002/lsm.20890
PG 8
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 567LY
UT WOS:000275449600003
PM 20166161
ER
PT J
AU Haedersdal, M
Sakamoto, FH
Farinelli, WA
Doukas, AG
Tam, J
Anderson, RR
AF Haedersdal, Merete
Sakamoto, Fernanda H.
Farinelli, William A.
Doukas, Apostolos G.
Tam, Josh
Anderson, R. Rox
TI Fractional CO2 Laser-Assisted Drug Delivery
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE fractional ablative resurfacing; photodynamic therapy; photosensitizer;
topical drugs
ID TOPICAL PHOTODYNAMIC THERAPY; BASAL-CELL CARCINOMA; PROTOPORPHYRIN-IX
ACCUMULATION; ERBIUM-YAG LASER; 5-AMINOLEVULINIC ACID; IN-VIVO;
ENDOGENOUS PROTOPORPHYRIN; PERCUTANEOUS-ABSORPTION; AMINOLEVULINIC-ACID;
RESURFACING DEVICE
AB Background and Objectives: Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO2 laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug.
Materials and Methods: Two Yorkshire swine were treated with single-hole CO2 laser AFR and subsequent topical application of MAL (Metvix(R), Photocure ASA, Oslo, Not-way), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800 mu m. AFR was performed with a 10.6 mu m wavelength Prototype CO2 laser, using stacked single pulses of 3 millisecond and 91.6 mJ pet, pulse.
Results: AFR created cone-shaped channels of approximately 300 mu m diameter and 1,850 mu m depth that were Surrounded by a 70 mu m thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P < 0.0011) and dermis (P < 0.0433) versus MAL alone at skin depths of 120, 500, 1,000, 1,500, and 1,800 pro. AFR before MAL application also enhanced skin surface (epidermal) porphyrin fluorescence. Radial diffusion of MAL from the laser-created channels into surrounding dermis was evidenced by uniform porphyrin fluorescence up to 1,500 mu m from the holes (1,000, 1,800 mu m depths). Skin massage after MAL application did not affect MAL-induced porphyrin fluorescence after AFR.
Conclusions: Ablative fractional laser treatment facilitates delivery of topical MAL deeply into the skin. For the conditions of this study, laser channels approximately 3 mm apart followed by MAL application could produce porphyrins throughout essentially the entire skin. AFR appears to be a clinically practical means for enhancing uptake of MAL, a photodynamic therapy drug, and presumably many other topical skin medications. Lasers Surg. Med. 42:113-122, 2010. (C) 2009Wiley-Liss, Inc.
C1 [Haedersdal, Merete; Sakamoto, Fernanda H.; Farinelli, William A.; Doukas, Apostolos G.; Tam, Josh; Anderson, R. Rox] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Haedersdal, Merete] Univ Copenhagen, Dept Dermatol, Bispebjerg Hosp, DK-2400 Copenhagen, Denmark.
[Sakamoto, Fernanda H.] Univ Fed Sao Paulo, Dept Dermatol, Escola Paulista Med, BR-04023900 Sao Paulo, Brazil.
RP Haedersdal, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, BHX 630-55 Fruit St, Boston, MA 02114 USA.
EM mhaedersdal@dadlnet.dk
NR 37
TC 102
Z9 105
U1 0
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD FEB
PY 2010
VL 42
IS 2
SI SI
BP 113
EP 122
DI 10.1002/lsm.20860
PG 10
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 567LY
UT WOS:000275449600004
PM 20166154
ER
PT J
AU Yao, M
Yaroslavsky, A
Henry, FP
Redmond, RW
Kochevar, IE
AF Yao, Min
Yaroslavsky, Anna
Henry, Frank P.
Redmond, Robert W.
Kochevar, Irene E.
TI Phototoxicity Is Not Associated With Photochemical Tissue Bonding of
Skin
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE tissue bonding; wound repair; Rose Bengal; protein crosslinks; skin
incisions; wound healing; skin
ID ACID-PHOTODYNAMIC THERAPY; SINGLET OXYGEN; ROSE-BENGAL; CORNEAL
INCISIONS; KERATODESMOS; KINASE; GROWTH
AB Background and Objective: We have developed a light-activated method called photochemical tissue bonding (PTB) for closing wounds using green light and a photosensitizing dye (Rose Bengal-RB) to initiate photochemical crosslinking of wound surface proteins. These studies were designed to determine whether RB causes phototoxicity during closure of skin incisions with PTB.
Study Design/Materials and Methods: RB phototoxicity was evaluated after sealing incisions in porcine skin ex 2 vivo and rabbit skin in vivo using PTB (1 mM RB, 100 J/cm(2), 532 nm, 0.3 or 0.5 W/cm(2).) Dead cells were identified by pyknotic nuclei and eosinophilic cytoplasm on H&E-stained sections. The influence on RB phototoxicity of penetration of RB into the wound wall (by confocal microscopy), RB concentration in the tissue (by extraction), and fluence of 532 nm reaching depths in skin (calculated from skin optical properties) were investigated.
Results: No significant differences were found in the percent dead cells in PTB-treated and control incisions in porcine skin at 24 hours or in rabbit skin at 2 hours and 3 and 7 days after surgery. RB was retained in a similar to 100 mu m wide band next to the Wound wall. The mean RB concentration within this band was 0.42 +/- 0.03 mM. Monte Carlo modeling of light distribution indicated that the fluence rate decreased from the subsurface peak to 0.5 W/cm(2) in the mid-dermis (similar to 350 mu m.) In vitro RB phototoxicity to dermal fibroblasts yielded an LD(50) of 0.50 +/- 0.09 J/cm(2) when the cells contained 0.46 nM RB.
Conclusions: PTB does not cause phototoxicity when used to repair skin wounds even though the RB concentration and 532 nm fluence in the mid-dermis during PTB are much greater than the LD50 for RB phototoxicity in vitro. These results indicate that phototoxicity is not a concern when using PTB for tissue repair. Lasers Surg. Med. 42:123-131, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Yao, Min; Yaroslavsky, Anna; Henry, Frank P.; Redmond, Robert W.; Kochevar, Irene E.] Harvard Univ, Massachusetts Gen Hosp, Harvard MIT Hlth Sci Technol Program, Wellman Ctr Photomed,Sch Med, Boston, MA 02114 USA.
RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Harvard MIT Hlth Sci Technol Program, Wellman Ctr Photomed,Sch Med, Thier 224,50 Fruit St, Boston, MA 02114 USA.
EM kochevar@helix.mgh.harvard.edu
OI Henry, Francis P./0000-0003-4170-7806
FU DOD Medical Free Electron Laser Program [FA9550-04-1-0079]
FX Contract grant sponsor: DOD Medical Free Electron Laser Program;
Contract grant number: FA9550-04-1-0079.
NR 34
TC 32
Z9 37
U1 0
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD FEB
PY 2010
VL 42
IS 2
SI SI
BP 123
EP 131
DI 10.1002/lsm.20869
PG 9
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 567LY
UT WOS:000275449600005
PM 20166159
ER
PT J
AU Silverman, LB
Stevenson, KE
O'Brien, JE
Asselin, BL
Barr, RD
Clavell, L
Cole, PD
Kelly, KM
Laverdiere, C
Michon, B
Schorin, MA
Schwartz, CL
O'Holleran, EW
Neuberg, DS
Cohen, HJ
Sallan, SE
AF Silverman, L. B.
Stevenson, K. E.
O'Brien, J. E.
Asselin, B. L.
Barr, R. D.
Clavell, L.
Cole, P. D.
Kelly, K. M.
Laverdiere, C.
Michon, B.
Schorin, M. A.
Schwartz, C. L.
O'Holleran, E. W.
Neuberg, D. S.
Cohen, H. J.
Sallan, S. E.
TI Long-term results of Dana-Farber Cancer Institute ALL Consortium
protocols for children with newly diagnosed acute lymphoblastic leukemia
(1985-2000)
SO LEUKEMIA
LA English
DT Article
DE acute lymphoblastic leukemia; long-term follow-up; asparaginase;
anthracycline
ID INTENSIVE ASPARAGINASE; CUMULATIVE INCIDENCE; CHILDHOOD; GENE;
CHEMOTHERAPY; DEXRAZOXANE; NEOPLASMS; THERAPY; RISK; MLL
AB The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium has been conducting multi-institutional clinical trials in childhood ALL since 1981. The treatment backbone has included 20-30 consecutive weeks of asparaginase during intensification and frequent vincristine/corticosteroid pulses during the continuation phase. Between 1985 and 2000, 1457 children aged 0-18 years were treated on four consecutive protocols: 85-01 (1985-1987), 87-01 (1987-1991), 91-01 (1991-1955) and 95-01 (1996-2000). The 10-year event-free survival (EFS) +/- s. e. by protocol was 77.9 +/- 2.8% (85-01), 74.2 +/- 2.3% (87-01), 80.8 +/- 2.1% (91-01) and 80.5 +/- 1.8% (95-01). Approximately 82% of patients treated in the 1980s and 88% treated in the 1990s were long-term survivors. Both EFS and overall survival (OS) rates were significantly higher for patients treated in the 1990s compared with the 1980s (P = 0.05 and 0.01, respectively). On the two protocols conducted in the 1990s, EFS was 79-85% for T-cell ALL patients and 75-78% for adolescents (age 10-18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely affecting EFS or OS in high-risk (HR) patients, and frequently dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk (SR) patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities. Leukemia (2010) 24, 320-334; doi: 10.1038/leu.2009.253; published online 17 December 2009
C1 [Silverman, L. B.] Dana Farber Canc Inst, Div Hematol Oncol, Dept Pediat Oncol, Boston, MA 02115 USA.
[Silverman, L. B.; Stevenson, K. E.; O'Brien, J. E.; O'Holleran, E. W.; Neuberg, D. S.; Sallan, S. E.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
[Silverman, L. B.; Stevenson, K. E.; O'Brien, J. E.; O'Holleran, E. W.; Neuberg, D. S.; Sallan, S. E.] Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02115 USA.
[Silverman, L. B.; Sallan, S. E.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Asselin, B. L.] Univ Rochester, Med Ctr, Div Pediat Hematol Oncol, Rochester, NY 14642 USA.
[Barr, R. D.] McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada.
[Clavell, L.] San Jorge Childrens Hosp, Div Pediat Hematol Oncol, San Juan, PR USA.
[Cole, P. D.] Montefiore Med Ctr, Div Pediat Hematol Oncol, New York, NY USA.
[Kelly, K. M.] Columbia Univ, Morgan Stanley Childrens Hosp New York Presbyteri, Med Ctr, Div Pediat Oncol, New York, NY USA.
[Laverdiere, C.] Univ Montreal, Hop St Justine, Div Hematol & Oncol, Montreal, PQ H3T 1C5, Canada.
[Michon, B.] CHU Quebec, Div Hematol Oncol, Quebec City, PQ, Canada.
[Schorin, M. A.] Inova Fairfax Hosp, Falls Church, VA USA.
[Schwartz, C. L.] Brown Univ, Div Pediat Hematol Oncol, Hasbro Childrens Hosp, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Cohen, H. J.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
RP Silverman, LB (reprint author), Dana Farber Canc Inst, Div Hematol Oncol, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM lewis_silverman@dfci.harvard.edu
FU National Institute of Health (NCI) [5P01CA068484]
FX These trials were supported in part by a grant from the National
Institute of Health (NCI Grant 5P01CA068484). We thank the patients,
families, physicians, nurses, clinical research coordinators and all
others who participated in these trials. We acknowledge the important
contributions of Jennifer Cronin, Annette Dalton, Virginia Dalton,
Meghan Eaton and Richard D Gelber.
NR 31
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Z9 122
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD FEB
PY 2010
VL 24
IS 2
BP 320
EP 334
DI 10.1038/leu.2009.253
PG 15
WC Oncology; Hematology
SC Oncology; Hematology
GA 553WO
UT WOS:000274397700007
PM 20016537
ER
PT J
AU Chanudet, E
Huang, Y
Ichimura, K
Dong, G
Hamoudi, RA
Radford, J
Wotherspoon, AC
Isaacson, PG
Ferry, J
Du, MQ
AF Chanudet, E.
Huang, Y.
Ichimura, K.
Dong, G.
Hamoudi, R. A.
Radford, J.
Wotherspoon, A. C.
Isaacson, P. G.
Ferry, J.
Du, M-Q
TI A20 is targeted by promoter methylation, deletion and inactivating
mutation in MALT lymphoma
SO LEUKEMIA
LA English
DT Letter
ID B-CELL LYMPHOMA; NF-KAPPA-B; TNFAIP3 A20
C1 [Chanudet, E.; Huang, Y.; Ichimura, K.; Dong, G.; Hamoudi, R. A.; Du, M-Q] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Radford, J.] Christie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England.
[Radford, J.] Univ Manchester, Manchester, Lancs, England.
[Wotherspoon, A. C.] Royal Marsden Hosp, Dept Histopathol, London SW3 6JJ, England.
[Isaacson, P. G.] UCL, Dept Histopathol, London, England.
[Ferry, J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Chanudet, E (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England.
EM ec338@cam.ac.uk; mqd20@cam.ac.uk
RI Radford, John/N-1331-2015; Chanudet, Estelle/N-4064-2015
OI Radford, John/0000-0001-7898-2786;
NR 8
TC 60
Z9 69
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD FEB
PY 2010
VL 24
IS 2
BP 483
EP 487
DI 10.1038/leu.2009.234
PG 6
WC Oncology; Hematology
SC Oncology; Hematology
GA 553WO
UT WOS:000274397700026
PM 19907439
ER
PT J
AU Butt, AA
McGinnis, KA
Skanderson, M
Justice, AC
AF Butt, Adeel A.
McGinnis, Kathleen A.
Skanderson, Melissa
Justice, Amy C.
TI Hepatitis C treatment completion rates in routine clinical care
SO LIVER INTERNATIONAL
LA English
DT Article
DE anaemia; depression; hepatitis C; HIV infection; pegylated interferon;
practice variation; treatment completion
ID CHRONIC KIDNEY-DISEASE; INTERFERON-ALPHA-2B PLUS RIBAVIRIN;
IMMUNODEFICIENCY-VIRUS-INFECTION; UNITED-STATES VETERANS; COMBINATION
THERAPY; PEGINTERFERON ALPHA-2A; EPOETIN-ALPHA;
HEPATOCELLULAR-CARCINOMA; ANTIVIRAL THERAPY; HIV
AB Background
Treatment completion rates for hepatitis C virus (HCV) infection in clinical practice settings are unknown.
Methods
We assembled a national cohort of HCV-infected veterans-in-care from 1998 to 2003, using the VA National Patient Care Database for demographical/clinical information, Pharmacy Benefits Management database for pharmacy records and the Decision Support Systems database for laboratory data. We used logistic regression to determine the factors predicting treatment non-completion for HCV.
Results
We identified 134 934 HCV-infected veterans of whom 16 043 [11.9%; 95% confidence interval (CI) 11.7-12.1] were prescribed treatment for HCV. Among the 10 641 veterans with > 1 year of follow-up, 2396 (22.5%; 95% CI 21.7-23.3) completed a 48-week course. Non-completers were more likely to have pre-treatment anaemia, coronary artery disease, depression, substance abuse, used standard interferon, higher comorbidity count, and been treated at a low-volume treatment site (defined as sites initiating HCV treatment for < 200 individuals). In multivariable analyses, treatment completion was positively associated with pegylated interferon use [odds ratio (OR) 1.59, 95% CI 1.40-1.80] and site treatment volume (OR 1.87, 95% CI 1.56-2.24 for sites initiating treatment for > 200 individuals) and negatively associated with pre-treatment anaemia (OR 0.68, 95% CI 0.58-0.80 for haemoglobin 10-14 g/dl) and depression (OR 0.78, 95% CI 0.69-0.89). Human immunodeficiency virus coinfection and minority race were not associated with failing to complete treatment.
Conclusions
Among veterans-in-care with known HCV, 11.9% initiate therapy of whom 22.5% (one in 56 with known HCV infection) complete a 48-week course of treatment. Higher completion rates among higher volume treatment sites suggest that some factors associated with non-completion (pre-treatment depression and anaemia), may be modifiable with experience.
C1 [Butt, Adeel A.] Univ Pittsburgh, Med Ctr, Ctr Hlth Equ Res & Promot, Sch Med,VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA.
[Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Justice, Amy C.] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, New Haven, CT USA.
RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, Ctr Hlth Equ Res & Promot, Sch Med,VA Pittsburgh Healthcare Syst, 3601 5th Ave,Suite 3A, Pittsburgh, PA 15213 USA.
EM butta@dom.pitt.edu
FU National Institutes of Health/National Institute on Drug Abuse
[DA016175-01A1]; National Institutes of Health/National Institute on
Alcohol Abuse and Alcoholism [U10AA13566]; Valeant Pharmaceuticals
FX This study was funded by the National Institutes of Health/National
Institute on Drug Abuse (DA016175-01A1, Dr Butt). Dr Justice's time was
supported by National Institutes of Health/National Institute on Alcohol
Abuse and Alcoholism (U10AA13566). This material is the result of work
supported with resources and the use of facilities at the VA Pittsburgh
Healthcare System and the central data repositories maintained by the VA
Information Resource center, including the National Patient Care
Database, Decisions Support System database and the Pharmacy Benefits
Management database. Disclaimer/Conflict: The views expressed in this
article are those of the authors and do not necessarily reflect the
position or policy of the Department of Veterans Affairs. Dr Butt has
received grant funding from Valeant Pharmaceuticals.
NR 43
TC 32
Z9 32
U1 1
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1478-3223
J9 LIVER INT
JI Liver Int.
PD FEB
PY 2010
VL 30
IS 2
BP 240
EP 250
DI 10.1111/j.1478-3231.2009.02156.x
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 536DB
UT WOS:000273021300012
PM 19889081
ER
PT J
AU Sun, HY
Cacciarelli, TV
Singh, N
AF Sun, Hsin-Yun
Cacciarelli, Thomas V.
Singh, Nina
TI Impact of Pretransplant Infections on Clinical Outcomes of Liver
Transplant Recipients
SO LIVER TRANSPLANTATION
LA English
DT Article
ID SPONTANEOUS BACTERIAL PERITONITIS; HEPATITIS-C; PREEMPTIVE THERAPY;
CIRRHOSIS; CYTOMEGALOVIRUS; VALGANCICLOVIR; SUSCEPTIBILITY; RECURRENCE;
SEPSIS
AB Whether pretransplant nonviral infections influence outcomes after transplantation in liver transplant recipients in the current era is not well defined. One hundred consecutive patients undergoing liver transplantation in 2005-2008 were studied. Demographics, posttransplant clinical events, and mortality were compared between recipients with and without infections within 12 months before transplantation. In all, 32% of the patients (32/100) developed 45 episodes of pretransplant infections, which included spontaneous bacterial peritonitis (35.6%), bloodstream infections (28.9%), cellulitis (13.3%), pneumonia (8.9%), urinary tract infections (6.7%), and other infections (6.7%). Compared with 68 recipients without pretransplant infections, those with infections had a higher Model for End-Stage Liver Disease score and a lower likelihood of transplantation from home and required longer and more frequent hospital care before and after transplantation (P < 0.05). Mortality at 90 (9.4% versus 2.9%) and 180 days (15.6% versus 10.3%) post-transplant did not differ significantly between recipients with and without pretransplant infections (P = not significant). A higher Model for End-Stage Liver Disease score (P < 0.05) and posttransplant infections (P < 0.05 and P < 0.001), but not pretransplant infections, were associated with posttransplant mortality at 90 and 180 days. In conclusion, pretransplant infections that have been adequately treated do not pose a significant risk for poor outcomes, including posttransplant mortality. Liver Transpl 16:222-228, 2010. (C) 2010 AASLD.
C1 [Sun, Hsin-Yun; Cacciarelli, Thomas V.; Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan.
[Sun, Hsin-Yun] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan.
[Cacciarelli, Thomas V.; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA.
RP Singh, N (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA.
EM nis5@pitt.edu
OI SUN, HSIN-YUN/0000-0003-0074-7721
NR 22
TC 15
Z9 16
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1527-6465
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD FEB
PY 2010
VL 16
IS 2
BP 222
EP 228
DI 10.1002/lt.21982
PG 7
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA 554LZ
UT WOS:000274437800014
PM 20104499
ER
PT J
AU Bendlin, BB
Carlsson, CM
Gleason, CE
Johnson, SC
Sodhi, A
Gallagher, CL
Puglielli, L
Engelman, CD
Ries, ML
Xu, G
Wharton, W
Asthana, S
AF Bendlin, B. B.
Carlsson, C. M.
Gleason, C. E.
Johnson, S. C.
Sodhi, A.
Gallagher, C. L.
Puglielli, L.
Engelman, C. D.
Ries, M. L.
Xu, G.
Wharton, W.
Asthana, S.
TI Midlife predictors of Alzheimer's disease
SO MATURITAS
LA English
DT Review
DE Alzheimer's disease; Dementia; Midlife; Genes; Family history; Estrogen;
Vascular risk; Education; MRI
ID APOLIPOPROTEIN-E EPSILON-4; ESTROGEN REPLACEMENT THERAPY; RANDOMIZED
CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; HEALTH INITIATIVE MEMORY;
GENOME-WIDE ASSOCIATION; SYSTOLIC BLOOD-PRESSURE; WHITE-MATTER
INTEGRITY; FEMALE 3XTG-AD MICE; WOMENS HEALTH
AB Factors contributing to increased risk for Alzheimer's disease (AD) include age, sex, genes, and family history of AD. Several risk factors for AD are endogenous; however, accumulating evidence implicates modifiable risk factors in the pathogenesis of AD. Although the continued task of identifying new genes will be critical to learning more about the disease, several research findings suggest that potentially alterable environmental factors influence genetic contributions, providing targets for disease prevention and treatment. Here, we review midlife risk factors for AD, and address the potential for therapeutic intervention in midlife. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Bendlin, B. B.; Carlsson, C. M.; Gleason, C. E.; Johnson, S. C.; Sodhi, A.; Gallagher, C. L.; Puglielli, L.; Ries, M. L.; Xu, G.; Wharton, W.; Asthana, S.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA.
[Bendlin, B. B.; Carlsson, C. M.; Gleason, C. E.; Johnson, S. C.; Sodhi, A.; Gallagher, C. L.; Puglielli, L.; Ries, M. L.; Xu, G.; Wharton, W.; Asthana, S.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA.
[Engelman, C. D.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA.
RP Bendlin, BB (reprint author), Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA.
EM bbb@medicine.wisc.edu
OI Bendlin, Barbara/0000-0002-0580-9875
FU University of Wisconsin, Madison
FX Completion of this work was supported by the help of the Section of
Geriatrics and Gerontology, Department of Medicine at the University of
Wisconsin, Madison, and the Geriatric Research, Education and Clinical
Center (GRECC manuscript number 2009-16), William S. Middleton Memorial
Veterans Hospital.
NR 132
TC 16
Z9 18
U1 4
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-5122
J9 MATURITAS
JI Maturitas
PD FEB
PY 2010
VL 65
IS 2
SI SI
BP 131
EP 137
DI 10.1016/j.maturitas.2009.12.014
PG 7
WC Geriatrics & Gerontology; Obstetrics & Gynecology
SC Geriatrics & Gerontology; Obstetrics & Gynecology
GA 560ZO
UT WOS:000274944600009
PM 20044221
ER
PT J
AU Fonseca, R
Richardson, P
Giralt, S
Lonial, S
Rajkumar, SV
Stewart, AK
Bensinger, W
Somlo, G
Vescio, R
Mikhael, J
Reeder, C
Tiedemann, R
Tricot, G
Rifkin, R
Shaughnessy, J
Munshi, N
Raje, N
Ghobrial, I
Laubach, J
Schlossman, R
Treon, S
Mahindra, A
Avigan, D
Rosenblatt, J
Jagannath, S
Niesvizky, R
Landau, H
Chen-Kiang, S
Siegel, DS
Zimmerman, T
Mehta, J
Vesole, D
Rosen, S
Hofmeister, C
Lacy, M
Dispenziere, A
Borrello, I
Hayman, SR
Kumar, S
Buadi, F
Dingli, D
Russell, S
Alsina, M
Fernandez, H
Roy, V
Pereira, D
Stadtmauer, E
Vaj, R
Jakubowiak, A
Lentzsch, S
Song, K
Bahlis, N
Trudel, S
Chen, C
Reece, D
Stewart, D
Singhal, S
Comenzo, R
Gertz, MA
Greipp, PR
Durie, B
Barlogie, B
Anderson, K
Dalton, W
Coleman, M
Novis, S
Kyle, RA
AF Fonseca, Rafael
Richardson, Paul
Giralt, Sergio
Lonial, Sagar
Rajkumar, S. Vincent
Stewart, A. Keith
Bensinger, William
Somlo, George
Vescio, Robert
Mikhael, Joseph
Reeder, Craig
Tiedemann, Rodger
Tricot, Guido
Rifkin, Robert
Shaughnessy, John
Munshi, Nikhil
Raje, Noopur
Ghobrial, Irene
Laubach, Jacob
Schlossman, Robert
Treon, Steven
Mahindra, Anuj
Avigan, David
Rosenblatt, Jacalyn
Jagannath, Sundar
Niesvizky, Ruben
Landau, Heather
Chen-Kiang, Selina
Siegel, David S.
Zimmerman, Todd
Mehta, Jayesh
Vesole, David
Rosen, Steven
Hofmeister, Craig
Lacy, Martha
Dispenziere, Angela
Borrello, Ivan
Hayman, Suzanne R.
Kumar, Shaji
Buadi, Frances
Dingli, David
Russell, Stephen
Alsina, Melissa
Fernandez, Hugo
Roy, Vivek
Pereira, Denise
Stadtmauer, Edward
Vaj, Ravi
Jakubowiak, Andrezej
Lentzsch, Suzanne
Song, Kevin
Bahlis, Nizar
Trudel, Suzanne
Chen, Christine
Reece, Donna
Stewart, Douglas
Singhal, Seema
Comenzo, Raymond
Gertz, Morie A.
Greipp, Philip R.
Durie, Brian
Barlogie, Bart
Anderson, Kenneth
Dalton, William
Coleman, Morton
Novis, Susie
Kyle, Robert A.
TI Conflicts of Interest, Authorship, and Disclosures in Industry-Related
Scientific Publications
SO MAYO CLINIC PROCEEDINGS
LA English
DT Letter
ID LENALIDOMIDE PLUS DEXAMETHASONE; REFRACTORY MULTIPLE-MYELOMA; IMPROVED
SURVIVAL; MEDICAL JOURNALS; BORTEZOMIB
C1 [Fonseca, Rafael; Stewart, A. Keith; Mikhael, Joseph; Reeder, Craig; Tiedemann, Rodger] Mayo Clin, Scottsdale, AZ USA.
[Richardson, Paul; Munshi, Nikhil; Ghobrial, Irene; Laubach, Jacob; Schlossman, Robert; Treon, Steven; Avigan, David; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA USA.
[Giralt, Sergio] MD Anderson Canc Ctr, Houston, TX USA.
[Lonial, Sagar] Emory Univ, Winship Canc Ctr, Atlanta, GA USA.
[Rajkumar, S. Vincent; Lacy, Martha; Dispenziere, Angela; Hayman, Suzanne R.; Kumar, Shaji; Buadi, Frances; Dingli, David; Russell, Stephen; Roy, Vivek; Gertz, Morie A.; Greipp, Philip R.; Kyle, Robert A.] Mayo Clin, Rochester, MN USA.
[Bensinger, William] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Somlo, George] City Hope Natl Med Ctr, Duarte, CA USA.
[Vescio, Robert; Durie, Brian] Cedars Sinai Med Ctr, Los Angeles, CA USA.
[Tricot, Guido] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Rifkin, Robert] Rocky Mt Canc Ctr, Denver, CO USA.
[Shaughnessy, John; Barlogie, Bart] Univ Arkansas, Little Rock, AR USA.
[Raje, Noopur] Massachusetts Gen Hosp, Boston, MA USA.
[Mahindra, Anuj] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA.
[Rosenblatt, Jacalyn] Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Jagannath, Sundar] St Vincent Comprehens Canc Ctr, New York, NY USA.
[Niesvizky, Ruben; Chen-Kiang, Selina; Coleman, Morton] Cornell Univ, Weill Cornell Med Coll, New York, NY USA.
[Landau, Heather; Comenzo, Raymond] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Siegel, David S.] Hackensack Univ Med Ctr, Canc Ctr, Hackensack, NJ USA.
[Zimmerman, Todd] Univ Chicago, Chicago, IL USA.
[Mehta, Jayesh; Rosen, Steven; Singhal, Seema] Northwestern Mem Hosp, Chicago, IL USA.
[Vesole, David] Loyola Univ, Med Ctr, Maywood, IL USA.
[Hofmeister, Craig] Ohio State Univ, Columbus, OH USA.
[Borrello, Ivan] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Alsina, Melissa; Fernandez, Hugo; Dalton, William] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Pereira, Denise] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA.
[Stadtmauer, Edward] Univ Penn, Abramson Canc Ctr, Philadelphia, PA USA.
[Vaj, Ravi] Washington Univ, St Louis, MO USA.
[Jakubowiak, Andrezej] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI USA.
[Lentzsch, Suzanne] Univ Pittsburgh, Canc Inst, Pittsburgh, PA USA.
[Song, Kevin] British Columbia Canc Agcy, Vancouver, BC, Canada.
[Bahlis, Nizar; Stewart, Douglas] Univ Calgary, Calgary, AB, Canada.
[Trudel, Suzanne; Chen, Christine; Reece, Donna] Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada.
RP Fonseca, R (reprint author), Mayo Clin, Scottsdale, AZ USA.
RI Hofmeister, Craig/E-3256-2011; Kumar, Shaji/A-9853-2008;
OI Hofmeister, Craig/0000-0003-4816-1607; Kumar, Shaji/0000-0001-5392-9284;
Fonseca, Rafael/0000-0002-5938-3769; Rajkumar, S.
Vincent/0000-0002-5862-1833; Dispenzieri, Angela/0000-0001-8780-9512
FU NCI NIH HHS [P30 CA016672]
NR 12
TC 2
Z9 2
U1 0
U2 0
PU MAYO CLINIC PROCEEDINGS
PI ROCHESTER
PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA
SN 0025-6196
J9 MAYO CLIN PROC
JI Mayo Clin. Proc.
PD FEB
PY 2010
VL 85
IS 2
BP 197
EP 199
DI 10.4065/mcp.2009.0559
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 556QW
UT WOS:000274607200017
PM 20118399
ER
PT J
AU Bianchi, MT
AF Bianchi, Matt T.
TI Promiscuous modulation of ion channels by anti-psychotic and
anti-dementia medications
SO MEDICAL HYPOTHESES
LA English
DT Article
ID METHYL-D-ASPARTATE; NICOTINIC ACETYLCHOLINE-RECEPTOR;
ALZHEIMERS-DISEASE; SODIUM-CHANNELS; K+ CHANNEL; DIFFERENTIAL
INHIBITION; ATYPICAL ANTIPSYCHOTICS; NONCOMPETITIVE MANNER;
HIPPOCAMPAL-NEURONS; POTASSIUM CHANNELS
AB There is growing interest in the concept of network pharmacology, as opposed to specific pharmacological targets, as an important drug discovery paradigm. Also known as the "magic shotgun" paradigm, this strategy involves individual drugs interacting with multiple targets to achieve clinical benefit. Pharmacological promiscuity consistent with this paradigm has been suggested in vitro for antidepressants and anticonvulsants, which interact with many classes of ion channels (among other receptor targets). Although the link between certain "off-target" interactions and drug side effects is well-accepted, the potential linkage between promiscuity and clinical efficacy remains poorly understood. Here we summarize interactions of clinically useful anti-psychotic and anti-dementia medications with a diverse array of ligand- and voltage-gated ion channels. We hypothesize that promiscuous ion channel modulation may contribute to the efficacy of drugs used to treat psychosis and dementia. (C) 2009 Elsevier Ltd. All rights reserved.
C1 Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA.
RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Wang Ambulatory Ctr 7th Floor, Boston, MA 02114 USA.
EM thebianchi@gmail.com
NR 80
TC 10
Z9 11
U1 1
U2 2
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
J9 MED HYPOTHESES
JI Med. Hypotheses
PD FEB
PY 2010
VL 74
IS 2
BP 297
EP 300
DI 10.1016/j.mehy.2009.09.003
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 556CH
UT WOS:000274564700028
PM 19786325
ER
PT J
AU Malcolm, JG
Michailovich, O
Bouix, S
Westin, CF
Shenton, ME
Rathi, Y
AF Malcolm, James G.
Michailovich, Oleg
Bouix, Sylvain
Westin, Carl-Fredrik
Shenton, Martha E.
Rathi, Yogesh
TI A filtered approach to neural tractography using the Watson directional
function
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Diffusion-weighted MRI; Tractography; Kalman filtering; Watson
directional function
ID MULTIPLE FIBER ORIENTATIONS; DIFFUSION-WEIGHTED MRI; SPHERICAL
DECONVOLUTION; TENSOR MRI; RESOLUTION; TRACKING; DISTRIBUTIONS; MODEL;
RECONSTRUCTION; DECOMPOSITION
AB We propose a technique to simultaneously estimate the local fiber orientations and perform multi-fiber tractography. Existing techniques estimate the local fiber orientation at each voxel independently so there is no running knowledge of confidence in the measured signal or estimated fiber orientation. Further, to overcome noise, many algorithms use a filter as a post-processing step to obtain a smooth trajectory. We formulate fiber tracking as causal estimation: at each step of tracing the fiber, the current estimate of the signal is guided by the previous. To do this, we model the signal as a discrete mixture of Watson directional functions and perform tractography within a filtering framework. Starting from a seed point, each fiber is traced to its termination using an unscented Kalman filter to simultaneously fit the signal and propagate in the most consistent direction. Despite the presence of noise and uncertainty, this provides an accurate estimate of the local structure at each point along the fiber. We choose the Watson function since it provides a compact representation of the signal parameterized by the principal diffusion direction and a scaling parameter describing anisotropy, and also allows analytic reconstruction of the oriented diffusion function from those parameters. Using a mixture of two and three components (corresponding to two-fiber and three-fiber models) we demonstrate in synthetic experiments that this approach reduces signal reconstruction error and significantly improves the angular resolution at crossings and branchings. In vivo experiments examine the corpus callosum and internal capsule and confirm the ability to trace through regions known to contain such crossing and branching while providing inherent path regularization. (C) 2009 Elsevier B. V. All rights reserved.
C1 [Malcolm, James G.; Bouix, Sylvain; Shenton, Martha E.; Rathi, Yogesh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA 02215 USA.
[Michailovich, Oleg] Univ Waterloo, Dept Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada.
[Westin, Carl-Fredrik] Harvard Univ, Sch Med, Dept Radiol, Lab Math Imaging, Boston, MA 02215 USA.
[Shenton, Martha E.] VA Boston Healthcare Syst, Brockton Div, Brockton, MA USA.
RP Malcolm, JG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA 02215 USA.
EM malcolm@bwh.harvard.edu
OI Bouix, Sylvain/0000-0003-1326-6054
FU Department of Veteran Affairs Merit Award; VA Schizophrenia Center; NIH
[P41 RR13218, K05 MH 070047, 1P50MH080272-01, R01 MH 50740, R01 MH
082918, P50 MH080272-01, R01 MH50740-15, R03 TW008134-01]; Center for
Integration of Medicine and Innovative Technology Soldier in Medicine
Award
FX This work was supported in part by a Department of Veteran Affairs Merit
Award (Shenton, R McCarley), the VA Schizophrenia Center Grant
(McCarley, Shenton) and NIH Grants: P41 RR13218 (Shenton), K05 MH 070047
(Shenton), 1P50MH080272-01 (Shenton), R01 MH 50740 (Shenton), R01 MH
082918 (Bouix), P50 MH080272-01 (McCarley), R01 MH50740-15 (Shenton),
R03 TW008134-01 (Shenton), and the Center for Integration of Medicine
and Innovative Technology Soldier in Medicine Award (Bouix).
NR 55
TC 20
Z9 21
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1361-8415
EI 1361-8423
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD FEB
PY 2010
VL 14
IS 1
BP 58
EP 69
DI 10.1016/j.media.2009.10.003
PG 12
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Engineering, Biomedical; Radiology,
Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
Imaging
GA 528QB
UT WOS:000272460400007
PM 19914856
ER
PT J
AU Hooker, RS
AF Hooker, Roderick S.
TI The future of the physician assistant movement
SO MEDICAL JOURNAL OF AUSTRALIA
LA English
DT Editorial Material
ID BRAIN-DRAIN
C1 [Hooker, Roderick S.] Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Ft Worth, TX USA.
[Hooker, Roderick S.] US Dept Vet Affairs, Vet Hlth Adm, Dallas, TX USA.
RP Hooker, RS (reprint author), Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Ft Worth, TX USA.
EM roderick.hooker@va.gov
NR 6
TC 3
Z9 3
U1 0
U2 0
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 FEB 1
PY 2010
VL 192
IS 3
BP 116
EP 116
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 563RF
UT WOS:000275150400001
PM 20121674
ER
PT J
AU Craft, D
Monz, M
AF Craft, David
Monz, Michael
TI Simultaneous navigation of multiple Pareto surfaces, with an application
to multicriteria IMRT planning with multiple beam angle configurations
SO MEDICAL PHYSICS
LA English
DT Article
DE dosimetry; optimisation; radiation therapy
ID FLUENCE MAP OPTIMIZATION
AB Methods: The authors assume a convex optimization setting and represent the Pareto surface for each modality or given beam set by a set of discrete points on the surface. Weighted averages of these discrete points produce a continuous representation of each Pareto surface. The authors calculate a set of Pareto surfaces and use linear programming to navigate across the individual surfaces, allowing switches between surfaces. The switches are organized such that the plan profits in the requested way, while trying to keep the change in dose as small as possible.
Results: The system is demonstrated on a phantom pancreas IMRT case using 100 different five beam configurations and a multicriteria formulation with six objectives. The system has intuitive behavior and is easy to control. Also, because the underlying linear programs are small, the system is fast enough to offer real-time exploration for the Pareto surfaces of the given beam configurations.
Conclusions: The system presented offers a sound starting point for building clinical systems for multicriteria exploration of different modalities and offers a controllable way to explore hundreds of beam angle configurations in IMRT planning, allowing the users to focus their attention on the dose distribution and treatment planning objectives instead of spending excessive time on the technicalities of delivery.
C1 [Craft, David] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Monz, Michael] Fraunhofer Inst Ind Math, Dept Optimizat, D-67663 Kaiserslautern, Germany.
RP Craft, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM dcraft@partners.org
FU NCI [1 R01 CA103904-01 Al]
FX This work was sponsored by NCI Grant No. 1 R01 CA103904-01 Al:
Multicriteria IMRT Optimization and by RaySearch Laboratories.
NR 13
TC 15
Z9 15
U1 0
U2 2
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD FEB
PY 2010
VL 37
IS 2
BP 736
EP 741
DI 10.1118/1.3292636
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 549SW
UT WOS:000274075600035
PM 20229883
ER
PT J
AU McHenry, CR
Phitayakorn, R
AF McHenry, C. R.
Phitayakorn, R.
TI Difficult problems in thyroid cancer surgery
SO MINERVA CHIRURGICA
LA English
DT Review
DE Thyroid neoplasms; Lymph node excision; Tracheal diseases; Esophageal
diseases
ID RECURRENT-LARYNGEAL NERVE; POSTOPERATIVE THYROGLOBULIN LEVELS;
SUFFICIENT SURGICAL-TREATMENT; UNILATERAL TOTAL LOBECTOMY; HURTHLE
CELL-CARCINOMA; PAPILLARY CARCINOMA; TRACHEAL RESECTION; UNITED-STATES;
PREOPERATIVE ULTRASONOGRAPHY; ESOPHAGEAL INVOLVEMENT
AB vThe incidence of thyroid cancer has increased dramatically, yet the mortality has remained unchanged. There remain many challenges and "difficult problems" in diagnosing and treating patients with differentiated thyroid cancer (DTC). A significant percentage of patients with DTC will present with a thyroid nodule and an indeterminate fine needle aspiration biopsy underscoring the importance of proper evaluation and management. It is important when considering the extent of thyroidectomy and the management of lymph node metastases to balance the outcome of treatment-in terms of recurrence and mortality with the morbidity of the procedure. Total thyroidectomy and lymphadenectomy for macroscopic lymph node metastases appear to be the optimal therapy for most patients with DTC. Preservation of function is a priority in managing patients with DTC invading the recurrent laryngeal nerve, trachea, esophagus, or the larynx.
C1 [McHenry, C. R.] Case Western Reserve Univ, Dept Surg, Metrohlth Med Ctr, Sch Med, Cleveland, OH 44109 USA.
[Phitayakorn, R.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Gastrointestinal & End, Boston, MA 02115 USA.
RP McHenry, CR (reprint author), Case Western Reserve Univ, Dept Surg, Metrohlth Med Ctr, Sch Med, 2500 Metrohlth Dr, Cleveland, OH 44109 USA.
EM cmchenry@metrohealth.org
OI Phitayakorn, Roy/0000-0002-8327-1484
NR 74
TC 1
Z9 1
U1 0
U2 1
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0026-4733
J9 MINERVA CHIR
JI Minerva Chir.
PD FEB
PY 2010
VL 65
IS 1
BP 83
EP 93
PG 11
WC Surgery
SC Surgery
GA 586FH
UT WOS:000276887900010
PM 20212420
ER
PT J
AU Antonescu, CR
Zhang, L
Chang, NE
Pawel, BR
Travis, W
Rosenberg, AE
Nielsen, GP
Dal Cin, P
Fletcher, CD
AF Antonescu, C. R.
Zhang, L.
Chang, N. E.
Pawel, B. R.
Travis, W.
Rosenberg, A. E.
Nielsen, G. P.
Dal Cin, P.
Fletcher, C. D.
TI Novel EWSR1-POU5F1 Fusion in Soft Tissue Myoepithelial Tumors. A
Molecular Analysis of 29 Cases, Including Soft Tissue, Bone and Visceral
Locations Showing Common Involvement of EWSR1 Gene Rearrangement
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
RI Pawel, Bruce/G-5466-2011
NR 0
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 49
BP 14A
EP 15A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500050
ER
PT J
AU Bridge, JA
Streblow, R
Frayer, RW
Dal Cin, P
Rosenberg, A
Meloni-Ehrig, A
Sumegi, J
AF Bridge, J. A.
Streblow, R.
Frayer, R. W.
Dal Cin, P.
Rosenberg, A.
Meloni-Ehrig, A.
Sumegi, J.
TI Recurrent (2;2) and (2;8) Translocations in Rhabdomyosarcoma without the
Canonical PAX-FOXO1 Fuse PAX3 to Members of the Nuclear Receptor
Transcriptional Coactivator (NCOA) Family
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Univ Nebraska, Med Ctr, Omaha, NE USA.
Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
Harvard Univ, Sch Med, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Quest Diagnost Nichols Inst, Chantilly, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 55
BP 16A
EP 16A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500056
ER
PT J
AU Demicco, EG
Rosenberg, AE
Antonescu, CR
Kobler, JB
Nielsen, GP
AF Demicco, E. G.
Rosenberg, A. E.
Antonescu, C. R.
Kobler, J. B.
Nielsen, G. P.
TI Benign Notochordal Cell Proliferations in the Ferret: An Animal with a
High Incidence of Chordoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 69
BP 19A
EP 19A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500070
ER
PT J
AU Lee, AF
Hayes, MM
Rosenberg, AE
Nielsen, TO
Lee, CH
AF Lee, A. F.
Hayes, M. M.
Rosenberg, A. E.
Nielsen, T. O.
Lee, C. H.
TI FLI-1 Distinguishes Ewing Sarcoma from Small Cell Osteosarcoma and
Mesenchymal Chondrosarcoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Vancouver Gen Hosp, Vancouver, BC, Canada.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 87
BP 22A
EP 22A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500088
ER
PT J
AU Lee, CH
Liebsch, NJ
Nielsen, GP
Ganguly, A
Rosenberg, AE
AF Lee, C. H.
Liebsch, N. J.
Nielsen, G. P.
Ganguly, A.
Rosenberg, A. E.
TI Morphologic and Immunohistochemical Characterization of a Series of
Clinically Atypical Skull Base Chordomas in the Paediatric Population
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Vancouver Gen Hosp, Vancouver, BC, Canada.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 89
BP 23A
EP 23A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500090
ER
PT J
AU Romeo, S
Duim, RAJ
Bridge, JA
Mertens, F
De Jong, D
Dal Cin, P
Wijers-Koster, PM
Debiec-Rychter, M
Sciot, R
Rosenberg, A
Szuhai, K
Hogendoorn, PCW
AF Romeo, S.
Duim, R. A. J.
Bridge, J. A.
Mertens, F.
De Jong, D.
Dal Cin, P.
Wijers-Koster, P. M.
Debiec-Rychter, M.
Sciot, R.
Rosenberg, A.
Szuhai, K.
Hogendoorn, P. C. W.
TI Heterogeneous and Complex Rearragements of the Long Arm of Chromosome 6
in Chondromyxoid Fibroma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Treviso Re Hosp, Treviso, Italy.
Leiden Univ, Med Ctr, Leiden, Netherlands.
Univ Nebraska Med Ctr, Omaha, NE USA.
Univ Lund Hosp, S-22185 Lund, Sweden.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Catholic Univ Louvain, B-3000 Louvain, Belgium.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Szuhai, Karoly/A-1100-2008
OI Szuhai, Karoly/0000-0002-1228-4245
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 107
BP 27A
EP 27A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500108
ER
PT J
AU Imielinski, M
Cha, S
Richardson, EA
Thakur, D
Rejtar, T
Wu, SL
Karger, B
Sgroi, D
AF Imielinski, M.
Cha, S.
Richardson, E. A.
Thakur, D.
Rejtar, T.
Wu, S-L
Karger, B.
Sgroi, D.
TI Combined Proteomic-Transcriptomic Profiling of Laser Capture
Microdissected Normal and Breast Cancer Epithelium Reveals Systematic
Biochemical Network Alterations
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Northeastern Univ, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 225
BP 52A
EP 53A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500225
ER
PT J
AU Johnson, MM
Dialani, V
Johnson, NB
AF Johnson, M. M.
Dialani, V.
Johnson, N. B.
TI Histologic Characteristics of Benign Breast Lesions Identified for
Biopsy by Magnetic Resonance Imaging
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 231
BP 54A
EP 54A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500231
ER
PT J
AU Kaplan, J
Schnitt, S
Collins, L
Wang, Y
Garber, J
Montgomery, K
West, R
Tung, N
AF Kaplan, J.
Schnitt, S.
Collins, L.
Wang, Y.
Garber, J.
Montgomery, K.
West, R.
Tung, N.
TI Histologic and Immunophenotypic Comparison of Estrogen Receptor
(ER)-Positive Breast Cancers in BRCA1 Mutation Carriers and Sporadic
ER-Positive Breast Cancers: A Case-Control Study
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Stanford Univ, Palo Alto, CA 94304 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 235
BP 55A
EP 55A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500235
ER
PT J
AU Marotti, JD
Collins, LC
Gelber, S
Ruddy, K
Kereakoglow, S
Brachtel, EF
Winer, E
Partridge, A
AF Marotti, J. D.
Collins, L. C.
Gelber, S.
Ruddy, K.
Kereakoglow, S.
Brachtel, E. F.
Winer, E.
Partridge, A.
TI Pathologic Features and Distribution of Molecular Phenotype among Young
Women with Breast Cancer: Results from the Young Women's Breast Cancer
Study
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 266
BP 62A
EP 62A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500266
ER
PT J
AU Stone, JR
Khosroshahi, A
Deshpande, V
Stone, JH
AF Stone, J. R.
Khosroshahi, A.
Deshpande, V.
Stone, J. H.
TI Thoracic Lymphoplasmacytic Aortitis Is Often Associated with
IgG4-Related Systemic Disease
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
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 NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 370
BP 84A
EP 84A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500370
ER
PT J
AU Wang, H
Smith, RN
Stone, JR
AF Wang, H.
Smith, R. N.
Stone, J. R.
TI Ascending Giant Cell Aortitis without Systemic Symptoms Is Associated
with an Increased Frequency of Subsequent Distal Aortic Events
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 375
BP 85A
EP 85A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500375
ER
PT J
AU Chebib, I
Yeager, K
Mino-Kenudsen, M
Brugge, W
Pitman, MB
AF Chebib, I.
Yeager, K.
Mino-Kenudsen, M.
Brugge, W.
Pitman, M. B.
TI The Role of Cytopathology in the Diagnosis and Management of Pancreatic
Cysts Greater Than 3 cm
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 [Chebib, I.; Yeager, K.; Mino-Kenudsen, M.; Brugge, W.; Pitman, M. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 394
BP 90A
EP 90A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500394
ER
PT J
AU Moatamed, NA
Apple, SK
Moatamed, F
AF Moatamed, N. A.
Apple, S. K.
Moatamed, F.
TI Inclusion of the Uniform Tetraploid Cells Reduces the Specificity of the
Urine FISH Assay
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
VA Greater Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 447
BP 102A
EP 102A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500447
ER
PT J
AU Baran, JL
Laga, AC
Duncan, LM
Murphy, GF
AF Baran, J. L.
Laga, A. C.
Duncan, L. M.
Murphy, G. F.
TI The Embryonic Stem Cell Transcription Factor SOX2 Is Expressed by Spitz
Nevi
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 489
BP 111A
EP 111A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500489
ER
PT J
AU Baran, JL
Scott, K
Muzikansky, A
Chin, L
Duncan, LM
AF Baran, J. L.
Scott, K.
Muzikansky, A.
Chin, L.
Duncan, L. M.
TI MITF Expression in Cutaneous Melanoma and Spitz Nevi: A Genomic and
Immunohistochemical Study
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 490
BP 111A
EP 111A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500490
ER
PT J
AU Sepehr, A
Chao, E
Mihm, MC
Tsao, H
AF Sepehr, A.
Chao, E.
Mihm, M. C., Jr.
Tsao, H.
TI Comparative Analysis of Spitz Tumors: A Clinicopathologic Follow-Up of
163 Cases
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
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 NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 536
BP 121A
EP 121A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500536
ER
PT J
AU Ryan, R
Brodsky, V
Louissaint, A
Gilbertson, J
Yagi, Y
AF Ryan, R.
Brodsky, V.
Louissaint, A.
Gilbertson, J.
Yagi, Y.
TI Usage and Participation in a Resident-Built Virtual Slide-Based Atlas of
Anatomic Pathology
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Weill Cornell Med Coll, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 552
BP 125A
EP 125A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500552
ER
PT J
AU Kolman, OK
Sadow, PM
Hunt, JL
AF Kolman, O. K.
Sadow, P. M.
Hunt, J. L.
TI Sampling, Assessment, and Reporting of Thyroid Follicular Lesions:
Survey of 165 Pathologists
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
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 NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 567
BP 128A
EP 129A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500567
ER
PT J
AU Agoston, AT
Lauwers, GY
Odze, RD
AF Agoston, A. T.
Lauwers, G. Y.
Odze, R. D.
TI Evidence That Dysplasia Begins in the Bases of the Pits in the
Pathogenesis of Gastric Cancer
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 593
BP 134A
EP 134A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500593
ER
PT J
AU Coco, D
Goldblum, J
Hornick, J
Lauwers, GY
Montgomery, E
Srivastava, A
Wang, H
Odze, RD
AF Coco, D.
Goldblum, J.
Hornick, J.
Lauwers, G. Y.
Montgomery, E.
Srivastava, A.
Wang, H.
Odze, R. D.
TI Interobserver Variability in the Diagnosis of Crypt Dysplasia in
Barrett's Esophagus
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Cleveland Clin, Cleveland, OH 44106 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
Dartmouth Med Ctr, Lebanon, NH USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 621
BP 140A
EP 140A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500621
ER
PT J
AU Courville, EL
Srivastava, A
Hong, TS
Yilmaz, OH
Calvo, LN
Zaki, BI
Mino-Kenudson, M
AF Courville, E. L.
Srivastava, A.
Hong, T. S.
Yilmaz, O. H.
Calvo, L. N.
Zaki, B. I.
Mino-Kenudson, M.
TI Lack of ERCC1 and Olfactomedin 4 (Olfm4) Protein Expression Predicts
Neoadjuvant Therapy Sensitivity in GE Junction Adenocarcinoma (GEJAd)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 625
BP 141A
EP 141A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500625
ER
PT J
AU Demicco, EG
Farris, AB
Iafrate, AJ
Gaissert, HA
Fukuoka, J
Cohen, C
Zukerberg, LR
Lauwers, GY
Mino-Kenudson, M
AF Demicco, E. G.
Farris, A. B.
Iafrate, A. J.
Gaissert, H. A.
Fukuoka, J.
Cohen, C.
Zukerberg, L. R.
Lauwers, G. Y.
Mino-Kenudson, M.
TI Microsatellite Unstable Barrett's Esophagus-Associated Adenocarcinomas
Are Rare, but Clinicopathologically Similar to the Colonic Counterpart
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Emory Univ, Atlanta, GA 30322 USA.
Toyama Med Univ, Toyama, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 630
BP 142A
EP 143A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500630
ER
PT J
AU Demicco, EG
Farris, AB
Agbor-Etang, B
Fukuoka, J
Daives, D
Snimizu, M
Gaissert, HA
Mino-Kenudson, M
AF Demicco, E. G.
Farris, A. B.
Agbor-Etang, B.
Fukuoka, J.
Daives, D.
Snimizu, M.
Gaissert, H. A.
Mino-Kenudson, M.
TI Validation of a Topographic-Anatomic Subclassification for
Adenocarcinoma of the GE Junction (GEJ)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Emory Univ, Atlanta, GA 30322 USA.
Toyama Univ Hosp, Toyama, Japan.
Saitama Med Univ, Saitama, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 631
BP 143A
EP 143A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500631
ER
PT J
AU Golden, KL
Baba, Y
Fuchs, CS
Ogino, S
AF Golden, K. L.
Baba, Y.
Fuchs, C. S.
Ogino, S.
TI Loss of CDH1 Expression in Colorectal Cancer Is Independently Associated
with Microsatellite Instability and Female Gender
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 645
BP 146A
EP 146A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582500645
ER
PT J
AU Kolman, OK
Brown, I
Moran, CJ
Russell, GJ
Mino-Kenudson, M
AF Kolman, O. K.
Brown, I.
Moran, C. J.
Russell, G. J.
Mino-Kenudson, M.
TI Neutrophilic Infiltration in Gluten Sensitive Enteropathy (GSE): A
Series of 100 Pediatric Patients
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Sullivan Nicolaides Pathol, Taringa, Australia.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 671
BP 152A
EP 152A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501007
ER
PT J
AU Lennerz, JK
Srivastava, A
Batten, J
Chen, JH
Iafrate, AJ
Lauwers, G
AF Lennerz, J. K.
Srivastava, A.
Batten, J.
Chen, J. H.
Iafrate, A. J.
Lauwers, G.
TI Molecular Profile of Crohn's Colitis-Associated Colorectal
Adenocarcinoma Is More Similar to the 'Sporadic' Rather Than Ulcerative
Colitis-Associated Profile
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
Indiana Univ, Indianapolis, IN 46204 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 678
BP 153A
EP 153A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501014
ER
PT J
AU Ogino, S
Nosho, K
Glickman, JN
Mino-Kenudson, M
Fuchs, CS
AF Ogino, S.
Nosho, K.
Glickman, J. N.
Mino-Kenudson, M.
Fuchs, C. S.
TI Lymphoid Reaction to Colorectal Cancer Predicts Patient Survival
Independent of Lymph Node Count and MSI, and Explains the Association
between CIMP and Good Prognosis
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
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 NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 701
BP 158A
EP 159A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501037
ER
PT J
AU Ogino, S
Nosho, K
Tanaka, N
Hornick, JL
Fuchs, CS
AF Ogino, S.
Nosho, K.
Tanaka, N.
Hornick, J. L.
Fuchs, C. S.
TI Can We Predict Lymph Node Count in Colorectal Cancer Resection Specimen
Using Clinical, Pathologic and Molecular Variables?
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 703
BP 159A
EP 160A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501039
ER
PT J
AU Ogino, S
Nosho, K
Mino-Kenudson, M
Meyerhardt, JA
Fuchs, CS
AF Ogino, S.
Nosho, K.
Mino-Kenudson, M.
Meyerhardt, J. A.
Fuchs, C. S.
TI Negative Lymph Node Count in Colorectal Cancer Resection Predicts
Patient Survival, Independent of Positive Node Count, Tumoral Molecular
Alterations and Lymphocytic Reaction
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
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 NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 702
BP 159A
EP 159A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501038
ER
PT J
AU Park, DY
Kang, HJ
Shin, DH
Choi, KU
Lee, CH
Huh, GY
Sol, MY
Lauwers, GY
AF Park, D. Y.
Kang, H. J.
Shin, D. H.
Choi, K. U.
Lee, C. H.
Huh, G. Y.
Sol, M. Y.
Lauwers, G. Y.
TI Gastric Foveolar Hyperplasia, Foveolar Dysplasia and Pit Dysplasia in
414 Gastric Cancers-Prevalence and Clinicopathological Significance
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Pusan Natl Univ Hosp, Pusan, South Korea.
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 NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 708
BP 160A
EP 161A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501044
ER
PT J
AU Shima, K
Nosho, K
Chen, L
Fuchs, CS
Ogino, S
AF Shima, K.
Nosho, K.
Chen, L.
Fuchs, C. S.
Ogino, S.
TI Loss of PPARG Expression Is Common in CpG Island Methylator
Phenotype-Low (CIMP-Low) Colorectal Cancer
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 738
BP 167A
EP 168A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501074
ER
PT J
AU Yilmaz, OH
Bhan, AK
Lauwers, GY
Deshpande, V
AF Yilmaz, O. H.
Bhan, A. K.
Lauwers, G. Y.
Deshpande, V.
TI Olfactomedin-4, a Novel Marker of Intestinal Stem Cell Identity, Is
Upregulated in Long-Standing Ulcerative Colitis and Accompanying Low
Grade Dysplasia
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Yilmaz, O. H.; Bhan, A. K.; Lauwers, G. Y.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 763
BP 173A
EP 173A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501099
ER
PT J
AU Sangoi, AR
Beck, AH
Amin, MB
Cheng, L
Epstein, JI
Hansel, DE
Iczkowski, KA
Ro, JY
Lopez-Beltran, A
Oliva, E
Paner, GP
Reuter, VE
Shah, RB
Shen, SS
Tamboli, P
McKenney, JK
AF Sangoi, A. R.
Beck, A. H.
Amin, M. B.
Cheng, L.
Epstein, J. I.
Hansel, D. E.
Iczkowski, K. A.
Ro, J. Y.
Lopez-Beltran, A.
Oliva, E.
Paner, G. P.
Reuter, V. E.
Shah, R. B.
Shen, S. S.
Tamboli, P.
McKenney, J. K.
TI Interobserver Reproducibility (IOR) in the Diagnosis of Invasive
Micropapillary Carcinoma (MPC) of the Genitourinary Tract among Expert
Urologic Pathologists
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Cedars Sinai, Los Angeles, CA USA.
U Indiana, Indianapolis, IN USA.
Johns Hopkins, Baltimore, MD USA.
Cleveland Clin, Cleveland, OH 44106 USA.
U Colorado, Aurora, CO USA.
Methodist, Houston, TX USA.
Univ Cordoba, Fac Med, Anat Pathol Unit, E-14071 Cordoba, Spain.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Northwestern, Chicago, IL USA.
Mem Sloan Kettering, New York, NY USA.
U Michigan, Ann Arbor, MI USA.
UT MD Anderson, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 965
BP 216A
EP 216A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501300
ER
PT J
AU Chiang, S
Fazlollahi, L
Nguyen, A
Roberts, DJ
Iafrate, AJ
AF Chiang, S.
Fazlollahi, L.
Nguyen, A.
Roberts, D. J.
Iafrate, A. J.
TI In Situ Genetic Analysis of Hydatidiform Moles by Polymorphic Deletion
Probe Fluorescence In Situ Hybridization
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Chiang, S.; Fazlollahi, L.; Nguyen, A.; Roberts, D. J.; Iafrate, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1061
BP 237A
EP 237A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501396
ER
PT J
AU Han, G
Soslow, RA
Reuter, VE
Oliva, E
Gilks, CB
Asad, H
Tickoo, SK
AF Han, G.
Soslow, R. A.
Reuter, V. E.
Oliva, E.
Gilks, C. B.
Asad, H.
Tickoo, S. K.
TI Hypoxia-Inducible Factor (HIF) and Mammalian Target of Rapamycin (mTOR)
Pathway Markers in Ovarian Clear Cell Carcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Vancouver Gen Hosp, Vancouver, BC, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1098
BP 246A
EP 246A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501433
ER
PT J
AU Kindelberger, DW
Matulonis, U
AF Kindelberger, D. W.
Matulonis, U.
TI The Utility of Circulating Tumor Cells in Monitoring Patients with
Recurrent Ovarian Cancer
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1117
BP 250A
EP 250A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501451
ER
PT J
AU Knoepp, SM
Kuebler, DL
Wilbur, DC
AF Knoepp, S. M.
Kuebler, D. L.
Wilbur, D. C.
TI Correlation of the Hybrid Capture II High-Risk HPV DNA Test
Chemiluminescense Intensity from Cervical Samples with Follow-Up
Histologic Results: A Cytologic/Histologic Review of 367 Cases
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Univ Michigan, Ann Arbor, MI 48109 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1118
BP 250A
EP 250A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501452
ER
PT J
AU Laury, AR
Hornick, JL
Corson, JM
Krane, JF
Drapkin, R
Hirsch, MS
AF Laury, A. R.
Hornick, J. L.
Corson, J. M.
Krane, J. F.
Drapkin, R.
Hirsch, M. S.
TI PAX8 Distinguishes Serous Ovarian Neoplasms from Malignant Mesothelioma
with High Sensitivity and Specificity
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RI Drapkin, Ronny/E-9944-2016
OI Drapkin, Ronny/0000-0002-6912-6977
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1125
BP 251A
EP 252A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501459
ER
PT J
AU Mutter, GL
Monte, NM
Webster, KA
Neuberg, D
Dressler, GR
AF Mutter, G. L.
Monte, N. M.
Webster, K. A.
Neuberg, D.
Dressler, G. R.
TI Interaction of PAX2 and PTEN Drives Emergence of Endometrial Precancers
from a Preclinical Latent Phase
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1146
BP 256A
EP 256A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501480
ER
PT J
AU Schulte, S
Roh, M
Folkins, AK
Jarboe, EA
Garber, J
Hecht, J
Crum, CP
AF Schulte, S.
Roh, M.
Folkins, A. K.
Jarboe, E. A.
Garber, J.
Hecht, J.
Crum, C. P.
TI BRCA 1 or 2-Associated (BRCA plus ) Pelvic Serous Carcinomas Arise from
Both the Ovaries and Fallopian Tubes: The Contrast between Symptomatic
and Asymptomatic Women
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Univ Penn, Philadelphia, PA 19104 USA.
Univ Michigan, Med Ctr, Ann Arbor, MI USA.
Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA.
Univ Utah, Med Ctr, Salt Lake City, UT USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1171
BP 262A
EP 262A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501505
ER
PT J
AU Van De Vijver, KK
Castilla, MA
Romero, L
Biscuola, M
Moreno-Bueno, G
Palacios, J
Oliva, E
AF Van De Vijver, K. K.
Castilla, M. A.
Romero, L.
Biscuola, M.
Moreno-Bueno, G.
Palacios, J.
Oliva, E.
TI Study of Epithelial-Mesenchymal Transition in 70 Endometrial
Carcinosarcomas (ECS)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Maastricht Univ Med Ctr, Maastricht, Netherlands.
Hosp Univ Virgen del Rocio, Seville, Spain.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
CSIC, Inst Invest Biomed, Madrid, Spain.
RI Castilla, M Angeles/C-9454-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1199
BP 267A
EP 267A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501533
ER
PT J
AU Xian, W
Mehra, KK
Vathipadiekal, V
Tay, SW
Birrer, M
Crum, CP
AF Xian, W.
Mehra, K. K.
Vathipadiekal, V.
Tay, S. W.
Birrer, M.
Crum, C. P.
TI Ovarian Cancer Risk Assessment Via Expression Profiling of the Distal
Fallopian Tube Epithelium
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Inst Mol Biol, Singapore, Singapore.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1207
BP 269A
EP 269A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501541
ER
PT J
AU Xian, W
Mehra, KK
Miron, A
Oliva, E
Garber, J
Roh, M
Quade, BJ
Crum, CP
AF Xian, W.
Mehra, K. K.
Miron, A.
Oliva, E.
Garber, J.
Roh, M.
Quade, B. J.
Crum, C. P.
TI The Li Fraumeni Syndrome: A New Paradigm for p53 Signature Initiation in
the Distal Fallopian Tube and In Vitro Modeling
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Inst Mol Biol, Singapore, Singapore.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Michigan, Med Ctr, Ann Arbor, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1206
BP 269A
EP 269A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501540
ER
PT J
AU Hafezi, S
Seethalu, RR
Stelow, EB
Mills, S
Perez-Ordonez, B
Leong, I
Hunt, JL
Weinreb, I
AF Hafezi, S.
Seethalu, R. R.
Stelow, E. B.
Mills, S.
Perez-Ordonez, B.
Leong, I.
Hunt, J. L.
Weinreb, I.
TI Ewing Family of Tumors of the Sinonasal Tract
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Univ Hlth Network, Toronto, ON, Canada.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Virginia Hlth Syst, Charlottesville, VA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1229
BP 274A
EP 274A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501563
ER
PT J
AU Adam, P
Vela-Chavez, T
Cremer, M
Bink, K
Ferry, JA
Fend, F
Jaffe, E
Quintanilla-Martinez, L
AF Adam, P.
Vela-Chavez, T.
Cremer, M.
Bink, K.
Ferry, J. A.
Fend, F.
Jaffe, E.
Quintanilla-Martinez, L.
TI Cyclin D1 Positive Diffuse Large B-Cell Lymphomas Feature a
Post-Germinal Center - Immunophenotype and Lack Alterations in the CCND1
Gene Locus
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Univ Tubingen, Tubingen, Germany.
Tech Univ Munich, Munich, Germany.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1267
BP 282A
EP 282A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582501601
ER
PT J
AU Gibson, SE
Swerdlow, SH
Ferry, JA
Surti, U
Harris, NL
Hasserjian, RP
AF Gibson, S. E.
Swerdlow, S. H.
Ferry, J. A.
Surti, U.
Harris, N. L.
Hasserjian, R. P.
TI Reassessment of Small Lymphocytic Lymphoma (SLL) in the Era of
Monoclonal B Lymphocytosis (MBL)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1328
BP 296A
EP 297A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502009
ER
PT J
AU Klepeis, VE
Deshpande, V
Sohani, AR
Ferry, JA
AF Klepeis, V. E.
Deshpande, V.
Sohani, A. R.
Ferry, J. A.
TI Sclerosing Inflammatory Pseudotumor of the Orbit: An IgG4-Related
Disease
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Klepeis, V. E.; Deshpande, V.; Sohani, A. R.; Ferry, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 2
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1371
BP 307A
EP 307A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502052
ER
PT J
AU Nardi, V
Abramson, JS
Hasserjian, RP
AF Nardi, V.
Abramson, J. S.
Hasserjian, R. P.
TI Morphologic Dysplasia in Staging Marrow from High-Grade Non-Hodgkin's
Lymphoma Patients: A Paraneoplastic Phenomenon Associated with Adverse
Clinical Outcome
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Nardi, V.; Abramson, J. S.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1403
BP 314A
EP 314A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502084
ER
PT J
AU Ahmad, BR
Viswanathan, SR
Daley, GQ
Frazier, AL
Perez-Atayde, AR
AF Ahmad, B. R.
Viswanathan, S. R.
Daley, G. Q.
Frazier, A. L.
Perez-Atayde, A. R.
TI Lin28 a Novel, Lineage-Specific, Marker of Germ Cell Neoplasia
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT Spring Meeting of the Society-for-Pediatric-Patholoy
CY MAR 20-21, 2010
CL Washington, DC
SP Soc Pediat Pathol
C1 Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
IS 2
MA 20
BP 315
EP 315
PG 1
WC Pathology
SC Pathology
GA 551TL
UT WOS:000274233100036
ER
PT J
AU Rodig, SJ
Kutok, JL
Paterson, JC
Zhang, W
Shipp, MA
Grogan, T
Pileri, SA
Montes-Moreno, S
Johnson, NA
Ben-Neriah, S
Farinha, P
Piris, MA
Gascoyne, R
Marafioti, T
AF Rodig, S. J.
Kutok, J. L.
Paterson, J. C.
Zhang, W.
Shipp, M. A.
Grogan, T.
Pileri, S. A.
Montes-Moreno, S.
Johnson, N. A.
Ben-Neriah, S.
Farinha, P.
Piris, M. A.
Gascoyne, R.
Marafioti, T.
TI VpreB3, a Pre-BCR Associated Protein, Is Expressed by a Subset of
Mature, Germinal Center B Cells and a Biomarker of Burkitt Lymphoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Univ Oxford, Oxford, England.
Ventana Med Syst, Tucson, AZ USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Arizona, Tucson, AZ USA.
Univ Bologna, Sch Med, Bologna, Italy.
Spanish Natl Canc Ctr CNIO, Madrid, Spain.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1424
BP 318A
EP 319A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502105
ER
PT J
AU Ryan, RJH
Zukerberg, L
Sloan, JM
Collins, B
Ferry, J
AF Ryan, R. J. H.
Zukerberg, L.
Sloan, J. M.
Collins, B.
Ferry, J.
TI MALT Lymphoma with Associated Amyloid Deposition - A
Clinico-Pathological Study of 18 Cases
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Boston Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1430
BP 320A
EP 320A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502111
ER
PT J
AU Wang, SA
Abruzzo, LV
Hasserjian, RP
Medeiros, LJ
Miranda, RN
AF Wang, S. A.
Abruzzo, L. V.
Hasserjian, R. P.
Medeiros, L. J.
Miranda, R. N.
TI Myelodysplastic Syndromes with Interstitial Deletions of 11q Lack
Cryptic 11q23 Translocations and Exhibit Characteristic
Clinicopathologic Features
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acad Pathol
C1 UT MD Anderson, Houston, TX USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1460
BP 327A
EP 327A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502141
ER
PT J
AU Louissaint, A
Ferry, JA
Harris, NL
Zukerberg, LR
AF Louissaint, A.
Ferry, J. A.
Harris, N. L.
Zukerberg, L. R.
TI Morphology and Immunophenotype of Infectious Mononucleosis Presenting in
Axillary and Inguinal Lymph Nodes and Other Unusual Locations
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Louissaint, A.; Ferry, J. A.; Harris, N. L.; Zukerberg, L. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1491
BP 334A
EP 334A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502172
ER
PT J
AU Farris, AB
Taheri, D
Fazlollahi, L
Iafrate, AJ
Smith, RN
Collins, AB
Tolkoff-Rubin, N
Spitzer, TR
Kawai, T
Cosimi, AB
Sachs, DH
Colvin, RB
AF Farris, A. B.
Taheri, D.
Fazlollahi, L.
Iafrate, A. J.
Smith, R. N.
Collins, A. B.
Tolkoff-Rubin, N.
Spitzer, T. R.
Kawai, T.
Cosimi, A. B.
Sachs, D. H.
Colvin, R. B.
TI Distinctive Renal Biopsy Pathology in the Engraftment Syndrome: A
Response to Combined Kidney and Bone Marrow Transplantation
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Emory U, Atlanta, GA USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1512
BP 339A
EP 339A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502193
ER
PT J
AU Farris, AB
Coban, I
Klimstra, DS
Kim, G
Deshpande, V
Ohike, N
Adsay, N
AF Farris, A. B.
Coban, I.
Klimstra, D. S.
Kim, G.
Deshpande, V.
Ohike, N.
Adsay, N.
TI Necrotizing Arteritis Presenting as a Pancreatic Mass: A New Addition to
the Immune-Related Tumoral Pancreatitides
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Emory U, Atlanta, GA USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
UCSF, San Francisco, CA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1576
BP 354A
EP 355A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502257
ER
PT J
AU Gupta, RK
Genevay, M
Johnson, NB
Lauwers, GY
Deshpande, V
AF Gupta, R. K.
Genevay, M.
Johnson, N. B.
Lauwers, G. Y.
Deshpande, V.
TI Is Autoimmune Pancreatitis Associated with an Increased Risk of
Malignancy? A Retrospective and Comparative Study
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Geneva, Geneva, Switzerland.
Beth Israel Deaconess Med Ctr, Boston, MA USA.
NR 0
TC 1
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1584
BP 356A
EP 357A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502265
ER
PT J
AU Lennerz, JK
Chapman, WC
Brunt, EM
AF Lennerz, J. K.
Chapman, W. C.
Brunt, E. M.
TI Epithelial-Mesenchymal Transition (EMT) of K19 Structures within the
Stromal Compartment of HCV Cirrhosis Parallels Hepatocarcinogenesis
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Washington Univ, St Louis, MO 63130 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1604
BP 361A
EP 361A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502285
ER
PT J
AU Lisovsky, M
Dresser, K
Woda, B
Mino-Kenudson, M
AF Lisovsky, M.
Dresser, K.
Woda, B.
Mino-Kenudson, M.
TI Differentiation of Pancreatic Intraepithelial Neoplasia-3 (PanIN-3) and
Ductal Adenocarcinoma of the Pancreas from Lower Grade PanINs Utilizing
Immunohistochemistry for Cell Polarity Protein Lethal Giant Larva 2
(IgI2)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
UMassMem Med Ctr, Worcester, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1615
BP 363A
EP 363A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502296
ER
PT J
AU Nagata, K
Lauwers, GY
Murata, S
Shimizu, M
AF Nagata, K.
Lauwers, G. Y.
Murata, S.
Shimizu, M.
TI Gallbladder Intramural Papillary Mucinous Neoplasm: A New Entity Similar
to IPMN of the Pancreas
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Saitama Med Univ, Saitama Int Med Ctr, Hidaka, Saitama, Japan.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1628
BP 366A
EP 366A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502309
ER
PT J
AU Shen, J
Konstantinidis, I
Ferrone, CR
Deshpande, V
AF Shen, J.
Konstantinidis, I.
Ferrone, C. R.
Deshpande, V.
TI Intrapancreatic Cholangiocarcinomas: A Clinicopathological and
Immunohistochemical Analysis
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Shen, J.; Konstantinidis, I.; Ferrone, C. R.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1651
BP 371A
EP 371A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502332
ER
PT J
AU Xiao, HD
Yamaguchi, H
Dias-Santagata, D
Kuboki, Y
Akhavanfard, S
Hatori, T
Yamamoto, M
Shiratori, K
Kobayashi, M
Shimizu, M
Mino-Kenudson, M
Furukawa, T
AF Xiao, H. D.
Yamaguchi, H.
Dias-Santagata, D.
Kuboki, Y.
Akhavanfard, S.
Hatori, T.
Yamamoto, M.
Shiratori, K.
Kobayashi, M.
Shimizu, M.
Mino-Kenudson, M.
Furukawa, T.
TI Molecular Characteristics and Biological Behavior of Intraductal
Papillary-Mucinous Neoplasm, Oncocytic Type (IPMN-O)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Saitama Med Univ, Saitama, Japan.
Int Res & Educ Inst Integrated Med Sci, Tokyo, Japan.
Tokyo Womens Med Univ, Tokyo, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1667
BP 374A
EP 375A
PG 2
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502348
ER
PT J
AU Laury, AR
Hornick, JL
Piao, H
Perets, R
Barletta, J
Chirieac, LR
Krane, JF
Lis, R
Loda, M
Drapkin, R
Hirsch, MS
AF Laury, A. R.
Hornick, J. L.
Piao, H.
Perets, R.
Barletta, J.
Chirieac, L. R.
Krane, J. F.
Lis, R.
Loda, M.
Drapkin, R.
Hirsch, M. S.
TI PAX8 Is Highly Sensitive and Specific for Mullerian, Renal and Thyroid
Neoplasms: A Study of 1500 Epithelial Tumors
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1730
BP 388A
EP 388A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502411
ER
PT J
AU Cheng, L
Janne, PA
Jackman, DM
Johnson, BE
Joshi, VA
Lindeman, NI
AF Cheng, L.
Janne, P. A.
Jackman, D. M.
Johnson, B. E.
Joshi, V. A.
Lindeman, N. I.
TI Mutational Analysis of EGFR, KRAS, BRAF, PIK3CA, and ERBB2 in
Non-Small-Cell Lung Carcinomas (NSCLC)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Mol Med Lab, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1783
BP 399A
EP 399A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502464
ER
PT J
AU Klepeis, VE
Mark, EG
Dias-Santagata, D
Iafrate, AJ
Mino-Kenudson, M
AF Klepeis, V. E.
Mark, E. G.
Dias-Santagata, D.
Iafrate, A. J.
Mino-Kenudson, M.
TI Genotype-Phenotype Correlation in Lung Adenocarcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
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 NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1812
BP 406A
EP 406A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502493
ER
PT J
AU Hunt, JL
Smith, MT
Black-Schaffer, WS
AF Hunt, J. L.
Smith, M. T.
Black-Schaffer, W. S.
TI Joint Commission Standards for Ongoing and Focused Performance
Evaluation in Anatomic Pathology: Current Trends in Practice
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Med Univ S Carolina, Charleston, SC 29425 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1870
BP 418A
EP 418A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502551
ER
PT J
AU Morgan, EA
Oh, KY
Waghorne, CG
Neuberg, D
Stevenson, K
Kutok, JL
AF Morgan, E. A.
Oh, K. Y.
Waghorne, C. G.
Neuberg, D.
Stevenson, K.
Kutok, J. L.
TI Flow Cytometry Underestimates the Bone Marrow CD34-Positive Blast
Population Compared to Immunohistochemical and Morphologic Assessments
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1874
BP 419A
EP 419A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502555
ER
PT J
AU Ryan, RJH
Snuderl, M
Black-Schaffer, WS
Hunt, J
AF Ryan, R. J. H.
Snuderl, M.
Black-Schaffer, W. S.
Hunt, J.
TI Improvements in Training and Credentialing of Residents for Independent
Frozen Section Sign-Out Responsibility
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 20-26, 2010
CL Washington, DC
SP US & Canadian Acac Pathol
C1 [Ryan, R. J. H.; Snuderl, M.; Black-Schaffer, W. S.; Hunt, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2010
VL 23
SU 1
MA 1880
BP 421A
EP 421A
PG 1
WC Pathology
SC Pathology
GA 556HX
UT WOS:000274582502561
ER
PT J
AU Park, ES
Rabinovsky, R
Carey, M
Hennessy, BT
Agarwal, R
Liu, WB
Ju, ZL
Deng, WL
Lu, YL
Woo, HG
Kim, SB
Cheong, JH
Garraway, LA
Weinstein, JN
Mills, GB
Lee, JS
Davies, MA
AF Park, Eun Sung
Rabinovsky, Rosalia
Carey, Mark
Hennessy, Bryan T.
Agarwal, Roshan
Liu, Wenbin
Ju, Zhenlin
Deng, Wanleng
Lu, Yiling
Woo, Hyun Goo
Kim, Sang-Bae
Cheong, Jae-Ho
Garraway, Levi A.
Weinstein, John N.
Mills, Gordon B.
Lee, Ju-Seog
Davies, Michael A.
TI Integrative Analysis of Proteomic Signatures, Mutations, and Drug
Responsiveness in the NCI 60 Cancer Cell Line Set
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID GENE-EXPRESSION PATTERNS; CHEMOSENSITIVITY PREDICTION; MOLECULAR
PHARMACOLOGY; TUMOR PROGRESSION; PANEL; PROFILES; SENSITIVITY;
MICROARRAY; DATABASE; OVARIAN
AB Aberrations in oncogenes and tumor suppressors frequently affect the activity of critical signal transduction pathways. To analyze systematically the relationship between the activation status of protein networks and other characteristics of cancer cells, we did reverse phase protein array (RPPA) profiling of the NCI60 cell lines for total protein expression and activation-specific markers of critical signaling pathways. To extend the scope of the study, we merged those data with previously published RPPA results for the NCI60. Integrative analysis of the expanded RPPA data set revealed five major clusters of cell lines and five principal proteomic signatures. Comparison of mutations in the NCI60 cell lines with patterns of protein expression showed significant associations for PTEN, PIK3CA, BRAF, and APC mutations with proteomic clusters. PIK3CA and PTEN mutation enrichment were not cell lineage-specific but were associated with dominant yet distinct groups of proteins. The five RPPA-defined clusters were strongly associated with sensitivity to standard anticancer agents. RPPA analysis identified 27 protein features significantly associated with sensitivity to paclitaxel. The functional status of those proteins was interrogated in a paclitaxel whole genome small interfering RNA ( siRNA) library synthetic lethality screen and confirmed the predicted associations with drug sensitivity. These studies expand our understanding of the activation status of protein networks in the NCI60 cancer cell lines, demonstrate the importance of the direct study of protein expression and activation, and provide a basis for further studies integrating the information with other molecular and pharmacological characteristics of cancer. Mol Cancer Ther; 9(2); 257-67. (C) 2010 AACR.
C1 [Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Unit 0904, Houston, TX 77030 USA.
[Park, Eun Sung; Carey, Mark; Hennessy, Bryan T.; Agarwal, Roshan; Lu, Yiling; Kim, Sang-Bae; Cheong, Jae-Ho; Weinstein, John N.; Mills, Gordon B.; Lee, Ju-Seog; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Hennessy, Bryan T.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Med Oncol, Houston, TX 77030 USA.
[Liu, Wenbin; Ju, Zhenlin; Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Rabinovsky, Rosalia; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Woo, Hyun Goo] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Davies, MA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Unit 0904, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM mdavies@mdanderson.org
FU M.D. Anderson Cancer Center (MDACC); National Cancer Institute (NCI)
[CA-16672]
FX M.D. Anderson Cancer Center (MDACC) Melanoma Spore Development Grant (M.
A. Davies). The M.D. Anderson Reverse Phase Protein Array Core Facility
is supported by a National Cancer Institute (NCI) Cancer Center Support
Grant (CA-16672).
NR 33
TC 54
Z9 55
U1 1
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD FEB
PY 2010
VL 9
IS 2
BP 257
EP 267
DI 10.1158/1535-7163.MCT-09-0743
PG 11
WC Oncology
SC Oncology
GA 607GN
UT WOS:000278487200001
PM 20124458
ER
PT J
AU Biswas, S
Heetveld, S
Wolf, P
Cao, Y
Norton, S
Haggarty, S
Cotman, S
AF Biswas, Sunita
Heetveld, Sasja
Wolf, Pavlina
Cao, Yi
Norton, Stephanie
Haggarty, Stephen
Cotman, Susan
TI A chemical genetic approach to identifying therapeutictargets for NCL
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 6th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 10-12, 2010
CL Miami, FL
SP Lysosomal Dis Network
C1 [Biswas, Sunita; Heetveld, Sasja; Wolf, Pavlina; Cao, Yi; Cotman, Susan] Harvard Univ, Sch Med, Boston, MA USA.
[Biswas, Sunita; Heetveld, Sasja; Norton, Stephanie; Haggarty, Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wolf, Pavlina] Broad Inst MIT & Harvard, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2010
VL 99
IS 2
MA 16
BP S11
EP S11
DI 10.1016/j.ymgme.2009.10.033
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 548XV
UT WOS:000274004300029
ER
PT J
AU Cotman, S
Cao, Y
Biswas, S
Wolf, P
Massey, A
Cuervo, AM
MacDonald, M
Lee, JM
AF Cotman, Susan
Cao, Yi
Biswas, Sunita
Wolf, Pavlina
Massey, Ashish
Cuervo, Ana Maria
MacDonald, Marcy
Lee, Jong-Min
TI Distinct features of disease phenotypes in two genetic models of NCL
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 6th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 10-12, 2010
CL Miami, FL
SP Lysosomal Dis Network
C1 [Cotman, Susan; Cao, Yi; Biswas, Sunita; Wolf, Pavlina; MacDonald, Marcy; Lee, Jong-Min] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Massey, Ashish; Cuervo, Ana Maria] Albert Einstein Coll Med, Bronx, NY 10467 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2010
VL 99
IS 2
MA 32
BP S14
EP S15
DI 10.1016/j.ymgme.2009.10.049
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 548XV
UT WOS:000274004300045
ER
PT J
AU Curcio-Morelli, C
Charles, FA
Micsenyi, MC
Cao, Y
Venugopal, B
Browning, MF
Dobrenis, K
Cotman, SL
Walkley, SU
Slaugenhaupt, SA
AF Curcio-Morelli, Cyntia
Charles, Florie A.
Micsenyi, Matthew C.
Cao, Yi
Venugopal, Bhuvarahamurthy
Browning, Marsha F.
Dobrenis, Kostantin
Cotman, Susan L.
Walkley, Steven U.
Slaugenhaupt, Susan A.
TI Macroautophagy is defective in mucolipin 1-deficient mouse neurons
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 6th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 10-12, 2010
CL Miami, FL
SP Lysosomal Dis Network
C1 [Curcio-Morelli, Cyntia; Charles, Florie A.; Cao, Yi; Venugopal, Bhuvarahamurthy; Browning, Marsha F.; Cotman, Susan L.; Slaugenhaupt, Susan A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Micsenyi, Matthew C.; Dobrenis, Kostantin; Walkley, Steven U.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10467 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2010
VL 99
IS 2
MA 34
BP S15
EP S15
DI 10.1016/j.ymgme.2009.10.051
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 548XV
UT WOS:000274004300047
ER
PT J
AU Sleat, D
Ding, L
Wang, SD
Zhao, CF
Wang, YH
Xin, W
Zheng, HY
Moore, D
Sims, K
Lobel, P
AF Sleat, David
Ding, Lin
Wang, Shudan
Zhao, Caifeng
Wang, Yanhong
Xin, Winnie
Zheng, Haiyan
Moore, Dirk
Sims, Katherine
Lobel, Peter
TI Comparative proteomics and lysosomal disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 6th Annual World Symposium of the Lysosomal-Disease-Network
CY FEB 10-12, 2010
CL Miami, FL
SP Lysosomal Dis Network
C1 [Sleat, David; Ding, Lin; Zhao, Caifeng; Wang, Yanhong; Zheng, Haiyan] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Sleat, David; Lobel, Peter] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA.
[Sleat, David; Wang, Shudan] McGill Univ, Montreal, PQ, Canada.
[Sleat, David; Xin, Winnie; Sims, Katherine] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sleat, David; Moore, Dirk] Univ Med & Dent New Jersey, Sch Publ Hlth, Dept Biostat, Piscataway, NJ 08854 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2010
VL 99
IS 2
MA 127
BP S34
EP S34
DI 10.1016/j.ymgme.2009.10.144
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 548XV
UT WOS:000274004300140
ER
PT J
AU Encinales, L
Zuniga, J
Granados-Montiel, J
Yunis, M
Granados, J
Almeciga, I
Clavijo, O
Awad, C
Collazos, V
Vargas-Rojas, MI
Banales-Mendez, JL
Vazquez-Castaneda, L
Stern, JN
Romero, V
Frindkis-Hareli, M
Terreros, D
Fernandez-Vina, M
Yunis, EJ
AF Encinales, Liliana
Zuniga, Joaquin
Granados-Montiel, Julio
Yunis, Maria
Granados, Julio
Almeciga, Ingrid
Clavijo, Olga
Awad, Carlos
Collazos, Vilma
Ines Vargas-Rojas, Maria
Luis Banales-Mendez, Jose
Vazquez-Castaneda, Lilia
Stern, Joel N.
Romero, Viviana
Frindkis-Hareli, Masha
Terreros, Daniel
Fernandez-Vina, Marcelo
Yunis, Edmond J.
TI Humoral immunity in tuberculin skin test anergy and its role in
high-risk persons exposed to active tuberculosis
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Humoral immunity; Tuberculosis; Immunoglobulins; Anergy; Cell-mediated
immunity
ID T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS; LATENT TUBERCULOSIS;
MOLECULAR MIMICRY; INFECTION; CYTOKINES; ANTIGENS; SUBSETS; PROTEIN
AB The most common test to identify latent tuberculosis is the tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis patients as shown in this report, we studied antibody profiles to explain the anergy Of Such responses in high-risk individuals without active infection
Our results showed that humoral immunity against tuberculin, regardless of the result of the tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator of infection latency suggesting that latency can be based on the levels of antibodies together with in vitro proliferation of peripheral blood mononuclear cells in the presence of the purified protein derivative Importantly, anti-tuberculin IgG antibody levels mediate the anergy described herein, which Could also prevent reactivation of disease in high-risk individuals with high antibody titers. Such anti-tuberculin IgG antibodies were also found associated with blocking and/or stimulation of in vitro cultures of PBMC with tuberculin In this regard. future studies need to establish if immune responses to Mycobacterium tuberculosis can generate a broad spectrum of reactions either toward Th1 responses favoring stimulation by cytokines or by antibodies and those toward diminished responses by Th2 cytokines or blocking by antibodies; possibly involving mechanisms of antibody dependent protection from Mtb by different subclasses of IgG Published by Elsevier Ltd.
C1 [Encinales, Liliana; Granados-Montiel, Julio; Almeciga, Ingrid; Clavijo, Olga; Stern, Joel N.; Romero, Viviana; Frindkis-Hareli, Masha; Yunis, Edmond J.] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA.
[Encinales, Liliana; Granados-Montiel, Julio; Almeciga, Ingrid; Clavijo, Olga; Stern, Joel N.; Romero, Viviana; Frindkis-Hareli, Masha; Yunis, Edmond J.] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA.
[Zuniga, Joaquin; Ines Vargas-Rojas, Maria; Luis Banales-Mendez, Jose; Vazquez-Castaneda, Lilia] Inst Nacl Enfermedades Respiratorias, Lab Immunobiol & Genet, Mexico City, DF, Mexico.
[Luis Banales-Mendez, Jose] Inst Nacl Cardiol Ignacio Chavez, Mol Biol Lab, Mexico City, DF, Mexico.
[Granados, Julio] Inst Nacl Ciencias Med & Nutr Mexico City, Dept Immunol & Rheumatol, Mexico City, DF, Mexico.
[Terreros, Daniel] Paul L Foster SOM, Texas Tech Hlth Sci Ctr, Dept Biomed Sci, El Paso, TX 79905 USA.
[Fernandez-Vina, Marcelo] Univ Texas MD Anderson Canc Ctr, Dept Lab Med, Houston, TX 77030 USA.
[Fernandez-Vina, Marcelo] Univ Texas Houston, Sch Med, Div Immunol & Organ Transplantat, Houston, TX 77030 USA.
[Awad, Carlos] Hosp Santa Clara, Bogota, Colombia.
[Yunis, Maria] MyDesign, Arlington, MA USA.
RP Yunis, EJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, 44 Binney St, Boston, MA 02115 USA.
OI Stern, Joel N.H./0000-0002-1259-2256
FU NIH [AI49213, HL29583, HL59838]; department of Cancer Immunology and
AIDS, Dana Farber Cancer Institute
FX This work was Supported by NIH grants AI49213, HL29583 and HL59838, and
funds from the department of Cancer Immunology and AIDS, Dana Farber
Cancer Institute.
NR 31
TC 11
Z9 13
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD FEB
PY 2010
VL 47
IS 5
BP 1066
EP 1073
DI 10.1016/j.molimm.2009.11.005
PG 8
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 560ZT
UT WOS:000274945100014
PM 20004475
ER
PT J
AU Cowart, LA
Shotwell, M
Worley, ML
Richards, AJ
Montefusco, DJ
Hannun, YA
Lu, XH
AF Cowart, L. Ashley
Shotwell, Matthew
Worley, Mitchell L.
Richards, Adam J.
Montefusco, David J.
Hannun, Yusuf A.
Lu, Xinghua
TI Revealing a signaling role of phytosphingosine-1-phosphate in yeast
SO MOLECULAR SYSTEMS BIOLOGY
LA English
DT Article
DE information integration; lipidomics; signal transduction; sphingolipids;
transcriptomics
ID HEAT-STRESS RESPONSE; TRANSCRIPTIONAL REGULATORY NETWORKS;
SACCHAROMYCES-CEREVISIAE; COMPONENT ANALYSIS; GENE-EXPRESSION; SPHINGOID
BASE; SPHINGOLIPIDS; SPHINGOSINE-1-PHOSPHATE; BIOSYNTHESIS; METABOLOMICS
AB Sphingolipids including sphingosine-1-phosphate and ceramide participate innumerous cell programs through signaling mechanisms. This class of lipids has important functions in stress responses; however, determining which sphingolipid mediates specific events has remained encumbered by the numerous metabolic interconnections of sphingolipids,such that modulating a specific lipid of interest through manipulating metabolic enzymes causes 'ripple effects', which change levels of many other lipids. Here, we develop a method of integrative analysis for genomic, transcriptomic, and lipidomic data to address this previously intractable problem. This method revealed a specific signaling role for phytosphingosine-1-phosphate, a lipid with no previously defined specific function in yeast, in regulating genes required for mitochondrial respiration through the HAP complex transcription factor. This approach could be applied to extract meaningful biological information from a similar experimental design that produces multiple sets of high-throughput data. Molecular Systems Biology 6: 349; published online 16 February 2010; doi:10.1038/msb.2010.3
C1 [Cowart, L. Ashley; Worley, Mitchell L.; Richards, Adam J.; Montefusco, David J.; Hannun, Yusuf A.; Lu, Xinghua] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Shotwell, Matthew] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Lu, XH (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 174 Ashley Ave, Charleston, SC 29425 USA.
EM hannun@musc.edu; lux@musc.edu
FU Department of Veterans' Affairs Merit award [5R01LM009153, 3T15LM07438,
5T32GM074934]; [P20 RR017677-]; [1R01LM10144]; [5R01GM63265]
FX We acknowledge the following grant supports: P20 RR017677-07 (to LAC and
XL). 1R01LM10144 to XL, 5R01GM63265 to YAH, the Department of Veterans'
Affairs Merit award to LAC, 5R01LM009153, 3T15LM07438 to XL and AJR, and
5T32GM074934 to MS. We thank Alan Wilder and Jason Gandy for technical
assistance. We also acknowledge the MUSC Lipidomics Core Facility of the
COBRE in Lipidomics and Pathobiology for sample analysis, the MUSC
Proteogenomics Core Facility for microarray assays, the MUSC department
of Art Services for assistance with figure preparation, and Dr Hiroko
Hama for critical reading of the paper.
NR 39
TC 27
Z9 27
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1744-4292
J9 MOL SYST BIOL
JI Mol. Syst. Biol.
PD FEB
PY 2010
VL 6
AR 349
DI 10.1038/msb.2010.3
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 564AU
UT WOS:000275183700002
PM 20160710
ER
PT J
AU Hardcastle, J
Kurozumi, K
Dmitrieva, N
Sayers, MP
Ahmad, S
Waterman, P
Weissleder, R
Chiocca, EA
Kaur, B
AF Hardcastle, Jayson
Kurozumi, Kazuhiko
Dmitrieva, Nina
Sayers, Martin P.
Ahmad, Sarwat
Waterman, Peter
Weissleder, Ralph
Chiocca, E. Antonio
Kaur, Balveen
TI Enhanced Antitumor Efficacy of Vasculostatin (Vstat120) Expressing
Oncolytic HSV-1
SO MOLECULAR THERAPY
LA English
DT Article
ID HERPES-SIMPLEX-VIRUS; BRAIN ANGIOGENESIS INHIBITOR-1; GROWTH-FACTOR;
TUMOR-GROWTH; IN-VIVO; GENE-EXPRESSION; CANCER; GLIOMA; MUTANT; G207
AB Oncolytic viral (OV) therapy is a promising therapeutic modality for brain tumors. Vasculostatin (Vstat120) is the cleaved and secreted extracellular fragment of brain-specific angiogenesis inhibitor 1 (BAI1), a brain-specific receptor. To date, the therapeutic efficacy of Vstat120 delivery into established tumors has not been investigated. Here we tested the therapeutic efficacy of combining Vstat120 gene delivery in conjunction with OV therapy. We constructed RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus), which expresses Vstat120 under the control of the herpes simplex virus (HSV) IE4/5 promoter. Secreted Vstat120 was detected as soon as 4 hours postinfection in vitro and was retained for up to 13 days after OV therapy in subcutaneous tumors. RAMBO-produced Vstat120 efficiently inhibited endothelial cell migration and tube formation in vitro (P = 0.0005 and P = 0.0184, respectively) and inhibited angiogenesis (P = 0.007) in vivo. There was a significant suppression of intracranial and subcutaneous glioma growth in mice treated with RAMBO compared to the control virus, HSVQ (P = 0.0021 and P < 0.05, respectively). Statistically significant reduction in tumor vascular volume fraction (VVF) and microvessel density (MVD) was observed in tumors treated with RAMBO. This is the first study to report the antitumor effects of Vstat120 delivery into established tumors and supports the further development of RAMBO as a possible cancer therapy.
C1 [Kaur, Balveen] Ohio State Univ, Dardinger Lab Neurooncol & Neurosci, Dept Neurol Surg, James Comprehens Canc Ctr, Columbus, OH 43210 USA.
[Hardcastle, Jayson] Ohio State Univ, Med Ctr, Integrated Biomed Sci Grad Program, Columbus, OH 43210 USA.
[Ahmad, Sarwat] Ohio State Univ, Med Ctr, Coll Med, Columbus, OH 43210 USA.
[Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA.
[Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA USA.
RP Kaur, B (reprint author), Ohio State Univ, Dardinger Lab Neurooncol & Neurosci, Dept Neurol Surg, James Comprehens Canc Ctr, 385-D OSUCCC,410 W 12th Ave, Columbus, OH 43210 USA.
EM Balveen.Kaur@osumc.edu
RI kaur, Balveen/E-3355-2011
FU National Institutes of Health [1K01NS059575, R01NS064607, R21NS056203,
P01 CA069246, R24 CA92782]; American Association for Neurological
Surgeons/Congress of Neurological Surgeons, Section on Tumors/BrainLAB
International Research Fellowship; American Brain Tumor Association;
Alex Lemonade Stand Foundation
FX This work was supported by funding from the National Institutes of
Health grant (1K01NS059575, R01NS064607, and R21NS056203 to B.K.; P01
CA069246 to E. A. C. and R. W.; and R24 CA92782 to R.W.); American
Association for Neurological Surgeons/Congress of Neurological Surgeons,
Section on Tumors/BrainLAB International Research Fellowship (to K.K.);
American Brain Tumor Association medical student summer fellowship (to
S.A.); and the Alex Lemonade Stand Foundation young investigator award
(to B.K.).
NR 50
TC 42
Z9 45
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD FEB
PY 2010
VL 18
IS 2
BP 285
EP 294
DI 10.1038/mt.2009.232
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 554PQ
UT WOS:000274447300008
PM 19844198
ER
PT J
AU Kim, SS
Peer, D
Kumar, P
Subramanya, S
Wu, HQ
Asthana, D
Habiro, K
Yang, YG
Manjunath, N
Shimaoka, M
Shankar, P
AF Kim, Sang-Soo
Peer, Dan
Kumar, Priti
Subramanya, Sandesh
Wu, Huaquan
Asthana, Deshratan
Habiro, Katsuyoshi
Yang, Yong-Guang
Manjunath, N.
Shimaoka, Motomu
Shankar, Premlata
TI RNAi-mediated CCR5 Silencing by LFA-1-targeted Nanoparticles Prevents
HIV Infection in BLT Mice
SO MOLECULAR THERAPY
LA English
DT Article
ID SMALL INTERFERING RNA; T-CELLS; ENTRY INHIBITORS; IMMUNE-SYSTEM;
TARGET-CELLS; MOUSE MODEL; DELIVERY; SIRNA; LIPOSOMES; LFA-1
AB RNA interference (RNAi)-mediated knockdown of gene expression offers a novel treatment strategy for human immunodeficiency virus (HIV) infection. However, the major hurdle for clinical use is a practical strategy for small interfering RNA (siRNA) delivery to the multiple immune cell types important in viral pathogenesis. We have developed a novel immunoliposome method targeting the lymphocyte function-associated antigen-1 (LFA-1) integrin expressed on all leukocytes and evaluated it for systemic delivery of siRNA in a humanized mouse model. We show that in vivo administration of the LFA-1 integrin-targeted and stabilized nanoparticles (LFA-1 I-tsNPs) results in selective uptake of siRNA by T cells and macrophages, the prime targets of HIV. Further, in vivo administration of anti-CCR5 siRNA/LFA-1 I-tsNPs resulted in leukocyte-specific gene silencing that was sustained for 10 days. Finally, humanized mice challenged with HIV after anti-CCR5 siRNA treatment showed enhanced resistance to infection as assessed by the reduction in plasma viral load and disease-associated CD4 T-cell loss. This study demonstrates the potential in vivo applicability of LFA-1-directed siRNA delivery as anti-HIV prophylaxis.
C1 [Kim, Sang-Soo; Subramanya, Sandesh; Wu, Huaquan; Manjunath, N.; Shankar, Premlata] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Biomed Sci,Ctr Excellence Infect Dis, El Paso, TX 79905 USA.
[Kim, Sang-Soo; Peer, Dan; Subramanya, Sandesh; Wu, Huaquan; Manjunath, N.; Shimaoka, Motomu; Shankar, Premlata] Immune Dis Inst, Boston, MA USA.
[Peer, Dan; Shimaoka, Motomu] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Peer, Dan; Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Peer, Dan] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, Lab Nanomed, IL-69978 Tel Aviv, Israel.
[Kumar, Priti] Yale Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT USA.
[Asthana, Deshratan] Univ Miami, Miller Sch Med, Lab Clin & Biol Studies, Miami, FL 33136 USA.
[Habiro, Katsuyoshi; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA.
RP Shankar, P (reprint author), Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Biomed Sci,Ctr Excellence Infect Dis, 5001 El Paso Dr, El Paso, TX 79905 USA.
EM shimaoka@idi.harvard.edu; premlata.shankar@ttuhsc.edu
RI Peer, Dan/A-1785-2011; Kumar, Priti/C-5699-2009
OI Peer, Dan/0000-0001-8238-0673;
FU NIH (National Institutes of Health) [AI071882, AI063421]; Leukemia &
Lymphoma Society; KRF (Korea Research Foundation); MOEHRD (Ministry of
Education and Human Resource Development) [KRF-2006-352-D00070]; CFAR
(Center for AIDS Research) [P30 A060354]
FX This work was supported by grants from NIH (National Institutes of
Health), AI071882 (P.S.) and AI063421 (M.S.); the Leukemia & Lymphoma
Society (M.S.); the KRF (Korea Research Foundation) and MOEHRD (Ministry
of Education and Human Resource Development), KRF-2006-352-D00070
(S.-S.K.); and the CFAR (Center for AIDS Research) fellowship P30
A060354 (P.K.). We thank Erica Nakajima from the Yale School of Medicine
for technical assistance and critical reading of the manuscript.
NR 31
TC 102
Z9 112
U1 2
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD FEB
PY 2010
VL 18
IS 2
BP 370
EP 376
DI 10.1038/mt.2009.271
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 554PQ
UT WOS:000274447300017
PM 19997090
ER
PT J
AU Liu, XH
Lee, DJ
Skittone, LK
Natsuhara, K
Kim, HT
AF Liu, Xuhui
Lee, David J.
Skittone, Laura K.
Natsuhara, Kyle
Kim, Hubert T.
TI ROLE OF GELATINASES IN DISUSE-INDUCED SKELETAL MUSCLE ATROPHY
SO MUSCLE & NERVE
LA English
DT Article
DE gelatinases; muscular atrophy; extracellular matrix; disuse; basement
membrane
ID MATRIX METALLOPROTEINASES; IV COLLAGENASE; HINDLIMB IMMOBILIZATION;
HUMAN-FIBROBLASTS; EXPRESSION; RATS; INHIBITOR; SECRETION; RECOVERY
AB Gelatinases are a subgroup of the family of matrix metalloproteinases, which contains two members-gelatinase A and B. These enzymes play an important role in basement membrane homeostasis. Previous studies have associated basement membrane degradation with skeletal muscle atrophy. However, the specific contribution of gelatinases to the pathobiology of muscle atrophy remains unknown. In this study we examined the specific roles of gelatinase A and B in disuse-induced skeletal muscle atrophy using knockout mice. Although both gelatinase A and B are highly upregulated in disused muscle, only gelatinase A null mice had significantly reduced muscle atrophy as compared to wildtype littermates. Type IV collagen and laminin, two major components of basement membrane, were relatively well-preserved in disused muscle in gelatinase A null mice, but not in gelatinase B null mice. These findings suggest that gelatinase A, and not gelatinase B, plays a critical role in disuse-induced skeletal muscle atrophy. Muscle Nerve 41: 174-178, 2010
C1 [Liu, Xuhui; Skittone, Laura K.; Natsuhara, Kyle; Kim, Hubert T.] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA 94121 USA.
[Liu, Xuhui; Lee, David J.; Kim, Hubert T.] Univ Calif San Francisco, Dept Orthoped Surg, San Francisco, CA 94143 USA.
RP Kim, HT (reprint author), San Francisco VA Med Ctr, Dept Vet Affairs, 4150 Clement St 112, San Francisco, CA 94121 USA.
EM Kimh@orthosurg.ucsf.edu
FU Orthopedic Research & Education Foundation; Illinois Bone and Joint
Institute
FX Supported by the Orthopedic Research & Education Foundation and the
Illinois Bone and Joint Institute. We thank Dr. Rajabrata Sarkar for
gifts of MMP-2 and MMP-9 knockout, mice. We think Dr. Mostafa Gabr for
technique help in histology.
NR 26
TC 5
Z9 5
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD FEB
PY 2010
VL 41
IS 2
BP 174
EP 178
DI 10.1002/mus.21463
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 550LZ
UT WOS:000274130700003
PM 19790245
ER
PT J
AU Kim, J
Orkin, SH
AF Kim, Jonghwan
Orkin, Stuart H.
TI Systematic tracking of cell fate changes
SO NATURE BIOTECHNOLOGY
LA English
DT Editorial Material
ID EMBRYONIC STEM-CELLS; NANOG; PLURIPOTENCY
C1 [Kim, Jonghwan; Orkin, Stuart H.] Childrens Hosp, Boston, MA 02115 USA.
[Kim, Jonghwan; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Kim, J (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
EM stuart_orkin@dfci.harvard.edu
NR 9
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD FEB
PY 2010
VL 28
IS 2
BP 146
EP 147
DI 10.1038/nbt0210-146
PG 2
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 552TT
UT WOS:000274317200022
PM 20139953
ER
PT J
AU Mootha, VK
Hirschhorn, JN
AF Mootha, Vamsi K.
Hirschhorn, Joel N.
TI Inborn variation in metabolism
SO NATURE GENETICS
LA English
DT Editorial Material
ID VARIANTS; ASSOCIATION; DISEASE
AB Advances in analytical biochemistry have recently made it possible to obtain global snapshots of metabolism. A new study couples such technology with genome-wide genetic analysis to explore inherited variation in human metabolism.
C1 [Mootha, Vamsi K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Mootha, Vamsi K.; Hirschhorn, Joel N.] Broad Inst Metab Initiat, Cambridge, MA USA.
[Hirschhorn, Joel N.] Harvard Univ, Childrens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Mootha, VK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM vamsi@hms.harvard.edu; joeth@broadinstitute.org
FU NIDDK NIH HHS [R01 DK081457, R01 DK081457-02]
NR 15
TC 10
Z9 10
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD FEB
PY 2010
VL 42
IS 2
BP 97
EP 98
DI 10.1038/ng0210-97
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 549WG
UT WOS:000274084400002
PM 20104246
ER
PT J
AU Dupuis, J
Langenberg, C
Prokopenko, I
Saxena, R
Soranzo, N
Jackson, AU
Wheeler, E
Glazer, NL
Bouatia-Naji, N
Gloyn, AL
Lindgren, CM
Magi, R
Morris, AP
Randall, J
Johnson, T
Elliott, P
Rybin, D
Thorleifsson, G
Steinthorsdottir, V
Henneman, P
Grallert, H
Dehghan, A
Hottenga, JJ
Franklin, CS
Navarro, P
Song, K
Goel, A
Perry, JRB
Egan, JM
Lajunen, T
Grarup, N
Sparso, T
Doney, A
Voight, BF
Stringham, HM
Li, M
Kanoni, S
Shrader, P
Cavalcanti-Proenca, C
Kumari, M
Qi, L
Timpson, NJ
Gieger, C
Zabena, C
Rocheleau, G
Ingelsson, E
An, P
O'Connell, J
Luan, J
Elliott, A
McCarroll, SA
Payne, F
Roccasecca, RM
Pattou, F
Sethupathy, P
Ardlie, K
Ariyurek, Y
Balkau, B
Barter, P
Beilby, JP
Ben-Shlomo, Y
Benediktsson, R
Bennett, AJ
Bergmann, S
Bochud, M
Boerwinkle, E
Bonnefond, A
Bonnycastle, LL
Borch-Johnsen, K
Bottcher, Y
Brunner, E
Bumpstead, SJ
Charpentier, G
Chen, YDI
Chines, P
Clarke, R
Coin, LJM
Cooper, MN
Cornelis, M
Crawford, G
Crisponi, L
Day, INM
de Geus, EJC
Delplanque, J
Dina, C
Erdos, MR
Fedson, AC
Fischer-Rosinsky, A
Forouhi, NG
Fox, CS
Frants, R
Franzosi, MG
Galan, P
Goodarzi, MO
Graessler, J
Groves, CJ
Grundy, S
Gwilliam, R
Gyllensten, U
Hadjadj, S
Hallmans, G
Hammond, N
Han, XJ
Hartikainen, AL
Hassanali, N
Hayward, C
Heath, SC
Hercberg, S
Herder, C
Hicks, AA
Hillman, DR
Hingorani, AD
Hofman, A
Hui, J
Hung, J
Isomaa, B
Johnson, PRV
Jorgensen, T
Jula, A
Kaakinen, M
Kaprio, J
Kesaniemi, YA
Kivimaki, M
Knight, B
Koskinen, S
Kovacs, P
Kyvik, KO
Lathrop, GM
Lawlor, DA
Le Bacquer, O
Lecoeur, C
Li, Y
Lyssenko, V
Mahley, R
Mangino, M
Manning, AK
Martinez-Larrad, MT
McAteer, JB
McCulloch, LJ
McPherson, R
Meisinger, C
Melzer, D
Meyre, D
Mitchell, BD
Morken, MA
Mukherjee, S
Naitza, S
Narisu, N
Neville, MJ
Oostra, BA
Orru, M
Pakyz, R
Palmer, CNA
Paolisso, G
Pattaro, C
Pearson, D
Peden, JF
Pedersen, NL
Perola, M
Pfeiffer, AFH
Pichler, I
Polasek, O
Posthuma, D
Potter, SC
Pouta, A
Province, MA
Psaty, BM
Rathmann, W
Rayner, NW
Rice, K
Ripatti, S
Rivadeneira, F
Roden, M
Rolandsson, O
Sandbaek, A
Sandhu, M
Sanna, S
Sayer, AA
Scheet, P
Scott, LJ
Seedorf, U
Sharp, SJ
Shields, B
Sigurosson, G
Sijbrands, EJG
Silveira, A
Simpson, L
Singleton, A
Smith, NL
Sovio, U
Swift, A
Syddall, H
Syvanen, AC
Tanaka, T
Thorand, B
Tichet, J
Tonjes, A
Tuomi, T
Uitterlinden, AG
van Dijk, KW
van Hoek, M
Varma, D
Visvikis-Siest, S
Vitart, V
Vogelzangs, N
Waeber, G
Wagner, PJ
Walley, A
Walters, GB
Ward, KL
Watkins, H
Weedon, MN
Wild, SH
Willemsen, G
Witteman, JCM
Yarnell, JWG
Zeggini, E
Zelenika, D
Zethelius, B
Zhai, GJ
Zhao, JH
Zillikens, MC
Borecki, IB
Loos, RJF
Meneton, P
Magnusson, PKE
Nathan, DM
Williams, GH
Hattersley, AT
Silander, K
Salomaa, V
Smith, GD
Bornstein, SR
Schwarz, P
Spranger, J
Karpe, F
Shuldiner, AR
Cooper, C
Dedoussis, GV
Serrano-Rios, M
Morris, AD
Lind, L
Palmer, LJ
Hu, FB
Franks, PW
Ebrahim, S
Marmot, M
Kao, WHL
Pankow, JS
Sampson, MJ
Kuusisto, J
Laakso, M
Hansen, T
Pedersen, O
Pramstaller, PP
Wichmann, HE
Illig, T
Rudan, I
Wright, AF
Stumvoll, M
Campbell, H
Wilson, JF
Bergman, RN
Buchanan, TA
Collins, FS
Mohlke, KL
Tuomilehto, J
Valle, TT
Altshuler, D
Rotter, JI
Siscovick, DS
Penninx, BWJH
Boomsma, DI
Deloukas, P
Spector, TD
Frayling, TM
Ferrucci, L
Kong, A
Thorsteinsdottir, U
Stefansson, K
van Duijn, CM
Aulchenko, YS
Cao, A
Scuteri, A
Schlessinger, D
Uda, M
Ruokonen, A
Jarvelin, MR
Waterworth, DM
Vollenweider, P
Peltonen, L
Mooser, V
Abecasis, GR
Wareham, NJ
Sladek, R
Froguel, P
Watanabe, RM
Meigs, JB
Groop, L
Boehnke, M
McCarthy, MI
Florez, JC
Barroso, I
AF Dupuis, Josee
Langenberg, Claudia
Prokopenko, Inga
Saxena, Richa
Soranzo, Nicole
Jackson, Anne U.
Wheeler, Eleanor
Glazer, Nicole L.
Bouatia-Naji, Nabila
Gloyn, Anna L.
Lindgren, Cecilia M.
Magi, Reedik
Morris, Andrew P.
Randall, Joshua
Johnson, Toby
Elliott, Paul
Rybin, Denis
Thorleifsson, Gudmar
Steinthorsdottir, Valgerdur
Henneman, Peter
Grallert, Harald
Dehghan, Abbas
Hottenga, Jouke Jan
Franklin, Christopher S.
Navarro, Pau
Song, Kijoung
Goel, Anuj
Perry, John R. B.
Egan, Josephine M.
Lajunen, Taina
Grarup, Niels
Sparso, Thomas
Doney, Alex
Voight, Benjamin F.
Stringham, Heather M.
Li, Man
Kanoni, Stavroula
Shrader, Peter
Cavalcanti-Proenca, Christine
Kumari, Meena
Qi, Lu
Timpson, Nicholas J.
Gieger, Christian
Zabena, Carina
Rocheleau, Ghislain
Ingelsson, Erik
An, Ping
O'Connell, Jeffrey
Luan, Jian'an
Elliott, Amanda
McCarroll, Steven A.
Payne, Felicity
Roccasecca, Rosa Maria
Pattou, Francois
Sethupathy, Praveen
Ardlie, Kristin
Ariyurek, Yavuz
Balkau, Beverley
Barter, Philip
Beilby, John P.
Ben-Shlomo, Yoav
Benediktsson, Rafn
Bennett, Amanda J.
Bergmann, Sven
Bochud, Murielle
Boerwinkle, Eric
Bonnefond, Amelie
Bonnycastle, Lori L.
Borch-Johnsen, Knut
Boettcher, Yvonne
Brunner, Eric
Bumpstead, Suzannah J.
Charpentier, Guillaume
Chen, Yii-Der Ida
Chines, Peter
Clarke, Robert
Coin, Lachlan J. M.
Cooper, Matthew N.
Cornelis, Marilyn
Crawford, Gabe
Crisponi, Laura
Day, Ian N. M.
de Geus, Eco J. C.
Delplanque, Jerome
Dina, Christian
Erdos, Michael R.
Fedson, Annette C.
Fischer-Rosinsky, Antje
Forouhi, Nita G.
Fox, Caroline S.
Frants, Rune
Franzosi, Maria Grazia
Galan, Pilar
Goodarzi, Mark O.
Graessler, Juergen
Groves, Christopher J.
Grundy, Scott
Gwilliam, Rhian
Gyllensten, Ulf
Hadjadj, Samy
Hallmans, Goeran
Hammond, Naomi
Han, Xijing
Hartikainen, Anna-Liisa
Hassanali, Neelam
Hayward, Caroline
Heath, Simon C.
Hercberg, Serge
Herder, Christian
Hicks, Andrew A.
Hillman, David R.
Hingorani, Aroon D.
Hofman, Albert
Hui, Jennie
Hung, Joe
Isomaa, Bo
Johnson, Paul R. V.
Jorgensen, Torben
Jula, Antti
Kaakinen, Marika
Kaprio, Jaakko
Kesaniemi, Y. Antero
Kivimaki, Mika
Knight, Beatrice
Koskinen, Seppo
Kovacs, Peter
Kyvik, Kirsten Ohm
Lathrop, G. Mark
Lawlor, Debbie A.
Le Bacquer, Olivier
Lecoeur, Cecile
Li, Yun
Lyssenko, Valeriya
Mahley, Robert
Mangino, Massimo
Manning, Alisa K.
Teresa Martinez-Larrad, Maria
McAteer, Jarred B.
McCulloch, Laura J.
McPherson, Ruth
Meisinger, Christa
Melzer, David
Meyre, David
Mitchell, Braxton D.
Morken, Mario A.
Mukherjee, Sutapa
Naitza, Silvia
Narisu, Narisu
Neville, Matthew J.
Oostra, Ben A.
Orru, Marco
Pakyz, Ruth
Palmer, Colin N. A.
Paolisso, Giuseppe
Pattaro, Cristian
Pearson, Daniel
Peden, John F.
Pedersen, Nancy L.
Perola, Markus
Pfeiffer, Andreas F. H.
Pichler, Irene
Polasek, Ozren
Posthuma, Danielle
Potter, Simon C.
Pouta, Anneli
Province, Michael A.
Psaty, Bruce M.
Rathmann, Wolfgang
Rayner, Nigel W.
Rice, Kenneth
Ripatti, Samuli
Rivadeneira, Fernando
Roden, Michael
Rolandsson, Olov
Sandbaek, Annelli
Sandhu, Manjinder
Sanna, Serena
Sayer, Avan Aihie
Scheet, Paul
Scott, Laura J.
Seedorf, Udo
Sharp, Stephen J.
Shields, Beverley
Sigurosson, Gunnar
Sijbrands, Eric J. G.
Silveira, Angela
Simpson, Laila
Singleton, Andrew
Smith, Nicholas L.
Sovio, Ulla
Swift, Amy
Syddall, Holly
Syvanen, Ann-Christine
Tanaka, Toshiko
Thorand, Barbara
Tichet, Jean
Tonjes, Anke
Tuomi, Tiinamaija
Uitterlinden, Andre G.
van Dijk, Ko Willems
van Hoek, Mandy
Varma, Dhiraj
Visvikis-Siest, Sophie
Vitart, Veronique
Vogelzangs, Nicole
Waeber, Gerard
Wagner, Peter J.
Walley, Andrew
Walters, G. Bragi
Ward, Kim L.
Watkins, Hugh
Weedon, Michael N.
Wild, Sarah H.
Willemsen, Gonneke
Witteman, Jaqueline C. M.
Yarnell, John W. G.
Zeggini, Eleftheria
Zelenika, Diana
Zethelius, Bjorn
Zhai, Guangju
Zhao, Jing Hua
Zillikens, M. Carola
Borecki, Ingrid B.
Loos, Ruth J. F.
Meneton, Pierre
Magnusson, Patrik K. E.
Nathan, David M.
Williams, Gordon H.
Hattersley, Andrew T.
Silander, Kaisa
Salomaa, Veikko
Smith, George Davey
Bornstein, Stefan R.
Schwarz, Peter
Spranger, Joachim
Karpe, Fredrik
Shuldiner, Alan R.
Cooper, Cyrus
Dedoussis, George V.
Serrano-Rios, Manuel
Morris, Andrew D.
Lind, Lars
Palmer, Lyle J.
Hu, Frank B.
Franks, Paul W.
Ebrahim, Shah
Marmot, Michael
Kao, W. H. Linda
Pankow, James S.
Sampson, Michael J.
Kuusisto, Johanna
Laakso, Markku
Hansen, Torben
Pedersen, Oluf
Pramstaller, Peter Paul
Wichmann, H. Erich
Illig, Thomas
Rudan, Igor
Wright, Alan F.
Stumvoll, Michael
Campbell, Harry
Wilson, James F.
Bergman, Richard N.
Buchanan, Thomas A.
Collins, Francis S.
Mohlke, Karen L.
Tuomilehto, Jaakko
Valle, Timo T.
Altshuler, David
Rotter, Jerome I.
Siscovick, David S.
Penninx, Brenda W. J. H.
Boomsma, Dorret I.
Deloukas, Panos
Spector, Timothy D.
Frayling, Timothy M.
Ferrucci, Luigi
Kong, Augustine
Thorsteinsdottir, Unnur
Stefansson, Kari
van Duijn, Cornelia M.
Aulchenko, Yurii S.
Cao, Antonio
Scuteri, Angelo
Schlessinger, David
Uda, Manuela
Ruokonen, Aimo
Jarvelin, Marjo-Riitta
Waterworth, Dawn M.
Vollenweider, Peter
Peltonen, Leena
Mooser, Vincent
Abecasis, Goncalo R.
Wareham, Nicholas J.
Sladek, Robert
Froguel, Philippe
Watanabe, Richard M.
Meigs, James B.
Groop, Leif
Boehnke, Michael
McCarthy, Mark I.
Florez, Jose C.
Barroso, Ines
CA DIAGRAM Consortium
GIANT Consortium
Global BPgen Consortium
Anders Hamsten Procardis Consortiu
MAGIC Investigators
TI New genetic loci implicated in fasting glucose homeostasis and their
impact on type 2 diabetes risk
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BETA-CELL DYSFUNCTION; PLASMA-GLUCOSE;
INSULIN-SECRETION; TRIGLYCERIDE LEVELS; ESSENTIAL COMPONENTS; MODEL
ASSESSMENT; COMMON VARIANTS; CIRCADIAN CLOCK; DISEASE RISK
AB Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
C1 [Jackson, Anne U.; Stringham, Heather M.; Han, Xijing; Li, Yun; Lyssenko, Valeriya; Scott, Laura J.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Dupuis, Josee; Manning, Alisa K.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dupuis, Josee; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Langenberg, Claudia; Luan, Jian'an; Forouhi, Nita G.; Sandhu, Manjinder; Sharp, Stephen J.; Zhao, Jing Hua; Loos, Ruth J. F.; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England.
[Prokopenko, Inga; Gloyn, Anna L.; Lindgren, Cecilia M.; Magi, Reedik; Bennett, Amanda J.; Groves, Christopher J.; Hassanali, Neelam; Johnson, Paul R. V.; McCulloch, Laura J.; Neville, Matthew J.; Rayner, Nigel W.; Karpe, Fredrik; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Prokopenko, Inga; Lindgren, Cecilia M.; Magi, Reedik; Morris, Andrew P.; Randall, Joshua; Goel, Anuj; Peden, John F.; Rayner, Nigel W.; Watkins, Hugh; Zeggini, Eleftheria; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Saxena, Richa; Voight, Benjamin F.; Elliott, Amanda; McCarroll, Steven A.; Crawford, Gabe; McAteer, Jarred B.; Altshuler, David; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Saxena, Richa; Voight, Benjamin F.; Elliott, Amanda; McCarroll, Steven A.; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Soranzo, Nicole; Bumpstead, Suzannah J.; Gwilliam, Rhian; Hammond, Naomi; Potter, Simon C.; Varma, Dhiraj; Zeggini, Eleftheria; Deloukas, Panos; Spector, Timothy D.; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England.
[Soranzo, Nicole; Mangino, Massimo; Zhai, Guangju; Spector, Timothy D.] Kings Coll London, Twin Res & Genet Epidemiol Dept, London WC2R 2LS, England.
[Wheeler, Eleanor; Payne, Felicity; Roccasecca, Rosa Maria; Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge, England.
[Glazer, Nicole L.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Glazer, Nicole L.; Psaty, Bruce M.; Ferrucci, Luigi] Univ Washington, Dept Med, Seattle, WA USA.
[Bouatia-Naji, Nabila; Cavalcanti-Proenca, Christine; Bonnefond, Amelie; Delplanque, Jerome; Dina, Christian; Le Bacquer, Olivier; Lecoeur, Cecile; Meyre, David; Froguel, Philippe] Univ Lille 2, Inst Pasteur, CNRS, Unite Mixte Rech 8090, Lille, France.
[Johnson, Toby; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Johnson, Toby; Bochud, Murielle] CHU Vaudois, Univ Inst Social & Preventat Med, CH-1011 Lausanne, Switzerland.
[Johnson, Toby; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Elliott, Paul; Coin, Lachlan J. M.; Sovio, Ulla; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Publ Hlth, London, England.
[Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Walters, G. Bragi; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Henneman, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Grallert, Harald; Gieger, Christian; Meisinger, Christa; Thorand, Barbara; Wichmann, H. Erich; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany.
[Dehghan, Abbas; Hofman, Albert; Rivadeneira, Fernando; Sijbrands, Eric J. G.; Uitterlinden, Andre G.; Witteman, Jaqueline C. M.; van Duijn, Cornelia M.; Aulchenko, Yurii S.] Erasmus Med Coll, Dept Epidemiol, Rotterdam, Netherlands.
[Hottenga, Jouke Jan; de Geus, Eco J. C.; Posthuma, Danielle; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Franklin, Christopher S.; Wild, Sarah H.; Rudan, Igor; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Navarro, Pau; Hayward, Caroline; Vitart, Veronique; Wright, Alan F.] Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Song, Kijoung; Waterworth, Dawn M.; Mooser, Vincent] GlaxoSmithKline Inc, Div Genet Res & Dev, King Of Prussia, PA USA.
[Goel, Anuj; Peden, John F.; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Perry, John R. B.; Knight, Beatrice; Melzer, David; Shields, Beverley; Weedon, Michael N.; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Inst Biomed & Clin Sci, Exeter, Devon, England.
[Thorsteinsdottir, Unnur; Stefansson, Kari] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Lajunen, Taina] Univ Oulu, Bioctr, Natl Inst Hlth & Welf, Unit Child & Adolescent Hlth & Welf, Oulu, Finland.
[Grarup, Niels; Sparso, Thomas; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark.
[Doney, Alex] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med & Therapeut, Level 7, Dundee DD1 9SY, Scotland.
[Li, Man] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Kanoni, Stavroula; Dedoussis, George V.] Harokopio Univ, Dept Nutr Dietet, Athens, Greece.
[Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Kumari, Meena; Brunner, Eric; Hingorani, Aroon D.; Kivimaki, Mika; Marmot, Michael] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Qi, Lu; Cornelis, Marilyn; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Qi, Lu; Cornelis, Marilyn; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Timpson, Nicholas J.; Day, Ian N. M.; Lawlor, Debbie A.; Smith, George Davey] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England.
[Zabena, Carina; Teresa Martinez-Larrad, Maria; Serrano-Rios, Manuel] Hosp Clin San Carlos, Fdn Invest Biomed, Madrid, Spain.
[Rocheleau, Ghislain; Sladek, Robert] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Rocheleau, Ghislain; Sladek, Robert] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Rocheleau, Ghislain; Sladek, Robert] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Ingelsson, Erik; Pedersen, Nancy L.; Magnusson, Patrik K. E.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Ingelsson, Erik; Zethelius, Bjorn] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[An, Ping; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
[O'Connell, Jeffrey; Mitchell, Braxton D.; Pakyz, Ruth; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Pattou, Francois] Univ Lille Nord France, INSERM, U859, Lille, France.
[Sethupathy, Praveen; Bonnycastle, Lori L.; Chines, Peter; Erdos, Michael R.; Morken, Mario A.; Narisu, Narisu; Pearson, Daniel; Swift, Amy; Collins, Francis S.; Schlessinger, David] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Ariyurek, Yavuz] Leiden Univ, Med Ctr, Leiden Genome Technol Ctr, Leiden, Netherlands.
[Balkau, Beverley] Univ Paris 11, INSERM, U780, Villejuif, France.
[Barter, Philip] Heart Res Inst, Sydney, NSW, Australia.
[Beilby, John P.; Hui, Jennie] QEII Med Ctr, Dept Mol Genet, PathW Lab Western Australia, Nedlands, WA, Australia.
[Beilby, John P.] Univ Western Australia, Sch Surg & Pathol, Nedlands, WA 6009, Australia.
[Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Benediktsson, Rafn; Sigurosson, Gunnar] Landspitali Univ Hosp, Reykjavik, Iceland.
[Benediktsson, Rafn; Sigurosson, Gunnar] Iceland Heart Assoc, Kopavogur, Iceland.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Borch-Johnsen, Knut] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Borch-Johnsen, Knut; Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark.
[Boettcher, Yvonne; Tonjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Charpentier, Guillaume] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Essonnes, France.
[Chen, Yii-Der Ida; Goodarzi, Mark O.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England.
[Clarke, Robert] Univ Oxford, Epidemiol Studies Unit, Oxford, England.
[Cooper, Matthew N.; Fedson, Annette C.; Simpson, Laila; Ward, Kim L.; Palmer, Lyle J.] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Perth, WA 6009, Australia.
[Crisponi, Laura; Naitza, Silvia; Orru, Marco; Sanna, Serena; Cao, Antonio; Scuteri, Angelo; Uda, Manuela] Cittadella Univ Monserrato, CNR, INN, Cagliari, Italy.
[Fedson, Annette C.; Hillman, David R.; Mukherjee, Sutapa; Simpson, Laila; Ward, Kim L.; Palmer, Lyle J.] Queen Elizabeth II Med Ctr, Western Australian Sleep Disorders Res Inst, Perth, WA, Australia.
[Fischer-Rosinsky, Antje; Pfeiffer, Andreas F. H.; Spranger, Joachim] Charite, Dept Endocrinol Diabetol & Nutr, D-13353 Berlin, Germany.
[Fischer-Rosinsky, Antje; Pfeiffer, Andreas F. H.; Spranger, Joachim] German Inst Human Nutr Potsdam Rehbrucke, Dept Clin Nutr, Nuthetal, Germany.
[Fox, Caroline S.; Williams, Gordon H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Frants, Rune; van Dijk, Ko Willems] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Franzosi, Maria Grazia] Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
[Galan, Pilar] Univ Paris 13, INRA, INSERM, Bobigny, France.
[Graessler, Juergen; Bornstein, Stefan R.; Schwarz, Peter] Univ Dresden, Dept Med 3, Div Prevent & Care Diabet, Dresden, Germany.
[Grundy, Scott] Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dallas, TX 75390 USA.
[Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden.
[Hadjadj, Samy] Univ Poitiers, Unite Format & Rech, Ctr Hosp Univ Poitiers, INSERM,U927,CIC 0802, Poitiers, France.
[Hallmans, Goeran] Umea Univ, Sect Nutr Res, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Hartikainen, Anna-Liisa] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland.
[Heath, Simon C.; Lathrop, G. Mark; Zelenika, Diana] CEA, Inst Genom, Ctr Natl Genotypage, Evry, France.
[Hercberg, Serge; Meneton, Pierre] Fac Med Paris Descartes, INSERM, U872, Paris, France.
[Herder, Christian; Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.
[Hicks, Andrew A.; Pattaro, Cristian; Pichler, Irene; Pramstaller, Peter Paul] European Acad Bozen Bolzano, Inst Med Genet, Bolzano, Italy.
[Hicks, Andrew A.; Pattaro, Cristian; Pichler, Irene; Pramstaller, Peter Paul] Univ Lubeck, Affiliated Inst, Lubeck, Germany.
[Hillman, David R.; Mukherjee, Sutapa] Sir Charles Gairdner Hosp, Dept Pulm Physiol, Perth, WA, Australia.
[Hui, Jennie; Palmer, Lyle J.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Fdn, Perth, WA, Australia.
[Hung, Joe] Sir Charles Gairdner Hosp, Heart Inst Western Australia, Nedlands, WA 6009, Australia.
[Hung, Joe] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia.
[Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland.
[Isomaa, Bo] Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland.
[Johnson, Paul R. V.] Univ Oxford, Nuffield Dept Surg, Oxford, England.
[Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.
[Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark.
[Jula, Antti] Natl Inst Hlth & Welf, Unit Populat Studies, Turku, Finland.
[Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Kaprio, Jaakko; Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Fac Med, Helsinki, Finland.
[Kaprio, Jaakko] Natl Inst Hlth & Welf, Unit Child & Adolescent Mental Hlth, Helsinki, Finland.
[Kaprio, Jaakko; Perola, Markus; Ripatti, Samuli; Wagner, Peter J.; Silander, Kaisa; Peltonen, Leena] Univ Helsinki, Inst tute Mol Med Finland FIMM, Helsinki, Finland.
[Kesaniemi, Y. Antero] Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland.
[Koskinen, Seppo] Natl Inst Hlth & Welf, Unit Living Condit Hlth & Wellbeing, Helsinki, Finland.
[Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
[Kyvik, Kirsten Ohm] Univ So Denmark, Inst Publ Hlth, Danish Twin Registry, Odense, Denmark.
[Lyssenko, Valeriya; Groop, Leif] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
[Mahley, Robert] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA.
[McAteer, Jarred B.; Nathan, David M.; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[McAteer, Jarred B.; Nathan, David M.; Williams, Gordon H.; Altshuler, David; Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[McPherson, Ruth] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON, Canada.
[Neville, Matthew J.; Karpe, Fredrik; McCarthy, Mark I.] Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England.
[Oostra, Ben A.] Erasmus Med Coll, Dept Clin Genet, Rotterdam, Netherlands.
[Palmer, Colin N. A.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Inst, Dundee DD1 9SY, Scotland.
[Paolisso, Giuseppe] Univ Naples 2, Dept Geriatr Med & Metab Dis, Naples, Italy.
[Perola, Markus; Ripatti, Samuli; Wagner, Peter J.; Silander, Kaisa; Peltonen, Leena] Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki, Finland.
[Perola, Markus; Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Polasek, Ozren] Univ Zagreb, Andrija Stampar Sch Publ Hlth, Sch Med, Dept Med Stat Epidemiol & Med Informat, Zagreb 41000, Croatia.
[Posthuma, Danielle] VU Univ & Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Pouta, Anneli] Oulu Univ Hosp, Dept Obstet & Gynaecol, Oulu, Finland.
[Psaty, Bruce M.; Smith, Nicholas L.; Ferrucci, Luigi] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany.
[Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Rivadeneira, Fernando; Sijbrands, Eric J. G.; Uitterlinden, Andre G.; van Hoek, Mandy; Zillikens, M. Carola] Erasmus Med Coll, Dept Internal Med, Rotterdam, Netherlands.
[Roden, Michael] Univ Dusseldorf, Dept Metab Dis, Dusseldorf, Germany.
[Rolandsson, Olov] Umea Univ, Sect Family Med, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Sandbaek, Annelli] Univ Aarhus, Dept Gen Practice, Sch Publ Hlth, Aarhus, Denmark.
[Sandhu, Manjinder] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
[Sayer, Avan Aihie; Syddall, Holly; Cooper, Cyrus] Univ Southampton, Southampton Gen Hosp, MRC, Epidemiol Resource Ctr, Southampton, Hants, England.
[Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Seedorf, Udo] Univ Munster, Leibniz Inst Arterioskleroseforsch, Munster, Germany.
[Silveira, Angela; Anders Hamsten Procardis Consortiu] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, Stockholm, Sweden.
[Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA USA.
[Syvanen, Ann-Christine; Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Tanaka, Toshiko] MedStar Res Inst, Baltimore, MD USA.
[Tichet, Jean] Inst Interreg Sante IRSA, La Riche, France.
[Tonjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany.
[Tuomi, Tiinamaija] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland.
[van Dijk, Ko Willems] Leiden Univ, Med Ctr, Dept Internal Med, Leiden, Netherlands.
[Visvikis-Siest, Sophie] Nancy Univ Henri Poincare, Res Unit, Nancy, France.
[Vogelzangs, Nicole; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Waeber, Gerard; Vollenweider, Peter] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Walley, Andrew; Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England.
[Yarnell, John W. G.] Queens Univ Belfast, Belfast, Antrim, North Ireland.
[Zethelius, Bjorn] Med Prod Agcy, Uppsala, Sweden.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Unit Chron Dis Epidemiol & Prevent, Helsinki, Finland.
[Hu, Frank B.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Franks, Paul W.] Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden.
[Ebrahim, Shah] London Sch Hyg & Trop Med, London WC1, England.
[Kao, W. H. Linda] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Kao, W. H. Linda] Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Sampson, Michael J.] Norfolk & Norwich Univ Hosp Natl Hlth Serv Trust, Dept Endocrinol & Diabet, Norwich, Norfolk, England.
[Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark.
[Pramstaller, Peter Paul] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter Paul] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Wichmann, H. Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H. Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Rudan, Igor] Univ Split, Sch Med, Split, Croatia.
[Rudan, Igor] Gen Info Ltd, Zagreb, Croatia.
[Bergman, Richard N.; Buchanan, Thomas A.; Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol, Dept Med, Los Angeles, CA 90033 USA.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Tuomilehto, Jaakko; Valle, Timo T.] Natl Inst Hlth & Welf, Unit Diabet Prevent, Helsinki, Finland.
[Siscovick, David S.] S Ostrobothnia Cent Hosp, Seinajoki, Finland.
[Scuteri, Angelo] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Ruokonen, Aimo] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Jarvelin, Marjo-Riitta] Univ Oulu, Dept Clin Sci Clin Chem, Oulu, Finland.
Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC, Hlth Protect Agcy Ctr Environm & Hlth, London, England.
RP Boehnke, M (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
EM boehnke@umich.edu; mark.mccarthy@drl.ox.ac.uk; jcflorez@partners.org;
ib1@sanger.ac.uk
RI Elliott, Amanda/G-5120-2012; Kaprio, Jaakko/A-1820-2008; Rudan,
Igor/I-1467-2012; Heath, Simon/J-4138-2012; Rice, Kenneth/A-4150-2013;
Deloukas, Panos/B-2922-2013; Lajunen, Taina/J-7337-2013; Colaus,
PsyColaus/K-6607-2013; Aulchenko, Yurii/M-8270-2013; van Hoek,
Mandy/B-9325-2014; Meisinger, Christine/B-5358-2014; Visvikis-Siest,
Sophie/H-2324-2014; Walley, Andrew/D-2573-2009; Grarup,
Niels/K-2807-2015; Kyvik, Kirsten /K-5680-2016; Study,
GoDARTS/K-9448-2016; mangino, massimo/F-5134-2011; Hayward,
Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Coin,
Lachlan/A-9001-2014; Schwarz, Peter/B-5127-2013; Davey Smith,
George/A-7407-2013; Magnusson, Patrik/C-4458-2017; Naitza,
Silvia/D-5620-2017; Hicks, Andrew/E-9518-2017; Pramstaller,
Peter/C-2357-2008; Thorand, Barbara/B-5349-2014; Cooper,
Matthew/J-4420-2014; Palmer, Lyle/K-3196-2014; Dina,
Christian/D-3535-2015; SIMPSON, LAILA/O-7281-2014; Boehm,
Bernhard/F-8750-2015; Grallert, Harald/B-3424-2013; Ripatti,
Samuli/H-9446-2014; Wilson, James F/A-5704-2009; de Geus,
Eco/M-9318-2015; Rivadeneira, Fernando/O-5385-2015; Prokopenko,
Inga/H-3241-2014; Willems van Dijk, Ko/A-1798-2008; Abecasis,
Goncalo/B-7840-2010; Bochud, Murielle/A-3981-2010; Polasek,
Ozren/B-6002-2011; Altshuler, David/A-4476-2009; Meyre,
David/D-7315-2011; Singleton, Andrew/C-3010-2009; Voight,
Benjamin/F-1775-2011; Brunner, Eric/H-2114-2011; Aihie Sayer,
Avan/A-4359-2012; Palmer, Colin/C-7053-2008; Kivimaki, Mika/B-3607-2012;
Spector, Tim/F-6533-2012
OI Lawlor, Debbie A/0000-0002-6793-2262; Payne,
Felicity/0000-0003-4228-581X; Pankow, James/0000-0001-7076-483X;
Bergmann, Sven/0000-0002-6785-9034; Dehghan, Abbas/0000-0001-6403-016X;
Rudan, Igor/0000-0001-6993-6884; Rice, Kenneth/0000-0001-5779-4495;
Deloukas, Panos/0000-0001-9251-070X; Aulchenko,
Yurii/0000-0002-7899-1575; Visvikis-Siest, Sophie/0000-0001-8104-8425;
sanna, serena/0000-0002-3768-1749; Kivimaki, Mika/0000-0002-4699-5627;
Monsalve, Beatriz Elena/0000-0002-5994-866X; Johnson,
Toby/0000-0002-5998-3270; Aihie Sayer, Avan/0000-0003-1283-6457;
Abecasis, Goncalo/0000-0003-1509-1825; Zeggini,
Eleftheria/0000-0003-4238-659X; Tuomi, Tiinamaija/0000-0002-8306-6202;
Karpe, Fredrik/0000-0002-2751-1770; Jorgensen,
Torben/0000-0001-9453-2830; Watkins, Hugh/0000-0002-5287-9016; Sladek,
Robert/0000-0002-2730-1204; Marmot, Michael/0000-0002-2431-6419;
Mitchell, Braxton/0000-0003-4920-4744; Kaprio,
Jaakko/0000-0002-3716-2455; Timpson, Nicholas/0000-0002-7141-9189;
Dupuis, Josee/0000-0003-2871-3603; Gieger,
Christian/0000-0001-6986-9554; Kumari, Meena/0000-0001-9716-1035;
Melzer, David/0000-0002-0170-3838; Forouhi, Nita/0000-0002-5041-248X;
Seedorf, Udo/0000-0003-4652-5358; Magi, Reedik/0000-0002-2964-6011;
Soranzo, Nicole/0000-0003-1095-3852; Bouatia-Naji,
Nabila/0000-0001-5424-2134; Meisinger, Christa/0000-0002-9026-6544;
Kaakinen, Marika/0000-0002-9228-0462; Walley,
Andrew/0000-0001-7707-7549; Pichler, Irene/0000-0001-8251-0757;
Sijbrands, Eric/0000-0001-8857-7389; Paolisso,
Giuseppe/0000-0002-2137-455X; Rybin, Denis/0000-0002-3657-4829; Grarup,
Niels/0000-0001-5526-1070; Kyvik, Kirsten /0000-0003-2981-0245; mangino,
massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550;
Coin, Lachlan/0000-0002-4300-455X; Schwarz, Peter/0000-0001-6317-7880;
Davey Smith, George/0000-0002-1407-8314; Hicks,
Andrew/0000-0001-6320-0411; Thorand, Barbara/0000-0002-8416-6440;
Cooper, Matthew/0000-0003-1139-3682; Palmer, Lyle/0000-0002-1628-3055;
Dina, Christian/0000-0002-7722-7348; SIMPSON, LAILA/0000-0001-7189-4791;
Ripatti, Samuli/0000-0002-0504-1202; Wilson, James
F/0000-0001-5751-9178; de Geus, Eco/0000-0001-6022-2666; Rivadeneira,
Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457;
Willems van Dijk, Ko/0000-0002-2172-7394; Bochud,
Murielle/0000-0002-5727-0218; Polasek, Ozren/0000-0002-5765-1862;
Altshuler, David/0000-0002-7250-4107; Palmer, Colin/0000-0002-6415-6560;
FU British Heart Foundation [RG/07/008/23674]; Chief Scientist Office
[CZB/4/710]; Medical Research Council [G0100222, G0600331, G0600705,
G0601261, G0700222, G0700222(81696), G0701863, G0801056, G0902037,
G19/35, G8802774, MC_U106179471, MC_U106188470, MC_U127561128,
MC_U127592696, MC_U137686857, MC_UP_A620_1014, MC_UP_A620_1015]; NIDDK
NIH HHS [K24 DK080140, P30 DK040561, P30 DK040561-14, R01 DK029867, R01
DK072193, R01 DK078616, R01 DK078616-01A1]; The Dunhill Medical Trust
[R69/0208]; Wellcome Trust [064890, 077011, 077016, 081682, 088885,
089061, 090532, 091746]
NR 74
TC 927
Z9 946
U1 21
U2 155
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD FEB
PY 2010
VL 42
IS 2
BP 105
EP U32
DI 10.1038/ng.520
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 549WG
UT WOS:000274084400005
PM 20081858
ER
PT J
AU Saxena, R
Hivert, MF
Langenberg, C
Tanaka, T
Pankow, JS
Vollenweider, P
Lyssenko, V
Bouatia-Naji, N
Dupuis, J
Jackson, AU
Kao, WHL
Li, M
Glazer, NL
Manning, AK
Luan, J
Stringham, HM
Prokopenko, I
Johnson, T
Grarup, N
Boesgaard, TW
Lecoeur, C
Shrader, P
O'Connell, J
Ingelsson, E
Couper, DJ
Rice, K
Song, KJ
Andreasen, CH
Dina, C
Kottgen, A
Le Bacquer, O
Pattou, F
Taneera, J
Steinthorsdottir, V
Rybin, D
Ardlie, K
Sampson, M
Qi, L
van Hoek, M
Weedon, MN
Aulchenko, YS
Voight, BF
Grallert, H
Balkau, B
Bergman, RN
Bielinski, SJ
Bonnefond, A
Bonnycastle, LL
Borch-Johnsen, K
Boettcher, Y
Brunner, E
Buchanan, TA
Bumpstead, SJ
Cavalcanti-Proenca, C
Charpentier, G
Chen, YDI
Chines, PS
Collins, FS
Cornelis, M
Crawford, GJ
Delplanque, J
Doney, A
Egan, JM
Erdos, MR
Firmann, M
Forouhi, NG
Fox, CS
Goodarzi, MO
Graessler, J
Hingorani, A
Isomaa, B
Jorgensen, T
Kivimaki, M
Kovacs, P
Krohn, K
Kumari, M
Lauritzen, T
Levy-Marchal, C
Mayor, V
McAteer, JB
Meyre, D
Mitchell, BD
Mohlke, KL
Morken, MA
Narisu, N
Palmer, CNA
Pakyz, R
Pascoe, L
Payne, F
Pearson, D
Rathmann, W
Sandbaek, A
Sayer, AA
Scott, LJ
Sharp, SJ
Sijbrands, E
Singleton, A
Siscovick, DS
Smith, NL
Sparso, T
Swift, AJ
Syddall, H
Thorleifsson, G
Tonjes, A
Tuomi, T
Tuomilehto, J
Valle, TT
Waeber, G
Walley, A
Waterworth, DM
Zeggini, E
Zhao, JH
Illig, T
Wichmann, HE
Wilson, JF
van Duijn, C
Hu, FB
Morris, AD
Frayling, TM
Hattersley, AT
Thorsteinsdottir, U
Stefansson, K
Nilsson, P
Syvanen, AC
Shuldiner, AR
Walker, M
Bornstein, SR
Schwarz, P
Williams, GH
Nathan, DM
Kuusisto, J
Laakso, M
Cooper, C
Marmot, M
Ferrucci, L
Mooser, V
Stumvoll, M
Loos, RJF
Altshuler, D
Psaty, BM
Rotter, JI
Boerwinkle, E
Hansen, T
Pedersen, O
Florez, JC
McCarthy, MI
Boehnke, M
Barroso, I
Sladek, R
Froguel, P
Meigs, JB
Groop, L
Wareham, NJ
Watanabe, RM
AF Saxena, Richa
Hivert, Marie-France
Langenberg, Claudia
Tanaka, Toshiko
Pankow, James S.
Vollenweider, Peter
Lyssenko, Valeriya
Bouatia-Naji, Nabila
Dupuis, Josee
Jackson, Anne U.
Kao, W. H. Linda
Li, Man
Glazer, Nicole L.
Manning, Alisa K.
Luan, Jian'an
Stringham, Heather M.
Prokopenko, Inga
Johnson, Toby
Grarup, Niels
Boesgaard, Trine W.
Lecoeur, Cecile
Shrader, Peter
O'Connell, Jeffrey
Ingelsson, Erik
Couper, David J.
Rice, Kenneth
Song, Kijoung
Andreasen, Camilla H.
Dina, Christian
Koettgen, Anna
Le Bacquer, Olivier
Pattou, Francois
Taneera, Jalal
Steinthorsdottir, Valgerdur
Rybin, Denis
Ardlie, Kristin
Sampson, Michael
Qi, Lu
van Hoek, Mandy
Weedon, Michael N.
Aulchenko, Yurii S.
Voight, Benjamin F.
Grallert, Harald
Balkau, Beverley
Bergman, Richard N.
Bielinski, Suzette J.
Bonnefond, Amelie
Bonnycastle, Lori L.
Borch-Johnsen, Knut
Boettcher, Yvonne
Brunner, Eric
Buchanan, Thomas A.
Bumpstead, Suzannah J.
Cavalcanti-Proenca, Christine
Charpentier, Guillaume
Chen, Yii-Der Ida
Chines, Peter S.
Collins, Francis S.
Cornelis, Marilyn
Crawford, Gabriel J.
Delplanque, Jerome
Doney, Alex
Egan, Josephine M.
Erdos, Michael R.
Firmann, Mathieu
Forouhi, Nita G.
Fox, Caroline S.
Goodarzi, Mark O.
Graessler, Juergen
Hingorani, Aroon
Isomaa, Bo
Jorgensen, Torben
Kivimaki, Mika
Kovacs, Peter
Krohn, Knut
Kumari, Meena
Lauritzen, Torsten
Levy-Marchal, Claire
Mayor, Vladimir
McAteer, Jarred B.
Meyre, David
Mitchell, Braxton D.
Mohlke, Karen L.
Morken, Mario A.
Narisu, Narisu
Palmer, Colin N. A.
Pakyz, Ruth
Pascoe, Laura
Payne, Felicity
Pearson, Daniel
Rathmann, Wolfgang
Sandbaek, Annelli
Sayer, Avan Aihie
Scott, Laura J.
Sharp, Stephen J.
Sijbrands, Eric
Singleton, Andrew
Siscovick, David S.
Smith, Nicholas L.
Sparso, Thomas
Swift, Amy J.
Syddall, Holly
Thorleifsson, Gudmar
Toenjes, Anke
Tuomi, Tiinamaija
Tuomilehto, Jaakko
Valle, Timo T.
Waeber, Gerard
Walley, Andrew
Waterworth, Dawn M.
Zeggini, Eleftheria
Zhao, Jing Hua
Illig, Thomas
Wichmann, H. Erich
Wilson, James F.
van Duijn, Cornelia
Hu, Frank B.
Morris, Andrew D.
Frayling, Timothy M.
Hattersley, Andrew T.
Thorsteinsdottir, Unnur
Stefansson, Kari
Nilsson, Peter
Syvanen, Ann-Christine
Shuldiner, Alan R.
Walker, Mark
Bornstein, Stefan R.
Schwarz, Peter
Williams, Gordon H.
Nathan, David M.
Kuusisto, Johanna
Laakso, Markku
Cooper, Cyrus
Marmot, Michael
Ferrucci, Luigi
Mooser, Vincent
Stumvoll, Michael
Loos, Ruth J. F.
Altshuler, David
Psaty, Bruce M.
Rotter, Jerome I.
Boerwinkle, Eric
Hansen, Torben
Pedersen, Oluf
Florez, Jose C.
McCarthy, Mark I.
Boehnke, Michael
Barroso, Ines
Sladek, Robert
Froguel, Philippe
Meigs, James B.
Groop, Leif
Wareham, Nicholas J.
Watanabe, Richard M.
CA GIANT Consortium
MAGIC Investigators
TI Genetic variation in GIPR influences the glucose and insulin responses
to an oral glucose challenge
SO NATURE GENETICS
LA English
DT Article
ID FASTING PLASMA-GLUCOSE; GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE
PEPTIDE-1; BETA-CELL FUNCTION; ASSOCIATION; RISK; RECEPTOR; SENSITIVITY;
EXPRESSION; VARIANTS
AB Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).
C1 [Bergman, Richard N.; Buchanan, Thomas A.; Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Saxena, Richa; Voight, Benjamin F.; Crawford, Gabriel J.; McAteer, Jarred B.; Altshuler, David; Florez, Jose C.] Harvard & Massachusetts Inst Technol, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Saxena, Richa; Voight, Benjamin F.; McAteer, Jarred B.; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Hivert, Marie-France; Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Hivert, Marie-France; Williams, Gordon H.; Nathan, David M.; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Langenberg, Claudia; Luan, Jian'an; Forouhi, Nita G.; Sharp, Stephen J.; Zhao, Jing Hua; Loos, Ruth J. F.; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England.
[Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Vollenweider, Peter; Firmann, Mathieu; Mayor, Vladimir; Waeber, Gerard] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Lyssenko, Valeriya; Taneera, Jalal; Groop, Leif] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
[Bouatia-Naji, Nabila; Lecoeur, Cecile; Dina, Christian; Le Bacquer, Olivier; Bonnefond, Amelie; Cavalcanti-Proenca, Christine; Delplanque, Jerome; Meyre, David; Froguel, Philippe] Univ Lille 2, Inst Pasteur, CNRS, Unite Mixte Rech 8090, Lille, France.
[Dupuis, Josee; Manning, Alisa K.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Jackson, Anne U.; Stringham, Heather M.; Scott, Laura J.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Kao, W. H. Linda; Li, Man; Koettgen, Anna] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Kao, W. H. Linda] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Kao, W. H. Linda] Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
[Glazer, Nicole L.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Glazer, Nicole L.; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Johnson, Toby] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Grarup, Niels; Boesgaard, Trine W.; Andreasen, Camilla H.; Sparso, Thomas; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark.
[O'Connell, Jeffrey; Mitchell, Braxton D.; Pakyz, Ruth; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Ingelsson, Erik] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[Couper, David J.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA.
[Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Song, Kijoung; Waterworth, Dawn M.; Mooser, Vincent] GlaxoSmithKline Inc, Drug Discovery, Genet, King Of Prussia, PA USA.
[Pattou, Francois] Univ Lille Nord France, INSERM, Lille, France.
[Pattou, Francois] Ctr Hosp Reg & Univ Lille, F-59037 Lille, France.
[Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Sampson, Michael] Norfolk & Norwich Univ Hosp Natl Hlth Serv Trust, Dept Endocrinol & Diabet, Norwich, Norfolk, England.
[Qi, Lu; Cornelis, Marilyn; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Qi, Lu; Cornelis, Marilyn; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[van Hoek, Mandy; Sijbrands, Eric; van Duijn, Cornelia] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Weedon, Michael N.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Aulchenko, Yurii S.] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
[Grallert, Harald; Illig, Thomas; Wichmann, H. Erich] Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany.
[Balkau, Beverley] INSERM, Villejuif, France.
[Balkau, Beverley] Univ Paris 11, Orsay, France.
[Bielinski, Suzette J.] Mayo Clin, Coll Med, Rochester, MN USA.
[Bonnycastle, Lori L.; Chines, Peter S.; Collins, Francis S.; Erdos, Michael R.; Morken, Mario A.; Narisu, Narisu; Pearson, Daniel; Swift, Amy J.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Borch-Johnsen, Knut] Steno Diabet Ctr, Copenhagen, Denmark.
[Borch-Johnsen, Knut] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark.
[Boettcher, Yvonne; Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Brunner, Eric; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena; Marmot, Michael] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Div Endocrinol, Dept Med, Los Angeles, CA 90033 USA.
[Bumpstead, Suzannah J.; Payne, Felicity; Zeggini, Eleftheria; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge, England.
[Charpentier, Guillaume] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Essonnes, France.
[Chen, Yii-Der Ida; Goodarzi, Mark O.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Doney, Alex] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med & Therapeut, Dundee DD1 9SY, Scotland.
[Egan, Josephine M.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA.
[Fox, Caroline S.; Williams, Gordon H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Graessler, Juergen; Bornstein, Stefan R.; Schwarz, Peter] Univ Dresden, Div Prevent & Care Diabet, Dept Med 3, Dresden, Germany.
[Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland.
[Isomaa, Bo] Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland.
[Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.
[Kovacs, Peter; Krohn, Knut] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
[Lauritzen, Torsten; Sandbaek, Annelli] Univ Aarhus, Dept Gen Practice, Aarhus, Denmark.
[Levy-Marchal, Claire] Robert Debre Hosp, INSERM, Paris, France.
[Levy-Marchal, Claire] Paris Diderot Univ, Paris, France.
[McAteer, Jarred B.; Nathan, David M.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Palmer, Colin N. A.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Inst, Dundee DD1 9SY, Scotland.
[Pascoe, Laura; Walker, Mark] Fac Med Sci, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
[Rathmann, Wolfgang] German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany.
[Sayer, Avan Aihie; Syddall, Holly; Cooper, Cyrus] Univ Southampton, Southampton Gen Hosp, MRC, Epidemiol Resource Ctr, Southampton, Hants, England.
[Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Siscovick, David S.; Smith, Nicholas L.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Smith, Nicholas L.] Off Res & Dev, Dept Vet Affairs, Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Toenjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany.
[Tuomi, Tiinamaija; Tuomilehto, Jaakko] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland.
[Tuomilehto, Jaakko] Natl Publ Hlth Inst, Diabet Unit, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
[Valle, Timo T.] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland.
[Walley, Andrew; Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England.
[Wichmann, H. Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H. Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Hu, Frank B.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Frayling, Timothy M.; Hattersley, Andrew T.] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Nilsson, Peter] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden.
[Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Hansen, Torben] Univ So Denmark, Fac Hlth Sci, Odense, Denmark.
[Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed, DK-1168 Copenhagen, Denmark.
[McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res Biomed Res Ctr, Oxford OX3 7LJ, England.
[Sladek, Robert] McGill Univ, Fac Med, Dept Human Genet, Montreal, PQ, Canada.
[Sladek, Robert] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
RP Watanabe, RM (reprint author), Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
EM jmeigs@partners.org; Leif.Groop@med.lu.se;
nick.wareham@mrc-epid.cam.ac.uk; rwatanab@usc.edu
RI van Hoek, Mandy/B-9325-2014; Dina, Christian/D-3535-2015; Grallert,
Harald/B-3424-2013; Wilson, James F/A-5704-2009; Prokopenko,
Inga/H-3241-2014; Bielinski, Suzette/A-2238-2009; Grarup,
Niels/K-2807-2015; Study, GoDARTS/K-9448-2016; BOUATIA-NAJI,
NABILA/D-5863-2013; Schwarz, Peter/B-5127-2013; Walley,
Andrew/D-2573-2009; Singleton, Andrew/C-3010-2009; Voight,
Benjamin/F-1775-2011; Brunner, Eric/H-2114-2011; Aihie Sayer,
Avan/A-4359-2012; Kivimaki, Mika/B-3607-2012; Kottgen, Anna/D-2920-2012;
Rice, Kenneth/A-4150-2013; Colaus, PsyColaus/K-6607-2013; Aulchenko,
Yurii/M-8270-2013; Palmer, Colin/C-7053-2008; Altshuler,
David/A-4476-2009; Meyre, David/D-7315-2011;
OI Dina, Christian/0000-0002-7722-7348; Wilson, James
F/0000-0001-5751-9178; Prokopenko, Inga/0000-0003-1624-7457; Bielinski,
Suzette/0000-0002-2905-5430; Grarup, Niels/0000-0001-5526-1070; Schwarz,
Peter/0000-0001-6317-7880; Bouatia-Naji, Nabila/0000-0001-5424-2134;
Walley, Andrew/0000-0001-7707-7549; Sijbrands, Eric/0000-0001-8857-7389;
Rice, Kenneth/0000-0001-5779-4495; Aulchenko, Yurii/0000-0002-7899-1575;
Palmer, Colin/0000-0002-6415-6560; Altshuler, David/0000-0002-7250-4107;
Forouhi, Nita/0000-0002-5041-248X; Tuomi,
Tiinamaija/0000-0002-8306-6202; Jorgensen, Torben/0000-0001-9453-2830;
Sladek, Robert/0000-0002-2730-1204; Marmot, Michael/0000-0002-2431-6419;
Mitchell, Braxton/0000-0003-4920-4744; Pankow,
James/0000-0001-7076-483X; Taneera, Jalal/0000-0002-3341-1063; Rybin,
Denis/0000-0002-3657-4829; Kivimaki, Mika/0000-0002-4699-5627; Johnson,
Toby/0000-0002-5998-3270; Aihie Sayer, Avan/0000-0003-1283-6457;
Zeggini, Eleftheria/0000-0003-4238-659X; Dupuis,
Josee/0000-0003-2871-3603; Kumari, Meena/0000-0001-9716-1035
FU British Heart Foundation [RG/07/008/23674]; Chief Scientist Office
[CZB/4/710]; Intramural NIH HHS [Z01 HG000024-14]; Medical Research
Council [G0100222, G0600331, G0701863, G0902037, G19/35, G8802774,
MC_U106179471, MC_U106188470, MC_UP_A620_1014, MC_UP_A620_1015]; NCI NIH
HHS [P01 CA087969, P01 CA087969-12]; NCRR NIH HHS [M01 RR000052, M01
RR000052-46, M01 RR001066-26, M01 RR016500, M01 RR016500-08]; NHGRI NIH
HHS [U01 HG004399, U01 HG004399-02, U01 HG004402, U01 HG004402-02];
NHLBI NIH HHS [N01 HC055022, N01 HC015103, N01 HC025195, N01 HC035129,
N01 HC045133, N01 HC055015, N01 HC055016, N01 HC055018, N01 HC055019,
N01 HC055020, N01 HC055021, N01 HC055222, N01 HC075150, N01 HC085079,
N01 HC085080, N01 HC085081, N01 HC085082, N01 HC085083, N01 HC085084,
N01 HC085085, N01 HC085086, N02 HL64278, R01 HL036310, R01 HL036310-21,
R01 HL059367, R01 HL059367-10, R01 HL086694, R01 HL086694-03, R01
HL087641, R01 HL087641-03, R01 HL087652, R01 HL087652-03, U01 HL072515,
U01 HL072515-06, U01 HL080295, U01 HL080295-04]; NIA NIH HHS [R01
AG013196, R01 AG013196-16]; NIDA NIH HHS [U54 DA021519, U54
DA021519-04]; NIDDK NIH HHS [K23 DK065978, K23 DK065978-05, K24
DK080140, K24 DK080140-04, P30 DK072488, P30 DK072488-06, P30 DK079637,
P60 DK079637, P60 DK079637-04, R01 DK029867, R01 DK054261, R01
DK054261-09, R01 DK058845, R01 DK058845-11, R01 DK062370, R01
DK062370-05, R01 DK069922, R01 DK069922-03, R01 DK072193, R01
DK072193-04, R01 DK078616, R01 DK078616-03, R01 DK091718]; Wellcome
Trust [077016, 088885]
NR 35
TC 300
Z9 307
U1 2
U2 22
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD FEB
PY 2010
VL 42
IS 2
BP 142
EP U75
DI 10.1038/ng.521
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 549WG
UT WOS:000274084400011
PM 20081857
ER
PT J
AU Pfeufer, A
van Noord, C
Marciante, KD
Arking, DE
Larson, MG
Smith, AV
Tarasov, KV
Muller, M
Sotoodehnia, N
Sinner, MF
Verwoert, GC
Li, M
Kao, WHL
Kottgen, A
Coresh, J
Bis, JC
Psaty, BM
Rice, K
Rotter, JI
Rivadeneira, F
Hofman, A
Kors, JA
Stricker, BHC
Uitterlinden, AG
van Duijn, CM
Beckmann, BM
Sauter, W
Gieger, C
Lubitz, SA
Newton-Cheh, C
Wang, TJ
Magnani, JW
Schnabel, RB
Chung, MK
Barnard, J
Smith, JD
Van Wagoner, DR
Vasan, RS
Aspelund, T
Eiriksdottir, G
Harris, TB
Launer, LJ
Najjar, SS
Lakatta, E
Schlessinger, D
Uda, M
Abecasis, GR
Muller-Myhsok, B
Ehret, GB
Boerwinkle, E
Chakravarti, A
Soliman, EZ
Lunetta, KL
Perz, S
Wichmann, HE
Meitinger, T
Levy, D
Gudnason, V
Ellinor, PT
Sanna, S
Kaab, S
Witteman, JCM
Alonso, A
Benjamin, EJ
Heckbert, SR
AF Pfeufer, Arne
van Noord, Charlotte
Marciante, Kristin D.
Arking, Dan E.
Larson, Martin G.
Smith, Albert Vernon
Tarasov, Kirill V.
Mueller, Martina
Sotoodehnia, Nona
Sinner, Moritz F.
Verwoert, Germaine C.
Li, Man
Kao, W. H. Linda
Koettgen, Anna
Coresh, Josef
Bis, Joshua C.
Psaty, Bruce M.
Rice, Kenneth
Rotter, Jerome I.
Rivadeneira, Fernando
Hofman, Albert
Kors, Jan A.
Stricker, Bruno H. C.
Uitterlinden, Andre G.
van Duijn, Cornelia M.
Beckmann, Britt M.
Sauter, Wiebke
Gieger, Christian
Lubitz, Steven A.
Newton-Cheh, Christopher
Wang, Thomas J.
Magnani, Jared W.
Schnabel, Renate B.
Chung, Mina K.
Barnard, John
Smith, Jonathan D.
Van Wagoner, David R.
Vasan, Ramachandran S.
Aspelund, Thor
Eiriksdottir, Gudny
Harris, Tamara B.
Launer, Lenore J.
Najjar, Samer S.
Lakatta, Edward
Schlessinger, David
Uda, Manuela
Abecasis, Goncalo R.
Mueller-Myhsok, Bertram
Ehret, Georg B.
Boerwinkle, Eric
Chakravarti, Aravinda
Soliman, Elsayed Z.
Lunetta, Kathryn L.
Perz, Siegfried
Wichmann, H-Erich
Meitinger, Thomas
Levy, Daniel
Gudnason, Vilmundur
Ellinor, Patrick T.
Sanna, Serena
Kaeaeb, Stefan
Witteman, Jacqueline C. M.
Alonso, Alvaro
Benjamin, Emelia J.
Heckbert, Susan R.
TI Genome-wide association study of PR interval
SO NATURE GENETICS
LA English
DT Article
ID ATRIAL-FIBRILLATION; COMMON VARIANTS; SODIUM-CHANNEL; HEART-RATE;
ATHEROSCLEROSIS RISK; NATIONAL HEART; SYSTEM; DESIGN; INDIVIDUALS;
VARIABILITY
AB The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-nalysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX25 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.
C1 [Pfeufer, Arne; Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80804 Munich, Germany.
[Pfeufer, Arne; Meitinger, Thomas] German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[van Noord, Charlotte; Verwoert, Germaine C.; Rivadeneira, Fernando; Hofman, Albert; Stricker, Bruno H. C.; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[van Noord, Charlotte] Dutch Med Evaluat Board, The Hague, Netherlands.
[van Noord, Charlotte; Witteman, Jacqueline C. M.] Netherlands Consortium Healthy Aging Leiden, Leiden, Netherlands.
[Sotoodehnia, Nona] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA.
[Arking, Dan E.; Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Larson, Martin G.; Wang, Thomas J.; Schnabel, Renate B.; Vasan, Ramachandran S.; Levy, Daniel; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Smith, Albert Vernon; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Heart Prevent Clin & Res Inst, Iceland Heart Assoc, Kopavogur, Iceland.
[Tarasov, Kirill V.; Najjar, Samer S.; Lakatta, Edward] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
[Tarasov, Kirill V.; Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Mueller, Martina; Sauter, Wiebke; Gieger, Christian; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Mueller, Martina; Sinner, Moritz F.; Beckmann, Britt M.; Kaeaeb, Stefan] Univ Munich, Klinikum Grosshadern, Dept Med 1, D-80804 Munich, Germany.
[Verwoert, Germaine C.; Rivadeneira, Fernando; Stricker, Bruno H. C.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Li, Man; Kao, W. H. Linda; Koettgen, Anna; Coresh, Josef] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Res Inst, Seattle, WA USA.
[Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Dept Common Dis Genet Program, Inst Med Genet, W Hollywood, CA USA.
[Kors, Jan A.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
[Stricker, Bruno H. C.] Inspectorate Hlth Care, The Hague, Netherlands.
[Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Lubitz, Steven A.; Newton-Cheh, Christopher; Wang, Thomas J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Newton-Cheh, Christopher; Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Newton-Cheh, Christopher; Wang, Thomas J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Med Clin Cardiol 2, Mainz, Germany.
[Chung, Mina K.; Barnard, John; Smith, Jonathan D.; Van Wagoner, David R.] Cleveland Clin, Heart & Vasc Res Inst, Cleveland, OH 44106 USA.
[Chung, Mina K.; Barnard, John; Smith, Jonathan D.; Van Wagoner, David R.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Heart Prevent Clin & Res Inst, Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA.
[Uda, Manuela; Sanna, Serena] CNR, Ist Neurogenet Neurofarmacol, Cagliari, Italy.
[Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Chakravarti, Aravinda] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Soliman, Elsayed Z.] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Epidemiol Cardiol Res Ctr EPICARE,Med Ctr, Winston Salem, NC 27109 USA.
[Perz, Siegfried] Helmholtz Ctr, Inst Biol & Med Imaging, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiol & Prevent Med Div,Evans Dept Med, Boston, MA 02118 USA.
RP Pfeufer, A (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80804 Munich, Germany.
EM arne.pfeufer@web.de; heckbert@u.washington.edu
RI Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015;
Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; EHRET,
Georg/A-9532-2009; Van Wagoner, David/C-6783-2008; Abecasis,
Goncalo/B-7840-2010; Alonso, Alvaro/A-4917-2010; Soliman,
Elsayed/D-8124-2011; Aspelund, Thor/F-4826-2011; Aspelund,
Thor/C-5983-2008; Kottgen, Anna/D-2920-2012; Kaab, Stefan/H-3915-2012;
Muller-Myhsok, Bertram/A-3289-2013; Rice, Kenneth/A-4150-2013; Pfeufer,
Arne/B-6634-2013; Schnabel, Renate/F-6527-2014;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845;
Lunetta, Kathryn/0000-0002-9268-810X; Larson,
Martin/0000-0002-9631-1254; sanna, serena/0000-0002-3768-1749; Abecasis,
Goncalo/0000-0003-1509-1825; Ramachandran, Vasan/0000-0001-7357-5970;
EHRET, Georg/0000-0002-5730-0675; Van Wagoner,
David/0000-0001-8250-9828; Alonso, Alvaro/0000-0002-2225-8323; Soliman,
Elsayed/0000-0001-5632-8150; Aspelund, Thor/0000-0002-7998-5433; Rice,
Kenneth/0000-0001-5779-4495; Benjamin, Emelia/0000-0003-4076-2336;
Gieger, Christian/0000-0001-6986-9554
FU US National Institutes of Health [N01-AG-12100]; US National Institute
on Aging (NIA); Hjartavernd (Icelandic Heart Association); Althingi
(Icelandic parliament); US National Heart, Lung, and Blood Institute
(NHLBI); US National Eye Institute; US National Institute on Deafness
and Other Communication Disorders; NHLBI [N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55022, R01-HL-087641, R01-HL-59367, R01-HL-086694,
R01-HL-054512, R01-HL090620, P50-HL077107, N01-HC85079, N01-HC-85086,
N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133,
U01-HL-080295, R01-HL-087652]; US National Human Genome Research
Institute (NHGRI) [U01-HG004402]; NIH [HHSN268200625226C, UL1-RR025005,
N01-HC-25195, HL-076784, AG-028321, N01-HC25195, HL-080025,
6R01-NS-17950]; Donald W. Reynolds Cardiovascular Clinical Research
Center; Heart and Vascular Institute, Department of Cardiovascular
Medicine, Cleveland Clinic; US National Center for Research Resources
[M01-RR-00425]; National Institute of Diabetes and Digestive and Kidney
Diseases [DK063491]; US National Institute of Neurological Disorders and
Stroke; Cedars-Sinai Board of Governors; Boston University School of
Medicine and Boston Medical Center (LINGA-II); Robert Dawson Evans
Endowment; Doris Duke Charitable Foundation; Deutsche
Forschungsgemeinschaft [SCHN 1149/1-1]; Pfizer; Bundesministerium fur
Bildung und Forschung Nationales Genomforschungsnetz; Leducq Foundation
[07-03 Ludvig 03]; Ludwig-Maximilians University (LMU) [FuFoLe 557/569];
Helmholtz Zentrum Munchen fur Gesundheit und Umwelt; The Netherlands
Organisation for Scientific Research [175.010.2005.011, 911.03.012,
050-060-810]; European Commission; Erasmus Medical Center, Erasmus
University Rotterdam; NIA [NO1-AG-1-2109, 263-MA-410953]; [01-GS-0499];
[01-GR-0103]; [01-GR-0803]; [AFNET 01-GI-0204 01-GS-0838]
FX We gratefully acknowledge all of the participants in the studies. AGES:
US National Institutes of Health (NIH) N01-AG-12100, US National
Institute on Aging (NIA) and NIH Intramural Research Programs,
Hjartavernd (Icelandic Heart Association), Althingi (Icelandic
parliament), US National Heart, Lung, and Blood Institute (NHLBI), US
National Eye Institute and US National Institute on Deafness and Other
Communication Disorders. ARIC: NHLBI N01-HC-55015, N01-HC-55016,
N01-HC-55018 through N01-HC-55022, R01-HL-087641, R01-HL-59367,
R01-HL-086694 and R01-HL-054512; US National Human Genome Research
Institute (NHGRI) U01-HG004402; NIH HHSN268200625226C; and the Donald W.
Reynolds Cardiovascular Clinical Research Center. Infrastructure was
supported by NIH UL1-RR025005. CCAF: NHLBI R01-HL090620 and
P50-HL077107, and intramural funding from the Heart and Vascular
Institute, Department of Cardiovascular Medicine, Cleveland Clinic. CHS:
NHLBI N01-HC85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103,
N01-HC-55222, N01-HC-75150, N01-HC-45133, U01-HL-080295, R01-HL-087652
and R01-HL088456; US National Center for Research Resources
M01-RR-00425; National Institute of Diabetes and Digestive and Kidney
Diseases DK063491; US National Institute of Neurological Disorders and
Stroke; and the Cedars-Sinai Board of Governors. FHS: NIH N01-HC-25195,
HL-076784, AG-028321, N01-HC25195, HL-080025 and 6R01-NS-17950; NHLBI
N01-HC-25195; Boston University School of Medicine and Boston Medical
Center (LINGA-II); the Robert Dawson Evans Endowment; the Doris Duke
Charitable Foundation; the SHARe project; Deutsche
Forschungsgemeinschaft fellowship SCHN 1149/1-1; Affymetrix contract for
genotyping services (N02-HL-6-4278); and Pfizer. KORA/AFNET: We thank B.
Putz, M. Putz and G. Fischer for their contributions to genotyping and
imputation. Bundesministerium fur Bildung und Forschung Nationales
Genomforschungsnetz; 01-GS-0499, 01-GR-0103, 01-GR-0803, AFNET
01-GI-0204 01-GS-0838, the Leducq Foundation 07-03 Ludvig 03,
Ludwig-Maximilians University (LMU) FuFoLe 557/569, the LMU Excellence
Initiative, MC Health as part of LMUinnovativ, the Helmholtz Zentrum
Munchen fur Gesundheit und Umwelt and the state of Bavaria. Rotterdam
Study: We thank P. Arp, M. Jhamai, M. Moorhouse, M. Verkerk and S.
Bervoets for their help in creating the database, K. Estrada for his
help with the analyses and M. Struchalin for contributions to genotype
imputation. Nederlandse Organisatie voor Wetenschappelijk Onderzoek (The
Netherlands Organisation for Scientific Research) 175.010.2005.011,
911.03.012 and 050-060-810, the Research Institute of Diseases in the
Elderly, Netherlands Genome Initiative, Stichting Zorgonderzoek
Nederland-Medische Wetenschappen (The Netherlands Organisation for
Health Research and Development), Netherlands Hartstichting, Netherlands
Ministry of Education Culture and Science, Netherlands Ministry of
Health Welfare and Sports; the European Commission; Erasmus Medical
Center, Erasmus University Rotterdam and the municipality of Rotterdam.
SardiNIA: We thank A. Scuteri and M. Orr for longstanding, continual
support of the project and for phenotype characterization. NIA
NO1-AG-1-2109, 263-MA-410953, NIH and NIA Intramural Research Programs,
NHGRI and NHLBI. Role of the sponsors: None of the funding organizations
had any role in the design and conduct of the study; collection,
management, analysis and interpretation of the data; or preparation,
review or approval of the manuscript. More detailed acknowledgments can
be found in the Supplementary Note.
NR 51
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD FEB
PY 2010
VL 42
IS 2
BP 153
EP U89
DI 10.1038/ng.517
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 549WG
UT WOS:000274084400013
PM 20062060
ER
PT J
AU Deng, HX
Klein, CJ
Yan, JH
Shi, Y
Wu, YH
Fecto, F
Yau, HJ
Yang, Y
Zhai, H
Siddique, N
Hedley-Whyte, ET
DeLong, R
Martina, M
Dyck, PJ
Siddique, T
AF Deng, Han-Xiang
Klein, Christopher J.
Yan, Jianhua
Shi, Yong
Wu, Yanhong
Fecto, Faisal
Yau, Hau-Jie
Yang, Yi
Zhai, Hong
Siddique, Nailah
Hedley-Whyte, E. Tessa
DeLong, Robert
Martina, Marco
Dyck, Peter J.
Siddique, Teepu
TI Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders
caused by alterations in TRPV4
SO NATURE GENETICS
LA English
DT Article
ID MARIE-TOOTH-DISEASE; ANKYRIN REPEAT DOMAIN; HEREDITARY MOTOR; CATION
CHANNEL; NEUROPATHY; MUTATIONS; VARIANTS; GENE; MICE
AB Scapuloperoneal spinal muscular atrophy (SPSMA) and hereditary motor and sensory neuropathy type IIC (HMSN IIC, also known as HMSN2C or Charcot-Marie-Tooth disease type 2C (CMT2C)) are phenotypically heterogeneous disorders involving topographically distinct nerves and muscles. We originally described a large New England family of French-Canadian origin with SPSMA and an American family of English and Scottish descent with CMT2C(1,2). We mapped SPSMA and CMT2C risk loci to 12q24.1-q24.31 with an overlapping region between the two diseases(3,4). Further analysis reduced the CMT2C risk locus to a 4-Mb region(5). Here we report that SPSMA and CMT2C are allelic disorders caused by mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 4 (TRPV4). Functional analysis revealed that increased calcium channel activity is a distinct property of both SPSMA- and CMT2C-causing mutant proteins. Our findings link mutations in TRPV4 to altered calcium homeostasis and peripheral neuropathies, implying a pathogenic mechanism and possible options for therapy for these disorders.
C1 [Deng, Han-Xiang; Yan, Jianhua; Shi, Yong; Fecto, Faisal; Yang, Yi; Zhai, Hong; Siddique, Nailah; Siddique, Teepu] Northwestern Univ, Feinberg Sch Med, Davee Dept Neurol & Clin Neurosci, Div Neuromuscular Med, Chicago, IL 60611 USA.
[Klein, Christopher J.; Dyck, Peter J.] Mayo Clin Fdn, Dept Neurol, Div Peripheral Nerve Dis, Rochester, MN USA.
[Wu, Yanhong] Mayo Clin Fdn, Dept Lab Med & Pathol, Rochester, MN USA.
[Fecto, Faisal; Siddique, Teepu] Northwestern Univ, Interdept Neurosci Program, Feinberg Sch Med, Chicago, IL 60611 USA.
[Yau, Hau-Jie; Martina, Marco] Northwestern Univ, Dept Physiol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[DeLong, Robert] Duke Univ, Dept Pediat, Sch Med, Durham, NC 27706 USA.
RP Deng, HX (reprint author), Northwestern Univ, Feinberg Sch Med, Davee Dept Neurol & Clin Neurosci, Div Neuromuscular Med, Chicago, IL 60611 USA.
EM h-deng@northwestern.edu; t-siddique@northwestern.edu
OI YAU, HAU-JIE/0000-0001-7454-7971
FU National Institute of Neurological Disorders and Stroke [NS050641]; Les
Turner ALS Foundation; Vena E. Schaff ALS Research Fund; Harold Post
Research Professorship; Herbert and Florence C. Wenske Foundation; David
C. Asselin MD Memorial Fund; Help America Foundation; Les Turner ALS
Foundation/Herbert C. Wenske Foundation; Epilepsy Foundation
FX The authors acknowledge the support from the National Institute of
Neurological Disorders and Stroke (NS050641), the Les Turner ALS
Foundation, the Vena E. Schaff ALS Research Fund, the Harold Post
Research Professorship, the Herbert and Florence C. Wenske Foundation,
the David C. Asselin MD Memorial Fund, the Help America Foundation, the
Les Turner ALS Foundation/Herbert C. Wenske Foundation Professorship and
the Epilepsy Foundation. We thank R.J. Miller and A. Belmadani for help
with the calcium imaging studies and J. Caliendo for proofreading this
manuscript.
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD FEB
PY 2010
VL 42
IS 2
BP 165
EP U102
DI 10.1038/ng.509
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 549WG
UT WOS:000274084400015
PM 20037587
ER
PT J
AU Stewart, CR
Stuart, LM
Wilkinson, K
van Gils, JM
Deng, JS
Halle, A
Rayner, KJ
Boyer, L
Zhong, RQ
Frazier, WA
Lacy-Hulbert, A
El Khoury, J
Golenbock, DT
Moore, KJ
AF Stewart, Cameron R.
Stuart, Lynda M.
Wilkinson, Kim
van Gils, Janine M.
Deng, Jiusheng
Halle, Annett
Rayner, Katey J.
Boyer, Laurent
Zhong, Ruiqin
Frazier, William A.
Lacy-Hulbert, Adam
El Khoury, Joseph
Golenbock, Douglas T.
Moore, Kathryn J.
TI CD36 ligands promote sterile inflammation through assembly of a
Toll-like receptor 4 and 6 heterodimer
SO NATURE IMMUNOLOGY
LA English
DT Article
ID ALZHEIMERS-DISEASE; SCAVENGER RECEPTORS; ASP299GLY POLYMORPHISM;
SIGNALING CASCADE; APOLIPOPROTEIN-E; IMMUNE-RESPONSE; INNATE IMMUNITY;
LIPID UPTAKE; ATHEROSCLEROSIS; TOLL-LIKE-RECEPTOR-4
AB In atherosclerosis and Alzheimer's disease, deposition of the altered self components oxidized low-density lipoprotein (LDL) and amyloid-beta triggers a protracted sterile inflammatory response. Although chronic stimulation of the innate immune system is believed to underlie the pathology of these diseases, the molecular mechanisms of activation remain unclear. Here we show that oxidized LDL and amyloid-beta trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 and 6. Assembly of this newly identified heterodimer is regulated by signals from the scavenger receptor CD36, a common receptor for these disparate ligands. Our results identify CD36-TLR4-TLR6 activation as a common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate sterile inflammation and suggest a new model of TLR heterodimerization triggered by coreceptor signaling events.
C1 [Stuart, Lynda M.; Boyer, Laurent; Lacy-Hulbert, Adam] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp,Lab Dev Immunol, Boston, MA 02115 USA.
[Halle, Annett; Golenbock, Douglas T.] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA USA.
[Zhong, Ruiqin; Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[El Khoury, Joseph] Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Sch Med, Charlestown, MA USA.
[Stewart, Cameron R.; Wilkinson, Kim; van Gils, Janine M.; Deng, Jiusheng; Rayner, Katey J.; Moore, Kathryn J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Lipid Metab Unit, Boston, MA USA.
RP Moore, KJ (reprint author), NYU, Sch Med, Dept Med, Leon H Charney Div Cardiol, New York, NY 10003 USA.
EM kathryn.moore@nyumc.org
RI Stewart, Cameron/E-6823-2011; Rayner, Katey/K-8914-2012; Boyer,
laurent/F-8921-2015;
OI Boyer, laurent/0000-0002-1375-1706; Lacy-Hulbert,
Adam/0000-0003-2162-0156; Moore, kathryn/0000-0003-2505-2547
FU US National Institutes of Health [R01AG20255, R01NS059005, R01
AG032349]; Ellison Medical Foundation; American Health Assistance
Foundation [A2008-130]; Wellcome Trust [068089/Z/02/Z]
FX We thank S. Akira (Osaka University) and K. Miyake (Japan Science and
Technology Agency) for knockout mice. Supported by the US National
Institutes of Health (R01AG20255 to K. J. M.; R01NS059005 to J. E. K.;
R01 AG032349 to K. J. M. and J. E. K.), the Ellison Medical Foundation
(K. J. M.), the American Health Assistance Foundation (A2008-130 to K.
J. M.) and the Wellcome Trust (068089/Z/02/Z to L. M. S.).
NR 42
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U1 4
U2 56
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD FEB
PY 2010
VL 11
IS 2
BP 155
EP U75
DI 10.1038/ni.1836
PG 8
WC Immunology
SC Immunology
GA 545KF
UT WOS:000273730200013
PM 20037584
ER
PT J
AU Hettmer, S
Wagers, AJ
AF Hettmer, Simone
Wagers, Amy J.
TI Muscling in Uncovering the origins of rhabdomyosarcoma
SO NATURE MEDICINE
LA English
DT Editorial Material
ID ALVEOLAR RHABDOMYOSARCOMA; STEM-CELLS; MOUSE; GENE
C1 [Hettmer, Simone; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Hettmer, Simone; Wagers, Amy J.] Joslin Diabet Ctr, Cambridge, MA USA.
[Hettmer, Simone] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Hettmer, Simone] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
RP Hettmer, S (reprint author), Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
EM amy.wagers@joslin.harvard.edu
FU Howard Hughes Medical Institute
NR 14
TC 48
Z9 49
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD FEB
PY 2010
VL 16
IS 2
BP 171
EP 173
DI 10.1038/nm0210-171
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 552MZ
UT WOS:000274297000037
PM 20134473
ER
PT J
AU Li, Y
Zou, LH
Li, QY
Haibe-Kains, B
Tian, RY
Li, Y
Desmedt, C
Sotiriou, C
Szallasi, Z
Iglehart, JD
Richardson, AL
Wang, ZC
AF Li, Yang
Zou, Lihua
Li, Qiyuan
Haibe-Kains, Benjamin
Tian, Ruiyang
Li, Yan
Desmedt, Christine
Sotiriou, Christos
Szallasi, Zoltan
Iglehart, J. Dirk
Richardson, Andrea L.
Wang, Zhigang Charles
TI Amplification of LAPTM4B and YWHAZ contributes to chemotherapy
resistance and recurrence of breast cancer
SO NATURE MEDICINE
LA English
DT Article
ID GENE-EXPRESSION PROFILES; MULTIDRUG-RESISTANCE; HISTOLOGIC GRADE;
SURVIVAL; SIGNATURE; TUMORS; ABERRATIONS; 14-3-3-ZETA; METASTASIS;
PREDICTION
AB Adjuvant chemotherapy for breast cancer after surgery has effectively lowered metastatic recurrence rates(1). However, a considerable proportion of women suffer recurrent cancer at distant metastatic sites despite adjuvant treatment. Identification of the genes crucial for tumor response to specific chemotherapy drugs is a challenge but is necessary to improve outcomes(2). By using integrated genomics, we identified a small number of overexpressed and amplified genes from chromosome 8q22 that were associated with early disease recurrence despite anthracycline-based adjuvant chemotherapy. We confirmed the association in an analysis of multiple independent cohorts. SiRNA-mediated knockdown of either of two of these genes, the antiapoptotic gene YWHAZ and a lysosomal gene LAPTM4B, sensitized tumor cells to anthracyclines, and overexpression of either of the genes induced anthracycline resistance. Overexpression of LAPTM4B resulted in sequestration of the anthracycline doxorubicin, delaying its appearance in the nucleus. Overexpression of these two genes was associated with poor tumor response to anthracycline treatment in a neoadjuvant chemotherapy trial in women with primary breast cancer. Our results suggest that 8q22 amplification and overexpression of LAPTM4B and YWHAZ contribute to de novo chemoresistance to anthracyclines and are permissive for metastatic recurrence. Overexpression of these two genes may predict anthracycline resistance and influence selection of chemotherapy.
C1 [Li, Yang; Zou, Lihua; Tian, Ruiyang; Li, Yan; Iglehart, J. Dirk; Richardson, Andrea L.; Wang, Zhigang Charles] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Li, Yang; Iglehart, J. Dirk; Wang, Zhigang Charles] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Zou, Lihua] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Li, Qiyuan; Szallasi, Zoltan] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
[Haibe-Kains, Benjamin; Desmedt, Christine; Sotiriou, Christos] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium.
[Haibe-Kains, Benjamin] Univ Libre Bruxelles, Machine Learning Grp, Brussels, Belgium.
[Szallasi, Zoltan] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA USA.
[Richardson, Andrea L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Richardson, AL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM arichardson@partners.org; zhigang_wang@dfci.harvard.edu
RI Zou, Lihua/E-6748-2010; Haibe-Kains, Benjamin/D-3702-2011;
OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Szallasi,
Zoltan/0000-0001-5395-7509; Desmedt, Christine/0000-0002-5223-5579
FU NCI NIH HHS [BC053041, CA89393, P50 CA089393, P50 CA089393-01, P50
CA089393-10]
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U1 2
U2 26
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD FEB
PY 2010
VL 16
IS 2
BP 214
EP U121
DI 10.1038/nm.2090
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 552MZ
UT WOS:000274297000043
PM 20098429
ER
PT J
AU Houghton, AM
Rzymkiewicz, DM
Ji, HB
Gregory, AD
Egea, EE
Metz, HE
Stolz, DB
Land, SR
Marconcini, LA
Kliment, CR
Jenkins, KM
Beaulieu, KA
Mouded, M
Frank, SJ
Wong, KK
Shapiro, SD
AF Houghton, A. McGarry
Rzymkiewicz, Danuta M.
Ji, Hongbin
Gregory, Alyssa D.
Egea, Eduardo E.
Metz, Heather E.
Stolz, Donna B.
Land, Stephanie R.
Marconcini, Luiz A.
Kliment, Corrine R.
Jenkins, Kimberly M.
Beaulieu, Keith A.
Mouded, Majd
Frank, Stuart J.
Wong, Kwok K.
Shapiro, Steven D.
TI Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor
growth
SO NATURE MEDICINE
LA English
DT Article
ID INSULIN-RECEPTOR SUBSTRATE-1; LEUKOCYTE ELASTASE; G972R VARIANT; K-RAS;
CANCER; INTERLEUKIN-8; ASSOCIATION; EXPRESSION; PHOSPHORYLATION;
INFLAMMATION
AB Lung cancer is the leading cause of cancer death worldwide(1). Recent data suggest that tumor-associated inflammatory cells may modify lung tumor growth and invasiveness(2,3). To determine the role of neutrophil elastase (encoded by Elane) on tumor progression, we used the loxP-Stop-loxP K-ras(G12D) (LSL-K-ras) model of mouse lung adenocarcinoma(4) to generate LSL-K-ras-Elane(-/-) mice. Tumor burden was markedly reduced in LSL-K-ras-Elane(-/-) mice at all time points after induction of mutant K-ras expression. Kaplan-Meier survival analysis showed that whereas all LSL-K-ras-Elane(+/+) mice died, none of the mice lacking neutrophil elastase died. Neutrophil elastase directly induced tumor cell proliferation in both human and mouse lung adenocarcinomas by gaining access to an endosomal compartment within tumor cells, where it degraded insulin receptor substrate-1 (IRS-1). Immunoprecipitation studies showed that, as neutrophil elastase degraded IRS-1, there was increased interaction between phosphatidylinositol 3-kinase (PI3K) and the potent mitogen platelet-derived growth factor receptor (PDGFR), thereby skewing the PI3K axis toward tumor cell proliferation. The inverse relationship identified between neutrophil elastase and IRS-1 in LSL-K-ras mice was also identified in human lung adenocarcinomas, thus translating these findings to human disease. This study identifies IRS-1 as a key regulator of PI3K within malignant cells. Additionally, to our knowledge, this is the first description of a secreted proteinase gaining access to the inside of a cell and altering intracellular signaling.
C1 [Houghton, A. McGarry; Gregory, Alyssa D.; Egea, Eduardo E.; Metz, Heather E.; Kliment, Corrine R.; Jenkins, Kimberly M.; Beaulieu, Keith A.; Mouded, Majd; Shapiro, Steven D.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA.
[Houghton, A. McGarry; Gregory, Alyssa D.; Egea, Eduardo E.; Metz, Heather E.; Jenkins, Kimberly M.; Beaulieu, Keith A.; Mouded, Majd; Shapiro, Steven D.] Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Houghton, A. McGarry; Stolz, Donna B.; Land, Stephanie R.; Shapiro, Steven D.] Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA USA.
[Rzymkiewicz, Danuta M.; Marconcini, Luiz A.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Ji, Hongbin] Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China.
[Ji, Hongbin] Chinese Acad Sci, Shanghai, Peoples R China.
[Stolz, Donna B.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA.
[Land, Stephanie R.] Univ Pittsburgh, Sch Med, Dept Biostat, Pittsburgh, PA USA.
[Frank, Stuart J.] Univ Alabama, Div Endocrinol Diabet & Metab, Birmingham, AL USA.
[Wong, Kwok K.] Dana Farber Canc Inst, Dept Med, Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA.
[Wong, Kwok K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wong, Kwok K.] Harvard Univ, Sch Med, Boston, MA USA.
RP Houghton, AM (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA.
EM houghtonm@dom.pitt.edu
FU US National Institutes of Health National Heart, Lung, and Blood
Institute [K08HL085286, RO1HL054853, RO1DK058259]
FX This work was supported by grants K08HL085286 and RO1HL054853 from the
US National Institutes of Health National Heart, Lung, and Blood
Institute ( A. M. H. and S. D. S.) and by grant RO1DK058259 from the US
National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases (S.J.F.). ONO Pharmaceutical provided the
ONO-5046. LSL-K-ras mice were provided by T. Jacks ( Massachusetts
Institute of Technology). AdenoCre was obtained from the University of
Iowa Gene Transfer Vector Core. We would like to recognize members of
the Shapiro lab for their assistance and comments regarding the
preparation of this manuscript.
NR 32
TC 160
Z9 169
U1 3
U2 15
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD FEB
PY 2010
VL 16
IS 2
BP 219
EP U127
DI 10.1038/nm.2084
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 552MZ
UT WOS:000274297000044
PM 20081861
ER
PT J
AU Joung, JK
Voytas, DF
Cathomen, T
AF Joung, J. Keith
Voytas, Daniel F.
Cathomen, Toni
TI Genome editing with modularly assembled zinc-finger nucleases reply
SO NATURE METHODS
LA English
DT Letter
C1 [Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA.
[Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA.
[Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.
[Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN USA.
[Cathomen, Toni] Hannover Med Sch, Dept Expt Hematol, D-3000 Hannover, Germany.
RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA.
EM jjoung@partners.org; voytas@umn.edu; cathomen.toni@mh-hannover.de
NR 7
TC 16
Z9 16
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD FEB
PY 2010
VL 7
IS 2
BP 91
EP 92
DI 10.1038/nmeth0210-91b
PG 3
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 549WW
UT WOS:000274086200004
ER
PT J
AU Neal, JW
Sequist, LV
AF Neal, Joel W.
Sequist, Lecia V.
TI TARGETED THERAPIES Optimal first-line therapy for NSCLC with EGFR
mutations
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; GEFITINIB; ERLOTINIB
C1 [Neal, Joel W.; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Ctr Thorac Canc, Boston, MA 02114 USA.
[Neal, Joel W.; Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Thorac Canc, 32 Fruit St,Suite 7B, Boston, MA 02114 USA.
EM lvsequist@partners.org
NR 10
TC 5
Z9 5
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD FEB
PY 2010
VL 7
IS 2
BP 70
EP 71
DI 10.1038/nrclinonc.2009.191
PG 2
WC Oncology
SC Oncology
GA 549VO
UT WOS:000274082600002
PM 20118973
ER
PT J
AU Lantermann, AB
Straub, T
Stralfors, A
Yuan, GC
Ekwall, K
Korber, P
AF Lantermann, Alexandra B.
Straub, Tobias
Stralfors, Annelie
Yuan, Guo-Cheng
Ekwall, Karl
Korber, Philipp
TI Schizosaccharomyces pombe genome-wide nucleosome mapping reveals
positioning mechanisms distinct from those of Saccharomyces cerevisiae
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID DIFFERENTIAL COFACTOR REQUIREMENTS; TRANSCRIPTION FACTOR-BINDING;
HISTONE-DNA INTERACTIONS; FISSION YEAST DNA; CHROMATIN STRUCTURE;
HIGH-RESOLUTION; IN-VIVO; ORGANIZATION; PROMOTERS; GENES
AB Positioned nucleosomes limit the access of proteins to DNA and implement regulatory features encoded in eukaryotic genomes. Here we have generated the first genome-wide nucleosome positioning map for Schizosaccharomyces pombe and annotated transcription start and termination sites genome wide. Using this resource, we found surprising differences from the previously published nucleosome organization of the distantly related yeast Saccharomyces cerevisiae. DNA sequence guides nucleosome positioning differently: for example, poly(dA-dT) elements are not enriched in S. pombe nucleosome-depleted regions. Regular nucleosomal arrays emanate more asymmetrically-mainly codirectionally with transcription-from promoter nucleosome-depleted regions, but promoters harboring the histone variant H2A.Z also show regular arrays upstream of these regions. Regular nucleosome phasing in S. pombe has a very short repeat length of 154 base pairs and requires a remodeler, Mit1, that is conserved in humans but is not found in S. cerevisiae. Nucleosome positioning mechanisms are evidently not universal but evolutionarily plastic.
C1 [Stralfors, Annelie; Ekwall, Karl] Karolinska Inst, Dept Biosci & Nutr, Ctr Biosci NOVUM, Huddinge, Sweden.
[Lantermann, Alexandra B.; Straub, Tobias; Korber, Philipp] Univ Munich, Adolf Butenandt Inst, Munich, Germany.
[Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Ekwall, K (reprint author), Karolinska Inst, Dept Biosci & Nutr, Ctr Biosci NOVUM, Huddinge, Sweden.
EM karl.ekwall@ki.se; pkorber@lmu.de
RI Straub, Tobias/B-2023-2009
OI Straub, Tobias/0000-0002-0547-0453
FU German Research Community; European Union; Swedish Cancer Society;
Swedish Research Council; Claudia Adams Barr Program
FX We thank H. Bhuiyan and J. Walfridsson for generating the S. pombe
expression data during their work in the group of K. Ekwall, R. R.
Barrales (group of J. J. Ibeas, Universidad Pablo de Olavide, Sevilla,
Spain) for bringing the first S. pombe strains into the Korber group, F.
Thoma (ETH Zurich, Switzerland) for advice on chromatin analysis in S.
pombe, F. Fagerstrom-Billai at the BEA microarray facility at Novum,
Karolinska Institutet, for assistance, and F. Muller-Planitz
(Adolf-Butenandt-Institut, Univ. Munich) for help with MATLAB. We are
grateful for the communication of replication origin coordinates by C.
Heichinger (Univ. Zurich) and of TSS coordinates by W. Lee (Stanford
Univ.) and N. Dutrow (Univ. Utah). We thank H. Madhani and co-workers
(Univ. California San Francisco) for sharing data before publication and
for comments on the manuscript. This work was funded by the German
Research Community (Transregio 5; P. K. and co-workers), the 6th
Framework Programme of the European Union (NET programme; P. K. and K.
E. and co-workers), the Swedish Cancer Society and Swedish Research
Council (K. E. laboratory) and the Claudia Adams Barr Program (G.-C.
Y.).
NR 56
TC 133
Z9 134
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD FEB
PY 2010
VL 17
IS 2
BP 251
EP U15
DI 10.1038/nsmb.1741
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 551RZ
UT WOS:000274228400021
PM 20118936
ER
PT J
AU Clauss, A
Ng, V
Liu, J
Piao, HY
Russo, M
Vena, N
Sheng, Q
Hirsch, MS
Bonome, T
Matulonis, U
Ligon, AH
Birrer, MJ
Drapkin, R
AF Clauss, Adam
Ng, Vivian
Liu, Joyce
Piao, Huiying
Russo, Moises
Vena, Natalie
Sheng, Qing
Hirsch, Michelle S.
Bonome, Tomas
Matulonis, Ursula
Ligon, Azra H.
Birrer, Michael J.
Drapkin, Ronny
TI Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains
and Activation of the Nuclear Factor kappa B Pathway and Is Associated
with Poor Overall Survival
SO NEOPLASIA
LA English
DT Article
ID LEUKOCYTE PROTEASE INHIBITOR; ELASTASE-SPECIFIC INHIBITOR; MAMMARY
EPITHELIAL-CELLS; IMMUNOHISTOCHEMICAL EXPRESSION; DIFFERENTIAL
EXPRESSION; PROTEINASE-INHIBITORS; CANCER CELLS; GENES; IDENTIFICATION;
SKALP/ELAFIN
AB Ovarian cancer is a leading cause of cancer mortality in women. The aim of this study was to elucidate whether whey acidic protein (WAP) genes on chromosome 20q13.12, a region frequently amplified in this cancer, are expressed in serous carcinoma, the most common form of the disease. Herein, we report that a trio of WAP genes (HE4, SLPI, and Elafin) is overexpressed and secreted by serous ovarian carcinomas. To our knowledge, this is the first report linking Elafin to ovarian cancer. Fluorescence in situ hybridization analysis of primary tumors demonstrates genomic gains of the Elafin locus in a majority of cases. In addition, a combination of peptidomimetics, RNA interference, and chromatin immunoprecipitation experiments shows that Elafin expression can be transcriptionally upregulated by inflammatory cytokines through activation of the nuclear factor kappa B pathway. Importantly, using a clinically annotated tissue microarray composed of late-stage, high-grade serous ovarian carcinomas, we show that Elafin expression correlates with poor overall survival. These results, combined with our observation that Elafin is secreted by ovarian tumors and is minimally expressed in normal tissues, suggest that Elafin may serve as a determinant of poor survival in this disease.
C1 [Clauss, Adam; Ng, Vivian; Liu, Joyce; Piao, Huiying; Russo, Moises; Matulonis, Ursula; Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Clauss, Adam; Liu, Joyce; Russo, Moises; Sheng, Qing; Hirsch, Michelle S.; Matulonis, Ursula; Ligon, Azra H.; Birrer, Michael J.; Drapkin, Ronny] Harvard Univ, Sch Med, Boston, MA USA.
[Vena, Natalie; Ligon, Azra H.; Drapkin, Ronny] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Sheng, Qing] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Hirsch, Michelle S.; Ligon, Azra H.; Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Bonome, Tomas] NIH, Mol Mech Sect, Bethesda, MD 20892 USA.
[Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Drapkin, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, JF215D,44 Binney St, Boston, MA 02115 USA.
EM ronny_drapkin@dfci.harvard.edu
RI Drapkin, Ronny/E-9944-2016
OI Drapkin, Ronny/0000-0002-6912-6977
FU National Cancer Institute (NCI) [P50-CA105009, K08 CA108748, K12
CA87723]; Robert and Deborah First Fund; Randi and Joel Cutler Ovarian
Cancer Research Fund; Fannie E. Ripple Foundation; Phi Beta Psi Sorority
Charitable Trust; Ovarian Cancer Research Fund; Madeline Franchi Ovarian
Cancer Foundation; Harvard Medical School Center of Excellence in
Women's Health
FX This work was supported by National Cancer Institute (NCI) P50-CA105009
SPORE in Ovarian Cancer (Career Development Award, to R.D.), NCI K08
CA108748 (R.D.), NCI K12 CA87723 (J.L.), The Robert and Deborah First
Fund (R.D.), The Randi and Joel Cutler Ovarian Cancer Research Fund ( R.
D.), The Fannie E. Ripple Foundation (R.D. and U.M.), Phi Beta Psi
Sorority Charitable Trust (R.D.), Ovarian Cancer Research Fund (A.C. and
R. D.), The Madeline Franchi Ovarian Cancer Foundation (A.C.), and the
Harvard Medical School Center of Excellence in Women's Health Award
(M.S.H. and U.M.).
NR 47
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U1 0
U2 1
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD FEB
PY 2010
VL 12
IS 2
BP 161
EP U88
DI 10.1593/neo.91542
PG 14
WC Oncology
SC Oncology
GA 554AX
UT WOS:000274409000006
PM 20126474
ER
PT J
AU Odden, MC
Tager, IB
Gansevoort, RT
Bakker, SJL
Katz, R
Fried, LF
Newman, AB
Canada, RB
Harris, T
Sarnak, MJ
Siscovick, D
Shlipak, MG
AF Odden, Michelle C.
Tager, Ira B.
Gansevoort, Ron T.
Bakker, Stephan J. L.
Katz, Ronit
Fried, Linda F.
Newman, Anne B.
Canada, Robert B.
Harris, Tamara
Sarnak, Mark J.
Siscovick, David
Shlipak, Michael G.
TI Age and cystatin C in healthy adults: a collaborative study
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE ageing; chronic kidney disease; cystatin C; epidemiology
ID URINARY ALBUMIN EXCRETION; SERUM CREATININE; RENAL-FUNCTION;
PULMONARY-FUNCTION; KIDNEY-FUNCTION; UNITED-STATES; DISEASE;
DYSFUNCTION; POPULATION; DECLINE
AB Methods. The authors pooled individual-level cross-sectional data from 18 253 persons aged 28-100 years in four studies: the Cardiovascular Health Study; the Health, Aging and Body Composition Study; the Multi-Ethnic Study of Atherosclerosis and the Prevention of Renal and Vascular End-Stage Disease cohort. Kidney function was measured by cystatin C. Clinical risk factors for kidney disease included diabetes, hypertension, obesity, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease and heart failure.
Results. Across the age range, there was a strong, non-linear association of age with cystatin C concentration. This association was substantial, even among participants free of clinical risk factors for kidney disease; mean cystatin C levels were 46% higher in participants 80 and older compared with those < 40 years (1.06 versus 0.72 mg/L, P < 0.001). Participants with one or more risk factors had higher cystatin C concentrations for a given age, and the age association was slightly stronger (P < 0.001 for age and risk factor interaction).
Conclusions. There is a strong, non-linear association of age with kidney function, even in healthy individuals. An important area for research will be to investigate the mechanisms that lead to deterioration of kidney function in apparently healthy persons.
C1 [Odden, Michelle C.; Tager, Ira B.] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA.
[Odden, Michelle C.] Univ Calif San Francisco, Dept Gen Internal Med, San Francisco, CA 94143 USA.
[Gansevoort, Ron T.; Bakker, Stephan J. L.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands.
[Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
[Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Epidemiol, Pittsburgh, PA USA.
[Canada, Robert B.] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA.
[Canada, Robert B.] Univ Tennessee, Ctr Hlth Sci, Dept Nephrol, Memphis, TN 38163 USA.
[Harris, Tamara] NIA, Lab Epidemiol, Demog Biometry Program, NIH, Bethesda, MD 20892 USA.
[Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA.
[Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA.
[Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA.
RP Odden, MC (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA.
EM michelle.odden@ucsf.edu
RI Newman, Anne/C-6408-2013; Bakker, Stephan/J-4023-2015
OI Newman, Anne/0000-0002-0106-1150; Bakker, Stephan/0000-0003-3356-6791
FU National Heart, Lung and Blood Institute [N01HC-85079, N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295, R01-HL-63963-01A1, N01-HC-95159, N01-HC-95165,
N01-HC-95169]; National Institute on Aging [N01-AG-6-2101, N01AG-6-2103,
N01-AG-6-2106, R01AG027002]; NIH, National Institute on Aging; Dutch
Kidney Foundation, Bussum, The Netherlands [E013]; National Institute of
Diabetes and Digestive, and Kidney Diseases [T32DK07791, DK52866];
institutional Health Resources & Services Administration National
Research Service Award [T32HP19025]; American Federation for Aging
Research; Robert Wood Johnson Foundation; American Heart Association
FX CHS was supported by contract numbers N01HC-85079 through N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
grant number U01 HL080295 from the National Heart, Lung and Blood
Institute, with additional contribution from the National Institute of
Neurological Disorders and Stroke. A full list of principal CHS
investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm. Health ABC was supported through the
National Institute on Aging contracts N01-AG-6-2101, N01AG-6-2103 and
N01-AG-6-2106 and in part by the Intramural Research Program of the NIH,
National Institute on Aging. MESA was supported by grant
R01-HL-63963-01A1 and by contracts N01-HC-95159 through N01-HC-95165 and
N01-HC-95169 from the National Heart, Lung and Blood Institute. PREVEND
is supported by grant E013 of the Dutch Kidney Foundation, Bussum, The
Netherlands, and grants T32DK07791 and DK52866 from the National
Institute of Diabetes and Digestive, and Kidney Diseases. This project
was also supported by grant R01AG027002 from the National Institutes on
Aging. Dr Odden is supported by an institutional Health Resources &
Services Administration National Research Service Award (T32HP19025). Dr
Shlipak was supported by the American Federation for Aging Research and
National Institute on Aging (Paul Beeson Scholars Program), by the
Robert Wood Johnson Foundation (Generalist Faculty Scholars Program),
and the American Heart Association.
NR 34
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U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD FEB
PY 2010
VL 25
IS 2
BP 463
EP 469
DI 10.1093/ndt/gfp474
PG 7
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 547LY
UT WOS:000273891600024
PM 19749145
ER
PT J
AU Salat, DH
Tuch, DS
van der Kouwe, AJW
Greve, DN
Pappu, V
Lee, SY
Hevelone, ND
Zaleta, AK
Growdon, JH
Corkin, S
Fischl, B
Rosas, HD
AF Salat, D. H.
Tuch, D. S.
van der Kouwe, A. J. W.
Greve, D. N.
Pappu, V.
Lee, S. Y.
Hevelone, N. D.
Zaleta, A. K.
Growdon, J. H.
Corkin, S.
Fischl, B.
Rosas, H. D.
TI White matter pathology isolates the hippocampal formation in Alzheimer's
disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer; Aging; Diffusion tensor imaging; Fractional anisotropy;
Diffusivity; MRI; White matter; Dementia; Hippocampus; Entorhinal;
Memory; Axial diffusivity; Radial diffusivity; Tractography; Volume;
Hyperintensities; T2; Myelin; Axon
ID MILD COGNITIVE IMPAIRMENT; DIFFUSION-TENSOR MRI; MEMORY IMPAIRMENT;
TEMPORAL-LOBE; SPIN-ECHO; IN-VIVO; DEMENTIA; BRAIN; AGE; CORTEX
AB Prior work has demonstrated that the memory dysfunction of Alzheimer's disease (AD) is accompanied by marked cortical pathology in medial temporal lobe (MTL) gray matter. In contrast, changes in white matter (WM) of pathways associated with the MTL have rarely been studied. We used diffusion tensor imaging (DTI) to examine regional patterns of WM tissue changes in individuals with AD. Alterations of diffusion properties with AD were found in several regions including parahippocampal WM, and in regions with direct and secondary connections to the MTL. A portion of the changes measured, including effects in the parahippocampal WM, were independent of gray matter degeneration as measured by hippocampal volume. Examination of regional changes in unique diffusion parameters including anisotropy and axial and radial diffusivity demonstrated distinct zones of alterations, potentially stemming from differences in underlying pathology, with a potential myelin specific pathology in the parahippocampal WM. These results demonstrate that deterioration of neocortical connections to the hippocampal formation results in part from the degeneration of critical MTL and associated fiber pathways. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Salat, D. H.] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, MGH Dept Radiol, Charlestown, MA 02129 USA.
[Salat, D. H.; Tuch, D. S.; van der Kouwe, A. J. W.; Greve, D. N.; Fischl, B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Pappu, V.; Lee, S. Y.; Hevelone, N. D.; Zaleta, A. K.; Growdon, J. H.; Rosas, H. D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Corkin, S.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
RP Salat, DH (reprint author), MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, MGH Dept Radiol, Bldg 149,13th St,Mail Code 149 2301, Charlestown, MA 02129 USA.
EM salat@nmr.mgh.harvard.edu
OI Hevelone, Nathanael/0000-0003-4740-2085
FU NIH [K01 AG024898]; Massachusetts Alzheimer's Disease Research Center
Pilot [AG05886]; National Center for Research Resources [P41RR14075];
Mental Illness and Neuroscience Discovery (MIND) Institute; National
Alliance for Medical Image Computing (NAMIC) [U54 EB05149]
FX This work was supported in part by NIH K01 AG024898, a Massachusetts
Alzheimer's Disease Research Center Pilot Grant 2001/2002 (AG05886), the
National Center for Research Resources (P41RR14075), the Mental Illness
and Neuroscience Discovery (MIND) Institute, and a grant from the
National Alliance for Medical Image Computing (NAMIC U54 EB05149). We
thank Dr. Francine Grodstein and the Nurses' Health Study for a portion
of the participant recruitment and imaging.
NR 90
TC 148
Z9 150
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2010
VL 31
IS 2
BP 244
EP 256
DI 10.1016/j.neurobiolaging.2008.03.013
PG 13
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 584NN
UT WOS:000276759400006
PM 18455835
ER
PT J
AU Lopez-Meraz, ML
Wasterlain, CG
Rocha, LL
Allen, S
Niquet, J
AF Lopez-Meraz, Maria-Leonor
Wasterlain, Claude G.
Rocha, Luisa L.
Allen, Suni
Niquet, Jerome
TI Vulnerability of postnatal hippocampal neurons to seizures varies
regionally with their maturational stage
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Necrosis; Apoptosis; Caspase; Doublecortin; Hippocampus; Status
epilepticus; Pilocarpine; Development
ID PILOCARPINE STATUS EPILEPTICUS; LONG-TERM POTENTIATION; Q-VD-OPH;
CELL-DEATH; RAT HIPPOCAMPUS; DENTATE GYRUS; CASPASE INHIBITOR; IMMATURE
RATS; NEONATAL-RAT; CA1 REGION
AB The mechanism of status epilepticus-induced neuronal death in the immature brain is not fully understood. In the present study, we examined the contribution of caspases in our lithium-pilocarpine model of status epilepticus in 14 days old rat pups. In CA1, upregulation of caspase-8, but not caspase-9, preceded caspase-3 activation in morphologically necrotic cells. Pretreatment with a pan-caspase inhibitor provided neuroprotection, showing that caspase activation was not an epiphenomenon but contributed to neuronal necrosis. By contrast, upregulation of active caspase-9 and caspase-3, but not caspase-8, was detected in apoptotic dentate gyrus neurons. which were immunoreactive for doublecortin and calbindin-negative, two features of immature neurons. These results suggest that, in cells which are aligned in series as parts of the same excitatory hippocampal circuit, the same seizures induce neuronal death through different mechanisms. The regional level of neuronal maturity may be a determining factor in the execution of a specific death program. (c) 2009 Elsevier Inc. All rights reserved.
C1 [Lopez-Meraz, Maria-Leonor; Wasterlain, Claude G.; Allen, Suni; Niquet, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Lopez-Meraz, Maria-Leonor; Wasterlain, Claude G.; Allen, Suni; Niquet, Jerome] VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, Los Angeles, CA 90073 USA.
[Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
[Rocha, Luisa L.] Ctr Res & Adv Studies, Pharmacobiol Dept, Mexico City, DF, Mexico.
[Lopez-Meraz, Maria-Leonor] Univ Veracruzana, Programa Neurobiol, Xalapa 91000, Veracruz, Mexico.
RP Niquet, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
EM jniquet@ucla.edu
FU Epilepsy Foundation; VHA Research Service; NINDS [R01 NS13515]; UC
MEXUS-CONACyT
FX This work is supported by Epilepsy Foundation (JN), VHA Research Service
(CW), NINDS (grant R01 NS13515; CW), and UC MEXUS-CONACyT (CW and LR).
MLLM received a UC MEXUS-CONACYT postdoctoral fellowship.
NR 44
TC 24
Z9 25
U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD FEB
PY 2010
VL 37
IS 2
SI SI
BP 394
EP 402
DI 10.1016/j.nbd.2009.10.019
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 551QP
UT WOS:000274224400019
PM 19879360
ER
PT J
AU Sheth, KN
Cushing, TA
Wendell, L
Lev, MH
Romero, JM
Schwab, K
Smith, EE
Greenberg, SM
Rosand, J
Goldstein, JN
AF Sheth, Kevin N.
Cushing, Tracy A.
Wendell, Lauren
Lev, Michael H.
Romero, Javier M.
Schwab, Kristin
Smith, Eric E.
Greenberg, Steven M.
Rosand, Jonathan
Goldstein, Joshua N.
TI Comparison of Hematoma Shape and Volume Estimates in Warfarin Versus
Non-Warfarin-Related Intracerebral Hemorrhage
SO NEUROCRITICAL CARE
LA English
DT Article
DE Cerebral hemorrhage; Tomography; X-ray computed; Warfarin
ID ABC/2 ESTIMATION TECHNIQUE; ACTIVATED FACTOR-VII; ENLARGEMENT;
PREDICTORS; SCORE
AB Background Hematoma volume is a major determinant of outcome in patients with intracerebral hemorrhage (ICH). Accurate volume measurements are critical for predicting outcome and are thought to be more difficult in patients with oral anticoagulation-related ICH (OAT-ICH) due to a higher frequency of irregular shape. We examined hematoma shape and methods of volume assessment in patients with OAT-ICH.
Methods We performed a case-control analysis of a prospectively identified cohort of consecutive patients with ICH. We retrospectively reviewed 50 consecutive patients with OAT-ICH and 50 location-matched non-OAT-ICH controls. Two independent readers analyzed CT scans for hematoma shape and volume using both ABC/2 and ABC/3 methods. Readers were blinded to all clinical variables including warfarin status. Gold-standard ICH volumes were determined using validated computer-assisted planimetry.
Results Within this cohort, median INR in patients with OAT-ICH was 3.2. Initial ICH volume was not significantly different between non-OAT-ICH and OAT-ICH (35 +/- 38 cc vs. 53 +/- 56 cc, P = 0.4). ICH shape did not differ by anticoagulation status (round shape in 10% of OAT-ICH vs. 16% of non-OAT-ICH, P = 0.5). The ABC/3 calculation underestimated median volume by 9 (3-28) cc, while the ABC/2 calculation did so by 4 (0.8-12) cc.
Conclusions Hematoma shape was not statistically significantly different in patients with OAT-ICH. Among bedside approaches, the standard ABC/2 method offers reasonable approximation of hematoma volume in OAT-ICH and non-OAT-ICH.
C1 [Sheth, Kevin N.] Univ Maryland, Med Ctr, Div Neurol, Baltimore, MD 21201 USA.
[Wendell, Lauren; Schwab, Kristin; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Cushing, Tracy A.] Mt Auburn Hosp, Dept Emergency Med, Boston, MA USA.
[Lev, Michael H.; Romero, Javier M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Smith, Eric E.; Rosand, Jonathan] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB, Canada.
[Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Sheth, KN (reprint author), Univ Maryland, Med Ctr, Div Neurol, Baltimore, MD 21201 USA.
EM ksheth@som.umaryland.edu
RI Goldstein, Joshua/H-8953-2016;
OI Smith, Eric/0000-0003-3956-1668
FU National Institute of Neurological Disorders and Stroke [R01 NS059727,
K23NS059774]; Deane Institute for Integrative Study of Atrial
Fibrillation and Stroke
FX Funding was provided by The National Institute of Neurological Disorders
and Stroke (NIH R01 NS059727 and K23NS059774), American Heart
Association Grant-in-Aid # 0755984T, and the Deane Institute for
Integrative Study of Atrial Fibrillation and Stroke.
NR 21
TC 16
Z9 17
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1541-6933
J9 NEUROCRIT CARE
JI Neurocrit. Care
PD FEB
PY 2010
VL 12
IS 1
BP 30
EP 34
DI 10.1007/s12028-009-9296-7
PG 5
WC Critical Care Medicine; Clinical Neurology
SC General & Internal Medicine; Neurosciences & Neurology
GA 571HL
UT WOS:000275742800006
PM 19859832
ER
PT J
AU Parkman, HP
Camilleri, M
Farrugia, G
McCallum, RW
Bharucha, AE
Mayer, EA
Tack, JF
Spiller, R
Horowitz, M
Vinik, AI
Galligan, JJ
Pasricha, PJ
Kuo, B
Szarka, LA
Marciani, L
Jones, K
Parrish, CR
Sandroni, P
Abell, T
Ordog, T
Hasler, W
Koch, KL
Sanders, K
Norton, NJ
Hamilton, F
AF Parkman, H. P.
Camilleri, M.
Farrugia, G.
McCallum, R. W.
Bharucha, A. E.
Mayer, E. A.
Tack, J. F.
Spiller, R.
Horowitz, M.
Vinik, A. I.
Galligan, J. J.
Pasricha, P. J.
Kuo, B.
Szarka, L. A.
Marciani, L.
Jones, K.
Parrish, C. R.
Sandroni, P.
Abell, T.
Ordog, T.
Hasler, W.
Koch, K. L.
Sanders, K.
Norton, N. J.
Hamilton, F.
TI Gastroparesis and functional dyspepsia: excerpts from the AGA/ANMS
meeting
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Review
DE functional dyspepsia; gastric emptying; gastroparesis
ID NITRIC-OXIDE SYNTHASE; GASTRIC-ELECTRICAL-STIMULATION;
IRRITABLE-BOWEL-SYNDROME; CARDINAL SYMPTOM INDEX; UPPER GASTROINTESTINAL
DISORDERS; DEPENDENT DIABETES-MELLITUS; GLYCATION END-PRODUCTS; ENTERIC
NERVOUS-SYSTEM; QUALITY-OF-LIFE; INTERSTITIAL-CELLS
AB P>Background
Despite the relatively high prevelance of gastroparesis and functional dyspepsia, the aetiology and pathophysiology of these disorders remain incompletely understood. Similarly, the diagnostic and treatment options for these two disorders are relatively limited despite recent advances in our understanding of both disorders.
Purpose
This manuscript reviews the advances in the understanding of the epidemiology, pathophysiology, diagnosis, and treatment of gastroparesis and functional dyspepsia as discussed at a recent conference sponsored by the American Gastroenterological Association (AGA) and the American Neurogastroenterology and Motility Society (ANMS). Particular focus is placed on discussing unmet needs and areas for future research.
C1 [Parkman, H. P.] Temple Univ, Sch Med, Gastroenterol Sect, Dept Med, Philadelphia, PA 19140 USA.
[Camilleri, M.; Farrugia, G.; Bharucha, A. E.; Szarka, L. A.] Mayo Clin, Coll Med, Dept Med, Rochester, MN USA.
[McCallum, R. W.] Univ Texas El Paso, Dept Med, El Paso, TX 79968 USA.
[Mayer, E. A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Tack, J. F.] Univ Hosp, Dept Med, Louvain, Belgium.
[Spiller, R.] Univ Hosp, Dept Med, Nottingham, England.
[Horowitz, M.; Jones, K.] Univ Adelaide, Dept Med, Adelaide, SA 5001, Australia.
[Vinik, A. I.] Eastern Virginia Med Sch, Dept Med, Norfolk, VA 23501 USA.
[Galligan, J. J.] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA.
[Pasricha, P. J.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Kuo, B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Marciani, L.] Queens Med Ctr, Dept Radiol, Nottingham NG7 2UH, England.
[Parrish, C. R.] Univ Virginia Hlth Syst, Dept Nutr, Charlottesville, VA USA.
[Sandroni, P.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA.
[Abell, T.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Ordog, T.] Mayo Clin, Coll Med, Dept Physiol, Rochester, MN USA.
[Hasler, W.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Koch, K. L.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA.
[Sanders, K.] Univ Nevada, Dept Physiol, Reno, NV USA.
[Norton, N. J.] Int Fdn Funct Disorders, Milwaukee, MN USA.
[Hamilton, F.] NIH, Bethesda, MD 20892 USA.
RP Parkman, HP (reprint author), Temple Univ, Sch Med, Gastroenterol Sect, Dept Med, Parkinson Pavil,8th Floor,3401 N Broad St, Philadelphia, PA 19140 USA.
EM henry.parkman@temple.edu
OI spiller, robin/0000-0001-6371-4500; Marciani, Luca/0000-0001-9092-4300;
Jones, Karen/0000-0002-1155-5816
FU NIDDK NIH HHS [R01 DK058185, P01 DK068055, R01 DK058185-08]
NR 187
TC 58
Z9 63
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1350-1925
EI 1365-2982
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD FEB
PY 2010
VL 22
IS 2
BP 113
EP 133
DI 10.1111/j.1365-2982.2009.01434.x
PG 21
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 540WH
UT WOS:000273370800004
PM 20003077
ER
PT J
AU Mulert, C
Leicht, G
Hepp, P
Kirsch, V
Karch, S
Pogarell, O
Reiser, M
Hegerl, U
Jager, L
Moller, HJ
McCarley, RW
AF Mulert, C.
Leicht, G.
Hepp, P.
Kirsch, V.
Karch, S.
Pogarell, O.
Reiser, M.
Hegerl, U.
Jaeger, L.
Moller, H. J.
McCarley, R. W.
TI Single-trial coupling of the gamma-band response and the corresponding
BOLD signal
SO NEUROIMAGE
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; SIMULTANEOUS EEG-FMRI; EVENT-RELATED
POTENTIALS; BRAIN ACTIVITY; AUDITORY-CORTEX; ALPHA-RHYTHM; SIMULTANEOUS
EEG/FMRI; SELECTIVE ATTENTION; TARGET DETECTION; TASK-DIFFICULTY
AB Oscillations in the gamma-band frequency range have been described to be more closely connected to hemodynamic changes as assessed with functional magnetic resonance imaging (fMRI) than other aspects of neuronal activity. In addition. gamma-band oscillations have attracted much interest during the last few years since they are thought to play a Crucial role in many aspects of brain function related to perception and cognition. It was the aim of the present simultaneous EEG-fMRI Study to identify brain regions specifically involved in the generation of the auditory gamma-band response (GBR) using single-trial coupling of EEG and fMRI. Ten healthy Subjects participated in this study Three different runs of an auditory choice reaction task with increasing difficulty were performed Brain activity was recorded simultaneously with high density FEG (61 channels) and fMRI (1.5 T). BOLD correlates of the GBR have been predicted using the sing-le-trial amplitude of the GBR
Reaction times (p<0.001). error rates (p<005) and self-ratings of task difficulty and effort demands (p<0.001) were related to the level of difficulty in the task In addition,we found a significant influence of task difficulty oil the amplitude of the GBR at Cz (p<0.05). Using single-trial Coupling of EEG and fMRI GBR-specific activations were found only in the auditory cortex, the thalamus and the anterior cingulate cortex (ACC) in the most difficult run. Single-trial coupling might be a useful method in order to increase our knowledge about the functional neuroanatomy of "neural ensembles" coupled by 40 Hz oscillations (C) 2009 Elsevier Inc. All rights reserved
C1 [Mulert, C.; Leicht, G.; Hepp, P.; Kirsch, V.; Karch, S.; Pogarell, O.; Hegerl, U.; Moller, H. J.] Univ Munich, Dept Psychiat & Psychotherapy, D-80336 Munich, Germany.
[Mulert, C.; Kirsch, V.; McCarley, R. W.] Harvard Univ, Dept Psychiat, Sch Med, Brockton, MA 02401 USA.
[Mulert, C.; Kirsch, V.; McCarley, R. W.] VA Boston Healthcare Syst, Brockton, MA USA.
[Mulert, C.] Univ Med Ctr Hamburg Eppendorf, Ctr Psychosocial Med, Dept Psychiat & Psychotherapy, Hamburg, Germany.
[Reiser, M.; Jaeger, L.] Univ Munich, Inst Clin Radiol, D-80336 Munich, Germany.
[Hegerl, U.] Univ Leipzig, Dept Psychiat & Psychotherapy, Leipzig, Germany.
RP Mulert, C (reprint author), Univ Munich, Dept Psychiat, Nussbaumstr 7, D-80336 Munich, Germany.
RI Mulert, Christoph/F-2576-2012; McCarley, Robert/N-5562-2014;
OI McCarley, Robert/0000-0001-5705-7495; Hegerl, Ulrich/0000-0002-3039-7470
NR 58
TC 43
Z9 44
U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2010
VL 49
IS 3
BP 2238
EP 2247
DI 10.1016/j.neuroimage.2009.10.058
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 544BN
UT WOS:000273626400030
PM 19878729
ER
PT J
AU Upadhyay, J
Pendse, G
Anderson, J
Schwarz, AJ
Baumgartner, R
Coimbra, A
Bishop, J
Knudsen, J
George, E
Grachev, I
Iyengar, S
Bleakman, D
Hargreaves, R
Borsook, D
Becerra, L
AF Upadhyay, Jaymin
Pendse, Gautam
Anderson, Julie
Schwarz, Adam J.
Baumgartner, Richard
Coimbra, Alexandre
Bishop, James
Knudsen, Jamie
George, Ed
Grachev, Igor
Iyengar, Smriti
Bleakman, David
Hargreaves, Richard
Borsook, David
Becerra, Lino
TI Improved characterization of BOLD responses for evoked sensory stimuli
SO NEUROIMAGE
LA English
DT Article
DE Somatosensory cortex; Pain; fMRI; Biphasic response
ID PRIMARY SOMATOSENSORY CORTEX; NOXIOUS THERMAL STIMULI; REGIONAL PAIN
SYNDROME; BRAIN ACTIVITY; HEMODYNAMIC-RESPONSE; FUNCTIONAL MRI; TEMPORAL
ANALYSIS; FMRI; ACTIVATION; MODULATION
AB Pain and somatosensory processing involves an interaction of multiple neuronal networks One result Of these complex interactions is the presence of differential responses across brain regions that may be incompletely modeled by a straightforward application of standard general linear model (GLM) approaches based solely on the applied stimulus We examined temporal blood oxygenation-level dependent (BOLD) signatures elicited by two Stimulation paradigms (brush and hear) providing innocuous and noxious stimuli Data were acquired from 32 healthy male subjects (2 independent cohorts) Regional time courses and model-free analyses of the first cohort revealed distinct temporal features of the BOLD responses elicited during noxious versus innocuous Stimulation Specifically. a biphasic (dual peak) BOLD signal was observed in response to heat but much less so in response to brush Stimuli This signal was characterized by a stimulus-locked response along with a second peak delayed by similar to 12.5 s A cross-validation error analysis determined a modified design matrix comprising two explanatory variables (EVs) as a parsimonious means to model the biphasic responses within a GLM framework. One EV was directly derived from the stimulation paradigm (EVI), while the second EV (EV2) was EVI shifted by 12 5 s. The 2EV GLM analysis enabled a more detailed characterization of the elicited BOLD responses. particularly during pain processing This was confirmed by application of the model to a second. independent cohort[ALI] Further more, the delayed component of the biphasic response was strongly associated with the noxious heat stimuli. suggesting that this may represent a sensitive fMRI link of pain processing (C) 2009 Elsevier Inc All rights reserved
C1 [Upadhyay, Jaymin] Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr,PAIN Grp, Belmont, MA 02478 USA.
[Schwarz, Adam J.; Iyengar, Smriti; Bleakman, David] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Baumgartner, Richard] Merck Res Labs, Biometr Res Dept, Rahway, NJ 07065 USA.
[Coimbra, Alexandre] Merck Res Labs, Dept Imaging, West Point, PA 19486 USA.
[George, Ed; Grachev, Igor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA 02129 USA.
[Hargreaves, Richard] Merck Res Labs, Basic Neurosci Dept, West Point, PA 19486 USA.
[Borsook, David; Becerra, Lino] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Upadhyay, J (reprint author), Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr,PAIN Grp, 115 Mill St, Belmont, MA 02478 USA.
FU Imaging Consortium for Drug Development
FX The authors would like to thank the MR technical staff at the Mclean
Hospital Brain Imaging Center, Eric Moulton, PhD and Diana Wallin, BS
for assistance during the preparation of this manuscript. This work was
supported by the Imaging Consortium for Drug Development.
NR 52
TC 14
Z9 14
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2010
VL 49
IS 3
BP 2275
EP 2286
DI 10.1016/j.neuroimage.2009.10.053
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 544BN
UT WOS:000273626400033
PM 19854280
ER
PT J
AU Anderson, A
Dinov, ID
Sherin, JE
Quintana, J
Yuille, AL
Cohen, MS
AF Anderson, Ariana
Dinov, Ivo D.
Sherin, Jonathan E.
Quintana, Javier
Yuille, A. L.
Cohen, Mark S.
TI Classification of spatially unaligned fMRI scans
SO NEUROIMAGE
LA English
DT Article
DE Classification; FMRI; Discrimination; Schizophrenia; Dementia; Machine
learning; Independent components analysis
ID SCHIZOPHRENIA; MRI
AB The analysis of fMRI data is challenging because they consist generally of a relatively modest signal contained in a high-dimensional space: a single scan can contain millions of voxel recordings over space and time We present a method for classification and discrimination among fMRI that is based on modeling the scans as distance matrices, where each matrix measures the divergence of spatial network signals that fluctuate over time. We used single-subject independent components analysis (ICA). decomposing an fMRI scan into a set of statistically independent spatial networks, to extract spatial networks and time courses front each Subject unique relationship with the other components within that Subject Mathematical properties of that have these relationships reveal information about the infrastructure of the brain by measuring the interaction between and strength of the components Our technique IS unique, in that it does not require spatial alignment of the scans across subjects Instead, the classifications are made solely on the temporal activity taken by the subject's unique ICs. Multiple scans are not required and multivariate classification is implementable, and the algorithm is effectively blind to the subject-uniform underlying task paradigm Classification accuracy of Lip to 90% was realized on a resting-scanned schizophrenia/normal dataset and a tasked multivariate Alzheimer's/old/young dataset We propose that the ICs represent a plausible set of imaging basis functions consistent with network-driven theories Of Mural activity in which the observed signal is an aggregate of independent spatial networks having possibly dependent temporal activity (C) 2009 Elsevier Inc. All rights reserved
C1 [Anderson, Ariana; Dinov, Ivo D.; Yuille, A. L.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA.
[Anderson, Ariana; Cohen, Mark S.] Univ Calif Los Angeles, Ctr Cognit Neurosci, Los Angeles, CA 90095 USA.
[Sherin, Jonathan E.; Quintana, Javier; Cohen, Mark S.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA.
[Anderson, Ariana; Dinov, Ivo D.; Sherin, Jonathan E.; Quintana, Javier; Cohen, Mark S.] UCLA Sch Med, Los Angeles, CA 90095 USA.
[Dinov, Ivo D.] Univ Calif Los Angeles, Ctr Computat Biol, Los Angeles, CA 90095 USA.
[Sherin, Jonathan E.; Quintana, Javier] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA.
[Yuille, A. L.] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA.
[Yuille, A. L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
RP Cohen, MS (reprint author), UCLA Ctr Cognit Neurosci, Suite C8-881,740 Westwood Plaza, Los Angeles, CA 90095 USA.
RI Cohen, Mark/C-6610-2011;
OI Cohen, Mark/0000-0001-6731-4053; Dinov, Ivo/0000-0003-3825-4375
FU NCRR NIH HHS [U54 RR021813]; NIDA NIH HHS [R21 DA026109-01, R21
DA026109, R21 DA026109-02, R21DA026109, R33 DA026109, R90 DA023422, R90
DA023422-01, T90 DA022768, T90DA022768]
NR 22
TC 12
Z9 12
U1 2
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2010
VL 49
IS 3
BP 2509
EP 2519
DI 10.1016/j.neuroimage.2009.08.036
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 544BN
UT WOS:000273626400053
PM 19712744
ER
PT J
AU Zivkovic, SA
Abdel-Hamid, H
AF Zivkovic, Sasa A.
Abdel-Hamid, Hoda
TI Neurologic Manifestations of Transplant Complications
SO NEUROLOGIC CLINICS
LA English
DT Article
DE Posttransplant recovery; Neurotoxicity; Opportunistic infections;
Transplant complications
ID BONE-MARROW-TRANSPLANTATION; SOLID-ORGAN TRANSPLANTATION; STEM-CELL
TRANSPLANTATION; INDUCED PAIN SYNDROME; LIVER-TRANSPLANTATION; LUNG
TRANSPLANTATION; CARDIAC TRANSPLANTATION; RENAL-TRANSPLANTATION;
PEDIATRIC-PATIENTS; TACROLIMUS FK506
AB Neurologic complications affect posttransplant recovery of more than 20% of transplant recipients. Etiology is usually related to surgical procedure of transplantation, primary disorders causing failure of transplanted organ, opportunistic infections, and neurotoxicity of immunosuppressive medications. Risk of opportunistic infections and immunosuppressant neurotoxicity is greatest within the first six months, but it persists along with long-term maintenance immunosuppression required to prevent graft rejection. Neurotoxicity may require alteration of immunosuppressive regimen, and prompt therapy of opportunistic infections improves outcomes.
C1 [Zivkovic, Sasa A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA.
[Zivkovic, Sasa A.] VA Pittsburgh Healthcare Syst, Neurol Serv, Pittsburgh, PA 15240 USA.
[Abdel-Hamid, Hoda] Univ Pittsburgh, Div Pediat Neurol, Childrens Hosp Pittsburgh, Sch Med, Pittsburgh, PA 15201 USA.
RP Zivkovic, SA (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, PUH F878,200 Lothrop St, Pittsburgh, PA 15213 USA.
EM zivkovics@upmc.edu
FU Health Resources and Services Administration [231-00-0115]
FX This work was supported in part by Health Resources and Services
Administration contract 231-00-0115. The content is the responsibility
of the authors alone and does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government.
NR 97
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U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0733-8619
J9 NEUROL CLIN
JI Neurol. Clin.
PD FEB
PY 2010
VL 28
IS 1
BP 235
EP +
DI 10.1016/j.ncl.2009.09.011
PG 18
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 617CL
UT WOS:000279258300014
PM 19932384
ER
PT J
AU Belanto, JJ
Diaz-Perez, SV
Magyar, CE
Maxwell, MM
Yilmaz, Y
Topp, K
Boso, G
Jamieson, CH
Cacalano, NA
Jamieson, CAM
AF Belanto, Joseph J.
Diaz-Perez, Silvia V.
Magyar, Clara E.
Maxwell, Michele M.
Yilmaz, Yasemin
Topp, Kasey
Boso, Guney
Jamieson, Catriona H.
Cacalano, Nicholas A.
Jamieson, Christina A. M.
TI Dexamethasone induces dysferlin in myoblasts and enhances their myogenic
differentiation
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE Dysferlinopathy; Limb-girdle muscular dystrophy type 2B; Miyoshi
myopathy; Glucocorticoid; Myotube; C2C12; Myoblast differentiation;
Dysferlin; Dexamethasone
ID GIRDLE MUSCULAR-DYSTROPHY; MUSCLE STEM-CELLS; SKELETAL-MUSCLE;
GENE-EXPRESSION; MESSENGER-RNA; IN-VITRO; INFLAMMATION; DEFICIENCY;
MYOPATHY; RECEPTOR
AB Glucocorticoids are beneficial in many muscular dystrophies but they are ineffective in treating dysferlinopathy, a rare muscular dystrophy caused by loss of dysferlin. We sought to understand the molecular basis for this disparity by studying the effects Of a glucocorticoid on differentiation of the myoblast cell line, C2C12, and dysferlin-deficient C2C12s. We found that pharmacologic doses of dexamethasone enhanced the myogenic fusion efficiency of C2C12s and increased the induction of dysferlin, along with specific myogenic transcription factors, sarcolemmal and structural proteins. In contrast, the dysferlin-deficient C2C12 cell line demonstrated a reduction in long myotubes and early induction of particular muscle differentiation proteins, most notably, myosin heavy chain. Dexamethasone partially reversed the defect in myogenic fusion in the dysferlin-deficient C2C12 cells. We hypothesize that a key therapeutic benefit Of glucocorticoids may be the up-regulation of dysferlin as an important component of glucocorticoid-enhanced myogenic differentiation. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Belanto, Joseph J.; Yilmaz, Yasemin; Jamieson, Christina A. M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
[Belanto, Joseph J.; Diaz-Perez, Silvia V.; Topp, Kasey; Boso, Guney; Jamieson, Christina A. M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Magyar, Clara E.] Univ Calif Los Angeles, David Geffen Sch Med, Translat Pathol Core Lab, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Maxwell, Michele M.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA.
[Jamieson, Catriona H.] Univ Calif San Diego, Sch Med, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA.
[Cacalano, Nicholas A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA.
RP Jamieson, CAM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 4554 Gonda Ctr 708822,695 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM CJamieson@mednet.ucla.edu
FU C.B. Day Investment Company; ViaCell, Inc.; Thayer family; Jain
Foundation, Inc; NIH-NCRR [CJX1-443835-WS-29646, CBRP U19]; NSF
[CHE-0722519]; University of California at Los Angeles Center for
Biological Radioprotectors [U19 A1067769/NIAID]
FX We thank Drs. Michele M. Maxwell and Robert H. Brown, Jr. for generously
providing the dysferlin-deficient C2C12 cells the development of which
was supported by the C.B. Day Investment Company, ViaCell, Inc., the
Thayer family and the Jain Foundation, Inc. We are grateful to Dr.
Matthew J. Schibler for help with confocal microscopy. Confocal laser
scanning microscopy was performed at the CNSI Advanced Light
Microscopy/Spectroscopy Shared Resource Facility at UCLA, supported with
funding from NIH-NCRR shared resources grant (CJX1-443835-WS-29646) and
NSF Major Research Instrumentation grant (CHE-0722519). This work was
supported by a grant from the Jain Foundation, Inc. (C.A.M. Jamieson)
and NIH CBRP U19 (C.A.M. Jamieson, N. Cacalano) University of California
at Los Angeles Center for Biological Radioprotectors grant U19
A1067769/NIAID.
NR 62
TC 23
Z9 23
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD FEB
PY 2010
VL 20
IS 2
BP 111
EP 121
DI 10.1016/j.nmd.2009.12.003
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 563RP
UT WOS:000275151400005
PM 20080405
ER
PT J
AU Kubrusly, RCC
Bhide, PG
AF Kubrusly, Regina C. C.
Bhide, Pradeep G.
TI Cocaine exposure modulates dopamine and adenosine signaling in the fetal
brain
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Cocaine; Dopamine; Adenosine; Brain development
ID ADENYLYL-CYCLASE ACTIVITY; GABA NEURON MIGRATION; PRENATAL COCAINE;
CEREBRAL-CORTEX; RECEPTOR INTERACTIONS; GANGLIONIC EMINENCE; A(2A)
RECEPTORS; GENE-EXPRESSION; MOUSE MODEL; RAT-BRAIN
AB Exposure to cocaine during the fetal period can produce significant lasting changes in the structure and function of the brain. Cocaine exerts its effects on the developing brain by blocking monoamine transporters and impairing monoamine receptor signaling. Dopamine is a major central target of cocaine. In a mouse model, we show that cocaine exposure from embryonic day 8 (E8) to EA produces significant reduction in dopamine transporter activity, attenuation of dopamine D1-receptor function and upregulation of dopamine D2-receptor function. Cocaine's effects on the D1-receptor are at the level of protein expression as well as activity. The cocaine exposure also produces significant increases in basal cAMP levels in the striatum and cerebral cortex. The increase in the basal cAMP levels was independent of dopamine receptor activity. In contrast, blocking the adenosine A2a receptor down regulated the basal CAMP levels in the cocaine-exposed brain to physiological levels, suggesting the involvement of adenosine receptors in mediating cocaine's effects on the embryonic brain. In support of this suggestion, we found that the cocaine exposure downregulated adenosine transporter function. We also found that dopamine D2- and adenosine A2a-receptors antagonize each other's function in the embryonic brain in a manner consistent with their interactions in the mature brain. Thus, our data show that prenatal cocaine exposure produces direct effects on both the dopamine and adenosme systems. Furthermore, the dopamine D2 and adenosine A2a receptor interactions in the embryonic brain discovered in this study unveil a novel substrate for cocaine's effects on the developing brain. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Kubrusly, Regina C. C.; Bhide, Pradeep G.] Massachusetts Gen Hosp, Dev Neurobiol Neurol Dept, Boston, MA 02129 USA.
[Kubrusly, Regina C. C.; Bhide, Pradeep G.] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Kubrusly, Regina C. C.] Univ Fed Fluminense, Dept Fisiol & Farmacol, Lab Neurofarmacol, Rio De Janeiro, Brazil.
RP Bhide, PG (reprint author), Massachusetts Gen Hosp, 149,13th St, Charlestown, MA 02129 USA.
EM bhide@helix.mgh.harvard.edu
RI Neurociencia, Inct/I-1011-2013;
OI Bhide, Pradeep/0000-0003-4236-9415
FU USPHS [R01 DA020796, P30NS045776]; Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (CNPq), Brazil
FX Supported by USPHS grants R01 DA020796 and P30NS045776 to PGB and a
fellowship from the Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico (CNPq), Brazil to RCCK. We gratefully acknowledge advice and
assistance from our colleagues Deirdre McCarthy, Jia-Qian Ren and John
Sims in the course of this work.
NR 48
TC 14
Z9 15
U1 2
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD FEB
PY 2010
VL 58
IS 2
BP 436
EP 443
DI 10.1016/j.neuropharm.2009.09.007
PG 8
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 557MX
UT WOS:000274674500015
PM 19765599
ER
PT J
AU Costello, MR
Mandelkern, MA
Shoptaw, S
Shulenberger, S
Baker, SK
Abrams, AL
Xia, C
London, ED
Brody, AL
AF Costello, Matthew R.
Mandelkern, Mark A.
Shoptaw, Stephen
Shulenberger, Stephanie
Baker, Stephanie K.
Abrams, Anna L.
Xia, Catherine
London, Edythe D.
Brody, Arthur L.
TI Effects of Treatment for Tobacco Dependence on Resting Cerebral Glucose
Metabolism
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE tobacco dependence; nicotine; cigarette; 18F-fluorodeoxyglucose-positron
emission tomography (FDG-PET); statistical parametric mapping; bupropion
HCl
ID SUSTAINED-RELEASE BUPROPION; SMOKING-CESSATION; CIGARETTE-SMOKING;
CONTROLLED-TRIAL; DOPAMINE TRANSPORTER; RELAPSE PREVENTION; PLASMA
NICOTINE; DEFAULT MODE; HUMAN BRAIN; BLOOD-FLOW
AB While bupropion HCl and practical group counseling (PGC) are commonly used treatments for tobacco dependence, the effects of these treatments on brain function are not well established. For this study, 54 tobacco-dependent cigarette smokers underwent resting (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning before and after 8 weeks of treatment with bupropion HCl, PGC, or pill placebo. Using Statistical Parametric Mapping (SPM 2), changes in cerebral glucose metabolism from before to after treatment were compared between treatment groups and correlations were determined between amount of daily cigarette usage and cerebral glucose metabolism. Compared with placebo, the two active treatments (bupropion HCl and PGC) had reductions in glucose metabolism in the posterior cingulate gyrus. Further analysis suggested that PGC had a greater effect than bupropion HCl on glucose metabolism in this region. We also found positive correlations between daily cigarette use and glucose metabolism in the left occipital gyrus and parietal-temporal junction. There were no significant negative correlations between daily cigarette use and glucose metabolism. Our findings suggest that bupropion HCl and PGC reduce neural activity much as the performance of a goal-oriented task does in the default mode network of the brain, including the posterior cingulate gyrus. Thus, this study supports the theory that active treatments for tobacco dependence move the brain into a more goal-oriented state. Neuropsychopharmacology (2010) 35, 605-612; doi:10.1038/npp.2009.165; published online 28 October 2009
C1 [Shoptaw, Stephen; London, Edythe D.; Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Costello, Matthew R.; Mandelkern, Mark A.; Shulenberger, Stephanie; Baker, Stephanie K.; Abrams, Anna L.; Xia, Catherine; Brody, Arthur L.] Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA.
[Mandelkern, Mark A.] UCI, Dept Phys, Irvine, CA USA.
[London, Edythe D.; Brody, Arthur L.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA.
[London, Edythe D.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA.
EM abrody@ucla.edu
FU National Institute on Drug Abuse [R01 DA20872]; Veterans Administration;
Tobacco-Related Disease Research Program [16RT-0098]; Office of National
Drug Control Policy [DABT 63-00C-1003]; National Alliance for Research
on Schizophrenia and Depression
FX Supported by the National Institute on Drug Abuse ( ALB ( R01 DA20872)),
the Veterans Administration ( ALB ( Merit Review Type I Award)), the
Tobacco-Related Disease Research Program ( ALB ( 16RT-0098)), the Office
of National Drug Control Policy ( EDL ( DABT 63-00C-1003)), and the
National Alliance for Research on Schizophrenia and Depression ( ALB).
Initial study results were presented at the 2008 Society for Research on
Nicotine and Tobacco meeting. We thank Josephine Ribe and Michael Clark
for technical support in performing positron emission tomography and
magnetic resonance imaging scans, respectively.
NR 54
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Z9 4
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD FEB
PY 2010
VL 35
IS 3
BP 605
EP 612
DI 10.1038/npp.2009.165
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 544EK
UT WOS:000273635100002
PM 19865076
ER
PT J
AU Blake, KD
Viswanath, K
Blendon, RJ
Vallone, D
AF Blake, Kelly D.
Viswanath, K.
Blendon, Robert J.
Vallone, Donna
TI The role of tobacco-specific media exposure, knowledge, and smoking
status on selected attitudes toward tobacco control
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID UNITED-STATES; CANCER; SUPPORT; SMOKERS; BEHAVIOR; RESTRICTIONS;
INDIVIDUALS; NONSMOKERS; RISKS; AIR
AB Background: In August 2007, the President's Cancer Panel urged the leadership of the nation to "summon the political will to address the public health crisis caused by tobacco use" (President's Cancer Panel, N, 2007, Promoting healthy lifestyles: Policy, program, and personal recommendations for reducing cancer risk. http://deainfo.nci.nih.gov/advisory/pcp/pcp07rpt/pcp07rpt.pdf). While some research has examined predictors of public support for tobacco control measures, little research has examined modifiable factors that may influence public attitudes toward tobacco control.
Methods: We used the American Legacy Foundation's 2003 American Smoking and Health Survey 2 to examine the contribution of smoking status, knowledge of the negative effects of tobacco, and tobacco-specific media exposure (antitobacco messages, news coverage of tobacco issues, and protobacco advertising) on U. S. adults' attitudes toward tobacco control. In addition, we assessed whether smoking status moderates the relationship between tobacco-specific media exposure and policy attitudes. Weighted multivariable logistic regression models were employed.
Results: Results suggest that knowledge of the negative effects of tobacco and smoking status are associated with attitudes toward tobacco control and that exposure to tobacco-specific information in the media plays a role only in some instances. We found no evidence of effect modification by smoking status on the impact of exposure to tobacco-specific media on attitudes toward tobacco control.
Discussion: Understanding the impact of readily modifiable factors that shape policy attitudes is essential if we are to target outreach and education in a way that is likely to sway public support for tobacco control.
C1 [Blake, Kelly D.; Viswanath, K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Blake, Kelly D.; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Blendon, Robert J.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Vallone, Donna] Amer Legacy Fdn, Washington, DC USA.
RP Blake, KD (reprint author), Dana Farber Canc Inst, 44 Binney St,MS LW703, Boston, MA 02115 USA.
EM kellyblake@post.harvard.edu
FU National Cancer Institute [5R25CA057711-14]
FX This study was made possible by the Harvard Education Program in Cancer
Prevention and Control, grant 5R25CA057711-14 from the National Cancer
Institute.
NR 31
TC 18
Z9 18
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD FEB
PY 2010
VL 12
IS 2
BP 117
EP 126
DI 10.1093/ntr/ntp184
PG 10
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 553CQ
UT WOS:000274342900005
PM 20018944
ER
PT J
AU Gray, KM
DeSantis, SM
Carpenter, MJ
Saladin, ME
LaRowe, SD
Upadhyaya, HP
AF Gray, Kevin M.
DeSantis, Stacia M.
Carpenter, Matthew J.
Saladin, Michael E.
LaRowe, Steven D.
Upadhyaya, Himanshu P.
TI Menstrual cycle and cue reactivity in women smokers
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID SMOKING-BEHAVIOR; CIGARETTE-SMOKING; PHASE; NICOTINE; ABSTINENCE;
CESSATION; SESSIONS; RELAPSE
AB Introduction: Emerging research suggests potential effects of the menstrual cycle on various aspects of smoking behavior in women, but results to date have been mixed. The present study sought to explore the influence of menstrual cycle phase on reactivity to smoking in vivo and stressful imagery cues in a sample of non-treatment-seeking women smokers.
Methods: Via a within-subjects design, nicotine-dependent women (N = 37) participated in a series of four cue reactivity sessions, each during a distinct biologically verified phase of the menstrual cycle (early follicular [EF], mid-follicular [MF], midluteal [ML], and late luteal [LL]). Subjective (Questionnaire of Smoking Urges-Brief; QSU-B) and physiological (skin conductance and heart rate) measures of craving and reactivity were collected and compared across phases.
Results: Subjective reactive craving (QSU-B) to smoking in vivo cues varied significantly across the menstrual cycle (p = .02) and was higher in both EF and MF phases versus ML and LL phases, but this finding was not sustained when controlling for reactivity to neutral cues. Heart rate reactivity to stressful imagery cues (p = .01) and skin conductance reactivity to smoking in vivo cues (p = .05) varied significantly across the menstrual cycle upon controlling for reactivity to neutral cues, with highest reactivity during the MF phase.
Discussion: Menstrual cycle phase may have an effect on reactivity to smoking-related and stressful cues among women smokers. These findings contribute to an expanding literature, suggesting menstrual cycle effects on smoking behaviors in women.
C1 [Gray, Kevin M.] Med Univ S Carolina, Youth Div, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[DeSantis, Stacia M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Carpenter, Matthew J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Saladin, Michael E.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
[LaRowe, Steven D.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Gray, KM (reprint author), Med Univ S Carolina, Youth Div, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA.
EM graykm@musc.edu
FU National Institute on Drug Abuse [P50 DA016511, K12 DA000357, K23
DA020482]; United States Public Health Service [M01 RR01070]
FX This research was supported by National Institute on Drug Abuse grants
P50 DA016511 (HPU, component PI; Drs. Kathleen T. Brady and Ronald See,
Center PIs), K12 DA000357 (KMG), and K23 DA020482 (MJC) as well as
United States Public Health Service grant M01 RR01070 (Medical
University of South Carolina Clinical and Translational Research
Center).
NR 27
TC 11
Z9 11
U1 4
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD FEB
PY 2010
VL 12
IS 2
BP 174
EP 178
DI 10.1093/ntr/ntp179
PG 5
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 553CQ
UT WOS:000274342900013
PM 19996146
ER
PT J
AU Lattanzi, R
Grant, AK
Polimeni, JR
Ohliger, MA
Wiggins, GC
Wald, LL
Sodickson, DK
AF Lattanzi, Riccardo
Grant, Aaron K.
Polimeni, Jonathan R.
Ohliger, Michael A.
Wiggins, Graham C.
Wald, Lawrence L.
Sodickson, Daniel K.
TI Performance evaluation of a 32-element head array with respect to the
ultimate intrinsic SNR
SO NMR IN BIOMEDICINE
LA English
DT Article
DE Magnetic Resonance Imaging; RE coils; phased-array; coil performance;
coil design; parallel imaging; electrodynamics; ultimate intrinsic SNR
ID TO-NOISE RATIO; PHASED-ARRAY; COIL ARRAYS; MRI; SENSE; DESIGN; IMAGES
AB The quality of an RF detector coil design is commonly judged on how it compares with other coil configurations. The aim of this article is to develop a tool for evaluating the absolute performance of RF coil arrays. An algorithm to calculate the ultimate intrinsic signal-to-noise ratio (SNR) was implemented for a spherical geometry. The same imaging tasks modeled in the calculations were reproduced experimentally using a 32-element head array. Coil performance maps were then generated based on the ratio of experimentally measured SNR to the ultimate intrinsic SNR, for different acceleration factors associated with different degrees of parallel imaging. The relative performance in all cases was highest near the center of the samples (where the absolute SNR was lowest). The highest performance was found in the unaccelerated case and a maximum of 85% was observed with a phantom whose electrical properties are consistent with values in the human brain. The performance remained almost constant for 2-fold acceleration, but deteriorated at higher acceleration factors, suggesting that larger arrays are needed for effective highly-accelerated parallel imaging. The method proposed here can serve as a tool for the evaluation of coil designs, as well as a tool to guide the development of original designs which may begin to approach the optimal performance. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Lattanzi, Riccardo; Wiggins, Graham C.; Sodickson, Daniel K.] NYU, Langone Med Ctr, Ctr Biomed Imaging, Dept Radiol, New York, NY 10016 USA.
[Grant, Aaron K.] Beth Israel Deaconess Med Ctr, Dept Radiol, Div Magnet Resonance Res, Boston, MA 02215 USA.
[Grant, Aaron K.] Harvard Univ, Sch Med, Boston, MA USA.
[Polimeni, Jonathan R.; Wald, Lawrence L.] MGH HMS MIT, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Polimeni, Jonathan R.; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Ohliger, Michael A.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
RP Sodickson, DK (reprint author), NYU, Med Ctr, Dept Radiol, 660 1st Ave,4th Floor, New York, NY 10016 USA.
EM Daniel.Sodickson@nyumc.org
RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009;
OI Polimeni, Jonathan/0000-0002-1348-1179; , Riccardo/0000-0002-8240-5903;
Sodickson, Daniel/0000-0002-2436-4664
FU AIIH [R01-EB000447, R01-EB002468, R01-1EB00684, P41-RR14075]; Siemens
Medical Solutions
FX Contract/grant sponsor: AIIH; contract/grant numbers: R01-EB000447,
RO1-EB002468, R01-1EB00684, P41-RR14075.; Contract/grant sponsor:
Siemens Medical Solutions.
NR 29
TC 7
Z9 7
U1 1
U2 9
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD FEB
PY 2010
VL 23
IS 2
BP 142
EP 151
DI 10.1002/nbm.1435
PG 10
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 570VQ
UT WOS:000275706800004
PM 19904727
ER
PT J
AU Espana, S
Fraile, LM
Herraiz, JL
Udias, JM
Desco, M
Vaquero, JJ
AF Espana, S.
Fraile, L. M.
Herraiz, J. L.
Udias, J. M.
Desco, M.
Vaquero, J. J.
TI Performance evaluation of SiPM photodetectors for PET imaging in the
presence of magnetic fields
SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS
SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT
LA English
DT Article
DE Silicon photomultiplier; Positron emission tomography; Magnetic
resonance imaging
ID DETECTOR MODULE; IDENTIFICATION; READOUT; LSO
AB The multi-pixel photon counter (MPPC) or silicon photomultiplier (SiPM), recently introduced as a solid-state photodetector, consists of an array of Geiger-mode photodiodes (microcells). It is a promising device for PET due to its potential for high photon detection efficiency (PDE) and its foreseeable immunity to magnetic fields. It is also easy to use with simple read-outs, has a high gain and a small size. In this work we evaluate the in field performance of three I X I mm(2) (With 100, 400 and 1600 microcells, respectively) and one 6 x 6 mm(2) (arranged as a 2 x 2 array) Hamamatsu MPPCs for their use in PET imaging. We examine the dependence of the energy resolution and the gain of these devices on the temperature and reverse bias voltage, when coupled to LYSO scintillator crystals under conditions that one would find in a PET system. We find that the 400 and 1600 microcells models and the 2 x 2 array are suitable for small-size crystals, like those employed in high resolution small animal scanners. We have confirmed the good performance of these devices up to magnetic fields of 7T as well as their suitability for performing PET acquisitions in the presence of fast switching gradients and high duty radiofrequency MRI sequences. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.
C1 [Espana, S.; Fraile, L. M.; Herraiz, J. L.; Udias, J. M.] Univ Complutense Madrid, Dpto Fis Atom Mol & Nucl, Grp Fis Nucl, E-28040 Madrid, Spain.
[Desco, M.; Vaquero, J. J.] Hosp Gen Univ Gregorio Maranon, Unidad Med & Cirugia Expt, Madrid, Spain.
RP Espana, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM samuel@nuclear.fis.ucm.es
RI LOPEZ HERRAIZ, JOAQUIN/E-9234-2010; Fraile, Luis/B-8668-2011; Udias,
Jose/A-7523-2010; Vaquero, Juan Jose/D-3033-2009; Desco,
Manuel/D-2822-2009; Espana, Samuel/E-9240-2010
OI LOPEZ HERRAIZ, JOAQUIN/0000-0001-7208-8863; Fraile,
Luis/0000-0002-6281-3635; Udias, Jose/0000-0003-3714-764X; Vaquero, Juan
Jose/0000-0001-9200-361X; Desco, Manuel/0000-0003-0989-3231; Espana,
Samuel/0000-0001-9092-4597
FU Ministerio de Ciencia e Innovacion [FPA2007-62216TEC2008-06715-C02-01];
UCM [910059]; CPAN [CSPD-200700042]; UE
FX This work was supported in part by the CDTEAM project of the CENIT
program, and by Ministerio de Ciencia e Innovacion under projects
FPA2007-62216TEC2008-06715-C02-01, UCM (Grupos UCM: 910059), CPAN
(Consolider-Ingenio 2010) CSPD-200700042 projects, and project
SENSORCZT-S-0505/MAT/000279, Comunidad de Madrid. Part of the
computations of this work were done at the "High Capacity Cluster for
Physical Techniques" of UCM, funded in part by the UE under the FEDER
program and in part by UCM.
NR 17
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U1 4
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-9002
J9 NUCL INSTRUM METH A
JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc.
Equip.
PD FEB 1
PY 2010
VL 613
IS 2
BP 308
EP 316
DI 10.1016/j.nima.2009.11.066
PG 9
WC Instruments & Instrumentation; Nuclear Science & Technology; Physics,
Nuclear; Physics, Particles & Fields
SC Instruments & Instrumentation; Nuclear Science & Technology; Physics
GA 560DK
UT WOS:000274882000020
ER
PT J
AU Brubaker, L
Rickey, L
Xu, Y
Markland, A
Lemack, G
Ghetti, C
Kahn, MA
Nagaraju, P
Norton, P
Chang, TD
Stoddard, A
AF Brubaker, Linda
Rickey, Leslie
Xu, Yan
Markland, Alayne
Lemack, Gary
Ghetti, Chiara
Kahn, Margie A.
Nagaraju, Pradeep
Norton, Peggy
Chang, T. Debuene
Stoddard, Anne
CA Urinary Incontinence Treatment Net
TI Symptoms of Combined Prolapse and Urinary Incontinence in Large Surgical
Cohorts
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID PELVIC ORGAN PROLAPSE; QUALITY-OF-LIFE; UROGENITAL DISTRESS INVENTORY;
STRESS-INCONTINENCE; IMPACT QUESTIONNAIRE; FLOOR DISORDERS; WOMEN;
PREVALENCE; SEVERITY; STANDARDIZATION
AB OBJECTIVE: To estimate whether prolapse severity is a major contributor to urinary incontinence severity, as measured by validated incontinence questionnaires.
METHODS: We analyzed data from two large female stress urinary incontinence (SUI) surgical cohorts: the Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) study (N=655) and the subsequent Trial of Mid-Urethral Slings (TOMUS) study (N=597). All participants completed a standardized baseline assessment including validated measures of symptom severity, quality of life, objective measures of urine loss (Urogenital Distress Inventory [UDI], Medical, Epidemiologic, and Social Aspects of Aging questionnaire, Incontinence Impact Questionnaire, and pad test), as well as the Pelvic Organ Prolapse Quantification assessment. Groups were compared using the) chi(2); test (categorical measures) or the one-way analysis of variance (continuous measures). Statistical significance was defined as P<.05.
RESULTS: The SISTEr and TOMUS samples were similar for many variables including age (52 and 53 years, respectively), nulliparity (9% and 12%), prior urinary incontinence (UI) surgery (14% and 13%), and prior hysterectomy (31% and 28%), but other differences necessitated separate analysis of the two cohorts. There was not a statistically significant difference in UDI scores according to prolapse stage in either study population. Patients with prior surgery for pelvic organ prolapse and SUI had more incontinence symptoms and were more bothered by their UI regardless of prolapse stage.
CONCLUSION: Prolapse stage is not strongly or consistently associated with incontinence severity in women who select surgical treatment of SUI. Prior pelvic organ prolapse and UI surgery is associated with worse UI severity and bother.
C1 Loyola Univ, Stritch Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
Loyola Univ, Stritch Sch Med, Dept Urol, Chicago, IL 60611 USA.
Univ Maryland, Dept Urol, Baltimore, MD 21201 USA.
New England Res Inst, Watertown, MA 02172 USA.
Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA.
Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
Kaiser Permanente, San Diego, CA USA.
William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA.
Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
NIDDK, NIH, Bethesda, MD USA.
RP Brubaker, L (reprint author), Loyola Univ Chicago, Stritch Sch Med, 2160 S 1st Ave,Bldg 103, Maywood, IL 60153 USA.
EM LBrubaker@lumc.edu
FU Pfizer (New York, AT); Allergan (Irvine, CA)
FX Dr. Brubaker has received research funding from Pfizer (New York, AT)
and Allergan (Irvine, CA) and. has been a research consultant for
Pfizer. Dr. Lemak has been a clinical trial participant for Allergan, a
consultant and lecturer for Astellas (Deerfield, IL) and Pfizer, and a
lecturer for Novartis (Basel, Switzerland). Dr. Ghetti served as a
co-investigator for the Bridges study with the University of California,
San Francisco, which was partially funded by Pfizer. The other authors
did not report any potential conflicts of interest.
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U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD FEB
PY 2010
VL 115
IS 2
BP 310
EP 316
PN 1
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 547FS
UT WOS:000273872500015
PM 20093904
ER
PT J
AU Huang, YJ
Kim, E
Cox, MJ
Brodie, EL
Brown, R
Wiener-Kronish, JP
Lynch, SV
AF Huang, Yvonne J.
Kim, Eugenia
Cox, Michael J.
Brodie, Eoin L.
Brown, Ron
Wiener-Kronish, Jeanine P.
Lynch, Susan V.
TI A Persistent and Diverse Airway Microbiota Present during Chronic
Obstructive Pulmonary Disease Exacerbations
SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
LA English
DT Article
ID PSEUDOMONAS-AERUGINOSA; CYSTIC-FIBROSIS; NOSOCOMIAL PNEUMONIA; GASTRIC
COLONIZATION; BACTERIAL DIVERSITY; INFECTIONS; DNA; IDENTIFICATION;
BACTEREMIA; CHILDREN
AB Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases.
C1 [Huang, Yvonne J.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA.
[Kim, Eugenia; Cox, Michael J.; Brown, Ron; Lynch, Susan V.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Brodie, Eoin L.] Lawrence Berkeley Natl Lab, Dept Ecol, Div Earth Sci, Berkeley, CA USA.
[Wiener-Kronish, Jeanine P.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
RP Lynch, SV (reprint author), Univ Calif San Francisco, Dept Med, Div Gastroenterol, 513 Parnassus Ave,S-357, San Francisco, CA 94143 USA.
EM susan.lynch@ucsf.edu
RI Cox, Michael/A-6959-2010; Lynch, Susan/B-6272-2009; Brodie,
Eoin/A-7853-2008;
OI Brodie, Eoin/0000-0002-8453-8435; Cox, Michael/0000-0002-4002-1506
FU University of California [DOE DE-AC02-05CH11231]; American Lung
Association; NIH [AI075410]
FX The authors thank Yvette Piceno, Todd DeSantis, and Gary Andersen at
Lawrence Berkeley National Laboratory for their advice and technical
support in this study, and to Homer Boushey, M.D., for his critique of
the manuscript. Part of this work was performed at Lawrence Berkeley
National Laboratory under the auspices of the University of California
under contract number DOE DE-AC02-05CH11231. Research was supported by a
Tobacco-Related Disease Research Program (Univ. of California)
fellowship to Y.J.H. and an American Lung Association grant to S.V.L.
S.V.L. and E.L.B. are funded also by NIH Award (AI075410).
NR 43
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U1 1
U2 13
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1536-2310
J9 OMICS
JI OMICS
PD FEB
PY 2010
VL 14
IS 1
BP 9
EP 59
DI 10.1089/omi.2009.0100
PG 51
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 554GO
UT WOS:000274423700002
PM 20141328
ER
PT J
AU Borgaonkar, SP
Hocker, H
Shin, HJ
Markey, MK
AF Borgaonkar, Sanket P.
Hocker, Harrison
Shin, Hyunjin
Markey, Mia K.
TI Comparison of Normalization Methods for the Identification of Biomarkers
Using MALDI-TOF and SELDI-TOF Mass Spectra
SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
LA English
DT Article
ID ENHANCED LASER-DESORPTION; SPECTROMETRY DATA; BREAST-CANCER; CLINICAL
PROTEOMICS; COLORECTAL-CANCER; FEATURE-SELECTION; BLOOD-SERUM;
CLASSIFICATION; DISEASE; SAMPLES
AB Proteomic profiling by mass spectrometry has tremendous potential for identifying disease biomarkers. A key limitation of mass spectrometry is that the information provided on the abundance of the various peptides is only relative. Thus, normalization is typically employed. Several normalization methods have been proposed and implemented in the literature. However, it is not clear if there is any reason to prefer one method over another. The goal of this study was to investigate the effect of normalization strategy on the identification of putative biomarkers from MALDI-TOF and SELDI-TOF mass spectra. Our results demonstrate that many of the putative biomarkers identified by mass spectrometry will be the same regardless of which data normalization scheme is applied. However, there can be substantial differences in the m/z values identified as being most discriminatory based on choice of normalization method. As there is no consistent pattern as to which normalization method yields the most promising targets for follow up study, we recommend that investigators routinely repeat their analysis with multiple normalization methods and consider the top several candidates identified in each case.
C1 [Borgaonkar, Sanket P.; Hocker, Harrison; Markey, Mia K.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
[Shin, Hyunjin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
RP Borgaonkar, SP (reprint author), Univ Texas Austin, Dept Biomed Engn, 1 Univ Stn C0800, Austin, TX 78712 USA.
EM sanborg@gmail.comM
OI Markey, Mia/0000-0001-8186-4959
NR 44
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U1 1
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1536-2310
J9 OMICS
JI OMICS
PD FEB
PY 2010
VL 14
IS 1
BP 115
EP 126
DI 10.1089/omi.2009.0082
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 554GO
UT WOS:000274423700008
PM 20141334
ER
PT J
AU Henderson, BA
Kim, JY
Golnik, KC
Oetting, TA
Lee, AG
Volpe, NJ
Aaron, M
Uhler, TA
Arnold, A
Dunn, JP
Prajna, NV
Lane, AM
Loewenstein, JI
AF Henderson, Bonnie An
Kim, Jae Yong
Golnik, Karl C.
Oetting, Thomas A.
Lee, Andrew G.
Volpe, Nicholas J.
Aaron, Maria
Uhler, Tara A.
Arnold, Anthony
Dunn, James P.
Prajna, N. Venkatesh
Lane, Anne Marie
Loewenstein, John I.
TI Evaluation of the Virtual Mentor Cataract Training Program
SO OPHTHALMOLOGY
LA English
DT Article
ID NONTECHNICAL SKILLS; TECHNICAL SKILLS; SURGEONS; PHACOEMULSIFICATION;
RESIDENTS; SIMULATOR; TOOL
AB Objective: Evaluate the effectiveness of an interactive cognitive computer simulation for teaching the hydrodissection portion of cataract surgery compared with standard teaching and to assess the attitudes of residents about the teaching tools and their perceived confidence in the knowledge gained after using the tools.
Design: Case-control study.
Participants and Controls: Residents at academic institutions.
Methods: Prospective, multicenter, single-masked, controlled trial was performed in 7 academic departments of ophthalmology (Harvard Medical School/Massachusetts Eye and Ear Infirmary, University of Iowa, Emory University, University of Cincinnati, University of Pennsylvania/Scheie Eye Institute, Jefferson Medical College of Thomas Jefferson University/Wills Eye Institute, and the Aravind Eye Institute). All residents from these centers were asked to participate and were randomized into 2 groups. Group A (n = 30) served as the control and received traditional teaching materials; group B (n = 38) received a digital video disc of the Virtual Mentor program. This program is an interactive cognitive simulation, specifically designed to separate cognitive aspects (such as decision making and error recognition) from the motor aspects. Both groups took online anonymous pretests (n = 68) and posttests (n = 58), and answered satisfaction questionnaires (n = 53). Wilcoxon tests were completed to compare pretest and posttest scores between groups. Analysis of variance was performed to assess differences in mean scores between groups.
Main Outcome Measures: Scores on pretests, posttests, and satisfaction questionnaires.
Results: There was no difference in the pretest scores between the 2 groups (P = 0.62). However, group B (Virtual Mentor [VM]) scored significantly higher on the posttest (P = 0.01). Mean difference between pretest and posttest scores were significantly better in the VM group than in the traditional learning group (P = 0.04). Questionnaire revealed that the VM program was "more fun" to use (24.1% vs 4.2%) and residents were more likely to use this type of program again compared with the likelihood of using the traditional tools (58.6% vs 4.2%).
Conclusions: The VM, a cognitive computer simulation, augmented teaching of the hydrodissection step of phacoemulsification surgery compared with traditional teaching alone. The program was more enjoyable and more likely to be used repetitively by ophthalmology residents.
Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references. Ophthalmology 2010; 117: 253-258 (C) 2010 by the American Academy of Ophthalmology.
C1 [Lane, Anne Marie; Loewenstein, John I.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA.
[Kim, Jae Yong] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea.
[Golnik, Karl C.] Univ Cincinnati, Cincinnati, OH USA.
[Golnik, Karl C.] Cincinnati Eye Inst, Cincinnati, OH USA.
[Oetting, Thomas A.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
[Oetting, Thomas A.] Vet Affairs Med Ctr, Cincinnati, OH 45267 USA.
[Lee, Andrew G.] Methodist Hosp, Dept Ophthalmol, Houston, TX 77030 USA.
[Volpe, Nicholas J.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA.
[Aaron, Maria] Emory Univ, Sch Med, Atlanta, GA USA.
[Uhler, Tara A.] Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Inst, Philadelphia, PA 19107 USA.
[Arnold, Anthony] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
[Dunn, James P.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
[Prajna, N. Venkatesh] Aravind Eye Hosp, Madurai, Tamil Nadu, India.
RP Henderson, BA (reprint author), Ophthalm Consultants Boston, Wollongong, NSW 2500, Australia.
EM bahenderson@eyeboston.com
FU Massachusetts Lions Club; Norman Knight Ophthalmology Fund
FX Sponsored in part by a grant from the Massachusetts Lions Club and the
Norman Knight Ophthalmology Fund.
NR 19
TC 7
Z9 7
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2010
VL 117
IS 2
BP 253
EP 258
DI 10.1016/j.ophtha.2009.07.009
PG 6
WC Ophthalmology
SC Ophthalmology
GA 555RB
UT WOS:000274530300010
PM 19969355
ER
PT J
AU Pujari, SS
Kempen, JH
Newcomb, CW
Gangaputra, S
Daniel, E
Suhler, EB
Thorne, JE
Jabs, DA
Levy-Clarke, GA
Nussenblatt, RB
Rosenbaum, JT
Foster, CS
AF Pujari, Siddharth S.
Kempen, John H.
Newcomb, Craig W.
Gangaputra, Sapna
Daniel, Ebenezer
Suhler, Eric B.
Thorne, Jennifer E.
Jabs, Douglas A.
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Rosenbaum, James T.
Foster, C. Stephen
TI Cyclophosphamide for Ocular Inflammatory Diseases
SO OPHTHALMOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; KOYANAGI-HARADA-SYNDROME;
WEGENERS-GRANULOMATOSIS; INTRAVENOUS CYCLOPHOSPHAMIDE;
RHEUMATOID-ARTHRITIS; IMMUNOSUPPRESSIVE THERAPY; PULSE CYCLOPHOSPHAMIDE;
FOLLOW-UP; DRUGS; MANAGEMENT
AB Purpose: To evaluate the outcomes of cyclophosphamide therapy for noninfectious ocular inflammation.
Design: Retrospective cohort study.
Participants: Two hundred fifteen patients with noninfectious ocular inflammation observed from initiation of cyclophosphamide.
Methods: Patients initiating cyclophosphamide, without other immunosuppressive drugs (other than corticosteroids), were identified at 4 centers. Dose of cyclophosphamide, response to therapy, corticosteroid-sparing effects, frequency of discontinuation, and reasons for discontinuation were obtained by medical record review of every visit.
Main Outcome Measures: Control of inflammation, corticosteroid-sparing effects, and discontinuation of therapy.
Results: The 215 patients (381 involved eyes) meeting eligibility criteria carried diagnoses of uveitis (20.4%), scleritis (22.3%), ocular mucous membrane pemphigoid (45.6%), or other forms of ocular inflammation (11.6%). Overall, approximately 49.2% (95% confidence interval [CI], 41.7%-57.2%) gained sustained control of inflammation (for at least 28 days) within 6 months, and 76% (95% CI, 68.3%-83.7%) gained sustained control of inflammation within 12 months. Corticosteroid-sparing success (sustained control of inflammation while tapering prednisone to 10 mg or less among those not meeting success criteria initially) was gained by 30.0% and 61.2% by 6 and 12 months, respectively. Disease remission leading to discontinuation of cyclophosphamide occurred at the rate of 0.32/person-year (95% CI, 0.24-0.41), and the estimated proportion with remission at or before 2 years was 63.1% (95% CI, 51.5%-74.8%). Cyclophosphamide was discontinued by 33.5% of patients within 1 year because of side effects, usually of a reversible nature.
Conclusions: The data suggest that cyclophosphamide is effective for most patients for controlling inflammation and allowing tapering of systemic corticosteroids to 10 mg prednisone or less, although 1 year of therapy may be needed to achieve these goals. Unlike with most other immunosuppressive drugs, disease remission was induced by treatment in most patients who were able to tolerate therapy. To titrate therapy properly and to minimize the risk of serious potential side effects, a systematic program of laboratory monitoring is required. Judicious use of cyclophosphamide seems to be beneficial for severe ocular inflammation cases where the potentially vision-saving benefits outweigh the substantial potential side effects of therapy, or when indicated for associated systemic inflammatory diseases.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2010; 117: 356-365 (C) 2010 by the American Academy of Ophthalmology.
C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
[Pujari, Siddharth S.; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Kempen, John H.; Newcomb, Craig W.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Kempen, John H.; Newcomb, Craig W.] Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA.
[Kempen, John H.; Newcomb, Craig W.] Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA.
[Gangaputra, Sapna] Univ Wisconsin, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI USA.
[Gangaputra, Sapna; Daniel, Ebenezer; Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.
[Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
OI Daniel, Ebenezer/0000-0002-2027-2316
FU National Eye Institute, Bethesda, Maryland [EY014943]; Research to
Prevent Blindness, Inc., New York; Paul and Evanina Mackall Foundation,
New York; National Eye Institute; Veterans' Administration, Washington,
DC
FX Supported primarily by the National Eye Institute, Bethesda, Maryland
(grant no.: EY014943 [JHK]). Additional support was provided by Research
to Prevent Blindness, Inc., New York, New York, and the Paul and Evanina
Mackall Foundation, New York, NY. Dr Kempen is a Research to Prevent
Blindness James S. Adams Special Scholar Award recipient. Drs. Jabs and
Rosenbaum are Research to Prevent Blindness Senior Scientific
Investigator Award recipients. Dr. Thorne is a Research to Prevent
Blindness Harrington Special Scholar Award recipient. Dr Levy- Clarke
previously was supported by and Dr. Nussenblatt continues to be
supported by intramural funds of the National Eye Institute. Dr Suhler
also received support from the Veterans' Administration, Washington, DC.
None of the sponsors had any role in the design and conduct of the
report; collection, management, analysis, and interpretation of the
data; nor in the preparation, review, and approval of this manuscript.
NR 65
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2010
VL 117
IS 2
BP 356
EP 365
DI 10.1016/j.ophtha.2009.06.060
PG 10
WC Ophthalmology
SC Ophthalmology
GA 555RB
UT WOS:000274530300024
PM 19969366
ER
PT J
AU Zaidi, AA
Ying, GS
Daniel, E
Gangaputra, S
Rosenbaum, JT
Suhler, EB
Thorne, JE
Foster, CS
Jabs, DA
Levy-Clarke, GA
Nussenblatt, RB
Kempen, JH
AF Zaidi, Ali A.
Ying, Gui-Shuang
Daniel, Ebenezer
Gangaputra, Sapna
Rosenbaum, James T.
Suhler, Eric B.
Thorne, Jennifer E.
Foster, C. Stephen
Jabs, Douglas A.
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Kempen, John H.
CA Systemic Immunosuppressive Therapy
TI Hypopyon in Patients with Uveitis
SO OPHTHALMOLOGY
LA English
DT Article
ID BEHCETS-DISEASE
AB Purpose: To evaluate the risk of and risk factors for hypopyon among patients with uveitis and to evaluate the risk of visual changes and complications after hypopyon.
Design: Retrospective cohort study.
Participants: Patients with uveitis at 4 academic ocular inflammation subspecialty practices.
Methods: Data were ascertained by standardized chart review.
Main Outcome Measures: Prevalence and incidence of hypopyon, risk factors for hypopyon, and incidence of visual acuity changes and ocular complications after hypopyon.
Results: Among 4911 patients with uveitis, 41 (8.3/1000) cases of hypopyon were identified at the time of cohort entry. Of these, 2885 initially free of hypopyon were followed over 9451 person-years, during which 81 patients (2.8%) developed hypopyon (8.57/1000 person-years). Risk factors for incident hypopyon included Behcet's disease (adjusted relative risk [RR] = 5.30; 95% confidence interval [CI], 2.76-10.2), spondyloarthropathy (adjusted RR = 2.86; 95% CI, 1.48-5.52), and human leukocyte antigen (HLA)-B27 positivity (adjusted RR = 2.04; 95% CI, 1.17-3.56). Patients with both a spondyloarthropathy and HLA-B27 had a higher risk than either factor alone (crude RR = 4.39; 95% CI, 2.26-8.51). Diagnosis of intermediate uveitis (+/- anterior uveitis) was associated with a lower risk of hypopyon (with respect to anterior uveitis only, adjusted RR = 0.35; 95% CI, 0.15-0.85). Hypopyon incidence tended to be lower among patients with sarcoidosis (crude RR = 0.22; 95% CI, 0.06-0.90; adjusted RR = -0.28; 95% CI, 0.07-1.15). Post-hypopyon eyes and eyes not developing hypopyon had a similar incidence of band keratopathy, posterior synechiae, ocular hypertension, hypotony, macular edema, epiretinal membrane, cataract surgery, or glaucoma surgery. Post-hypopyon eyes were more likely than eyes not developing hypopyon to gain 3 lines of vision (crude RR = 1.54; 95% CI, 1.05-2.24) and were less likely to develop 20/200 or worse visual acuity (crude RR = 0.41; 95% CI, 0.17-0.99); otherwise, visual outcomes were similar in these groups.
Conclusions: Hypopyon is an uncommon occurrence in patients with uveitis. Risk factors included Behcet's disease, HLA-B27 positivity, and spondyloarthropathy. Intermediate uveitis cases (+/- anterior uveitis) had a lower risk of hypopyon. On average, post-hypopyon eyes were no more likely than other eyes with uveitis to develop structural ocular complications or lose visual acuity.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2010; 117: 366-372 (C) 2010 by the American Academy of Ophthalmology.
C1 [Zaidi, Ali A.; Ying, Gui-Shuang; Daniel, Ebenezer; Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
[Zaidi, Ali A.; Ying, Gui-Shuang; Daniel, Ebenezer; Kempen, John H.] Univ Penn, Ocular Inflammat Serv, Philadelphia, PA 19104 USA.
[Ying, Gui-Shuang; Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat, Philadelphia, PA 19104 USA.
[Ying, Gui-Shuang; Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Epidemiol, Philadelphia, PA 19104 USA.
[Daniel, Ebenezer; Gangaputra, Sapna; Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Gangaputra, Sapna] Univ Wisconsin, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI USA.
[Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
OI Daniel, Ebenezer/0000-0002-2027-2316
FU National Eye Institute [EY014943]; Research to Prevent Blindness; Paul
and Evanina Mackall Foundation; Prevent Blindness James S. Adams Special
Scholar Award; National Eye Institute
FX Supported primarily by National Eye Institute Grant EY014943 (Dr.
Kempen). Additional support was provided by Research to Prevent
Blindness and the Paul and Evanina Mackall Foundation. Dr Kempen is a
Research to Prevent Blindness James S. Adams Special Scholar Award
recipient. Drs. Jabs and Rosenbaum are Research to Prevent Blindness
Senior Scientific Investigator Award recipients. Dr. Thorne is a
Research to Prevent Blindness Harrington Special Scholar Award
recipient. Dr. Suhler also received support from the Veteran's Affairs
Administration. Dr. Levy-Clarke was previously supported by and Dr.
Nussenblatt continues to be supported by intramural funds of the
National Eye Institute.
NR 12
TC 16
Z9 16
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2010
VL 117
IS 2
BP 366
EP 372
DI 10.1016/j.ophtha.2009.07.025
PG 7
WC Ophthalmology
SC Ophthalmology
GA 555RB
UT WOS:000274530300025
PM 20006905
ER
PT J
AU Srinivasan, VJ
Sakadzic, S
Gorczynska, I
Ruvinskaya, S
Wu, WC
Fujimoto, JG
Boas, DA
AF Srinivasan, Vivek J.
Sakadzic, Sava
Gorczynska, Iwona
Ruvinskaya, Svetlana
Wu, Weicheng
Fujimoto, James G.
Boas, David A.
TI Quantitative cerebral blood flow with Optical Coherence Tomography
SO OPTICS EXPRESS
LA English
DT Article
ID IN-VIVO; DOPPLER TOMOGRAPHY; MICRO-ANGIOGRAPHY; SCATTERING MEDIA; RAT
NEOCORTEX; PERFUSION; VELOCITY; SPECKLE; HEMODYNAMICS; ARTIFACTS
AB Absolute measurements of cerebral blood flow (CBF) are an important endpoint in studies of cerebral pathophysiology. Currently no accepted method exists for in vivo longitudinal monitoring of CBF with high resolution in rats and mice. Using three-dimensional Doppler Optical Coherence Tomography and cranial window preparations, we present methods and algorithms for regional CBF measurements in the rat cortex. Towards this end, we develop and validate a quantitative statistical model to describe the effect of static tissue on velocity sensitivity. This model is used to design scanning protocols and algorithms for sensitive 3D flow measurements and angiography of the cortex. We also introduce a method of absolute flow calculation that does not require explicit knowledge of vessel angles. We show that OCT estimates of absolute CBF values in rats agree with prior measures by autoradiography, suggesting that Doppler OCT can perform absolute flow measurements in animal models. (C) 2010 Optical Society of America
C1 [Srinivasan, Vivek J.; Sakadzic, Sava; Ruvinskaya, Svetlana; Wu, Weicheng; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Photon Migrat Imaging Lab,Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
[Gorczynska, Iwona; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Gorczynska, Iwona; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
RP Srinivasan, VJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Photon Migrat Imaging Lab,Sch Med, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
EM vjsriniv@nmr.mgh.harvard.edu
RI Gorczynska, Iwona/P-9367-2015
OI Gorczynska, Iwona/0000-0002-6120-8791
FU National Institutes of Health [R01-NS057476, P01NS055104, P50NS010828,
K99NS067050, R01-CA075289-13]; Air Force Office of Scientific Research
[FA9550-07-1-0014]; Medical Free Electron Laser Program
[FA9550-07-10101]
FX We would like to acknowledge scientific contributions and helpful advice
from Chao Zhou at MIT, and James Jiang and Alex Cable from Thorlabs. Dr.
Iwona Gorczynska's present address is the Institute of Physics, Nicolaus
Copernicus University, Torun, Poland. We acknowledge support by the
National Institutes of Health (R01-NS057476, P01NS055104, P50NS010828,
K99NS067050 and R01-CA075289-13), the Air Force Office of Scientific
Research FA9550-07-1-0014, and the Medical Free Electron Laser Program
FA9550-07-10101.
NR 41
TC 129
Z9 130
U1 1
U2 19
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 FEB 1
PY 2010
VL 18
IS 3
BP 2477
EP 2494
DI 10.1364/OE.18.002477
PG 18
WC Optics
SC Optics
GA 559AD
UT WOS:000274791200068
PM 20174075
ER
PT J
AU Joo, C
Evans, CL
Stepinac, T
Hasan, T
de Boer, JF
AF Joo, Chulmin
Evans, Conor L.
Stepinac, Thomas
Hasan, Tayyaba
de Boer, Johannes F.
TI Diffusive and directional intracellular dynamics measured by field-based
dynamic light scattering
SO OPTICS EXPRESS
LA English
DT Article
ID IMAGE SUBMICROSCOPIC MOTIONS; OPTICAL COHERENCE TOMOGRAPHY; PHASE
MICROSCOPY; SLOW DYNAMICS; LIVE CELLS; INTERFEROMETRY; CONTRAST; DOMAIN;
SPECTROSCOPY
AB Quantitative measurement of diffusive and directional processes of intracellular structures is not only critical in understanding cell mechanics and functions, but also has many applications, such as investigation of cellular responses to therapeutic agents. We introduce a label-free optical technique that allows non-perturbative characterization of localized intracellular dynamics. The method combines a field-based dynamic light scattering analysis with a confocal interferometric microscope to provide a statistical measure of the diffusive and directional motion of scattering structures inside a microscopic probe volume. To demonstrate the potential of this technique, we examined the localized intracellular dynamics in human epithelial ovarian cancer cells. We observed the distinctive temporal regimes of intracellular dynamics, which transitions from random to directional processes on a timescale of similar to 0.01 sec. In addition, we observed disrupted directional processes on the timescale of 1 similar to 5 sec by the application of a microtubule polymerization inhibitor, Colchicine, and ATP depletion. (C) 2010 Optical Society of America
C1 [Joo, Chulmin; Evans, Conor L.; Stepinac, Thomas; Hasan, Tayyaba; de Boer, Johannes F.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Joo, Chulmin; Evans, Conor L.; Stepinac, Thomas; Hasan, Tayyaba; de Boer, Johannes F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Joo, Chulmin] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[de Boer, Johannes F.] Vrije Univ Amsterdam, Dept Phys & Astron, NL-1081 HV Amsterdam, Netherlands.
RP Joo, C (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM cmjoo@alum.mit.edu; jfdeboer@few.vu.nl
RI de Boer, Johannes/B-7590-2012;
OI de Boer, Johannes/0000-0003-1253-4950; Joo, Chulmin/0000-0002-1812-2976
FU National Institute of Health [R01 RR19768, EY14975]; U. S. Department of
Defense [F4 9620-01-1-0014]; Center for Integration of Medicine and
Innovative Technology; Wellman Graduate Fellowship; MIT Department of
Mechanical Engineering
FX This work was supported by grants from National Institute of Health (R01
RR19768, EY14975), the U. S. Department of Defense (F4 9620-01-1-0014),
and the Center for Integration of Medicine and Innovative Technology. C.
J. would like to thank the support through a Wellman Graduate Fellowship
and a Hatsopoulos Innovation Award from the MIT Department of Mechanical
Engineering.
NR 40
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U1 0
U2 7
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 FEB 1
PY 2010
VL 18
IS 3
BP 2858
EP 2871
DI 10.1364/OE.18.002858
PG 14
WC Optics
SC Optics
GA 559AD
UT WOS:000274791200108
PM 20174115
ER
PT J
AU Niedre, M
Ntziachristos, V
AF Niedre, Mark
Ntziachristos, Vasilis
TI Comparison of fluorescence tomographic imaging in mice with
early-arriving and quasi-continuous-wave photons
SO OPTICS LETTERS
LA English
DT Article
ID TURBID MEDIA; MOLECULAR TOMOGRAPHY
AB The highly diffuse nature of light propagation in biological tissue is a major challenge for obtaining high-fidelity fluorescence tomographic images. In this work we investigated the use of time-gated detection of early-arriving photons for reducing the effects of light scatter in mice relative to quasi-cw photons. When analyzing sinographic representations of the measured data, it was determined that early photons allowed a reduction in the measured FWHM of fluorescent targets by a factor of approximately 2-3, yielding a significant improvement in the tomographic image reconstruction quality. (C) 2010 Optical Society of America
C1 [Ntziachristos, Vasilis] Tech Univ Munich, Inst Biol & Med Imaging, D-85764 Munich, Germany.
[Niedre, Mark] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA.
[Ntziachristos, Vasilis] Helmholtz Ctr Munich, D-85764 Munich, Germany.
[Niedre, Mark; Ntziachristos, Vasilis] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA.
[Niedre, Mark; Ntziachristos, Vasilis] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Ntziachristos, V (reprint author), Tech Univ Munich, Inst Biol & Med Imaging, Ismaningerstr 21, D-85764 Munich, Germany.
EM v.ntziachristos@tum.de
FU National Institutes of Health (NIH) [R01 EB000750]
FX This research was supported in part by the National Institutes of Health
(NIH) grant R01 EB000750. The authors wish to thank Mr. Joshua Dunham
and Mr. Gregory Wojtkiewicz for assistance in the experiments.
NR 14
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U1 0
U2 2
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 FEB 1
PY 2010
VL 35
IS 3
BP 369
EP 371
PG 3
WC Optics
SC Optics
GA 551GX
UT WOS:000274196100034
PM 20125724
ER
PT J
AU Dodson, TB
AF Dodson, Thomas B.
TI Outcomes Research and the Challenge of Evidence-Based Surgery
SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Outcomes research; Quality assurance; Evidence-based surgical practice;
Patient-oriented research
ID TRIGEMINAL NERVE REPAIR; RISK-FACTORS; PATIENT SATISFACTION;
COMPLICATIONS; EXTRACTION; STRATEGY
AB Outcomes research is focused on measuring the results or end products of health care interventions, processes, and practices. Data derived from outcomes research informs clinical practice, quality assurance, and patient safety activities, and can be the nidus for hypothesis-driven, patient-oriented research. This article introduces a definition of outcomes research, reviews how outcomes research may guide evidence-based surgical practice and health care processes, and reviews a model for outcomes research.
C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA.
[Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA.
RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,Warren Bldg Suite 1201, Boston, MA 02114 USA.
EM tbdodson@partners.org
FU Massachusetts General Hospital Department of Oral and Maxillofacial
Surgery's Center for Applied Clinical Investigation and Education and
Research; Massachusetts General Physician Organization
FX Article preparation was supported by the Massachusetts General Hospital
Department of Oral and Maxillofacial Surgery's Center for Applied
Clinical Investigation and Education and Research Fund and Massachusetts
General Physician Organization.
NR 10
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U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1042-3699
J9 ORAL MAXIL SURG CLIN
JI Oral Maxillofac. Surg. Clin. N. Am.
PD FEB
PY 2010
VL 22
IS 1
BP 1
EP +
DI 10.1016/j.coms.2009.10.004
PG 5
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 864TT
UT WOS:000298263700002
PM 20159473
ER
PT J
AU Fernandez, C
Jami, S
Loredo, G
Ko, F
Hahn, T
McDougall, S
Peters, JH
AF Fernandez, C.
Jami, S.
Loredo, G.
Ko, F.
Hahn, T.
McDougall, S.
Peters, J. H.
TI Recognition of the alternatively spliced segments of fibronectin by the
RCJ 3.1C5.18 chondrocytic rat cell line
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Article
DE Chondrocyte; Mulipotential stem cell; Differentiation; Fibronectin
alternative splicing; Cartilage
ID ISOFORM DISTRIBUTION; BINDING PROTEIN-3; PROGENITOR CELLS;
MESSENGER-RNA; V-SEGMENT; CARTILAGE; DIFFERENTIATION; EIIIA;
IDENTIFICATION; POPULATION
AB Objectives. To define, for the C5.18 chondrocyte-restricted rat cell line, (1) the capacities for recognition of alternatively spliced segments of the adhesion protein fibronectin (FN), (2) the integrin subunits required for such recognition, and (3) differences in such FN recognition vs the multipotential chondroprogenitor line, RCJ 3 1
Methods C5 18 and RCJ 3 1 cells were tested for their capacities to adhere to recombinant alternatively spliced segments of rat FN, presented on plastic surfaces either in isolation or in partial FNs spanning the 7th through 15th type III repeats (III7-15 FNs) The effects on such adhesion of cations and integrin subunit-specific antibodies were tested
Results Despite significant augmentation in chondrocyte-specific gene expression in C5.18 relative to the RCJ 3 1 cells, the two lines exhibited similar recognition of FN spliced segments and partial isoforms Specifically, both lines adhered to the extra type III repeat A (EIIIA) and V, but not extra type III repeat B (EIIIB), segments There were different cation and integrin subunit requirements for adhesion to EIIIA vs V segments, and only the V segment was recognized in the context of a III7-15 FN Such recognition was mediated via a "second" arginineglycine-aspartic acid (RGD) sequence that is present in the V95 subsegment in rat, but not human, FN
Conclusion The chondrocyte lineage-committed C5 18 cell line, similar to its multipotential chondroprogenitor, RCJ 3 1, recognizes the "cartilage-restricted" EIIIA and V segments of FN with cation, integrin, and molecular context requirements that are specific to each of these segments Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International
C1 [Peters, J. H.] UC Davis, Med Ctr, Ctr Healthy Aging, Dept Internal Med,Sch Med, Sacramento, CA 95817 USA.
[Fernandez, C.; Jami, S.; Loredo, G.; Peters, J. H.] VA No Calif Hlth Care Syst, Sacramento Med Ctr, Mather, CA 95655 USA.
[Ko, F.; Hahn, T.; McDougall, S.] Greater Los Angeles VA Healthcare Syst, W LA VA Med Ctr, Los Angeles, CA USA.
[Hahn, T.; McDougall, S.] Univ Calif Los Angeles, Sch Med, Dept Internal Med, Div Geriatr Med, Los Angeles, CA 90024 USA.
RP Peters, JH (reprint author), UC Davis, Med Ctr, Ctr Healthy Aging, Dept Internal Med,Sch Med, Room 2351,Oak Pk Bldg,2700 StocktonBlvd, Sacramento, CA 95817 USA.
OI Jami, Shekib/0000-0001-5478-1963
FU Career Development Award; Department of Veterans Affairs; Charles See
Foundation; UC Davis Center for Healthy Aging
FX We thank Jane Aubin of the University of Toronto for generously
supplying the RCJ 3 1 and RCJ 3 1 C5 18 cell lines, Richard Hynes of
M.I.T for providing the cDNA constructs used to produce the III7-15
fusion proteins. J.H.P was supported by a Career Development Award and a
Merit Review Award from the Department of Veterans Affairs, a gift from
the Charles See Foundation and an intramural grant from the UC Davis
Center for Healthy Aging during this study
NR 31
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U1 1
U2 2
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1063-4584
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD FEB
PY 2010
VL 18
IS 2
BP 228
EP 239
DI 10.1016/j.joca.2009.09.005
PG 12
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 566HK
UT WOS:000275360500011
PM 19822234
ER
PT J
AU Shargorodsky, J
Curhan, SG
Eavey, R
Curhan, GC
AF Shargorodsky, Josef
Curhan, Sharon G.
Eavey, Roland
Curhan, Gary C.
TI A prospective study of vitamin intake and the risk of hearing loss in
men
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation
CY OCT 04-07, 2009
CL San Diego, CA
SP Amer Acad Otolaryngol Head & Neck Surg Fdn
ID NUTRITION EXAMINATION SURVEY; RADICAL SCAVENGERS; NATIONAL-HEALTH;
OLDER-ADULTS; EXPOSURE; FOLATE
AB OBJECTIVE: Hearing loss is the most common sensory disorder in the United States, afflicting more than 36 million people. Higher intakes of vitamins C, E, beta carotene, B12, and folate have been proposed to reduce the risk of hearing loss.
STUDY DESIGN: We prospectively evaluated the association between intake from foods and supplements of vitamins C, E, beta carotene, B12, and folate, and the incidence of hearing loss.
SETTING: Health Professionals Follow-up Study.
SUBJECTS AND METHODS: A total of 26,273 men aged 40 to 74 years at baseline in 1986. Participants completed questionnaires about lifestyle and medical history every two years and diet every four years. Information on self-reported professionally diagnosed hearing loss and year of diagnosis was obtained from the 2004 questionnaire, and cases were defined as hearing loss diagnosed between 1986 and 2004. Cox proportional hazards multivariate regression was used to adjust for potential confounders.
RESULTS: There were 3559 cases of hearing loss identified. Overall, there was no significant association between vitamin intake and risk of hearing loss. Among men aged 60 years, total folate intake was associated with a reduced risk of hearing loss; the relative risk for men aged >= 60 years old in the highest quintile compared with the lowest quintile of folate intake was 0.79 (95% confidence interval 0.65-0.96).
CONCLUSIONS: Higher intake of vitamin C, E, beta carotene, or B12 does not reduce the risk of hearing loss in adult males. Men aged years may benefit from higher folate intake to reduce the risk of developing hearing loss. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.
C1 [Shargorodsky, Josef; Curhan, Sharon G.; Curhan, Gary C.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Curhan, Gary C.] Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA.
[Shargorodsky, Josef] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Eavey, Roland] Vanderbilt Univ, Dept Otolaryngol, Vanderbilt Bill Wilkerson Ctr Otolaryngol & Commu, Nashville, TN USA.
[Curhan, Gary C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Shargorodsky, J (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM Josef_Shargorodsky@meei.harvard.edu
FU NCI NIH HHS [P01 CA055075-18, P01 CA055075]
NR 20
TC 21
Z9 21
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD FEB
PY 2010
VL 142
IS 2
BP 231
EP 236
DI 10.1016/j.otohns.2009.10.049
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 582CZ
UT WOS:000276574500015
PM 20115980
ER
PT J
AU Lindsay, RW
Hadlock, TA
Cheney, ML
AF Lindsay, Robin W.
Hadlock, Tessa A.
Cheney, Mack L.
TI Upper lip elongation in Mobius syndrome
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
C1 [Lindsay, Robin W.] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
[Lindsay, Robin W.; Hadlock, Tessa A.; Cheney, Mack L.] Harvard Univ, Sch Med, Boston, MA USA.
[Lindsay, Robin W.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA.
RP Lindsay, RW (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM robin_lindsay@meei.harvard.edu
NR 4
TC 2
Z9 2
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD FEB
PY 2010
VL 142
IS 2
BP 286
EP 287
DI 10.1016/j.otohns.2009.09.034
PG 2
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 582CZ
UT WOS:000276574500026
PM 20115991
ER
PT J
AU Benoit, MM
Fink, DS
Brigger, MT
Keamy, DG
AF Benoit, Margo McKenna
Fink, Daniel S.
Brigger, Matthew T.
Keamy, Donald G., Jr.
TI Lobular capillary hemangioma of the nasal cavity in a five-year-old boy
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
ID PYOGENIC GRANULOMA
C1 [Benoit, Margo McKenna; Fink, Daniel S.; Keamy, Donald G., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Brigger, Matthew T.] USN, Med Ctr, Dept Otolaryngol Head & Neck Surg, San Diego, CA 92152 USA.
RP Benoit, MM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM Margo_Benoit@meei.harvard.edu
NR 5
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD FEB
PY 2010
VL 142
IS 2
BP 290
EP 291
DI 10.1016/j.otohns.2009.09.035
PG 2
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 582CZ
UT WOS:000276574500028
PM 20115993
ER
PT J
AU Kong, J
Loggia, ML
Zyloney, C
Tu, PC
LaViolette, P
Gollub, RL
AF Kong, Jian
Loggia, Marco L.
Zyloney, Carolyn
Tu, Peichi
LaViolette, Peter
Gollub, Randy L.
TI Exploring the brain in pain: Activations, deactivations and their
relation
SO PAIN
LA English
DT Article
DE fMRI; Resting state; Default network; Cross-modal interaction;
Functional connectivity; Gender difference
ID POSITRON-EMISSION-TOMOGRAPHY; ACUPUNCTURE ANALGESIA; PLACEBO ANALGESIA;
SEX-DIFFERENCES; RATIO SCALES; DEFAULT MODE; MUSCLE PAIN; CORTEX; FMRI;
INTENSITY
AB The majority of neuroimaging studies on pain focuses on the study of BOLD activations, and more rarely on deactivations. In this study, in a relatively large cohort of subjects (N = 61), we assess (a) the extent of brain activation and deactivation during the application of two different heat pain levels (HIGH and LOW) and (b) the relations between these two directions of fMRI signal change. Furthermore, in a subset of our subjects (N = 12), we assess (c) the functional connectivity of pain-activated or -deactivated regions during resting states. As previously observed, we find that pain stimuli induce intensity dependent (HIGH pain > LOW pain) fMRI signal increases across the pain matrix. Simultaneously, the noxious stimuli induce activity decreases in several brain regions, including some of the 'core structures' of the default network (DMN). In contrast to what we observe with the signal increases, the extent of deactivations is greater for LOW than HIGH pain stimuli. The functional dissociation between activated and deactivated networks is further supported by correlational and functional connectivity analyses. Our results illustrate the absence of a linear relationship between pain activations and deactivations, and therefore suggest that these brain signal changes underlie different aspects of the pain experience. (C) 2009 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Kong, Jian; Loggia, Marco L.; Zyloney, Carolyn; Tu, Peichi; LaViolette, Peter; Gollub, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA.
[Kong, Jian; Loggia, Marco L.; LaViolette, Peter; Gollub, Randy L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,MIT, Charlestown, MA 02129 USA.
[Gollub, Randy L.] Massachusetts Gen Hosp, MIT, CRC Biomed Imaging Core, Charlestown, MA USA.
[Loggia, Marco L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
RP Kong, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,Suite 2661, Charlestown, MA 02129 USA.
EM kongj@nmr.mgh.harvard.edu
OI Gollub, Randy L./0000-0002-9434-4044
FU NIH (NCCAM) [PO1-AT002048, M01-RR-01066]; National Center for Research
Resources (NCRR) [UL1 RR025758-01, P41RR14075]; MIND Research Network
[DE-FG03-99ER62764]; [KO1AT003883]; [R21AT004497]; [R21AT00949]
FX Funding and support for this study came from KO1AT003883 and R21AT004497
to Jian Kong, R21AT00949 to Randy Gollub, NIH (NCCAM) PO1-AT002048 to
Bruce Rosen, M01-RR-01066 and UL1 RR025758-01 for Clinical Research
Center Biomedical Imaging Core from National Center for Research
Resources (NCRR), P41RR14075 for Center for Functional Neuroimaging
Technologies from NCRR and the MIND Research Network, DE-FG03-99ER62764
to Bruce Rosen. The authors have no conflicts of interest or competing
financial interests to declare.
NR 48
TC 77
Z9 83
U1 3
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD FEB
PY 2010
VL 148
IS 2
BP 257
EP 267
DI 10.1016/j.pain.2009.11.008
PG 11
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 547MV
UT WOS:000273894600013
PM 20005043
ER
PT J
AU Vrooman, LM
Supko, JG
Neuberg, DS
Asselin, BL
Athale, UH
Clavell, L
Kelly, KM
Laverdiere, C
Michon, B
Schorin, M
Cohen, HJ
Sallan, SE
Silverman, LB
AF Vrooman, Lynda M.
Supko, Jeffrey G.
Neuberg, Donna S.
Asselin, Barbara L.
Athale, Uma H.
Clavell, Luis
Kelly, Kara M.
Laverdiere, Caroline
Michon, Bruno
Schorin, Marshall
Cohen, Harvey J.
Sallan, Stephen E.
Silverman, Lewis B.
TI Erwinia Asparaginase After Allergy to E. coli Asparaginase in Children
With Acute Lymphoblastic Leukemia
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE asparaginase; childhood; Erwinia; leukemia
ID ESCHERICHIA-COLI; DANA-FARBER; INTENSIVE ASPARAGINASE;
CEREBROSPINAL-FLUID; ONCOLOGY-GROUP; CHILDHOOD; THERAPY; ANTIBODIES;
CANCER; PHARMACOKINETICS
AB Background. Escherichia coli asparaginase is an important component of treatment for childhood acute lymphoblastic leukemia (ALL); however, hypersensitivity develops in up to 30% of patients. We assessed the nadir enzyme activity and tolerability of Erwinia asparaginase, an alternative preparation, in E. coli asparaginase-allergic patients. Patients and Methods. Between 2000 and 2002, 215 children with newly diagnosed ALL were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 and were to receive 30 weekly doses of intramuscular E. coli asparaginase. If E. coli asparaginase allergy developed, patients were switched to twice-weekly intramuscular Erwinia asparaginase (25,000 IU/m(2)). Nadir serum asparaginase activity (NSAA) was measured every 3 weeks. Results. Forty-two patients (20%) developed E. coli asparaginase allergy and switched to Erwinia. Of 38 patients with evaluable samples, 34 (89%) Erwinia-treated patients had at least one therapeutic NSAA (>= 0.1 IU/ml). The median NSAA was 0.247 IU/ml 3 days and 0.077 IU/ml 4 days after an Erwinia dose. Associated toxicities included allergy in 14 (33%) and pancreatitis in 3 patients (7%). At a median follow-up of 5.4 years, event-free survival (+/- standard error) of the 42 patients who switched to Erwinia was 86 +/- 5% compared with 81 +/- 3% for the 170 patients without E. coli asparaginase allergy (P=0.55). Conclusions. Twice-weekly Erwinia asparaginase was well tolerated and achieved a therapeutically effective NSAA in most E. coli asparaginase-allergic patients. Development of E. coli allergy and subsequent treatment with twice-weekly Erwinia did not adversely impact event-free Survival. Erwinia asparaginase Should be considered for E. coli asparaginase-allergic patients. Pediatr Blood Cancer 2010;54:199-205. (C) 2009 Wiley-Liss, Inc.
C1 [Vrooman, Lynda M.; Neuberg, Donna S.; Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol Biostat & Computat Biol, Boston, MA 02115 USA.
[Vrooman, Lynda M.; Sallan, Stephen E.; Silverman, Lewis B.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Supko, Jeffrey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Asselin, Barbara L.] Univ Rochester, Med Ctr, Div Pediat Oncol, Rochester, NY 14642 USA.
[Athale, Uma H.] McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada.
[Clavell, Luis] San Jorge Childrens Hosp, Div Pediat Oncol, San Juan, PR USA.
[Kelly, Kara M.] Columbia Univ, Med Ctr, Div Pediat Oncol, Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA.
[Laverdiere, Caroline] Univ Montreal, Hop St Justine, Div Hematol & Oncol, Montreal, PQ H3T 1C5, Canada.
[Michon, Bruno] Ctr Hosp U Quebec, Div Hematol Oncol, Quebec City, PQ, Canada.
[Schorin, Marshall] Inova Fairfax Hosp, Falls Church, VA USA.
[Cohen, Harvey J.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
RP Vrooman, LM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Binney St, Boston, MA 02115 USA.
EM lynda_vrooman@dfci.harvard.edu
FU National Cancer Institute [5 P01CA068484]
FX This work was supported in part by grant 5 P01CA068484 from the National
Cancer Institute.
NR 34
TC 57
Z9 62
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD FEB
PY 2010
VL 54
IS 2
BP 199
EP 205
DI 10.1002/pbc.22225
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 538TK
UT WOS:000273206700006
PM 19672973
ER
PT J
AU Bergmann, AK
Campagna, DR
McLoughlin, EM
Agarwal, S
Fleming, MD
Bottomley, SS
Neufeld, EJ
AF Bergmann, Anke K.
Campagna, Dean R.
McLoughlin, Erin M.
Agarwal, Suneet
Fleming, Mark D.
Bottomley, Sylvia S.
Neufeld, Ellis J.
TI Systematic Molecular Genetic Analysis of Congenital Sideroblastic
Anemia: Evidence for Genetic Heterogeneity and Identification of Novel
Mutations
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE iron; microcytic anemia; ringed sideroblasts; sideroblastic anemia
ID MARROW PANCREAS SYNDROME; MITOCHONDRIAL MYOPATHY; MEGALOBLASTIC-ANEMIA;
MISSENSE MUTATION; PUS1 GENE; ATAXIA; DISORDER; ABC7; POLYMORPHISM;
TRANSPORTER
AB Background. Sideroblastic anemias are heterogeneous congenital and acquired bone marrow disorders characterized by pathologic iron deposits in mitochondria of erythroid precursors. Among the congenital sideroblastic anemias (CSAs), the most common form is X-linked sideroblastic anemia, due to Mutations in 5-aminolevulinate synthase (ALAS2). A novel autosomal recessive CSA, caused by mutations in the erythroid specific mitochondrial transporter SLC25A38, was recently defined. Other known etiologies include mutations in genes encoding the thiamine transporter SLC19A2, the RNA-modifying enzyme pSeLldouridine synthase 1 (PUS1), a mitochondrial ATP-binding cassette transporter (ABCB7), glutaredoxin 5 (GLRX5), as well as mitochondrial DNA deletions. Despite these known diverse causes, in a Substantial portion of CSA cases a presumed genetic defect remains unknown. Procedure. In the context of the recent discovery of SLC25A38 as a major novel cause, we systematically analyzed a large cohort of previously unreported CSA patients. Sixty CSA probands (28 females, 32 males) were examined for ALAS2, SLC25A38, PUS1, GLRX5, and ABCB7 mutations. SLC19A2 and mitochondrial DNA were only analyzed if characteristic syndromic features were apparent. Results. Twelve probands had biallelic mutations in SLC25A38. Seven ALAS2 mutations were detected in eight sporadic CSA cases, two being novel. We also identified a novel homozygous null PUSI mutation and novel mitochondrial DNA deletions in two patients with Pearson syndrome. No mutations were encountered in GLRX5, ABCB7, or SLC19A2. Conclusions. The remaining undefined probands (43%) can be grouped according to gender, family, and clinical characteristics, suggesting novel X-linked and autosomal recessive forms of CSA. Pediatr Blood Cancer 2010;54:273-278. (C) 2009 Wiley-Liss, Inc.
C1 [Campagna, Dean R.; Fleming, Mark D.] Harvard Univ, Dept Pathol, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA.
[Bergmann, Anke K.; McLoughlin, Erin M.; Agarwal, Suneet; Neufeld, Ellis J.] Harvard Univ, Div Hematol Oncol, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA.
[Agarwal, Suneet; Neufeld, Ellis J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bottomley, Sylvia S.] Univ Oklahoma, Coll Med, Hematol Oncol Sect, Oklahoma City, OK 73190 USA.
RP Fleming, MD (reprint author), Harvard Univ, Dept Pathol, Childrens Hosp Boston, Sch Med, 300 Longwood Ave,Enders 1116-1, Boston, MA 02115 USA.
EM mark.fleming@childrens.harvard.edu
RI Neufeld, Ellis/F-9331-2011
FU NIH [R01 DK080011, K08 HL089150, K24 HL004184]; The U.S. Department of
Veterans, Affairs, University of Oklahoma Health Sciences Center
Provost's Fund; The Oklahoma Center for Advancement of Science and
Technology
FX We express our gratitude to the patients, their families and referring
physicians. We thank Mathew Heeney for help with consenting some of the
patients, Philip Wise and Eric Wasson for technical assistance, and Mark
Samuels and his colleagues at the Atlantic Medical Genetics and Genomics
Initiative for discussions concerning SLC25A38 in advance Of
publication. This work was supported in part by NIH grant R01 DK080011
(M.D.F.); The U.S. Department of Veterans, Affairs, University of
Oklahoma Health Sciences Center Provost's Fund and The Oklahoma Center
for Advancement of Science and Technology (S.S.B.); NIH grant K08
HL089150 (S.A.), and NIH grant K24 HL004184 (E.J.N.).
NR 34
TC 51
Z9 59
U1 1
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD FEB
PY 2010
VL 54
IS 2
BP 273
EP 278
DI 10.1002/pbc.22244
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 538TK
UT WOS:000273206700019
PM 19731322
ER
PT J
AU Adams, EE
Aluquin, VPR
Bingham, CA
Stone, JR
Pauliks, LB
AF Adams, Elizabeth E.
Aluquin, Vincent P. R.
Bingham, C. April
Stone, James R.
Pauliks, Linda B.
TI Cardiac Tumor in Juvenile Onset Behcet's Disease: Case Report and Review
of the Literature
SO PEDIATRIC CARDIOLOGY
LA English
DT Review
DE Behcet's disease; Child; Echocardiography; Heart neoplasm; Pulmonary
embolism
ID THROMBUS
AB Beh double dagger et's disease is a chronic multisystemic inflammatory disorder characterized by orogenital ulcerations, uveitis, and occasional cardiac involvement. This report describes an atypical presentation of pediatric Beh double dagger et's disease with pulmonary emboli and a cardiac mass. A 16-year-old boy with a 2-year history of oral ulcers presented with weight loss, fever, joint pain, and a large tumor adhering to the free wall of the heart's right ventricle. Surgical biopsy demonstrated endomyocarditis with thrombus formation and led to the diagnosis. At the 2-year follow-up evaluation, intracardiac thrombus and pulmonic emboli had not recurred. Symptom control with immunosuppressive therapy was good.
C1 [Adams, Elizabeth E.; Aluquin, Vincent P. R.; Bingham, C. April; Pauliks, Linda B.] Penn State Hershey Childrens Hosp, Dept Pediat Cardiol, Hershey, PA 17033 USA.
[Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Pauliks, LB (reprint author), Penn State Hershey Childrens Hosp, Dept Pediat Cardiol, Mailbox HP14,500 Univ Dr, Hershey, PA 17033 USA.
EM lpauliks@hmc.psu.edu
OI Pauliks, Linda/0000-0003-1031-3994
NR 12
TC 3
Z9 4
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0172-0643
J9 PEDIATR CARDIOL
JI Pediatr. Cardiol.
PD FEB
PY 2010
VL 31
IS 2
BP 277
EP 279
DI 10.1007/s00246-009-9565-4
PG 3
WC Cardiac & Cardiovascular Systems; Pediatrics
SC Cardiovascular System & Cardiology; Pediatrics
GA 552ZN
UT WOS:000274333900017
PM 19859764
ER
PT J
AU Profit, J
Petersen, LA
McCormick, MC
Escobar, GJ
Coleman-Phox, K
Zheng, Z
Pietz, K
Zupancic, JAF
AF Profit, Jochen
Petersen, Laura A.
McCormick, Marie C.
Escobar, Gabriel J.
Coleman-Phox, Kim
Zheng, Zheng
Pietz, Kenneth
Zupancic, John A. F.
TI Patient-to-Nurse Ratios and Outcomes of Moderately Preterm Infants
SO PEDIATRICS
LA English
DT Article
DE infant; newborn; health services research; nurse-staffing; outcomes
ID NEONATAL INTENSIVE-CARE; BIRTH-WEIGHT INFANTS; STAFF RATIOS; MORTALITY;
RISK; UNIT; WORKLOAD; QUALITY
AB OBJECTIVE: Moderately preterm infants (30-346/7 weeks' gestational age) represent the largest population of NICU residents. Whether their clinical outcomes are associated with differences in NICU nurse-staffing arrangements has not been assessed. The objective of this study was to test the influence of patient-to-nurse ratios (PNRs) on outcomes of care provided to moderately preterm infants.
PATIENTS AND METHODS: Using data from a prospective, multicenter, observational cohort study of 850 moderately preterm infants from 10 NICUs in California and Massachusetts, we tested for associations between PNR and several important clinical outcomes by using multivariate random-effects models. To correct for the influence of NICU size, we dichotomized the sample into those with an average daily census of <20 or >= 20 infants.
RESULTS: Overall, we found few clinically significant associations between PNR and clinical outcomes of care. Mean PNRs were higher in large compared with small NICUs (2.7 vs 2.1; P < .001). In bivariate analyses, an increase in PNR was associated with a slightly higher daily weight gain (5 g/day), greater gestational age at discharge, any intraventricular hemorrhage, and severe retinopathy of prematurity. After controlling for case mix, NICU size, and site of care, an additional patient per nurse was associated with a decrease in daily weight gain by 24%. Other variables were no longer independently associated with PNR.
CONCLUSIONS: In this population of moderately preterm infants, the PNR was associated with a decrease in daily weight gain, but was not associated with other measures of quality. In contrast with findings in the adult intensive care literature, measured clinical outcomes were similar across the range of nurse-staffing arrangements among participating NICUs. We conclude that the PNR is not useful for profiling hospitals' quality of care delivery to moderately preterm infants. Pediatrics 2010; 125: 320-326
C1 [Profit, Jochen] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Profit, Jochen; Petersen, Laura A.; Pietz, Kenneth] Texas Childrens Hosp, Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Profit, Jochen; Petersen, Laura A.; Pietz, Kenneth] Houston Vet Affairs Hlth Serv, Res & Dev Ctr Excellence, Hlth Policy & Qual Program, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[McCormick, Marie C.; Zheng, Zheng; Zupancic, John A. F.] Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA 02215 USA.
[McCormick, Marie C.; Zupancic, John A. F.] Harvard Univ, Sch Med, Div Newborn Med, Boston, MA USA.
[McCormick, Marie C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Escobar, Gabriel J.; Coleman-Phox, Kim] Kaiser Permanente Med Care Program, Perinatal Res Unit, Oakland, CA USA.
RP Profit, J (reprint author), Houston Vet Affairs Hlth Serv, Res & Dev Ctr Excellence 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM profit@bcm.edu
OI Zupancic, John/0000-0003-1734-7193; McCormmick,
Marie/0000-0002-3938-1707
FU Agency for Healthcare Research and Quality [5 R01 HS 10131-02, T32 HS
000063]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development [K23 HD056298-01]; American Heart Association
[0540043N]; Veterans Administration Center [CoE HFP90-20]
FX This project was supported by the Agency for Healthcare Research and
Quality (grant 5 R01 HS 10131-02, "Unstudied Infants: Low Risk Babies in
a High Risk Place" [to Dr McCormick]). Dr Profit's contribution is
supported in part by the Agency for Healthcare Research and Quality
(grant T32 HS 000063) and Eunice Kennedy Shriver National Institute of
Child Health and Human Development grant K23 HD056298-01. Dr Petersen is
a recipient of the American Heart Association Established Investigator
Award (grant 0540043N). Drs Petersen and Profit also receive support
from a Veterans Administration Center grant (Veterans Affairs Health
Services Research and Development CoE HFP90-20).
NR 18
TC 14
Z9 14
U1 0
U2 4
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD FEB
PY 2010
VL 125
IS 2
BP 320
EP 326
DI 10.1542/peds.2008-3140
PG 7
WC Pediatrics
SC Pediatrics
GA 573VH
UT WOS:000275942900017
PM 20064868
ER
PT J
AU Prosser, LA
Kong, CY
Rusinak, D
Waisbren, SL
AF Prosser, Lisa A.
Kong, Chung Yin
Rusinak, Donna
Waisbren, Susan L.
TI Projected Costs, Risks, and Benefits of Expanded Newborn Screening for
MCADD
SO PEDIATRICS
LA English
DT Article
DE newborn screening; cost-effectiveness; economic; QALY
ID TANDEM MASS-SPECTROMETRY; COA DEHYDROGENASE-DEFICIENCY; INFLUENZA
VACCINATION; ECONOMIC-EVALUATION; HEALTH STATES; CHILDREN; DISORDERS;
PREFERENCES; PHENYLKETONURIA; INTERVENTIONS
AB OBJECTIVE: To evaluate the cost-effectiveness of newborn screening for medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) incorporating quality-of-life effects for false-positive newborn screens and recommended dietary treatment.
METHODS: A computer simulation model was developed to predict costs and health outcomes for expanded newborn screening for MCADD compared with clinical identification. The modeled target population was a hypothetical cohort of 100 000 newborns in the United States. Probabilities, costs, and quality-of-life weights were derived from a long-term follow-up study of newborn screening compared with clinical identification, primary data collection, published data, and expert opinion. We used a lifetime time horizon and the societal perspective. The main outcome measure was the incremental cost-effectiveness ratio in dollars per quality-adjusted life-year (QALY) gained. Secondary outcomes included averted deaths and hospitalizations.
RESULTS: Using base-case assumptions, the cost-effectiveness of newborn screening for MCADD was $21 273 per QALY gained. The cost-effectiveness ratio increased to $21 278/QALY when the loss in quality of life associated with false-positive test results was incorporated and to $27 423/QALY when the quality of life associated with lifelong dietary recommendations for treating MCADD was incorporated. Results were sensitive to the false-positive rate for the newborn screening test and the cost of the initial screen.
CONCLUSIONS: Expanded newborn screening for MCADD is cost-effective compared with well-accepted pediatric health interventions. Losses in quality of life associated with dietary treatment for MCADD, however, may offset some of the gains in QALYs from newborn screening. Consideration of new disorders for expanded newborn screening panels should include the potential reduction in quality of life associated with treatments. Pediatrics 2010; 125:e286-e294
C1 [Prosser, Lisa A.] Univ Michigan, Sch Med, Div Gen Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI USA.
[Prosser, Lisa A.; Rusinak, Donna] Harvard Univ, Sch Med, Ctr Child Hlth Care Studies, Boston, MA USA.
[Prosser, Lisa A.; Rusinak, Donna] Harvard Pilgrim Hlth Care, Boston, MA USA.
[Kong, Chung Yin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Waisbren, Susan L.] Childrens Hosp Boston, Dept Genet, Boston, MA USA.
RP Prosser, LA (reprint author), Univ Michigan Hlth Syst, Div Gen Pediat, Child Hlth Evaluat & Res Unit, 300 N Ingalls St,Room 6E14, Ann Arbor, MI 48109 USA.
EM lisapros@med.umich.edu
FU National Human Genome Research Institute, Division of Ethical, Legal and
Social Implications [2R01HG002085-04]
FX Funding for this study was provided by the National Human Genome
Research Institute, Division of Ethical, Legal and Social Implications
(grant 2R01HG002085-04).
NR 46
TC 24
Z9 24
U1 2
U2 6
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD FEB
PY 2010
VL 125
IS 2
BP E286
EP E294
DI 10.1542/peds.2009-0605
PG 9
WC Pediatrics
SC Pediatrics
GA 573VH
UT WOS:000275942900042
PM 20123779
ER
PT J
AU Inhoff, T
Stengel, A
Peter, L
Goebel, M
Tache, Y
Bannert, N
Wiedenmann, B
Klapp, BF
Monnikes, H
Kobelt, P
AF Inhoff, Tobias
Stengel, Andreas
Peter, Lisa
Goebel, Miriam
Tache, Yvette
Bannert, Norbert
Wiedenmann, Bertram
Klapp, Burghard F.
Moennikes, Hubert
Kobelt, Peter
TI Novel insight in distribution of nesfatin-1 and phospho-mTOR in the
arcuate nucleus of the hypothalamus of rats
SO PEPTIDES
LA English
DT Article
DE Arcuate nucleus; Rat; Nesfatin-1; Phospho-mTOR; CART; NPY
ID AMPHETAMINE-REGULATED TRANSCRIPT; NEUROPEPTIDE-Y; FEEDING-BEHAVIOR; CART
NEURONS; SPINAL-CORD; FOOD-INTAKE; PEPTIDE; PROTEIN; GHRELIN; BRAIN
AB Recently, two proteins have been localized in the arcuate nucleus (ARC) and implicated in the regulation of food intake: the serine-threonine-kinase mammalian target of rapamycin (mTOR) as part of the TOR signaling complex 1 (TORC1), and nesfatin-1 derived from the precursor protein nucleobindin2. However, the exact cell types are not well described. Therefore, we performed double-labeling studies for NPY, CART, nesfatin-1 and pmTOR in the ARC. In this study, we showed that nesfatin-1 is not only intracellularly co-localized with cocaine- and amphetamine-regulated transcript (CART) peptide as reported before, but also with phospho-mTOR (pmTOR) and neuropeptide Y (NPY) in ARC neurons. Quantification revealed that 59 +/- 5% of the pmTOR-immunoreactive (it) neurons were immunoreactive for nesfatin-1. Moreover, double labeling for nesfatin-1 and NPY exhibited that 19 +/- 5% of the NPY positive cells were also immunoreactive for nesfatin-1. Furthermore, we could also confirm results from previous studies, showing that the majority of nesfatin-1 neurons are also positive for CART peptide, whereas most of the pmTOR is co-localized with NPY and only to a lesser extent with CART. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Inhoff, Tobias; Peter, Lisa; Wiedenmann, Bertram; Kobelt, Peter] Univ Med Berlin, Dept Med, Div Hepatol Gastroenterol & Endocrinol, Charite, D-10117 Berlin, Germany.
[Klapp, Burghard F.; Kobelt, Peter] Univ Med Berlin, Dept Med, Div Psychosomat Med & Psychotherapy, Charite, D-10117 Berlin, Germany.
[Stengel, Andreas; Goebel, Miriam; Tache, Yvette] Univ Calif Los Angeles, Dept Med, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA.
[Stengel, Andreas; Goebel, Miriam; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol Stress, Los Angeles, CA 90024 USA.
[Stengel, Andreas; Goebel, Miriam; Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Bannert, Norbert] Robert Koch Inst, D-1000 Berlin, Germany.
[Moennikes, Hubert] Martin Luther Hosp, Dept Med, Berlin, Germany.
[Moennikes, Hubert] Martin Luther Hosp, Inst Neurogastroenterol, Berlin, Germany.
RP Kobelt, P (reprint author), Univ Med Berlin, Dept Med, Div Hepatol Gastroenterol & Endocrinol, Charite, Campus Virchow, D-10117 Berlin, Germany.
EM peter.kobelt@charite.de
FU German Research Foundation [DFG KO 3864/2-1, DFG STE 1765/1-1, GO
1718/1-1]; Charite-Universitatsmedizin Berlin [UFF 09/41730, 09/42458];
Veterans Administration Research Career Scientist Award; Veterans
Administration Merit Award; NIHDK [33061]; [DK-41301]
FX This work was supported by grants from the German Research Foundation to
PX (DFG KO 3864/2-1), A.S. (DFG STE 1765/1-1), M.G. (GO 1718/1-1), and
from Charite-Universitatsmedizin Berlin to PX (UFF 09/41730 and
09/42458) as well as Veterans Administration Research Career Scientist
Award (Y.T.), Veterans Administration Merit Award (Y.T.), NIHDK 33061
(Y.T.), Center Grant DK-41301 (Animal Core) (Y.T.).
NR 32
TC 40
Z9 44
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
J9 PEPTIDES
JI Peptides
PD FEB
PY 2010
VL 31
IS 2
BP 257
EP 262
DI 10.1016/j.peptides.2009.11.024
PG 6
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 560BQ
UT WOS:000274877200010
PM 19961888
ER
PT J
AU Yuan, PQ
Wu, SV
Wang, L
Tache, Y
AF Yuan, P. -Q
Wu, S. V.
Wang, L.
Tache, Y.
TI Corticotropin releasing factor in the rat colon: Expression,
localization and upregulation by endotoxin
SO PEPTIDES
LA English
DT Article
DE Corticotropin releasing factor; Enterochromaffin cells; Enteric nervous
system; Lipopolysaccharide; Colon; Stress; Defecation; Corticosterone
ID ENTERIC NERVOUS-SYSTEM; IRRITABLE-BOWEL-SYNDROME; MYENTERIC NEURONS;
INTESTINAL INFLAMMATION; CONSCIOUS RATS; MAST-CELLS;
TRYPTOPHAN-HYDROXYLASE; ENTEROCHROMAFFIN CELLS; 5-HT3 RECEPTORS;
CHALLENGED RATS
AB Little is known about CRF expression and regulation in the rat colon compared to the brain. We investigated CRF gene expression, cellular location, and regulation by endotoxin and corticosterone in the male rat colon at 6 h after intraperitoneal (ip) injection. CRF mRNA level, detected by reverse transcription-polymerase chain reaction (RT-PCR) was 1.3-fold higher in the distal than proximal colon and 3.4-fold higher in the proximal colonic submucosa plus muscle layers than in mucosa. CRF immunoreactivity was located in the epithelia, lamina propria and crypts, and co-localized with tryptophan hydroxylase. a marker for enterochromaffin (EC) cells, and in enteric neurons. Lipopolysaccharide (LPS, 100 mu g/kg, ip) increased defecation by 2.9-fold and upregulated CRF mRNA by 2.5-fold in the proximal and 1.1-fold in the distal colon while there was no change induced by corticosterone as monitored by quantitative PCR. LPS-induced increased CRF mRNA expression occurred in the submucosa plus muscle layers (1.5-fold) and the mucosa of proximal colon (0.9-fold). LIPS increased significantly CRF immunoreactivity in the submucosal and myenteric plexuses of proximal and distal colon compared to saline groups. These results indicate that in rats, CRF is expressed in both proximal and distal colon and more prominently in enteric neurons of the submucosa plus muscle layers and subject to upregulation at the gene and protein levels by LPS through corticosteroid independent pathways. These data suggests that colonic CRF may be part of the local effector limb of the CRF, receptor mediated colonic alterations induced by acute stress. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Yuan, P. -Q] Univ Calif Los Angeles, CURE, DDRC, VA GLAHS, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Ctr Neurobiol Stress, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Div Digest Dis, Dept Med, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA.
RP Yuan, PQ (reprint author), Univ Calif Los Angeles, CURE, DDRC, VA GLAHS, Bldg 115,Rm 213B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM pqyuan@mednet.ucla.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [R01
DK-57238]; VA Career Scientist Award and Merit Award [DK-41301];
[P01-DK 33506]
FX We thank Drs. Wylie W. Vale and jean Rivier(Salk institute, San Diego,
CA) for the generous donation of the rabbit anti-CRF antiserum, and rat
CRF, respectively and Ms Honghui Liang for technical assistance. This
work was supported by the National Institute of Diabetes and Digestive
and Kidney Diseases, grants R01 DK-57238 (YT), VA Career Scientist Award
and Merit Award (YT), DK-41301 (Animal Core, YT), P01-DK 33506 (C.
Pothoulakis, PI).
NR 55
TC 20
Z9 20
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
J9 PEPTIDES
JI Peptides
PD FEB
PY 2010
VL 31
IS 2
BP 322
EP 331
DI 10.1016/j.peptides.2009.11.012
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 560BQ
UT WOS:000274877200020
PM 19944726
ER
PT J
AU Stengel, A
Goebel, M
Wang, LX
Tache, Y
AF Stengel, Andreas
Goebel, Miriam
Wang, Lixin
Tache, Yvette
TI Ghrelin, des-acyl ghrelin and nesfatin-1 in gastric X/A-like cells: Role
as regulators of food intake and body weight
SO PEPTIDES
LA English
DT Review
DE Body weight; Endocrine cell; Food intake; Ghrelin; Nesfatin-1; NUCB2;
Obesity; Stomach
ID GROWTH-HORMONE SECRETAGOGUE; GLUCAGON-LIKE PEPTIDE-1; STIMULATES
LOCOMOTOR-ACTIVITY; O-ACYLTRANSFERASE GOAT; COUPLED RECEPTOR GPR39;
AGOUTI-RELATED PROTEIN; RAT ARCUATE NUCLEUS; PLASMA GHRELIN; PERIPHERAL
GHRELIN; SLEEVE GASTRECTOMY
AB Numerous peptides released from endocrine cells in the intestinal mucosa were established early on to be involved in the physiological regulation of food intake with a prominent role in termination of food ingestion when nutrients pass along the intestinal tract. Recently, peptides released from X/A-like endocrine cells of the gastric oxyntic mucosa were recognized as additional key players in the regulation of feeding and energy expenditure. Gastric X/A-like cells release the octanoylated peptide, ghrelin, the only known peripherally produced hormone stimulating food intake through interaction with growth hormone secretagogue I a receptor(GHS-R1a). Additionally, non-octanoylated (des-acyl) ghrelin present in the circulation at higher levels than ghrelin is currently discussed as potential modulator of food intake by opposing ghrelin's action independent from GHS-R1a although the functional significance remains to be established. Obestatin, a ghrelin-associated peptide was initially reported as anorexigenic modulator of ghrelin's orexigenic action. However, subsequent reports did not support this contention. Interesting is the recent identification of nesfatin-1, a peptide derived from the nucleobindin2 gene prominently expressed in gastric X/A-like cells in different vesicles than ghrelin. Circulating nesfatin-1 levels vary with metabolic state and peripheral or central injection inhibits dark phase feeding in rodents. Overall, these data point to an important role of gastric X/A-like cells in food intake regulation through the expression of the orexigenic peptide ghrelin along with des-acyl ghrelin and nesfatin-1 capable of reducing food intake upon exogenous injection although their mechanisms of action and functional significance remain to be established. Published by Elsevier Inc
C1 [Tache, Yvette] Univ Calif Los Angeles, Digest Dis Res Ctr, CURE, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Div Digest Dis, David Geffen Sch Med, Los Angeles, CA 90073 USA.
RP Tache, Y (reprint author), Univ Calif Los Angeles, Digest Dis Res Ctr, CURE, VA Greater Los Angeles Healthcare Syst, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM astengel@mednet.ucla.edu; ytache@mednet.ucla.edu
FU VA Research Career Scientist Award; NIH [DK-33061, DK-57238]; VA Merit
Award; German Research Foundation [STE 1765/1-1 and GO 1718/1-1]
FX Y.T. is in receipt of VA Research Career Scientist Award and NIH R01
grants DK-33061, DK-57238 and VA Merit Award. A.S. and M.G. are
supported by the German Research Foundation grants STE 1765/1-1 and GO
1718/1-1 respectively. We thank Ms. Eugenia Hu for careful reading of
the manuscript.
NR 170
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Z9 61
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
J9 PEPTIDES
JI Peptides
PD FEB
PY 2010
VL 31
IS 2
BP 357
EP 369
DI 10.1016/j.peptides.2009.11.019
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 560BQ
UT WOS:000274877200025
PM 19944123
ER
PT J
AU Blais, MA
AF Blais, Mark A.
TI The common structure of normal personality and psychopathology:
Preliminary exploration in a non-patient sample
SO PERSONALITY AND INDIVIDUAL DIFFERENCES
LA English
DT Article
DE Normal personality; Psychopathology; Common structure; Factor analysis
ID HIGHER-ORDER FACTORS; MENTAL-DISORDERS; MODEL; INSTRUMENTS; TRAITS;
SCALES
AB Normal personality and psychopathology have traditionally been conceptualized as separate or distinct areas of inquiry. However recent research exploring the hierarchical nature of personality traits suggests the possibility of integrating findings across these domains. This study used the Personality Assessment Inventory (Morey, 1991) and NEO-Personality Inventory-Revised (Costa & McCrae, 1992) to investigate the joint factor structure of normal personality and psychopathology. Factor analysis revealed a well defined three factor structure with scales from both instruments having prominent loadings on all the factors. The first joint PAI-NEO factor was marked by Neuroticism, Anxiety, Depression and Borderline Personality traits, the second factor had negative loadings for Agreeableness and Conscientiousness and positive loadings for Drug Abuse and Antisocial Personality traits. The third joint factor had positive loadings for Extraversion, Openness and Mania plus a secondary negative loading for Depression. The joint PAI-NEO factor structure bore a clear resemblance to the Big Three model of personality traits depicted in Markon, Krueger, and Watson's (2005) personality hierarchy. While preliminary the current findings suggest that normal personality and psychopathology may share a common latent structure and their shared structure may integrate into the broader hierarchy of personality traits. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Blais, Mark A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Blais, Mark A.] Harvard Univ, Sch Med, Psychol Evaluat & Res Lab, Boston, MA 02114 USA.
RP Blais, MA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM Mblais@partners.org
NR 28
TC 8
Z9 8
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0191-8869
J9 PERS INDIV DIFFER
JI Pers. Individ. Differ.
PD FEB
PY 2010
VL 48
IS 3
BP 322
EP 326
DI 10.1016/j.paid.2009.10.028
PG 5
WC Psychology, Social
SC Psychology
GA 557OE
UT WOS:000274678000012
ER
PT J
AU Deo, RC
Hunter, L
Lewis, GD
Pare, G
Vasan, RS
Chasman, D
Wang, TJ
Gerszten, RE
Roth, FP
AF Deo, Rahul C.
Hunter, Luke
Lewis, Gregory D.
Pare, Guillaume
Vasan, Ramachandran S.
Chasman, Daniel
Wang, Thomas J.
Gerszten, Robert E.
Roth, Frederick P.
TI Interpreting Metabolomic Profiles using Unbiased Pathway Models
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID CITRIN DEFICIENCY; PROSTATE-CANCER; BREAST-CANCER; HUMAN-DISEASE;
NETWORK; INSULIN; ASSOCIATION; CLASSIFICATION; PREDICTION; SIGNATURES
AB Human disease is heterogeneous, with similar disease phenotypes resulting from distinct combinations of genetic and environmental factors. Small-molecule profiling can address disease heterogeneity by evaluating the underlying biologic state of individuals through non-invasive interrogation of plasma metabolite levels. We analyzed metabolite profiles from an oral glucose tolerance test (OGTT) in 50 individuals, 25 with normal (NGT) and 25 with impaired glucose tolerance (IGT). Our focus was to elucidate underlying biologic processes. Although we initially found little overlap between changed metabolites and preconceived definitions of metabolic pathways, the use of unbiased network approaches identified significant concerted changes. Specifically, we derived a metabolic network with edges drawn between reactant and product nodes in individual reactions and between all substrates of individual enzymes and transporters. We searched for "active modules''-regions of the metabolic network enriched for changes in metabolite levels. Active modules identified relationships among changed metabolites and highlighted the importance of specific solute carriers in metabolite profiles. Furthermore, hierarchical clustering and principal component analysis demonstrated that changed metabolites in OGTT naturally grouped according to the activities of the System A and L amino acid transporters, the osmolyte carrier SLC6A12, and the mitochondrial aspartate-glutamate transporter SLC25A13. Comparison between NGT and IGT groups supported blunted glucose- and/or insulin-stimulated activities in the IGT group. Using unbiased pathway models, we offer evidence supporting the important role of solute carriers in the physiologic response to glucose challenge and conclude that carrier activities are reflected in individual metabolite profiles of perturbation experiments. Given the involvement of transporters in human disease, metabolite profiling may contribute to improved disease classification via the interrogation of specific transporter activities.
C1 [Deo, Rahul C.; Hunter, Luke; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Deo, Rahul C.; Lewis, Gregory D.; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Lewis, Gregory D.; Gerszten, Robert E.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Pare, Guillaume; Chasman, Daniel] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA.
[Pare, Guillaume; Chasman, Daniel] Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Ctr Cardiovasc Res, Boston, MA 02115 USA.
[Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Boston, MA USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
RP Deo, RC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM fritz_roth@hms.harvard.edu
RI Roth, Frederick/H-6308-2011;
OI Ramachandran, Vasan/0000-0001-7357-5970; Roth,
Frederick/0000-0002-6628-649X
FU NIH [T32 HL007208, HL096738, DK081572-02, HL081341, HG004233, HG0017115,
NS035611, HG003224]; AHA; Leducq Foundation; Canadian Institute for
Advanced Research
FX RCD was supported by NIH grant T32 HL007208; REG was supported by NIH
Grants HL096738, DK081572-02, the AHA Established Investigator Award and
the Leducq Foundation; and FPR was supported by NIH grants HL081341,
HG004233, HG0017115, NS035611, HG003224 and by the Canadian Institute
for Advanced Research. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 42
TC 32
Z9 32
U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-734X
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2010
VL 6
IS 2
AR e1000692
DI 10.1371/journal.pcbi.1000692
PG 14
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 565AI
UT WOS:000275260000012
PM 20195502
ER
PT J
AU Kim, SY
Dunn, IF
Firestein, R
Gupta, P
Wardwell, L
Repich, K
Schinzel, AC
Wittner, B
Silver, SJ
Root, DE
Boehm, JS
Ramaswamy, S
Lander, ES
Hahn, WC
AF Kim, So Young
Dunn, Ian F.
Firestein, Ron
Gupta, Piyush
Wardwell, Leslie
Repich, Kara
Schinzel, Anna C.
Wittner, Ben
Silver, Serena J.
Root, David E.
Boehm, Jesse S.
Ramaswamy, Sridhar
Lander, Eric S.
Hahn, William C.
TI CK1 epsilon Is Required for Breast Cancers Dependent on beta-Catenin
Activity
SO PLOS ONE
LA English
DT Article
ID WNT SIGNALING PATHWAY; COLON-CANCER; EXPRESSION; ACTIVATION; GENE;
INHIBITOR; GROWTH; CELLS; MEMBRANE; ONCOGENE
AB Background: Aberrant beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate beta-catenin activity for therapeutic purposes have proven elusive to date.
Methodology: To uncover genetic dependencies in breast cancer cells that harbor active beta-catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized beta-catenin activity. Here we identify CSNK1E, the gene encoding casein kinase 1 epsilon (CK1 epsilon) as required specifically for the proliferation of breast cancer cells with activated beta-catenin and confirm its role as a positive regulator of beta-catenin-driven transcription. Furthermore, we demonstrate that breast cancer cells that harbor activated beta-catenin activity exhibit enhanced sensitivity to pharmacological blockade of Wnt/beta-catenin signaling. We also find that expression of CK1e is able to promote oncogenic transformation of human cells in a beta-catenin-dependent manner.
Conclusions/Significance: These studies identify CK1 epsilon as a critical contributor to activated beta-catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active beta-catenin. More generally, these observations delineate an approach that can be used to identify druggable synthetic lethal interactions with signaling pathways that are frequently activated in cancer but are difficult to target with the currently available small molecule inhibitors.
C1 [Kim, So Young; Dunn, Ian F.; Firestein, Ron; Wardwell, Leslie; Repich, Kara; Schinzel, Anna C.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wittner, Ben; Ramaswamy, Sridhar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Firestein, Ron] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Kim, So Young; Schinzel, Anna C.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kim, So Young; Firestein, Ron; Schinzel, Anna C.; Boehm, Jesse S.; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Kim, So Young; Dunn, Ian F.; Firestein, Ron; Gupta, Piyush; Repich, Kara; Schinzel, Anna C.; Silver, Serena J.; Root, David E.; Boehm, Jesse S.; Ramaswamy, Sridhar; Lander, Eric S.; Hahn, William C.] Broad Inst, Cambridge, MA USA.
[Wittner, Ben; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Ramaswamy, Sridhar] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Kim, SY (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM William_Hahn@dfci.harvard.edu
OI Boehm, Jesse/0000-0002-6795-6336
FU Department of Defense postdoctoral fellowship; National Institutes of
Health (NIH) [K08 CA134836-01]; Mentored Clinical Scientist Award [P50
CA127003]; GI SPORE Career Development [R33 CA128625, R01 CA130988];
Department of Defense Idea Award [W81XWH-07-1-0408]; Dana-Farber Harvard
Cancer Center SPORE in Breast Cancer [P50 CA89393]
FX This work was supported in part by a Department of Defense postdoctoral
fellowship (S.Y.K.), the Brain Science Foundation and
Warren-Whitman-Richardson Foundation (I. D.), K08 CA134836-01 from
National Institutes of Health (NIH): Mentored Clinical Scientist Award
and P50 CA127003: GI SPORE Career Development Grant (R.F.), R33 CA128625
(W.C.H.), R01 CA130988 (W.C.H.), Department of Defense Idea Award
W81XWH-07-1-0408 (W.C.H.), Dana-Farber Harvard Cancer Center SPORE in
Breast Cancer P50 CA89393 (S.R.). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 38
TC 46
Z9 49
U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 1
PY 2010
VL 5
IS 2
AR e8979
DI 10.1371/journal.pone.0008979
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 551LF
UT WOS:000274209700008
PM 20126544
ER
PT J
AU Evans, CT
Li, K
Burns, SP
Smith, B
Lee, TA
Weaver, FM
AF Evans, Charlesnika T.
Li, Keran
Burns, Stephen P.
Smith, Bridget
Lee, Todd A.
Weaver, Frances M.
TI Antibiotic Prescribing for Acute Respiratory Infection and Subsequent
Outpatient and Hospital Utilization in Veterans With Spinal Cord Injury
and Disorder
SO PM&R
LA English
DT Article
AB Objective: To assess the association between antibiotic prescribing for acute respiratory infection (ARI) and subsequent health-care utilization in veterans with spinal cord injury and disorder (SCI/D).
Design: Retrospective cohort of veterans with SCI/D.
Setting: Veterans Affairs medical facilities that provide outpatient care.
Patients: Veterans with SCI/D with a diagnosis of acute bronchitis or upper respiratory infection during an outpatient visit between fiscal year 2006 and 2007 that did not result in same-clay hospitalization.
Independent Variable: Receipt of a new antibiotic prescription occurring within 3 clays before or after an ARI visit.
Main Outcome Measure: Subsequent outpatient visit or hospitalization within 30 days of the index ARI visit.
Results: A total of 1277 patients were identified with ARI; 53.2% were prescribed an antibiotic. An outpatient clinic visit within 30 days of the index ARI visit occurred in 47.0% of patients. Receipt of an antibiotic prescription was not associated with a subsequent outpatient visit. However, in those with certain chronic respiratory conditions (cough, shortness of breath, bronchitis not specified as acute or chronic, and allergic rhinitis), those prescribed antibiotics were less likely to return for an outpatient visit than those not prescribed antibiotics (adjusted relative risk = 0.77, 95% confidence interval = 0.61-0.97); no association was observed in those patients without these conditions. A total of 7.9% of patients were hospitalized within 30 days and did not differ by prescribing group. The 30-day mortality rate was 0.6%.
Conclusions: Certain chronic respiratory conditions in veterans with SCI/D may be risk factors for increased health-care utilization and potentially poor outcomes if a patient is not treated with antibiotics for ARI. However, in those without these conditions, those with ARI who were prescribed antibiotics have similar utilization to those not prescribed antibiotics. These data suggest that in the absence of chronic respiratory conditions, antibiotic use for ARI can be curbed in this population that is at high risk for respiratory complications. PM R 2010;2:101-109
C1 [Evans, Charlesnika T.] Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care Spinal Cord Inj, Dept Vet Affairs VA, Hines, IL USA.
[Evans, Charlesnika T.; Li, Keran; Smith, Bridget; Weaver, Frances M.] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA.
[Li, Keran] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Burns, Stephen P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Burns, Stephen P.] Univ Washington, Seattle, WA 98195 USA.
[Lee, Todd A.] Univ Illinois, Chicago, IL USA.
[Weaver, Frances M.] Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA.
RP Evans, CT (reprint author), Vet Affairs Edward Hines Jr Hosp, Ctr Management Complex Chron Care Spinal Cord Inj, Dept Vet Affairs VA, 5th Ave & Roosevelt Rd,POB 5000,Room D302, Hines, IL USA.
EM Charlesnika.Evans@va.gov
FU Department of Veterans Affairs, Office at Research and Development,
Health Services Research and Development Service Locally Initiated
Project [LIP 42-503]; Paralyzed Veterans of America Research Foundation
[2562]
FX Supported by the Department of Veterans Affairs, Office at Research and
Development, Health Services Research and Development Service Locally
Initiated Project (LIP 42-503), and the Paralyzed Veterans of America
Research Foundation (Project #2562).
NR 39
TC 3
Z9 4
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD FEB
PY 2010
VL 2
IS 2
BP 101
EP 109
DI 10.1016/j.pmrj.2009.11.002
PG 9
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V23RY
UT WOS:000208361100004
PM 20117971
ER
PT J
AU Stirman, SW
Bhar, SS
Spokas, M
Brown, GK
Creed, TA
Perivoliotis, D
Farabaugh, DT
Grant, PM
Beck, AT
AF Stirman, Shannon Wiltsey
Bhar, Sunil S.
Spokas, Megan
Brown, Gregory K.
Creed, Torrey A.
Perivoliotis, Dimitri
Farabaugh, Danielle T.
Grant, Paul M.
Beck, Aaron T.
TI Training and Consultation in Evidence-Based Psychosocial Treatments in
Public Mental Health Settings: The ACCESS Model
SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE
LA English
DT Article
DE evidence-based psychotherapies; training; consultation; implementation
ID EMPIRICALLY SUPPORTED TREATMENTS; COGNITIVE-BEHAVIORAL THERAPY; STAFF
TURNOVER; IMPLEMENTATION; DISSEMINATION; PSYCHOTHERAPY; ADHERENCE;
COMMUNITY; YOUTH; INTERVENTIONS
AB We present a model of training in evidence-based psychosocial treatments (EBTs). The ACCESS (assess and adapt, convey basics, consult, evaluate. study outcomes, sustain) model integrates principles and findings from adult education and training literatures, research. and practical suggestions based on a community-based clinician training program. Descriptions of the steps are provided as a means of guiding implementation efforts and facilitating training partnerships between public mental health agencies and practitioners of EBTs.
C1 [Stirman, Shannon Wiltsey] Boston Univ, Womens Hlth Sci Div, Natl Ctr PTSD, Med Ctr, Boston, MA 02130 USA.
[Bhar, Sunil S.] Swinbourne Univ Technol, Melbourne, Vic, Australia.
[Spokas, Megan] La Salle Univ, Philadelphia, PA USA.
[Perivoliotis, Dimitri] Univ Penn, Dept Psychiat, Psychopathol Res Unit, Philadelphia, PA 19104 USA.
[Grant, Paul M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Creed, Torrey A.] Childrens Hosp Philadelphia, Ctr Family Intervent Sci, Philadelphia, PA USA.
[Creed, Torrey A.] Univ Penn, Beck Initiat, Philadelphia, PA 19104 USA.
[Farabaugh, Danielle T.] Coatesville Vet Affairs Med Ctr, Inpatient Posttraumat Stress Disorder Program, Coatesville, PA USA.
RP Stirman, SW (reprint author), Boston Univ, Womens Hlth Sci Div, Natl Ctr PTSD, Med Ctr, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA.
EM Shannon.Wiltsey-Stirman@va.gov
FU NIMH NIH HHS [K99 MH080100, K99 MH080100-01A1, P20 MH071905, R00
MH080100]
NR 63
TC 24
Z9 24
U1 2
U2 5
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7028
J9 PROF PSYCHOL-RES PR
JI Prof. Psychol.-Res. Pract.
PD FEB
PY 2010
VL 41
IS 1
BP 48
EP 56
DI 10.1037/a0018099
PG 9
WC Psychology, Multidisciplinary
SC Psychology
GA 554ZL
UT WOS:000274475600007
PM 22872783
ER
PT J
AU Conklin, SM
Runyan, CA
Leonard, S
Reddy, RD
Muldoon, MF
Yao, JK
AF Conklin, Sarah M.
Runyan, Caroline A.
Leonard, Sherry
Reddy, Ravinder D.
Muldoon, Matthew F.
Yao, Jeffrey K.
TI Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the
anterior cingulate cortex of individuals with major depressive disorder
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Depression; Anterior cingulate cortex; Postmortem; n-6 fatty acids;
Arachidonic acid; n-3 fatty acids; Eicosapentaenoic acid;
Docosahexaenoic acid; Age
ID OMEGA-3-FATTY-ACID DOCOSAHEXAENOIC ACID; POSTMORTEM ORBITOFRONTAL
CORTEX; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL;
PRELIMINARY DOUBLE-BLIND; BLOOD-CELL MEMBRANES; ARACHIDONIC-ACID;
BIPOLAR DISORDER; FISH CONSUMPTION; FRONTAL-CORTEX
AB Accumulating evidence finds a relative deficiency of peripheral membrane fatty acids in persons with affective disorders such as unipolar and bipolar depression. Here we sought to investigate whether postmortem brain fatty acids within the anterior cingulate cortex (BA-24) varied according to the presence of major depression at the time of death. Using capillary gas chromatography we measured fatty acids in a depressed group (n = 12), and in a control group without lifetime history of psychiatric diagnosis (n = 14). Compared to the control group, the depressed group showed significantly lower concentrations of numerous saturated and polyunsaturated fatty acids including both the n-3 and n-6 fatty acids. Additionally, significant correlations between age at death and precursor (or metabolites) in the n-3 fatty acid pathway were demonstrated in the depressed group but not in control subjects. In the n-6 fatty acid family, the ratio of 20:3(n-6)/18:2(n-6) was higher in patients than in control groups, whereas the ratio of 20A(n-6)/20:3(n-6) was relatively decreased in patients. Lastly, a significant negative correlation between age and the ratio of 20:4(n-6) to 22:6(n-3) was found in patients, but not in controls. Taken together, decreases in 22:6(n-3) may be caused, at least in part, by the diminished formation of 20:5(n-3), which is derived from 20:4(n-3) through a Delta 5 desaturase reaction. The present findings from postmortem brain tissue raise the possibility that an increased ratio of 20:4(n-6) to 22:6(n-3) may provide us with a biomarker for depression. Future research should further investigate these relationships. Published by Elsevier Ltd.
C1 [Conklin, Sarah M.; Reddy, Ravinder D.; Muldoon, Matthew F.; Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA.
[Conklin, Sarah M.] Allegheny Coll, Neurosci Program, Meadville, PA 16335 USA.
[Conklin, Sarah M.] Allegheny Coll, Dept Psychol, Meadville, PA 16335 USA.
[Runyan, Caroline A.] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
[Leonard, Sherry] Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO USA.
[Leonard, Sherry] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA.
[Leonard, Sherry] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA.
[Reddy, Ravinder D.; Yao, Jeffrey K.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA.
[Muldoon, Matthew F.] Univ Pittsburgh, Sch Med, Ctr Clin Pharmacol, Pittsburgh, PA USA.
[Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA.
EM jkyao@pitt.edu
FU Office of Research and Development, Department of Veterans Affairs; NIH
[T32 HL007560]; Highland Drive VA Pittsburgh Healthcare System
FX This study was supported in parts by the Office of Research and
Development, Department of Veterans Affairs [Merit Reviews (JKY,SL) and
Research Career Scientist Awards (JKY,SL)], NIH T32 HL007560 (SMC, MFM),
and the Highland Drive VA Pittsburgh Healthcare System. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript. The contents of this article
do not represent the views of the Department of Veterans Affairs or the
United States Government.
NR 57
TC 28
Z9 28
U1 6
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD FEB-MAR
PY 2010
VL 82
IS 2-3
BP 111
EP 119
DI 10.1016/j.plefa.2009.12.002
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 569RQ
UT WOS:000275617500007
PM 20060277
ER
PT J
AU Vera, M
Perez-Pedrogo, C
Huertas, SE
Reyes-Rabanillo, ML
Juarbe, D
Huertas, A
Reyes-Rodriguez, ML
Chaplin, W
AF Vera, Mildred
Perez-Pedrogo, Coralee
Huertas, Sarah Enid
Reyes-Rabanillo, Maria Leticia
Juarbe, Deborah
Huertas, Aracelis
Reyes-Rodriguez, Mae Lynn
Chaplin, William
TI Collaborative Care for Depressed Patients With Chronic Medical
Conditions: A Randomized Trial in Puerto Rico
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID COMORBID DEPRESSION; HEALTH-SERVICES; CHRONIC DISEASE; TERM OUTCOMES;
MANAGEMENT; METAANALYSIS; POPULATION; VALIDATION; SYMPTOMS; VALIDITY
AB Objective: This study examined whether a collaborative care model for depression would improve clinical and functional outcomes for depressed patients with chronic general medical conditions in primary care practices in Puerto Rico. Methods: A total of 179 primary care patients with major depression and chronic general medical conditions were randomly assigned to receive collaborative care or usual care. The collaborative care intervention involved enhanced collaboration among physicians, mental health specialists, and care managers paired with depression-specific treatment guidelines, patient education, and follow-up. In usual care, study personnel informed the patient and provider of the diagnosis and encouraged patients to discuss treatment options with their provider. Depression severity was assessed with the Hopkins Symptom Checklist; social functioning was assessed with the 36-item Short Form. Results: Compared with usual care, collaborative care significantly reduced depressive symptoms and improved social functioning in the six months after randomization. Integration of collaborative care in primary care practices considerably increased depressed patients' use of mental health services. Conclusions: Collaborative care significantly improved clinical symptoms and functional status of depressed patients with coexisting chronic general medical conditions receiving treatment for depression in primary care practices in Puerto Rico. These findings highlight the promise of the collaborative care model for strengthening the relationship between mental health and primary care services in Puerto Rico. (Psychiatric Services 61:144-150, 2010)
C1 [Vera, Mildred; Perez-Pedrogo, Coralee; Juarbe, Deborah] Univ Puerto Rico, Ctr Evaluat & Sociomed Res, Grad Sch Publ Hlth, San Juan, PR 00936 USA.
[Huertas, Aracelis] Univ Puerto Rico, Sch Hlth Profess, San Juan, PR 00936 USA.
[Huertas, Sarah Enid] Univ Puerto Rico, Dept Psychiat, Sch Med, San Juan, PR 00936 USA.
[Vera, Mildred] Univ Puerto Rico, Dept Hlth Serv Adm, San Juan, PR 00936 USA.
[Reyes-Rabanillo, Maria Leticia] US Dept Vet Affairs, VA Caribbean Healthcare Syst, San Juan, PR USA.
[Reyes-Rodriguez, Mae Lynn] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA.
[Chaplin, William] St Johns Univ, Dept Psychol, New York, NY USA.
RP Vera, M (reprint author), Univ Puerto Rico, Ctr Evaluat & Sociomed Res, Grad Sch Publ Hlth, Med Sci Campus,POB 365067, San Juan, PR 00936 USA.
EM mildred.vera@upr.edu
FU National Institute of General Medical Sciences [S06-GM008224]; Pfizer,
Inc [WS297211]; National Center for Research Resources [P20-RR11126]
FX This project was supported by grant S06-GM008224 from the National
Institute of General Medical Sciences, grant WS297211 from Pfizer, Inc.,
and grant P20-RR11126 from the National Center for Research Resources.
NR 36
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Z9 19
U1 2
U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD FEB
PY 2010
VL 61
IS 2
BP 144
EP 150
PG 7
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 550VN
UT WOS:000274160300008
PM 20123819
ER
PT J
AU Gonzalez, JM
Bowden, CL
Berman, N
Frank, E
Bauer, MS
Kogan, JN
Alegria, M
Miklowitz, DJ
AF Gonzalez, Jodi M.
Bowden, Charles L.
Berman, Nancy
Frank, Ellen
Bauer, Mark S.
Kogan, Jane N.
Alegria, Margarita
Miklowitz, David J.
TI One-Year Treatment Outcomes of African-American and Hispanic Patients
With Bipolar I or II Disorder in STEP-BD
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID NATIONAL-COMORBIDITY-SURVEY; R PSYCHIATRIC-DISORDERS; SEVERE
MENTAL-ILLNESS; UNITED-STATES; RACIAL-DIFFERENCES; 12-MONTH PREVALENCE;
CULTURAL MISTRUST; WHITE PATIENTS; RATING-SCALE; DIAGNOSIS
AB Objective: Few studies have compared treatment outcomes of African-American, Hispanic, and non-Hispanic white patients with bipolar disorder. The U. S. Systematic Treatment Enhancement Program for Bipolar Disorder compared one-year outcomes for bipolar I or II disorder from each of these racial-ethnic groups. Methods: African Americans (N=155) were retrospectively compared with a matched group of non-Hispanic whites (N=729), and Hispanics (N=152) were compared with a separate matched group of non-Hispanic whites (N=822). Response and recovery outcomes were examined. Survival analysis was used to compare time to treatment response for depression (Montgomery-Asberg Depression Rating Scale) and mania (Young Mania Rating Scale) as well as global assessment of functioning (Global Assessment of Functioning). Results: For manic and depressive symptoms, time to response and proportion of responders were similar across groups. Over the study year the proportion of days well was similar across groups. A smaller proportion of African Americans met criteria for improved global functioning. Depression response among African Americans with psychotic symptoms was slower than the response among African Americans without psychotic symptoms and among non-Hispanic whites with or without psychotic symptoms. No differences between Hispanics and non-Hispanic whites in response times and recovery were observed. Conclusions: Results are consistent with U. S. clinical trials for other psychiatric disorders, which have reported similar outcomes for ratings of primary symptoms. Baseline psychotic symptoms are likely a significant contributor when African Americans with bipolar disorder are slow to recover. These results may be less generalizable to uninsured patients. (Psychiatric Services 61:164-172, 2010)
C1 [Gonzalez, Jodi M.; Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Berman, Nancy] MIT, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02139 USA.
[Frank, Ellen; Kogan, Jane N.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Bauer, Mark S.] Harvard Univ, Sch Med, Harvard S Shore Psychiat Residency Training Progr, Cambridge, MA 02138 USA.
[Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA.
[Alegria, Margarita] Cambridge Hlth Alliance, Ctr Multicultural Mental Hlth Res, Cambridge, MA USA.
[Miklowitz, David J.] Univ Calif Los Angeles, Sch Med, Div Child & Adolescent Psychiat, Los Angeles, CA 90024 USA.
RP Gonzalez, JM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM gonzalezjm1@uthscsa.edu
FU National Institute of Mental Health (NIMH) [1MH-80001, P20-MH068662]
FX This study was conducted with the support of contracts 1MH-80001 and
P20-MH068662 from the National Institute of Mental Health (NIMH).
Opinions, findings, and conclusions or recommendations expressed in this
article are those of the authors and do not necessarily reflect the
views of the NIMH. This article was approved by the STEP-BD Publication
Committee.
NR 41
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Z9 9
U1 2
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD FEB
PY 2010
VL 61
IS 2
BP 164
EP 172
PG 9
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 550VN
UT WOS:000274160300011
PM 20123822
ER
PT J
AU Leuchter, AF
Husain, MM
Cook, IA
Trivedi, MH
Wisniewski, SR
Gilmer, WS
Luther, JF
Fava, M
Rush, AJ
AF Leuchter, A. F.
Husain, M. M.
Cook, I. A.
Trivedi, M. H.
Wisniewski, S. R.
Gilmer, W. S.
Luther, J. F.
Fava, M.
Rush, A. J.
TI Painful physical symptoms and treatment outcome in major depressive
disorder: a STAR*D (Sequenced Treatment Alternatives to Relieve
Depression) report
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Antidepressant medication; major depression; pain; treatment response
ID DIAGNOSTIC SCREENING QUESTIONNAIRE; REPORT QIDS-SR; QUICK INVENTORY;
RATING-SCALE; PRIMARY-CARE; PSYCHOMETRIC EVALUATION; BACK-PAIN;
SYMPTOMATOLOGY; TRIAL; ANTIDEPRESSANTS
AB Background. Painful physical symptoms (PPS) are both common and reduce the likelihood of remission in major depressive disorder (MDD), based upon results of clinical trials in selected populations. Whether PI'S significantly contribute to poorer treatment outcome overall in primary or specialty psychiatric care settings remains Unclear.
Method. Out-patients (n = 2876) with MDD were treated in the first step of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial with citalopram up to 60 mg/day for LIP to 14 weeks. Presence of painful symptoms, as well as severity of depression, physical illness, and demographic and treatment factors were examined. Time to and overall rates of remission were analysed in relation to the presence of PPS.
Results. Of the participants, 80% complained of PPS. These patients, both in primary and specialty psychiatric settings, had significantly, lower remission rates and took longer to remit. Increasing severity of PIS was associated with greater physical illness burden, lower socio-economic status, absence of private insurance and being female, African-American or Hispanic. After adjustment for these factors, patients with PPS no longer had significantly poorer treatment outcomes.
Conclusions. Presence and severity of PPS is an indicator of MDD that may have poorer treatment outcome with in initial selective serotonin reuptake inhibitor. These poorer treatment outcomes are multifactorial, however, and are not explained by the presence and severity of pain per se.
C1 [Leuchter, A. F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Lab Brain Behav & Pharmacol,Semel Inst Neurosci &, Los Angeles, CA 90024 USA.
[Husain, M. M.; Trivedi, M. H.; Rush, A. J.] Univ Texas SW Med Sch, Dept Psychiat, Dallas, TX 75230 USA.
[Wisniewski, S. R.; Luther, J. F.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Gilmer, W. S.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA.
[Fava, M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Leuchter, AF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Lab Brain Behav & Pharmacol,Semel Inst Neurosci &, 760 Westwood Plaza,Room 37-452, Los Angeles, CA 90024 USA.
EM afl@ucla.edu
FU NIMH; National Institutes of Health [N01MH90003]
FX This project has been funded with Federal funds from the NIMH, National
Institutes of Health, under contract N01MH90003 to the University of
Texas Southwestern Medical Center at Dallas (principal investigator AJR)
[ClinicalTrials.gov no. NCT000215281.
NR 44
TC 42
Z9 45
U1 2
U2 5
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD FEB
PY 2010
VL 40
IS 2
BP 239
EP 251
DI 10.1017/S0033291709006035
PG 13
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 554GD
UT WOS:000274422600007
PM 19493369
ER
PT J
AU Jha, AK
Prasopa-Plaizier, N
Larizgoitia, I
Bates, DW
AF Jha, A. K.
Prasopa-Plaizier, N.
Larizgoitia, I.
Bates, D. W.
CA WHO World Alliance Patient Safety
TI Patient safety research: an overview of the global evidence
SO QUALITY & SAFETY IN HEALTH CARE
LA English
DT Article
ID ADVERSE DRUG EVENTS; INTENSIVE-CARE UNITS; SURGICAL-SITE INFECTIONS;
AUSTRALIAN HEALTH-CARE; HOSPITALIZED-PATIENTS; RISK-FACTORS; NOSOCOMIAL
INFECTIONS; NURSING-HOMES; WORK HOURS; INTERNS
AB Background Unsafe medical care may cause substantial morbidity and mortality globally, despite imprecise estimates of the magnitude of the problem. To better understand the extent and nature of the problem of unsafe care, the WHO World Alliance for Patient Safety commissioned an overview of the world's literature on patient safety research.
Methods Major patient safety topics were identified through a consultative and investigative process and were categorised into the framework of structure, process and outcomes of unsafe care. Lead experts examined current evidence and identified major knowledge gaps relating to topics in developing, transitional and developed nations. The report was reviewed by internal and external experts and underwent improvements based on the feedback.
Findings Twenty-three major patient safety topics were examined. Much of the evidence of the outcomes of unsafe care is from developed nations, where prevalence studies demonstrate that between 3% and 16% of hospitalised patients suffer harm from medical care. Data from transitional and developing countries also suggest substantial harm from medical care. However, considerable gaps in knowledge about the structural and process factors that underlie unsafe care globally make solutions difficult to identify, especially in resource-poor settings.
Interpretation Harm from medical care appears to pose a substantial burden to the world's population. However, much of the evidence base comes from developed nations. Understanding the scope of and solutions for unsafe care for the rest of the world is a critical component of delivering safe, effective care to all of the world's citizens.
C1 [Jha, A. K.; Bates, D. W.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Jha, A. K.; Bates, D. W.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
[Jha, A. K.] VA Boston Healthcare Syst, Boston, MA USA.
[Prasopa-Plaizier, N.; Larizgoitia, I.] WHO, WHO World Alliance Patient Safety, CH-1211 Geneva, Switzerland.
RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 665 Huntington Ave, Boston, MA 02115 USA.
EM ajha@hsph.harvard.edu
RI Bright, Roselie/D-2240-2016
FU WHO World Alliance for Patient Safety, World Health Organization,
Geneva, Switzerland
FX Funding The project was funded by the WHO World Alliance for Patient
Safety, World Health Organization, Geneva, Switzerland.
NR 77
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U1 1
U2 13
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1475-3898
J9 QUAL SAF HEALTH CARE
JI Qual. Saf. Health Care
PD FEB
PY 2010
VL 19
IS 1
BP 42
EP 47
DI 10.1136/qshc.2008.029165
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 557BC
UT WOS:000274641500009
PM 20172882
ER
PT J
AU Feuchtner, GM
Alkadhi, H
Karlo, C
Sarwar, A
Meier, A
Dichtl, W
Leschka, S
Blankstein, R
Gruenenfelder, J
Stolzmann, P
Cury, RC
AF Feuchtner, Gudrun M.
Alkadhi, Hatem
Karlo, Christoph
Sarwar, Ammar
Meier, Andreas
Dichtl, Wolfgang
Leschka, Sebastian
Blankstein, Ron
Gruenenfelder, Juerg
Stolzmann, Paul
Cury, Ricardo C.
TI Cardiac CT Angiography for the Diagnosis of Mitral Valve Prolapse:
Comparison with Echocardiography
SO RADIOLOGY
LA English
DT Article
ID MULTISLICE COMPUTED-TOMOGRAPHY; CARDIOVASCULAR-MAGNETIC-RESONANCE;
CORONARY-ARTERY-DISEASE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; TRANSTHORACIC
ECHOCARDIOGRAPHY; REGURGITATION; ACCURACY; QUANTIFICATION; STENOSIS;
SURGERY
AB Purpose: To evaluate the diagnostic performance of coronary computed tomographic (CT) angiography for the diagnosis of mitral valve prolapse (MVP).
Materials and Methods: The retrospective case-controlled multicenter study protocol was approved by the institutional review boards. The U. S. part of the study was HIPAA compliant. One hundred twelve patients who underwent electrocardiographically gated 64-section coronary CT angiography (n = 60) or dual-source coronary CT angiography (n = 52) and transthoracic echocardiography (TTE) were included. Fifty-three patients with MVP were matched for age and sex with 59 patients without MVP. CT images were analyzed on three-, two-, and four-chamber (CH) views by two independent observers. MVP was defined as a greater than 2-mm displacement of leaflets below the annulus plane and was subclassified as "billowing" (bowing) or "flail leaflet" (free leaflet margin displacement). Leaflet thickness was measured and defined as thickened if it was greater than 2 mm.
Results: The diagnostic performance of CT when three- and two- CH views were combined for the diagnosis of MVP was as follows: sensitivity, 96%; specificity, 93%; positive predictive value (PPV), 93%; and negative predictive value, 96%. On four-CH views, the excursion of billowing was higher than it was on three- CH views (P<.001), and the PPV of the four-CH view for diagnosis of MVP was 89%. The correlation between CT and TTE for excursion of billowing was high (r = 0.80-0.91). In a subset of 32 patients, the agreement between CT and TTE for differentiation of billowing (n = 13) and flail leaflet (n = 2) was 100%. Leaflet thickening was more prevalent in patients with MVP than it was in those without (71% vs 20%, P<.001), and correlation with TTE was good (r = 0.81 [anterior leaflet] and 0.77 [posterior leaflet]).
Conclusion: The combined use of three- and two-CH views allows an accurate diagnosis of MVP at coronary CT angiography.
C1 [Feuchtner, Gudrun M.; Dichtl, Wolfgang] Innsbruck Med Univ, Dept Radiol 2, A-6020 Innsbruck, Austria.
[Feuchtner, Gudrun M.; Sarwar, Ammar; Blankstein, Ron; Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Alkadhi, Hatem; Karlo, Christoph; Meier, Andreas; Leschka, Sebastian; Stolzmann, Paul] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland.
[Gruenenfelder, Juerg] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland.
[Cury, Ricardo C.] Baptist Miami Cardiac & Vasc Inst, Dept Radiol, Miami, FL USA.
RP Feuchtner, GM (reprint author), Innsbruck Med Univ, Dept Radiol 2, Anichstr 35, A-6020 Innsbruck, Austria.
EM Gudrun.Feuchtner@i-med.ac.at
FU National Center of Competence in Research, Computer Aided; Image Guided
Medical Interventions of the Swiss National Science Foundation
FX From the Department of Radiology II, Innsbruck Medical University,
Anichstrasse 35, A-6020 Innsbruck, Austria ( G. M. F., W. D.);
Department of Radiology, Massachusetts General Hospital, Boston, Mass (
G. M. F., A. S., R. B., R. C. C.); Institute of Diagnostic Radiology (
H. A., C. K., A. M., S. L., P. S.) and Clinic for Cardiovascular Surgery
(J.G.), University Hospital Zurich, Zurich, Switzerland; and Department
of Radiology, Baptist ( Miami) Cardiac and Vascular Institute, Miami,
Fla ( R. C. C.). Received March 4, 2009; revision requested March 30;
final revision received June 16; accepted June 19; final version
accepted July 24. H. A. supported by the National Center of Competence
in Research, Computer Aided and Image Guided Medical Interventions of
the Swiss National Science Foundation. Address correspondence to G. M.
F. (e-mail: Gudrun.Feuchtner@i-med.ac.at).
NR 32
TC 27
Z9 28
U1 0
U2 3
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD FEB
PY 2010
VL 254
IS 2
BP 374
EP 383
DI 10.1148/radiol.2541090393
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 546QF
UT WOS:000273824600008
PM 20093510
ER
PT J
AU Rocha, JA
Blankstein, R
Shturman, LD
Bezerra, HG
Okada, DR
Rogers, IS
Ghoshhajra, B
Hoffmann, U
Feuchtner, G
Mamuya, WS
Brady, TJ
Cury, RC
AF Rocha-Filho, Jose A.
Blankstein, Ron
Shturman, Leonid D.
Bezerra, Hiram G.
Okada, David R.
Rogers, Ian S.
Ghoshhajra, Brian
Hoffmann, Udo
Feuchtner, Gudrun
Mamuya, Wilfred S.
Brady, Thomas J.
Cury, Ricardo C.
TI Incremental Value of Adenosine-induced Stress Myocardial Perfusion
Imaging with Dual-Source CT at Cardiac CT Angiography
SO RADIOLOGY
LA English
DT Article
ID TOMOGRAPHY CORONARY-ANGIOGRAPHY; 64-SLICE COMPUTED-TOMOGRAPHY;
AMERICAN-HEART-ASSOCIATION; ARTERY-DISEASE; DIAGNOSTIC-ACCURACY; PRETEST
PROBABILITY; CLINICAL CARDIOLOGY; INTERVENTION; INTERMEDIATE;
PERFORMANCE
AB Purpose: First, to assess the feasibility of a protocol involving stress-induced perfusion evaluated at computed tomography (CT) combined with cardiac CT angiography in a single examination and second, to assess the incremental value of perfusion imaging over cardiac CT angio graphy in a dual-source technique for the detection of obstructive coronary artery disease ( CAD) in a high-risk population.
Materials and Methods: Institutional review board approval and informed patient consent were obtained before patient enrollment in the study. The study was HIPAA compliant. Thirty-five patients at high risk for CAD were prospectively enrolled for evaluation of the feasibility of CT perfusion imaging. All patients underwent retrospectively electrocardiographically gated ( helical) adenosine stress CT perfusion imaging followed by prospectively electrocardiographically gated ( axial) rest myocardial CT perfusion imaging. Analysis was performed in three steps: ( a) Coronary arterial stenoses were scored for severity and reader confidence at cardiac CT angiography, (b) myocardial perfusion defects were identified and scored for severity and reversibility at CT perfusion imaging, and ( c) coronary stenosis severity was reclassified according to perfusion findings at combined cardiac CT angiography and CT perfusion imaging. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of cardiac CT angiography before and after CT perfusion analysis were calculated.
Results: With use of a reference standard of greater than 50% stenosis at invasive angiography, all parameters of diagnostic accuracy increased after CT perfusion analysis: Sensitivity increased from 83% to 91%; specificity, from 71% to 91%; PPV, from 66% to 86%; and NPV, from 87% to 93%. The area under the receiver operating characteristic curve increased significantly, from 0.77 to 0.90 (P < .005).
Conclusion: A combination protocol involving adenosine perfusion CT imaging and cardiac CT angiography in a dual-source technique is feasible, and CT perfusion adds incremental value to cardiac CT angiography in the detection of significant CAD.
C1 [Rocha-Filho, Jose A.; Blankstein, Ron; Shturman, Leonid D.; Bezerra, Hiram G.; Okada, David R.; Rogers, Ian S.; Ghoshhajra, Brian; Hoffmann, Udo; Feuchtner, Gudrun; Mamuya, Wilfred S.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Cury, RC (reprint author), Baptist Cardiac & Vasc Inst, Cardiovasc MRI & CT Program, 8900 N Kendall Dr, Miami, FL 33176 USA.
EM rcury@baptisthealth.net
FU Astellas Pharma; New York Cardiac Center; National Institutes of Health
[1T32 HL076136]
FX From the Department of Radiology, Massachusetts General Hospital,
Boston, Mass. Received June 9, 2009; revision requested July 27;
revision received August 26; accepted September 16; final version
accepted October 1. Supported in part by a grant from Astellas Pharma
and the New York Cardiac Center. R. C. C. supported by Astellas Pharma.
R. B., L. D. S., I. S. R., and B. G. supported by National Institutes of
Health grant 1T32 HL076136. Address correspondence to R. C. C.,
Cardiovascular MRI and CT Program, Baptist Cardiac and Vascular
Institute, 8900 N Kendall Dr, Miami, FL 33176 (e-mail:
rcury@baptisthealth.net).
NR 28
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Z9 148
U1 1
U2 7
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD FEB
PY 2010
VL 254
IS 2
BP 410
EP 419
DI 10.1148/radiol.09091014
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 546QF
UT WOS:000273824600012
PM 20093513
ER
PT J
AU Mohamed, MA
Lentz, MR
Lee, V
Halpern, EF
Sacktor, N
Selnes, O
Barker, PB
Pomper, MG
AF Mohamed, Mona A.
Lentz, Margaret R.
Lee, Vallent
Halpern, Elkan F.
Sacktor, Ned
Selnes, Ola
Barker, Peter B.
Pomper, Martin G.
TI Factor Analysis of Proton MR Spectroscopic Imaging Data in HIV
Infection: Metabolite-derived Factors Help Identify Infection and
Dementia
SO RADIOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE CHEMOATTRACTANT PROTEIN-1;
MAGNETIC-RESONANCE-SPECTROSCOPY; PRINCIPAL COMPONENT ANALYSIS;
CENTRAL-NERVOUS-SYSTEM; COMMON FACTOR-ANALYSIS; AIDS DEMENTIA; HUMAN
BRAIN; NEUROLOGICAL DISEASES; IMMUNE ACTIVATION
AB Purpose: To develop a relevant pathophysiologic model of human immunodeficiency virus (HIV)-associated dementia by studying regional variations in metabolite levels measured with magnetic resonance (MR) spectroscopic imaging and their relationship to immunologic measures and cognitive dysfunction.
Materials and Methods: This was a HIPAA-compliant, institutional review board-approved study involving written informed consent. Distributions of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) concentrations in 94 subjects (20 seronegative controls and 74 HIV-positive subjects; 34 of the HIV-positive subjects having HIV-associated dementia; 63 men, 31 women; mean age, 40 years) were determined with proton (hydrogen 1 [(1)H]) MR spectroscopic imaging. HIV-positive subjects underwent neuropsychological testing and blood and cerebrospinal fluid (CSF) analysis. Factor analysis was utilized to determine associations between metabolites across regions. Analysis of variance and t tests were used to isolate differences between cohorts.
Results: A "Cho factor" differentiated seronegative controls from HIV-infected cohorts, indicating elevated Cho levels across deep gray and white matter regions of HIV-positive individuals. An "NAA factor" differentiated those with dementia from those without and correlated best with psychomotor and executive function tests. A "Cr factor" indicated Cr elevations correlated with CSF monocyte chemoattractant protein-1 levels. NAA and Cr factor scores were strongly weighted to metabolite changes in white matter regions.
Conclusion: These results highlight the importance of white matter involvement in HIV-associated dementia and support the current pathogenesis model of glial cell proliferation in HIV infection, denoted by regional Cho elevations, and neuronal dysfunction and/or death, denoted by NAA decreases, associated with dementia. Factor analysis of MR spectroscopic imaging data is a useful method for determining regional metabolic variations in HIV infection and its neuropsychological correlates. (C) RSNA, 2010
C1 [Mohamed, Mona A.; Barker, Peter B.; Pomper, Martin G.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21231 USA.
[Mohamed, Mona A.; Barker, Peter B.] Johns Hopkins Med Inst, FM Kirby Ctr Funct Brain Imaging, Baltimore, MD 21231 USA.
[Sacktor, Ned; Selnes, Ola] Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21231 USA.
[Lentz, Margaret R.; Lee, Vallent; Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Neuroradiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Pomper, MG (reprint author), Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, 1550 Orleans St,492 CRB 2, Baltimore, MD 21231 USA.
EM mpomper@jhmi.edu
FU National Institutes of Health [R01 MH61438, K25 NS051129]
FX This research was supported by the National Institutes of Health [grants
R01 MH61438 and K25 NS051129].
NR 47
TC 13
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U1 0
U2 3
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD FEB
PY 2010
VL 254
IS 2
BP 577
EP 586
DI 10.1148/radiol.09081867
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 546QF
UT WOS:000273824600029
PM 20093528
ER
PT J
AU Abujudeh, H
Kaewlai, R
AF Abujudeh, Hani
Kaewlai, Rathachai
TI E-mail Alert for Important Imaging Findings Response
SO RADIOLOGY
LA English
DT Letter
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Abujudeh, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 213D, Boston, MA 02114 USA.
EM habujudeh@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD FEB
PY 2010
VL 254
IS 2
BP 635
EP 636
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 546QF
UT WOS:000273824600041
ER
PT J
AU Burns, SM
Boyd, BL
Hill, J
Hough, S
AF Burns, Shaun Michael
Boyd, Briana L.
Hill, Justin
Hough, Sigmund
TI Psychosocial Predictors of Employment Status Among Men Living With
Spinal Cord Injury
SO REHABILITATION PSYCHOLOGY
LA English
DT Article
DE employment; gender; masculinity; spinal cord injury; Web-based research
ID QUALITY-OF-LIFE; PROSTATE-CANCER; SOCIAL SUPPORT; HEALTH-STATUS;
HELP-SEEKING; WORK; DEPRESSION; RETURN; MASCULINITY; ADJUSTMENT
AB Objective: To explore the relationship between employment status and community access, perceived community discrimination, social support from significant others, depressive symptoms, and gender-related variables for 83 men living with spinal cord injury. Study Design: Correlational research. Selling: Internet-based investigation employing spinal cord injury listservs. Main Outcome Measure: Participant employment status. Results: A forced-entry hierarchical logistic regression indicated that means of injury, community access and perceived community discrimination, social support from significant others, depressive symptoms, and men's adherence to masculine norms for primacy of work, self-reliance, and emotional control significantly predicted employment status. Conclusions: Psychosocial variables such as community access, perceived discrimination. social support from significant others. depressive symptoms, and gender identity represent important and understudied predictors of employment status among men living with spinal cord injury.
C1 [Burns, Shaun Michael] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Primary Care Behav Hlth Program, W Roxbury, MA 02132 USA.
[Boyd, Briana L.] Univ Calif San Diego, San Diego, CA 92103 USA.
RP Burns, SM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Primary Care Behav Hlth Program, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM shaun.burns@va.gov
NR 61
TC 9
Z9 9
U1 4
U2 9
PU EDUCATIONAL PUBLISHING FOUNDATION
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0090-5550
J9 REHABIL PSYCHOL
JI Rehabil. Psychol.
PD FEB
PY 2010
VL 55
IS 1
BP 81
EP 90
DI 10.1037/a0018583
PG 10
WC Psychology, Clinical; Rehabilitation
SC Psychology; Rehabilitation
GA 563NJ
UT WOS:000275139000010
PM 20175638
ER
PT J
AU Lee, HJ
Elmoazzen, H
Wright, D
Biggers, J
Rueda, BR
Heo, YS
Toner, M
Toth, TL
AF Lee, Ho-Joon
Elmoazzen, Heidi
Wright, Diane
Biggers, John
Rueda, Bo R.
Heo, Yun Seok
Toner, Mehmet
Toth, Thomas L.
TI Ultra-rapid vitrification of mouse oocytes in low cryoprotectant
concentrations
SO REPRODUCTIVE BIOMEDICINE ONLINE
LA English
DT Article
DE cryopreservation; oocyte; quartz capillary; slush nitrogen; ultra-rapid;
vitrification
ID HIGHLY EFFICIENT VITRIFICATION; EMBRYONIC STEM-CELLS; ASSISTED
REPRODUCTION; AQUEOUS-SOLUTIONS; CRYOPRESERVATION; SURVIVAL;
PERSPECTIVES; BLASTOCYSTS; NITROGEN; CULTURE
AB The ideal. cryopreservation protocol would combine the benefits of slow freezing with the benefits of vitrification. This report describes a method for the ultra-rapid vitrification of oocytes using slush nitrogen in quartz capillaries. The approach minimizes the thermal mass of the vitrification vessel by using open microcapillaries made of highly conductive quartz and achieves cooling rates of 250,000 degrees C/min. The process of vitrification can be optimized by maximizing the rate at which the sample is cooled, which allows for the use of tower cryoprotectant concentrations. Mouse oocytes can be successfully vitrified using 1.5 mol/l 1,2-propanediol and 0.5 mol/l trehalose and achieve survival rates of 90.0%(36/40). Fertilization and blastocyst formation rates of vitrified-warmed and fresh oocytes were not significantly different. A total of 120 blastocysts from each of the vitrified-warmed and fresh oocytes were transferred to surrogate mothers and 23 and 27 offspring were born respectively. All offspring in both groups were healthy, grew and bred normally and gave rise to a second generation of pups. Thus, an ultra-rapid vitrification technique has been developed for mouse oocytes that uses low concentrations of cryoprotectants and slush nitrogen in quartz capillaries, which combines the benefits of slow freezing and vitrification. (C) 2009, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
C1 [Lee, Ho-Joon; Wright, Diane; Rueda, Bo R.; Toth, Thomas L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA.
[Heo, Yun Seok; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA.
[Heo, Yun Seok; Toner, Mehmet] Shriners Hosp Children, Boston, MA 02114 USA.
[Biggers, John] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
RP Lee, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA.
EM hjlee@partners.org; tltoth@partners.org
FU National Institutes of Health [R21HD061297]
FX The authors would like to thank Gloria Lee and Dr. Kaisa Selesniemi for
technical assistance, Dr. Jonathan Tilly for guidance of this project
and critical reading and Dr Isaac Schiff for his vision and personal
support. This study was partially funded by National Institutes of
Health (R21HD061297) and a special thanks are due to Susan and George
Domolky for providing additional financial support.
NR 38
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U1 1
U2 8
PU REPRODUCTIVE HEALTHCARE LTD
PI CAMBRIDGE
PA DUCK END FARM, DRY DRAYTON, CAMBRIDGE, CB3 8DB, ENGLAND
SN 1472-6483
J9 REPROD BIOMED ONLINE
JI Reprod. Biomed. Online
PD FEB
PY 2010
VL 20
IS 2
BP 201
EP 208
DI 10.1016/j.rbmo.2009.11.012
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 561EO
UT WOS:000274958800007
PM 20113958
ER
PT J
AU Chang, HL
Senaratne, TN
Zhang, LH
Szotek, PP
Stewart, E
Dombkowski, D
Preffer, F
Donahoe, PK
Teixeira, J
AF Chang, Henry L.
Senaratne, Tharanga N.
Zhang, LiHua
Szotek, Paul P.
Stewart, Ethan
Dombkowski, David
Preffer, Frederic
Donahoe, Patricia K.
Teixeira, Jose
TI Uterine Leiomyomas Exhibit Fewer Stem/Progenitor Cell Characteristics
When Compared With Corresponding Normal Myometrium
SO REPRODUCTIVE SCIENCES
LA English
DT Article
DE Uterine leiomyomas; fibroids; stem cells
ID HEMATOPOIETIC STEM-CELL; REPRODUCTIVE-TRACT FIBROBLASTS; SIDE-POPULATION
CELLS; MENSTRUAL-CYCLE; CANCER-CELLS; EXPRESSION; THY-1; IDENTIFICATION;
BCL-2; PROLIFERATION
AB Uterine leiomyomas (also known as uterine fibroids) are the most common benign tumors of female reproductive tract and are the single most common indication for hysterectomies. Despite their high prevalence, the exact pathogenesis of these benign tumors is still unknown. One possible mechanism for leiomyoma formation. is dysregulation of mesenchymal stein cell activity. Mesenchymal stein cells have been identified in both human. and murine uteri and cancer stein cells have been identified in female reproductive malignancies. We compared stem/progenitor cell characteristics in both normal myometrium and the corresponding leiomyoma of patient's undergoing hysterectomies. We found that leiomyoma cells form fewer mesenchymal stein cell colonies and exhibit less Hoechst dye-excluding side population (SP) activity, which is a function associated with progenitor cells in other tissues, than cells isolated from normal myometrium. Whereas in normal myometrium, we observed heterogeneous expression of CD90, a cell surface marker associated the with differentiation potential of uterine fibroblasts, in leiomyomas, we observed homogenous expression of CD90, suggesting leiomyoma cells are more terminally differentiated. Furthermore, we found that while leiomyoma cells could only produce CD90 expressing cells, both CD90+ and CD90- myometrial cells could reestablish their original heterogeneous CD90 profile when expanded in vitro. These results suggest that normal myometrium contains cells with stem/progenitor cell activities that are absent in leiomyomas.
C1 [Zhang, LiHua; Stewart, Ethan; Teixeira, Jose] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Chang, Henry L.; Senaratne, Tharanga N.; Szotek, Paul P.; Donahoe, Patricia K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA.
[Dombkowski, David; Preffer, Frederic] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Flow Cytometry Lab,Dept Pathol, Boston, MA 02114 USA.
RP Teixeira, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Thier 931,55 Fruit St, Boston, MA 02114 USA.
EM teixeira@helix.mgh.harvard.edu
OI Teixeira, Jose/0000-0002-6438-5064
FU NIH/MGH T32 in Cancer Biology [T32CA071345]; Harvard Stem Cell Institute
Internship Program; Harvard Stem Cell Institute [DP-0010-07-00]; NICHD
[HD052701]
FX The authors would like to thank Dr Drucilla J. Roberts for helping us
with the analysis of the immunohistochemistry and immunofluorescence and
Dr David T. MacLaughlin for critically reviewing an early version of
this manuscript. HLC and PPS were supported by NIH/MGH T32 in Cancer
Biology T32CA071345. TNS was supported by the Harvard Stem Cell
Institute Internship Program Aug-2007. PKD is supported in part from the
Harvard Stem Cell Institute DP-0010-07-00. JT is supported by a grant
from NICHD, HD052701.
NR 34
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Z9 35
U1 1
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD FEB
PY 2010
VL 17
IS 2
BP 158
EP 167
DI 10.1177/1933719109348924
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 545SL
UT WOS:000273757000007
PM 19805552
ER
PT J
AU Moorer, OW
Meterko, M
Alt-White, AC
Sullivan, JL
AF Moorer, Oyweda W.
Meterko, Mark
Alt-White, Anna C.
Sullivan, Jennifer L.
TI Adding a Nursing Information Technology Subscale to the Practice
Environment Scale of the Nursing Work Index
SO RESEARCH IN NURSING & HEALTH
LA English
DT Article
DE information systems; computers technology; methodological research;
instrument development and validation; work; job satisfaction; PES-NWI;
nursing practice environment
ID RELIABILITY; NURSES
AB In the Past decade, the use of information technology (IT) to support healthcare delivery has greatly expanded. introducing new clinical information systems and updating existing systems require continued learning and training among registered nurses (RNs) and other clinicians. Consequently, a 5-item measure was designed as a subscale to the Practice Environment Scale of the Nursing Work Index. This new subscale, the Nursing Information Technology Subscale (NITS) measures RNs' Perception of the extent to which IT in their Practice environment supports Patient care delivery. A psychometric evaluation of the NITS was conducted at 8 Veterans Affairs hospitals. The findings demonstrated that this brief subscale has acceptable reliability as well as convergent and discriminant validity. (C) 2009 Wiley Periodicals, Inc. Res Nurs Health 33:48-59, 2010
C1 [Moorer, Oyweda W.] Off Qual & Safety, Dept Vet Affairs, Washington, DC 20420 USA.
[Meterko, Mark] HSR&D Ctr Org Leadership & Management Res, VA Boston Hlth Care Syst, Methodol & Survey Unit, Boston, MA USA.
[Alt-White, Anna C.] DVA Off Nursing Serv, Res & Acad Initiat, Washington, DC USA.
[Sullivan, Jennifer L.] HSR&D Ctr Org Leadership & Management Res, VA Boston Hlth Care Syst, Boston, MA USA.
RP Moorer, OW (reprint author), Off Qual & Safety, Dept Vet Affairs, 810 Vermont Ave, Washington, DC 20420 USA.
OI Sullivan, Jennifer/0000-0003-2906-2232
NR 24
TC 5
Z9 5
U1 13
U2 26
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0160-6891
J9 RES NURS HEALTH
JI Res. Nurs. Health
PD FEB
PY 2010
VL 33
IS 1
BP 48
EP 59
DI 10.1002/nur.20360
PG 12
WC Nursing
SC Nursing
GA 544PI
UT WOS:000273670300005
PM 20014031
ER
PT J
AU Siobal, MS
Hess, DR
AF Siobal, Mark S.
Hess, Dean R.
TI Are Inhaled Vasodilators Useful in Acute Lung Injury and Acute
Respiratory Distress Syndrome?
SO RESPIRATORY CARE
LA English
DT Article
DE acute lung injury; acute respiratory distress syndrome; inhaled nitric
oxide; prostacyclin; pulmonary hypertension
ID EXPERIMENTAL PULMONARY-HYPERTENSION; MECHANICALLY VENTILATED PATIENTS;
RIGHT-VENTRICULAR FAILURE; NITRIC-OXIDE THERAPY; RECEPTOR ANTAGONIST
LU-135252; MULTICENTER CLINICAL-TRIAL; RANDOMIZED DOUBLE-BLIND;
AEROSOLIZED PROSTACYCLIN; PROSTAGLANDIN E-1; NITROGLYCERIN INHALATION
AB In patients with acute respiratory distress syndrome (ARDS), inhaled vasodilator can result in important physiologic benefits (eg, improved hypoxemia, lower pulmonary arterial pressure, and improved right-ventricular function and cardiac output) without systemic hemodynamic effects. Inhaled nitric oxide (INO) and aerosolized prostacyclins are currently the most frequently used inhaled vasodilators. Inhaled prostacyclins are as effective physiologically as INO and cost less. Randomized controlled trials of INO in the treatment of ARDS have shown short-term physiologic benefits, but no benefit in long-term outcomes. No outcome studies have been reported on the use of prostacyclin in patients with ARDS. There is no role for the routine use of inhaled vasodilators in patients with ARDS. Inhaled vasodilator as a rescue therapy for severe refractory hypoxemia in patients with ARDS may be reasonable, but is controversial.
C1 [Siobal, Mark S.] San Francisco Gen Hosp, Resp Care Serv, NH GA2, San Francisco, CA 94110 USA.
[Siobal, Mark S.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA.
[Hess, Dean R.] Harvard Univ, Sch Med, Boston, MA USA.
[Hess, Dean R.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA.
RP Siobal, MS (reprint author), San Francisco Gen Hosp, Resp Care Serv, NH GA2, 1001 Potrero Ave, San Francisco, CA 94110 USA.
EM msiobal@sfghsom.ucsf.edu
NR 132
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U1 0
U2 1
PU DAEDALUS ENTERPRISES INC
PI IRVING
PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA
SN 0020-1324
J9 RESP CARE
JI Respir. Care
PD FEB
PY 2010
VL 55
IS 2
SI SI
BP 144
EP 161
PG 18
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 561MM
UT WOS:000274981600001
PM 20105341
ER
PT J
AU Joo, MJ
Au, DH
Fitzgibbon, ML
Lee, TA
AF Joo, Min J.
Au, David H.
Fitzgibbon, Marian L.
Lee, Todd A.
TI Inhaled corticosteroids and risk of pneumonia in newly diagnosed COPD
SO RESPIRATORY MEDICINE
LA English
DT Article
DE Chronic obstructive pulmonary disease; Pneumonia; Corticosteroids; Drug
therapy; Case-control studies
ID OBSTRUCTIVE PULMONARY-DISEASE; SALMETEROL/FLUTICASONE PROPIONATE;
FLUTICASONE PROPIONATE; THERAPEUTIC TRIALS; EXACERBATIONS; METAANALYSIS;
SALMETEROL
AB Introduction: The use of inhaled corticosteroids (ICS) in COPD may be associated with an increased risk of pneumonia. Little is known of this risk in newly diagnosed COPD patients. The objective of this study was to determine if the use of ICS among newly diagnosed COPD patients is associated with an increased risk of pneumonia hospitalizations.
Methods: Using data from the Department of Veterans Affairs and Centers for Medicare and Medicaid Services, a nested case-control study was performed. We identified patients 65 years of age or older with a new diagnosis of COPD from 1998 to 2002. A total of 145,586 patients were identified. Cases were defined based on hospitalization for pneumonia and exposure was prior use of ICS. Up to 10 controls were matched for each case based on age, sex, month and year of the case. The association between ICS use and pneumonia was evaluated with conditional logistic regression controlling for age, comorbidities, medication classes associated with the risk of pneumonia, and markers of COPD severity.
Results: There were 13,995 cases of pneumonia. The cohort was predominantly mate with an average age of 75.1 (SD = 5.4) years. The rate of pneumonia was 6.4 per 100 person-years. After adjustment for covariates, patients with current use of ICS were 1.38 (95% CI, 1.31-1.45) times more likely to have a hospitalization for pneumonia than those without current use of ICS.
Conclusions: The use of ICS among patients with newly diagnosed COPD is associated with an increased risk of hospitalization for pneumonia. Published by Elsevier Ltd.
C1 [Joo, Min J.] Univ Illinois, Dept Med, Sect Pulm Crit Care & Sleep Med, Chicago, IL USA.
[Joo, Min J.; Lee, Todd A.] Hines VA Hosp, Ctr Management Complex Chron Care CMC3, Hines, IL USA.
[Joo, Min J.; Fitzgibbon, Marian L.] Jesse Brown VA Med Ctr, CMC3, Chicago, IL USA.
[Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[Lee, Todd A.] Univ Illinois, Dept Pharm, Chicago, IL USA.
RP Joo, MJ (reprint author), 840 S Wood St,M-C 719, Chicago, IL 60612 USA.
EM joo@uic.edu
FU Health Services Research & Development Service, Center for Management of
Complex Chronic Care, Center of Excellence, Hines VA Hospital
FX This research was supported in part by the Health Services Research &
Development Service, Center for Management of Complex Chronic Care,
Center of Excellence, Hines VA Hospital. The views expressed in this
manuscript reflect those of the authors and not necessarily those of the
Department of Veterans Affairs.
NR 23
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U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0954-6111
J9 RESP MED
JI Respir. Med.
PD FEB
PY 2010
VL 104
IS 2
BP 246
EP 252
DI 10.1016/j.rmed.2009.10.002
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 558QJ
UT WOS:000274759400013
PM 19879745
ER
PT J
AU Klein, RS
Morganroth, PA
Werth, VP
AF Klein, Rachel S.
Morganroth, Pamela A.
Werth, Victoria P.
TI Cutaneous Lupus and the Cutaneous Lupus Erythematosus Disease Area and
Severity Index Instrument
SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
LA English
DT Article
DE Cutaneous lupus erythematosus; Disease classification; Rowell syndrome;
CLASI; Clinical outcome instrument
ID EPIDERMOLYSIS-BULLOSA-ACQUISITA; QUALITY-OF-LIFE; SYSTEMIC-LUPUS;
CLINICAL-MANIFESTATIONS; OUTCOME INSTRUMENT; ATOPIC-DERMATITIS; REVISED
CRITERIA; ROWELLS-SYNDROME; SURFACE-AREA; INVOLVEMENT
AB This article provides an overview of cutaneous lupus erythematosus, including classification schemes, disease subtypes, and therapy. It also describes the Cutaneous Lupus Erythematosus Disease Area and Severity Index, a novel clinical outcome instrument that quantifies cutaneous activity and damage in cutaneous lupus erythematosus.
C1 [Klein, Rachel S.; Morganroth, Pamela A.; Werth, Victoria P.] Univ Penn, Dept Dermatol, Sch Med, Philadelphia, PA 19104 USA.
[Klein, Rachel S.; Morganroth, Pamela A.; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, Sch Med, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM werth@mail.med.upenn.edu
FU National Institutes of Health; NIH [K24-AR 02207, T32-AR007465-25];
Department of Veterans Affairs; Veterans Health Administration; Office
of Research and Development; Biomedical Laboratory Research and
Development
FX This material is based upon work supported by the National Institutes of
Health, including NIH grant K24-AR 02207 (Werth) and NIH training grant
T32-AR007465-25 (Klein). This work was also partially supported by a
Merit Review Grant from the Department of Veterans Affairs, Veterans
Health Administration, Office of Research and Development, Biomedical
Laboratory Research and Development.
NR 78
TC 12
Z9 13
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-857X
J9 RHEUM DIS CLIN N AM
JI Rheum. Dis. Clin. North Am.
PD FEB
PY 2010
VL 36
IS 1
BP 33
EP +
DI 10.1016/j.rdc.2009.12.001
PG 20
WC Rheumatology
SC Rheumatology
GA 576OE
UT WOS:000276153400004
PM 20202590
ER
PT J
AU Perlick, DA
Rosenheck, RA
Kaczynski, R
Swartz, MS
Canive, JM
Lieberman, JA
AF Perlick, Deborah A.
Rosenheck, Robert A.
Kaczynski, Richard
Swartz, Marvin S.
Canive, Jose M.
Lieberman, Jeffrey A.
TI Impact of antipsychotic medication on family burden in schizophrenia:
Longitudinal results of CATIE trial
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Family burden; Second-generation antipsychotics
ID BIPOLAR DISORDER; MENTAL-HEALTH; OLANZAPINE; CAREGIVERS; HALOPERIDOL;
SCALE; DRUGS
AB Background: This study evaluated the effectiveness of first- and second-generation antipsychotics in reducing family burden associated with schizophrenia.
Methods: The family caregivers of 623 SCID-diagnosed patients enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) randomly assigned to a first-generation antipsychotic (perphenazine) or one of four second-generation drugs (olanzapine, quetiapine, risperidone or ziprasidone) were interviewed about resources provided and stresses experienced at baseline and followed for 18 months. Patient symptoms, side effects and service use were assessed as well. Hierarchical regression analyses evaluated the effect of treatment assignment on four burden factors: problem behavior, resource demands and disruption, impairment in activities of daily living and patient helpfulness. Intention-to-treat analyses with all available observations classified based on initial treatment assignment, including observations after medications changed were followed by secondary analyses excluding observations after the first medication change, i.e. only considering initial medication.
Results: Despite significant reductions on the problem behavior and resource demands/disruption factors, there were no significant differences between perphenazine and any of the second-generation medications. When only initial treatment period observations were included, patients were perceived as more helpful when medicated with perphenazine as compared to risperidone. in comparisons between second-generation drugs, patients on quetiapine were perceived as more helpful than those on risperidone (p = 0.004).
Conclusion: In this 18-month randomized trial. there was no evidence of superiority of second-generation antipsychotics in relieving family burden. (C) 2009 Published by Elsevier B.V.
C1 [Perlick, Deborah A.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Perlick, Deborah A.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY 10468 USA.
[Rosenheck, Robert A.] VA Connecticut Hlth Care Syst, New England Mental Illness, Res Educ & Clin Ctr, West Haven, CT 06516 USA.
[Rosenheck, Robert A.; Kaczynski, Richard] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA.
[Rosenheck, Robert A.; Kaczynski, Richard] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Swartz, Marvin S.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27708 USA.
[Canive, Jose M.] Univ New Mexico, Dept Psychiat, VA Med Ctr, Albuquerque, NM 87108 USA.
[Canive, Jose M.] Univ New Mexico, New Mexico VA Hlth Care Syst, VA Med Ctr, Albuquerque, NM 87108 USA.
[Lieberman, Jeffrey A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
RP Perlick, DA (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
EM debbieperlick@aol.com; robert.rosenheck@yale.edu;
richard.kaczynski@yale.edu; Marvin.swartz@duke.edu; jose.canive@va.gov;
jlieberman@pi.cpmc.Columbia.edu
FU NIMH NIH HHS [N01 MH90001]
NR 27
TC 6
Z9 8
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD FEB
PY 2010
VL 116
IS 2-3
BP 118
EP 125
DI 10.1016/j.schres.2009.09.026
PG 8
WC Psychiatry
SC Psychiatry
GA 561AB
UT WOS:000274946000003
PM 19864114
ER
PT J
AU Koerner, F
AF Koerner, Frederick
TI Papilloma and papillary carcinoma
SO SEMINARS IN DIAGNOSTIC PATHOLOGY
LA English
DT Article
DE Papilloma; Papillary carcinoma; Breast; Diagnosis
ID IN-SITU; BREAST; FORM
AB Papillomas and papillary carcinomas differ in their 3 fundamental characteristics: the geometric properties of their fronds, the amount of their stroma, and the characteristics of their epithelium. Fibrosis at the edge of papillomas often entraps glands and creates the spurious impression of invasion. The proliferation of surface epithelial cells of papillomas does not give rise to unexpected diagnostic difficulties, but glandular proliferation within the stalks of papillomas often simulates the appearance of cribriform ductal carcinoma in situ. Needle biopsies of papillomas can deposit clusters of benign cells in a distribution that resembles an invasive carcinoma. Although papillomas overrun by ductal carcinoma in situ exhibit a papillary architecture, other features differentiate them from conventional papillary carcinomas. The presence of basal carcinoma cells with clear cytoplasm ("dimorphic" cells) and the formation of short stubby fronds sometimes cause pathologists to mistake papillary carcinomas for papillomas, and the bland cytologic characteristics of solid papillary carcinomas can lead to the same error. Conventional papillary carcinomas typically invade in a blunt manner. This phenomenon complicates the recognition of invasion by many papillary carcinomas and has given rise to controversy about the nature of the lesion classically known as "intracystic papillary carcinoma." (C) 2010 Elsevier Inc. All rights reserved.
C1 [Koerner, Frederick] Massachusetts Gen Hosp, Pathol Serv, James Homer Wright Lab Pathol, Boston, MA 02114 USA.
[Koerner, Frederick] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Koerner, F (reprint author), Massachusetts Gen Hosp, Pathol Serv, James Homer Wright Lab Pathol, Boston, MA 02114 USA.
EM FKOERNER@partners.org
NR 15
TC 13
Z9 14
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 0740-2570
J9 SEMIN DIAGN PATHOL
JI Semin. Diagn. Pathol.
PD FEB
PY 2010
VL 27
IS 1
BP 13
EP 30
DI 10.1053/j.semdp.2009.12.004
PG 18
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 642OX
UT WOS:000281226700004
PM 20306827
ER
PT J
AU Hoshida, Y
Toffanin, S
Lachenmayer, A
Villanueva, A
Minguez, B
Llovet, JM
AF Hoshida, Yujin
Toffanin, Sara
Lachenmayer, Anja
Villanueva, Augusto
Minguez, Beatriz
Llovet, Josep M.
TI Molecular Classification and Novel Targets in Hepatocellular Carcinoma:
Recent Advancements
SO SEMINARS IN LIVER DISEASE
LA English
DT Review
DE Hepatocellular carcinoma; molecular classification; meta-analysis;
signaling pathway
ID HEPATITIS-B-VIRUS; GENE-EXPRESSION PROFILES; TUMOR-SUPPRESSOR GENE;
METHYLATOR PHENOTYPE ASSOCIATION; PHASE-II TRIAL; MICRORNA EXPRESSION;
DNA METHYLATION; LIVER-CANCER; PROMOTER METHYLATION; THERAPEUTIC TARGETS
AB Hepatocellular carcinoma (HCC) is one of most lethal cancers worldwide. Strategic decisions for the advancement of molecular therapies in this neoplasm require a clear understanding of its molecular classification. Studies indicate aberrant activation of signaling pathways involved in cellular proliferation (e.g., epidermal growth factor and RAS/mitogen-activated protein kinase pathways), survival (e.g., Akt/mechanistic target of rapamycin pathway), differentiation (e.g., Wnt and Hedgehog pathways), and angiogenesis (e.g., vascular endothelial growth factor and platelet-derived growth factor), which is heterogeneously presented in each tumor. Integrative analysis of accumulated genomic datasets has revealed a global scheme of molecular classification of HCC tumors observed across diverse etiologic factors and geographic locations. Such a framework will allow systematic understanding of the frequently co-occurring molecular aberrations to design treatment strategy for each specific subclass of tumors. Accompanied by a growing number of clinical trials of molecular targeted drugs, diagnostic and prognostic biomarker development will be facilitated with special attention on study design and with new assay technologies specialized for archived fixed tissues. A new class of genomic information, microRNA dysregulation and epigenetic alterations, will provide insight for more precise understanding of disease mechanism and expand the opportunity of biomarker/therapeutic target discovery. These efforts will eventually enable personalized management of HCC.
C1 [Toffanin, Sara; Lachenmayer, Anja; Minguez, Beatriz; Llovet, Josep M.] Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, New York, NY 10029 USA.
[Hoshida, Yujin] Broad Inst, Canc Program, Cambridge, MA USA.
[Hoshida, Yujin] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Villanueva, Augusto; Llovet, Josep M.] IDIBAPS, Hosp Clin,CIBERehd, Liver Unit, Barcelona Clin Liver Canc Grp BCLC, Barcelona, Spain.
[Llovet, Josep M.] ICREA, Barcelona, Spain.
RP Llovet, JM (reprint author), Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, 1425 Madison Ave,11F-70,Box 1123, New York, NY 10029 USA.
EM Josep.Llovet@mssm.edu
RI Augusto, Villanueva/F-9378-2012; Minguez, Beatriz/N-4456-2014; Llovet,
Josep M /D-4340-2014
OI Augusto, Villanueva/0000-0003-3585-3727; Minguez,
Beatriz/0000-0002-7276-9666; Llovet, Josep M /0000-0003-0547-2667
FU German Research Foundation (DFG); Programa de Estancias de Movilidad
Postdoctoral en el Extranjero incluidas las ayudas MICINN/Fulbright
[EX2008-P632]; National Institute of Health-NIDDK [1R01DK076986-01];
National Institute of Health (Spain) [SAF-2007-61898]; Samuel Waxman
Cancer Research Foundation
FX Augusto Villanueva is a recipient of a Sheila Sherlock fellowship
(European Association for the Study of the Liver). Sara Toffanin is
supported by a fellowship from Istituto Nazionale dei Tumori, Milan,
Italy. Anja Lachenmayer is the recipient of a postdoctoral fellowship
grant from German Research Foundation (DFG). Beatriz Minguez is the
recipient of a grant from Programa de Estancias de Movilidad
Postdoctoral en el Extranjero incluidas las ayudas MICINN/Fulbright
(EX2008-P632). Josep M. Llovet has grants from National Institute of
Health-NIDDK 1R01DK076986-01, National Institute of Health (Spain) grant
I+D Program (SAF-2007-61898), and the Samuel Waxman Cancer Research
Foundation.
NR 185
TC 147
Z9 154
U1 1
U2 37
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0272-8087
J9 SEMIN LIVER DIS
JI Semin. Liver Dis.
PD FEB
PY 2010
VL 30
IS 1
BP 35
EP 51
DI 10.1055/s-0030-1247131
PG 17
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 557JJ
UT WOS:000274665100005
PM 20175032
ER
PT J
AU Devidas, M
London, WB
Anderson, JR
AF Devidas, Meenakshi
London, Wendy B.
Anderson, James R.
TI The Use of Central Laboratories and Remote Electronic Data Capture to
Risk-Adjust Therapy for Pediatric Acute Lymphoblastic Leukemia and
Neuroblastoma
SO SEMINARS IN ONCOLOGY
LA English
DT Review
AB The Children's Oncology Group (COG) is a National Cancer Institute (NIH)-sponsored cooperative clinical trials group with the primary mission of conducting pediatric cancer clinical trials. COG has complex risk classification systems that are used to deliver risk-stratified therapy for many pediatric cancers, including clinical trials for acute lymphoblastic leukemia (ALL) and neuroblastoma (NB). Classification of patients is based on biological, clinical, and genomic data obtained at initial diagnosis and during the initial phases of therapy. The COG Web-based remote data entry (RDE) system enables submission of data in real time from central laboratories and treating institutions. The data are then used in an automated fashion to determine the risk group and corresponding treatment assignment for individual patients enrolled in COG clinical trials. Semin Oncol 37:53-59. (C) 2010 Published by Elsevier Inc.
C1 [Devidas, Meenakshi] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Gainesville, FL 32601 USA.
[Anderson, James R.] Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE USA.
[London, Wendy B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[London, Wendy B.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA.
RP Devidas, M (reprint author), Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, 104 N Main St,Suite 600, Gainesville, FL 32601 USA.
EM mdevidas@cog.ufl.edu
FU NCI NIH HHS [U10 CA029139-22, U10 CA098543-01, U10 CA098413-05, U10
CA098543, U10 CA098413]
NR 4
TC 3
Z9 3
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 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2010
VL 37
IS 1
BP 53
EP 59
DI 10.1053/j.seminoncol.2009.12.007
PG 7
WC Oncology
SC Oncology
GA 601QW
UT WOS:000278079300009
PM 20172365
ER
PT J
AU Tsapaki, V
Rehani, M
Saini, S
AF Tsapaki, Virginia
Rehani, Madan
Saini, Sanjay
TI Radiation Safety in Abdominal Computed Tomography
SO SEMINARS IN ULTRASOUND CT AND MRI
LA English
DT Article
ID MULTIDETECTOR CT UROGRAPHY; DOSE REDUCTION; RADIOFREQUENCY ABLATION;
ACUTE APPENDICITIS; IMAGE QUALITY; CANCER-RISKS; PATIENT; EXPOSURE;
DETECTABILITY; OPTIMIZATION
C1 [Tsapaki, Virginia] Konstantopoulio Hosp, Med Phys Unit, Athens 14569, Greece.
[Rehani, Madan] IAEA, NSRW, Radiat Protect Patients Unit, RSM, A-1400 Vienna, Austria.
[Saini, Sanjay] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Tsapaki, V (reprint author), Konstantopoulio Hosp, Med Phys Unit, 1 Ifaistou St,14569 Anixi, Athens 14569, Greece.
NR 72
TC 14
Z9 16
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0887-2171
J9 SEMIN ULTRASOUND CT
JI Semin. Ultrasound CT MRI
PD FEB
PY 2010
VL 31
IS 1
BP 29
EP 38
DI 10.1053/j.sult.2009.09.004
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 584LN
UT WOS:000276753500005
PM 20102693
ER
PT J
AU Mayer, KH
O'Cleirigh, C
Skeer, M
Covahey, C
Leidolf, E
Vanderwarker, R
Safren, SA
AF Mayer, K. H.
O'Cleirigh, C.
Skeer, M.
Covahey, C.
Leidolf, E.
Vanderwarker, R.
Safren, S. A.
TI Which HIV-infected men who have sex with men in care are engaging in
risky sex and acquiring sexually transmitted infections: findings from a
Boston community health centre
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Article
ID CD4 CELL COUNTS; VIRAL LOAD; SYPHILIS INFECTION; WESTERN-EUROPE;
UNITED-STATES; DISEASES; TRANSMISSION; BEHAVIOR; MSM
AB Objectives The primary objective was to determine the prevalence of sexually transmitted infections (STI) in a cohort of HIV-infected men who have sex with men (MSM) in their primary care setting, and to identify the demographic and behavioural characteristics of those infected with STI and the correlates of sexual transmission risk behaviour.
Methods At study entry, participants (n = 398) were tested for STI and their medical charts were reviewed for STI results in the previous year. Data on demographics, substance use, sexual behaviour and HIV disease characteristics were collected through a computer-assisted self-assessment and medical record extraction. Logistic regression analyses assessed characteristics of those with recent STI and recent transmission risk behaviour.
Results The sample was predominantly white (74.6%) and college educated (51.7%). On average, participants were 41.5 years old (SD 8.4) and had been HIV infected for 8.6 years (SD 6.7); 9% of the sample had an STI, with 6.4% testing positive for syphilis, 3.1% for gonorrhoea and 0.25% for chlamydia. Age and years since HIV diagnosis were significantly associated with testing positive for an STI, as was engaging in transmission risk behaviour and using methamphetamine, ketamine and inhalants. Substance use, particularly methamphetamine use, and being more recently diagnosed with HIV were each uniquely associated with transmission risk behaviour in a multivariable model.
Conclusions These results underscore the need to develop more effective secondary prevention interventions for HIV-infected MSM, tailored to more recently diagnosed patients, particularly those who are younger and substance users.
C1 [Mayer, K. H.; O'Cleirigh, C.; Skeer, M.; Covahey, C.; Leidolf, E.; Vanderwarker, R.; Safren, S. A.] Fenway Inst, Boston, MA 02215 USA.
[Mayer, K. H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA.
[O'Cleirigh, C.; Safren, S. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Skeer, M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Mayer, KH (reprint author), Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA.
EM Kenneth_Mayer@brown.edu
FU NIMH [5R01MH068746-05]; HRSA [H97HA01293]
FX Funding This study was supported by NIMH grant 5R01MH068746-05 and HRSA
grant H97HA01293 awarded to KHM and SAS.
NR 28
TC 42
Z9 43
U1 2
U2 6
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD FEB
PY 2010
VL 86
IS 1
BP 66
EP 70
DI 10.1136/sti.2009.036608
PG 5
WC Infectious Diseases
SC Infectious Diseases
GA 555PO
UT WOS:000274525800016
PM 19720603
ER
PT J
AU Cryder, CE
London, AJ
Volpp, KG
Loewenstein, G
AF Cryder, Cynthia E.
London, Alex John
Volpp, Kevin G.
Loewenstein, George
TI Informative inducement: Study payment as a signal of risk
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE Risk; Incentives; Ethics; Participant payments; Human Participants
research; USA, informed consent
ID RESEARCH PARTICIPATION; UNDUE; ETHICS
AB In research involving human subjects, large participation payments often are deemed undesirable because they may provide 'undue inducement' for potential participants to expose themselves to risk. However, although large incentives may encourage participation, they also may signal the riskiness of a study's procedures. In three experiments, we measured people's interest in participating in potentially risky research studies, and their perception of the risk associated with those studies, as functions of participation payment amounts. All experiments took place 2007-2008 with an on-line nationwide sample or a sample from a northeastern U.S. city. We tested whether people judge studies that offer higher participation payments to be riskier, and, if so, whether this increased perception of risk increases time and effort spent learning about the risks. We found that high participation payments increased willingness to participate, but, consistent with the idea that people infer riskiness from payment amount, high payments also increased perceived risk and time spent viewing risk information. Moreover, when a link between payment amount and risk level was made explicit in Experiment 3, the relationship between high payments and perceived risk strengthened. Research guidelines usually prohibit studies from offering participation incentives that compensate for risks, yet these experiments' results indicate that potential participants naturally assume that the magnitude of risks and incentives are related. This discrepancy between research guidelines and participants' assumptions about those guidelines has implications for informed consent in human subjects research. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Cryder, Cynthia E.] Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA.
[London, Alex John; Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
[Volpp, Kevin G.] Univ Penn, Sch Med, Philadelphia VA Med Ctr, CHERP, Philadelphia, PA 19104 USA.
RP Cryder, CE (reprint author), Washington Univ, John M Olin Sch Business, CB 1133,1 Brookings Dr, St Louis, MO 63130 USA.
EM cryder@wustl.edu
OI London, Alex/0000-0002-6450-0309
NR 17
TC 30
Z9 30
U1 2
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD FEB
PY 2010
VL 70
IS 3
BP 455
EP 464
DI 10.1016/j.socscimed.2009.10.047
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 552VK
UT WOS:000274321500015
PM 19926187
ER
PT J
AU Conboy, LA
Macklin, E
Kelley, J
Kokkotou, E
Lembo, A
Kaptchuk, T
AF Conboy, Lisa Ann
Macklin, Eric
Kelley, John
Kokkotou, Efi
Lembo, Anthony
Kaptchuk, Ted
TI Which patients improve: Characteristics increasing sensitivity to a
supportive patient-practitioner relationship
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE USA; Patient-practitioner relationship; Social factors; Randomized
controlled trial; False discovery rate analysis
ID IRRITABLE-BOWEL-SYNDROME; RANDOMIZED CONTROLLED-TRIAL;
PLACEBO-CONTROLLED TRIAL; BECK ANXIETY INVENTORY; IMMUNE FUNCTION;
SOCIAL SUPPORT; STRESS; SCALE; ALOSETRON; PARTICIPATION
AB Supportive social relationships, including a positive patient-practitioner relationship, have been associated with positive health outcomes. Using the data from a randomized controlled trial (RCT) undertaken in the Boston area of the United States, this study sought to identify baseline factors predictive of patients' response to an experimentally applied supportive patient-practitioner relationship. To sort through the hundreds of potential attributes affecting the patient-practitioner relationship, we applied a false discovery rate method borrowed from the field of genomics and bioinformatics. To our knowledge such a method has not previously been applied to generate hypotheses from clinical trial data. In a previous RCT, our team investigated the effect of the patient-practitioner relationship on symptom improvement in patients with irritable Bowel syndrome (IBS). Data were collected on a sample of 289 individuals with IBS using a three-week, single blind, three arm, randomized controlled design. We found that a supportive patient-practitioner relationship significantly improved symptomatology and quality of life. A complex, multi-level measurement package was used to prospectively measure change and identify factors associated with improvement. Using a local false discovery rate procedure, we examined the association of 452 baseline subject variables with sensitivity to treatment. Out of 452 variables, only two baseline factors, reclusiveness, and previous trial experience increased sensitivity to the supportive patient-practitioner relationship. A third variable, additional opportunity during the study for subjects to discuss their illness through experiential interview, was associated with improved outcomes among subjects who did not receive the supportive patient-practitioner relationship. The few variables associated with differential benefit suggest that a patient-centered supportive patient-practitioner relationship may be beneficial for most patients. This may be especially important for reclusive individuals. Within the context of our study, additional study attention in the form of repeated experiential interviews compensated for a lack of positive patient-practitioner support. A supportive patient-practitioner relationship may also help overcome low provider expectations for subjects with previous trial experience. These results converge with the results of the parent trial, implicating the importance of the social world in healing. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Conboy, Lisa Ann; Kaptchuk, Ted] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA 02215 USA.
[Macklin, Eric] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
[Kelley, John] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Kokkotou, Efi; Lembo, Anthony] Beth Israel Hosp, Dept Gastroenterol, Boston, MA USA.
RP Conboy, LA (reprint author), Harvard Univ, Sch Med, Osher Res Ctr, 401 Pk Dr,Suite 22A, Boston, MA 02215 USA.
EM lisa_conboy@hms.harvard.edu
RI Macklin, Eric/E-2955-2013
OI Macklin, Eric/0000-0003-1618-3502
FU NCCIH NIH HHS [1R01 AT01414-01, 1R21 AT002860-01, K24 AT004095, R01
AT001414, R01 AT001414-01, R01 AT004662, R21 AT002860, 1K24 AT004095]
NR 47
TC 20
Z9 20
U1 0
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD FEB
PY 2010
VL 70
IS 3
BP 479
EP 484
DI 10.1016/j.socscimed.2009.10.024
PG 6
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 552VK
UT WOS:000274321500018
PM 19900742
ER
PT J
AU Yi-Frazier, JP
Smith, RE
Vitaliano, PP
Yi, JC
Mai, S
Hillman, M
Weinger, K
AF Yi-Frazier, Joyce P.
Smith, Ronald E.
Vitaliano, Peter P.
Yi, Jean C.
Mai, Scarlett
Hillman, Matthew
Weinger, Katie
TI A Person-Focused Analysis of Resilience Resources and Coping in Patients
with Diabetes
SO STRESS AND HEALTH
LA English
DT Article
DE diabetes; resilience; coping; HbA(1c)
ID QUALITY-OF-LIFE; GLYCEMIC CONTROL; SELF-CARE; MALTREATED CHILDREN;
METABOLIC-CONTROL; SEX-DIFFERENCES; ADJUSTMENT; STRESS; STYLES; HEALTH
AB This study investigated the resilience resources and coping profiles of patients with diabetes. A total of 145 patients with diabetes completed a questionnaire packet including two measurements of coping (COPE and Coping Styles Questionnaires) and personal resources. Glycosylated haemoglobin (HbA(1c)) was also assessed. Resilience was defined by a factor score derived from measures of self-esteem, self-efficacy, self-mastery and optimism. All of the maladaptive coping subscales were negatively associated with resilience (r's range from -0.34 to -0.56, all p values are <0.001). Of the adaptive coping subscales, only acceptance, emotional support and pragmatism were positively associated with resilience. The upper, middle and lower tertiles of the resilience factor were identified, and the coping profiles of these groups differed significantly, with low-resilience patients favouring maladaptive strategies much more than those with high- or moderate-resilience resources do. Resilience groups did not differ in HbA(1c) levels; correlation coefficients of the coping subscales with HbA(1c) were explored. This study demonstrates a link between maladaptive coping and low resilience, suggesting that resilience impacts one's ability to manage the difficult treatment and lifestyle requirements of diabetes. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Behav & Mental Hlth Res, Boston, MA 02215 USA.
[Yi-Frazier, Joyce P.] Seattle Childrens Res Inst, Dept Endocrinol Diabet, Seattle, WA USA.
[Smith, Ronald E.; Mai, Scarlett] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
[Vitaliano, Peter P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Yi, Jean C.] Fred Hutchinson Canc Res Ctr, Dept Biobehav Sci, Seattle, WA 98104 USA.
[Hillman, Matthew] Univ Washington, Dept Biol, Seattle, WA 98195 USA.
RP Weinger, K (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Behav & Mental Hlth Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM katie.weinger@joslin.harvard.edu
FU National Science Foundation; National Institute of Mental Health [R01
MH57663]; Harvard Medical School Priscilla White Fellowship; National
Institute of Diabetes and Digestive and Kidney Diseases [R01 NIDDK60115,
P30 NIDDK36836]
FX This research was supported by the National Science Foundation (National
Science Foundation Graduate Research Fellowship Grant), the National
Institute of Mental Health (R01 MH57663) and the Harvard Medical School
Priscilla White Fellowship, National Institute of Diabetes and Digestive
and Kidney Diseases (R01 NIDDK60115, P30 NIDDK36836).
NR 48
TC 21
Z9 22
U1 2
U2 10
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1532-3005
J9 STRESS HEALTH
JI Stress Health
PD FEB
PY 2010
VL 26
IS 1
BP 51
EP 60
DI 10.1002/smi.1258
PG 10
WC Psychology, Applied; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 556KR
UT WOS:000274590300007
PM 20526415
ER
PT J
AU Smith, EE
Pan, WQ
Olson, D
Reeves, MJ
Ovbiagele, B
Peterson, ED
Fonarow, GC
Schwamm, LH
AF Smith, Eric E.
Pan, Wenqin
Olson, DaiWai
Reeves, Mathew J.
Ovbiagele, Bruce
Peterson, Eric D.
Fonarow, Gregg C.
Schwamm, Lee H.
TI Frequency and Determinants of Lipid Testing in Ischemic Stroke and
Transient Ischemic Attack Findings From Get With The Guidelines-Stroke
SO STROKE
LA English
DT Article
DE cholesterol; health services research; ischemic stroke; LDL; stroke;
transient ischemic attack
ID HEALTH-CARE PROFESSIONALS; CARDIOVASCULAR RADIOLOGY; VASCULAR-DISEASE;
CHOLESTEROL; PREVENTION; ASSOCIATION; COUNCIL; PROGRAM; STATINS;
INTERVENTION
AB Background and Purpose-National guidelines recommend lipid testing for all patients with ischemic stroke and transient ischemic attack. This study examined the frequency and predictors for in-hospital low-density lipoprotein testing using data from a nationwide stroke registry.
Methods-Between 2003 and 2008, Get With The Guideline-Stroke (GWTG-Stroke) hospitals (n = 981) contributed 479 284 consecutive ischemic stroke or transient ischemic attack admissions. Logistic regression models were used to determine patient and hospital characteristics associated with lipid testing.
Results-Frequency of LDL measurement increased from 54.3% in 2003 to 81.9% in 2008 (P < 0.001), the adjusted OR for LDL measurement was 1.23 per additional calendar year (95% CI, 1.18 to 1.29; P < 0.001). The frequency of LDL measurement also increased with longer hospital program participation; the adjusted OR was 1.17 per additional year of GWTG-Stroke participation (95% CI, 1.12 to 1.23; P < 0.001). LDL measurement was lower in women, nonsmokers, those with atrial fibrillation, those with a history of stroke or transient ischemic attack, and in those with transient ischemic attack (versus ischemic stroke; all P < 0.001). LDL >= 100 mg/dL was seen in 52.1% of those tested, including in 35.5% of patients already prescribed lipid-lowering therapy before admission.
Conclusions-Rates of LDL measurement in hospitalized patients with ischemic stroke and transient ischemic attack have improved dramatically in this large quality improvement program, although disparities in testing still exist. Testing frequently revealed an LDL level that could prompt a change in clinical management. (Stroke. 2010; 41: 232-238.)
C1 [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Foothills Med Ctr, Calgary Stroke Program, Calgary, AB T2N 2T9, Canada.
[Pan, Wenqin; Olson, DaiWai; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA.
[Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
[Ovbiagele, Bruce] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA 90024 USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA.
RP Smith, EE (reprint author), Univ Calgary, Dept Clin Neurosci, Foothills Med Ctr, Calgary Stroke Program, 1403 29th St NW, Calgary, AB T2N 2T9, Canada.
EM eesmith@ucalgary.ca
RI Smith, Eric/C-5443-2012;
OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145
FU American Heart Association; American Stroke Association; Pfizer, Inc,
New York, NY; Merck-Schering Plough Partnership; National Institutes of
Health [R01 NS062028]; Heart and Stroke Foundation of Canada; Canadian
Institutes for Health Research; Michigan Stroke Paul Coverdell Registry;
BMS-Sanofi; Pfizer; National Institutes of Health
FX The GWTG is funded by the American Heart Association and the American
Stroke Association. The program is also supported in part by
unrestricted educational grants to the American Heart Association by
Pfizer, Inc, New York, NY, and the Merck-Schering Plough Partnership (
North Wales, Pa), who did not participate in the design, analysis,
manuscript preparation, or approval.; E. E. S. serves as a member of the
Get With The Guidelines (GWTG) Science Subcommittee and receives
research support from the National Institutes of Health (National
Institute of Neurological Diseases and Stroke R01 NS062028) and the
Canadian Stroke Network and salary support from the Heart and Stroke
Foundation of Canada and the Canadian Institutes for Health Research. W.
P., E. D. P., and D. O. are members of the Duke Clinical Research
Institute, which serves as the American Heart Association (AHA) GWTG
data coordinating center. M. J. R. has received salary support from the
Michigan Stroke Paul Coverdell Registry and serves as a member of the
AHA's GWTG Quality Improvement Subcommittee. E. D. P. reports research
support from BMS-Sanofi. G. C. F. chairs the AHA GWTG Steering
Committee; serves as a consultant to Pfizer, Merck, Schering Plough,
Bristol Myers Squibb, and Sanofi-Aventis; receives speaker honoraria
from Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and
Sanofi-Aventis; and receives research support from Pfizer and the
National Institutes of Health. L. H. S. serves as vice chair of the AHA
GWTG Steering Committee; serves as a consultant to the Research Triangle
Institute, CryoCath, and to the Massachusetts Department of Public
Health; and has provided expert medical opinions in malpractice lawsuits
regarding stroke treatment and prevention.
NR 21
TC 6
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2010
VL 41
IS 2
BP 232
EP 238
DI 10.1161/STROKEAHA.109.567693
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 548HR
UT WOS:000273951600008
PM 20035071
ER
PT J
AU Ziegler, PD
Glotzer, TV
Daoud, EG
Wyse, DG
Singer, DE
Ezekowitz, MD
Koehler, JL
Hilker, CE
AF Ziegler, Paul D.
Glotzer, Taya V.
Daoud, Emile G.
Wyse, D. George
Singer, Daniel E.
Ezekowitz, Michael D.
Koehler, Jodi L.
Hilker, Christopher E.
TI Incidence of Newly Detected Atrial Arrhythmias via Implantable Devices
in Patients With a History of Thromboembolic Events
SO STROKE
LA English
DT Article
DE ambulatory electrocardiography; atrial fibrillation; diagnostic methods;
stroke
ID FOLLOW-UP; FIBRILLATION; STROKE; ABLATION; DIAGNOSTICS; CATHETER;
FLUTTER
AB Background and Purpose-Evidence of atrial tachycardia/atrial fibrillation (AT/AF) is often sought in patients with ischemic stroke or transient ischemic attack. We studied patients with previous thromboembolic events (TE) who were implanted with devices capable of continuous arrhythmia monitoring to comprehensively quantify the incidence and duration of newly detected AT/AF.
Methods-This study represents a subgroup analysis of the TRENDS trial, which included patients with clinical indications for pacemakers or defibrillators and >= 1 stroke risk factors (heart failure, hypertension, age 65 or older, diabetes, or previous TE). A history of AF was not required. All implanted devices were capable of continuously monitoring the cumulative time spent in AT/AF each day. This analysis focuses primarily on the incidence and duration of newly detected AT/AF (defined as >= 5 minutes of AT/AF on any day) in patients with previous TE, no documented history of AF, and no warfarin or antiarrhythmic drug use.
Results-A total of 319 patients had a history of TE and >= 1 day of device data. Patients with a documented history of AF (n = 80), warfarin use (n = 56), or antiarrhythmic drug use (n = 20) were excluded from analysis. Of the remaining 163 patients, newly detected AT/AF was identified via the device in 45 patients (28%) over a mean follow-up of 1.1 +/- 0.7 years. AT/AF recurred infrequently, with only 12 patients experiencing AT/AF on >10% of follow-up days.
Conclusion-Newly detected episodes of AT/AF were found via continuous monitoring in 28% of patients with previous TE. Most episodes would not have been detected by standard intermittent monitoring techniques. (Stroke. 2010; 41: 256-260.)
C1 [Ziegler, Paul D.; Koehler, Jodi L.; Hilker, Christopher E.] Medtronic Inc, Minneapolis, MN USA.
[Glotzer, Taya V.] Hackensack Univ Med Ctr, Hackensack, NJ USA.
[Daoud, Emile G.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
[Wyse, D. George] Libin Cardiovasc Inst Alberta, Calgary, AB, Canada.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ezekowitz, Michael D.] Lankenau Inst Med Res, Philadelphia, PA USA.
RP Ziegler, PD (reprint author), Medtron Cardiac Rhythm Dis Management, 8200 Coral Sea St NE,Mailstop MVN 41, Mounds View, MN 55112 USA.
EM paul.david.ziegler@medtronic.com
FU Medtronic
FX This study was funded by Medtronic.
NR 16
TC 75
Z9 76
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2010
VL 41
IS 2
BP 256
EP 260
DI 10.1161/STROKEAHA.109.571455
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 548HR
UT WOS:000273951600012
PM 20044517
ER
PT J
AU Hoh, BL
Chi, YY
Lawson, MF
Mocco, J
Barker, FG
AF Hoh, Brian L.
Chi, Yueh-Yun
Lawson, Matthew F.
Mocco, J.
Barker, Fred G., II
TI Length of Stay and Total Hospital Charges of Clipping Versus Coiling for
Ruptured and Unruptured Adult Cerebral Aneurysms in the Nationwide
Inpatient Sample Database 2002 to 2006
SO STROKE
LA English
DT Article
DE aneurysm; clipping; coiling; hospital charges; length of hospitalization
ID INTRACRANIAL ANEURYSMS; UNITED-STATES; SUBARACHNOID HEMORRHAGE;
ENDOVASCULAR TREATMENT; RESOURCE USE; COST; MORTALITY
AB Background and Purpose-We have previously reported the difference in length of stay and hospital charges for patients with cerebral aneurysms treated with either clipping or coiling at our institution. We now report an analysis of the same comparison at a national level conducted using the Nationwide Inpatient Sample database.
Methods-We obtained the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project, Agency for Healthcare Quality and Research. The Nationwide Inpatient Sample is the largest all-payer inpatient care database in the US and represents approximate to 20% of all inpatient admissions to US nonfederal hospitals. Hospitalizations for clipping or coiling of ruptured and unruptured cerebral aneurysms from 2002 to 2006 were identified by cross-matching International Classification of Diseases-9 codes for diagnoses of subarachnoid hemorrhage (430) or unruptured cerebral aneurysm (437.3) with procedure codes for clipping (39.51) or coiling (39.79, 39.72, or 39.52) of cerebral aneurysms. Length of hospital stay and total hospital charges for clipping and coiling were compared using linear mixed models adjusted for the following patient and hospital-specific factors: gender, age, race/ethnicity, admission source and type, median income level in patient's postal code of residence, payer for care, comorbidities, and hospital cerebral aneurysm case volume, bed size, teaching status, rural/urban location, and geographic region.
Results-There were 9635 hospitalizations for ruptured aneurysm treatments (6019 clipping, 3616 coiling) and 9399 hospitalizations for unruptured aneurysm treatments (4700 clipping, 4699 coiling). For ruptured aneurysm patients, after adjusting for the effects of patient-specific and hospital-specific factors, clipping compared to coiling was associated with significantly longer length of stay (P < 0.0001) and significantly higher total hospital charges (P < 0.0001). For unruptured aneurysm patients, clipping compared to coiling was associated with significantly longer length of stay (P < 0.0001) and significantly higher total hospital charges (P < 0.0001). After adjusting for the effects of hospital-level and patient-level characteristics, clipping as compared to coiling was associated with an average of 1.2-times more days in hospitalization for ruptured patients and was associated with an average of 1.8-times more days in hospitalization for unruptured patients. On average, clipping resulted in $15 325 more in total charge for ruptured patients and resulted in $11 263 more in total charge for unruptured patients after considering all relevant hospital and patient characteristics.
Conclusions-The results of this nationwide analysis differed from the findings of our single institution study. Clipping compared to coiling was associated with significantly longer lengths of stay and significantly higher total hospital charges for both ruptured and unruptured aneurysm patients. (Stroke. 2010;41:337-342.)
C1 [Hoh, Brian L.; Lawson, Matthew F.; Mocco, J.] Univ Florida, Dept Neurol Surg, Gainesville, FL 32610 USA.
[Chi, Yueh-Yun] Univ Florida, Dept Epidemiol & Hlth Policy Res, Gainesville, FL 32610 USA.
[Barker, Fred G., II] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Hoh, BL (reprint author), Univ Florida, Dept Neurol Surg, POB 100265, Gainesville, FL 32610 USA.
EM brian.hoh@neurosurgery.ufl.edu
NR 15
TC 54
Z9 57
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2010
VL 41
IS 2
BP 337
EP 342
DI 10.1161/STROKEAHA.109.569269
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 548HR
UT WOS:000273951600025
PM 20044522
ER
PT J
AU Saver, JL
Liebeskind, DS
Nogueira, RG
Jahan, R
AF Saver, Jeffrey L.
Liebeskind, David S.
Nogueira, Raul G.
Jahan, Reza
TI Need to Clarify Thrombolysis In Myocardial Ischemia (TIMI) Scale Scoring
Method in the Penumbra Pivotal Stroke Trial
SO STROKE
LA English
DT Letter
ID RECANALIZATION; REPERFUSION
C1 [Saver, Jeffrey L.; Liebeskind, David S.] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Saver, Jeffrey L.; Liebeskind, David S.; Jahan, Reza] Univ Calif Los Angeles, Stroke Ctr, Ronald Reagen Med Ctr, Los Angeles, CA 90024 USA.
[Nogueira, Raul G.] Harvard Univ, Dept Radiol, Endovasc Neurosurg Intervent Neuroradiol Sect, Massachusetts Gen Hosp,Sch Med, Boston, MA 02115 USA.
[Jahan, Reza] Univ Calif Los Angeles, Div Intervent Neuroradiol, Dept Radiol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
RP Saver, JL (reprint author), Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
OI Saver, Jeffrey/0000-0001-9141-2251
FU NINDS NIH HHS [U01 NS 44364, K23 NS054084, P50 NS044378]
NR 6
TC 17
Z9 17
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2010
VL 41
IS 2
BP E115
EP E116
DI 10.1161/STROKEAHA.109.566406
PG 2
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 548HR
UT WOS:000273951600056
PM 20035075
ER
PT J
AU Sorensen, AG
Heiss, WD
AF Sorensen, A. Gregory
Heiss, Wolf-Dieter
TI Advances in Imaging 2009
SO STROKE
LA English
DT Editorial Material
DE imaging; advances
ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; ACUTE STROKE TRIAGE;
INTRAVENOUS THROMBOLYSIS; ADVANCED CT; MR; IDENTIFICATION; CONNECTIVITY;
PERFORMANCE; THERAPIES
AB Imaging remains a mainstay of stroke diagnosis and treatment. 2009 brought much that was new: increased scrutiny of the safety of imaging; evidence of improved technical capabilities of imaging; new findings based on imaging; and as a result of the above, evidence that the field has definite needs. We will briefly cover each of these in turn. (Stroke. 2010; 41: e91-e92.)
C1 [Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA.
[Sorensen, A. Gregory] Harvard Univ, Sch Med, Boston, MA USA.
[Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, Cologne, Germany.
RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 32 Fruit St, Boston, MA 02114 USA.
EM sorensen@nmr.mgh.harvard.edu
NR 34
TC 0
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2010
VL 41
IS 2
BP E91
EP E92
DI 10.1161/STROKEAHA.109.575407
PG 2
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 548HR
UT WOS:000273951600047
PM 20075337
ER
PT J
AU Surbone, A
Baider, L
Weitzman, TS
Brames, MJ
Rittenberg, CN
Johnson, J
AF Surbone, Antonella
Baider, Lea
Weitzman, Tammy S.
Brames, Mary Jacqueline
Rittenberg, Cynthia N.
Johnson, Judith
CA MASCC Psychosocial Study Grp
TI Psychosocial care for patients and their families is integral to
supportive care in cancer: MASCC position statement
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Cancer; Supportive care; Patients' psychosocial concerns;
Unmetpsychosocial needs; Psychosocial interventions
ID QUALITY-OF-LIFE; YOUNG-ADULT CANCER; BREAST-CANCER; PSYCHOLOGICAL
DISTRESS; MULTINATIONAL-ASSOCIATION; COMMUNICATION-SKILLS; HEALTH-CARE;
RISK-INDEX; LONG-TERM; SURVIVORS
AB This position paper, written on behalf of the MASCC Psychosocial Study Group, reviews the most common psychosocial concerns and needs of cancer patients during all phases of the cancer continuum, from diagnosis to death or survivorship. Developments in psychosocial care at both individual and systems levels are surveyed and summarized, along with gaps in knowledge and research and needed improvements in the dissemination and application of acquired knowledge and expertise. The roles of culture, spirituality, and religion as part of psychosocial care are reviewed, along with families' and caregivers' specific psychosocial concerns and needs, and areas of needed psychosocial interventions in supportive cancer care. Deficits in recognizing and meeting patients' psychosocial needs at the system level are examined, and international guidelines and models of psychosocial care are reviewed, including their potential applications to local contexts. The paper calls for a shift to a new paradigm of care through adoption of an integrated approach to identify and meet the psychosocial needs of cancer patients and survivors as part of supportive care worldwide.
C1 [Surbone, Antonella] NYU, Sch Med, Dept Med, New York, NY 10016 USA.
[Baider, Lea] Hadassah Univ, Med Ctr, Sharett Inst, Dept Psychooncol, Jerusalem, Israel.
[Weitzman, Tammy S.] Dana Farber Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA.
[Brames, Mary Jacqueline] Indiana Canc Pavil, Simon Canc Ctr, Indianapolis, IN USA.
[Rittenberg, Cynthia N.] Multinatl Assoc Support Care Canc, Metairie, LA USA.
[Johnson, Judith] Multinatl Assoc Support Care Canc, Minneapolis, MN USA.
RP Surbone, A (reprint author), NYU, Sch Med, Dept Med, New York, NY 10016 USA.
EM dr.surbone@libero.it
NR 96
TC 50
Z9 50
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD FEB
PY 2010
VL 18
IS 2
BP 255
EP 263
DI 10.1007/s00520-009-0693-4
PG 9
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 534OA
UT WOS:000272905800013
PM 19609571
ER
PT J
AU Sohn, DK
Turner, BG
Gee, DW
Willingham, FF
Sylla, P
Cizginer, S
Konuk, Y
Brugge, WR
Rattner, DW
AF Sohn, Dae Kyung
Turner, Brian G.
Gee, Denise W.
Willingham, Field F.
Sylla, Patricia
Cizginer, Sevdenur
Konuk, Yusuf
Brugge, William R.
Rattner, David W.
TI Reducing the unexpectedly high rate of injuries caused by NOTES
gastrotomy creation
SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
Society-for-American-Gastrointestinal-and-Endoscopic-Surgeons
CY APR 22-24, 2009
CL Phoenix, AZ
SP Soc Amer Gastrointestinal & Endoscop Surg
DE NOTES; Transgastric; Gastrotomy; Intraoperative complications
ID TRANSLUMINAL ENDOSCOPIC SURGERY; PERITONEAL-CAVITY; PORCINE MODEL;
DISTAL PANCREATECTOMY; TRANSGASTRIC ACCESS; SURVIVAL
AB Despite the wide range of natural orifice transluminal endoscopic surgery (NOTES) procedures reported to date using a transgastric endoscopic approach, complications associated with gastrotomy creation have not been described. This study was conducted to identify the incidence and types of complications related to gastrotomy creation with the needle knife puncture and balloon dilatation technique for NOTES access to the peritoneal cavity.
Between May 2007 and August 2008, transgastric procedures were performed in 76 swine at a single institution. A total of 58 gastrotomies were created using the needle knife puncture and balloon dilatation technique without laparoscopic observation and 18 gastrotomies were created under laparoscopic visualization after CO(2) insufflation through a laparoscopic port. In all cases, a needle knife with an electrosurgical current of 25-W coagulation and/or 25-W cut and a wire-guided endoscopic balloon dilated to 20 mm were used to create the gastrotomy. All complications were collected prospectively and reviewed from laboratory medical records, operative reports, and necropsy findings.
NOTES gastrotomy-related complications occurred in 10/76 (13.2%) animals. Major complications occurred in six animals (7.9%), including four splenic lacerations, a mesenteric tear, and a fatal diaphragmatic injury. Minor complications occurred in four animals (5.3%), including three abdominal wall injuries and minor gastrotomy site bleeding. When pregastrotomy laparoscopic guidance was used, only one injury occurred in 18 animals (5.5%), but 9/58 (15.5%) gastrotomies performed without laparoscopic visualization caused some type of injury. The difference in rate of injury did not achieve statistical significance. No learning curve effect could be identified.
Injuries to adjacent viscera occur more often than is reported with the traditional transgastric needle knife NOTES access technique. Gastric punctures should be made either with laparoscopic visualization or by other techniques such as the PEG approach or with noncutting devices to reduce the incidence of visceral injury associated with transgastric peritoneal entry.
C1 [Sohn, Dae Kyung; Gee, Denise W.; Sylla, Patricia; Konuk, Yusuf; Rattner, David W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Turner, Brian G.; Willingham, Field F.; Cizginer, Sevdenur; Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA 02115 USA.
[Sohn, Dae Kyung] Natl Canc Ctr, Res Inst & Hosp, Ctr Colorectal Canc, Goyang, South Korea.
RP Rattner, DW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 15 Parkman St,WACC 460, Boston, MA 02114 USA.
EM drattner@partners.org
OI Willingham, Field/0000-0002-7071-3001
NR 17
TC 17
Z9 17
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0930-2794
J9 SURG ENDOSC
JI Surg. Endosc.
PD FEB
PY 2010
VL 24
IS 2
BP 277
EP 282
DI 10.1007/s00464-009-0570-8
PG 6
WC Surgery
SC Surgery
GA 550PW
UT WOS:000274141400005
PM 19533234
ER
PT J
AU Silverdale, MA
Kobylecki, C
Hallett, PJ
Li, Q
Dunah, AW
Ravenscroft, P
Bezard, E
Brotchie, JM
AF Silverdale, Monty A.
Kobylecki, Christopher
Hallett, Penelope J.
Li, Qin
Dunah, Anthone W.
Ravenscroft, Paula
Bezard, Erwan
Brotchie, Jonathan M.
TI Synaptic Recruitment of AMPA Glutamate Receptor Subunits in
Levodopa-Induced Dyskinesia in the MPTP-Lesioned Nonhuman Primate
SO SYNAPSE
LA English
DT Article
DE macaque; MPTP; Parkinson's disease; trafficking; Western blotting;
cellular fractionation
ID DOPA-INDUCED DYSKINESIA; INDUCED MOTOR COMPLICATIONS;
PARKINSONS-DISEASE; MACAQUE MODEL; RAT MODEL; PHOSPHORYLATION; MONKEYS;
NMDA; BLOCKADE; TRAFFICKING
C1 [Silverdale, Monty A.; Kobylecki, Christopher] Salford Royal Hosp, Greater Manchester Neurosci Ctr, Salford M6 8HD, Lancs, England.
[Hallett, Penelope J.; Dunah, Anthone W.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Hallett, Penelope J.; Dunah, Anthone W.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA.
[Li, Qin] China Acad Med Sci, Inst Lab Anim Sci, Beijing, Peoples R China.
[Ravenscroft, Paula; Bezard, Erwan] Univ Victor Segalen Bordeaux 2, CNRS, Bordeaux Inst Neurosci, UMR 5227, Bordeaux, France.
[Brotchie, Jonathan M.] Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada.
RP Silverdale, MA (reprint author), Salford Royal Hosp, Greater Manchester Neurosci Ctr, Stott Lane, Salford M6 8HD, Lancs, England.
EM monty.silverdale@srft.nhs.uk
OI Hallett, Penelope/0000-0002-8858-9096; Bezard, Erwan/0000-0002-0410-4638
NR 34
TC 38
Z9 38
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD FEB
PY 2010
VL 64
IS 2
BP 177
EP 180
DI 10.1002/syn.20739
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 538PD
UT WOS:000273195500011
PM 19852073
ER
PT J
AU Saboisky, J
Eckert, D
Malhotra, A
AF Saboisky, Julian
Eckert, Danny
Malhotra, Atul
TI Stable breathing through deeper sleeping
SO THORAX
LA English
DT Editorial Material
ID SLOW-WAVE SLEEP; AROUSAL RESPONSE; AIRWAY OCCLUSION; APNEA;
PATHOGENESIS; INSTABILITY; MECHANISMS; TRAZODONE; INCREASES; PRESSURE
C1 [Malhotra, Atul] Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Malhotra, A (reprint author), Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, 75 Francis St, Boston, MA 02115 USA.
EM amalhotra1@partners.org
RI Eckert, Danny/A-6145-2012; Saboisky, Julian/P-5782-2014
OI Eckert, Danny/0000-0003-3503-2363; Saboisky, Julian/0000-0002-9450-6023
NR 28
TC 4
Z9 4
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
J9 THORAX
JI Thorax
PD FEB
PY 2010
VL 65
IS 2
BP 95
EP 96
DI 10.1136/thx.2009.127860
PG 2
WC Respiratory System
SC Respiratory System
GA 553WS
UT WOS:000274398100002
PM 20147587
ER
PT J
AU Park, H
Karajanagi, S
Wolak, K
Aanestad, J
Daheron, L
Kobler, JB
Lopez-Guerra, G
Heaton, JT
Langer, RS
Zeitels, SM
AF Park, Hyoungshin
Karajanagi, Sandeep
Wolak, Kathryn
Aanestad, Jon
Daheron, Laurence
Kobler, James B.
Lopez-Guerra, Gerardo
Heaton, James T.
Langer, Robert S.
Zeitels, Steven M.
TI Three-Dimensional Hydrogel Model Using Adipose-Derived Stem Cells for
Vocal Fold Augmentation
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID HYALURONIC-ACID; STROMAL CELLS; VASCULAR CONSTRUCTS; LENTIVIRUS VECTOR;
COLLAGEN; FIBRIN; INJECTION; BIOMATERIALS; MICE; DIFFERENTIATION
AB Adipose-derived stem cells (ASCs) may provide a clinical option for rebuilding damaged superficial lamina propria of the vocal fold. We investigated the effects of five hydrogels (hyaluronic acid [HA], collagen, fibrin, and cogels of fibrin-collagen and fibrin-HA) on the differentiation of ASCs, with the long-term goal of establishing the conditions necessary for controlling the differentiation of ASC into the functional equivalent of superficial lamina propria fibroblasts. Human ASCs were isolated and characterized by fluorescence-activated cell sorting and real-time polymerase chain reaction. According to fluorescence-activated cell sorting and gene analysis, over 90% of isolated ASCs expressed adult stem cell surface markers and expressed adult stem cell genes. Scaffold-specific gene expression and morphology were assessed by culturing the ASCs in three-dimensional hydrogels. Twofold higher amounts of total DNA were detected in fibrin and cogel cultures than in collagen and HA cultures. Elastin expression was significantly higher in cells grown in fibrin-based gels than in cells grown in other gels. Cells grown in the cogels showed elongated morphology, expressed decorin marker, and exhibited glycosaminoglycan synthesis, which indicate ASC differentiation. Our data suggest that it may be possible to control the differentiation of ASCs using scaffolds appropriate for vocal fold tissue engineering applications. In particular, cogels of HA or collagen with fibrin enhanced proliferation, differentiation, and elastin expression.
C1 [Park, Hyoungshin; Wolak, Kathryn; Aanestad, Jon; Kobler, James B.; Lopez-Guerra, Gerardo; Heaton, James T.; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Dept Surg, Boston, MA 02114 USA.
[Karajanagi, Sandeep; Langer, Robert S.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Daheron, Laurence] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Dept Surg, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA.
EM zeitels.steven@mgh.harvard.edu
OI Lopez-Guerra, Gerardo/0000-0003-0305-4680
FU Institute of Laryngology and Voice Restoration; Eugene B. Casey
Foundation
FX This research was supported in part by the Institute of Laryngology and
Voice Restoration and the Eugene B. Casey Foundation. The authors thank
William G. Austen, M. D., Division of Plastic Surgery, Massachusetts
General Hospital, for his assistance with this investigation. The
authors also thank Drs. Victoria Herrera and Yoshihiko Kumai for their
critical discussion.
NR 38
TC 25
Z9 26
U1 0
U2 9
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD FEB
PY 2010
VL 16
IS 2
BP 535
EP 543
DI 10.1089/ten.tea.2009.0029
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 552XT
UT WOS:000274329000018
PM 19728785
ER
PT J
AU Tennis, MA
Vanscoyk, M
Keith, RL
Winn, RA
AF Tennis, Meredith A.
Vanscoyk, Michelle
Keith, Robert L.
Winn, Robert A.
TI The role of prostacyclin in lung cancer
SO TRANSLATIONAL RESEARCH
LA English
DT Article
ID VASCULAR SMOOTH-MUSCLE; ACTIVATED RECEPTOR-GAMMA; CELL-LINES;
GENE-EXPRESSION; CARCINOMA-CELLS; MURINE MODEL; PROSTAGLANDIN; SYNTHASE;
ANALOGS; GROWTH
AB Prostanoids are bioactive lipids that interact with 7-membrane-spanning G-protein-coupled receptors on target cells to impart their biologic effects.(1) They include prostaglandins, prostacyclin, and thromboxane. Prostanoids are widely distributed; mediate several diverse biologic effects like platelet aggregation and smooth-muscle contraction; and are known to be involved in allergies, acquired immunity, and cancer metastasis.(2) Prostanoids have also been associated with breast and endometrial cancer promotion, and with the inhibition of melanoma. The role of prostanoids in the development of lung disease has been poorly understood. In particular, prostacyclin possesses significant anti-inflammatory and antimetastatic properties and is the main product of cyclooxygenase-2 activity in the lung. In fact, the balance of the various members of the prostanoids family, specifically the prosoglandins PGE(2) and prostacyclin (PGI(2)), seems to play an increasingly important role in the development of lung cancer. Gaining a better understanding of prostanoids and their associated pathways is critical to the future development of molecular-based and pharmaceutical treatments of lung disease. (Translational Research 2010;155:57-61)
C1 [Winn, Robert A.] Univ Colorado Denver, Hlth Sci Ctr, Dept Med, Div Pulm & Crit Care Med, Aurora, CO 80045 USA.
Denver VA Med Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO USA.
RP Winn, RA (reprint author), Univ Colorado Denver, Hlth Sci Ctr, Dept Med, Div Pulm & Crit Care Med, 12700 E 19th Ave, Aurora, CO 80045 USA.
EM robert.winn@ucdenver.edu
NR 53
TC 6
Z9 7
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1931-5244
J9 TRANSL RES
JI Transl. Res.
PD FEB
PY 2010
VL 155
IS 2
BP 57
EP 61
DI 10.1016/j.trsl.2009.06.010
PG 5
WC Medical Laboratory Technology; Medicine, General & Internal; Medicine,
Research & Experimental
SC Medical Laboratory Technology; General & Internal Medicine; Research &
Experimental Medicine
GA 593GH
UT WOS:000277440500002
PM 20129485
ER
PT J
AU Tomas, E
Habener, JF
AF Tomas, Eva
Habener, Joel F.
TI Insulin-like actions of glucagon-like peptide-1: a dual receptor
hypothesis
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID MEDIATED GLUCOSE-UPTAKE; NEUTRAL ENDOPEPTIDASE-24.11; GLP-1 RECEPTOR;
DIABETES-MELLITUS; GENE-THERAPY; RAT-HEART; LIVER; MITOCHONDRIA;
AGONIST; AMIDE
AB GLP-1 (9-36)amide is the cleavage product of GLP-1 (7-36) amide, formed by the action of diaminopeptidyl peptidase-4 (Dpp4), and is the major circulating form in plasma. Whereas GLP-1(7-36)amide stimulates glucose-dependent insulin secretion, GLP-1(9-36)amide has only weak partial insulinotropic agonist activities on the GLP-1 receptor, but suppresses hepatic glucose production, exerts antioxidant cardioprotective actions and reduces oxidative stress in vasculature tissues. These insulin-like activities suggest a role for GLP-1 (936)amide in the modulation of mitochondrial functions by mechanisms independent of the GLP-1 receptor. In this paper, we discuss the current literature suggesting that GLP-1(9-36)amide is an active peptide with important insulin-like actions. These findings have implications in nutrient assimilation, energy homeostasis, obesity, and the use of Dpp4 inhibitors for the treatment of diabetes.
C1 [Tomas, Eva; Habener, Joel F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA.
RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA.
EM jhabener@partners.org
FU Merck Company; USPHS [DK030834]
FX We thank Violeta Stanojevic for thoughtful comments on the manuscript.
Supported in part by an Investigator Initiated Studies Program grant
from Merck & Company and by USPHS DK030834 to JFH.
NR 60
TC 61
Z9 67
U1 0
U2 9
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD FEB
PY 2010
VL 21
IS 2
BP 59
EP 67
DI 10.1016/j.tem.2009.11.007
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 563TJ
UT WOS:000275156800001
PM 20018525
ER
PT J
AU Gupta, M
de Leval, L
Selig, M
Oliva, E
Nielsen, GP
AF Gupta, Mamta
de Leval, Laurence
Selig, Martin
Oliva, Esther
Nielsen, G. Petur
TI Uterine Tumors Resembling Ovarian Sex Cord Tumors: An Ultrastructural
Analysis of 13 Cases
SO ULTRASTRUCTURAL PATHOLOGY
LA English
DT Article
DE electron microscopy; immunohistochemistry; ovary; sex cord tumors;
uterus
ID ENDOMETRIAL STROMAL SARCOMA; GRANULOSA-CELL TUMORS; INHIBIN EXPRESSION;
DIFFERENTIATION; NEOPLASMS; PHENOTYPE; MARKERS; AREAS
AB Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are tumors of unclear histogenesis. The authors analyzed the ultrastructural features of 13 UTROSCT and correlated the findings with their immunohistochemical profile. Features included cells with frequent organoid, nested or cord-like arrangement (8), lumen formation (2; one of which showed surface microvilli), nuclei with irregular indentations (8), intermediate filaments (13), prominent paranuclear aggregates (5), cell junctions (9), desmosome-like junctions (2), tonofilaments (2), basal lamina (1), and cytoplasmic lipid droplets (7; prominent in 3). No dense bodies, subplasmalemmal densities or pinocytotic vesicles were seen. Ultrastructural epithelial differentiation was present in 2 tumors (positive for keratin or epithelial membrane antigen). Prominent lipid droplets correlated with sex cord markers positivity in 2 tumors. Ultrastructural features of smooth muscle differentiation were lacking and abundant paranuclear filaments did not correlate with myoid markers. UTROSCT are polyphenotypic neoplasms ultrastructurally with focal epithelial and variable sex cord-like differentiation. These findings suggest that UTROSCT may result from divergent differentiation in endometrial stromal tumors or represent a distinct group of uterine tumors with sex cord-like differentiation that are closer in histogenesis to ovarian sex cord stromal tumors. 60% diameter) was determined by peak systolic velocity (PSV) > 300 cm/s and renal aortic ratio (RAR) > 4.0. Renal function (creatinine) and blood pressure were measured at baseline and follow-up. SESs were implanted in 16 patients (22 renal arteries) during the study period. The study cohort was predominantly female (75%) with a mean age of 68 +/- 12 years. RA-ISR was treated with SESs with a mean diameter of 3.5 mm and mean length of 17.9 +/- 3.8 mm. The mean post-dilation balloon diameter was 4.8 +/- 0.6. The baseline renal artery PSV was 445 +/- 131 cm/s with a mean RAR of 5.0 +/- 1.6. Follow-up information was available in 21 renal arteries. During a median follow-up of 12 months (range: 9-15 months), 15 renal arteries (71.4%) developed recurrence of ISR by ultrasonographic criteria. Univariate analysis revealed that female sex was an independent predictor of recurrence of ISR after SES implantation (p < 0.05). In conclusion, placement of a SES for the treatment of ISR in renal arteries is associated with high initial technical success but significant restenosis on duplex ultrasonography at follow-up.
C1 [Kiernan, Thomas J.; Yan, Bryan P.; Eisenberg, Jonathan D.; Ruggiero, Nicholas J.; Gupta, Vishal; Drachman, Douglas; Schainfeld, Robert M.; Jaff, Michael R.; Rosenfield, Kenneth; Garasic, Joseph] Massachusetts Gen Hosp, Dept Intervent Cardiol & Vasc Med, Boston, MA 02114 USA.
RP Kiernan, TJ (reprint author), Massachusetts Gen Hosp, Dept Intervent Cardiol & Vasc Med, Boston, MA 02114 USA.
EM tom_kiernan@hotmail.com
RI Yan, Bryan/P-5928-2015
NR 14
TC 6
Z9 7
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
J9 VASC MED
JI Vasc. Med.
PD FEB
PY 2010
VL 15
IS 1
BP 3
EP 7
DI 10.1177/1358863X09106897
PG 5
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 545WX
UT WOS:000273768800001
PM 19793778
ER
PT J
AU Wilkie, D
Berry, D
Cain, K
Huang, HY
Mekwa, J
Lewis, F
Gallucci, B
Lin, YC
Chen, ACC
Ko, NY
AF Wilkie, Diana
Berry, Donna
Cain, Kevin
Huang, Hsiu-Ying
Mekwa, Julia
Lewis, Frances
Gallucci, Betty
Lin, Yu-Chuan
Chen, Angela Chia-Chen
Ko, Nai-Ying
TI Effects of Coaching Patients With Lung Cancer to Report Cancer Pain
SO WESTERN JOURNAL OF NURSING RESEARCH
LA English
DT Article
DE lung cancer; pain; coaching; self-monitoring; self-reporting;
patient-centered communications
ID LOW-BACK-PAIN; BREAST-CANCER; COPING STRATEGIES; MANAGEMENT;
INTERVENTION; EDUCATION; TRIAL; COMMUNICATION; QUESTIONNAIRE;
OUTPATIENTS
AB The authors have examined the effects of coaching sensory self-monitoring and reporting on pain-related variables in patients with lung cancer. Randomly assigned to coached or not-coached groups, 2 15 patients have their interactions with their providers audiotaped and complete study measures pre- and postintervention. Of the 151 patients who complete the 4-week study, those coached are more likely than those not coached to give their providers unsolicited sensory pain information and to mention it before their providers ask for it. The mean number of pain parameters discussed during the audiotaped clinic visit is statistically larger at study end for the coached group. Scores for analgesic adequacy, all pain indices except one, anxiety, depression, and catastrophizing coping are not significantly different. Although coaching increases the amount of pain data communicated to providers by patients with lung cancer, the magnitude is small and does not lead to improved adequacy of analgesics prescribed for each patient's pain level.
C1 [Wilkie, Diana] Univ Illinois, Chicago, IL USA.
[Berry, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Cain, Kevin; Lewis, Frances; Gallucci, Betty] Univ Washington, Seattle, WA 98195 USA.
[Huang, Hsiu-Ying] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Mekwa, Julia] Univ Zululand, ZA-3886 Kwa Dlangezwa, South Africa.
[Lin, Yu-Chuan] Tzu Chi Univ, Hualien, Taiwan.
[Chen, Angela Chia-Chen] Arizona State Univ, Tempe, AZ USA.
[Ko, Nai-Ying] Natl Cheng Kung Univ, Tainan 70101, Taiwan.
RP Wilkie, D (reprint author), 845 S Damen, Chicago, IL 60612 USA.
EM dwilkie@uic.edu
FU National Institutes of Health, National Cancer Institute [R29 CA62477,
2R01 CA62477, 2 R01 CA081918]; University of Washington [2-S07RR05758];
University of Washington Graduate School Research Fund [10-3647]
FX The authors disclosed receipt of the following financial support for the
research and/or authorship of this article: This research was made
possible by Grants R29 CA62477 (data collection), 2R01 CA62477 (data
analysis and publication preparation), and 2 R01 CA081918 (publication
revision) from the National Institutes of Health, National Cancer
Institute. Its contents are solely the responsibility of the authors and
do not necessarily represent the official views of the National Cancer
Institute. The sample included five participants from a pilot study
funded by the University of Washington, School of Nursing Biomedical
Research Support Grant (2-S07RR05758) and the University of Washington
Graduate School Research Fund (10-3647).
NR 55
TC 26
Z9 27
U1 2
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0193-9459
J9 WESTERN J NURS RES
JI West. J. Nurs. Res.
PD FEB
PY 2010
VL 32
IS 1
BP 23
EP 46
DI 10.1177/0193945909348009
PG 24
WC Nursing
SC Nursing
GA 553YF
UT WOS:000274402000003
PM 20164474
ER
PT J
AU Figueiredo, JL
Siegel, C
Nahrendorf, M
Weissleder, R
AF Figueiredo, Jose-Luiz
Siegel, Cory
Nahrendorf, Matthias
Weissleder, Ralph
TI Intraoperative Near-Infrared Fluorescent Cholangiography (NIRFC) in
Mouse Models of Bile Duct Injury
SO WORLD JOURNAL OF SURGERY
LA English
DT Article
ID LAPAROSCOPIC CHOLECYSTECTOMY; BILIARY RECONSTRUCTION; INDOCYANINE GREEN;
MANAGEMENT; SYSTEM; VISUALIZATION; TOMOGRAPHY; THICKNESS; SURGEONS;
LEAKS
AB Accidental injury to the common bile duct is a rare but serious complication of laparoscopic cholecystectomy. Accurate visualization of the biliary ducts may prevent injury or allow its early detection. Conventional X-ray cholangiography is often used and can mitigate the severity of injury when correctly interpreted. However, it may be useful to have an imaging method that could provide real-time extrahepatic bile duct visualization without changing the field of view from the laparoscope. The purpose of the present study was to test a new near-infrared (NIR) fluorescent agent that is rapidly excreted via the biliary route in preclinical models to evaluate intraoperative real-time near infrared fluorescent cholangiography (NIRFC).
To investigate probe function and excretion, a lipophilic near-infrared fluorescent agent with hepatobiliary excretion was injected intravenously into one group of C57/BL6 control mice and four groups of C57/BL6 mice under the following experimentally induced conditions: (1) chronic biliary obstruction, (2) acute biliary obstruction (3) bile duct perforation, and (4) choledocholithiasis, respectively. The biliary system was imaged intravitally for 1 h with near-infrared fluorescence (NIRF) with an intraoperative small animal imaging system (excitation 649 nm, emission 675 nm).
The extrahepatic ducts and extraluminal bile were clearly visible due to the robust fluorescence of the excreted fluorochrome. Twenty-five minutes after intravenous injection, the target-to-background ratio peaked at 6.40 +/- A 0.83 but signal was clearly visible for similar to 60 min. The agent facilitated rapid identification of biliary obstruction and bile duct perforation. Implanted beads simulating choledocholithiasis were promptly identifiable within the common bile duct lumen.
Near-infrared fluorescent agents with hepatobiliary excretion may be used intraoperatively to visualize extrahepatic biliary anatomy and physiology. Used in conjunction with laparoscopic imaging technologies, the use of this technique should enhance hepatobiliary surgery.
C1 [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Figueiredo, Jose-Luiz; Siegel, Cory; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA.
[Figueiredo, Jose-Luiz; Siegel, Cory; Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, CPZN 5206,185 Cambridge St, Boston, MA 02114 USA.
EM rweissleder@mgh.harvard.edu
FU NCI NIH HHS [P50 CA086355, P50 CA086355-08]; NIBIB NIH HHS [R01
EB006432-04, R01 EB006432]
NR 41
TC 25
Z9 26
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
J9 WORLD J SURG
JI World J.Surg.
PD FEB
PY 2010
VL 34
IS 2
BP 336
EP 343
DI 10.1007/s00268-009-0332-8
PG 8
WC Surgery
SC Surgery
GA 542DI
UT WOS:000273471200022
PM 20033407
ER
PT J
AU Gerton, BK
Theeler, B
Samii, A
AF Gerton, Brooke K.
Theeler, Brett
Samii, Ali
TI Backpack Treatment for Camptocormia
SO MOVEMENT DISORDERS
LA English
DT Letter
ID PARKINSONS-DISEASE; PATHOGENESIS
C1 [Gerton, Brooke K.; Samii, Ali] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ Ctr, Dept Neurol, Seattle, WA USA.
[Gerton, Brooke K.; Samii, Ali] Vet Affairs Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA USA.
[Gerton, Brooke K.; Samii, Ali] Univ Washington, Seattle, WA 98195 USA.
[Theeler, Brett] Madigan Army Med Ctr, Dept Med, Neurol Serv, Tacoma, WA 98431 USA.
RP Gerton, BK (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ Ctr, Dept Neurol, Seattle, WA USA.
EM bgerton@u.washington.edu
NR 6
TC 18
Z9 18
U1 0
U2 0
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 JAN 30
PY 2010
VL 25
IS 2
BP 247
EP 248
DI 10.1002/mds.22909
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 586TY
UT WOS:000276937600018
PM 20077473
ER
PT J
AU Lin, HZ
Liu, DP
Zhou, XH
AF Lin, Huazhen
Liu, Danping
Zhou, Xiao-Hua
TI A correlated random-effects model for normal longitudinal data with
nonignorable missingness
SO STATISTICS IN MEDICINE
LA English
DT Article
DE nonignorable missing; correlated random effects; Laplace approximation;
longitudinal data
ID DROP-OUT; INFORMATIVE DROPOUT; DATA SUBJECT; BINARY DATA; NONRESPONSE;
REGRESSION; TIME; INFERENCE; OUTCOMES; COUNT
AB The missing data problem is common in longitudinal or hierarchical structure studies. In this paper, we propose a correlated random-effects model to fit normal longitudinal or cluster data when the missingness mechanism is nonignorable. Computational challenges arise in the model fitting due to intractable numerical integrations. We obtain the estimates of the parameters based on an accurate approximation of the log likelihood, which has higher-order accuracy but with less computational burden than the existing approximation. We apply the proposed method to a real data set arising from an autism study. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Liu, Danping; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Lin, Huazhen] Sichuan Univ, Sch Math, Chengdu 610064, Sichuan, Peoples R China.
[Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA.
RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
EM azhou@u.washington.edu
RI Liu, Danping/D-2544-2013
FU National Natural Science Foundation of China [10771148]; AHRQ
[R01HS013105]; U.S. Department of Veterans Affairs, Veterans Affairs
Health Administration, HSRD [ECI-03-206]; National Science Foundation of
China [30728019]
FX Contract/grant sponsor: National Natural Science Foundation of China;
contract/grant number: 10771148; Contract/grant sponsor: AHRQ
contract/grant number: R01HS013105; Contract/grant sponsor: U.S.
Department of Veterans Affairs, Veterans Affairs Health Administration,
HSR&D, contract/grant number. ECI-03-206; Contract/grant sponsor:
National Science Foundation of China; contract/grant number: 30728019
NR 23
TC 4
Z9 4
U1 0
U2 8
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD JAN 30
PY 2010
VL 29
IS 2
BP 236
EP 247
DI 10.1002/sim.3760
PG 12
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 544OD
UT WOS:000273666600007
PM 19941316
ER
PT J
AU Pipkin, ME
Sacks, JA
Cruz-Guilloty, F
Lichtenheld, MG
Bevan, MJ
Rao, A
AF Pipkin, Matthew E.
Sacks, Jilian A.
Cruz-Guilloty, Fernando
Lichtenheld, Mathias G.
Bevan, Michael J.
Rao, Anjana
TI Interleukin-2 and Inflammation Induce Distinct Transcriptional Programs
that Promote the Differentiation of Effector Cytolytic T Cells
SO IMMUNITY
LA English
DT Article
ID HISTONE ACETYLATION; MEMORY DEVELOPMENT; CLONAL EXPANSION;
VIRAL-INFECTION; CYTOKINE GENES; CD8(+) MEMORY; CUTTING EDGE; BET;
EXPRESSION; PERFORIN
AB Interleukin(IL)-2 and inflammation regulate effector and memory cytolytic T-lymphocyte (CTL) generation during infection. We demonstrate a complex interplay between IL-2 and inflammatory signals during CTL differentiation. IL-2 stimulation induced the transcription factor eomesodermin (Eomes), upregulated perforin (Prf1) transcription, and repressed re-expression of memory CTL markers Bcl6 and IL-7R alpha. Binding of Eomes and STAT5 to Prf1 cis-regulatory regions correlated with transcriptional initiation (increased recruitment of RNA polymerase II to the Prf1 promoter). Inflammation (CpG, IL-12) enhanced expression of IL-2R alpha and the transcription factor T-bet, but countered late Eomes and perforin induction while preventing IL-7R alpha repression by IL-2. After infection of mice with lymphocytic choriomeningitis virus, IL-2R alpha-deficient effector CD8(+) T cells expressed more Bcl6 but less perforin and granzyme B, formed fewer KLRG-1(+) and T-bet-expressing CTL, and killed poorly. Thus, inflammation influences both effector and memory CTL differentiation, whereas persistent IL-2 stimulation promotes effector at the expense of memory CTL development.
C1 [Pipkin, Matthew E.; Cruz-Guilloty, Fernando; Rao, Anjana] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Pipkin, Matthew E.; Cruz-Guilloty, Fernando; Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA.
[Sacks, Jilian A.; Bevan, Michael J.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
[Sacks, Jilian A.; Bevan, Michael J.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
[Lichtenheld, Mathias G.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Dev Ctr AIDS Res,Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
RP Rao, A (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
EM arao@cbr.med.harvard.edu
FU NIH [AI44432, AI707088, AI19335]; University of Miami Developmental
Center for AIDS Research [5P30AI073961]; National Cancer Institute
[F32CA126247]; Ford Foundation Predoctoral Fellowship
FX We thank Dr. S. Reiner for generously providing the Eomes-VP16
retroviral construct. This work was funded by NIH grants AI44432 and
AI707088 A.R.) and AI19335 (to M.J.B.); University of Miami
Developmental Center for AIDS Research 5P30AI073961 (to M.G.L.); and the
National Cancer Institute F32CA126247 (to M.E.P). F.C.G. was a
predoctoral fellow of the Ryan Foundation and was supported by a Ford
Foundation Predoctoral Fellowship.
NR 50
TC 298
Z9 303
U1 2
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JAN 29
PY 2010
VL 32
IS 1
BP 79
EP 90
DI 10.1016/j.immuni.2009.11.012
PG 12
WC Immunology
SC Immunology
GA 550HW
UT WOS:000274119900013
PM 20096607
ER
PT J
AU Kalia, V
Sarkar, S
Subramaniam, S
Haining, WN
Smith, KA
Ahmed, R
AF Kalia, Vandana
Sarkar, Surojit
Subramaniam, Shruti
Haining, W. Nicholas
Smith, Kendall A.
Ahmed, Rafi
TI Prolonged Interleukin-2R alpha Expression on Virus-Specific CD8(+) T
Cells Favors Terminal-Effector Differentiation In Vivo
SO IMMUNITY
LA English
DT Article
ID IMMUNOLOGICAL MEMORY; CLONAL EXPANSION; VIRAL-INFECTION;
GENE-EXPRESSION; FLOW-CYTOMETRY; IL-2 RECEPTOR; BLIMP-1; PROLIFERATION;
LYMPHOCYTES; ACTIVATION
AB CD25, the high-affinity interleukin-2 (IL-2) receptor alpha chain, is rapidly upregulated by antigen-specific CD8(+) T cells after T cell receptor stimulation. Here, we demonstrate that during an acute viral infection, CD25 expression is quite dynamic-after initial upregulation, a subset of virus-specific T cells sustains CD25 expression longer than the rest. At this time when there is distinct heterogeneity in CD25 expression, examination of the in vivo fate of effector cells revealed that CD25(lo) cells, which are relatively less sensitive to IL-2, preferentially upregulate CD127 and CD62L and give rise to functional long-lived memory cells. In contrast, CD25(hi) cells perceiving prolonged IL-2 signals proliferate more rapidly, are prone to apoptosis, exhibit a more pronounced effector phenotype, and appear to be terminally differentiated. Consistent with this, sustained IL-2 receptor signaling during expansion drove terminal-effector differentiation. These data support the hypothesis that prolonged IL-2 signals during priming promote terminal-effector differentiation.
C1 [Kalia, Vandana; Sarkar, Surojit; Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Subramaniam, Shruti] Loma Linda Univ, Loma Linda, CA 92350 USA.
[Haining, W. Nicholas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp, Boston, MA 02115 USA.
[Smith, Kendall A.] Cornell Univ, New York, NY 14853 USA.
RP Ahmed, R (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM rahmed@emory.edu
FU NIH [AI30048]; Bill and Melinda Gates Foundation [CAVD 38645]; Elizabeth
Glaser Pediatric AIDS Foundation
FX The authors wish to acknowledge support from NIH Grant AI30048 (RA),
Bill and Melinda Gates Foundation Grant CAVD 38645 (R.A.), and Elizabeth
Glaser Pediatric AIDS Foundation Scholar awards (S.S. and V.K.). We wish
to thank B.T. Konieczny, R. Karaffa and M. Hulsey for their excellent
technical assistance.
NR 45
TC 247
Z9 248
U1 2
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JAN 29
PY 2010
VL 32
IS 1
BP 91
EP 103
DI 10.1016/j.immuni.2009.11.010
PG 13
WC Immunology
SC Immunology
GA 550HW
UT WOS:000274119900014
PM 20096608
ER
PT J
AU Fujikawa, DG
Zhao, S
Ke, XR
Shinmei, SS
Allen, SG
AF Fujikawa, Denson G.
Zhao, Shuangping
Ke, Xingrao
Shinmei, Steve S.
Allen, Suni G.
TI Mild as well as severe insults produce necrotic, not apoptotic, cells:
Evidence from 60-min seizures
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Apoptosis; Caspase-3; Excitotoxicity; Necrosis; Programmed cell death;
Status epilepticus
ID INTERNUCLEOSOMAL DNA CLEAVAGE; INDUCED STATUS EPILEPTICUS; ACID-INDUCED
SEIZURES; NEURONAL DAMAGE; KAINIC ACID; TEMPORAL EVOLUTION;
CEREBRAL-CORTEX; BRAIN-DAMAGE; RAT-BRAIN; NECROSIS
AB We tested the hypothesis that mild insults produce apoptotic, and severe insults necrotic, cells by subjecting adult Wistar rats to 60-min instead of 3-h generalized seizures. Rats' brains were evaluated 6 and 24 h later for evidence of neuronal necrosis by light and electron microscopy, the presence of TUNEL staining and active caspase-3 immunoreactivity, and for evidence of DNA laddering 24 h after seizures. Apoptotic neurons from the retrosplenial cortex of postnatal day 8 rat pups served as positive controls. Six and 24 h after seizures, 16 and 15 brain regions respectively out of 24 showed significant numbers of acidophilic neurons by hematoxylin and eosin stain. Three brain regions had significant numbers of TUNEL-positive neurons 24 h after seizures. No neurons showed active caspase-3 immunoreactivity. Acidophilic neurons were necrotic by electron-microscopic examination. Ultrastructurally, they were shrunken and electron-dense, with shrunken, pyknotic nuclei and swollen mitochondria with disrupted cristae. Nuclei did not contain the irregular chromatin clumps found after 3-h seizures. None of the six brain regions studied ultrastructurally that show DNA laddering 24 h after 3-h seizures showed DNA laddering 24 h after 60-min seizures, probably because there were too few damaged neurons, although the lack of chromatin clumping might have been a contributing factor. Following seizures, a mild as well as a severe insult produces caspase-3-negative necrotic neurons. These results do not support the hypothesis that mild insults produce apoptotic, and severe insults, necrotic, cells. Published by Elsevier Ireland Ltd.
C1 [Fujikawa, Denson G.; Zhao, Shuangping; Allen, Suni G.] VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, North Hills, CA 91343 USA.
[Fujikawa, Denson G.] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Fujikawa, Denson G.] Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Ke, Xingrao] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Shinmei, Steve S.] Univ Calif Davis, Adm Univ Extens, Davis, CA 95616 USA.
RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, Mail Code 151B4,16111 Plummer St, North Hills, CA 91343 USA.
EM dfujikaw@ucla.edu
FU Office of Research and Development, Department of Veterans Affairs
FX This study was funded by the Office of Research and Development,
Department of Veterans Affairs. Dr. Jeffrey A. Gornbein, a UCLA
biomathematician, provided expert assistance in the statistical analysis
of data.
NR 24
TC 9
Z9 11
U1 1
U2 2
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 JAN 29
PY 2010
VL 469
IS 3
BP 333
EP 337
DI 10.1016/j.neulet.2009.12.022
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 558DX
UT WOS:000274722100011
PM 20026247
ER
PT J
AU Naeger, DM
Martin, JN
Sinclair, E
Hunt, PW
Bangsberg, DR
Hecht, F
Hsue, P
McCune, JM
Deeks, SG
AF Naeger, David M.
Martin, Jeffrey N.
Sinclair, Elizabeth
Hunt, Peter W.
Bangsberg, David R.
Hecht, Frederick
Hsue, Priscilla
McCune, Joseph M.
Deeks, Steven G.
TI Cytomegalovirus-Specific T Cells Persist at Very High Levels during
Long-Term Antiretroviral Treatment of HIV Disease
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; LYMPHOCYTE SUBPOPULATIONS;
HIGH-FREQUENCIES; AIDS PATIENTS; RNA LEVELS; INFECTION; CD4(+); IMMUNE;
LOAD; IMMUNOSENESCENCE
AB Background: In healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging ("immunosenesence") in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined.
Methodology/Principal Findings: We measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller.
Conclusions/Significance: Long-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence.
C1 [Naeger, David M.; Martin, Jeffrey N.; Sinclair, Elizabeth; Hunt, Peter W.; Hecht, Frederick; Hsue, Priscilla; McCune, Joseph M.; Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA USA.
RP Naeger, DM (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM sdeeks@php.ucsf.edu
FU National Institutes of Health [AI41531, AI052745, AI069994, DPI
OD00329]; University of California San Francisco-Gladstone Institute of
Virology & Immunology Center for AIDS Research [P30 MH59037]; UCSF
Clinical and Translational Research Institute Clinical Research Center
[UL1 RR024131]; Center for AIDS Prevention Studies [P30 MH62246]; Doris
Duke Charitable Foundation; American Foundation for AIDS Research
[106710-40-RGRL]
FX Funding: This research was supported by a grants from the National
Institutes of Health (AI41531, AI052745, AI069994)), University of
California San Francisco-Gladstone Institute of Virology & Immunology
Center for AIDS Research, P30 MH59037; the UCSF Clinical and
Translational Research Institute Clinical Research Center (UL1
RR024131); the Center for AIDS Prevention Studies (P30 MH62246); The
Doris Duke Charitable Foundation and the American Foundation for AIDS
Research (106710-40-RGRL). JMM is a recipient of the Burroughs Wellcome
Fund Clinical Scientist Award in Translational Research and the NIH
Director's Pioneer Award Program, part of the NIH Roadmap for Medical
Research, through grant number DPI OD00329. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 58
TC 85
Z9 85
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 JAN 29
PY 2010
VL 5
IS 1
AR e8886
DI 10.1371/journal.pone.0008886
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 550PA
UT WOS:000274139100003
PM 20126452
ER
PT J
AU Tan, YHC
Krishnaswamy, S
Nandi, S
Kanteti, R
Vora, S
Onel, K
Hasina, R
Lo, FY
El-Hashani, E
Cervantes, G
Robinson, M
Kales, SC
Lipkowitz, S
Karrison, T
Sattler, M
Vokes, EE
Wang, YC
Salgia, R
AF Tan, Yi-Hung Carol
Krishnaswamy, Soundararajan
Nandi, Suvobroto
Kanteti, Rajani
Vora, Sapana
Onel, Kenan
Hasina, Rifat
Lo, Fang-Yi
El-Hashani, Essam
Cervantes, Gustavo
Robinson, Matthew
Kales, Stephen C.
Lipkowitz, Stanley
Karrison, Theodore
Sattler, Martin
Vokes, Everett E.
Wang, Yi-Ching
Salgia, Ravi
TI CBL Is Frequently Altered in Lung Cancers: Its Relationship to Mutations
in MET and EGFR Tyrosine Kinases
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; ACQUIRED UNIPARENTAL DISOMY; C-CBL; UBIQUITIN
LIGASE; BINDING-SITE; OF-FUNCTION; PROTEIN; DOMAIN; AMPLIFICATION;
PHOSPHORYLATION
AB Background: Non-small cell lung cancer (NSCLC) is a heterogeneous group of disorders with a number of genetic and proteomic alterations. c-CBL is an E3 ubiquitin ligase and adaptor molecule important in normal homeostasis and cancer. We determined the genetic variations of c-CBL, relationship to receptor tyrosine kinases (EGFR and MET), and functionality in NSCLC.
Methods and Findings: Using archival formalin-fixed paraffin embedded (FFPE) extracted genomic DNA, we show that c-CBL mutations occur in somatic fashion for lung cancers. c-CBL mutations were not mutually exclusive of MET or EGFR mutations; however they were independent of p53 and KRAS mutations. In normal/tumor pairwise analysis, there was significant loss of heterozygosity (LOH) for the c-CBL locus (22%, n = 8/37) and none of these samples revealed any mutation in the remaining copy of c-CBL. The c-CBL LOH also positively correlated with EGFR and MET mutations observed in the same samples. Using select c-CBL somatic mutations such as S80N/H94Y, Q249E and W802* (obtained from Caucasian, Taiwanese and African-American samples, respectively) transfected in NSCLC cell lines, there was increased cell viability and cell motility.
Conclusions: Taking the overall mutation rate of c-CBL to be a combination as somatic missense mutation and LOH, it is clear that c-CBL is highly mutated in lung cancers and may play an essential role in lung tumorigenesis and metastasis.
C1 [Tan, Yi-Hung Carol; Lo, Fang-Yi] Natl Taiwan Normal Univ, Dept Life Sci, Taipei, Taiwan.
[Krishnaswamy, Soundararajan; Nandi, Suvobroto; Kanteti, Rajani; Hasina, Rifat; El-Hashani, Essam; Cervantes, Gustavo; Robinson, Matthew; Vokes, Everett E.; Salgia, Ravi] Univ Chicago, Pritzker Sch Med, Med Ctr, Canc Res Ctr,Dept Med, Chicago, IL 60637 USA.
[Vora, Sapana; Onel, Kenan] Univ Chicago, Pritzker Sch Med, Med Ctr, Canc Res Ctr,Dept Pediat, Chicago, IL 60637 USA.
[Kales, Stephen C.; Lipkowitz, Stanley] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Karrison, Theodore] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
[Sattler, Martin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Sattler, Martin] Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Yi-Ching] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan.
RP Tan, YHC (reprint author), Natl Taiwan Normal Univ, Dept Life Sci, Taipei, Taiwan.
EM rsalgia@medicine.bsd.uchicago.edu
FU National Institutes of Health (NIH)/National Cancer Institute (NCI)
[5RO1CA125541-03, 3RO1CA125541-03S109, 5RO1CA129501-02,
3RO1CA129501-02S109, 1R21CA140003-01]; MARF; V-Foundation; National
Science Council, Taiwan [NSC96-2628-B-006-048-MY3]
FX Funding: Supported by National Institutes of Health (NIH)/National
Cancer Institute (NCI) Grants: 5RO1CA125541-03, 3RO1CA125541-03S109,
5RO1CA129501-02, 3RO1CA129501-02S109, 1R21CA140003-01, MARF,
V-Foundation, Cancer Research Foundation and American Respiratory Health
Association of America (RS) and grant NSC96-2628-B-006-048-MY3 from the
National Science Council, Taiwan. This research was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. The funding agenices had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 40
TC 50
Z9 51
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 29
PY 2010
VL 5
IS 1
AR e8972
DI 10.1371/journal.pone.0008972
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 550PA
UT WOS:000274139100020
PM 20126411
ER
PT J
AU Boilard, E
Nigrovic, PA
Larabee, K
Watts, GFM
Coblyn, JS
Weinblatt, ME
Massarotti, EM
Remold-O'Donnell, E
Farndale, RW
Ware, J
Lee, DM
AF Boilard, Eric
Nigrovic, Peter A.
Larabee, Katherine
Watts, Gerald F. M.
Coblyn, Jonathan S.
Weinblatt, Michael E.
Massarotti, Elena M.
Remold-O'Donnell, Eileen
Farndale, Richard W.
Ware, Jerry
Lee, David M.
TI Platelets Amplify Inflammation in Arthritis via Collagen-Dependent
Microparticle Production
SO SCIENCE
LA English
DT Article
ID RHEUMATOID-ARTHRITIS; GLYCOPROTEIN-VI; ACTIVATION; DISEASE; COMPLEXES;
MECHANISM; RECEPTOR; PLASMA; CHAIN
AB In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles-submicrometer vesicles elaborated by activated platelets-in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases.
C1 [Boilard, Eric; Nigrovic, Peter A.; Larabee, Katherine; Watts, Gerald F. M.; Coblyn, Jonathan S.; Weinblatt, Michael E.; Massarotti, Elena M.; Lee, David M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Nigrovic, Peter A.] Childrens Hosp Boston, Div Immunol, Boston, MA 02115 USA.
[Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Farndale, Richard W.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England.
[Ware, Jerry] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
RP Lee, DM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
EM dlee@rics.bwh.harvard.edu
FU NIH [P01 AI065858, K08AR051321, HL091269]; Arthritis Foundation; Cogan
Family Foundation; British Heart Foundation and Medical Research
Council, UK; National Heart, Lung, and Blood Institute [HL50545]
FX Financial support for this work was provided by NIH grant P01 AI065858,
an Arthritis Foundation Investigator Award, and the Cogan Family
Foundation (D. M. L.); an Arthritis Foundation Postdoctoral Fellowship
Award (E. B.); NIH grants K08AR051321 (P. A. N.) and HL091269 (E.
R.-O.); the British Heart Foundation and Medical Research Council, UK
(R. W. F.); and National Heart, Lung, and Blood Institute grant HL50545
(J. W.). D. M. L., E. B., and J. W. have filed a provisional patent
application for glycoprotein VI as a target for treatment for
inflammatory arthritis.
NR 31
TC 388
Z9 413
U1 8
U2 69
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 JAN 29
PY 2010
VL 327
IS 5965
BP 580
EP 583
DI 10.1126/science.1181928
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 549CT
UT WOS:000274020500038
PM 20110505
ER
PT J
AU Ecker, AS
Berens, P
Keliris, GA
Bethge, M
Logothetis, NK
Tolias, AS
AF Ecker, Alexander S.
Berens, Philipp
Keliris, Georgios A.
Bethge, Matthias
Logothetis, Nikos K.
Tolias, Andreas S.
TI Decorrelated Neuronal Firing in Cortical Microcircuits
SO SCIENCE
LA English
DT Article
ID PRIMARY VISUAL-CORTEX; AREA MT; NOISE CORRELATIONS; INFORMATION;
VARIABILITY; DISCHARGE; ACCURACY; MACAQUE; CONNECTIVITY; SYNAPSES
AB Correlated trial-to-trial variability in the activity of cortical neurons is thought to reflect the functional connectivity of the circuit. Many cortical areas are organized into functional columns, in which neurons are believed to be densely connected and to share common input. Numerous studies report a high degree of correlated variability between nearby cells. We developed chronically implanted multitetrode arrays offering unprecedented recording quality to reexamine this question in the primary visual cortex of awake macaques. We found that even nearby neurons with similar orientation tuning show virtually no correlated variability. Our findings suggest a refinement of current models of cortical microcircuit architecture and function: Either adjacent neurons share only a few percent of their inputs or, alternatively, their activity is actively decorrelated.
C1 [Ecker, Alexander S.; Berens, Philipp; Tolias, Andreas S.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
[Ecker, Alexander S.; Berens, Philipp; Keliris, Georgios A.; Bethge, Matthias; Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany.
[Ecker, Alexander S.; Berens, Philipp; Bethge, Matthias] Univ Tubingen, Inst Theoret Phys, D-72076 Tubingen, Germany.
[Ecker, Alexander S.; Berens, Philipp; Bethge, Matthias] Univ Tubingen, Ctr Integrat Neurosci, D-72076 Tubingen, Germany.
[Logothetis, Nikos K.] Univ Manchester, Div Imaging Sci & Biomed Engn, Manchester M1 7HL, Lancs, England.
[Tolias, Andreas S.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Tolias, Andreas S.] Rice Univ, Dept Computat & Appl Math, Houston, TX 77005 USA.
RP Tolias, AS (reprint author), Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
EM atolias@cns.bcm.edu
RI Ecker, Alexander/A-5184-2010; Berens, Philipp/A-5653-2009; Bethge,
Matthias/B-1554-2008; Keliris, Georgios A/B-6692-2008;
OI Ecker, Alexander/0000-0003-2392-5105; Keliris, Georgios
A/0000-0001-6732-1261; Berens, Philipp/0000-0002-0199-4727
FU National Eye Institute, NIH [R01 EY018847]; Max Planck Society; U.S.
Department of Defense [W81XWH-08-2-0147]; Department of Veterans
Affairs; Arnold and Mabel Beckman Foundation; German Federal Ministry of
Education and Research (BMBF) [FKZ:01GQ0601]
FX We thank M. Subramanian, A. Hoenselaar, T. J. Williford, and D. Murray
for help with experiments; R. J. Cotton for his contribution in setting
up recording equipment; and the Siapas laboratory at Caltech for
providing the recording software. We thank R. J. Cotton, P. Dayan, S.
Deneve, K. D. Harris, E. V. Lubenov, W. J. Ma, J. H. Macke, A. Renart,
J. de la Rocha, A. G. Siapas, and S. M. Smirnakis for comments on the
manuscript and discussions. This work was supported by the National Eye
Institute, NIH (R01 EY018847), the Max Planck Society, the U.S.
Department of Defense (W81XWH-08-2-0147), a VA Merit Award from the
Department of Veterans Affairs, and an Arnold and Mabel Beckman
Foundation Young Investigator Award to A. S. T., and by the German
Federal Ministry of Education and Research (BMBF) through the Bernstein
award to M. B. (FKZ:01GQ0601).
NR 31
TC 279
Z9 283
U1 1
U2 24
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 JAN 29
PY 2010
VL 327
IS 5965
BP 584
EP 587
DI 10.1126/science.1179867
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 549CT
UT WOS:000274020500039
PM 20110506
ER
PT J
AU Kirsch, DG
Santiago, PM
di Tomaso, E
Sullivan, JM
Hou, WS
Dayton, T
Jeffords, LB
Sodha, P
Mercer, KL
Cohen, R
Takeuchi, O
Korsmeyer, SJ
Bronson, RT
Kim, CF
Haigis, KM
Jain, RK
Jacks, T
AF Kirsch, David G.
Santiago, Philip M.
di Tomaso, Emmanuelle
Sullivan, Julie M.
Hou, Wu-Shiun
Dayton, Talya
Jeffords, Laura B.
Sodha, Pooja
Mercer, Kim L.
Cohen, Rhianna
Takeuchi, Osamu
Korsmeyer, Stanley J.
Bronson, Roderick T.
Kim, Carla F.
Haigis, Kevin M.
Jain, Rakesh K.
Jacks, Tyler
TI p53 Controls Radiation-Induced Gastrointestinal Syndrome in Mice
Independent of Apoptosis
SO SCIENCE
LA English
DT Article
ID BONE-MARROW; CELL-DEATH; ENDOTHELIAL APOPTOSIS; GAMMA-IRRADIATION;
DNA-DAMAGE; IN-VIVO; RADIOSENSITIVITY; PUMA; PROLIFERATION; RADIOTHERAPY
AB Acute exposure to ionizing radiation can cause lethal damage to the gastrointestinal (GI) tract, a condition called the GI syndrome. Whether the target cells affected by radiation to cause the GI syndrome are derived from the epithelium or endothelium and whether the target cells die by apoptosis or other mechanisms are controversial issues. Studying mouse models, we found that selective deletion of the proapoptotic genes Bak1 and Bax from the GI epithelium or from endothelial cells did not protect mice from developing the GI syndrome after sub-total-body gamma irradiation. In contrast, selective deletion of p53 from the GI epithelium, but not from endothelial cells, sensitized irradiated mice to the GI syndrome. Transgenic mice overexpressing p53 in all tissues were protected from the GI syndrome after irradiation. These results suggest that the GI syndrome is caused by the death of GI epithelial cells and that these epithelial cells die by a mechanism that is regulated by p53 but independent of apoptosis.
C1 [Kirsch, David G.; Santiago, Philip M.; Hou, Wu-Shiun; Dayton, Talya; Sodha, Pooja; Mercer, Kim L.; Cohen, Rhianna; Kim, Carla F.; Haigis, Kevin M.; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Kirsch, David G.; di Tomaso, Emmanuelle; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Kirsch, David G.; di Tomaso, Emmanuelle; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Kirsch, David G.; Sullivan, Julie M.; Jeffords, Laura B.] Duke Univ, Med Ctr, Dept Radiat Oncol & Pharmacol, Durham, NC 27708 USA.
[Kirsch, David G.; Sullivan, Julie M.; Jeffords, Laura B.] Duke Univ, Med Ctr, Dept Canc Biol, Durham, NC 27708 USA.
[Takeuchi, Osamu; Korsmeyer, Stanley J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bronson, Roderick T.] Tufts Univ, Sch Med & Vet Med, North Grafton, MA 01536 USA.
[Jacks, Tyler] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Jacks, T (reprint author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM tjacks@mit.edu
RI Takeuchi, Osamu/D-6007-2011
FU Howard Hughes Medical Institute; National Cancer Institute [P30-CA14051,
KO8 CA 114176, P01 CA80124]; Dana Farber Cancer Center for Medical
Countermeasures Against Radiation [U19-AI06775]; National Institute of
Allergy and Infectious Diseases [RC1-AI078521]; American Society of
Clinical Oncology
FX We thank M. Serrano for the super-p53 mice; A. Berns for the
p53FL mice; P. Crawford and J. Gordon for advice; E. Travis
for providing a model jig; J. Down, C. Pope, and K. Doppke for
performing dosimetry measurements; and K. Held for critically reading
the manuscript. This work is funded by the Howard Hughes Medical
Institute (T. J.), partially funded by Cancer Center Support (core)
grant P30-CA14051 from the National Cancer Institute (NCI) (T. J.), NCI
grant KO8 CA 114176 (D. G. K.), the pilot project from the Dana Farber
Cancer Center for Medical Countermeasures Against Radiation U19-AI06775
(D. G. K.), grant RC1-AI078521 from the National Institute of Allergy
and Infectious Diseases (D. G. K.), an American Society of Clinical
Oncology Young Investigator Award (D. G. K.), and NCI grant P01 CA80124
(R. K. J.). T. J. is the David H. Koch Professor of Biology and a Daniel
K. Ludwig Scholar.
NR 33
TC 98
Z9 104
U1 1
U2 13
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 JAN 29
PY 2010
VL 327
IS 5965
BP 593
EP 596
DI 10.1126/science.1166202
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 549CT
UT WOS:000274020500042
PM 20019247
ER
PT J
AU Chauhan, D
Singh, AV
Ciccarelli, B
Richardson, PG
Palladino, MA
Anderson, KC
AF Chauhan, Dharminder
Singh, Ajita V.
Ciccarelli, Bryan
Richardson, Paul G.
Palladino, Michael A.
Anderson, Kenneth C.
TI Combination of novel proteasome inhibitor NPI-0052 and lenalidomide
trigger in vitro and in vivo synergistic cytotoxicity in multiple
myeloma
SO BLOOD
LA English
DT Article
ID MARROW STROMAL CELLS; BONE-MARROW; THERAPEUTIC APPLICATIONS; THALIDOMIDE
ANALOGS; DRUG-RESISTANCE; BORTEZOMIB; APOPTOSIS; SURVIVAL; ACTIVATION;
CASPASE-12
AB Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 is distinct from bortezomib (Velcade) and, importantly, triggers apoptosis in multiple myeloma (MM) cells resistant to bortezomib. Here we demonstrate that combining NPI-0052 and lenalidomide (Revlimid) induces synergistic anti-MM activity in vitro using MM-cell lines or patient MM cells. NPI-0052 plus lenalidomide-induced apoptosis is associated with (1) activation of caspase-8, caspase-9, caspase-12, caspase-3, and poly(ADP) ribose polymerase; (2) activation of BH-3 protein BIM; (3) translocation of BIM to endoplasmic reticulum; (4) inhibition of migration of MM cells and angiogenesis; and (5) suppression of chymotrypsin-like, caspase-like, and trypsin-like proteasome activities. Importantly, blockade of BIM using siRNA significantly abrogates NPI-0052 plus lenalidomide-induced apoptosis. Furthermore, studies using biochemical inhibitors of caspase-8 versus caspase-9 demonstrate that NPI-0052 plus lenalidomide-triggered apoptosis is primarily dependent on caspase-8 signaling. In animal tumor model studies, low-dose combination of NPI-0052 and lenalidomide is well tolerated, significantly inhibits tumor growth, and prolongs survival. Taken together, our study provides the preclinical rationale for clinical protocols evaluating lenalidomide together with NPI-0052 to improve patient outcome in MM. (Blood. 2010;115:834-845)
C1 [Chauhan, Dharminder; Singh, Ajita V.; Ciccarelli, Bryan; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
[Chauhan, Dharminder; Singh, Ajita V.; Ciccarelli, Bryan; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA.
[Palladino, Michael A.] Nereus Pharmaceut, San Diego, CA USA.
RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,LeBow Inst Myeloma Therapeut, Mayer Bldg Rm 561,44 Binney St, Boston, MA 02115 USA.
EM Dharminder_Chauhan@dfci.harvard.edu; Kenneth_Anderson@dfci.harvard.edu
FU National Institutes of Health [SPORE-P50100707, PO1-CA078378,
RO1CA050947]
FX This work was supported by the National Institutes of Health (grants
SPORE-P50100707, PO1-CA078378, and RO1CA050947).
NR 46
TC 66
Z9 68
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JAN 28
PY 2010
VL 115
IS 4
BP 834
EP 845
DI 10.1182/blood-2009-03-213009
PG 12
WC Hematology
SC Hematology
GA 549XA
UT WOS:000274086600015
PM 19965674
ER
PT J
AU Andrews, S
Burgess, SJ
Skaalrud, D
Kelly, JX
Peyton, DH
AF Andrews, Simeon
Burgess, Steven J.
Skaalrud, Deborah
Kelly, Jane Xu
Peyton, David H.
TI Reversal Agent and Linker Variants of Reversed Chloroquines: Activities
against Plasmodium falciparum
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID BETA-HEMATIN INHIBITION; DRUG-RESISTANCE; MALARIA; ANTIMALARIAL;
COMBINATIONS; TRANSPORTER
AB We have shown that "reversed chloroquine molecules" constructed from chloroquine-like and resistance "reversal-agent"-like cores can be powerful drugs against malaria (J. Med. Chem. 2006, 49, 5623-5625). Several reversed chloroquines are now presented that probe parameters governing the activities against chloroquine-resistant and chloroquine-sensitive malaria strains. The design is tolerant to linker and reversal agent changes, but it piperazinyl group adjacent to the quinoline, at least for the group Of Compounds studied here, may be detrimental.
C1 [Andrews, Simeon; Burgess, Steven J.; Skaalrud, Deborah; Kelly, Jane Xu; Peyton, David H.] Portland State Univ, Dept Chem, Portland, OR 97207 USA.
[Burgess, Steven J.; Kelly, Jane Xu] DesignMedix Inc, Portland, OR 97201 USA.
[Kelly, Jane Xu] Portland VA Med Ctr, Portland, OR 97239 USA.
RP Peyton, DH (reprint author), Portland State Univ, Dept Chem, POB 751, Portland, OR 97207 USA.
EM peytond@pdx.edu
FU Medical Research Foundation of Oregon [0530]; National Institutes of
Health [AI067837, AI072923]; Murdock Charitable Trust
FX The authors thank the following for supporting this research: the
Medical Research Foundation of Oregon (Grant 0530), the National
Institutes of Health (Grants AI067837 and AI072923) to DHP, and a grant
from the Murdock Charitable Trust for the NMR instruments.
NR 19
TC 54
Z9 54
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JAN 28
PY 2010
VL 53
IS 2
BP 916
EP 919
DI 10.1021/jm900972u
PG 4
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 544PX
UT WOS:000273672100037
PM 20088608
ER
PT J
AU Mayack, SR
Shadrach, JL
Kim, FS
Wagers, AJ
AF Mayack, Shane R.
Shadrach, Jennifer L.
Kim, Francis S.
Wagers, Amy J.
TI Systemic signals regulate ageing and rejuvenation of blood stem cell
niches (Retracted article. See vol. 467, pg. 872, 2010)
SO NATURE
LA English
DT Article; Retracted Publication
ID HEMATOPOIETIC-STEM; IGF-I; PROGENITOR CELLS; SKELETAL-MUSCLE; GROWTH;
OSTEOBLASTS; PATHWAYS; BONE; IDENTIFICATION; REGENERATION
AB Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it is unclear to what extent they reflect stem cell intrinsic alterations or age-related changes in the stem cell supportive microenvironment, or niche. Here, using complementary in vivo and in vitro heterochronic models, we show that age-associated changes in stem cell supportive niche cells deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Furthermore, we find that age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment. Together, these results show a new and critical role for local and systemic factors in signalling age-related haematopoietic decline, and highlight a new model in which blood-borne factors in aged animals act through local niche cells to induce age-dependent disruption of stem cell function.
C1 [Mayack, Shane R.; Shadrach, Jennifer L.; Kim, Francis S.; Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst,Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Wagers, AJ (reprint author), Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst,Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA.
EM amy.wagers@joslin.harvard.edu
FU Burroughs-Welcome Fund; WM Keck Foundation; Glenn Foundation; National
Institutes of Health (NIH) [1 DP2 OD004345-01, T32DK07260-29]; Iacocca
Foundation; Joslin Diabetes Center DERC [P30DK036836]
FX This work was supported in part by funding from the Burroughs-Welcome
Fund, WM Keck Foundation, Glenn Foundation, and National Institutes of
Health (NIH) 1 DP2 OD004345-01 (to A. J. W.), by fellowships from the
NIH (T32DK07260-29) and the Iacocca Foundation (to S. R. M.), and by the
Joslin Diabetes Center DERC (P30DK036836). We thank J. LaVecchio and G.
Buruzula for expert cell sorting, C. J. Luckey for anti-IGF-1 antibody,
and L. Zon, R. Lee, D. Rossi, L. P. Kane, S. Lowe and C. Dall'Osso for
helpful advice and critical reading of the manuscript. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIH.
NR 37
TC 80
Z9 87
U1 0
U2 0
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 JAN 28
PY 2010
VL 463
IS 7280
BP 495
EP U109
DI 10.1038/nature08749
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100041
PM 20110993
ER
PT J
AU Zhang, JM
Adrian, FJ
Jahnke, W
Cowan-Jacob, SW
Li, AG
Iacob, RE
Sim, T
Powers, J
Dierks, C
Sun, FX
Guo, GR
Ding, Q
Okram, B
Choi, Y
Wojciechowski, A
Deng, XM
Liu, GX
Fendrich, G
Strauss, A
Vajpai, N
Grzesiek, S
Tuntland, T
Liu, Y
Bursulaya, B
Azam, M
Manley, PW
Engen, JR
Daley, GQ
Warmuth, M
Gray, NS
AF Zhang, Jianming
Adrian, Francisco J.
Jahnke, Wolfgang
Cowan-Jacob, Sandra W.
Li, Allen G.
Iacob, Roxana E.
Sim, Taebo
Powers, John
Dierks, Christine
Sun, Fangxian
Guo, Gui-Rong
Ding, Qiang
Okram, Barun
Choi, Yongmun
Wojciechowski, Amy
Deng, Xianming
Liu, Guoxun
Fendrich, Gabriele
Strauss, Andre
Vajpai, Navratna
Grzesiek, Stephan
Tuntland, Tove
Liu, Yi
Bursulaya, Badry
Azam, Mohammad
Manley, Paul W.
Engen, John R.
Daley, George Q.
Warmuth, Markus
Gray, Nathanael S.
TI Targeting Bcr-Abl by combining allosteric with ATP-binding-site
inhibitors
SO NATURE
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; CELL LUNG-CANCER; KINASE-INHIBITOR; C-ABL;
TYROSINE KINASE; LYMPHOBLASTIC-LEUKEMIA; IMATINIB RESISTANCE; SELECTIVE
INHIBITOR; MUTATIONS; DYNAMICS
AB In an effort to find new pharmacological modalities to overcome resistance to ATP-binding-site inhibitors of Bcr-Abl, we recently reported the discovery of GNF-2, a selective allosteric Bcr-Abl inhibitor. Here, using solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry, we show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, when used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr-Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model. These results show that therapeutically relevant inhibition of Bcr-Abl activity can be achieved with inhibitors that bind to the myristate-binding site and that combining allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.
C1 [Adrian, Francisco J.; Li, Allen G.; Dierks, Christine; Sun, Fangxian; Guo, Gui-Rong; Ding, Qiang; Liu, Guoxun; Tuntland, Tove; Liu, Yi; Bursulaya, Badry] Novartis Res Fdn, Dept Chem, Genom Inst, San Diego, CA 92121 USA.
[Zhang, Jianming; Sim, Taebo; Choi, Yongmun; Wojciechowski, Amy; Deng, Xianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Zhang, Jianming; Sim, Taebo; Powers, John; Choi, Yongmun; Wojciechowski, Amy; Deng, Xianming; Azam, Mohammad; Daley, George Q.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Jahnke, Wolfgang; Cowan-Jacob, Sandra W.; Fendrich, Gabriele; Strauss, Andre; Manley, Paul W.] Novartis Inst Biomed Res, CH-4056 Basel, Switzerland.
[Iacob, Roxana E.; Engen, John R.] Northwestern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
[Iacob, Roxana E.; Engen, John R.] Northwestern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA.
[Sim, Taebo] Korea Inst Sci & Technol, Life Sci Res Div, Seoul 136791, South Korea.
[Powers, John; Azam, Mohammad; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Powers, John; Azam, Mohammad; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Powers, John; Azam, Mohammad; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Okram, Barun] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Okram, Barun] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
[Vajpai, Navratna; Grzesiek, Stephan] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland.
[Warmuth, Markus] Novartis Inst BioMed Res Inc, Cambridge, MA 02139 USA.
RP Adrian, FJ (reprint author), Novartis Res Fdn, Dept Chem, Genom Inst, 10675 John Jay Hopkins Dr, San Diego, CA 92121 USA.
EM fadrian@gnf.org; markus.warmuth@novartis.com;
nathanael_gray@dfci.harvard.edu
RI Dierks, Christine/L-4358-2013
FU NCI NIH HHS [R01 CA130876, R01 CA130876-03]
NR 41
TC 263
Z9 271
U1 8
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JAN 28
PY 2010
VL 463
IS 7280
BP 501
EP U116
DI 10.1038/nature08675
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548QK
UT WOS:000273981100042
PM 20072125
ER
PT J
AU Krishnamoorthy, KS
Eichler, FS
Goyal, NA
Small, JE
Snuderl, M
AF Krishnamoorthy, Kalpathy S.
Eichler, Florian S.
Goyal, Namita A.
Small, Juan E.
Snuderl, Matija
TI A Boy with Developmental Delay and Irritability Infantile Krabbe disease
(globoid-cell leukodystrophy)
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CEREBRAL-PALSY; TERM INFANTS; DEMYELINATIVE NEUROPATHIES; PERIPHERAL
NEUROPATHY; OPTIC-NERVE; CLASSIFICATION; ENLARGEMENT; CHILDREN; MRI
C1 [Krishnamoorthy, Kalpathy S.] Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA.
[Eichler, Florian S.; Goyal, Namita A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Small, Juan E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Snuderl, Matija] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Krishnamoorthy, Kalpathy S.] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA.
[Eichler, Florian S.; Goyal, Namita A.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA.
[Small, Juan E.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA.
[Snuderl, Matija] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP Krishnamoorthy, KS (reprint author), Massachusetts Gen Hosp, Div Pediat Neurol, Boston, MA 02114 USA.
NR 27
TC 4
Z9 4
U1 0
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 28
PY 2010
VL 362
IS 4
BP 346
EP 356
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 548OT
UT WOS:000273975000012
PM 20107221
ER
PT J
AU Wu, CL
Jordan, KW
Ratai, EM
Sheng, JH
Adkins, CB
DeFeo, EM
Jenkins, BG
Ying, L
McDougal, WS
Cheng, LL
AF Wu, Chin-Lee
Jordan, Kate W.
Ratai, Eva M.
Sheng, Jinhua
Adkins, Christen B.
DeFeo, Elita M.
Jenkins, Bruce G.
Ying, Leslie
McDougal, W. Scott
Cheng, Leo L.
TI Metabolomic Imaging for Human Prostate Cancer Detection
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID MAGNETIC-RESONANCE-SPECTROSCOPY; MR SPECTROSCOPY; BREAST-CANCER; 3 T;
RESOLUTION; PROFILES; TISSUE; MORTALITY; BIOPSIES; SEQUENCE
AB As current radiological approaches cannot accurately localize prostate cancer in vivo, biopsies are conducted at random within prostates for patients at risk for prostate cancer, leading to high false-negative rates. Metabolomic imaging can map cancer-specific biomolecular profile values onto anatomical structures to direct biopsy. In this preliminary study, we evaluated five whole prostates removed during prostatectomy from biopsy-proven cancer patients on a 7-tesla human whole-body magnetic resonance scanner. Localized, multi-cross-sectional, multivoxel magnetic resonance spectra were used to construct a malignancy index based on prostate cancer metabolomic profiles obtained from previous intact tissue analyses with a 14-tesla spectrometer. This calculated malignancy index is linearly correlated with lesion size and demonstrates a 93 to 97% overall accuracy for detecting the presence of prostate cancer lesions, suggesting the potential clinical utility of this approach.
C1 [Wu, Chin-Lee; Jordan, Kate W.; Adkins, Christen B.; DeFeo, Elita M.; Cheng, Leo L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Wu, Chin-Lee; McDougal, W. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA.
[Ratai, Eva M.; Jenkins, Bruce G.; Cheng, Leo L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Sheng, Jinhua; Ying, Leslie] Univ Wisconsin, Dept Elect Engn & Comp Sci, Milwaukee, WI 53201 USA.
RP Cheng, LL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
EM cheng@nmr.mgh.harvard.edu
OI Jordan, Kate/0000-0002-3089-2543
FU A. A. Martinos Center for Biomedical Imaging, Massachusetts General
Hospital; Claire and John Bertucci Prostate Cancer Research Fund;
[CA115746]; [CA095624]
FX CA115746 (L.L.C.); CA095624 (L.L.C.); A. A. Martinos Center for
Biomedical Imaging, Massachusetts General Hospital; and Claire and John
Bertucci Prostate Cancer Research Fund.
NR 34
TC 5
Z9 7
U1 0
U2 9
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JAN 27
PY 2010
VL 2
IS 16
AR 16ra8
DI 10.1126/scitranslmed.3000513
PG 7
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 590YO
UT WOS:000277264600004
PM 20371475
ER
PT J
AU Di Salvo, TG
Acker, MA
Dec, GW
Byrne, JG
AF Di Salvo, Thomas G.
Acker, Michael A.
Dec, G. William
Byrne, John G.
TI Mitral Valve Surgery in Advanced Heart Failure
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE mitral regurgitation; heart failure; cardiac surgery
ID CARDIAC RESYNCHRONIZATION THERAPY; LEFT-VENTRICULAR FUNCTION; ACORN
CLINICAL-TRIAL; COLLEGE-OF-CARDIOLOGY; LONG-TERM SURVIVAL; DILATED
CARDIOMYOPATHY; SYSTOLIC DYSFUNCTION; AFTERLOAD REDUCTION;
SURGICAL-TREATMENT; SUPPORT DEVICE
AB The appropriateness and timing of mitral valve surgery in patients with advanced heart failure and severe mitral regurgitation remains controversial. Recent surgical results provide evidence for beneficial effects on left ventricular remodeling and functional capacity. Given the absence of randomized trials comparing the outcomes of mitral valve surgery to medical therapy, however, clinical decision making regarding surgery for these fragile patients poses a dilemma to thoughtful clinicians. This paper reviews the pathophysiology of mitral regurgitation in heart failure and proposes an integrated approach to management. (J Am Coll Cardiol 2010; 55: 271-82) (C) 2010 by the American College of Cardiology Foundation
C1 [Di Salvo, Thomas G.; Byrne, John G.] Vanderbilt Univ, Nashville, TN USA.
[Acker, Michael A.] Univ Penn, Philadelphia, PA 19104 USA.
[Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Di Salvo, TG (reprint author), Vanderbilt Heart & Vasc Inst, 1215 21st Ave,MCE 5th Floor,Suite 5037, Nashville, TN 37232 USA.
EM thomas.g.disalvo@vanderbilt.edu
NR 87
TC 42
Z9 43
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 JAN 26
PY 2010
VL 55
IS 4
BP 271
EP 282
DI 10.1016/j.jacc.2009.08.059
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 546HP
UT WOS:000273802200001
PM 20117430
ER
PT J
AU Ix, JH
Katz, R
Peralta, CA
de Boer, IH
Allison, MA
Bluemke, DA
Siscovick, DS
Lima, JAC
Criqui, MH
AF Ix, Joachim H.
Katz, Ronit
Peralta, Carmen A.
de Boer, Ian H.
Allison, Matthew A.
Bluemke, David A.
Siscovick, David S.
Lima, Joao A. C.
Criqui, Michael H.
TI A High Ankle Brachial Index Is Associated With Greater Left Ventricular
Mass MESA (Multi-Ethnic Study of Atherosclerosis)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiovascular disease; heart failure; left ventricular mass; medial
arterial calcification; vascular stiffness
ID PERIPHERAL ARTERIAL-DISEASE; CARDIOVASCULAR HEALTH; RISK-FACTORS;
CALCIFICATION; PRESSURES; PREVALENCE; MORTALITY; EVENTS; ADULTS
AB Objectives This study sought to determine the association of high ankle brachial index (ABI) measurements with left ventricular (LV) mass, and to compare its strength with that of low ABI with LV mass.
Background Arterial stiffness leads to LV mass through nonatherosclerotic pathways in mice. In humans, a high ABI indicates stiff peripheral arteries and is associated with cardiovascular disease (CVD) events. Whether high ABI is associated with LV mass in humans and whether this might reflect consequences of arterial stiffness, atherosclerosis, or both is unknown.
Methods Among 4,972 MESA (Multi-Ethnic Study of Atherosclerosis) participants without clinical CVD, we used linear regression to evaluate the association of low (<0.90) and high (>1.40 or incompressible) ABI with LV mass by cardiac magnetic resonance imaging (MRI). Intermediate ABIs served as the reference category. To determine the effect of subclinical atherosclerosis, models were adjusted for common and internal carotid intima media thickness (cIMT) and natural log-transformed coronary artery calcification.
Results Compared with subjects with intermediate ABI, LV mass was higher with either low (2.70 g/m(2) higher, 95% confidence interval: 0.65 to 4.75) or high ABI (6.84 g/m2 higher, 95% confidence interval: 3.2 to 10.47) after adjustment for traditional CVD risk factors, kidney function, and C-reactive protein. However, further adjustment for cIMT and CAC substantially attenuated the association of low ABI with LV mass index (1.24 g/m(2) higher, 95% confidence interval: -0.84 to 3.33), whereas the association of high ABI was minimally altered (6.01 g/m(2) higher, 95% confidence interval: 2.36 to 9.67).
Conclusions High ABI is associated with greater LV mass; an association that is not attenuated with adjustment for subclinical atherosclerosis in nonperipheral arterial beds. High ABI might lead to greater LV mass through nonatherosclerotic pathways. (J Am Coll Cardiol 2010; 55: 342-9) (C) 2010 by the American College of Cardiology Foundation
C1 [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, San Diego VA Healthcare Syst, San Diego, CA 92161 USA.
[Ix, Joachim H.; Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent, San Diego, CA 92161 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
[Katz, Ronit] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[de Boer, Ian H.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Peralta, Carmen A.] Univ Calif San Diego, Div Nephrol, Dept Med, San Diego, CA 92161 USA.
[Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Bluemke, David A.] Natl Inst Hlth Clin Ctr, Bethesda, MD USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA.
RP Ix, JH (reprint author), Univ Calif San Diego, Div Nephrol & Hypertens, Dept Med, San Diego VA Healthcare Syst, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA.
EM joeix@ucsd.edu
OI Bluemke, David/0000-0002-8323-8086; Allison, Matthew/0000-0003-0777-8272
FU National Heart, Lung, and Blood Institute (NHLBI) [R21HL091217,
N01-HC-95159, N01-HC-95169]; American Heart Association Fellow to
Faculty Transition Award
FX From the *Division of Nephrology and Hypertension, Department of
Medicine, and the dagger Division of Preventive Medicine, Department of
Family and Preventive Medicine, University of California San Diego, San
Diego, California; Nephrology Section, Veterans Affairs San Diego
Healthcare System, San Diego, California; Collaborative Health Studies
Coordinating Center, Department of Biostatistics, ||Division of
Nephrology, Department of Medicine, and the Cardiovascular Health
Research Unit, Departments of Medicine and Epidemiology, University of
Washington, Seattle, Washington; #Division of Nephrology, Department of
Medicine, University of California San Francisco, San Francisco,
California; **San Francisco Veterans Affairs Medical Center, San
Francisco, California; dagger dagger Radiology and Imaging Sciences,
National Institutes of Health Clinical Center, Bethesda, Maryland; and
the Division of Cardiology, Department of Medicine, Johns Hopkins
University, Baltimore, Maryland. This study was supported by the
National Heart, Lung, and Blood Institute (NHLBI) grant R21HL091217 (to
Dr. Ix), an American Heart Association Fellow to Faculty Transition
Award, and contracts N01-HC-95159 through N01-HC-95169 from the NHLBI.
Michael R. Jaff, MD, served as Guest Editor for this article.
NR 28
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Z9 41
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JAN 26
PY 2010
VL 55
IS 4
BP 342
EP 349
DI 10.1016/j.jacc.2009.11.010
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 546HP
UT WOS:000273802200011
PM 20117440
ER
PT J
AU Huang, Y
Pastor, WA
Shen, YH
Tahiliani, M
Liu, DR
Rao, A
AF Huang, Yun
Pastor, William A.
Shen, Yinghua
Tahiliani, Mamta
Liu, David R.
Rao, Anjana
TI The Behaviour of 5-Hydroxymethylcytosine in Bisulfite Sequencing
SO PLOS ONE
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; DNA METHYLATION; TET2 MUTATIONS; CYTOSINE
METHYLATION; MAMMALIAN DEVELOPMENT; MLL RECOMBINOME; EUKARYOTIC DNA;
THYMINE GLYCOL; CPG SEQUENCES; CANCER
AB Background: We recently showed that enzymes of the TET family convert 5-mC to 5-hydroxymethylcytosine (5-hmC) in DNA. 5-hmC is present at high levels in embryonic stem cells and Purkinje neurons. The methylation status of cytosines is typically assessed by reaction with sodium bisulfite followed by PCR amplification. Reaction with sodium bisulfite promotes cytosine deamination, whereas 5-methylcytosine (5-mC) reacts poorly with bisulfite and is resistant to deamination. Since 5-hmC reacts with bisulfite to yield cytosine 5-methylenesulfonate (CMS), we asked how DNA containing 5-hmC behaves in bisulfite sequencing.
Methodology/Principal Findings: We used synthetic oligonucleotides with different distributions of cytosine as templates for generation of DNAs containing C, 5-mC and 5-hmC. The resulting DNAs were subjected in parallel to bisulfite treatment, followed by exposure to conditions promoting cytosine deamination. The extent of conversion of 5-hmC to CMS was estimated to be 99.7%. Sequencing of PCR products showed that neither 5-mC nor 5-hmC undergo C-to-T transitions after bisulfite treatment, confirming that these two modified cytosine species are indistinguishable by the bisulfite technique. DNA in which CMS constituted a large fraction of all bases (28/201) was much less efficiently amplified than DNA in which those bases were 5-mC or uracil (the latter produced by cytosine deamination). Using a series of primer extension experiments, we traced the inefficient amplification of CMS-containing DNA to stalling of Taq polymerase at sites of CMS modification, especially when two CMS bases were either adjacent to one another or separated by 1-2 nucleotides.
Conclusions: We have confirmed that the widely used bisulfite sequencing technique does not distinguish between 5-mC and 5-hmC. Moreover, we show that CMS, the product of bisulfite conversion of 5-hmC, tends to stall DNA polymerases during PCR, suggesting that densely hydroxymethylated regions of DNA may be underrepresented in quantitative methylation analyses.
C1 [Huang, Yun; Pastor, William A.; Tahiliani, Mamta; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Huang, Yun; Pastor, William A.; Tahiliani, Mamta; Rao, Anjana] Immune Dis Inst, Boston, MA USA.
[Shen, Yinghua; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Shen, Yinghua; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
RP Huang, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM arao@idi.harvard.edu
RI Duello, Theresa/P-5752-2015;
OI Huang, Yun/0000-0001-5950-9168
FU National Institutes of Health (NIH) [R01 AI044432, RC1 DA028422];
Juvenile Diabetes Research Foundation; Howard Hughes Medical Institute;
NIH/National Institute of General Medical Sciences (NIGMS) [R01
GM065865]; National Science Foundation and Department of Defense;
GlaxoSmithKline-Immune Disease Institute Alliance
FX This work was supported by National Institutes of Health (NIH) grants
R01 AI044432 and RC1 DA028422 and a Scholar Award from the Juvenile
Diabetes Research Foundation to A. R., Howard Hughes Medical Institute
and NIH/National Institute of General Medical Sciences (NIGMS) (R01
GM065865) funding to D. R. L., and National Science Foundation and
Department of Defense graduate fellowships to W. A. P. Y.H. is the
recipient of a fellowship from the GlaxoSmithKline-Immune Disease
Institute Alliance. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 45
TC 346
Z9 353
U1 11
U2 57
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 JAN 26
PY 2010
VL 5
IS 1
AR e8888
DI 10.1371/journal.pone.0008888
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 547NO
UT WOS:000273896500011
PM 20126651
ER
PT J
AU Scherer, EM
Leaman, DP
Zwick, MB
McMichael, AJ
Burton, DR
AF Scherer, Erin M.
Leaman, Daniel P.
Zwick, Michael B.
McMichael, Andrew J.
Burton, Dennis R.
TI Aromatic residues at the edge of the antibody combining site facilitate
viral glycoprotein recognition through membrane interactions
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE 4E10; gp41; HIV; neutralizing antibody; tryptophan
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROXIMAL EXTERNAL REGION; NEUTRALIZING
MONOCLONAL-ANTIBODY; GP41 ECTODOMAIN; EPITOPE RECOGNITION; TYPE-1
GLYCOPROTEIN; LIPID-COMPOSITION; HIV-ANTIBODIES; VACCINE DESIGN;
IN-VITRO
AB The broadly neutralizing anti-HIV antibody 4E10 recognizes an epitope very close to the virus membrane on the glycoprotein gp41. It was previously shown that epitope recognition improves in a membrane context and that 4E10 binds directly, albeit weakly, to lipids. Furthermore, a crystal structure of Fab 4E10 complexed to an epitope peptide revealed that the centrally placed, protruding H3 loop of the antibody heavy chain does not form peptide contacts. To investigate the hypothesis that the H3 loop apex might interact with the viral membrane, two Trp residues in this region were substituted separately or in combination with either Ala or Asp by site-directed mutagenesis. The resultant IgG variants exhibited similar affinities for an epitope peptide as WT 4E10 but lower apparent affinities for both viral membrane mimetic liposomes and Env(-) virus. Variants also exhibited lower apparent affinities for Env(+) virions and failed to significantly neutralize a number of 4E10-sensitive viruses. For the extremely sensitive HXB2 virus, variants did neutralize, but at 37- to >250-fold lower titers than WT 4E10, with Asp substitutions exerting a greater effect on neutralization potency than Ala substitutions. Because reductions in lipid binding reflect trends in neutralization potency, we conclude that Trp residues in the antibody H3 loop enable membrane proximal epitope recognition through favorable lipid interactions. The requirement for lipophilic residues such as Trp adjacent to the antigen binding site may explain difficulties in eliciting 4E10-like neutralizing antibody responses by immunization and helps define a unique motif for antibody recognition of membrane proximal antigens.
C1 [Leaman, Daniel P.; Zwick, Michael B.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Scherer, Erin M.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
[Leaman, Daniel P.; Zwick, Michael B.; Burton, Dennis R.] Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
[McMichael, Andrew J.] John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
[Burton, Dennis R.] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA.
RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM burton@scripps.edu
FU National Institutes of Health [AI33292, AI069993, T32 AI007606];
International AIDS Vaccine Initiative through the Neutralizing Antibody
Consortium
FX We thank Jillian Sola and Niccole Schultz for assistance with antibody
expression and purification. This work was funded in part through
National Institutes of Health Grants AI33292 (to D. R. B.) AI069993 (to
M. B. Z.), and T32 AI007606 (to M. B. Z.) and the International AIDS
Vaccine Initiative through the Neutralizing Antibody Consortium.
NR 50
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U1 3
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 JAN 26
PY 2010
VL 107
IS 4
BP 1529
EP 1534
DI 10.1073/pnas.0909680107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548OQ
UT WOS:000273974600055
PM 20080706
ER
PT J
AU Hung, KE
Maricevich, MA
Richard, LG
Chen, WY
Richardson, MP
Kunin, A
Bronson, RT
Mahmood, U
Kucherlapati, R
AF Hung, Kenneth E.
Maricevich, Marco A.
Richard, Larissa Georgeon
Chen, Wei Y.
Richardson, Michael P.
Kunin, Alexandra
Bronson, Roderick T.
Mahmood, Umar
Kucherlapati, Raju
TI Development of a mouse model for sporadic and metastatic colon tumors
and its use in assessing drug treatment
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE colon cancer; mouse model; adenovirus; colonoscopy; mammalian target of
rapamycin
ID ONCOGENIC K-RAS; BETA-CATENIN; CANCER; APC; MICE; PROGRESSION; LUNG;
COLONOSCOPY; CELL; TUMORIGENESIS
AB Most genetically engineered mouse (GEM) models for colon cancer are based on tissuewide or germline gene modification, resulting in tumors predominantly of the small intestine. Several of these models involve modification of the adenomatous polyposis coli (Apc) gene and are excellent models for familial cancer predisposition syndromes. We have developed a stochastic somatic mutation model for sporadic colon cancer that presents with isolated primary tumors in the distal colon and recapitulates the entire adenoma-carcinoma-metastasis axis seen in human colon cancer. Using this model, we have analyzed tumors that are either solely mutant in the Apc gene or in combination with another colon cancer-associated mutant gene, the Kras G12D allele. Because of the restricted location in the distal colon, the natural history of the tumors can be analyzed by serial colonoscopy. As the mammalian target of rapamycin (mTOR) pathway is a critical component of the complex signaling network in colon cancer, we used this model to assess the efficacy of mTOR blockade through rapamycin treatment of mice with established tumors. After treatment, Apc mutant tumors were more than 80% smaller than control tumors. However, tumors that possessed both Apc and Kras mutations did not respond to rapamycin treatment. These studies suggest that mTOR inhibitors should be further explored as potential colorectal cancer therapies in patients whose tumors do not have activating mutations in KRAS.
C1 [Hung, Kenneth E.; Chen, Wei Y.; Richardson, Michael P.] Tufts Med Ctr, Div Gastroenterol, Boston, MA 02111 USA.
[Maricevich, Marco A.; Kunin, Alexandra; Mahmood, Umar] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA.
[Richard, Larissa Georgeon; Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Richard, Larissa Georgeon; Kucherlapati, Raju] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Bronson, Roderick T.] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA.
RP Hung, KE (reprint author), 750 Washington St,Box 233, Boston, MA 02111 USA.
EM khung@tuftsmedicalcenter.org
OI Wong, Alexandra/0000-0002-8587-2494
FU American Gastroenterological Association; National Institute of Diabetes
and Digestive and Kidney Diseases [5K08DK078033]; National Institute of
Biomedical Imaging and Bioengineering [5R01EB001872]; National Cancer
Institute [5U01CA084301, 5P50CA127003]
FX We thank Eric Martin and Alain Charest for critical review of the
manuscript. The work reported here is supported by grants from the
American Gastroenterological Association (Research Scholar Award) and
from the National Institute of Diabetes and Digestive and Kidney
Diseases, Grant 5K08DK078033 (to K. H.); from the National Institute of
Biomedical Imaging and Bioengineering, Grant 5R01EB001872 (to U. M.);
and from the National Cancer Institute, Grant 5U01CA084301 (to R. K.)
and Grant 5P50CA127003 (to U. M. and R. K.).
NR 33
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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 JAN 26
PY 2010
VL 107
IS 4
BP 1565
EP 1570
DI 10.1073/pnas.0908682107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548OQ
UT WOS:000273974600061
PM 20080688
ER
PT J
AU Shaham, O
Slate, NG
Goldberger, O
Xu, QW
Ramanathan, A
Souza, AL
Clish, CB
Sims, KB
Mootha, VK
AF Shaham, Oded
Slate, Nancy G.
Goldberger, Olga
Xu, Qiuwei
Ramanathan, Arvind
Souza, Amanda L.
Clish, Clary B.
Sims, Katherine B.
Mootha, Vamsi K.
TI A plasma signature of human mitochondrial disease revealed through
metabolic profiling of spent media from cultured muscle cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE biochemical genetics; biomarker; metabolomics; mitochondria
ID MAGNETIC-RESONANCE SPECTROSCOPY; DISORDERS; CREATINE; CHILDREN;
CLASSIFICATION; BIOSYNTHESIS; PREVALENCE; CRITERIA; MUTANTS
AB Mutations in either the mitochondrial or nuclear genomes can give rise to respiratory chain disease (RCD), a large class of devastating metabolic disorders. Their clinical management is challenging, in part because we lack facile and accurate biomarkers to aid in diagnosis and in the monitoring of disease progression. Here we introduce a sequential strategy that combines biochemical analysis of spent media from cell culture with analysis of patient plasma to identify disease biomarkers. First, we applied global metabolic profiling to spotlight 32 metabolites whose uptake or secretion kinetics were altered by chemical inhibition of the respiratory chain in cultured muscle. These metabolites span a wide range of pathways and include lactate and alanine, which are used clinically as biomarkers of RCD. We next measured the cell culture-defined metabolites in human plasma to discover that creatine is reproducibly elevated in two independent cohorts of RCD patients, exceeding lactate and alanine in magnitude of elevation and statistical significance. In cell culture extracellular creatine was inversely related to the intracellular phosphocreatine: creatine ratio suggesting that the elevation of plasma creatine in RCD patients signals a low energetic state of tissues using the phosphocreatine shuttle. Our study identifies plasma creatine as a potential biomarker of human mitochondrial dysfunction that could be clinically useful. More generally, we illustrate how spent media from cellular models of disease may provide a window into the biochemical derangements in human plasma, an approach that could, in principle, be extended to a range of complex diseases.
C1 [Shaham, Oded; Slate, Nancy G.; Goldberger, Olga; Sims, Katherine B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Shaham, Oded; Ramanathan, Arvind; Souza, Amanda L.; Clish, Clary B.; Mootha, Vamsi K.] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA.
[Shaham, Oded; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Sims, Katherine B.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Xu, Qiuwei] Merck Res Labs, West Point, PA 19486 USA.
RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM vamsi@hms.harvard.edu
FU National Human Genome Research Institute; Eli and Dorothy Berman Fund;
Howard Hughes Medical Institute; Clinical Research Center at the
Massachusetts Institute of Technology [RR-01066]; National Center for
Research Resources; National Institutes of Health; Broad Institute
Scientific Planning and Allocation of Resources Committee [R01DK081457]
FX We thank R. Wei and E. Yang for assistance with MS; H. Vu and W.
Schaefer for assistance with NMR spectroscopy; and V. Gohil, M. Jain, T.
Kitami, R. Nilsson, S. Vafai, and R. Haller for valuable discussions and
comments on the manuscript. O. S. was supported by a training grant for
bioinformatics and integrative genomics from the National Human Genome
Research Institute and a fellowship from the Eli and Dorothy Berman
Fund. V. K. M. was supported by an Early Career Physician-Scientist
Award from the Howard Hughes Medical Institute. Clinical studies were
conducted in part at the Clinical Research Center at the Massachusetts
Institute of Technology funded by Grant RR-01066 from the National
Center for Research Resources, National Institutes of Health. This work
was supported by a grant from the Broad Institute Scientific Planning
and Allocation of Resources Committee and by Grant R01DK081457 from the
National Institutes of Health to V. K. M.
NR 28
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U1 0
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 JAN 26
PY 2010
VL 107
IS 4
BP 1571
EP 1575
DI 10.1073/pnas.0906039107
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548OQ
UT WOS:000273974600062
PM 20080599
ER
PT J
AU Kamruzzaman, M
Udden, SMN
Cameron, DE
Calderwood, SB
Nair, GB
Mekalanos, JJ
Faruque, SM
AF Kamruzzaman, M.
Udden, S. M. Nashir
Cameron, D. Ewen
Calderwood, Stephen B.
Nair, G. Balakrish
Mekalanos, John J.
Faruque, Shah M.
TI Quorum-regulated biofilms enhance the development of conditionally
viable, environmental Vibrio cholerae
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE biofilm formation; conditionally viable environmental cells (CVEC);
quorum sensing; transmissibility of cholera
ID SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; HOST; COLONIZATION;
EPIDEMIOLOGY; INFECTIVITY; BANGLADESH; RESISTANCE; MOTILITY; TOXIN
AB The factors that enhance the waterborne spread of bacterial epidemics and sustain the pathogens in nature are unclear. The epidemic diarrheal disease cholera caused by Vibrio cholerae spreads through water contaminated with the pathogen. However, the bacteria exist in water mostly as clumps of cells, which resist cultivation by standard techniques but revive into fully virulent form in the intestinal milieu. These conditionally viable environmental cells (CVEC), alternatively called viable but nonculturable cells, presumably play a crucial role in cholera epidemiology. However, the precise mechanism causing the transition of V. cholerae to the CVEC form and this form's significance in the biology of the pathogen are unknown. Here we show that this process involves biofilm formation that is dependent on quorum sensing, a regulatory response that is controlled by cell density. V. cholerae strains carrying mutations in genes required for quorum sensing and biofilm formation displayed altered CVEC formation in environmental water following intestinal infections. Analysis of naturally occurring V. cholerae CVEC showed that organisms that adopt this quiescent physiological state typically exist as clumps of cells that comprise a single clone closely related to isolates causing the most recent local cholera epidemic. These results support a model of cholera transmission in which in vivo-formed biofilms convert to CVEC upon the introduction of cholera stools into environmental water. Our data further suggest that a temporary loss of quorum sensing due to dilution of extracellular autoinducers confers a selective advantage to communities of V. cholerae by blocking quorum-mediated regulatory responses that would break down biofilms and thus interfere with CVEC formation.
C1 [Kamruzzaman, M.; Udden, S. M. Nashir; Nair, G. Balakrish; Faruque, Shah M.] Int Ctr Diarrhoeal Dis Res, Mol Genet Lab, Dhaka 1212, Bangladesh.
[Cameron, D. Ewen; Mekalanos, John J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
[Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Nair, G. Balakrish] Natl Inst Cholera & Enter Dis, Kolkata 700010, India.
RP Nair, GB (reprint author), Int Ctr Diarrhoeal Dis Res, Mol Genet Lab, Dhaka 1212, Bangladesh.
EM gbnair_2000@yahoo.com; john_mekalanos@hms.harvard.edu;
faruque@icddrb.org
FU National Institutes of Health [2R01-GM068851-5, AI070963-01A1,
U01-AI058935]
FX This research was funded in part by National Institutes of Health grants
2R01-GM068851-5, AI070963-01A1, and U01-AI058935 under different
sub-agreements between the Harvard Medical School, Massachusetts General
Hospital, and the International Centre for Diarrheal Disease Research in
Bangladesh. The International Centre for Diarrheal Disease Research in
Bangladesh is supported by countries and agencies that share its concern
for the health problems of developing countries.
NR 34
TC 31
Z9 34
U1 1
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 26
PY 2010
VL 107
IS 4
BP 1588
EP 1593
DI 10.1073/pnas.0913404107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548OQ
UT WOS:000273974600065
PM 20080633
ER
PT J
AU Cannon, CP
Harrington, RA
James, S
Ardissino, D
Becker, RC
Emanuelsson, H
Husted, S
Katus, H
Keltai, M
Khurmi, NS
Kontny, F
Lewis, BS
Steg, PG
Storey, RF
Wojdyla, D
Wallentin, L
AF Cannon, Christopher P.
Harrington, Robert A.
James, Stefan
Ardissino, Diego
Becker, Richard C.
Emanuelsson, Hakan
Husted, Steen
Katus, Hugo
Keltai, Matyas
Khurmi, Nardev S.
Kontny, Frederic
Lewis, Basil S.
Steg, Philippe Gabriel
Storey, Robert F.
Wojdyla, Daniel
Wallentin, Lars
CA PLATO Investigators
TI Comparison of ticagrelor with clopidogrel in patients with planned
invasive strategy for acute coronary syndromes (PLATO): a randomised
double-blind study
SO LANCET
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; P2Y(12) RECEPTOR
ANTAGONIST; COLLABORATIVE METAANALYSIS; PLATELET-AGGREGATION;
CLINICAL-TRIALS; UNSTABLE ANGINA; TASK-FORCE; PCI-CURE; INTERVENTION
AB Background Variation in and irreversibility of platelet inhibition with clopiclogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopiclogrel in such patients.
Methods At randomisation, an invasive strategy was planned for 13408 (72.0%) of 18624 patients hospitalised for acute coronary syndromes (with or without ST elevation). in a double-blind, double-dummy study, patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were given aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00391872.
Findings 6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopiclogrel group (569 [event rate at 360 days 9.0%] vs 668 [10.7%], hazard ratio 0.84, 95% CI 0.75-0.94; p=0.0025). There was no difference between clopiclogrel and ticagrelor groups in the rates of total major bleeding (691 [11.6%] vs 689 [11.5%], 0.99 [0.89-1.10]; p=0.8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3.2%] vs 185 [2.9%], 0.91 [0.74-1.12]; p=0.3785).
Interpretation Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned.
C1 [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA.
[Harrington, Robert A.; Becker, Richard C.; Wojdyla, Daniel] Duke Clin Res Inst, Durham, NC USA.
[James, Stefan; Wallentin, Lars] Uppsala Clin Res Ctr, Uppsala, Sweden.
[James, Stefan; Wallentin, Lars] Dept Med Sci, Uppsala, Sweden.
[Ardissino, Diego] Azienda Osped Univ Parma, Parma, Italy.
[Emanuelsson, Hakan] AstraZeneca, Molndal, Sweden.
[Khurmi, Nardev S.] AstraZeneca, Wilmington, DE USA.
[Husted, Steen] Arhus Univ Hosp, Aarhus, Denmark.
[Katus, Hugo] Univ Klinikum Heidelberg, Heidelberg, Germany.
[Keltai, Matyas] Hungarian Inst Cardiol, Budapest, Hungary.
[Kontny, Frederic] Volvat Med Ctr, Oslo, Norway.
[Lewis, Basil S.] Lady Davis Carmel Med Ctr, Haifa, Israel.
[Steg, Philippe Gabriel] APHP, INSERM, U698, Paris, France.
[Steg, Philippe Gabriel] Univ Paris, F-75252 Paris, France.
[Storey, Robert F.] Univ Sheffield, Sheffield, S Yorkshire, England.
RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM cpcannon@partners.org
RI Katus, Hugo/P-1712-2016
FU Accumetrics; AstraZeneca; Bristol-Myers Squibb; Sanofi-Aventis;
GlaxoSmithlKline; Merck; Intekrin Therapeutics; Novartis; Takeda;
Pfizer; Eli Lilly; Boehringer-Irigelheiin
FX CPC has received research or grant support from Accumetrics,
AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis, GlaxoSmithlKline,
Merck, Intekrin Therapeutics, Novartis, and Takeda; and owns equity in
ALItomedics Medical Systems. RAH has received consulting fees from
Bristol-Myers Squibb, Sanorfi-Aventis, Portola Pharmaceuticals,
Schering-Plough, arid AstraZeneca; lecture fees from Schering-Plough,
Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly; and grant support
from Millennium Phannaceuticals, Schering-Plough, Tlie Medicines
Company, Portola Pharmaceuticals, AstraZeneca, and Bristol-Myers Squibb.
SJ has received research grants arid advisory board fees from
AstraZeneca; and honoraria from AstraZeneca, Bristol-Myers Squibb,
Schering-Plough, and Eli Lilly. DA has received research grants from
AstraZeneca, Eli Lilly, Pfizer, and Boston Scientific; speaker's bureau
payments and honoraria from GIaxoSmithKline, Boehringer-Irigelheiin,
Sanofi-Aventis, Pfizer, Eli Lilly, AstraZeneca. Schering-Plough, Daiichi
Sankyo, Merck, arid Boston Scientific: and advisory board fees from
Sanofi-Aventis, Pfizer, Eli Lillv AstraZeneca, Schering-Plough, Daiichi
Sarikyo, and Mechionic. RCB has received consulting fees from Regado
Biosciences, AstraZeneca, Eli Lilly, and Bristol-Myers Squibb; and grant
support from Momenta Pharmaceuticals, The Medicines Company, and
Bristol-Myers Squibb. H E has been an employee ofand owned equity in
AstraZeneca. SH has received consulting fees from AstraZeneca,
Sanofi-Aventis, and Eli Lilly; and lecture fees from AstraZeneca,
Sanofi-Avenfis, and Bristol-Myers Squibb. H K has received consulting
arid lecture fees from AstraZeneca, Bayer Healthcare, Abbott, Roche, and
Menarim. MK has received consulting and lecture fees from AstraZeneca.
NSK has been an employee ofAstraZeneca. FK has received advisory board
fees from AstraZeneca and Boehringer-Ingelheim; consulting fees from
AstraZeneca, Boeh ringer-I ngelheim, and Sanofi-Aventis; grant support
froul Merck Sharp and Dohme, and Perseus Proteomics; and lecture fees
from AstraZerieca, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli
Lilly, Pfizer, and Sanofi-Aventis. BSL has received consulting fees
froni Bristol-Myers Squibb and Sanofi-Aventis; and grant support from
AstraZeneca. PGS has received research grants from Sanofi-Aventis arid
Servier; lecture fees from AstraZeneca, Boehringer-Ingelheirn '
Bristol-Myers Squibb, GlaxoSmith Kline, Menarim, Mechronic, Nyconied,
Pierre Fabre, Sanofi-Averitis, Servier, and The Medicines Company;
consulting or advisory board fees from Astellas, AstraZeneca, Bayer,
Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Endotis,
GlaxoSmith Kline, Medtronic, Merck Sharp and Dohme, Nycomed,
Sanofi-Aventis, Servier, and The Medicines Company; and has been a
stockholder ofAterovax. RFS has received consulting fees from
AstraZeneca. Eli Lilly, Daiichi Sankyo, Teva, and Schering-Plough;
lecture fees from Eli Lilly, Daiichi Sankyo, arid AstraZeneca; and grant
support from AstraZeneca, Eli Lilly, Daiichi Sankyo, arid
Schering-Plough. DW declares that he has no conflicts of interest. LW
has received consulting fees from Regado Biosciences and Athera
Biotechnologies; lecture fees from Boehringer-Ingelheim, AstraZeneca,
and Eli Lilly; and grant support from AstraZeneca, Boehringer-Ingelheim,
Bristol-Myers Squibb, GlaxoSmitliKline, and Schering-Plough.
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD JAN 23
PY 2010
VL 375
IS 9711
BP 283
EP 293
DI 10.1016/S0140-6736(09)62191-7
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 549QS
UT WOS:000274069300029
PM 20079528
ER
PT J
AU Kwong, LN
Chin, L
AF Kwong, Lawrence N.
Chin, Lynda
TI The Brothers RAF
SO CELL
LA English
DT Editorial Material
ID BRAF; CRAF; MUTATIONS; MELANOMA; INHIBITION; RESISTANCE; MECHANISM;
PATHWAYS; CANCER; CELLS
C1 [Kwong, Lawrence N.; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, 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
NR 9
TC 11
Z9 11
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 JAN 22
PY 2010
VL 140
IS 2
BP 180
EP 182
DI 10.1016/j.cell.2010.01.013
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 546QX
UT WOS:000273826500009
PM 20141832
ER
PT J
AU Zhong, L
D'Urso, A
Toiber, D
Sebastian, C
Henry, RE
Vadysirisack, DD
Guimaraes, A
Marinelli, B
Wikstrom, JD
Nir, T
Clish, CB
Vaitheesvaran, B
Iliopoulos, O
Kurland, I
Dor, Y
Weissleder, R
Shirihai, OS
Ellisen, LW
Espinosa, JM
Mostoslavsky, R
AF Zhong, Lei
D'Urso, Agustina
Toiber, Debra
Sebastian, Carlos
Henry, Ryan E.
Vadysirisack, Douangsone D.
Guimaraes, Alexander
Marinelli, Brett
Wikstrom, Jakob D.
Nir, Tomer
Clish, Clary B.
Vaitheesvaran, Bhavapriya
Iliopoulos, Othon
Kurland, Irwin
Dor, Yuval
Weissleder, Ralph
Shirihai, Orian S.
Ellisen, Leif W.
Espinosa, Joaquin M.
Mostoslavsky, Raul
TI The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1
alpha
SO CELL
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR-1; CALORIE RESTRICTION; MITOCHONDRIAL-FUNCTION;
GENOMIC INSTABILITY; GENE-EXPRESSION; LIFE-SPAN; HIF-1-ALPHA; CELLS;
HIF-1; ACETYLATION
AB SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1 alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1 alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.
C1 [Zhong, Lei; D'Urso, Agustina; Toiber, Debra; Sebastian, Carlos; Vadysirisack, Douangsone D.; Iliopoulos, Othon; Ellisen, Leif W.; Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Henry, Ryan E.; Espinosa, Joaquin M.] Univ Colorado, Dept Mol Cellular & Dev Biol, Howard Hughes Med Inst, Boulder, CO 80309 USA.
[Guimaraes, Alexander; Marinelli, Brett; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Iliopoulos, Othon] Massachusetts Gen Hosp, Dept Med, Hematol Oncol Unit, Boston, MA 02114 USA.
[Wikstrom, Jakob D.; Shirihai, Orian S.] Boston Univ, Sch Med, Dept Mol Med, Boston, MA 02118 USA.
[Nir, Tomer; Dor, Yuval] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
[Clish, Clary B.] Broad Inst MIT & Harvard, Ctr Prote, Cambridge, MA 02142 USA.
[Vaitheesvaran, Bhavapriya; Kurland, Irwin] Albert Einstein Coll Med, Michael F Price Ctr, Bronx, NY 10461 USA.
[Wikstrom, Jakob D.] Stockholm Univ, Arrhenius Labs F3, Wenner Gren Inst, SE-10691 Stockholm, Sweden.
RP Mostoslavsky, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM rmostoslavsky@mgh.harvard.edu
RI Dor, Yuval/C-2405-2011;
OI Wikstrom, Jakob/0000-0002-4287-1774
FU V Foundation; Sidney Kimmel Cancer Research Foundation; AFAR; The
Massachusetts Life Sciences Center; Joslin Diabetes Center; Metabolic
Physiology Core [P30 DK57521]; Brain Power for Israel Fund; NIH [RO1
CA117907]; Howard Hughes Medical Institute
FX This work was supported by the V Foundation (R.M.), the Sidney Kimmel
Cancer Research Foundation (R.M.), a New Investigator Grant from AFAR
(R.M.), A New Investigator Award from The Massachusetts Life Sciences
Center (R.M.), a P&F Award from the Joslin Diabetes Center (R.M.), and
Grant P30 DK57521 from the Metabolic Physiology Core (BADERC). D. T. is
supported by a fellowship from the Brain Power for Israel Fund. Y.D. is
supported by JDRF. J.M.E. is supported by NIH-RO1 CA117907 and the
Howard Hughes Medical Institute. We thank Magali Silberman, Daniel
Holoch, Pere Puigserver, John Dominy, Matthew Vander Heiden, Mike
Zimmer, David Lombard, Bjoern Schwer, Fred Alt, Katrin Chua, and members
of the Bardeesy, Hochedlinger, Hock, and Ramaswamy labs for reagents and
helpful discussions. We thank Kelly Shay, Laura Prickett-Rice, and Kate
Folz-Donahue for technical assistance. We are also thankful to Nabeel
Bardeesy and Hanno Hock for critically reading the manuscript and Jose
Polo for assistance with the ChIP assays.
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PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JAN 22
PY 2010
VL 140
IS 2
BP 280
EP 293
DI 10.1016/j.cell.2009.12.041
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 546QX
UT WOS:000273826500018
PM 20141841
ER
PT J
AU Giedraitis, V
Glaser, A
Sarajarvi, T
Brundin, R
Gunnarsson, MD
Schjeide, BM
Tanzi, RE
Helisalmi, S
Pirttila, T
Kilander, L
Lannfelt, L
Soininen, H
Bertram, L
Ingelsson, M
Hiltunen, M
AF Giedraitis, Vilmantas
Glaser, Anna
Sarajarvi, Timo
Brundin, RoseMarie
Gunnarsson, Malin Degerman
Schjeide, Brit-Maren
Tanzi, Rudolph E.
Helisalmi, Seppo
Pirttila, Tuula
Kilander, Lena
Lannfelt, Lars
Soininen, Hilkka
Bertram, Lars
Ingelsson, Martin
Hiltunen, Mikko
TI CALHM1 P86L polymorphism does not alter amyloid-beta or tau in
cerebrospinal fluid
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE CALHM1; Calcium homeostasis modulator-1; Amyloid-beta; Alzheimer's
disease; Cerebrospinal fluid; Biomarker; Total tau; Phospho-tau;
Genotyping SNP
ID ALZHEIMERS-DISEASE RISK; CLINICAL-DIAGNOSIS; APOLIPOPROTEIN-E; APOE;
ASSOCIATION; GENOTYPE; ALLELE
AB Recently, the P86L alteration in CALHM1 (calcium homeostasis modulator-1) was reported to be associated with Alzheimer's disease (AD). Moreover, the risk allele increased amyloid-beta (A beta) levels in conditioned media from cultured cells. Therefore, we hypothesized that CALHM1 P86L may modulate A beta or tau levels in cerebrospinal fluid (CSF). Nearly 200 individuals with AD or other cognitive disorders were included for CSF analysis and CALHM1 genotyping. No significant differences in CSF levels of A beta 42, tau or phospho-tau were found across the various CALHM1 genotypes. In conclusion, we found no evidence that CALHM1 P86L is associated with altered CSF levels of the investigated AD biomarkers. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Hiltunen, Mikko] Univ Kuopio, Dept Neurol, FIN-70211 Kuopio, Finland.
[Giedraitis, Vilmantas; Glaser, Anna; Brundin, RoseMarie; Gunnarsson, Malin Degerman; Kilander, Lena; Lannfelt, Lars; Ingelsson, Martin] Uppsala Univ, Dept Publ Hlth Geriatr, Rudbeck Lab, Uppsala, Sweden.
[Sarajarvi, Timo; Helisalmi, Seppo; Pirttila, Tuula; Soininen, Hilkka; Hiltunen, Mikko] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
[Schjeide, Brit-Maren; Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, Neuropsychiat Genet Grp, Berlin, Germany.
[Schjeide, Brit-Maren; Tanzi, Rudolph E.; Bertram, Lars] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIND,Genet & Aging Res Unit,Dept Neurol, Charlestown, MA USA.
RP Hiltunen, M (reprint author), Univ Kuopio, Dept Neurol, POB 1627, FIN-70211 Kuopio, Finland.
EM mhiltune@uku.fi
RI Bertram, Lars/K-3889-2015
OI Bertram, Lars/0000-0002-0108-124X
FU Swedish Research Council; Swedish Brain Foundation; Swedish Alzheimer
Foundation; Helsinki University Hospital; Kuopio University Hospital
[5772708]; Nordic Centre of Excellence of Neurodegeneration; University
of Kuopio Graduate School of Molecular Medicine; Cure Alzheimer's Fund
FX Financial support for this project was provided by the Swedish Research
Council, the Swedish Brain Foundation, the Swedish Alzheimer Foundation,
the EVO Research Fund of Helsinki University Hospital, the Health
Research Council of the Academy of Finland, EVO grant 5772708 of Kuopio
University Hospital, The Nordic Centre of Excellence of
Neurodegeneration, the University of Kuopio Graduate School of Molecular
Medicine and the Cure Alzheimer's Fund.
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U2 2
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 JAN 22
PY 2010
VL 469
IS 2
BP 265
EP 267
DI 10.1016/j.neulet.2009.12.011
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 555KD
UT WOS:000274508700019
PM 20005921
ER
PT J
AU Roccaro, AM
Sacco, A
Husu, EN
Pitsillides, C
Vesole, S
Azab, AK
Azab, F
Melhem, M
Ngo, HT
Quang, P
Maiso, P
Runnels, J
Liang, MC
Wong, KK
Lin, C
Ghobrial, IM
AF Roccaro, Aldo M.
Sacco, Antonio
Husu, Emanuel N.
Pitsillides, Costas
Vesole, Steven
Azab, Abdel Kareem
Azab, Feda
Melhem, Molly
Ngo, Hai T.
Quang, Phong
Maiso, Patricia
Runnels, Judith
Liang, Mei-Chih
Wong, Kwok-Kin
Lin, Charles
Ghobrial, Irene M.
TI Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in
Waldenstrom macroglobulinemia
SO BLOOD
LA English
DT Article
ID FORKHEAD TRANSCRIPTION FACTOR; MULTIPLE-MYELOMA; SIGNALING PATHWAYS;
BINDING PARTNER; KINASE PATHWAY; CANCER; PTEN; AKT; EXPRESSION;
RAPAMYCIN
AB We have previously shown clinical activity of a mammalian target of rapamycin (mTOR) complex 1 inhibitor in Waldenstrom macroglobulinemia (WM). However, 50% of patients did not respond to therapy. We therefore examined mechanisms of activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR in WM, and mechanisms of overcoming resistance to therapy. We first demonstrated that primary WM cells show constitutive activation of the PI3K/Akt pathway, supported by decreased expression of phosphate and tensin homolog tumor suppressor gene (PTEN) at the gene and protein levels, together with constitutive activation of Akt and mTOR. We illustrated that dual targeting of the PI3K/mTOR pathway by the novel inhibitor NVP-BEZ235 showed higher cytotoxicity on WM cells compared with inhibition of the PI3K or mTOR pathways alone. In addition, NVP-BEZ235 inhibited both rictor and raptor, thus abrogating the rictor-induced Akt phosphorylation. NVP-BEZ235 also induced significant cytotoxicity in WM cells in a caspase-dependent and -independent manner, through targeting the Forkhead box transcription factors. In addition, NVP-BEZ235 targeted WM cells in the context of bone marrow microenvironment, leading to significant inhibition of migration, adhesion in vitro, and homing in vivo. These studies therefore show that dual targeting of the PI3K/mTOR pathway is a better modality of targeted therapy for tumors that harbor activation of the PI3K/mTOR signaling cascade, such as WM. (Blood. 2010; 115: 559-569)
C1 [Roccaro, Aldo M.; Sacco, Antonio; Husu, Emanuel N.; Vesole, Steven; Azab, Abdel Kareem; Azab, Feda; Melhem, Molly; Ngo, Hai T.; Quang, Phong; Maiso, Patricia; Liang, Mei-Chih; Wong, Kwok-Kin; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pitsillides, Costas; Runnels, Judith; Lin, Charles] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 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
RI Sacco, Antonio/K-4681-2016;
OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924;
Roccaro, Aldo/0000-0002-1872-5128; wong, kwok kin/0000-0001-6323-235X
FU International Waldenstrom's Macroglobulinemia Foundation [R21
1R21CA126119-01]; Michelle and Steven Kirsch laboratory for
Waldenstrom's; Waldenstrom's
FX This work was supported in part by R21 1R21CA126119-01 and the
International Waldenstrom's Macroglobulinemia Foundation. This work was
also supported by the Michelle and Steven Kirsch laboratory for
Waldenstrom's and the Heje fellowship for Waldenstrom's.
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U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JAN 21
PY 2010
VL 115
IS 3
BP 559
EP 569
DI 10.1182/blood-2009-07-235747
PG 11
WC Hematology
SC Hematology
GA 546OR
UT WOS:000273820600017
PM 19965685
ER
PT J
AU Vardiman, J
Thiele, J
Arber, DA
Brunning, R
Borowitz, MJ
Porwit, A
Harris, NL
Le Beau, MM
Hellstrom-Lindberg, E
Tefferi, A
Bloomfield, CD
AF Vardiman, James
Thiele, Juergen
Arber, Daniel A.
Brunning, Richard
Borowitz, Michael J.
Porwit, Anna
Harris, Nancy Lee
Le Beau, Michelle M.
Hellstrom-Lindberg, Eva
Tefferi, Ayalew
Bloomfield, Clara D.
TI Factors considered in the 2008 WHO classification of myeloid neoplasms
and acute leukemias Response
SO BLOOD
LA English
DT Letter
ID INDEPENDENT PROGNOSTIC RELEVANCE; AML
C1 [Vardiman, James] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Thiele, Juergen] Univ Cologne, Cologne, Germany.
[Arber, Daniel A.] Stanford Univ, Stanford, CA 94305 USA.
[Brunning, Richard] Univ Minnesota, Minneapolis, MN USA.
[Borowitz, Michael J.] Johns Hopkins Univ, Baltimore, MD USA.
[Porwit, Anna; Hellstrom-Lindberg, Eva] Karolinska Univ Hosp, Stockholm, Sweden.
[Harris, Nancy Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Harris, Nancy Lee] Harvard Univ, Sch Med, Boston, MA USA.
[Tefferi, Ayalew] Mayo Clin, Rochester, MN USA.
[Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
RP Vardiman, J (reprint author), Univ Chicago, Med Ctr, 5841 S Maryland Ave,Mailcode 0008, Chicago, IL 60637 USA.
EM james.vardiman@uchospitals.edu
NR 4
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U1 0
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 JAN 21
PY 2010
VL 115
IS 3
BP 749
EP 750
DI 10.1182/blood-2009-11-250399
PG 4
WC Hematology
SC Hematology
GA 546OR
UT WOS:000273820600042
ER
PT J
AU Bienvenu, F
Jirawatnotai, S
Elias, JE
Meyer, CA
Mizeracka, K
Marson, A
Frampton, GM
Cole, MF
Odom, DT
Odajima, J
Geng, Y
Zagozdzon, A
Jecrois, M
Young, RA
Liu, XS
Cepko, CL
Gygi, SP
Sicinski, P
AF Bienvenu, Frederic
Jirawatnotai, Siwanon
Elias, Joshua E.
Meyer, Clifford A.
Mizeracka, Karolina
Marson, Alexander
Frampton, Garrett M.
Cole, Megan F.
Odom, Duncan T.
Odajima, Junko
Geng, Yan
Zagozdzon, Agnieszka
Jecrois, Marie
Young, Richard A.
Liu, X. Shirley
Cepko, Constance L.
Gygi, Steven P.
Sicinski, Piotr
TI Transcriptional role of cyclin D1 in development revealed by a
genetic-proteomic screen
SO NATURE
LA English
DT Article
ID KINASE-INDEPENDENT MECHANISM; CELL-CYCLE; ESTROGEN-RECEPTOR; MOUSE
RETINA; BREAST; TRANSFORMATION; RECRUITMENT; EXPRESSION; REPRESSES;
CANCER
AB Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers(1,2). The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag-and haemagglutinin-tagged cyclin D1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclin D1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclin D1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinas-an organ that critically requires cyclin D1 function(3,4)-cyclin D1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclin D1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null (Ccnd1(-/-)) retinas. Transduction of an activated allele of Notch1 into Ccnd1(-/-) retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclin D1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development. Our approach, which we term 'genetic-proteomic', can be used to study the in vivo function of essentially any protein.
C1 [Bienvenu, Frederic; Jirawatnotai, Siwanon; Odajima, Junko; Geng, Yan; Zagozdzon, Agnieszka; Jecrois, Marie; Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Bienvenu, Frederic; Jirawatnotai, Siwanon; Odajima, Junko; Geng, Yan; Zagozdzon, Agnieszka; Jecrois, Marie; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Elias, Joshua E.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Meyer, Clifford A.; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Mizeracka, Karolina; Cepko, Constance L.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Jirawatnotai, Siwanon] Mahidol Univ, Inst Mol Biosci, Salaya 73170, Nakhon Prathom, Thailand.
[Marson, Alexander; Frampton, Garrett M.; Cole, Megan F.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Marson, Alexander; Frampton, Garrett M.; Cole, Megan F.; Young, Richard A.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Odom, Duncan T.] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM Peter_Sicinski@dfci.harvard.edu
RI Young, Richard/F-6495-2012;
OI Young, Richard/0000-0001-8855-8647; Odom, Duncan/0000-0001-6201-5599
FU Cancer Research UK; European Research Council; EMBO Young Investigator
Award; [R01 CA108420]; [P01 CA080111]; [P01 CA109901]; [HG3456];
[R01 EYO9676]; [HG004069]
FX We thank T. Liu, Y. Ndassa-Colday, J. Marto, R. Bronson, B. Smith, E.
Jacobsen, M. Brown and members of the Brown laboratory for help at
different stages of the project, M. Ewen for p-Babe-puro-Cyclin D1 and
cyclin D1(K112E) plasmids, G. Seigel for R28 cells, T. Volkert, J. Love
and E. Fox for help with arrays, P. White and O. Smirnova for help with
BCBC arrays. This work was supported by grants R01 CA108420, P01
CA080111 and P01 CA109901 (to P. S.), HG3456 (to S. P. G.), R01 EYO9676
(to C. L. C.), HG004069 (to X. S. L.), Cancer Research UK, European
Research Council Starting Grant, and an EMBO Young Investigator Award
(all to D. T. O.). P. S. is a Leukemia and Lymphoma Society Scholar.
NR 30
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JAN 21
PY 2010
VL 463
IS 7279
BP 374
EP 378
DI 10.1038/nature08684
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545PM
UT WOS:000273748100048
PM 20090754
ER
PT J
AU Smits, P
Bolton, AD
Funari, V
Hong, M
Boyden, ED
Lu, L
Manning, DK
Dwyer, ND
Moran, JL
Prysak, M
Merriman, B
Nelson, SF
Bonafe, L
Superti-Furga, A
Ikegawa, S
Krakow, D
Cohn, DH
Kirchhausen, T
Warman, ML
Beier, DR
AF Smits, Patrick
Bolton, Andrew D.
Funari, Vincent
Hong, Minh
Boyden, Eric D.
Lu, Lei
Manning, Danielle K.
Dwyer, Noelle D.
Moran, Jennifer L.
Prysak, Mary
Merriman, Barry
Nelson, Stanley F.
Bonafe, Luisa
Superti-Furga, Andrea
Ikegawa, Shiro
Krakow, Deborah
Cohn, Daniel H.
Kirchhausen, Tom
Warman, Matthew L.
Beier, David R.
TI Lethal Skeletal Dysplasia in Mice and Humans Lacking the Golgin GMAP-210
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID THYROID-HORMONE RECEPTOR; RIBBON FORMATION; ER STRESS; PROTEIN;
APPARATUS; MOUSE; MECHANISMS; MUTATIONS; PHENOTYPE; CARTILAGE
AB BACKGROUND
Establishing the genetic basis of phenotypes such as skeletal dysplasia in model organisms can provide insights into biologic processes and their role in human disease.
METHODS
We screened mutagenized mice and observed a neonatal lethal skeletal dysplasia with an autosomal recessive pattern of inheritance. Through genetic mapping and positional cloning, we identified the causative mutation.
RESULTS
Affected mice had a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210); the affected mice lacked this protein. Golgi architecture was disturbed in multiple tissues, including cartilage. Skeletal development was severely impaired, with chondrocytes showing swelling and stress in the endoplasmic reticulum, abnormal cellular differentiation, and increased cell death. Golgi-mediated glycosylation events were altered in fibroblasts and chondrocytes lacking GMAP-210, and these chondrocytes had intracellular accumulation of perlecan, an extracellular matrix protein, but not of type II collagen or aggrecan, two other extracellular matrix proteins. The similarities between the skeletal and cellular phenotypes in these mice and those in patients with achondrogenesis type 1A, a neonatal lethal form of skeletal dysplasia in humans, suggested that achondrogenesis type 1A may be caused by GMAP-210 deficiency. Sequence analysis revealed loss-of-function mutations in the 10 unrelated patients with achondrogenesis type 1A whom we studied.
CONCLUSIONS
GMAP-210 is required for the efficient glycosylation and cellular transport of multiple proteins. The identification of a mutation affecting GMAP-210 in mice, and then in humans, as the cause of a lethal skeletal dysplasia underscores the value of screening for abnormal phenotypes in model organisms and identifying the causative mutations.
C1 [Smits, Patrick; Hong, Minh; Boyden, Eric D.; Warman, Matthew L.] Childrens Hosp, Dept Orthoped Surg, Orthoped Res Labs, Boston, MA 02115 USA.
[Warman, Matthew L.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Lu, Lei; Kirchhausen, Tom] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Bolton, Andrew D.; Manning, Danielle K.; Dwyer, Noelle D.; Moran, Jennifer L.; Prysak, Mary; Beier, David R.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Lu, Lei; Kirchhausen, Tom] Brigham & Womens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Lu, Lei; Kirchhausen, Tom] Brigham & Womens Hosp, Dept Cell Biol, Boston, MA 02115 USA.
[Warman, Matthew L.] Brigham & Womens Hosp, Dept Genet, Boston, MA 02115 USA.
[Funari, Vincent; Krakow, Deborah; Cohn, Daniel H.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Funari, Vincent; Merriman, Barry; Nelson, Stanley F.; Krakow, Deborah; Cohn, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90048 USA.
[Bonafe, Luisa] Univ Lausanne, CHU Vaudois, Div Mol Pediat, Lausanne, Switzerland.
[Superti-Furga, Andrea] Univ Freiburg, Dept Pediat, D-7800 Freiburg, Germany.
[Ikegawa, Shiro] RIKEN, Ctr Genom Med, Tokyo, Japan.
RP Warman, ML (reprint author), Childrens Hosp, Dept Orthoped Surg, Orthoped Res Labs, Enders 907-2,320 Longwood Ave, Boston, MA 02115 USA.
EM matthew.warman@childrens.harvard.edu
RI Nelson, Stanley/D-4771-2009; superti-furga, andrea/E-9162-2015; Lu,
Lei/A-2225-2011; Ikegawa, Shiro/N-6895-2015;
OI superti-furga, andrea/0000-0002-3543-7531; Lu, Lei/0000-0002-8192-1471;
Ikegawa, Shiro/0000-0003-0316-2147; Moran, Jennifer/0000-0002-5664-4716
FU National Institutes of Health [HD36404, UO1 HD43430, GM075252, A1063430,
AR050180]; Swiss National Research Foundation [320000-116506]; Arthritis
Foundation
FX Supported by grants from the National Institutes of Health (HD36404 and
UO1 HD43430, to Dr. Beier; GM075252 and A1063430, to Dr. Kirchhausen;
and AR050180, to Dr. Warman) and the Swiss National Research Foundation
(320000-116506, to Dr. Bonafe) and by an Arthritis Foundation
Investigator Award to Dr. Smits.
NR 40
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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 JAN 21
PY 2010
VL 362
IS 3
BP 206
EP 216
DI 10.1056/NEJMoa0900158
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 545NE
UT WOS:000273738400007
PM 20089971
ER
PT J
AU Pober, BR
AF Pober, Barbara R.
TI MEDICAL PROGRESS Williams-Beuren Syndrome
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID SUPRAVALVULAR AORTIC-STENOSIS; AUTOSOMAL-DOMINANT INHERITANCE;
VITAMIN-D; IDIOPATHIC HYPERCALCEMIA; MENTAL-RETARDATION; SUDDEN-DEATH;
CHILDREN; ADULTS; DELETION; ANOMALIES
C1 Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA.
RP Pober, BR (reprint author), Massachusetts Gen Hosp, Ctr Human Genet, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA.
EM pober.barbara@mgh.harvard.edu
FU Williams Syndrome Association for development of the Williams Syndrome
Patient and Clinical Research Registry
FX Supported in part by a grant from the Williams Syndrome Association for
development of the Williams Syndrome Patient and Clinical Research
Registry (see the Supplementary Appendix). No other potential conflict
of interest relevant to this article was reported.
NR 95
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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 JAN 21
PY 2010
VL 362
IS 3
BP 239
EP 252
DI 10.1056/NEJMra0903074
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 545NE
UT WOS:000273738400010
PM 20089974
ER
PT J
AU Isselbacher, EM
Kligerman, SJ
Lam, KM
Hurtado, RM
AF Isselbacher, Eric M.
Kligerman, Seth J.
Lam, Kaitlyn M.
Hurtado, Rocio M.
TI A Man with Abdominal and Flank Pain Chronic infection with Trypanosoma
cruzi (Chagas' disease) and cardiomyopathy, apical left ventricular
aneurysm, and thromboembolic disease with renal infarctions
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HEART-DISEASE; HYPERTROPHIC CARDIOMYOPATHY; ECHOCARDIOGRAPHY
C1 [Isselbacher, Eric M.; Lam, Kaitlyn M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Hurtado, Rocio M.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Kligerman, Seth J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kligerman, Seth J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Isselbacher, Eric M.; Lam, Kaitlyn M.; Hurtado, Rocio M.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Kligerman, Seth J.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA.
RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
NR 26
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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 JAN 21
PY 2010
VL 362
IS 3
BP 254
EP 262
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 545NE
UT WOS:000273738400013
PM 20089976
ER
PT J
AU Clay, R
Camann, W
AF Clay, Rayna
Camann, William
TI Case 33-2009: A Woman with Fever after Cesarean Section
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID PROPHYLAXIS; DELIVERY
C1 [Clay, Rayna; Camann, William] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Clay, R (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM wcamann@partners.org
NR 6
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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 JAN 21
PY 2010
VL 362
IS 3
BP 273
EP 273
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 545NE
UT WOS:000273738400025
PM 20089983
ER
PT J
AU del Carmen, MG
de Moya, MA
AF del Carmen, Marcela G.
de Moya, Marc A.
TI Case 33-2009: A Woman with Fever after Cesarean Section REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [del Carmen, Marcela G.; de Moya, Marc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 6
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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 JAN 21
PY 2010
VL 362
IS 3
BP 273
EP 274
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 545NE
UT WOS:000273738400026
ER
PT J
AU Chen, LL
Ulmer, S
Deisboeck, TS
AF Chen, L. Leon
Ulmer, Stephan
Deisboeck, Thomas S.
TI An agent-based model identifies MRI regions of probable tumor invasion
in a patient with glioblastoma
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID FUNCTIONAL DIFFUSION MAP; BRAIN-TUMORS; MALIGNANT GLIOMAS;
CELL-MIGRATION; BIOMARKER; GROWTH; BEVACIZUMAB; RESECTION; ONCOLOGY
AB We present an application of a previously developed agent-based glioma model (Chen et al 2009 Biosystems 95 234-42) for predicting spatio-temporal tumor progression using a patient-specific MRI lattice derived from apparent diffusion coefficient (ADC) data. Agents representing collections of migrating glioma cells are initialized based upon voxels at the outer border of the tumor identified on T1-weighted (Gd+) MRI at an initial time point. These simulated migratory cells exhibit a specific biologically inspired spatial search paradigm, representing a weighting of the differential contribution from haptotactic permission and biomechanical resistance on the migration decision process. ADC data from 9 months after the initial tumor resection were used to select the best search paradigm for the simulation, which was initiated using data from 6 months after the initial operation. Using this search paradigm, 100 simulations were performed to derive a probabilistic map of tumor invasion locations. The simulation was able to successfully predict a recurrence in the dorsal/posterior aspect long before it was depicted on T1-weighted MRI, 18 months after the initial operation.
C1 [Chen, L. Leon; Deisboeck, Thomas S.] Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA USA.
[Ulmer, Stephan] Univ Hosp Schleswig Holstein, Inst Neuroradiol, Kiel, Germany.
RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Complex Biosyst Modeling Lab, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Charlestown, MA USA.
EM DEISBOEC@helix.mgh.harvard.edu
FU NIH [CA 113004]; Harvard-MIT (HST) Athinoula A Martinos Center for
Biomedical Imaging and the Department of Radiology at Massachusetts
General Hospital
FX This work has been supported in part by NIH grant CA 113004 and by the
Harvard-MIT (HST) Athinoula A Martinos Center for Biomedical Imaging and
the Department of Radiology at Massachusetts General Hospital.
NR 30
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U1 0
U2 4
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JAN 21
PY 2010
VL 55
IS 2
BP 329
EP 338
DI 10.1088/0031-9155/55/2/001
PG 10
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 535IG
UT WOS:000272960400001
PM 20019405
ER
PT J
AU Chan, TCY
Tsitsiklis, JN
Bortfeld, T
AF Chan, Timothy C. Y.
Tsitsiklis, John N.
Bortfeld, Thomas
TI Optimal margin and edge-enhanced intensity maps in the presence of
motion and uncertainty
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID MODULATED RADIATION-THERAPY; X-RAY-BEAM; DOSE DISTRIBUTIONS; IMRT
OPTIMIZATION; RADIOTHERAPY; PROBABILITY; ORGAN; REDUCTION; PROFILES
AB In radiation therapy, intensity maps involving margins have long been used to counteract the effects of dose blurring arising from motion. More recently, intensity maps with increased intensity near the edge of the tumour (edge enhancements) have been studied to evaluate their ability to offset similar effects that affect tumour coverage. In this paper, we present a mathematical methodology to derive margin and edge-enhanced intensity maps that aim to provide tumour coverage while delivering minimum total dose. We show that if the tumour is at most about twice as large as the standard deviation of the blurring distribution, the optimal intensity map is a pure scaling increase of the static intensity map without any margins or edge enhancements. Otherwise, if the tumour size is roughly twice (or more) the standard deviation of motion, then margins and edge enhancements are preferred, and we present formulae to calculate the exact dimensions of these intensity maps. Furthermore, we extend our analysis to include scenarios where the parameters of the motion distribution are not known with certainty, but rather can take any value in some range. In these cases, we derive a similar threshold to determine the structure of an optimal margin intensity map.
C1 [Chan, Timothy C. Y.] Univ Toronto, Toronto, ON M5S 3G8, Canada.
[Tsitsiklis, John N.] MIT, Informat & Decis Syst Lab, Cambridge, MA 02139 USA.
[Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Chan, TCY (reprint author), Univ Toronto, Toronto, ON M5S 3G8, Canada.
EM tcychan@mie.utoronto.ca; jnt@mit.edu; tbortfeld@partners.org
FU NCI NIH HHS [R01-CA118200, R01-CA103904]
NR 30
TC 8
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U1 0
U2 0
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JAN 21
PY 2010
VL 55
IS 2
BP 515
EP 533
DI 10.1088/0031-9155/55/2/012
PG 19
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 535IG
UT WOS:000272960400012
PM 20023327
ER
PT J
AU Nakamura, K
Sasajima, J
Mizukami, Y
Sugiyama, Y
Yamazaki, M
Fujii, R
Kawamoto, T
Koizumi, K
Sato, K
Fujiya, M
Sasaki, K
Tanno, S
Okumura, T
Shimizu, N
Kawabe, J
Karasaki, H
Kono, T
Ii, M
Bardeesy, N
Chung, DC
Kohgo, Y
AF Nakamura, Kazumasa
Sasajima, Junpei
Mizukami, Yusuke
Sugiyama, Yoshiaki
Yamazaki, Madoka
Fujii, Rie
Kawamoto, Toru
Koizumi, Kazuya
Sato, Kazuya
Fujiya, Mikihiro
Sasaki, Katsunori
Tanno, Satoshi
Okumura, Toshikatsu
Shimizu, Norihiko
Kawabe, Jun-ichi
Karasaki, Hidenori
Kono, Toru
Ii, Masaaki
Bardeesy, Nabeel
Chung, Daniel C.
Kohgo, Yutaka
TI Hedgehog Promotes Neovascularization in Pancreatic Cancers by Regulating
Ang-1 and IGF-1 Expression in Bone-Marrow Derived Pro-Angiogenic Cells
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL PROGENITOR CELLS; MESENCHYMAL STEM-CELLS; SONIC HEDGEHOG;
BRANCHING MORPHOGENESIS; GENE-THERAPY; FACTOR-I; GROWTH; TUMOR;
DIFFERENTIATION; LUNG
AB Background: The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that the oncogenic function of Hh in PDAC involves signaling in the stromal cells rather than cell autonomous effects on the tumor cells. However, the origin and nature of the stromal cell type(s) that are responsive to Hh signaling remained unknown. Since Hh signaling plays a crucial role during embryonic and postnatal vasculogenesis, we speculated that Hh ligand may act on tumor vasculature specifically focusing on bone marrow (BM)-derived cells.
Methodology/Principal Findings: Cyclopamine was utilized to inhibit the Hh pathway in human PDAC cell lines and their xenografts. BM transplants, co-culture systems of tumor cells and BM-derived pro-angiogenic cells (BMPCs) were employed to assess the role of tumor-derived Hh in regulating the BM compartment and the contribution of BM-derived cells to angiogenesis in PDAC. Cyclopamine administration attenuated Hh signaling in the stroma rather than in the cancer cells as reflected by decreased expression of full length Gli2 protein and Gli1 mRNA specifically in the compartment. Cyclopamine inhibited the growth of PDAC xenografts in association with regression of the tumor vasculature and reduced homing of BM-derived cells to the tumor. Host-derived Ang-1 and IGF-1 mRNA levels were downregulated by cyclopamine in the tumor xenografts. In vitro co-culture and matrigel plug assays demonstrated that PDAC cell-derived Shh induced Ang-1 and IGF-1 production in BMPCs, resulting in their enhanced migration and capillary morphogenesis activity.
Conclusions/Significance: We identified the BMPCs as alternative stromal targets of Hh-ligand in PDAC suggesting that the tumor vasculature is an attractive therapeutic target of Hh blockade. Our data is consistent with the emerging concept that BM-derived cells make important contributions to epithelial tumorigenesis.
C1 [Nakamura, Kazumasa; Sasajima, Junpei; Mizukami, Yusuke; Sugiyama, Yoshiaki; Yamazaki, Madoka; Fujii, Rie; Kawamoto, Toru; Koizumi, Kazuya; Sato, Kazuya; Fujiya, Mikihiro; Sasaki, Katsunori; Tanno, Satoshi; Kohgo, Yutaka] Asahikawa Med Coll, Div Gastroenterol & Hematol Oncol, Dept Med, Asahikawa, Hokkaido 078, Japan.
[Tanno, Satoshi; Okumura, Toshikatsu] Asahikawa Med Coll, Dept Gen Med, Asahikawa, Hokkaido 078, Japan.
[Shimizu, Norihiko] Asahikawa Med Coll, Dept Anim Facil, Asahikawa, Hokkaido 078, Japan.
[Kawabe, Jun-ichi] Asahikawa Med Coll, Dept Cardiovasc Regenerat & Innovat, Asahikawa, Hokkaido 078, Japan.
[Karasaki, Hidenori; Kono, Toru] Asahikawa Med Coll, Div Gastroenterol & Gen Surg, Dept Surg, Asahikawa, Hokkaido 078, Japan.
[Ii, Masaaki] Inst Biomed Res & Innovat, Grp Vasc Regenerat Res, Kobe, Hyogo, Japan.
[Bardeesy, Nabeel; Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Bardeesy, Nabeel; Chung, Daniel C.] Harvard Univ, Sch Med, Boston, MA USA.
[Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Nakamura, K (reprint author), Asahikawa Med Coll, Div Gastroenterol & Hematol Oncol, Dept Med, Asahikawa, Hokkaido 078, Japan.
EM mizu@asahikawa-med.ac.jp
FU New Energy and Industrial Technology Development Organization of Japan
[07A05010a]
FX This work was supported by a grant to Y. M. from the New Energy and
Industrial Technology Development Organization of Japan (07A05010a). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 60
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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 JAN 21
PY 2010
VL 5
IS 1
AR e8824
DI 10.1371/journal.pone.0008824
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 546AJ
UT WOS:000273779100016
PM 20098680
ER
PT J
AU Gaziano, JM
AF Gaziano, J. Michael
TI Fifth Phase of the Epidemiologic Transition The Age of Obesity and
Inactivity
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CARDIOVASCULAR-DISEASE; UNITED-STATES; OVERWEIGHT; SMOKING; MORTALITY;
TRENDS; CHINA
C1 [Gaziano, J. Michael] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02130 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Cardiol, Dept Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA.
RP Gaziano, JM (reprint author), VA Boston Healthcare Syst, Massachusetts Vet Res & Informat Ctr 151MAV, 150 S Huntington Ave, Boston, MA 02130 USA.
EM jmgaziano@partners.org
NR 14
TC 44
Z9 46
U1 0
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 20
PY 2010
VL 303
IS 3
BP 275
EP 276
DI 10.1001/jama.2009.2025
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 544WM
UT WOS:000273690600027
PM 20071469
ER
PT J
AU Clough-Gorr, KM
Stuck, AE
Thwin, SS
Silliman, RA
AF Clough-Gorr, Kerri M.
Stuck, Andreas E.
Thwin, Soe Soe
Silliman, Rebecca A.
TI Older Breast Cancer Survivors: Geriatric Assessment Domains Are
Associated With Poor Tolerance of Treatment Adverse Effects and Predict
Mortality Over 7 Years of Follow-Up
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; FUNCTIONAL ASSESSMENT; ADJUVANT TAMOXIFEN;
CONTROLLED-TRIALS; SOCIAL SUPPORT; AGE; CHEMOTHERAPY; ONCOLOGY; WOMEN;
CARE
AB Purpose
To evaluate geriatric assessment (GA) domains in relation to clinically important outcomes in older breast cancer survivors.
Methods
Six hundred sixty women diagnosed with primary breast cancer in four US geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island) were selected with disease stage I to IIIA, age >= 65 years at date of diagnosis, and permission from attending physician to contact. Data were collected over 7 years of follow-up from consenting patients' medical records, telephone interviews, physician questionnaires, and the National Death Index. Outcomes included self-reported treatment tolerance and all-cause mortality. Four GA domains were described by six individual measures, as follows: sociodemographic by adequate finances; clinical by Charlson comorbidity index (CCI) and body mass index; function by number of physical function limitations; and psychosocial by the five-item Mental Health Index (MHI5) and Medical Outcomes Study Social Support Survey (MOS-SSS). Associations were evaluated using t tests, chi(2) tests, and regression analyses.
Results
In multivariable regression including age and stage, three measures from two domains (clinical and psychosocial) were associated with poor treatment tolerance; these were CCI >= 1 (odds ratio [OR] = 2.49; 95% CI, 1.18 to 5.25), MHI5 score less than 80 (OR = 2.36; 95% CI, 1.15 to 4.86), and MOS-SSS score less than 80 (OR = 3.32; 95% CI, 1.44 to 7.66). Four measures representing all four GA domains predicted mortality; these were inadequate finances (hazard ratio [HR] = 1.89; 95% CI, 1.24 to 2.88; CCI >= 1 (HR = 1.38; 95% CI, 1.01 to 1.88), functional limitation (HR = 1.40; 95% CI, 1.01 to 1.93), and MHI5 score less than 80 (HR = 1.34; 95% CI, 1.01 to 1.85). In addition, the proportion of women with these outcomes incrementally increased as the number of GA deficits increased.
Conclusion
This study provides longitudinal evidence that GA domains are associated with poor treatment tolerance and predict mortality at 7 years of follow-up, independent of age and stage of disease.
C1 [Clough-Gorr, Kerri M.] Boston Univ, Med Ctr, Sch Med, Sect Geriatr, Boston, MA 02118 USA.
Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
US Dept Vet Affairs, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
Univ Bern, ISPM, CH-3012 Bern, Switzerland.
Univ Hosp Bern, Inselspital, Dept Geriatr, CH-3010 Bern, Switzerland.
RP Clough-Gorr, KM (reprint author), Boston Univ, Med Ctr, Sch Med, Sect Geriatr, 88 E Newton St,Robinson 2, Boston, MA 02118 USA.
EM kmclough@bu.edu
FU National Cancer Institute, Bethesda, MD [CA106979, CA/AG 70818, CA84506]
FX Supported by Grants No. CA106979, CA/AG 70818, and CA84506 from the
National Cancer Institute, Bethesda, MD.
NR 67
TC 46
Z9 47
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 JAN 20
PY 2010
VL 28
IS 3
BP 380
EP 386
DI 10.1200/JCO.2009.23.5440
PG 7
WC Oncology
SC Oncology
GA 544MY
UT WOS:000273662700005
PM 20008637
ER
PT J
AU Balboni, TA
Paulk, ME
Balboni, MJ
Phelps, AC
Loggers, ET
Wright, AA
Block, SD
Lewis, EF
Peteet, JR
Prigerson, HG
AF Balboni, Tracy Anne
Paulk, Mary Elizabeth
Balboni, Michael J.
Phelps, Andrea C.
Loggers, Elizabeth Trice
Wright, Alexi A.
Block, Susan D.
Lewis, Eldrin F.
Peteet, John R.
Prigerson, Holly Gwen
TI Provision of Spiritual Care to Patients With Advanced Cancer:
Associations With Medical Care and Quality of Life Near Death
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TREATMENT PREFERENCES; TERMINALLY-ILL; ETHNIC-DIFFERENCES; PALLIATIVE
CARE; BREAST-CANCER; END; NEEDS; HOPE; ACKNOWLEDGMENT; ACCEPTABILITY
AB Purpose
To determine whether spiritual care from the medical team impacts medical care received and quality of life (QoL) at the end of life (EoL) and to examine these relationships according to patient religious coping.
Patients and Methods
Prospective, multisite study of patients with advanced cancer from September 2002 through August 2008. We interviewed 343 patients at baseline and observed them (median, 116 days) until death. Spiritual care was defined by patient-rated support of spiritual needs by the medical team and receipt of pastoral care services. The Brief Religious Coping Scale (RCOPE) assessed positive religious coping. EoL outcomes included patient QoL and receipt of hospice and any aggressive care (eg, resuscitation). Analyses were adjusted for potential confounders and repeated according to median-split religious coping.
Results
Patients whose spiritual needs were largely or completely supported by the medical team received more hospice care in comparison with those not supported (adjusted odds ratio [AOR] = 3.53; 95% CI, 1.53 to 8.12, P = .003). High religious coping patients whose spiritual needs were largely or completely supported were more likely to receive hospice (AOR = 4.93; 95% CI, 1.64 to 14.80; P = .004) and less likely to receive aggressive care (AOR = 0.18; 95% CI, 0.04 to 0.79; P = .02) in comparison with those not supported. Spiritual support from the medical team and pastoral care visits were associated with higher QOL scores near death (20.0 [95% CI, 18.9 to 21.1] v 17.3 [95% CI, 15.9 to 18.8], P = .007; and 20.4 [95% CI, 19.2 to 21.1] v 17.7 [95% CI, 16.5 to 18.9], P = .003, respectively).
Conclusion
Support of terminally ill patients' spiritual needs by the medical team is associated with greater hospice utilization and, among high religious copers, less aggressive care at EoL. Spiritual care is associated with better patient QoL near death.
C1 [Balboni, Tracy Anne] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 01225 USA.
Dana Farber Canc Inst, Dept Psychooncol & Palliat Care, Boston, MA 01225 USA.
Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 01225 USA.
Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 01225 USA.
Boston Univ, Dept Pract Theol, Boston, MA 02215 USA.
Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA USA.
Harvard Univ, Brigham & Womens Hosp, Ctr Palliat Care, Dept Med,Med Sch,Cardiovasc Div, Boston, MA 02115 USA.
Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
RP Balboni, TA (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Smith 275,44 Binney St, Boston, MA 01225 USA.
EM tbalboni@lroc.harvard.edu
FU National Institute of Mental Health [MH63892]; National Cancer Institute
[CA 106370]; Fetzer Foundation; American Society of Clinical Oncology
FX Supported in part by the following grants to H. G. P.: Grant No. MH63892
from the National Institute of Mental Health, Grant No. CA 106370 from
the National Cancer Institute, and a Fetzer Foundation grant. This
research was also supported in part by an American Society of Clinical
Oncology Young Investigator Award to T. A. B.
NR 37
TC 121
Z9 123
U1 4
U2 15
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 JAN 20
PY 2010
VL 28
IS 3
BP 445
EP 452
DI 10.1200/JCO.2009.24.8005
PG 8
WC Oncology
SC Oncology
GA 544MY
UT WOS:000273662700015
PM 20008625
ER
PT J
AU Santillan, AA
Messina, JL
Marzban, SS
Crespo, G
Sondak, VK
Zager, JS
AF Santillan, Alfredo A.
Messina, Jane L.
Marzban, Suroosh S.
Crespo, Gema
Sondak, Vernon K.
Zager, Jonathan S.
TI Pathology Review of Thin Melanoma and Melanoma in Situ in a
Multidisciplinary Melanoma Clinic: Impact on Treatment Decisions
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID AMERICAN-JOINT-COMMITTEE; PRIMARY CUTANEOUS MELANOMA; MANDATORY 2ND
OPINION; LYMPH-NODE POSITIVITY; MALIGNANT-MELANOMA; STAGING SYSTEM;
MITOTIC RATE; INTEROBSERVER VARIABILITY; BRESLOW DEPTH; CLARK LEVEL
AB Purpose
Patients with thin melanoma (<= 1.0 mm) and melanoma in situ (MIS) represent the majority of newly diagnosed melanoma. We estimated the impact of expert review of outside pathology material on the staging and thus treatment decisions affecting patients referred to a multidisciplinary clinic with early-stage melanoma.
Patients and Methods
We studied patients with a diagnosis of thin melanoma or MIS referred to H. Lee Moffitt Cancer Center from 2006 to 2009. After comparing the referring laboratory and in-house dermatopathologic interpretations, we calculated any differences in diagnosis and tumor staging and the potential impact of differences in diagnosis and staging on prognosis and surgical treatment using the National Comprehensive Cancer Network clinical guidelines.
Results
The overall pathologic discordance rate in diagnosis was 4% (15 of 420 patients; 95% CI, 2% to 6%). The overall change in tumor staging rate was 24% (97 of 405 patients; 95% CI, 20% to 28%). Pathology review led to changes in surgical excision margins in 12% of patients (52 of 420 patients; 95% CI, 9% to 16%) and in the decision about whether to perform a sentinel lymph node biopsy in 16% of patients (67 of 420 patients; 95% CI, 13% to 20%). Key pathologic factors, particularly mitotic rate, were frequently missing from outside pathology reports.
Conclusion
Our data suggest that review of thin melanoma or MIS by an expert dermatopathologist results in frequent, clinically meaningful alterations in diagnosis, staging, prognosis, and surgical treatment. Referral of these patients to a multidisciplinary melanoma clinic is appropriate, and management of such patients should include review of the biopsy whenever feasible.
C1 Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, Sect Surg Oncol, San Antonio, TX USA.
Audie L Murphy Vet Affairs Hosp, Sect Surg Oncol, San Antonio, TX USA.
Univ S Florida, Coll Med, Dept Oncol Sci, Tampa, FL USA.
Univ S Florida, Coll Med, Dept Dermatol, Tampa, FL USA.
Univ S Florida, Coll Med, Dept Surg, Tampa, FL 33612 USA.
RP Zager, JS (reprint author), 12902 Magnolia Dr,SRB4-24012, Tampa, FL 33602 USA.
EM jonathan.zager@moffitt.org
NR 29
TC 26
Z9 26
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2010
VL 28
IS 3
BP 481
EP 486
DI 10.1200/JCO.2009.24.7734
PG 6
WC Oncology
SC Oncology
GA 544MY
UT WOS:000273662700020
PM 20008627
ER
PT J
AU Wong, SL
Mangu, PB
Choti, MA
Crocenzi, TS
Dodd, GD
Dorfman, GS
Eng, C
Fong, YM
Giusti, AF
Lu, D
Marsland, TA
Michelson, R
Poston, GJ
Schrag, D
Seidenfeld, J
Benson, A
AF Wong, Sandra L.
Mangu, Pamela B.
Choti, Michael A.
Crocenzi, Todd S.
Dodd, Gerald D., III
Dorfman, Gary S.
Eng, Cathy
Fong, Yuman
Giusti, Andrew F.
Lu, David
Marsland, Thomas A.
Michelson, Rob
Poston, Graeme J.
Schrag, Deborah
Seidenfeld, Jerome
Benson, Al B., III
TI American Society of Clinical Oncology 2009 Clinical Evidence Review on
Radiofrequency Ablation of Hepatic Metastases From Colorectal Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID LONG-TERM SURVIVAL; POSITRON-EMISSION-TOMOGRAPHY; UNRESECTABLE
LIVER-TUMORS; THERMAL ABLATION; RISK-FACTORS; SURGICAL-TREATMENT;
HEPATOBILIARY MALIGNANCY; PERCUTANEOUS ABLATION; CARCINOMA METASTASES;
DIAPHRAGMATIC INJURY
AB Purpose
To review the evidence about the efficacy and utility of radiofrequency ablation (RFA) for hepatic metastases from colorectal cancer (CRHM).
Methods
The American Society of Clinical Oncology (ASCO) convened a panel to conduct and analyze a comprehensive systematic review of the RFA literature from Medline and the Cochrane Collaboration Library.
Results
Because data were considered insufficient to form the basis of a practice guideline, ASCO has instead published a clinical evidence review. The evidence is from single-arm, retrospective, and prospective trials. No randomized controlled trials have been included. The following three clinical issues were considered by the panel: the efficacy of surgical hepatic resection versus RFA for resectable tumors; the utility of RFA for unresectable tumors; and RFA approaches (open, laparoscopic, or percutaneous). Evidence suggests that hepatic resection improves overall survival (OS), particularly for patients with resectable tumors without extrahepatic disease. Careful patient and tumor selection is discussed at length in the literature. RFA investigators report a wide variability in the 5-year survival rate (14% to 55%) and local tumor recurrence rate (3.6% to 60%). The reported mortality rate was low (0% to 2%), and the major complications rate was commonly reported to be between 6% and 9%. RFA is currently performed with all three approaches.
Conclusion
There is a compelling need for more research to determine the efficacy and utility of RFA to increase local recurrence-free, progression-free, and disease-free survival as well as OS for patients with CRHM. Clinical trials have established that hepatic resection can improve OS for patients with resectable CRHM.
C1 [Wong, Sandra L.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Colorectal Canc Coalit, Alexandria, VA USA.
Johns Hopkins Univ, Baltimore, MD USA.
Oregon Clin, Portland, OR USA.
Univ Colorado, Sch Med, Denver, CO USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, New York, NY 10021 USA.
Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
Orange Pk Canc Ctr, Orange Pk, FL USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Northwestern Univ, Chicago, IL 60611 USA.
Aintree Univ Hosp NHS Fdn Trust, Liverpool L9 7AL, Merseyside, England.
RP Wong, SL (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd, Alexandria, VA 22314 USA.
EM guidelines@asco.org
NR 147
TC 173
Z9 194
U1 5
U2 15
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 JAN 20
PY 2010
VL 28
IS 3
BP 493
EP 508
DI 10.1200/JCO.2009.23.4450
PG 16
WC Oncology
SC Oncology
GA 544MY
UT WOS:000273662700022
PM 19841322
ER
PT J
AU Allen, PM
Liu, WH
Chauhan, VP
Lee, J
Ting, AY
Fukumura, D
Jain, RK
Bawendi, MG
AF Allen, Peter M.
Liu, Wenhao
Chauhan, Vikash P.
Lee, Jungmin
Ting, Alice Y.
Fukumura, Dai
Jain, Rakesh K.
Bawendi, Moungi G.
TI InAs(ZnCdS) Quantum Dots Optimized for Biological Imaging in the
Near-Infrared
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID CORE-SHELL NANOCRYSTALS; IN-VIVO; BIOTIN LIGASE; LIVING CELLS; SIZE
SERIES; MONOVALENT; PROTEINS
AB We present the synthesis of InAs quantum dots (QDs) with a ZnCdS shell with bright and stable emission in the near-infrared (NIR, 700-900 nm) region for biological imaging applications, We demonstrate how NIR QDs can image tumor vasculature in vivo at significantly deeper penetration depths and with higher contrast than visible emitting CdSe(CdS) QDs. Targeted cellular labeling is also presented and may enable multiplexed and low auto fluorescence cellular imaging.
C1 [Allen, Peter M.; Liu, Wenhao; Lee, Jungmin; Ting, Alice Y.; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Chauhan, Vikash P.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
[Chauhan, Vikash P.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM mgb@mit.edu
RI Chauhan, Vikash/H-8172-2013
OI Chauhan, Vikash/0000-0001-9126-2302
FU US NCI [R01-CA85140, R01-CA115767, R01-CA126642, P01-CA80124];
MIT-Harvard NIH CCNE [1U54-CA119349]; US ARO through the ISN
[W911NF-07-D-0004]; NSF-MRSEC [DMR-0117795]
FX This work was supported by the US NCI grants R01-CA85140, R01-CA115767
(R.K.J.), R01-CA126642 (R.K.J. and M.G.B.) and P01-CA80124 (R.K.J. and
D.F.), by the MIT-Harvard NIH CCNE (1U54-CA119349) (M.G.B.), by the US
ARO through the ISN (W911NF-07-D-0004) (M.G.B.), and the NSF-MRSEC
program (DMR-0117795). We thank D. Liu and P. Zou for providing cells
and plasmids.
NR 15
TC 106
Z9 107
U1 8
U2 77
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JAN 20
PY 2010
VL 132
IS 2
BP 470
EP +
DI 10.1021/ja908250r
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 562VY
UT WOS:000275084600021
PM 20025222
ER
PT J
AU Liu, WH
Greytak, AB
Lee, J
Wong, CR
Park, J
Marshall, LF
Jiang, W
Curtin, PN
Ting, AY
Nocera, DG
Fukumura, D
Jain, RK
Bawendi, MG
AF Liu, Wenhao
Greytak, Andrew B.
Lee, Jungmin
Wong, Cliff R.
Park, Jongnam
Marshall, Lisa F.
Jiang, Wen
Curtin, Peter N.
Ting, Alice Y.
Nocera, Daniel G.
Fukumura, Dai
Jain, Rakesh K.
Bawendi, Moungi G.
TI Compact Biocompatible Quantum Dots via RAFT-Mediated Synthesis of
Imidazole-Based Random Copolymer Ligand
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID SEMICONDUCTOR NANOCRYSTALS; MONOVALENT STREPTAVIDIN; SURFACE
MODIFICATION; BIOTIN LIGASE; LIVING CELLS; SIZE SERIES; LIVE CELLS;
CDSE; LUMINESCENT; RECEPTORS
AB We present a new class of polymeric ligands for quantum dot (OD) water solubilization to yield biocompatible and derivatizable QDs with compact size (similar to 10-12 nm diameter), high quantum yields (>50%), excellent stability across a large pH range (pH 5-10.5), and low nonspecific binding. To address the fundamental problem of thiol instability in traditional ligand exchange systems, the polymers here employ a stable multidentate imidazole binding motif to the OD surface. The polymers are synthesized via reversible addition-fragmentation chain transfer-mediated polymerization to produce molecular weight controlled monodisperse random copolymers from three types of monomers that feature imidazole groups for CID binding, polyethylene glycol (PEG) groups for water solubilization, and either primary amines or biotin groups for derivatization. The polymer architecture can be tuned by the monomer ratios to yield aqueous QDs with targeted surface functionalities. By incorporating amino-PEG monomers, we demonstrate covalent conjugation of a dye to form a highly efficient QD-dye energy transfer pair as well as covalent conjugation to streptavidin for high-affinity single molecule imaging of biotinylated receptors on live cells with minimal nonspecific binding. The small size and low serum binding of these polymer-coated QDs also allow us to demonstrate their utility for in vivo imaging of the tumor microenvironment in live mice.
C1 [Liu, Wenhao; Greytak, Andrew B.; Lee, Jungmin; Wong, Cliff R.; Park, Jongnam; Marshall, Lisa F.; Curtin, Peter N.; Ting, Alice Y.; Nocera, Daniel G.; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Jiang, Wen; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
[Jiang, Wen; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM mgb@mit.edu
RI Park, Jongnam/F-5085-2010;
OI Park, Jongnam/0000-0002-0954-0172; Greytak, Andrew/0000-0001-8978-6457;
Jiang, Wen/0000-0001-9154-633X
FU U.S. National Cancer Institute [R01-CA126642, R01-CA085140,
R01-CA115767, P01-CA080124, R01-CA096915]; MIT-Harvard NIH Center for
Cancer Nanotechnology Excellence [1U54-CA119349]; MIT DCIF [CHE-980806,
DBI-9729592]; ISN [W911NF-07-D-0004]; NSF-MRSEC [DMR-0117795]; Army
Research Office [W911NF-06-1-0101]; National Science Foundation; Life
Sciences Research Foundation
FX This research was supported by the U.S. National Cancer Institute Grants
Nos. R01-CA126642 (R.K.J., M.G.B., and D.G.N.), R01-CA085140,
R01-CA115767 (R.K.J.), P01-CA080124 (R.K.J. and D.F.), R01-CA096915
(D.F.); by the MIT-Harvard NIH Center for Cancer Nanotechnology
Excellence (1U54-CA119349) (M.G.B.); by the MIT DCIF (CHE-980806,
DBI-9729592); by the ISN (W911NF-07-D-0004) (M.G.B. and D.G.N.); by the
NSF-MRSEC program (DMR-0117795) via the use of its shared user
facilities; and by the Army Research Office (W911NF-06-1-0101) (D.G.N).
W.L. was supported by a National Science Foundation Graduate Research
Fellowship. A.B.G. was a Novartis fellow of the Life Sciences Research
Foundation. We would like to thank Dan Liu and Peng Zou for valuable
assistance with cells, plasmids, and cell culture protocols.
NR 52
TC 143
Z9 145
U1 8
U2 98
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JAN 20
PY 2010
VL 132
IS 2
BP 472
EP 483
DI 10.1021/ja908137d
PG 12
WC Chemistry, Multidisciplinary
SC Chemistry
GA 562VY
UT WOS:000275084600022
PM 20025223
ER
PT J
AU Wolpin, BM
Kraft, P
Fuchs, CS
AF Wolpin, Brian M.
Kraft, Peter
Fuchs, Charles S.
TI Re: ABO Blood Group and the Risk of Pancreatic Cancer Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID EXPRESSION; CARCINOMA
C1 [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Fuchs, Charles S.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab,Med Sch, Boston, MA 02115 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM bwolpin@partners.org
NR 4
TC 0
Z9 0
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JAN 20
PY 2010
VL 102
IS 2
BP 137
EP 137
DI 10.1093/jnci/djp449
PG 1
WC Oncology
SC Oncology
GA 549YO
UT WOS:000274091200016
ER
PT J
AU Ma, CHE
Bampton, ETW
Evans, MJ
Taylor, JSH
AF Ma, C. H. E.
Bampton, E. T. W.
Evans, M. J.
Taylor, J. S. H.
TI SYNERGISTIC EFFECTS OF OSTEONECTIN AND BRAIN-DERIVED NEUROTROPHIC FACTOR
ON AXOTOMIZED RETINAL GANGLION CELLS NEURITE OUTGROWTH VIA THE
MITOGEN-ACTIVATED PROTEIN KINASE-EXTRACELLULAR SIGNAL-REGULATED
KINASE1/2 PATHWAYS
SO NEUROSCIENCE
LA English
DT Article
DE MAPK-ERK1/2; neurite outgrowth; osteonectin; PI-3K-Akt; retinal ganglion
cell; Schwann cell
ID NERVE GROWTH-FACTOR; ENDOTHELIAL-CELLS; TYROSINE PHOSPHORYLATION;
NEURONAL SURVIVAL; GENE-EXPRESSION; SCHWANN-CELLS; AXON GROWTH;
MATRICELLULAR PROTEIN; MATRIX GLYCOPROTEIN; CELLULAR-SURVIVAL
AB Our previous study identified osteonectin (ON) in a screen of factors made by Schwann cells (SCs) which promoted peripheral and central neurons survival and neuritogenesis, however, the mechanisms of ON promoting effects are largely unknown. In the present study, we investigated the effects of ON-deficient SC-conditioned medium (SCCM) and molecular mechanisms of ON, in regulating retinal ganglion cells (RGCs) survival and neurite outgrowth. Neonatal rat RGCs and SCs were purified by immunopanning technique. RGC survival and neuritogenesis reduced significantly when treated with either ON-null mice SCCM or ON-immunodepleted (IP) SCCM (P<0.05). In contrast to wild type SCCM, in the presence of a tyrosine kinase receptor (Trk) inhibitor (K252a), ON-null mice SCCM-induced neuritogenesis were further reduced by 24%. The Trk-mediated signaling pathways became more sensitive to K252a inhibition in the absence of ON. We also showed the synergistic effects of ON and brain-derived neurotrophic factor (BDNF) in promoting RGCs growth and the involvement of ON in two major neurotrophin-mediated signaling pathways, PI-3K-Akt and MAPK-Erk1/2. ON alone activated Akt phosphorylation and increased survival. Blockage of TrkB signalling pathway by TrkB-Fc chimera (BDNF scavenger) or K252a in ON-treated cultures reduced Akt-P level significantly. This suggests that ON induces BDNF synthesis and secretion from RGCs. The enhancement of neuritogenesis and Erk1/2 phosphorylation by ON in BDNF-treated cultures further demonstrate the signaling pathways responsible for the synergistic effect of ON on BDNF-induced neurite outgrowth. To the best of our knowledge, this is the first report showing the synergistic effects of ON on classical neurotrophins which participate in the same signalling pathways in regulating RGC neurite outgrowth. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Ma, C. H. E.; Bampton, E. T. W.; Taylor, J. S. H.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
[Evans, M. J.] Cardiff Univ, Sch Biosci, Cardiff CF10 3US, S Glam, Wales.
RP Ma, CHE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 Bldg,13th St,Room 4309, Charlestown, MA 02129 USA.
EM chi.ma@mgh.harvard.edu
OI MA, Chi Him Eddie/0000-0003-2054-0445
FU Hong Kong Croucher Foundation (CHEM)
FX We thank the Hong Kong Croucher Foundation (CHEM) for financial support.
Dr. Chi Me is a recipient of the Hong Kong Croucher Foundation
Scholarship.
NR 91
TC 12
Z9 14
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD JAN 20
PY 2010
VL 165
IS 2
BP 463
EP 474
DI 10.1016/j.neuroscience.2009.10.026
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 545IC
UT WOS:000273724700017
PM 19837135
ER
PT J
AU Forsberg, EC
Passegue, E
Prohaska, SS
Wagers, AJ
Koeva, M
Stuart, JM
Weissman, IL
AF Forsberg, E. Camilla
Passegue, Emmanuelle
Prohaska, Susan S.
Wagers, Amy J.
Koeva, Martina
Stuart, Joshua M.
Weissman, Irving L.
TI Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating
Hematopoietic Stem Cells
SO PLOS ONE
LA English
DT Article
ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; MURINE BONE-MARROW;
SELF-RENEWAL; GENE-EXPRESSION; MYELOPROLIFERATIVE DISORDER;
TRANSCRIPTION FACTOR; PROGENITOR CELLS; NF-Y; DIFFERENTIATION
AB Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.
C1 [Forsberg, E. Camilla; Koeva, Martina; Stuart, Joshua M.] Univ Calif Santa Cruz, Dept Biomol Engn, Inst Biol Stem Cells, Santa Cruz, CA 95064 USA.
[Passegue, Emmanuelle] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
[Prohaska, Susan S.; Weissman, Irving L.] Stanford Univ, Sch Med, Dept Pathol, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
[Prohaska, Susan S.; Weissman, Irving L.] Stanford Univ, Sch Med, Dept Dev Biol, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
[Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Joslin Diabet Ctr, Cambridge, MA 02138 USA.
[Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Forsberg, EC (reprint author), Univ Calif Santa Cruz, Dept Biomol Engn, Inst Biol Stem Cells, Santa Cruz, CA 95064 USA.
EM cforsber@ucsc.edu
FU California Institute for Regenerative Medicine; American Society of
Hematology (ASH); Burroughs Wellcome Fund; National Institutes of Health
(NIH) [1RO1HL092471-01, 1RO1HL088582-01, R01CA086017, R01HL058770,
R01CA086065, P01DK053074]; California Institute for Regenerative
Medicine (CIRM); Department of Biomolecular Engineering, University of
California Santa Cruz; National Science Foundation's Division of
Biological Infrastructure [DBI-0543197]; Alfred P. Sloan Foundation
FX This work was supported by a New Faculty Award from the California
Institute for Regenerative Medicine (ECF); by an American Society of
Hematology (ASH) Scholar Award (EP), by grants from the Burroughs
Wellcome Fund (AJW) and the National Institutes of Health (NIH)
(1RO1HL092471-01 (EP) and 1RO1HL088582-01 (AJW)); a predoctoral
fellowship from the California Institute for Regenerative Medicine
(CIRM) stem cell training program at the Institute for Biology of Stem
Cells, Department of Biomolecular Engineering, University of California
Santa Cruz (MK); the National Science Foundation's Division of
Biological Infrastructure DBI-0543197 (JMS) and by a fellowship from the
Alfred P. Sloan Foundation (JMS); and by NIH grants R01CA086017,
R01HL058770, R01CA086065, and P01DK053074 (ILW). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 83
TC 60
Z9 61
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 20
PY 2010
VL 5
IS 1
AR e8785
DI 10.1371/journal.pone.0008785
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 546AI
UT WOS:000273779000014
PM 20098702
ER
PT J
AU Nandi, A
Lavine, CL
Wang, PC
Lipchina, I
Goepfert, PA
Shaw, GM
Tomaras, GD
Montefiori, DC
Haynes, BF
Easterbrook, P
Robinson, JE
Sodroski, JG
Yang, XZ
AF Nandi, Avishek
Lavine, Christine L.
Wang, Pengcheng
Lipchina, Inna
Goepfert, Paul A.
Shaw, George M.
Tomaras, Georgia D.
Montefiori, David C.
Haynes, Barton F.
Easterbrook, Philippa
Robinson, James E.
Sodroski, Joseph G.
Yang, Xinzhen
CA NIAID Ctr HIV AIDS Vaccine Immunol
TI Epitopes for broad and potent neutralizing antibody responses during
chronic infection with human immunodeficiency virus type 1
SO VIROLOGY
LA English
DT Article
DE HIV-1; Envelope glycoprotein; Neutralizing epitope; In vivo; Glycan; V3;
CD4BS
ID HUMAN MONOCLONAL-ANTIBODY; GP120 ENVELOPE GLYCOPROTEIN; CD4
BINDING-SITE; HIV-1 GP120; SENSITIVE EPITOPES; VARIABLE REGIONS;
CD4-BINDING SITE; MACAQUE MONKEYS; ENV CLONES; V3 LOOP
AB Neutralizing antibody (nAb) response is sporadic and has limited potency and breadth during infection with human immunodeficiency virus type 1 (HIV-1). In rare cases, broad and potent nAbs are actually induced in vivo. Identifying specific epitopes targeted by such broad and potent nAb response is valuable in guiding the design of a prophylactic vaccine aimed to induce nAb. In this study, we have defined neutralizing epitope usage in 7 out of 17 subjects with broad and potent nAbs by using targeted mutagenesis in known neutralizing epitopes of HIV-1 glycoproteins and by using in vitro depletion of serum neutralizing activity by various recombinant HIV-1 glycoproteins. Consistent with recent reports, the CD4 binding site (CD4BS) is targeted by nAbs in vivo (4 of the 7 subjects with defined neutralizing epitopes). The new finding from this study is that epitopes in the gp120 outer domain are also targeted by nAbs in vivo (5 of the 7 Subjects), The outer domain epitopes include glycan-dependent epitopes (2 Subjects), conserved nonlinear epitope in the V3 region (2 Subjects), and a CD4BS epitope composed mainly of the elements in the outer domain ( I subject). Importantly, we found indication for epitope poly-specificity, a dual usage of the V3 and CD4BS epitopes, in only one subject. This study provides a more complete profile of epitope usage for broad and potent nAb responses during HIV-1 infection. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Nandi, Avishek; Lavine, Christine L.; Wang, Pengcheng; Lipchina, Inna; Yang, Xinzhen] Beth Israel Deaconess Med Ctr, Dept Med, Div Viral Pathogenesis, Boston, MA 02215 USA.
[Goepfert, Paul A.; Shaw, George M.] Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA.
[Tomaras, Georgia D.; Montefiori, David C.; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Raleigh, NC USA.
[Easterbrook, Philippa] Kings Coll London, Dept HIV GUM, London WC2R 2LS, England.
[Robinson, James E.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA.
[Sodroski, Joseph G.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dept Pathol, Div Aids, Boston, MA 02215 USA.
[Sodroski, Joseph G.] Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Sch Publ Hlth, Boston, MA 02215 USA.
RP Yang, XZ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Viral Pathogenesis, E CLS-1011,3 Blackfan Circle, Boston, MA 02215 USA.
EM xyang1@bidmc.harvard.edu
RI Tomaras, Georgia/J-5041-2016
FU MAID Center for HIV/AIDS Vaccine Immunology [A1067854]; NIH [RO1
AI073133]
FX We think Dr. Connie Gee for help in preparing the manuscript. We
acknowledge the critical contributions of identifying and collecting
samples from study subjects by the CHAVI 001 and 008 clinical working
teams and the associates of Dr. Goepfert at UAB. We thank R. G. Overman
for technical assistance. This work is supported by the MAID Center for
HIV/AIDS Vaccine Immunology grant A1067854 and a grant from NIH to
XY.-RO1 AI073133.
NR 68
TC 26
Z9 26
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JAN 20
PY 2010
VL 396
IS 2
BP 339
EP 348
DI 10.1016/j.virol.2009.10.044
PG 10
WC Virology
SC Virology
GA 542OS
UT WOS:000273504600019
PM 19922969
ER
PT J
AU Marzocchetti, A
Lima, M
Tompkins, T
Kavanagh, DG
Gandhi, RT
O'Neill, DW
Bhardwaj, N
Koralnik, IJ
AF Marzocchetti, Angela
Lima, Marco
Tompkins, Troy
Kavanagh, Daniel G.
Gandhi, Rajesh T.
O'Neill, David W.
Bhardwaj, Nina
Koralnik, Igor J.
TI Efficient in vitro expansion of JC virus-specific CD8+ T-cell responses
by JCV peptide-stimulated dendritic cells from patients with progressive
multifocal leukoencephalopathy (vol 383, pg 173, 2009)
SO VIROLOGY
LA English
DT Correction
C1 [Lima, Marco; Koralnik, Igor J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Marzocchetti, Angela; Lima, Marco; Tompkins, Troy; Koralnik, Igor J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA.
[Lima, Marco] Fundacao Oswaldo Cruz, Neuroinfect & HTLV Lab, Rio De Janeiro, Brazil.
[Kavanagh, Daniel G.; Gandhi, Rajesh T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02215 USA.
[O'Neill, David W.; Bhardwaj, Nina] NYU, Sch Med, New York, NY 10003 USA.
RP Koralnik, IJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, E CLS-1005,330 Brookline Ave, Boston, MA 02215 USA.
EM ikoralni@bidmc.harvard.edu
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JAN 20
PY 2010
VL 396
IS 2
BP 349
EP 350
DI 10.1016/j.virol.2009.10.038
PG 2
WC Virology
SC Virology
GA 542OS
UT WOS:000273504600020
ER
PT J
AU Johnson, N
Bentley, J
Wang, LZ
Newell, DR
Robson, CN
Shapiro, GI
Curtin, NJ
AF Johnson, N.
Bentley, J.
Wang, L-Z
Newell, D. R.
Robson, C. N.
Shapiro, G. I.
Curtin, N. J.
TI Pre-clinical evaluation of cyclin-dependent kinase 2 and 1 inhibition in
anti-estrogen-sensitive and resistant breast cancer cells
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; CDK; NU2058; NU6102
ID ANTIESTROGEN RESISTANCE; DNA-DAMAGE; CDK2; P27(KIP1);
CYCLIN-DEPENDENT-KINASE-2; PHOSPHORYLATION; CHECKPOINT; TAMOXIFEN;
PROTEIN; PURINE
AB BACKGROUND: Cellular proliferation, driven by cyclin-dependent kinases (CDKs) and their cyclin partners, is deregulated in cancer. Anti-estrogens, such as tamoxifen, antagonise estrogen-induced ER alpha transactivation of cyclin D1, resulting in reduced CDK4/6 activity, p27(Kip1)-mediated inhibition of CDK2 and growth arrest. We hypothesised that direct inhibition of CDK2 and CDK1 may overcome the major clinical problem of anti-estrogen resistance.
METHODS: The cellular effects of CDK2/1 siRNA knockdown and purine-based CDK2/1 inhibitors, NU2058 and NU6102, were measured in anti-estrogen-sensitive and resistant breast cancer cell lines.
RESULTS: CDK2 knockdown caused G1 accumulation, whereas CDK1 depletion caused G2/M slowing, and dual CDK1/2 depletion resulted in further G2/M accumulation and cell death in both anti-estrogen-sensitive and resistant cells, confirming CDK2 and CDK1 as targets for breast cancer therapy. In contrast to tamoxifen, which only affected hormone-sensitive cells, NU2058 and NU6102 reduced CDK2-mediated phosphorylation of pRb, E2F transcriptional activity and proliferation, ultimately resulting in cell death, in both anti-estrogen-sensitive and resistant cells. Both drugs caused G2/M arrest, reflective of combined CDK2/1 knockdown, with a variable degree of G1 accumulation.
CONCLUSION: These studies confirm the therapeutic potential of CDK2 and CDK1 inhibitors for cancer therapy, and support their use as an alternative treatment for endocrine-resistant breast cancer. British Journal of Cancer (2010) 102, 342-350. doi:10.1038/sj.bjc.6605479 www.bjcancer.com Published online 15 December 2009 (C) 2010 Cancer Research UK
C1 [Johnson, N.; Bentley, J.; Wang, L-Z; Newell, D. R.; Robson, C. N.; Curtin, N. J.] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Johnson, N.; Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Curtin, NJ (reprint author), Newcastle Univ, No Inst Canc Res, Paul O Gorman Bldg,Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM n.j.curtin@ncl.ac.uk
FU Cancer Research UK; Breast Cancer Campaign; NIH [R01 CA90687, P50
CA089393, P20 CA090578, KG080773]
FX The research described in this paper was supported by the Cancer
Research UK and the Breast Cancer Campaign. GIS is supported by NIH
Grant R01 CA90687, P50 CA089393 (the DanaFarber/Harvard Cancer Center
(DF/HCC) Specialized Program of Research Excellence (SPORE) in Breast
Cancer) and P20 CA090578 (DF/HCC SPORE in Lung Cancer), as well as Susan
G. Komen Post-Doctoral Fellowship Award KG080773 (NJ and GIS). We would
also like to thank Professor Roger Griffin and colleagues in the Cancer
Research UK Drug Development Programme at the Northern Institute for
Cancer Research for the provision of NU2058 and NU6102, Professors Jane
Endicott and Martin Noble (Oxford University) for recombinant
CDK2/cyclin A3 enzyme, Dr Valerie Speirs (Leeds Univeristy) for
supplying MMU2 cells and Dr Robert Clarke (Georgetown University) for
LCC9 cells.
NR 27
TC 18
Z9 21
U1 0
U2 3
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 JAN 19
PY 2010
VL 102
IS 2
BP 342
EP 350
DI 10.1038/sj.bjc.6605479
PG 9
WC Oncology
SC Oncology
GA 545JO
UT WOS:000273728500014
PM 20010939
ER
PT J
AU Chen, J
Imanaka, N
Chen, J
Griffin, JD
AF Chen, J.
Imanaka, N.
Chen, J.
Griffin, J. D.
TI Hypoxia potentiates Notch signaling in breast cancer leading to
decreased E-cadherin expression and increased cell migration and
invasion
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE Notch; hypoxia; hypoxia inducible factor (HIF); breast cancer;
epithelial-to-mesenchymal transition (EMT)
ID EPITHELIAL-MESENCHYMAL TRANSITION; ACUTE LYMPHOBLASTIC-LEUKEMIA; MOUSE
MAMMARY EPITHELIUM; TRUNCATED INT3 GENE; TUMOR PROGRESSION; MIR-200
FAMILY; TUMORIGENESIS; METASTASIS; ACTIVATION; PHENOTYPE
AB BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is associated with decreased adhesion and acquisition of metastatic potential of breast cancer cells. Epithelial-to-mesenchymal transition is mediated, in part, by two transcription repressors, Snail and Slug, that are known to be targets of the Notch signaling pathway, and JAGGED1-induced Notch activation increases EMT. However, the events that lead to increased Notch activity during EMT of breast cancer cells are unknown.
METHODS: The accumulation of hypoxia inducible factors (HIFs) under hypoxia was detected by western blot analysis, and their effects on Notch signaling were measured by an in vitro Notch reporter assay. The expression of Notch target genes under hypoxia was tested by real-time PCR. The knockdown of HIF-1 alpha was mediated by retroviral delivery of shRNA. The expression of Slug and Snail under hypoxia was measured by real-time PCR. Breast cancer cell migration and invasion under hypoxia were tested with cell migration and invasion kits.
RESULTS: Hypoxia increased the expression of Notch target genes such as HES1 and HEY1 in breast cancer cells, as was expression of Notch receptors and ligands. The mechanism is likely to involve the accumulation of HIF-1 alpha and HIF-2 alpha in these cells by hypoxia, which synergised with the Notch co-activator MAML1 in potentiating Notch activity. Hypoxia inducible factor-1 alpha was found to bind to HES1 promoter under hypoxia. Knockdown of HIF-1 alpha with shRNA inhibited both HES1 and HEY1 expression under hypoxia. Hypoxia increased the expression of Slug and Snail, and decreased the expression of E-cadherin, hallmarks of EMT. Notch pathway inhibition abrogated the hypoxia-mediated increase in Slug and Snail expression, as well as decreased breast cancer cell migration and invasion.
CONCLUSION: Hypoxia-mediated Notch signaling may have an important role in the initiation of EMT and subsequent potential for breast cancer metastasis. British Journal of Cancer (2010) 102, 351-360. doi:10.1038/sj.bjc.6605486 www.bjcancer.com Published online 15 December 2009 (C) 2010 Cancer Research UK
C1 [Chen, J.; Imanaka, N.; Chen, J.; Griffin, J. D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM james_griffin@dfci.harvard.edu
FU NIH [CA-36167]
FX We thank Dr Tetsuo Sudo for the mHes1 antibody; Dr Qin Yan, Dr Yoji
Minamishima and Dr William Kaelin Jr. for pcDNA3/HIF-1 alpha
(P402A/P564A), pcDNA3/HIF-2 alpha (P405A/P531A) constructs and HIF-2
alpha antibody; Dr Tim Geistlinger for the advices of CHIP experiments.
J D Griffin is supported by NIH grant CA-36167.
NR 40
TC 128
Z9 142
U1 4
U2 40
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 JAN 19
PY 2010
VL 102
IS 2
BP 351
EP 360
DI 10.1038/sj.bjc.6605486
PG 10
WC Oncology
SC Oncology
GA 545JO
UT WOS:000273728500015
PM 20010940
ER
PT J
AU Bullinger, L
Armstrong, SA
AF Bullinger, Lars
Armstrong, Scott A.
TI HELP for AML: Methylation Profiling Opens New Avenues
SO CANCER CELL
LA English
DT Editorial Material
ID MYELOID-LEUKEMIA; MAPS
AB There is growing evidence that aberrant gene expression in cancer is linked to epigenetic deregulation like promoter cytosine methylation in CpG-islands. In this issue of Cancer Cell, Figueroa et al. show that genome-wide promoter DNA methylation profiling reveals unique AML subgroups and methylation patterns that are associated with clinical outcome.
C1 [Bullinger, Lars; Armstrong, Scott A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Bullinger, Lars] Univ Ulm, Dept Internal Med 3, D-89081 Ulm, Germany.
[Armstrong, Scott A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Armstrong, Scott A.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Armstrong, SA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM scott.armstrong@childrens.harvard.edu
NR 10
TC 10
Z9 10
U1 0
U2 3
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 JAN 19
PY 2010
VL 17
IS 1
BP 1
EP 3
DI 10.1016/j.ccr.2009.12.033
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 554YA
UT WOS:000274471300001
PM 20129241
ER
PT J
AU Turke, AB
Zejnullahu, K
Wu, YL
Song, Y
Dias-Santagata, D
Lifshits, E
Toschi, L
Rogers, A
Mok, T
Sequist, L
Lindeman, NI
Murphy, C
Akhavanfard, S
Yeap, BY
Xiao, Y
Capelletti, M
Iafrate, AJ
Lee, C
Christensen, JG
Engelman, JA
Janne, PA
AF Turke, Alexa B.
Zejnullahu, Kreshnik
Wu, Yi-Long
Song, Youngchul
Dias-Santagata, Dora
Lifshits, Eugene
Toschi, Luca
Rogers, Andrew
Mok, Tony
Sequist, Lecia
Lindeman, Neal I.
Murphy, Carly
Akhavanfard, Sara
Yeap, Beow Y.
Xiao, Yun
Capelletti, Marzia
Iafrate, A. John
Lee, Charles
Christensen, James G.
Engelman, Jeffrey A.
Jaenne, Pasi A.
TI Preexistence and Clonal Selection of MET Amplification in EGFR Mutant
NSCLC
SO CANCER CELL
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS;
CHRONIC MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROSPECTIVE
PHASE-II; ACQUIRED-RESISTANCE; GEFITINIB RESISTANCE; DOMAIN MUTATIONS;
T790M MUTATIONS
AB MET amplification activates ERBB3/PI3K/AKT signaling in EGFR mutant lung cancers and causes resistance to EGFR kinase inhibitors. We demonstrate that MET activation by its ligand, HGF, also induces drug resistance, but through GAB1 signaling. Using high-throughput FISH analyses in both cell lines and in patients with lung cancer, we identify subpopulations; of cells with MET amplification prior to drug exposure. Surprisingly, HGF accelerates the development of MET amplification both in vitro and in vivo. EGFR kinase inhibitor resistance, due to either MET amplification or autocrine HGF production, was cured in vivo by combined EGFR and MET inhibition. These findings highlight the potential to prospectively identify treatment naive, patients with EGFR-mutant lung cancer who will benefit from initial combination therapy.
C1 [Turke, Alexa B.; Song, Youngchul; Dias-Santagata, Dora; Lifshits, Eugene; Sequist, Lecia; Akhavanfard, Sara; Yeap, Beow Y.; Iafrate, A. John; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
[Turke, Alexa B.; Yeap, Beow Y.; Engelman, Jeffrey A.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Zejnullahu, Kreshnik; Toschi, Luca; Rogers, Andrew; Capelletti, Marzia; Jaenne, Pasi A.] Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Zejnullahu, Kreshnik; Toschi, Luca; Rogers, Andrew; Xiao, Yun; Capelletti, Marzia; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wu, Yi-Long] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China.
[Wu, Yi-Long] Guangdong Gen Hosp, Ctr Canc, Guangzhou, Guangdong, Peoples R China.
[Mok, Tony] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
[Lindeman, Neal I.; Murphy, Carly; Xiao, Yun; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Christensen, James G.] Pfizer Global Res & Dev, Dept Res Pharmacol, La Jolla Labs, La Jolla, CA 92121 USA.
[Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
EM jengelman@partners.org; pjanne@partners.org
RI Wu, Yi-Long/C-3396-2008
OI Wu, Yi-Long/0000-0002-3611-0258
FU National Institutes of Health [RO1CA114465, R01CA135257, CA120060,
R01CA137008, RO1CA140594]; National Cancer Institute Lung [P50CA090578];
DF/HCC Gastrointestinal Cancer [P50 CA127003]; American Association for
Cancer Research; V Foundation; American Cancer Society
[RSG-06-102-01-CCE]; Hazel and Samuel Bellin research fund; Ellison
Foundation Scholar; Pfizer
FX This study is Supported by the National Institutes of Health (grants
RO1CA114465 to P.A.J. and B.Y.Y.; R01CA135257 to P.A.J., B.Y.Y.. and
J.A.E.; K08 grant CA120060 to J.A.E.; R01CA137008 to J.A.E. and P.A.J.,
and RO1CA140594 to J.A.E). National Cancer Institute Lung (SPORE
P50CA090578 to P.A.J., B.Y.Y., and J.A.E.), DF/HCC Gastrointestinal
Cancer (SPORE P50 CA127003 to J.A.E.), the American Association for
Cancer Research (support to J.A.E.), the V Foundation (support to
J.A.E.), American Cancer Society (grant RSG-06-102-01-CCE to P.A.J.,
B.Y.Y., and J.A.E.), Hazel and Samuel Bellin research fund (support to
P.A.J.), and the Ellison Foundation Scholar (support to J.A.E.). We also
thank Mike Warring and Andrew Cosgrove, for FACS analysis, and Tatiana
Zolotarev, for technical histology assistance. J.G.C. is an employee and
shareholder of Pfizer. P.A.J. has received research support from Pfizer.
P.A.J. and J.A.E. are founders of Gatekeeper Pharmaceuticals.
NR 35
TC 478
Z9 501
U1 4
U2 47
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 JAN 19
PY 2010
VL 17
IS 1
BP 77
EP 88
DI 10.1016/j.ccr.2009.11.022
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 554YA
UT WOS:000274471300011
PM 20129249
ER
PT J
AU Verhaak, RGW
Hoadley, KA
Purdom, E
Wang, V
Qi, Y
Wilkerson, MD
Miller, CR
Ding, L
Golub, T
Mesirov, JP
Alexe, G
Lawrence, M
O'Kelly, M
Tamayo, P
Weir, BA
Gabriel, S
Winckler, W
Gupta, S
Jakkula, L
Feiler, HS
Hodgson, JG
James, CD
Sarkaria, JN
Brennan, C
Kahn, A
Spellman, PT
Wilson, RK
Speed, TP
Gray, JW
Meyerson, M
Getz, G
Perou, CM
Hayes, DN
AF Verhaak, Roel G. W.
Hoadley, Katherine A.
Purdom, Elizabeth
Wang, Victoria
Qi, Yuan
Wilkerson, Matthew D.
Miller, C. Ryan
Ding, Li
Golub, Todd
Mesirov, Jill P.
Alexe, Gabriele
Lawrence, Michael
O'Kelly, Michael
Tamayo, Pablo
Weir, Barbara A.
Gabriel, Stacey
Winckler, Wendy
Gupta, Supriya
Jakkula, Lakshmi
Feiler, Heidi S.
Hodgson, J. Graeme
James, C. David
Sarkaria, Jann N.
Brennan, Cameron
Kahn, Ari
Spellman, Paul T.
Wilson, Richard K.
Speed, Terence P.
Gray, Joe W.
Meyerson, Matthew
Getz, Gad
Perou, Charles M.
Hayes, D. Neil
CA Canc Genome Atlas Res Network
TI Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of
Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and
NF1
SO CANCER CELL
LA English
DT Article
ID NEURAL STEM-CELLS; RECURSIVE PARTITIONING ANALYSIS; MALIGNANT GLIOMA;
MOLECULAR SUBTYPES; MULTIFORME TUMORS; COPY NUMBER; EXPRESSION;
MUTATIONS; RECEPTOR; REVEALS
AB The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.
C1 [Hoadley, Katherine A.; Qi, Yuan; Wilkerson, Matthew D.; Miller, C. Ryan; Perou, Charles M.; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Verhaak, Roel G. W.; Golub, Todd; Mesirov, Jill P.; Alexe, Gabriele; Lawrence, Michael; O'Kelly, Michael; Tamayo, Pablo; Weir, Barbara A.; Gabriel, Stacey; Winckler, Wendy; Gupta, Supriya; Meyerson, Matthew; Getz, Gad] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.
[Verhaak, Roel G. W.; Golub, Todd; Mesirov, Jill P.; Alexe, Gabriele; Lawrence, Michael; O'Kelly, Michael; Tamayo, Pablo; Weir, Barbara A.; Gabriel, Stacey; Winckler, Wendy; Gupta, Supriya; Meyerson, Matthew; Getz, Gad] Harvard Univ, Cambridge, MA 02142 USA.
[Verhaak, Roel G. W.; Lawrence, Michael; O'Kelly, Michael; Weir, Barbara A.; Winckler, Wendy; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hoadley, Katherine A.; Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Qi, Yuan; Wilkerson, Matthew D.; Hayes, D. Neil] Univ N Carolina, Div Med Oncol, Dept Internal Med, Chapel Hill, NC 27599 USA.
[Miller, C. Ryan] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Purdom, Elizabeth; Speed, Terence P.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
[Wang, Victoria; Perou, Charles M.] Univ Calif Berkeley, Grp Biostat, Berkeley, CA 94720 USA.
[Ding, Li; Wilson, Richard K.] Washington Univ, Sch Med, Dept Genet, Genome Ctr, St Louis, MO 63108 USA.
[Golub, Todd] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Dept Pediat Oncol, Boston, MA 02115 USA.
[Jakkula, Lakshmi; Feiler, Heidi S.; Spellman, Paul T.; Gray, Joe W.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
[Hodgson, J. Graeme; James, C. David] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
[Sarkaria, Jann N.] Mayo Clin, Dept Radiat Oncol, Rochester, MN 55905 USA.
[Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
[Kahn, Ari] SRI Int, Fairfax, VA 22033 USA.
[Speed, Terence P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
RP Hayes, DN (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
EM hayes@med.unc.edu
RI Speed, Terence /B-8085-2009; leng, xianwei/F-9073-2011; Meyerson,
Matthew/E-7123-2012; James, Charles/E-2721-2012; Miller,
Ryan/B-9365-2008;
OI Speed, Terence /0000-0002-5403-7998; James, Charles/0000-0002-1027-203X;
Miller, Ryan/0000-0002-0096-8762; Brennan, Cameron/0000-0003-4064-8891;
Hayes, D. Neil/0000-0001-6203-7771; Perou, Charles/0000-0001-9827-2247
FU US Department of Energy; US National Institutes of Health [U54HG003067,
U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546,
U24CA126551, U24CA126554, U24CA126561, U24CA126563, P50CA58223,
RR023248, CA108961, CA127716, NS49720, CA097257, DE-AC02-05CH11231];
Dutch Cancer Society KWF
FX We thank the members of TCGA Research Network, in particular Lynda Chin,
for reviewing this manuscript. We thank Michele Hayward for editorial
assistance. This work was supported by the following grants from the US
Department of Energy and the US National Institutes of Health:
U54HG003067 and U54HG003079 to R. K. W.; U54HG003273, U24CA126543, and
U24CA126544 to C.M.P., U24CA126546 to M.M.; U24CA126551 to J.W.G.;
U24CA126554, U24CA126561, U24CA126563, and P50CA58223 to C.M.P.,
RR023248 to D.N.H.; CA108961 to J.N.S.; CA127716 to J.N.S.; NS49720 to
C.D.J.; CA097257 to C.D.J.; and DE-AC02-05CH11231 to J.W.G.). R.G.W.V.
is supported by a Fellowship from the Dutch Cancer Society KWF.
NR 50
TC 2000
Z9 2040
U1 52
U2 262
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 JAN 19
PY 2010
VL 17
IS 1
BP 98
EP 110
DI 10.1016/j.ccr.2009.12.020
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 554YA
UT WOS:000274471300013
PM 20129251
ER
PT J
AU Schnabel, RB
Larson, MG
Yamamoto, JF
Sullivan, LM
Pencina, MJ
Meigs, JB
Tofler, GH
Selhub, J
Jacques, PF
Wolf, PA
Magnani, JW
Ellinor, PT
Wang, TJ
Levy, D
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate B.
Larson, Martin G.
Yamamoto, Jennifer F.
Sullivan, Lisa M.
Pencina, Michael J.
Meigs, James B.
Tofler, Geoffrey H.
Selhub, Jacob
Jacques, Paul F.
Wolf, Philip A.
Magnani, Jared W.
Ellinor, Patrick T.
Wang, Thomas J.
Levy, Daniel
Vasan, Ramachandran S.
Benjamin, Emelia J.
TI Relations of Biomarkers of Distinct Pathophysiological Pathways and
Atrial Fibrillation Incidence in the Community
SO CIRCULATION
LA English
DT Article
DE atrial fibrillation; biomarkers; epidemiology; arrhythmia; risk
assessment
ID NATRIURETIC PEPTIDE LEVELS; POPULATION-BASED COHORT; C-REACTIVE PROTEIN;
CARDIOVASCULAR EVENTS; RISK-FACTORS; SECULAR TRENDS; HEART-FAILURE;
PREVALENCE; PREDICTORS; STROKE
AB Background-Biomarkers of multiple pathophysiological pathways have been related to incident atrial fibrillation (AF), but their predictive ability remains controversial.
Methods and Results-In 3120 Framingham cohort participants (mean age 58.4 +/- 9.7 years, 54% women), we related 10 biomarkers that represented inflammation (C-reactive protein and fibrinogen), neurohormonal activation (B-type natriuretic peptide [BNP] and N-terminal proatrial natriuretic peptide), oxidative stress (homocysteine), the renin-angiotensin-aldosterone system (renin and aldosterone), thrombosis and endothelial function (D-dimer and plasminogen activator inhibitor type 1), and microvascular damage (urinary albumin excretion; n = 2673) to incident AF (n = 209, 40% women) over a median follow-up of 9.7 years (range 0.05 to 12.8 years). In multivariable-adjusted analyses, the biomarker panel was associated with incident AF (P<0.0001). In stepwise-selection models (P<0.01 for entry and retention), log-transformed BNP (hazard ratio per SD 1.62, 95% confidence interval 1.41 to 1.85, P<0.0001) and C-reactive protein (hazard ratio 1.25, 95% confidence interval 1.07 to 1.45, P<0.004) were chosen. The addition of BNP to variables recently combined in a risk score for AF increased the C-statistic from 0.78 (95% confidence interval 0.75 to 0.81) to 0.80 (95% confidence interval 0.78 to 0.83) and showed an integrated discrimination improvement of 0.03 (95% confidence interval 0.02 to 0.04, P<0.0001), with 34.9% relative improvement in reclassification analysis. The combined analysis of BNP and C-reactive protein did not appreciably improve risk prediction over the model that incorporated BNP in addition to the risk factors.
Conclusions-BNP is a predictor of incident AF and improves risk stratification based on well-established clinical risk factors. Whether knowledge of BNP concentrations may be used to target individuals at risk of AF for more intensive monitoring or primary prevention requires further investigation. (Circulation. 2010; 121: 200-207.)
C1 [Schnabel, Renate B.; Larson, Martin G.; Wolf, Philip A.; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Framingham Study, Framingham, MA 01702 USA.
[Schnabel, Renate B.; Larson, Martin G.; Wolf, Philip A.; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Larson, Martin G.; Pencina, Michael J.] Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Magnani, Jared W.; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Med Dept, Boston, MA 02118 USA.
[Magnani, Jared W.; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Wolf, Philip A.] Boston Univ, Sch Med, Neurol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA.
[Yamamoto, Jennifer F.; Sullivan, Lisa M.; Pencina, Michael J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[Ellinor, Patrick T.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW, Australia.
[Selhub, Jacob; Jacques, Paul F.] Tufts Univ, Jean Mayer Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM emelia@bu.edu
RI Schnabel, Renate/F-6527-2014;
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin,
Emelia/0000-0003-4076-2336
FU National Institutes of Health/National Heart, Lung, and Blood Institute
[N01-IIC-25195, 6R01-NS 17950]; National Institutes of Health
[1R01HL092577-01A1, HL064753, HL076784, AG028321, 1 RO1HL71039, K24
HL04334, K24, DK080140]; American Diabetes Association; Deutsche
Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/1-1]
FX This study was supported by National Institutes of Health/National
Heart, Lung, and Blood Institute contracts N01-IIC-25195 and 6R01-NS
17950; National Institutes of Health grants 1R01HL092577-01A1 (Drs
Ellinor and Benjamin), HL064753, HL076784, and AG028321 (Dr Benjamin),
and 1 RO1HL71039 (Dr Vasan); National Institutes of Health Research
career award K24 HL04334 (Dr Vasan) and K24, DK080140 (Dr Meigs); an
American Diabetes Association career development award (Dr Meigs); and
Deutsche Forschungsgemeinschaft (German Research Foundation) research
fellowship SCHN 1149/1-1 (Dr Schnabel).
NR 45
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U1 2
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JAN 19
PY 2010
VL 121
IS 2
BP 200
EP U45
DI 10.1161/CIRCULATIONAHA.109.882241
PG 16
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 544XK
UT WOS:000273693500005
PM 20048208
ER
PT J
AU Rigotti, NA
Pipe, AL
Benowitz, NL
Arteaga, C
Garza, D
Tonstad, S
AF Rigotti, Nancy A.
Pipe, Andrew L.
Benowitz, Neal L.
Arteaga, Carmen
Garza, Dahlia
Tonstad, Serena
TI Efficacy and Safety of Varenicline for Smoking Cessation in Patients
With Cardiovascular Disease A Randomized Trial
SO CIRCULATION
LA English
DT Article
DE cardiovascular diseases; cerebrovascular disorders; peripheral vascular
diseases; smoking; trials
ID RECEPTOR PARTIAL AGONIST; NICOTINE REPLACEMENT THERAPY;
SUSTAINED-RELEASE BUPROPION; CORONARY-HEART-DISEASE; TRANSDERMAL
NICOTINE; TOBACCO DEPENDENCE; PLACEBO
AB Background-Smoking cessation is a key component of secondary cardiovascular disease prevention. Varenicline, a partial alpha 4 beta 2 nicotinic acetylcholine receptor agonist, is effective for smoking cessation in healthy smokers, but its efficacy and safety in smokers with cardiovascular disease are unknown.
Methods and Results-A multicenter, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease. Participants received varenicline (1 mg twice daily) or placebo, along with smoking-cessation counseling, for 12 weeks. Follow-up lasted 52 weeks. The primary end point was carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 (last 4 weeks of treatment). The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 (47.0% versus 13.9%; odds ratio, 6.11; 95% confidence interval [CI], 4.18 to 8.93) and weeks 9 through 52 (19.2% versus 7.2%; odds ratio, 3.14; 95% CI, 1.93 to 5.11). The varenicline and placebo groups did not differ significantly in cardiovascular mortality (0.3% versus 0.6%; difference, -0.3%; 95% CI, -1.3 to 0.7), all-cause mortality (0.6% versus 1.4%; difference, -0.8%; 95% CI, -2.3 to 0.6), cardiovascular events (7.1% versus 5.7%; difference, 1.4%; 95% CI, -2.3 to 5.0), or serious adverse events (6.5% and 6.0%; difference, 0.5%; 95% CI, -3.1 to 4.1). As a result of adverse events, 9.6% of varenicline and 4.3% of placebo participants discontinued study drug.
Conclusions-Varenicline is effective for smoking cessation in smokers with cardiovascular disease. It was well tolerated and did not increase cardiovascular events or mortality; however, trial size and duration limit definitive conclusions about safety. Clinical Trial Registration Information-URL: http://www.clinicaltrials.gov/ct2/show/NCT00282984. Unique identifier: NCT00282984. (Circulation. 2010; 121: 221-229.)
C1 [Rigotti, Nancy A.] Harvard Univ, Tobacco Res & Treatment Ctr, Div Gen Med, Dept Med,Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pipe, Andrew L.] Univ Ottawa, Inst Heart, Ottawa, ON, Canada.
[Benowitz, Neal L.] Univ Calif San Francisco, Div Clin Pharmacol & Expt Therapeut, Dept Med & Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Arteaga, Carmen; Garza, Dahlia] Pfizer Inc, New York, NY USA.
[Tonstad, Serena] Ullevaal Univ Hosp, Dept Prevent Cardiol, Oslo, Norway.
RP Rigotti, NA (reprint author), Harvard Univ, Tobacco Res & Treatment Ctr, Div Gen Med, Dept Med,Sch Med,Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM nrigotti@partners.org
FU Pfizer Inc.; sanofi-aventis; Nabi Biopharmaceuticals; Bristol-Myers
Squibb; Johnson Johnson; GlaxoSmithKline; Merrell-Dow
FX This study was funded by Pfizer Inc. Editorial support for the
development of this manuscript was provided by Alexandra Bruce, PhD, of
UBC Scientific Solutions and was funded by Pfizer Inc.; Drs Rigotti,
Pipe, Benowitz, and Tonstad have consulted for Pfizer. Dr Rigotti has
been the site principal investigator for clinical trials of smoking
cessation medications funded by Pfizer, sanofi-aventis, and Nabi
Biopharmaceuticals. Dr Pipe has received educational and research
support in the past from Bristol-Myers Squibb, Johnson & Johnson,
GlaxoSmithKline, and Merrell-Dow.
NR 24
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U1 1
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JAN 19
PY 2010
VL 121
IS 2
BP 221
EP U76
DI 10.1161/CIRCULATIONAHA.109.869008
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 544XK
UT WOS:000273693500008
PM 20048210
ER
PT J
AU Du, D
Xu, FL
Yu, LH
Zhang, CY
Lu, XF
Yuan, HX
Huang, Q
Zhang, F
Bao, HY
Jia, LH
Wu, XW
Zhu, XL
Zhang, XH
Zhang, Z
Chen, ZJ
AF Du, Dan
Xu, Feilai
Yu, Lihou
Zhang, Chenyi
Lu, Xuefeng
Yuan, Haixin
Huang, Qin
Zhang, Fan
Bao, Hongyan
Jia, Lianghui
Wu, Xunwei
Zhu, Xueliang
Zhang, Xiaohui
Zhang, Zhe
Chen, Zhengjun
TI The Tight Junction Protein, Occludin, Regulates the Directional
Migration of Epithelial Cells
SO DEVELOPMENTAL CELL
LA English
DT Article
ID DISTINCT ROLES; RHO-GTPASES; TYROSINE PHOSPHORYLATION; MEMBRANE-PROTEIN;
OXIDATIVE STRESS; LEADING-EDGE; POLARITY; CDC42; POLARIZATION; COMPLEX
AB Cell polarity proteins regulate tight junction formation and directional migration in epithelial cells. To date, the mechanism by which these polarity proteins assemble at the leading edge of migrating epithelial cells remains unclear. We report that occludin, a transmembrane protein, is localized at the leading edge of migrating cells and regulates directional cell migration. During migration, occludin knockdown disrupted accumulation of aPKC-Par3 and PATJ at the leading edge, and led to a disorganized microtubule network and defective reorientation of the microtubule organization center (MTOC). Phosphorylation of occludin at tyrosine 473 residue allowed recruitment of p85 alpha to the leading edge via association with its C-terminal SH2 domain. Loss of occludin attenuated activation of PI3K, leading to disorganization of the actin cytoskeleton and reduced cell protrusions. Our data indicate that occludin is required for the leading-edge localization of polarity proteins aPKC-Par3 and PATJ and promotes cell protrusion by regulating membrane-localized activation of PI3K.
C1 [Du, Dan; Xu, Feilai; Yu, Lihou; Zhang, Chenyi; Lu, Xuefeng; Yuan, Haixin; Huang, Qin; Zhang, Fan; Bao, Hongyan; Jia, Lianghui; Zhang, Xiaohui; Zhang, Zhe; Chen, Zhengjun] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.
[Zhu, Xueliang] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Mol Cell Biol, Shanghai 200031, Peoples R China.
[Wu, Xunwei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
RP Chen, ZJ (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.
EM zjchen@sibs.ac.cn
RI Yu, Lihou/A-8865-2015; Du, Dan/D-6106-2017
OI Du, Dan/0000-0002-3470-2890
FU National Natural Science Foundation of China [30730055, 30871270,
30623002]; National Key Scientific Program of China [2007CB914504];
National High Technology and Development Program of China
[2006AA021308]; Chinese Academy of Sciences [KSCX2-YW-R-108,
KSCX1-YW-R-67]; Program of Shanghai Subject [08XD14051]
FX We thank Dangsheng Li for critical comments on the manuscript. We also
thank Cord Brakebusch and Shaohua Li for providing Rac1-/- ES
cells. This research was supported by grants from National Natural
Science Foundation of China (30730055, 30871270, and 30623002), from the
National Key Scientific Program of China (2007CB914504), from the
National High Technology and Development Program of China
(2006AA021308), from the Chinese Academy of Sciences (KSCX2-YW-R-108 and
KSCX1-YW-R-67), and also from the Program of Shanghai Subject Chief
Scientist (08XD14051).
NR 64
TC 55
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U1 4
U2 14
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 JAN 19
PY 2010
VL 18
IS 1
BP 52
EP 63
DI 10.1016/j.devcel.2009.12.008
PG 12
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 546RZ
UT WOS:000273829800008
PM 20152177
ER
PT J
AU Moore, SA
Januzzi, JL
AF Moore, Stephanie A.
Januzzi, James L., Jr.
TI Found in Translation Soluble ST2 and Heart Disease
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE ST2; cardiac magnetic resonance; myocardial infarction; remodeling;
aldosterone
ID RECEPTOR FAMILY-MEMBER; ACUTE MYOCARDIAL-INFARCTION; ACUTE DYSPNEA;
SERUM-LEVELS; FAILURE; BIOMARKER; MORTALITY
C1 [Moore, Stephanie A.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Moore, Stephanie A.] Massachusetts Gen Hosp, Sect Heart Failure, Boston, MA 02114 USA.
[Moore, Stephanie A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA.
EM JJanuzzi@partners.org
NR 12
TC 4
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JAN 19
PY 2010
VL 55
IS 3
BP 251
EP 253
DI 10.1016/j.jacc.2009.08.049
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 543XI
UT WOS:000273613100011
PM 20117404
ER
PT J
AU Shen, Y
Liu, J
Estiu, G
Isin, B
Ahn, YY
Lee, DS
Barabasi, AL
Kapatral, V
Wiest, O
Oltvai, ZN
AF Shen, Y.
Liu, J.
Estiu, G.
Isin, B.
Ahn, Y-Y.
Lee, D-S.
Barabasi, A-L.
Kapatral, V.
Wiest, O.
Oltvai, Z. N.
TI Blueprint for antimicrobial hit discovery targeting metabolic networks
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antibiotics; flux balance analysis; virtual screening
ID CARRIER PROTEIN TRANSACYLASE; RESISTANT STAPHYLOCOCCUS-AUREUS;
FATTY-ACID SYNTHASE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; ANTIBIOTIC
PROPERTIES; GENE-EXPRESSION; RECONSTRUCTION; GENOME; INHIBITOR
AB Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy.
C1 [Shen, Y.; Estiu, G.; Wiest, O.] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA.
[Shen, Y.; Liu, J.; Isin, B.; Oltvai, Z. N.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA.
[Shen, Y.; Liu, J.; Isin, B.; Oltvai, Z. N.] Univ Pittsburgh, Dept Computat Biol, Pittsburgh, PA 15261 USA.
[Ahn, Y-Y.; Lee, D-S.; Barabasi, A-L.] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
[Ahn, Y-Y.; Lee, D-S.; Barabasi, A-L.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Ahn, Y-Y.; Lee, D-S.; Barabasi, A-L.] Northeastern Univ, Dept Biol, Boston, MA 02115 USA.
[Ahn, Y-Y.; Lee, D-S.; Barabasi, A-L.] Northeastern Univ, Dept Comp Sci, Boston, MA 02115 USA.
[Ahn, Y-Y.; Lee, D-S.; Barabasi, A-L.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Kapatral, V.] Integrated Genom Inc, Chicago, IL 60612 USA.
RP Wiest, O (reprint author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA.
EM owiest@nd.edu; oltvai@pitt.edu
RI Lee, Deok-Sun/D-1335-2011
FU NIAID [U01-0700499]; ChemistryBiochemistry-Biology Interface (CBBI)
Program [NIGMS T32-075762]
FX We thank Drs. I. Bahar, D. Tobi, B. Chen, and B. Shoichet for help with
the structural analyses and Dr. R. Lange (Actelion Pharmaceuticals Ltd.,
Switzerland) for providing plasmids, pDSNdeIacpPec and pDSNdeIacpSec.
This research was supported by NIAID U01-0700499 (to Z. N. O., A-L. B.,
V. K., and O. W.) and by a travel grant (Y. S.) from the
ChemistryBiochemistry-Biology Interface (CBBI) Program at the University
of Notre Dame, supported by training Grant NIGMS T32-075762.
NR 40
TC 65
Z9 66
U1 0
U2 13
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 JAN 19
PY 2010
VL 107
IS 3
BP 1082
EP 1087
DI 10.1073/pnas.0909181107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548BP
UT WOS:000273934100026
PM 20080587
ER
PT J
AU Hayashida, T
Takahashi, F
Chiba, N
Brachtel, E
Takahashi, M
Godin-Heymann, N
Gross, KW
Vivanco, MDM
Wijendran, V
Shioda, T
Sgroi, D
Donahoe, PK
Maheswaran, S
AF Hayashida, Tetsu
Takahashi, Fumiyuki
Chiba, Naokazu
Brachtel, Elena
Takahashi, Motomi
Godin-Heymann, Nadia
Gross, Kenneth W.
Vivanco, Maria D. M.
Wijendran, Vasuki
Shioda, Toshihiro
Sgroi, Dennis
Donahoe, Patricia K.
Maheswaran, Shyamala
TI HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity
and lung metastasis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE breast cancer; ErbB; TGF-beta; angiogenesis; epithelial to mesenchymal
transition
ID EPITHELIAL-MESENCHYMAL TRANSITION; EPIDERMAL-GROWTH-FACTOR;
PHOSPHATIDYLINOSITOL 3-KINASE; HOMEODOMAIN PROTEIN; EXPRESSION RATIO;
TGF-BETA; IN-VIVO; CELLS; ANGIOGENESIS; INHIBITOR
AB The mechanisms underlying tumoral secretion of signaling molecules into the microenvironment, which modulates tumor cell fate, angiogenesis, invasion, and metastasis, are not well understood. Aberrant expression of transcription factors, which has been implicated in the tumorigenesis of several types of cancers, may provide a mechanism that induces the expression of growth and angiogenic factors in tumors, leading to their local increase in the tumor microenvironment, favoring tumor progression. In this report, we demonstrate that the transcription factor HOXB9 is overexpressed in breast carcinoma, where elevated expression correlates with high tumor grade. HOXB9 induces the expression of several angiogenic factors (VEGF, bFGF, IL-8, and ANGPTL-2), as well as ErbB (amphiregulin, epiregulin, and neuregulins) and TGF-beta, which activate their respective pathways, leading to increased cell motility and acquisition of mesenchymal phenotypes. In vivo, HOXB9 promotes the formation of large, well-vascularized tumors that metastasize to the lung. Thus, deregulated expression of HOXB9 contributes to breast cancer progression and lung metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment.
C1 [Donahoe, Patricia K.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Charlestown, MA 02129 USA.
[Donahoe, Patricia K.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Hayashida, Tetsu; Takahashi, Fumiyuki; Chiba, Naokazu; Takahashi, Motomi; Maheswaran, Shyamala] Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA.
[Hayashida, Tetsu; Takahashi, Fumiyuki; Chiba, Naokazu; Takahashi, Motomi; Godin-Heymann, Nadia; Shioda, Toshihiro; Sgroi, Dennis; Maheswaran, Shyamala] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
[Brachtel, Elena; Sgroi, Dennis] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA.
[Gross, Kenneth W.] Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA.
[Vivanco, Maria D. M.] CIC bioGUNE, Cell Biol & Stem Cells Unit, Derio 48160, Bizkaia, Spain.
[Wijendran, Vasuki] Brandeis Univ, Foster Biomed Res Lab, Waltham, MA 02254 USA.
RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Charlestown, MA 02129 USA.
EM pdonahoe@partners.org; maheswaran@helix.mgh.harvard.edu
RI Vivanco, Maria/G-2393-2011; cancer, biogune/H-7276-2012
OI Vivanco, Maria/0000-0002-9540-247X;
FU National Institutes of Health/National Cancer Institute [CA89138];
[PDF0600282]; [KG090412]
FX We thank Drs. Kurt J. Isselbacher, Daniel A. Haber, and Jeffrey
Settleman for critically reading this manuscript. This work was
supported by National Institutes of Health/National Cancer Institute
Grant CA89138 and Susan G. Komen for the Cure Grants PDF0600282 and
KG090412 (to S. M.).
NR 44
TC 66
Z9 67
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 JAN 19
PY 2010
VL 107
IS 3
BP 1100
EP 1105
DI 10.1073/pnas.0912710107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548BP
UT WOS:000273934100029
PM 20080567
ER
PT J
AU Pancera, M
Majeed, S
Ban, YEA
Chen, L
Huang, CC
Kong, L
Kwon, YD
Stuckey, J
Zhou, TQ
Robinson, JE
Schief, WR
Sodroski, J
Wyatt, R
Kwong, PD
AF Pancera, Marie
Majeed, Shahzad
Ban, Yih-En Andrew
Chen, Lei
Huang, Chih-chin
Kong, Leopold
Kwon, Young Do
Stuckey, Jonathan
Zhou, Tongqing
Robinson, James E.
Schief, William R.
Sodroski, Joseph
Wyatt, Richard
Kwong, Peter D.
TI Structure of HIV-1 gp120 with gp41-interactive region reveals layered
envelope architecture and basis of conformational mobility
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HIV-1 viral spike; molecular motion; protein architecture;
receptor-triggered entry; type 1 fusion protein
ID MEMBRANE-FUSION; BINDING-SITE; VIRAL ENTRY; GLYCOPROTEIN; ANTIBODY;
NEUTRALIZATION; CD4; HEMAGGLUTININ; RECEPTOR; DEFINITION
AB The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug-and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate-and structurally plastic-layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanismin which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.
C1 [Pancera, Marie; Majeed, Shahzad; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Wyatt, Richard; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Ban, Yih-En Andrew; Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA.
[Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
RI Kwon, Young Do/A-6957-2010; Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
FU Intramural Research Program of the NIH; Melinda Gates Foundation Grand
Challenges in Global Heath Initiative; NIH; US Department of Energy,
Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
FX We thank A. Finzi, M. Gerstein, B. Korber, H. Langedijk, G. Nabel, R.
Sanders, Q. Sattentau, L. Shapiro, M. Shastri, I. Wilson, and members of
the Structural Biology Section, Vaccine Research Center, for discussions
or comments on the manuscript; J. Skinner for assistance with
statistical analysis; S. Subramaniam for ligand-oriented cryoelectron
tomograms; D. Dimitrov for antibodies X5, m6, and m9; M. Fung for
antibody 5A8, M. Posner for antibody F105, W. Hendrickson for support,
advice, and guidance during the early stages of the project, and the NIH
AIDS Research and Reference Reagent Program for CD4. Support for this
work was provided by the Intramural Research Program of the NIH, by the
International AIDS Vaccine Initiative, by a grant from the Bill and
Melinda Gates Foundation Grand Challenges in Global Heath Initiative,
and by grants from the NIH. Use of insertion device 22 (Southeast Region
Collaborative Access Team) at the Advanced Photon Source was supported
by the US Department of Energy, Basic Energy Sciences, Office of
Science, under Contract no. W-31-109-Eng-38. Atomic coordinates and
structure factors for the structure of gp120with intact gp41-interactive
region in complex with CD4 and antibody 48d for both orthorhombic and
tetragonal crystal forms have been deposited with the Protein Data Bank
under the accession codes 3JWD and 3JWO, respectively.
NR 35
TC 184
Z9 188
U1 4
U2 25
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 JAN 19
PY 2010
VL 107
IS 3
BP 1166
EP 1171
DI 10.1073/pnas.0911004107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 548BP
UT WOS:000273934100040
PM 20080564
ER
PT J
AU Bansal, A
Carlson, J
Yan, JY
Akinsiku, OT
Schaefer, M
Sabbaj, S
Bet, A
Levy, DN
Heath, S
Tang, JM
Kaslow, RA
Walker, BD
Ndung'u, T
Goulder, PJ
Heckerman, D
Hunter, E
Goepfert, PA
AF Bansal, Anju
Carlson, Jonathan
Yan, Jiyu
Akinsiku, Olusimidele T.
Schaefer, Malinda
Sabbaj, Steffanie
Bet, Anne
Levy, David N.
Heath, Sonya
Tang, Jianming
Kaslow, Richard A.
Walker, Bruce D.
Ndung'u, Thumbi
Goulder, Philip J.
Heckerman, David
Hunter, Eric
Goepfert, Paul A.
TI CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes
derived from antisense transcription
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL LOAD; CLASS-I; INFECTION; VACCINE;
RNA; ASSOCIATIONS; LYMPHOCYTES; EXPRESSION; CHALLENGE
AB Retroviruses pack multiple genes into relatively small genomes by encoding several genes in the same genomic region with overlapping reading frames. Both sense and antisense HIV-1 transcripts contain open reading frames for known functional proteins as well as numerous alternative reading frames (ARFs). At least some ARFs have the potential to encode proteins of unknown function, and their antigenic properties can be considered as cryptic epitopes (CEs). To examine the extent of active immune response to virally encoded CEs, we analyzed human leukocyte antigen class I-associated polymorphisms in HIV-1 gag, pol, and nef genes from a large cohort of South Africans with chronic infection. In all, 391 CEs and 168 conventional epitopes were predicted, with the majority (307; 79%) of CEs derived from antisense transcripts. In further evaluation of CD8 T cell responses to a subset of the predicted CEs in patients with primary or chronic infection, both sense- and antisense-encoded CEs were immunogenic at both stages of infection. In addition, CEs often mutated during the first year of infection, which was consistent with immune selection for escape variants. These findings indicate that the HIV-1 genome might encode and deploy a large potential repertoire of unconventional epitopes to enhance vaccine-induced antiviral immunity.
C1 [Bansal, Anju; Yan, Jiyu; Sabbaj, Steffanie; Heath, Sonya; Tang, Jianming; Goepfert, Paul A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Akinsiku, Olusimidele T.; Bet, Anne; Tang, Jianming; Goepfert, Paul A.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Kaslow, Richard A.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA.
[Carlson, Jonathan; Heckerman, David] Microsoft Res, Redmond, WA 98052 USA.
[Schaefer, Malinda; Hunter, Eric] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
[Schaefer, Malinda; Hunter, Eric] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30329 USA.
[Levy, David N.] NYU, Coll Dent, Dept Basic Sci, New York, NY 10010 USA.
[Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip J.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA.
[Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip J.] Harvard Univ, Boston, MA 02129 USA.
[Walker, Bruce D.; Ndung'u, Thumbi; Goulder, Philip J.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Program, ZA-4013 Durban, South Africa.
[Goulder, Philip J.] Univ Oxford, Dept Pediat, Oxford OX1 3SY, England.
RP Goepfert, PA (reprint author), Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
EM ABansal@uab.edu; paulg@uab.edu
OI Sabbaj, Steffanie/0000-0003-4052-6819; Tang,
Jianming/0000-0003-0137-7486; Ndung'u, Thumbi/0000-0003-2962-3992
FU National Institutes of Health (NIH) [R21 AI 73103, R01 AI 084772, AI
64060, P30 AI 050409]; Bill and Melinda Gates Foundation [37874];
University of Alabama at Birmingham-Centers for AIDS Research [P30 AI
027767]; Microsoft Research Corporation
FX This work was supported by National Institutes of Health (NIH) grants
R21 AI 73103 and R01 AI 084772 and Bill and Melinda Gates Foundation
grant 37874 (all to P. A. Goepfert), a University of Alabama at
Birmingham-Centers for AIDS Research supplement to grant P30 AI 027767
(to A. Bansal), and NIH grants AI 64060 and P30 AI 050409 (to E.
Hunter), and the Microsoft Research Corporation (J. Carlson and D.
Heckerman).
NR 40
TC 41
Z9 42
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JAN 18
PY 2010
VL 207
IS 1
BP 51
EP 59
DI 10.1084/jem.20092060
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 544WO
UT WOS:000273690800006
PM 20065064
ER
PT J
AU Berger, CT
Carlson, JM
Brumme, CJ
Hartman, KL
Brumme, ZL
Henry, LM
Rosato, PC
Piechocka-Trocha, A
Brockman, MA
Harrigan, PR
Heckerman, D
Kaufmann, DE
Brander, C
AF Berger, Christoph T.
Carlson, Jonathan M.
Brumme, Chanson J.
Hartman, Kari L.
Brumme, Zabrina L.
Henry, Leah M.
Rosato, Pamela C.
Piechocka-Trocha, Alicja
Brockman, Mark A.
Harrigan, P. Richard
Heckerman, David
Kaufmann, Daniel E.
Brander, Christian
TI Viral adaptation to immune selection pressure by HLA class I-restricted
CTL responses targeting epitopes in HIV frameshift sequences
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; OPEN READING
FRAME; CELL RESPONSES; INITIATION CODON; AMINO-ACIDS; RNA GENOME;
SET-POINT; INFECTION; TYPE-1
AB CD8(+) cytotoxic T lymphocyte (CTL)-mediated immune responses to HIV contribute to viral control in vivo. Epitopes encoded by alternative reading frame (ARF) peptides may be targeted by CTLs as well, but their frequency and in vivo relevance are unknown. Using host genetic (human leukocyte antigen [HLA]) and plasma viral sequence information from 765 HIV-infected subjects, we identified 64 statistically significant (q < 0.2) associations between specific HLA alleles and sequence polymorphisms in alternate reading frames of gag, pol, and nef that did not affect the regular frame protein sequence. Peptides spanning the top 20 HLA-associated imprints were used to test for ex vivo immune responses in 85 HIV-infected subjects and showed responses to 10 of these ARF peptides. The most frequent response recognized an HLA-A*03-restricted +2 frame-encoded epitope containing a unique A*03-associated polymorphism at position 6. Epitope-specific CTLs efficiently inhibited viral replication in vitro when viruses containing the wild-type sequence but not the observed polymorphism were tested. Mutating alternative internal start codons abrogated the CTL-mediated inhibition of viral replication. These data indicate that responses to ARF-encoded HIV epitopes are induced during natural infection, can contribute to viral control in vivo, and drive viral evolution on a population level.
C1 [Berger, Christoph T.; Brumme, Chanson J.; Hartman, Kari L.; Brumme, Zabrina L.; Henry, Leah M.; Rosato, Pamela C.; Piechocka-Trocha, Alicja; Brockman, Mark A.; Kaufmann, Daniel E.; Brander, Christian] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA.
[Berger, Christoph T.; Brumme, Chanson J.; Hartman, Kari L.; Brumme, Zabrina L.; Henry, Leah M.; Rosato, Pamela C.; Piechocka-Trocha, Alicja; Brockman, Mark A.; Kaufmann, Daniel E.; Brander, Christian] Harvard Univ, Boston, MA 02129 USA.
[Carlson, Jonathan M.; Heckerman, David] Microsoft Res, Seattle, WA 98033 USA.
[Brumme, Zabrina L.; Brockman, Mark A.; Harrigan, P. Richard] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V6B 5S8, Canada.
[Brumme, Zabrina L.; Brockman, Mark A.] Simon Fraser Univ, Burnaby, BC V5A 4Y7, Canada.
[Harrigan, P. Richard] Univ British Columbia, Div Aids, Vancouver, BC V6Z 1Y6, Canada.
[Brander, Christian] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Spain.
[Brander, Christian] Hosp Badalona Germans Trias & Pujol, Irsicaixa HIV Res Inst HIVACAT, Barcelona 08916, Spain.
RP Brander, C (reprint author), Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA.
EM cbrander@irsicaixa.es
OI Brander, Christian/0000-0002-0548-5778; Brumme,
Chanson/0000-0003-2722-5288; Brockman, Mark/0000-0001-6432-1426
FU National Institutes of Health [R01 A1-067077]; Swiss National Science
Foundation [PBBSP3-123141]; Freiwillige Akademische Gesellschaft Basel;
Canadian Institutes for Health Research
FX The work was supported by a grant from the National Institutes of Health
(R01 A1-067077 to C. Brander and D. E. Kaufmann). C. T. Berger is
supported by a postdoctoral fellowship from the Swiss National Science
Foundation (PBBSP3-123141) and by the Freiwillige Akademische
Gesellschaft Basel. Z. L. Brumme was supported by a postdoctoral
fellowship and, currently, a New Investigator award from the Canadian
Institutes for Health Research. C. Brander is an Institucio Catalana de
Recerca i Estudis Avancats Senior Research Professor at the Irsicaixa
AIDS Research Institute.
NR 61
TC 35
Z9 35
U1 0
U2 3
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JAN 18
PY 2010
VL 207
IS 1
BP 61
EP 75
DI 10.1084/jem.20091808
PG 15
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 544WO
UT WOS:000273690800007
PM 20065065
ER
PT J
AU Haghgooie, R
Toner, M
Doyle, PS
AF Haghgooie, Ramin
Toner, Mehmet
Doyle, Patrick S.
TI Squishy Non-Spherical Hydrogel Microparticles
SO MACROMOLECULAR RAPID COMMUNICATIONS
LA English
DT Article
DE crosslinking; deformable; hydrogel; microparticle; stop flow lithography
ID MECHANICAL-PROPERTIES; MICROFLUIDIC DEVICE; FLOW LITHOGRAPHY;
PHOTOPOLYMERIZATION; PHAGOCYTOSIS; CAPILLARIES; ERYTHROCYTE; GEOMETRY;
DESIGN; TARGET
AB Recent advances in the synthesis of polymeric colloids have opened the doors to new advanced materials. There is strong interest in using these new techniques to produce particles that mimic and/or interact with biological systems. An important characteristic of biological systems that has not yet been exploited in synthetic polymeric colloids is their wide range of deformability. A canonical example of this is the human red blood cell (RBC) which exhibits extreme reversible deformability under flow. Here we report the synthesis of soft polymeric colloids with sizes and shapes that mimic those of the RBC. Additionally, we demonstrate that the mechanical flexibility of the colloids can be reproducibly varied over a large range resulting in RBC-like deformability under physiological flow conditions. These materials have the potential to impact the interaction between biological and synthetic systems.
C1 [Doyle, Patrick S.] MIT, Cambridge, MA 02139 USA.
[Haghgooie, Ramin; Toner, Mehmet] Shriners Hosp Children, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Charlestown, MA 02129 USA.
[Haghgooie, Ramin; Toner, Mehmet] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Doyle, PS (reprint author), MIT, 77 Massachusetts Ave,Room 66-270, Cambridge, MA 02139 USA.
EM pdoyle@mit.edu
FU MIT-MGH Postdoctoral Fellowship; National Institute of Biomedical
Imaging and Bioengineering [P41 EB002503]; John Simon Guggenheim
Foundation; Rothschild-Yvette Mayent-Institute Curie Fellowship
FX We thank Octavio Hurtado for assistance with microfabrication and David
J. Quinn for useful discussions on design of the constriction devices.
This work was supported in part by the MIT-MGH Postdoctoral Fellowship
in Translational Research and the National Institute of Biomedical
Imaging and Bioengineering (BioMEMS Resource Center, P41 EB002503). PSD
acknowledges support from the John Simon Guggenheim Foundation and the
Rothschild-Yvette Mayent-Institute Curie Fellowship.
NR 27
TC 56
Z9 56
U1 1
U2 32
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1022-1336
J9 MACROMOL RAPID COMM
JI Macromol. Rapid Commun.
PD JAN 18
PY 2010
VL 31
IS 2
SI SI
BP 128
EP 134
DI 10.1002/marc.200900302
PG 7
WC Polymer Science
SC Polymer Science
GA 551SJ
UT WOS:000274229600004
PM 21590884
ER
PT J
AU Harjes, DI
Dubach, JM
Rosenzweig, A
Das, S
Clark, HA
AF Harjes, Daniel I.
Dubach, J. Matthew
Rosenzweig, Anthony
Das, Saumya
Clark, Heather A.
TI Ion-Selective Optodes Measure Extracellular Potassium Flux in Excitable
Cells
SO MACROMOLECULAR RAPID COMMUNICATIONS
LA English
DT Article
DE biological applications for polymers; fluorescence; microstructure;
sensors
ID SINGLE LIVING CELLS; OPTICAL NANOSENSORS; CARDIAC-ARRHYTHMIA;
CHEMICAL-ANALYSIS; PEBBLE SENSORS; BULK OPTODES
AB Optodes have been used for detection of ionic concentrations and fluxes for several years. However, their uses in biomedical applications have not yet been fully explored. This study investigates optodes as a potential sensor platform for monitoring cellular ion flux with attendant implications in the field of drug screening and toxicology. A prototype system was developed to quantitatively measure extracellular potassium flux from a monolayer of cardiomyocytes. Optodes were created and immobilized on a glass coverslip for fluorescent imaging. The system detected potassium (K(+)) ion flux during the repolarization phase of the cardiac action potential and further detected a decrease in the magnitude of the flux in the presence of a known K(+) channel inhibitor by optically monitoring local K(+) ion concentrations during field stimulation of the cardiomyocyte monolayer.
C1 [Harjes, Daniel I.; Dubach, J. Matthew; Clark, Heather A.] Charles Stark Draper Lab Inc, Biomed Engn Grp, Cambridge, MA 02139 USA.
[Rosenzweig, Anthony; Das, Saumya] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02155 USA.
[Das, Saumya] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA.
RP Clark, HA (reprint author), Charles Stark Draper Lab Inc, Biomed Engn Grp, 555 Technol Sq, Cambridge, MA 02139 USA.
EM hclark@draper.com
RI Clark, Heather/D-5247-2013
FU National Institutes of Health National Institute of General Medical
Sciences [R01 GM084366]; Draper Internal Research and Development;
Leducq Foundation Network of Research Excellence; Maxwell Hurston
Charitable Foundation; National Institutes of Health/NHLBI [K08
HL081319]
FX We thank Dr. Ling Li and Dr. Chunyang Xiao for technical help with
myocyte preparations. This work was supported by a grant from the
National Institutes of Health National Institute of General Medical
Sciences (R01 GM084366) and Draper Internal Research and Development. AR
also gratefully acknowledges support from the Leducq Foundation Network
of Research Excellence, Judith and David Ganz, and the Maxwell Hurston
Charitable Foundation. SD acknowledges the support of the Harvard-MIT
Health Sciences and Technology Clinical Investigation Training Program
Grant and is also supported by a grant from the National Institutes of
Health/NHLBI (K08 HL081319).
NR 10
TC 11
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U1 0
U2 13
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1022-1336
J9 MACROMOL RAPID COMM
JI Macromol. Rapid Commun.
PD JAN 18
PY 2010
VL 31
IS 2
SI SI
BP 217
EP 221
DI 10.1002/marc.200900297
PG 5
WC Polymer Science
SC Polymer Science
GA 551SJ
UT WOS:000274229600014
PM 21590894
ER
PT J
AU Heath, JA
Clarke, NE
Donath, SM
McCarthy, M
Anderson, VA
Wolfe, J
AF Heath, John A.
Clarke, Naomi E.
Donath, Susan M.
McCarthy, Maria
Anderson, Vicki A.
Wolfe, Joanne
TI Symptoms and suffering at the end of life in children with cancer: an
Australian perspective
SO MEDICAL JOURNAL OF AUSTRALIA
LA English
DT Article
ID PEDIATRIC PALLIATIVE CARE; HOME-CARE; DYING CHILDREN; CIRCUMSTANCES;
DEATH
AB Objective: To examine the symptoms, level of suffering, and care of Australian children with cancer at the end of life.
Design, setting and participants: In a study conducted at the Royal Children's Hospital, Melbourne, parents of children who had died of cancer over the period 1996-2004 were interviewed between February 2004 and August 2006. Parents also completed and returned self-report questionnaires.
Main outcome measures: Proportions of children suffering from and treated for various symptoms; proportion of children receiving cancer-directed therapy at the end of life; proportion of children whose treatment of symptoms was successful; location of death.
Results: Of 193 eligible families, 96 (50%) were interviewed. All interviews were conducted in person, and occurred a mean of 4.5 years (SD, 2.1 years) after the child's death. Eighty-four per cent of parents reported that their child had suffered "a lot" or "a great deal" from at least one symptom in their last month of life - most commonly pain (46%), fatigue (43%) and poor appetite (30%). Children who received cancer-directed therapy during the end-of-life period (47%) suffered from a greater number of symptoms than those who did not receive treatment (P = 0.03), but the severity of symptoms did not differ between these groups. Of the children treated for specific symptoms, treatment was successful in 47% of those with pain, 18% of those with fatigue and 17% of those with poor appetite. Of the 61 families who felt they had time to plan where their child would die, 89% preferred to have their child die at home. The majority of children (61%) died at home. Of those who died in hospital, less than a quarter died in the intensive care unit.
Conclusions: Relatively high rates of death at home and low rates of unsuccessful medical interventions suggest a realistic approach at the end of life for Australian children dying of cancer. However, many suffer from unresolved symptoms, and greater attention should be paid to palliative care for these children. MJA 2010; 192: 71-75
C1 [Heath, John A.; McCarthy, Maria] Royal Childrens Hosp, Childrens Canc Ctr, Psychooncol Program, Melbourne, Vic, Australia.
[Donath, Susan M.] Murdoch Childrens Res Inst, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.
[Anderson, Vicki A.] Royal Childrens Hosp, Dept Psychol, Melbourne, Vic, Australia.
[Wolfe, Joanne] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA.
RP Heath, JA (reprint author), Royal Childrens Hosp, Childrens Canc Ctr, Psychooncol Program, Melbourne, Vic, Australia.
EM john.heath@rch.org.au
OI Donath, Susan/0000-0003-2489-3977
NR 20
TC 33
Z9 35
U1 1
U2 9
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 JAN 18
PY 2010
VL 192
IS 2
BP 71
EP 75
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 552CN
UT WOS:000274264600006
PM 20078405
ER
PT J
AU Tartar, JL
McKenna, JT
Ward, CP
McCarley, RW
Strecker, RE
Brown, RE
AF Tartar, Jaime L.
McKenna, James T.
Ward, Christopher P.
McCarley, Robert W.
Strecker, Robert E.
Brown, Ritchie E.
TI Sleep fragmentation reduces hippocampal CA1 pyramidal cell excitability
and response to adenosine
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Sleep interruption; Input resistance; Whole cell; A1 receptor
ID CENTRAL-NERVOUS-SYSTEM; RAT HIPPOCAMPUS; IN-VITRO; SYNAPTIC PLASTICITY;
BASAL FOREBRAIN; DEPRIVATION; RECEPTORS; NEURONS; BRAIN; SITE
AB Sleep fragmentation (SF) impairs the restorative/cognitive benefits of sleep via as yet unidentified alterations in neural physiology. Previously,we found that hippocampal synaptic plasticity and spatial learning are impaired in a rat model of SF which utilizes a treadmill to awaken the animals every 2 min, mimicking the frequency of awakenings observed in human sleep apnea patients. Here, we investigated the cellular mechanisms responsible for these effects, using whole-cell patch-clamp recordings. 24 h of SF decreased the excitability of hippocampal CA1 pyramidal neurons via decreased input resistance, without alterations in other intrinsic membrane or action potential properties (when compared to cage controls, or to exercise controls that experienced the same total amount of treadmill movement as SF rats). Contrary to our initial prediction, the hyperpolarizing response to bath applied adenosine (30 mu M) was reduced in the CA1 neurons of SF treated rats. Our initial prediction was based on the evidence that sleep loss upregulates cortical adenosine A1 receptors; however, the present findings are consistent with a very recent report that hippocampal A1 receptors are not elevated by sleep loss. Thus. increased adenosinergic inhibition is unlikely to be responsible for reduced hippocampal long-term potentiation in SF rats. Instead, the reduced excitability of CA1 pyramidal neurons observed here may contribute to the loss of hippocampal long-term potentiation and hippocampus-dependent cognitive impairments associated with sleep disruption. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Brown, Ritchie E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA.
Harvard Univ, Sch Med, Brockton, MA 02301 USA.
RP Brown, RE (reprint author), VA Boston Healthcare Syst, Res 151-C,940 Belmont St, Brockton, MA 02301 USA.
EM ritchie_brown@hms.harvard.edu
RI McCarley, Robert/N-5562-2014;
OI McCarley, Robert/0000-0001-5705-7495; Ward,
Christopher/0000-0001-9932-3894; Tartar, Jaime/0000-0002-3452-0579;
Brown, Ritchie/0000-0002-7164-4132
FU [NHBLI-P50 HL060292]; [NHLBI-T32 HL0790]
FX We thank John Franco for care of the animals. This research was
supported by VA, NHBLI-P50 HL060292 (RES and RWM) and NHLBI-T32 HL07901
(JLT).
NR 30
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U1 0
U2 3
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 JAN 18
PY 2010
VL 469
IS 1
BP 1
EP 5
DI 10.1016/j.neulet.2009.11.032
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 556CN
UT WOS:000274565500001
PM 19914331
ER
PT J
AU Li, CQ
Pastila, RK
Pitsillides, C
Runnels, JM
Puoris'haag, M
Cote, D
Lin, CP
AF Li, Chunqiang
Pastila, Riikka K.
Pitsillides, Costas
Runnels, Judith M.
Puoris'haag, Mehron
Cote, Daniel
Lin, Charles P.
TI Imaging leukocyte trafficking in vivo with two-photon-excited endogenous
tryptophan fluorescence
SO OPTICS EXPRESS
LA English
DT Article
ID LASER-SCANNING MICROSCOPY; NONMELANOMA SKIN-CANCER; ULTRAVIOLET
MICROSCOPY; MULTIPHOTON MICROSCOPY; CONFOCAL MICROSCOPY; 3-PHOTON
EXCITATION; BONE-MARROW; INFLAMMATION; MIGRATION; PROTEINS
AB We describe a new method for imaging leukocytes in vivo by exciting the endogenous protein fluorescence in the ultraviolet (UV) spectral region where tryptophan is the major fluorophore. Two-photon excitation near 590 nm allows noninvasive optical sectioning through the epidermal cell layers into the dermis of mouse skin, where leukocytes can be observed by video-rate microscopy to interact dynamically with the dermal vascular endothelium. Inflammation significantly enhances leukocyte rolling, adhesion, and tissue infiltration. After exiting the vasculature, leukocytes continue to move actively in tissue as observed by time-lapse microscopy, and are distinguishable from resident autofluorescent cells that are not motile. Because the new method alleviates the need to introduce exogenous labels, it is potentially applicable for tracking leukocytes and monitoring inflammatory cellular reactions in humans. (C) 2010 Optical Society of America
C1 [Li, Chunqiang; Pastila, Riikka K.; Pitsillides, Costas; Runnels, Judith M.; Puoris'haag, Mehron; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA.
[Li, Chunqiang; Pastila, Riikka K.; Pitsillides, Costas; Runnels, Judith M.; Puoris'haag, Mehron; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA.
[Pastila, Riikka K.] Radiat & Nucl Safety Author, FI-00881 Helsinki, Finland.
[Pitsillides, Costas] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Runnels, Judith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Cote, Daniel] Univ Laval, Univ Laval Robert Giffard, Ctr Rech, Quebec City, PQ G1J2G3, Canada.
RP Li, CQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 185 Cambridge St, Boston, MA 02115 USA.
EM Li.Chunqiang@mgh.harvard.edu
RI Cote, Daniel/D-5185-2011
FU National Institutes of Health [CA111519-01]; Johnson Johnson Inc.;
Academy of Finland; Jenny and Antti Wihuri Foundation
FX We thank Drs. R. Rox Anderson, Nikiforos Kollias and Paulo Bargo for
insightful discussions about skin imaging. We also thank Dr. Irene
Ghobrial for supplying cultured multiple myeloma cells. Our work was
supported by grants from the National Institutes of Health
(CA111519-01), Johnson & Johnson Inc. (C. P. L.), Academy of Finland,
and Jenny and Antti Wihuri Foundation (R. K. P.).
NR 31
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U1 2
U2 12
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 JAN 18
PY 2010
VL 18
IS 2
BP 988
EP 999
DI 10.1364/OE.18.000988
PG 12
WC Optics
SC Optics
GA 547BP
UT WOS:000273860400062
PM 20173920
ER
PT J
AU Graham, DP
Savas, L
White, D
El-Serag, R
Laday-Smith, S
Tan, G
El-Serag, HB
AF Graham, D. P.
Savas, L.
White, D.
El-Serag, R.
Laday-Smith, S.
Tan, G.
El-Serag, H. B.
TI Irritable bowel syndrome symptoms and health related quality of life in
female veterans
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID FUNCTIONAL GASTROINTESTINAL DISORDERS; POSTTRAUMATIC-STRESS-DISORDER;
GENERALIZED ANXIETY DISORDER; GULF-WAR VETERANS; WOMEN VETERANS;
PSYCHOMETRIC PROPERTIES; MEDICAL PATIENTS; SURVEY SF-36; PREVALENCE;
INVENTORY
AB P>Background
The status and determinants of health-related quality of life (HRQOL) in female veterans with and without irritable bowel syndrome (IBS) are unknown.
Aim
To compare HRQOL in female veterans with and without IBS symptoms and examine the contribution of post-traumatic stress disorder, depression and anxiety to HRQOL.
Methods
A cross-sectional study of 339 female veterans. Self-report questionnaires were used to evaluate IBS symptoms, post-traumatic stress disorder, depression, anxiety and HRQOL.
Results
Symptoms consistent with IBS were present in 33.5% of participants. Female veterans with IBS symptoms had significant reductions in physical component score and 5 of 8 Health Related Quality of Life subscales and on 7 of 8 Irritable Bowel Syndrome Quality Of Life subscales than female veterans without IBS symptoms. Compared with the US general female population, female veterans had significantly lower Health Related Quality of Life physical component score and mental component scores (MCS) irrespective of IBS symptom status. Differences in the MCS score were most explained by depression, while those in the physical component score were most explained by anxiety.
Conclusions
Irritable bowel syndrome symptoms in female veterans are associated with considerable reduction in HRQOL. However, female veterans, regardless of IBS symptom status, have lower HRQOL compared with the general US female population.
Aliment Pharmacol Ther 31, 261-273.
C1 [Graham, D. P.; White, D.; El-Serag, H. B.] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX USA.
[Graham, D. P.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Savas, L.] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Savas, L.] Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA.
[White, D.; El-Serag, H. B.] Michael E DeBakey Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA.
[White, D.; El-Serag, H. B.] Baylor Coll Med, Gastroenterol Sect, Houston, TX 77030 USA.
[El-Serag, R.; Laday-Smith, S.] Michael E DeBakey Dept Vet Affairs Med Ctr, Womens Hlth Ctr, Houston, TX USA.
[Tan, G.] Baylor Coll Med, Dept Anesthesiol & Phys Med & Rehabil, Houston, TX 77030 USA.
RP Graham, DP (reprint author), Houston VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA.
EM david.graham@med.va.gov
RI Graham, David /J-1158-2014
FU Department of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development Service [H-17978]; Novartis
pharmaceuticals; Public Health Service [DK56338]; National Institute of
Health [K-24 DK078154-03]; National Research Service [5 T32 HP10031-09]
FX Disclosure of personal interests: Hashem El-Serag has served as a
consultant and an advisory board member for Novartis Pharmaceuticals.
None of the authors is an employee, owns stocks or shares, or has
patents that constitute a conflict of interest. Hashem B. ElSerag was
responsible for the study design. Hashem B. El-Serag and David P. Graham
were responsible for the interpretation of results and manuscript. Data
analysis was done by David P. Graham. All authors reviewed and revised
the manuscript of the paper and approved its final version. All analyses
and writing was conducted solely by the listed authors. There are no
conflicts of interest. The views expressed in this article are those of
the author(s) and do not necessarily represent the views of the
Department of Veterans Affairs. Declaration of funding interests: The
research reported/outlined here was supported by the Department of
Veterans Affairs, Veterans Health Administration, Health Services
Research and Development Service (HSR&D, project H-17978). This work was
also supported in part by a grant from Novartis pharmaceuticals to Dr
El-Serag, and by a Public Health Service Grant DK56338 which funds the
Texas Medical Center Digestive Disease Center. Dr El-Serag was supported
by National Institute of Health grant K-24 DK078154-03. Dr Savas was
supported by the National Research Service Award 5 T32 HP10031-09 funded
by the Health Resources and Services.
NR 59
TC 8
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U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD JAN 15
PY 2010
VL 31
IS 2
BP 261
EP 273
DI 10.1111/j.1365-2036.2009.04159.x
PG 13
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 533ZH
UT WOS:000272864600011
PM 19814746
ER
PT J
AU Huang, ES
Turner, BG
Fernandez-Del-Castillo, C
Brugge, WR
Hur, C
AF Huang, E. S.
Turner, B. G.
Fernandez-Del-Castillo, C.
Brugge, W. R.
Hur, C.
TI Pancreatic cystic lesions: clinical predictors of malignancy in patients
undergoing surgery
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID PAPILLARY MUCINOUS NEOPLASMS; PATHOLOGICAL CORRELATION; ENDOSCOPIC
ULTRASOUND; DIAGNOSIS; TUMORS; DUCT; CT; RESECTION; ACCURACY; OBSERVE
AB P>Background
Despite advances in cross-sectional imaging and the use of molecular markers, distinguishing between benign and malignant cysts remains a clinical challenge.
Aims
To identify both preoperative clinical and cyst characteristics at the time of EUS that predict malignancy.
Methods
A retrospective analysis was performed on consecutive patients with pancreatic cysts who underwent endoscopic ultrasound (EUS) and surgical resection from May 1996 to December 2007 at a tertiary centre. Clinical history, EUS characteristics, cytology, tumour markers and surgical histology were collected. Predictors of malignancy were determined by univariate and multivariate analysis using logistic regression.
Results
A total of 153 patients underwent a EUS and subsequent surgical intervention.Of the 153 patients, 57 (37%) had a histological diagnosis of malignancy. On univariate analysis, older age (P < 0.001), male gender (P = 0.010), jaundice (P = 0.039), history of other malignancy (P = 0.036), associated mass in cyst (P = 0.004) and malignant cytology (P < 0.001) were found to be associated with malignancy. History of pancreatitis (P = 0.008) and endoscopist impression of pseudocyst (P = 0.001) were found to be associated with benign cysts. Multivariate analysis found that only older age [Odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01-1.08], male gender (OR, 2.26; 95% CI, 1.08-4.73) and malignant cytology (OR, 6.60; 95% CI, 2.02-21.58) were independent predictors of malignancy.
Conclusions
Older age, male gender and malignant cytology from EUS predict malignancy at surgical resection. These characteristics may be used to estimate the probability of malignancy in a cyst and aid in management.
Aliment Pharmacol Ther 31, 285-294.
C1 [Huang, E. S.; Turner, B. G.; Brugge, W. R.; Hur, C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Fernandez-Del-Castillo, C.] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA.
[Huang, E. S.; Hur, C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Huang, E. S.; Turner, B. G.; Fernandez-Del-Castillo, C.; Brugge, W. R.; Hur, C.] Harvard Univ, Sch Med, Boston, MA USA.
RP Huang, ES (reprint author), 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM eshuang@partners.org
OI Hur, Chin/0000-0002-2819-7576
FU National Institutes of Health [T32DK007191, K07CA107060]
FX Declaration of personal interests: None. Declaration of funding
interests: This study was funded in part by National Institutes of
Health, grant numbers T32DK007191 (ESH, BGT) and K07CA107060 (CH).
NR 36
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U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD JAN 15
PY 2010
VL 31
IS 2
BP 285
EP 294
DI 10.1111/j.1365-2036.2009.04173.x
PG 10
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 533ZH
UT WOS:000272864600013
PM 19845568
ER
PT J
AU Sarosiek, I
Selover, KH
Katz, LA
Semler, JR
Wilding, GE
Lackner, JM
Sitrin, MD
Kuo, B
Chey, WD
Hasler, WL
Koch, KL
Parkman, HP
Sarosiek, J
McCallum, RW
AF Sarosiek, I.
Selover, K. H.
Katz, L. A.
Semler, J. R.
Wilding, G. E.
Lackner, J. M.
Sitrin, M. D.
Kuo, B.
Chey, W. D.
Hasler, W. L.
Koch, K. L.
Parkman, H. P.
Sarosiek, J.
McCallum, R. W.
TI The assessment of regional gut transit times in healthy controls and
patients with gastroparesis using wireless motility technology
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID GASTROESOPHAGEAL-REFLUX DISEASE; BOWEL BACTERIAL OVERGROWTH;
GASTROINTESTINAL TRANSIT; DIABETIC GASTROPARESIS; CONSTIPATION; PH;
SCINTIGRAPHY; SYMPTOMS; CAPSULE; MEAL
AB P>Background
Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times.
Aims
To analyse data from a multi-centre study of gastroparetic patients and healthy controls and to compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP).
Methods
A total of 66 healthy controls and 34 patients with GP (15 diabetic and 19 idiopathic) swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) were calculated using the wireless motility capsule.
Results
Gastric emptying time, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic aetiologies of gastroparetics had significantly slower WGTT (P < 0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls (P = 0.0054).
Conclusions
In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. The prolongation of CTT in gastroparetic patients indicates that dysmotility beyond the stomach in GP is present, and it could be contributing to symptom presentation.
Aliment Pharmacol Ther 31, 313-322.
C1 [Sarosiek, I.; Sarosiek, J.; McCallum, R. W.] Univ Kansas, Med Ctr, Ctr Gastrointestinal Nerve & Muscle Funct & GI Mo, Kansas City, KS 66103 USA.
[Selover, K. H.; Semler, J. R.] SmartPill Corp, Buffalo, NY USA.
[Katz, L. A.] SUNY Buffalo, Dept ofMedicine, Sch Med, Buffalo, NY 14260 USA.
[Wilding, G. E.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA.
[Lackner, J. M.] SUNY Buffalo, Behav Med Clin, Dept Gastroenterol Hepatol & Nutr, Sch Med, Buffalo, NY 14260 USA.
[Sitrin, M. D.] SUNY Buffalo, Western New York VA Med Ctr, Div Gastroenterol Hepatol & Nutr, Dept Med, Buffalo, NY 14260 USA.
[Kuo, B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Chey, W. D.; Hasler, W. L.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Koch, K. L.] Wake Forest Univ, Gastroenterol Sect, Baptist Med Ctr, Winston Salem, NC 27109 USA.
[Parkman, H. P.] Temple Univ, Gastroenterol Sect, Dept Med, Sch Med, Philadelphia, PA 19122 USA.
RP Sarosiek, I (reprint author), Texas Tech Univ, HSC, Paul Foster Sch Med, 4800 Albertson Ave, El Paso, TX 79905 USA.
EM Irene.sarosiek@ttuhsc.edu
FU SmartPill Corporation, Buffalo, New York; NYSTAR [C020118]; NIH
[DK069614]
FX Disclosure of personal interests: Drs I and J Sarosiek and Dr M Sitrin
did not receive funding support from The SmartPill Corporation. Drs
Chey, Hasler, Kuo, Lackner, McCallum, Parkman, Koch and Katz serve as
speakers, consultants, or advisory board members for The SmartPill
Corporation and have received research funding from The SmartPill
Corporation. Dr Wilding serves as a consultant to The SmartPill
Corporation. Dr Semler and Ms Selover are employees of The SmartPill
Corporation; Dr Semler owns stock in The SmartPill Corporation. Dr I
Sarosiek authored the manuscript; all other listed authors provided
insightful edits, feedback and approval of the final manuscript.
Declaration of funding interests: The study was sponsored by The
SmartPill Corporation, Buffalo, New York, manufacturers of the SmartPill
GI Monitoring System, and partially supported by NYSTAR grant C020118
and NIH grant DK069614.
NR 42
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Z9 51
U1 1
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD JAN 15
PY 2010
VL 31
IS 2
BP 313
EP 322
DI 10.1111/j.1365-2036.2009.04162.x
PG 10
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 533ZH
UT WOS:000272864600016
PM 19814743
ER
PT J
AU Hage, FG
Agel, R
Aljaroudi, WL
Heo, J
Pothineni, K
Hansalia, S
Lawson, D
Dubovsky, E
Iskandrian, AE
AF Hage, Fadi G.
Agel, Raed
Aljaroudi, Wad L.
Heo, Jaekyeong
Pothineni, Koteswara
Hansalia, Sachin
Lawson, David
Dubovsky, Eva
Iskandrian, Ami E.
TI Correlation Between Serum Cardiac Markers and Myocardial Infarct Size
Quantified by Myocardial Perfusion Imaging in Patients With Hypertrophic
Cardiomyopathy After Alcohol Septal Ablation
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID BRAIN NATRIURETIC PEPTIDE; PHOTON-EMISSION-TOMOGRAPHY; TROPONIN-T;
EJECTION FRACTION; CREATINE-KINASE; TC-99M-SESTAMIBI; REPERFUSION;
EXPRESSION; BIOMARKERS; SERIAL
AB Myocardial infarct (MI) size is a well-established prognostic marker but the association of serum markers with MI size, as measured by myocardial perfusion imaging (MPI), has not been well studied in patients with hypertrophic cardiomyopathy (NC) after alcohol septal ablation (ASA). Creatine kinase (CK), CK-MB, troponin I, and brain natriuretic peptide were measured before and at multiple points after ASA in patients with HC and were correlated with MI size measured by MPI. MPI at rest was performed in 54 patients with HC at a median of 2 days after ASA. CK, CK-MB, and troponin I increased after ASA to peak levels at 12 hours and their cumulative levels (area under the curve) showed significant correlation with size of MI by MPI (r = 0.544, 0.408, and 0.477, p <0.001, 0.003, and 0.001, respectively). The best marker was level of CK at 12 hours (r = 0.609, p <0.0001) after ASA. Brain natriuretic peptide level did not change significantly after ASA (p = 1.0) and only weakly correlated with MI size by MPI (r = 0.130, p = 0.007). In conclusion, CK, CK-MB, and troponin I measured at 12 hours, at peak, and as the area under the curve correlated well with infarct size, but CK level at 12 hours was the best marker. CK continues to be a useful marker of MI size despite the introduction of newer, more specific markers, especially when infarct onset is known with certainty as in patients with HC undergoing ASA. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:261-266)
C1 [Hage, Fadi G.; Agel, Raed; Aljaroudi, Wad L.; Heo, Jaekyeong; Pothineni, Koteswara; Hansalia, Sachin; Lawson, David; Dubovsky, Eva; Iskandrian, Ami E.] Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
[Hage, Fadi G.; Agel, Raed] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA.
RP Hage, FG (reprint author), Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
EM fadihage@uab.edu
OI Hage, Fadi/0000-0002-1397-4942
NR 25
TC 7
Z9 8
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 JAN 15
PY 2010
VL 105
IS 2
BP 261
EP 266
DI 10.1016/j.amjcard.2009.08.680
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 602JW
UT WOS:000278136400023
PM 20102929
ER
PT J
AU Kesavan, Y
Giovannucci, E
Fuchs, CS
Michaud, DS
AF Kesavan, Yamini
Giovannucci, Edward
Fuchs, Charles S.
Michaud, Dominique S.
TI A Prospective Study of Magnesium and Iron Intake and Pancreatic Cancer
in Men
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cohort studies; diet; iron, dietary; magnesium; pancreatic neoplasms
ID C-REACTIVE PROTEIN; FOOD FREQUENCY QUESTIONNAIRE; MALE
HEALTH-PROFESSIONALS; TOTAL-ENERGY-INTAKE; DRINKING-WATER; DIETARY
MAGNESIUM; INSULIN-RESISTANCE; DIABETES-MELLITUS; COLORECTAL-CANCER;
OXIDATIVE STRESS
AB Many studies have investigated the relation between magnesium and iron intake and diabetes and, separately, between diabetes and pancreatic cancer. However, no known study has examined the direct association of magnesium and iron intake with pancreatic cancer risk. The authors obtained magnesium and iron intake data using food frequency questionnaires from the US male Health Professionals Follow-up Study, which began in 1986. During 851,476 person-years and 20 years of follow-up, 300 pancreatic cancer cases were documented. Cox proportional hazards models were used to estimate relative risks, adjusting for age, smoking, and body mass index. No associations were observed between magnesium or iron intake and pancreatic cancer (highest vs. lowest quintile: relative risk (RR) = 0.94, 95% confidence interval (CI): 0.66, 1.32 and RR = 0.93, 95% CI: 0.65, 1.34, respectively). Similarly, iron or magnesium supplement use was not related to pancreatic cancer. A statistically significant inverse relation was noted between magnesium and pancreatic cancer for subjects with a body mass index of >= 25 kg/m(2) (RR = 0.67, 95% CI: 0.46, 0.99; P-trend = 0.04). Although, overall, no relation between magnesium or iron intake and pancreatic cancer was observed in this cohort of men, an inverse association with magnesium was suggested among overweight individuals, which should be examined in other studies.
C1 [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England.
[Kesavan, Yamini; Giovannucci, Edward; Michaud, Dominique S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Giovannucci, Edward; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP Michaud, DS (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, St Marys Campus,Norfolk Pl, London W2 1PG, England.
EM d.michaud@imperial.ac.uk
RI Michaud, Dominique/I-5231-2014
FU National Cancer Institute; National Institutes of Health, Bethesda,
Maryland [CA124908]
FX This study was supported by grants from the National Cancer Institute,
National Institutes of Health, Bethesda, Maryland ( grant CA124908).
NR 55
TC 11
Z9 11
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JAN 15
PY 2010
VL 171
IS 2
BP 233
EP 241
DI 10.1093/aje/kwp373
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 539AD
UT WOS:000273224700011
PM 20022893
ER
PT J
AU Chen, GD
Alberts, CJ
Rodriguez, W
Toner, M
AF Chen, Grace D.
Alberts, Catharina J.
Rodriguez, William
Toner, Mehmet
TI Concentration and Purification of Human Immunodeficiency Virus Type 1
Virions by Microfluidic Separation of Superparamagnetic Nanoparticles
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID RESOURCE-LIMITED SETTINGS; HIV-1 VIRAL LOAD; MAGNETIC NANOPARTICLES;
CELL-SEPARATION; ON-CHIP; SAMPLES; CAPTURE; SYSTEMS; MIXER;
MICROCHANNELS
AB The low concentration and complex sample matrix of many clinical and environmental viral samples presents a significant challenge in the development of low cost, point-of-care viral assays. To address this problem, we investigated the use of a microfluidic passive magnetic separator combined with on-chip mixer to both purify and concentrate whole-particle human immunodeficiency virus type 1 (HIV-1) virions. Virus-containing plasma samples are first mixed to allow specific binding of the viral particles with antibody-conjugated superparamagnetic nanoparticles, and several passive mixer geometries were assessed for their mixing efficiencies. The virus-nanoparticle complexes are then separated from the plasma in a novel magnetic separation chamber, where packed micrometer-sized ferromagnetic particles serve as high magnetic gradient concentrators for an externally applied magnetic field. Thereafter, a viral lysis buffer was flowed through the chip and the released HIV proteins were assayed off-chip. Viral protein extraction efficiencies of 62% and 45% were achieved at 10 and 30 mu L/min throughputs, respectively. More importantly, an 80-fold concentration was observed for an initial sample volume of 1 mL and a 44-fold concentration for an initial sample volume of 0.5 mL. The system is broadly applicable to microscale sample preparation of any viral sample and can be used for nucleic acid extraction as well as 40-80-fold enrichment of target viruses.
C1 [Chen, Grace D.; Alberts, Catharina J.; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Charlestown, MA 02129 USA.
[Rodriguez, William] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA.
RP Rodriguez, W (reprint author), Daktari Diagnost Inc, Arlington, MA 02476 USA.
EM wrodriguez@daktaridx.com; mtoner@hms.harvard.edu
FU Center for Integration of Medicine and Innovative Technology [09-441];
National Institute of Biomedical Imaging and Bioengineering [P41
EB002503]
FX We thank Mr. Octavio Hurtado for technical support with microfabrication
procedures and Ms. Alicja Trocha for assistance with the biosafety of
HIV handling. We thank Partners AIDS Research Center for provision of
HIV samples and use of tissue Culture facilities. This work was
supported by the Center for Integration of Medicine and Innovative
Technology under Grant 09-441 and the National Institute of Biomedical
Imaging and Bioengineering under Grant P41 EB002503 (BioMEMS Resource
Center).
NR 39
TC 50
Z9 52
U1 4
U2 56
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD JAN 15
PY 2010
VL 82
IS 2
BP 723
EP 728
DI 10.1021/ac9024522
PG 6
WC Chemistry, Analytical
SC Chemistry
GA 542HR
UT WOS:000273484200039
PM 19954210
ER
PT J
AU Chou, RC
Dinarello, CA
Ferry, JA
Dal Cin, P
AF Chou, Richard C.
Dinarello, Charles A.
Ferry, Judith A.
Dal Cin, Paola
TI A 36-Year-Old Woman With Recurrent High-Grade Fevers, Hypotension, and
Hypertriglyceridemia
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID MACROPHAGE-ACTIVATION SYNDROME; JUVENILE IDIOPATHIC ARTHRITIS;
APOPTOSIS-INDUCING LIGAND; ONSET STILLS-DISEASE; MYELODYSPLASTIC
SYNDROMES; SCHNITZLER-SYNDROME; CYCLOSPORINE-A; BONE-MARROW; EXPRESSION;
ANAKINRA
C1 [Ferry, Judith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Dinarello, Charles A.] Univ Colorado Sch Med Denver, Aurora, CO USA.
[Dal Cin, Paola] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Chou, RC (reprint author), Dartmouth Hitchcock Med Ctr, Rheumatol Sect, Dept Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM Richard.C.Chou@hitchcock.org
NR 36
TC 3
Z9 3
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2151-464X
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD JAN 15
PY 2010
VL 62
IS 1
BP 128
EP 136
DI 10.1002/acr.20024
PG 9
WC Rheumatology
SC Rheumatology
GA 639MI
UT WOS:000280978500018
PM 20191502
ER
PT J
AU Shinozaki, S
Inoue, Y
Yang, W
Fukaya, M
Carter, EA
Ming-Yu, Y
Fischman, A
Tompkins, R
Kaneki, M
AF Shinozaki, Shohei
Inoue, Yoko
Yang, Wen
Fukaya, Makiko
Carter, Edward A.
Ming-Yu, Young
Fischman, Alan
Tompkins, Ronald
Kaneki, Masao
TI Farnesyltransferase inhibitor improved survival following endotoxin
challenge in mice
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Farnesylation; Statin; HMG-CoA reductase; Lipopolysaccharide; Caspase-3;
c-Jun NH(2)-terminal kinase; Liver; Spleen
ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; ATHEROSCLEROSIS
DEVELOPMENT; REDUCTASE INHIBITORS; STATIN TREATMENT; SYRIAN-HAMSTERS;
CELL APOPTOSIS; SEVERE SEPSIS; LIVER-DAMAGE; SEPTIC SHOCK
AB Endotoxemia plays an important role in the pathogenesis of sepsis and is accompanied by dysregulated apoptosis of immune and non-immune cells. Treatment with statins reduces mortality in rodent models of sepsis and endotoxemia. Inhibition of protein isoprenylation, including farnesylation, has been proposed as a mechanism to mediate the lipid-lowering-independent effects of statins. Nonetheless, the effects of the inhibition of isoprenylation have not yet been studied. To investigate the role of farnesylation, we evaluated the effects of farnesyltransferase inhibitor and statin on survival following lipopolysaccharide (LPS) challenge in mice. Both simvastatin (2 mg/kg BW) and FTI-277 (20 mg/kg BW) treatment improved survival by twofold after LPS injection, as compared with vehicle alone (p < 0.01). LPS-induced cleavage (activation) of caspase-3, an indicator of apoptotic change, and increased protein expression of proapoptotic molecules, Bax and Bim, and activation of c-Jun NH(2)-terminal kinase (JNK/SAPK) in the liver and spleen were attenuated by both simvastatin and FTI-277. These results demonstrate that farnesyltransferase inhibitor as well as statin significantly reduced LPS-induced mortality in mice. Our findings also suggest that inhibition of protein farnesylation may contribute to the lipid-lowering-independent protective effects of statins in endotoxemia, and that protein farnesylation may play a role in LPS-induced stress response, including JNK/SAPK activation, and apoptotic change. Our data argue that farnesyltransferase may be a potential molecular target for treating patients with endotoxemia. (c) 2009 Elsevier Inc. All rights reserved.
C1 [Shinozaki, Shohei; Yang, Wen; Fukaya, Makiko; Carter, Edward A.; Ming-Yu, Young; Fischman, Alan; Tompkins, Ronald; Kaneki, Masao] Shriners Hosp Children, Boston, MA 02114 USA.
[Shinozaki, Shohei; Inoue, Yoko; Yang, Wen; Fukaya, Makiko; Kaneki, Masao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Carter, Edward A.; Ming-Yu, Young; Tompkins, Ronald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Burns & Trauma, Boston, MA 02114 USA.
[Fischman, Alan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nucl Med, Boston, MA 02114 USA.
RP Kaneki, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA.
EM mkaneki@partners.org
FU National Institutes of Health [GM21700, DK58127]; Shriners Hospitals for
Children
FX This work was supported by grants from the National Institutes of
Health, GM21700 (R. Tompkins) and DK58127 (M. Kaneki), and the Shriners
Hospitals for Children (M. Kaneki, R. Tompkins, A. Fischman, Y.
Ming-Yu).
NR 51
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Z9 20
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JAN 15
PY 2010
VL 391
IS 3
BP 1459
EP 1464
DI 10.1016/j.bbrc.2009.12.094
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 550AL
UT WOS:000274097800030
PM 20034462
ER
PT J
AU Nahas, Z
Anderson, BS
Borckardt, J
Arana, AB
George, MS
Reeves, ST
Takacs, I
AF Nahas, Ziad
Anderson, Berry S.
Borckardt, Jeff
Arana, Ashley B.
George, Mark S.
Reeves, Scott T.
Takacs, Istvan
TI Bilateral Epidural Prefrontal Cortical Stimulation for
Treatment-Resistant Depression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Anterior poles; brain stimulation; cingulate; depression; epidural
cortical stimulation; frontal lobes; medial prefrontal cortex
ID VAGUS NERVE-STIMULATION; DEEP BRAIN-STIMULATION; TRANSCRANIAL MAGNETIC
STIMULATION; MOTOR CORTEX STIMULATION; MAJOR DEPRESSION; NEUROPATHIC
PAIN; RATING-SCALE; OUTCOMES; BURDEN; VNS
AB Background: Treatment-resistant depression presents a serious challenge to both patients and clinicians. The anterior and midlateral prefrontal cortices play complementary roles in integrating emotional and cognitive experiences and in modulating subcortical regions. Both regions offer a distinct opportunity for targeted antidepressant treatments. We chose to pilot the safety and therapeutic benefits of chronic and intermittent epidural prefrontal cortical stimulation (EpCS) in patients with treatment-resistant depression.
Methods: We enrolled five adults with an average of 5.8 failed antidepressant treatments in their current depressive episode. All subjects underwent comprehensive clinical assessments, detailed neuropsychological testing, and presurgical magnetic resonance imaging. Four cortical stimulation paddle leads were stereotactically placed bilaterally over the anterior frontal poles and midlateral prefrontal cortex. We also acquired a postsurgical computed tomography scan and repeatedly assessed clinical outcomes over time of EpCS as an adjunctive treatment to constant medications.
Results: All patients tolerated the therapy. At 7-month follow-up, the average improvement from preimplant baseline on the Hamilton Rating Scale for Depression and the Inventory of Depressive Symptoms-Self-Report were 54.9% (+/- 37.7) and 60.1% (+/- 34.1), respectively. Three implanted subjects reached remission. One patient's left hemisphere leads were explanted 12 weeks postsurgery because of a scalp infection.
Conclusions: Bilateral EpCS over anterior and mid lateral frontal cortex is a promising new technology for treatment-resistant depression. Future double-blind studies are warranted.
C1 [Nahas, Ziad; Anderson, Berry S.; Borckardt, Jeff; Arana, Ashley B.; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Mood Disorders Program & Brain Stimulat Lab, Charleston, SC 29425 USA.
[Nahas, Ziad; George, Mark S.; Takacs, Istvan] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Borckardt, Jeff; Reeves, Scott T.] Med Univ S Carolina, Dept Anesthesia & Perioperat Med, Charleston, SC 29425 USA.
[George, Mark S.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA.
[Takacs, Istvan] Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA.
[George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Nahas, Z (reprint author), Inst Psychiat, 67 President St, Charleston, SC 29425 USA.
EM nahasz@musc.edu
FU National Alliance of Research for Depression and Schizophrenia (NARSAD)
Independent Investigator Award; Mood Disorders Program; The Brain
Stimulation Laboratory; General Clinical Research Center; Center for
Advanced Imaging Research at the Medical University of South Carolina;
Medtronic, Inc.; The National Institute of Mental Health (NIMH);
National Alliance Research for Schizophrenia and Depression; Hope for
Depression Research, Neuronetics, Inc.; Cyberonics, Inc.;
GlaxoSmithKline; Jazz Pharmaceuticals; National Institute on Drug Abuse;
National Institute of Neurological Disorders and Stroke; Ralph H.
Johnson VA Medical Center
FX This study was funded primarily by a National Alliance of Research for
Depression and Schizophrenia (NARSAD) Independent Investigator Award to
ZN. It was also made possible with general funds from the Mood Disorders
Program, The Brain Stimulation Laboratory, the General Clinical Research
Center, the Center for Advanced Imaging Research at the Medical
University of South Carolina, Medtronic, Inc. (Minneapolis, MN donated
the devices, but was otherwise not involved in the study particularly
data acquisition, analysis, or drafting the article. We thank Mark Rise
(Medtronic, Inc.) for technical assistance ill stimulation setups and
Sarah Coker (now a postgraduate year I psychiatry resident at Medical
University of South Carolina [MUSC]) for assistance in, The accuracy, of
lead placement analysis I. S.; Dr. Nahas reports having received
consulting fees from Neuronetics, Inc. and Cyberonics, Inc.; research
funding from the The National Institute of Mental Health (NIMH),
National Alliance Research for Schizophrenia and Depression, Hope for
Depression Research, Neuronetics, Inc., Cyberonics, Inc., Medtronic,
Inc. (in the form of device donations for this study), Brainsway, and
Integra. Dr. George reports research funding from GlaxoSmithKline, Jazz
Pharmaceuticals, NIMH, National Institute on Drug Abuse, National
Institute of Neurological Disorders and Stroke. and the Ralph H. Johnson
VA Medical Center. Dr. George reported consulting for ,
Bristol-Meyers-Squibb, DarPharma, , Jazz Pharmaceuticals, Parke Davis,
Aspect Medical, Brainsway (unpaid) , Cephos (unpaid), Cyberonics, Inc.,
Dantex, MediPhysics/Amersham, Neuronetics, Inc. (unpaid), and Neuropace.
Dr. George also reported that The Medical University of South Carolina
has filed eight patents or invention disclosures under his name
regarding brain imaging and brain stimulation. Dr, Borckardt receives
The National Institute for Neurological Disorders and Stroke and The
National Institute of Nursing Research at the National Institutes
Health, Cyberonics, Inc., and the Neurosciences Institute at MUSC. Dr.
Borckardt is a consultant for Neuropace. Dr. Reeves, Dr. Tackacs, Mr.
Anderson, and Ms. Arana reported no biomedical financial interests or
potential conflicts of interest.
NR 59
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U1 2
U2 5
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 JAN 15
PY 2010
VL 67
IS 2
BP 101
EP 109
DI 10.1016/j.biopsych.2009.08.021
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 538RN
UT WOS:000273201800003
PM 19819427
ER
PT J
AU Kenney, LB
Nancarrow, CM
Najita, J
Vrooman, LM
Rothwell, M
Recklitis, C
Li, FP
Diller, L
AF Kenney, Lisa B.
Nancarrow, Cheryl Medeiros
Najita, Julie
Vrooman, Lynda M.
Rothwell, Monica
Recklitis, Christopher
Li, Frederick P.
Diller, Lisa
TI Health Status of the Oldest Adult Survivors of Cancer During Childhood
SO CANCER
LA English
DT Article
DE childhood cancer survivor; health status; late effects; premature
mortality
ID LONG-TERM SURVIVORS; TUMOR STUDY-GROUP; 5-YEAR SURVIVORS; WILMS-TUMOR;
HODGKINS-DISEASE; ADOLESCENT CANCER; LATE MORTALITY; RISK; NEOPLASMS;
RADIOTHERAPY
AB BACKGROUND: Young adult survivors of childhood cancer have an increased risk for treatment-related morbidity and mortality. In this study, the authors assessed how treatment for childhood cancer affects older-adult health and health practices. METHODS: One hundred seven adults treated for childhood cancer between 1947 and 1968, known to have survived past age 50 years, were identified from a single-institution cohort established in 1975. Updated vital status on eligible cases was obtained from public records. Survivors and a control group of their age-matched siblings and cousins completed a mailed survey to assess physical and social function, healthcare practices, and the prevalence of common adult illnesses. RESULTS: Of the 107 survivors known to be alive at age 50 years, 16 were deceased at follow-up; 7 deaths could be associated with prior treatment (second malignancy in radiation field [3], small bowel obstruction after abdominal radiation [2], and cardiac disease after chest irradiation [2]). The 55 survivors (median age, 56 years; range, 51-71 years), and 32 family controls (median age, 58 years; range, 48-70 years), reported similar health practices, health-related quality of life, and social function. However, survivors reported more frequent visits to healthcare providers (P < .05), more physical impairments (P < .05), fatigue (P = .02), hypertension (P = .001), and coronary artery disease (P = .01). An increased risk of hypertension was associated with nephrectomy during childhood (odds ratio, 18.9; 95% confidence interval, 3.0-118.8). CONCLUSIONS: The oldest adult survivors of childhood cancer continue to be at risk for treatment-related complications that potentially decrease their life expectancy and compromise their quality of life. Cancer 2010;116:497-505. (C) 2010 American Cancer Society.
C1 [Kenney, Lisa B.; Nancarrow, Cheryl Medeiros; Vrooman, Lynda M.; Rothwell, Monica; Recklitis, Christopher; Diller, Lisa] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Kenney, Lisa B.; Vrooman, Lynda M.; Recklitis, Christopher; Diller, Lisa] Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA.
[Kenney, Lisa B.; Vrooman, Lynda M.; Recklitis, Christopher; Diller, Lisa] Harvard Univ, Sch Med, Boston, MA USA.
[Najita, Julie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Najita, Julie] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Li, Frederick P.] Dana Farber Canc Inst, Dept Populat Sci, Boston, MA 02115 USA.
RP Kenney, LB (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, D321,44 Binney St, Boston, MA 02115 USA.
EM Lisa_Kenney@DFCI.harvard.edu
FU David B. Perini, Jr Quality of Life Clinic at the Dana-Farber Cancer
Institute; Carl J. Herzog Foundation
FX Supported by the David B. Perini, Jr Quality of Life Clinic at the
Dana-Farber Cancer Institute and the Carl J. Herzog Foundation.
NR 42
TC 10
Z9 10
U1 1
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD JAN 15
PY 2010
VL 116
IS 2
BP 497
EP 505
DI 10.1002/cncr.24718
PG 9
WC Oncology
SC Oncology
GA 546QT
UT WOS:000273826000033
PM 19908254
ER
PT J
AU Wang, WY
Niendorf, KB
Patel, D
Blackford, A
Marroni, F
Sober, AJ
Parmigiani, G
Tsao, H
AF Wang, Wenyi
Niendorf, Kristin B.
Patel, Devanshi
Blackford, Amanda
Marroni, Fabio
Sober, Arthur J.
Parmigiani, Giovanni
Tsao, Hensin
TI Estimating CDKN2A Carrier Probability and Personalizing Cancer Risk
Assessments in Hereditary Melanoma Using MelaPRO
SO CANCER RESEARCH
LA English
DT Article
ID GERMLINE MUTATIONS; PANCREATIC-CANCER; FAMILY-HISTORY; BREAST-CANCER;
BRCA1; SUSCEPTIBILITY; STATISTICS; OVARIAN; MODEL
AB Personalized cancer risk assessment remains an essential imperative in postgenomic cancer medicine. In hereditary melanoma, germline CDKN2A mutations have been reproducibly identified in melanoma-prone kindreds worldwide. However, genetic risk counseling for hereditary melanoma remains clinically challenging. To address this challenge, we developed and validated MelaPRO, an algorithm that provides germline CDKN2A mutation probabilities and melanoma risk to individuals from melanoma-prone families. MelaPRO builds on comprehensive genetic information, and uses Mendelian modeling to provide fine resolution and high accuracy. In an independent validation of 195 individuals from 167 families, MelaPRO exhibited good discrimination with a concordance index (C) of 0.86 [95% confidence intervals (95% CI), 0.75-0.97] and good calibration, with no significant difference between observed and predicted carriers (26; 95% CI, 20-35, as compared with 22 observed). In cross-validation, MelaPRO outperformed the existing predictive model MELPREDICT (C, 0.82; 95% CI, 0.61-0.93), with a difference of 0.05 (95% CI, 0.007-0.17). MelaPRO is a clinically accessible tool that can effectively provide personalized risk counseling for all members of hereditary melanoma families. Cancer Res; 70(2); 552-9. (C)2010 AACR.
C1 [Sober, Arthur J.; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Wang, Wenyi] Stanford Univ, Dept Biochem, Stanford Genome Technol Ctr, Stanford, CA 94305 USA.
[Wang, Wenyi] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
[Niendorf, Kristin B.] Univ Minnesota, Minneapolis, MN USA.
[Patel, Devanshi; Tsao, Hensin] Massachusetts Gen Hosp, Ctr Canc Risk Assessment, Boston, MA 02114 USA.
[Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Blackford, Amanda] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Marroni, Fabio] Inst Appl Genom, Udine, Italy.
RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 622 Bartlett Hall,48 Blossom St, Boston, MA 02114 USA.
EM htsao@partners.org
OI Marroni, Fabio/0000-0002-1556-5907
FU American Cancer Society [RSG MGO-112970]; National Cancer Institute [P50
CA-93683, R01CA105090-01A1]
FX Grant Support; American Cancer Society grant RSG MGO-112970 (H. Tsao and
G. Parmigiani); National Cancer Institute grant nos. P50 CA-93683 (H.
Tsao) and R01CA105090-01A1 (G. Parmigiani); and the generous
philanthropic donors to the Massachusetts General Hospital.
NR 22
TC 13
Z9 14
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 JAN 15
PY 2010
VL 70
IS 2
BP 552
EP 559
DI 10.1158/0008-5472.CAN-09-2653
PG 8
WC Oncology
SC Oncology
GA 607FW
UT WOS:000278485500015
PM 20068151
ER
PT J
AU Davis, IJ
McFadden, AW
Zhang, YX
Coxon, A
Burgess, TL
Wagner, AJ
Fisher, DE
AF Davis, Ian J.
McFadden, Andrew W.
Zhang, Yixiang
Coxon, Angela
Burgess, Teresa L.
Wagner, Andrew J.
Fisher, David E.
TI Identification of the Receptor Tyrosine Kinase c-Met and Its Ligand,
Hepatocyte Growth Factor, as Therapeutic Targets in Clear Cell Sarcoma
SO CANCER RESEARCH
LA English
DT Article
ID MALIGNANT-MELANOMA; SOFT PARTS; SCATTER FACTOR; LUNG-CANCER; MUTATIONS;
APONEUROSES; TENDONS; TRANSLOCATION; INHIBITION; TUMORS
AB Clear cell sarcoma (CCS), a childhood tumor of the tendons and aponeuroses, is uniformly fatal once it has metastasized because of its profound therapeutic resistance. CCS is characterized by production of a chimeric transcription factor, EWS-ATF1, which is formed as the result of a disease-specific chromosomal translocation. EWS-ATF1 activates the melanocyte transcription factor MITF, which in turn activates transcription of c-Met, an oncogenic receptor tyrosine kinase recently shown to be activated in CCS. Based on this connection, we hypothesized that c-Met inhibition may offer a strategy to treat CCS, as an indirect tactic to defeat a transforming pathway downstream of EWS-ATF1. Here, we show that primary CCS and CCS-derived cell lines express c-Met, which is activated in an autocrine fashion by its ligand hepatocyte growth factor (HGF)/scatter factor in some CCS cell lines. c-Met expression is critical for CCS invasion, chemotaxis, and survival. Blocking c-Met activity with a small-molecule inhibitor (SU11274) or a neutralizing antibody to its ligand HGF (AMG 102) significantly reduced CCS cell growth in culture. Similarly, AMG 102 significantly suppressed in vivo tumor growth in an autocrine xenograft model of CCS. Collectively, these findings suggest the HGF: c-Met signaling axis as a candidate therapeutic target to improve clinical management of CCS. Cancer Res; 70(2); 639-45. (C)2010 AACR.
C1 [Davis, Ian J.; McFadden, Andrew W.] Univ N Carolina, N Carolina Childrens Hosp, Lineberger Comprehens Canc Ctr, Dept Pediat, Chapel Hill, NC 27599 USA.
[Davis, Ian J.; McFadden, Andrew W.] Univ N Carolina, N Carolina Childrens Hosp, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA.
[Coxon, Angela; Burgess, Teresa L.] Amgen Inc, Dept Oncol Res, Thousand Oaks, CA 91320 USA.
[Davis, Ian J.; Fisher, David E.] Dana Farber Canc Inst, Ludwig Ctr Canc Res, Dept Pediat Oncol, Boston, MA 02115 USA.
[Zhang, Yixiang; Wagner, Andrew J.] Dana Farber Canc Inst, Ludwig Ctr Canc Res, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
[Davis, Ian J.; Fisher, David E.] Childrens Hosp Boston, Dept Med, Div Hematol Oncol, Boston, MA USA.
[Wagner, Andrew J.; Fisher, David E.] Harvard Univ, Sch Med, Boston, MA USA.
RP Davis, IJ (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, C-B 7295, Chapel Hill, NC 27599 USA.
EM ian_davis@med.unc.edu; dfisher3@partners.org
FU NIH [K08CA100400, R01CA102309]; Doris Duke Medical Research Foundation;
Adelson Medical Research Foundation; Melanoma Research Alliance; V
Foundation for Cancer Research; Rita Allen Foundation; Corn-Hammond Fund
for Pediatric Oncology
FX Grant Support; NIH grant K08CA100400 (I.J. Davis), R01CA102309 (D. E.
Fisher), and the Doris Duke Medical Research Foundation (D. E. Fisher).
D. E. Fisher is Distinguished Clinical Investigator of the Doris Duke
Medical Research Foundation and also gratefully acknowledges support
from the NIH, the Adelson Medical Research Foundation, and the Melanoma
Research Alliance. I.J. Davis gratefully acknowledges support from the V
Foundation for Cancer Research, the Rita Allen Foundation, and the
Corn-Hammond Fund for Pediatric Oncology.
NR 39
TC 47
Z9 52
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 JAN 15
PY 2010
VL 70
IS 2
BP 639
EP 645
DI 10.1158/0008-5472.CAN-09-1121
PG 7
WC Oncology
SC Oncology
GA 607FW
UT WOS:000278485500024
PM 20068147
ER
PT J
AU Schatton, T
Schutte, U
Frank, NY
Zhan, QA
Hoerning, A
Robles, SC
Zhou, J
Hodi, FS
Spagnoli, GC
Murphy, GF
Frank, MH
AF Schatton, Tobias
Schuette, Ute
Frank, Natasha Y.
Zhan, Qian
Hoerning, Andre
Robles, Susanne C.
Zhou, Jun
Hodi, F. Stephen
Spagnoli, Giulio C.
Murphy, George F.
Frank, Markus H.
TI Modulation of T-Cell Activation by Malignant Melanoma Initiating Cells
SO CANCER RESEARCH
LA English
DT Article
ID CANCER STEM-CELLS; ACUTE MYELOID-LEUKEMIA; CLASS-I EXPRESSION;
METASTATIC MELANOMA; ANTITUMOR IMMUNITY; B-CELLS; IDENTIFICATION;
IMMUNOTHERAPY; ANTIGEN; CHEMORESISTANCE
AB Highly immunogenic cancers such as malignant melanoma are capable of inexorable tumor growth despite the presence of antitumor immunity. Thus, only a restricted minority of tumorigenic malignant cells may possess the phenotypic and functional characteristics needed to modulate tumor-directed immune activation. Here we provide evidence supporting this hypothesis. Tumorigenic ABCB5(+) malignant melanoma initiating cells (MMICs) possessed the capacity to preferentially inhibit IL-2-dependent T-cell activation and to support, in a B7.2-dependent manner, induction of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs). Compared with melanoma bulk cell populations, ABCB5(+) MMICs displayed lower levels of MHC class I, aberrant positivity for MHC class II, and lower expression levels of the melanoma-associated antigens MART-1, ML-IAP, NY-ESO-1, and MAGE-A. Additionally, these tumorigenic ABCB5(+) subpopulations preferentially expressed the costimulatory molecules B7.2 and PD-1, both in established melanoma xenografts and in clinical tumor specimens. In immune activation assays, MMICs inhibited mitogen-dependent human peripheral blood mononuclear cell (PBMC) proliferation and IL-2 production more efficiently than ABCB5(-)melanoma cell populations. Moreover, coculture with ABCB5(+) MMICs increased the abundance of Tregs, in a B7.2 signaling-dependent manner, along with IL-10 production by mitogen-activated PBMCs. Consistent with these findings, MMICs also preferentially inhibited IL-2 production and induced IL-10 secretion by cocultured patient-derived, syngeneic PBMCs. Our findings identify novel T-cell modulatory functions of ABCB5(+) melanoma subpopulations and suggest specific roles for these MMICs in the evasion of antitumor immunity and in cancer immunotherapeutic resistance. Cancer Res; 70(2); 697-708. (C)2010 AACR.
C1 [Schatton, Tobias; Schuette, Ute; Hoerning, Andre; Robles, Susanne C.; Frank, Markus H.] Childrens Hosp Boston, Transplantat Res Ctr, Boston, MA 02115 USA.
[Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Zhan, Qian; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Frank, Markus H.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Zhou, Jun; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Frank, Natasha Y.] VA Boston Healthcare Syst, Dept Med, W Roxbury, MA USA.
[Spagnoli, Giulio C.] Univ Basel Hosp, Dept Biomed, Inst Surg Res, CH-4031 Basel, Switzerland.
RP Frank, MH (reprint author), Childrens Hosp Boston, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA.
EM markus.frank@childrens.harvard.edu
RI Frank, Markus/O-1625-2014
OI Frank, Markus/0000-0002-1312-0488
FU NIH/National Cancer Institute [1RO1CA113796-01A1, 1R01CA138231-01,
2P50CA093683-06A20006]; American Heart Association Founders Affiliate
FX Grant Support; NIH/National Cancer Institute grants 1RO1CA113796-01A1
and 1R01CA138231-01 (M. H. Frank) and grant 2P50CA093683-06A20006 (M. H.
Frank and G. F. Murphy). T. Schatton is the recipient of a Postdoctoral
Fellowship Award from the American Heart Association Founders Affiliate.
NR 50
TC 90
Z9 96
U1 0
U2 12
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 JAN 15
PY 2010
VL 70
IS 2
BP 697
EP 708
DI 10.1158/0008-5472.CAN-09-1592
PG 12
WC Oncology
SC Oncology
GA 607FW
UT WOS:000278485500030
PM 20068175
ER
PT J
AU Pantuck, AJ
An, JB
Liu, HR
Rettig, MB
AF Pantuck, Allan J.
An, Jiabin
Liu, Huiren
Rettig, Matthew B.
TI NF-kappa-Dependent Plasticity of the Epithelial to Mesenchymal
Transition Induced by Von Hippel-Lindau Inactivation in Renal Cell
Carcinomas
SO CANCER RESEARCH
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR; TUMOR-SUPPRESSOR GENE; E-CADHERIN; B
ACTIVATION; CANCER; VHL; TRANSCRIPTION; EXPRESSION; PROTEIN; HIF-1-ALPHA
AB The critical downstream signaling consequences contributing to renal cancer as a result of loss of the tumor suppressor gene von Hippel-Lindau (VHL) have yet to be fully elucidated. Here, we report that VHL loss results in an epithelial to mesenchymal transition (EMT). In studies of paired isogenic cell lines, VHL silencing increased the levels of N-cadherin and vimentin and reduced the levels of E-cadherin relative to the parental VHL(+) cell line, which displayed the opposite profile. VHL(+) cells grew as clusters of cuboidal and rhomboid cells, whereas VHL-silenced cells took on an elongated, fibroblastoid morphology associated with a more highly invasive character in Matrigel chamber assays. Based on earlier evidence that VHL loss can activate NF-kappa B, a known mediator of EMT, we tested whether NF-kappa B contributed to VHL-mediated effects on EMT. On pharmacologic or molecular inhibition of NF-kappa B, VHL-silenced cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive phenotype. Introducing a pVHL-resistant hypoxia-inducible factor 1 alpha (HIF1 alpha) mutant (HIF alpha(M)) into VHL(+) cells heightened NF-kappa B activity, phenocopying EMT effects produced by VHL silencing. Conversely, inhibiting the heightened NF-kappa B activity in this setting reversed the EMT phenotype. Taken together, these results suggest that VHL loss induces an EMT that is largely dependent on HIF alpha-induced NF-kappa B. Our findings rationalize targeting the NF-kappa B pathway as a therapeutic strategy to treat renal tumors characterized by biallelic VHL inactivation. Cancer Res; 70(2); 752-61. (C)2010 AACR.
C1 [Pantuck, Allan J.; Rettig, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
[Rettig, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[An, Jiabin; Liu, Huiren; Rettig, Matthew B.] Vet Affairs Greater Los Angeles Healthcare Syst W, Dept Med, Los Angeles, CA USA.
RP Rettig, MB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA.
EM mrettig@mednet.ucla.edu
FU Department of Veterans Affairs; Pom Wonderful
FX Grant Support; Department of Veterans Affairs Merit Review Program (M.
B. Rettig) and Pom Wonderful (A.J. Pantuck).
NR 31
TC 42
Z9 46
U1 0
U2 4
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 JAN 15
PY 2010
VL 70
IS 2
BP 752
EP 761
DI 10.1158/0008-5472.CAN-09-2211
PG 10
WC Oncology
SC Oncology
GA 607FW
UT WOS:000278485500035
PM 20068166
ER
PT J
AU Coetzee, GA
Jia, L
Frenkel, B
Henderson, BE
Tanay, A
Haiman, CA
Freedman, ML
AF Coetzee, Gerhard A.
Jia, Li
Frenkel, Baruch
Henderson, Brian E.
Tanay, Amos
Haiman, Christopher A.
Freedman, Matthew L.
TI A systematic approach to understand the functional consequences of
non-protein coding risk regions
SO CELL CYCLE
LA English
DT Article
DE GWAS; cancer risk; SNP; functionality
ID COLORECTAL-CANCER; HUMAN GENOME; PROMOTERS; RS6983267; ENHANCERS;
VARIANTS; SEQ
AB A primary goal of genetic association studies is to elucidate genes and novel biological mechanisms involved in disease. Recently, genome-wide association studies have identified many common genetic variants that are significantly associated with complex diseases such as cancer. In contrast to Mendelian disorders, a sizable fraction of the variants lies outside known protein-coding regions; therefore, understanding their biological consequences presents a major challenge in human genetics. Here we describe an integrated framework to allow nonprotein coding loci to be annotated with respect to regulatory functions. This will facilitate identification of target genes as well as prioritize variants for functional testing.
C1 [Coetzee, Gerhard A.; Jia, Li; Frenkel, Baruch; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Tanay, Amos] Weizmann Inst Sci, IL-76100 Rehovot, Israel.
[Freedman, Matthew L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Freedman, Matthew L.] Broad Inst, Cambridge, MA USA.
RP Coetzee, GA (reprint author), Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
EM coetzee@usc.edu; freedman@broadinstitute.org
FU NIH [R01 CA109147, R01 CA129435]; Prostate Cancer Foundation; Whittier
Foundation; American Cancer Society Institutional [IRG-58-007-48]; Mayer
Foundation; Snyder Medical Foundation; DanaFarber/Harvard Cancer Center
Prostate Cancer SPORE; National Cancer Institute [5P50CA90381]; Israeli
Science Foundation
FX Work from the authors referred to in this paper was supported by the NIH
R01 CA109147 (G. A. C.) and R01 CA129435 (M. L. F.), the Prostate Cancer
Foundation (G. A. C.), the Whittier Foundation (G. A. C. and C. A. H.),
the American Cancer Society Institutional Research Grant IRG-58-007-48
(L. J.), the Mayer Foundation (M. L. F.) the H. L. Snyder Medical
Foundation (M. L. F.), the DanaFarber/Harvard Cancer Center Prostate
Cancer SPORE (National Cancer Institute Grant No. 5P50CA90381), the
Israeli Science Foundation (A. T.), the J. Harold and Edna L. LaBriola
Chair in Genetic Orthopaedic Research (held by B. F.). M. L. F. is a
Howard Hughes Medical Institute Physician- Scientist Early Career
Awardee.
NR 15
TC 8
Z9 8
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JAN 15
PY 2010
VL 9
IS 2
BP 256
EP 259
PG 4
WC Cell Biology
SC Cell Biology
GA 550PG
UT WOS:000274139800021
PM 20023379
ER
PT J
AU Wang, N
Tilly, JL
AF Wang, Ning
Tilly, Jonathan L.
TI Epigenetic status determines germ cell meiotic commitment in embryonic
and postnatal mammalian gonads
SO CELL CYCLE
LA English
DT Article
DE histone deacetylase; epigenetics; retinoic acid; Stra8; germ cell;
oogenesis; spermatogenesis; meiosis; ovary; testis
ID PREMATURE OVARIAN FAILURE; INHIBITOR TRICHOSTATIN-A; RETINOIC ACID;
BONE-MARROW; MEIOSIS; MOUSE; MICE; OOGENESIS; RECEPTORS; PROTEIN
AB The meiotic cell cycle is required for production of fertilization-competent gametes. Germ cell meiotic commitment requires expression of Stimulated by retinoic acid gene 8 (Stra8), which is transcriptionally activated by retinoic acid (RA). Meiotic suppression in embryonic male germ cells is believed to result from sex-specific differences in CYP26B1-catalyzed RA metabolism in the developing gonads. Here we show in mice that RA-induced Stra8 transcription is epigenetically controlled and requires a co-activator that binds proximal to the RA response elements (RAREs) in the Stra8 promoter. Embryonic male germ cells exposed in utero to the class I/II histone deacetylase (HDAC) inhibitor, trichostatin-A (TSA), show premature Stra8 activation and meiotic entry without altered Cyp26b1 expression. We also show that Stra8 expression is detectable and physiologically regulated in adult mouse ovaries. Further, oogenesis induction in adult females using TSA is associated with Stra8 activation, and these events are absent in mice deficient in the RA precursor vitamin A. Finally, all of the actions of TSA in premeiotic germ cells in vitro and in mouse ovaries in vivo can be reproduced with the small molecule HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA). Thus, the ability of RA to transcriptionally induce expression of the meiosis-commitment gene, Stra8, is epigenetically controlled and this process involves a novel co-activator that functions upstream of the RAREs. These events not only coordinate the sex-specific timing of meiotic entry during embryogenesis, but also contribute to the regulation of oogenesis in adult female mammals.
C1 [Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02115 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; Vincent Memorial Research Funds; Massachusetts General
Hospital Fund
FX We thank N.B. Hecht for MSY2 antibody; J. Dean for MATER antibody; D. C.
Page for testes from adult wild-type and Stra8-null mice; J. Teixeira,
K. Selesniemi and L. Prickett for technical assistance; and Y. Niikura
for helpful discussions. This work was supported by National Institute
on Aging MERIT Award R37-AG012279, the Rubin Shulsky Philanthropic Fund,
the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze
Foundation, and Vincent Memorial Research Funds. N. Wang is a recipient
of a Massachusetts General Hospital Fund for Medical Discovery award.
NR 39
TC 29
Z9 30
U1 0
U2 11
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JAN 15
PY 2010
VL 9
IS 2
BP 339
EP 349
PG 11
WC Cell Biology
SC Cell Biology
GA 550PG
UT WOS:000274139800030
PM 20009537
ER
PT J
AU Walensky, RP
Kuritzkes, DR
AF Walensky, Rochelle P.
Kuritzkes, Daniel R.
TI The Impact of The President's Emergency Plan for AIDS Relief (PEPfAR)
beyond HIV and Why It Remains Essential
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; SURVIVAL; OUTCOMES; MOTHER; CARE
AB Recent debate has addressed whether global health financing should prioritize interventions that maximize lives saved; focus on the young; and are most economically efficient (most cost-effective). In particular, some have argued that an expansion of the President's Emergency Plan for AIDS Relief (PEPfAR) is not the best use of international health funding, and that extending funding to treat diarrheal and respiratory disease could save more lives at substantially lower costs. We examine the methods of cost-effectiveness analysis and why their application, without context, may not be appropriate for priority setting in this fashion. We further address the substantial impact PEPfAR has achieved in general and more specifically toward improving maternal and child health and why continued PEPfAR investment remains essential.
C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA.
[Walensky, Rochelle P.; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA.
[Walensky, Rochelle P.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA.
RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Fl, Boston, MA 02114 USA.
EM rwalensky@partners.org
OI Walensky, Rochelle P./0000-0002-8795-379X
FU NIAID NIH HHS [R01 AI058736]
NR 34
TC 27
Z9 28
U1 0
U2 3
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JAN 15
PY 2010
VL 50
IS 2
BP 272
EP 275
DI 10.1086/649214
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 536UK
UT WOS:000273069100018
PM 19947830
ER
PT J
AU Berin, I
Engmann, LL
Benadiva, CA
Schmidt, DW
Nulsen, JC
Maier, DB
AF Berin, Inna
Engmann, Lawrence L.
Benadiva, Claudio A.
Schmidt, David W.
Nulsen, John C.
Maier, Donald B.
TI Transfer of two versus three embryos in women less than 40 years old
undergoing frozen transfer cycles
SO FERTILITY AND STERILITY
LA English
DT Article
DE Frozen embryo transfer; number of embryos to transfer; IVF; frozen cycle
outcome; multiple pregnancy
ID IN-VITRO FERTILIZATION; THAWED EMBRYOS; CRYOPRESERVATION; IMPLANTATION;
CONCEPTION; COHORT; RATES; RISK
AB Objective: To compare outcomes of frozen embryo transfer (FET) cycles when two or three embryos were transferred in women aged <40 years.
Design: Retrospective chart review.
Setting: A university-affiliated IVF program.
Patient(s): Women undergoing FET cycles between January 2004 and December 2005.
Intervention(S): Transfer of two or three embryos.
Main Outcome Measure(s): Clinical pregnancy rate (PR), multiple pregnancy rate (MPR), and live birth rate (LBR).
Result(s): In patients aged <35 (n = 145), two versus three embryo group had similar PR and LBR, but the MPR was significantly higher in the three-embryo group (41% for three embryos vs. 9.4% for two embryos). Clinical pregnancy in the fresh cycle from which the frozen embryos were obtained did not affect the PR, and an increase in MPR was still observed. In patients aged 35 to 39 (n = 93), there were no differences in the PR, MPR, or LBR between the two groups.
Conclusion(S): Transfer of two instead of three frozen embryos in patients <35 years old resulted in a significant decrease in MPR without compromising PR or LBR. Transferring additional embryos when a patient had an unsuccessful fresh cycle was not warranted. In the age group 35-39 years, transferring two instead of three embryos did not decrease PR or LBR, and had no effect on the risk of high-order multiples. (Fertil Steril (R) 2010;93:355-9. (C)2010 by American Society for Reproductive Medicine.)
C1 [Berin, Inna; Engmann, Lawrence L.; Benadiva, Claudio A.; Schmidt, David W.; Nulsen, John C.; Maier, Donald B.] Univ Connecticut, Ctr Hlth, Dept Obstet & Gynecol, Ctr Adv Reprod Serv,Div Reprod Endocrinol & Infer, Farmington, CT USA.
RP Berin, I (reprint author), Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, Vincent OB GYN Serv, 55 Fruit St,YAW 10-A, Boston, MA 02114 USA.
EM inna_berin@yahoo.com
NR 16
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JAN 15
PY 2010
VL 93
IS 2
BP 355
EP 359
DI 10.1016/j.fertnstert.2009.01.101
PG 5
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 554KL
UT WOS:000274433800006
PM 19324343
ER
PT J
AU Gundogan, F
Bianchi, DW
Scherjon, SA
Roberts, DJ
AF Gundogan, Fusun
Bianchi, Diana W.
Scherjon, Sicco A.
Roberts, Drucilla J.
TI Placental pathology in egg donor pregnancies
SO FERTILITY AND STERILITY
LA English
DT Article; Proceedings Paper
CT 14th Meeting of the
International-Federation-of-Placental-Associations/12th Meeting of the
European-Placenta-Group (IFPA/EPG)
CY SEP 10-13, 2008
CL Seggau Castle, AUSTRIA
SP Int Federat Placenta Assoc, European Placenta Grp
DE Egg donation; placenta; pathology; immunology
ID IN-VITRO FERTILIZATION; MATERNAL FLOOR INFARCTION; UNKNOWN ETIOLOGY;
OOCYTE DONATION; IMMUNE INTERACTIONS; CHRONIC VILLITIS; REFERENCE
VALUES; T-CELLS; PREECLAMPSIA; APOPTOSIS
AB Objective: To determine placental pathology and immune response at the maternal-fetal interface in pregnancies conceived by IVF via egg donation compared with nondonor IVF pregnancies.
Design: Retrospective case-control study.
Setting: Academic medical center.
Patient(S): The study population included 20 egg donor and 33 nondonor IVF pregnancies of >24 weeks' gestation.
Intervention(s): None.
Main Outcome Measure(s): Perinatal complications (gestational hypertension, abruption, preterm delivery, cesarean section), microscopic features indicating ail immune response and trophoblast damage, and characterization of inflammatory cells using immunohistochemistry.
Result(S): There was ail increase in gestational hypertension and preterm delivery in egg donor pregnancies. Dense fibrinoid deposition in the basal plate with severe chronic deciduitis containing significantly increased numbers of T helper and natural killer cells were demonstrated in egg donor placentas. Trophoblast damage was also increased in the preterm egg donor group.
Conclusion(S): There are significant histological and immunohistochemical differences between the placentas of egg donor and nondonor IVF pregnancies. The increased immune activity and fibrinoid deposition at the maternal-fetal interface of egg donor pregnancies Could represent a host versus graft rejection-like phenomenon. (Fertil Steril (R) 2010;93:397-404. (C)2010 by American Society for Reproductive Medicine.)
C1 [Gundogan, Fusun] Brown Univ, Women & Infants Hosp, Dept Pathol, Providence, RI 02905 USA.
[Bianchi, Diana W.] Tufts Med Ctr, Dept Pediat, Boston, MA USA.
[Scherjon, Sicco A.] Leiden Univ, Med Ctr, Dept Obstet, Leiden, Netherlands.
[Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Gundogan, F (reprint author), Brown Univ, Women & Infants Hosp, Dept Pathol, 101 Dudley St, Providence, RI 02905 USA.
EM fgundogan@wihri.org
NR 38
TC 26
Z9 27
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JAN 15
PY 2010
VL 93
IS 2
BP 397
EP 404
DI 10.1016/j.fertnstert.2008.12.144
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 554KL
UT WOS:000274433800013
PM 19249031
ER
PT J
AU Quaas, AM
Missmer, SA
Ginsburg, ES
AF Quaas, Alexander M.
Missmer, Stacey A.
Ginsburg, Elizabeth S.
TI Gonadotropin-releasing hormone antagonist use is associated with
increased pregnancy rates in ovulation induction-intrauterine
insemination to in vitro fertilization conversions, independent of age
and estradiol level on the day of human chorionic gonadotropin
administration
SO FERTILITY AND STERILITY
LA English
DT Article; Proceedings Paper
CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine
CY OCT 13-17, 2007
CL Washington, DC
SP Amer Soc Reprod Med
DE OI/IUI to IVF conversions; GnRH antagonists; pregnancy rate
ID OVARIAN HYPERSTIMULATION; GNRH ANTAGONISTS; STIMULATION; CYCLES
AB Objective: To determine whether the use of GnRH antagonist in cycles converted from ovulation induction-IUI to IVF affects cycle outcome and, pregnancy rates.
Design: Retrospective cohort study.
Setting: Academic research institution.
Patient(s): One hundred eighty-two consecutive patients with ovulation induction-IUI to IVF conversions undergoing oocyte retrieval conducted at our institution from 2004 to 2006.
Intervention(s): The relation between observation of fetal heartbeat and GnRH antagonist exposure was evaluated with use of multivariable logistic regression. The difference in intermediate cycle outcomes by antagonist exposure was estimated with use of linear regression.
Main Outcome Measure(s): Fetal cardiac activity on early ultrasound, intermediate cycle parameters.
Result(s): For patients given treatment with a GnRH antagonist, the odds ratio for achieving pregnancy was 2.13 (95% confidence interval = 1.03-4.39) compared with untreated patients, independent of age and E(2) levels on day of hCG. Patients given antagonist had 1.6 more follicles and 2.1 more oocytes retrieved, 1.9 more mature oocytes, and 2.3 more fertilized oocytes, and the fertilization rate was 9.7% higher.
Conclusion(s): Gonadotropin-releasing hormone antagonist use in ovulation induction-IUI to IVF conversions was associated with increased pregnancy rates and improved intermediate cycle parameters, controlled for age and E(2) levels on day of hCG. Addition of a GnRH antagonist should be considered in ovulation induction-IUI to IVF conversions. (Fertil Steril(R) 2010;93:605-8. (C)2010 by American Society for Reproductive Medicine.)
C1 [Quaas, Alexander M.; Missmer, Stacey A.; Ginsburg, Elizabeth S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Reprod Endocrinol, Boston, MA 02115 USA.
RP Quaas, AM (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, 55 Fruit St, Boston, MA 02114 USA.
EM aquaas@partners.org
NR 15
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JAN 15
PY 2010
VL 93
IS 2
BP 605
EP 608
DI 10.1016/j.fertnstert.2009.01.109
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 554KL
UT WOS:000274433800040
PM 19324340
ER
PT J
AU Okuya, M
Kurosawa, H
Kikuchi, J
Furukawa, Y
Matsui, H
Aki, D
Matsunaga, T
Inukai, T
Goto, H
Altura, RA
Sugita, K
Arisaka, O
Look, AT
Inaba, T
AF Okuya, Mayuko
Kurosawa, Hidemitsu
Kikuchi, Jiro
Furukawa, Yusuke
Matsui, Hirotaka
Aki, Daisuke
Matsunaga, Takayuki
Inukai, Takeshi
Goto, Hiroaki
Altura, Rachel A.
Sugita, Kenich
Arisaka, Osamu
Look, A. Thomas
Inaba, Toshiya
TI Up-regulation of Survivin by the E2A-HLF Chimera Is Indispensable for
the Survival of t(17;19)-positive Leukemia Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID APOPTOSIS-INDUCING FACTOR; ACUTE-LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC
PROGENITOR CELLS; PRO-B LYMPHOCYTES; TRANSCRIPTION FACTOR; IN-VIVO;
ANTIAPOPTOTIC ACTIVITY; DOWNSTREAM TARGET; GENE-EXPRESSION; E2A GENE
AB The E2A-HLF fusion transcription factor generated by t(17;19)(q22;p13) translocation is found in a small subset of pro-B cell acute lymphoblastic leukemias (ALLs) and promotes leukemogenesis by substituting for the antiapoptotic function of cytokines. Here we show that t(17;19)(+) ALL cells express Survivin at high levels and that a dominant negative mutant of E2A-HLF suppresses Survivin expression. Forced expression of E2A-HLF in t(17;19)(-) leukemia cells up-regulated Survivin expression, suggesting that Survivin is a downstream target of E2A-HLF. Analysis using a counterflow centrifugal elutriator revealed that t(17;19)(+) ALL cells express Survivin throughout the cell cycle. Reporter assays revealed that E2A-HLF induces survivin expression at the transcriptional level likely through indirect down-regulation of a cell cycle-dependent cis element in the promoter region. Down-regulation of Survivin function by a dominant negative mutant of Survivin or reduction of Survivin expression induced massive apoptosis throughout the cell cycle in t(17;19)(+) cells mainly through caspase-independent pathways involving translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus. AIF knockdown conferred resistance to apoptosis caused by down-regulation of Survivin function. These data indicated that reversal of AIF translocation by Survivin, which is induced by E2A-HLF throughout the cell cycle, is one of the key mechanisms in the protection of t(17;19)(+) leukemia cells from apoptosis.
C1 [Okuya, Mayuko; Kurosawa, Hidemitsu; Matsunaga, Takayuki; Sugita, Kenich; Arisaka, Osamu] Dokkyo Med Univ, Dept Pediat, Sch Med, Mibu, Tochigi 3210293, Japan.
[Matsui, Hirotaka; Aki, Daisuke; Inaba, Toshiya] Hiroshima Univ, Dept Mol Oncol, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan.
[Inukai, Takeshi] Univ Yamanashi, Sch Med, Dept Pediat, Yamanashi 4093898, Japan.
[Goto, Hiroaki] Yokohama City Univ, Sch Med, Dept Pediat, Kanagawa 2360004, Japan.
[Altura, Rachel A.] Brown Univ, Warren Alpert Med Sch, Dept Pediat, Providence, RI 02903 USA.
[Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Kurosawa, H (reprint author), Dokkyo Med Univ, Dept Pediat, Sch Med, Mibu, Tochigi 3210293, Japan.
EM hidekuro@dokkyomed.ac.jp
FU Japan Society for Promotion of Science [18591201]; Dokkyo Medical
University
FX This work was supported by Grant-in-aid for Scientific Research (C)
18591201 from the Japan Society for Promotion of Science (to H. K.) and
a young investigator award from Dokkyo Medical University (to M. O.).
NR 43
TC 9
Z9 10
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 JAN 15
PY 2010
VL 285
IS 3
BP 1850
EP 1860
DI 10.1074/jbc.M109.023762
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 541PJ
UT WOS:000273429100031
PM 19887369
ER
PT J
AU Astier, AL
Beriou, G
Eisenhaure, TM
Anderton, SM
Hafler, DA
Hacohen, N
AF Astier, Anne L.
Beriou, Gaelle
Eisenhaure, Thomas M.
Anderton, Stephen M.
Hafler, David A.
Hacohen, Nir
TI RNA Interference Screen in Primary Human T Cells Reveals FLT3 as a
Modulator of IL-10 Levels
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID COLONY-STIMULATING FACTOR; TYROSINE KINASE RECEPTOR; MULTIPLE-SCLEROSIS;
HEMATOPOIETIC-CELLS; MESSENGER-RNA; HUMAN HOMOLOG; MURINE FLT3; LIGAND;
EXPRESSION; GENE
AB Functional studies of human primary immune cells have been hampered by the lack of tools to silence gene functions. In this study, we report the application of a lentiviral RNA interference library in primary human T cells. Using a subgenomic short hair RNA library targeting similar to 1000 signaling genes, we identified novel genes that control the levels of IL-10 produced. IL-10 is a potent anti-inflammatory cytokine secreted by several cell types, including T regulatory type 1 cells, a subset of T regulatory cells that exert their suppressive activity through IL-10 secretion. FLT3, a known hematopoeitic growth factor, was found to be a negative regulator of IL-10 levels in activated T cells. This was based on several observations. First, FLT3 and its ligand (FL) were both induced by T cell activation. Second, silencing of FLT3 led to increased IL-10 levels, whereas addition of FL suppressed IL-10 secretion and increased FLT3 surface levels. Third, engagement of CD46, a known inducer of T regulatory type 1 cells, upregulated surface FLT3, and secreted FL, which then inhibited IL-10 production by T cells. Hence, FL and FLT3 form a novel regulatory feedback loop that limits IL-10 production in T cells. Our results identified FLT3 as a new regulator of T cell function and offer a strategy to genetically dissect specific pathways in T cells. The Journal of Immunology, 2010, 184: 685-693.
C1 [Astier, Anne L.; Anderton, Stephen M.] Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, Edinburgh EH16 4TJ, Midlothian, Scotland.
[Astier, Anne L.; Beriou, Gaelle; Hafler, David A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
[Astier, Anne L.; Beriou, Gaelle; Eisenhaure, Thomas M.; Hafler, David A.; Hacohen, Nir] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Astier, Anne L.; Beriou, Gaelle; Eisenhaure, Thomas M.; Hafler, David A.; Hacohen, Nir] MIT, Cambridge, MA 02142 USA.
[Eisenhaure, Thomas M.; Hacohen, Nir] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
RP Astier, AL (reprint author), Univ Edinburgh, Sch Biol Sci, Inst Immunol & Infect Res, 47 Little France Crescent, Edinburgh EH16 4TJ, Midlothian, Scotland.
EM a.astier@ed.ac.uk
OI Astier, Anne/0000-0002-0144-3431
FU National Institutes of Health [U19 AI070352, AI046130, P01 A1039671];
National Multiple Sclerosis Society [859/07]; National Institute of
Neurological Disorders and Stroke [NS24247]
FX The work was supported by National Institutes of Health grants to N.H.
(U19 AI070352) and by grants from the National Multiple Sclerosis
Society and from the National Institute of Health to D.A.H. (P01
AI045757, U19 AI046130, U19 AI070352, P01 A1039671). D.A.H. has a Jacob
Javits Merit Award (NS24247) from the National Institute of Neurological
Disorders and Stroke. A.A. was supported by an advanced fellowship from
the National Multiple Sclerosis Society followed by a research grant
from the Multiple Sclerosis Society (U.K.) (859/07).
NR 49
TC 15
Z9 15
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 JAN 15
PY 2010
VL 184
IS 2
BP 685
EP 693
DI 10.4049/jimmunol.0902443
PG 9
WC Immunology
SC Immunology
GA 541UT
UT WOS:000273447100019
PM 20018615
ER
PT J
AU Ahuja, SK
He, WJ
AF Ahuja, Sunil K.
He, Weijing
TI Double-Edged Genetic Swords and Immunity: Lesson from CCR5 and Beyond
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID WEST-NILE-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR CCR5;
MACROPHAGE-TROPIC HIV-1; IN-VITRO; MIP-1 ALPHA; VIRAL ENTRY; INFECTION;
DENSITY; SUSCEPTIBILITY
C1 [Ahuja, Sunil K.; He, Weijing] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Ahuja, Sunil K.; He, Weijing] Univ Texas Hlth Sci Ctr San Antonio, Vet Adm Res Ctr AIDS & HIV Infect 1, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Ahuja, SK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr,Rm 5-009R, San Antonio, TX 78229 USA.
EM ahujas@uthscsa.edu
FU NIAID NIH HHS [R37 AI046326]; PHS HHS [R37046326]
NR 43
TC 5
Z9 5
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 15
PY 2010
VL 201
IS 2
BP 171
EP 174
DI 10.1086/649427
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 536NN
UT WOS:000273051200001
PM 20025529
ER
PT J
AU Warren, HS
Fitting, C
Hoff, E
Adib-Conquy, M
Beasley-Topliffe, L
Tesini, B
Liang, XY
Valentine, C
Hellman, J
Hayden, D
Cavaillon, JM
AF Warren, H. Shaw
Fitting, Catherine
Hoff, Eva
Adib-Conquy, Minou
Beasley-Topliffe, Laura
Tesini, Brenda
Liang, Xueya
Valentine, Catherine
Hellman, Judith
Hayden, Douglas
Cavaillon, Jean-Marc
TI Resilience to Bacterial Infection: Difference between Species Could Be
Due to Proteins in Serum
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; STAPHYLOCOCCAL-ENTEROTOXIN-B;
MONOCLONAL-ANTIBODIES; ENDOTOXIN; LIPOPOLYSACCHARIDE; MICE; TOLERANCE;
SUSCEPTIBILITY; CELLS; SEPSIS
AB Vertebrates vary in resistance and resilience to infectious diseases, and the mechanisms that regulate the trade-off between these often opposing protective processes are not well understood. Variability in the sensitivity of species to the induction of damaging inflammation in response to equivalent pathogen loads (resilience) complicates the use of animal models that reflect human disease. We found that induction of proinflammatory cytokines from macrophages in response to inflammatory stimuli in vitro is regulated by proteins in the sera of species in inverse proportion to their in vivo resilience to lethal doses of bacterial lipopolysaccharide over a range of 10,000-fold. This finding suggests that proteins in serum rather than intrinsic cellular differences may play a role in regulating variations in resilience to microbe-associated molecular patterns between species. The involvement of circulating proteins as key molecules raises hope that the process might be manipulated to create better animal models and potentially new drug targets.
C1 [Warren, H. Shaw; Hoff, Eva; Beasley-Topliffe, Laura; Tesini, Brenda; Liang, Xueya; Valentine, Catherine] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Hellman, Judith] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Hayden, Douglas] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Fitting, Catherine; Adib-Conquy, Minou; Cavaillon, Jean-Marc] Inst Pasteur, Cytokines & Inflammat Unit, Paris, France.
RP Warren, HS (reprint author), Massachusetts Gen Hosp E, Infect Dis Unit, 149 13th St,5th Floor, Charlestown, MA 02129 USA.
EM swarren1@partners.org
FU National Institutes of Health [AI059010, GM59694]; Shriners Hospitals
for Children [8720]; Institut Pasteur
FX National Institutes of Health (grants AI059010 and GM59694); Shriners
Hospitals for Children (grant 8720); Institut Pasteur (institutional
funding).
NR 38
TC 70
Z9 71
U1 1
U2 10
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 15
PY 2010
VL 201
IS 2
BP 223
EP 232
DI 10.1086/649557
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 536NN
UT WOS:000273051200009
PM 20001600
ER
PT J
AU Gandhi, RT
Bosch, RJ
Aga, E
Albrecht, M
Demeter, LM
Dykes, C
Bastow, B
Para, M
Lai, J
Siliciano, RF
Siliciano, JD
Eron, JJ
AF Gandhi, Rajesh T.
Bosch, Ronald J.
Aga, Evgenia
Albrecht, Mary
Demeter, Lisa M.
Dykes, Carrie
Bastow, Barbara
Para, Michael
Lai, Jun
Siliciano, Robert F.
Siliciano, Janet D.
Eron, Joseph J.
CA AIDS Clinical Trials Grp A5173 Tea
TI No Evidence for Decay of the Latent Reservoir in HIV-1-Infected Patients
Receiving Intensive Enfuvirtide-Containing Antiretroviral Therapy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CD4(+) T-CELLS; HIV-1; INFECTION; VIRUS; REPLICATION; VIREMIA; DENSITY
AB Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. (ClinicalTrials.gov identifier: NCT00051831.)
C1 [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bosch, Ronald J.; Aga, Evgenia] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Albrecht, Mary] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Demeter, Lisa M.; Dykes, Carrie] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Bastow, Barbara; Para, Michael] Social & Sci Syst, Silver Spring, MD USA.
[Lai, Jun; Siliciano, Robert F.; Siliciano, Janet D.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Siliciano, Robert F.] Howard Hughes Med Inst, Baltimore, MD USA.
[Para, Michael] Ohio State Univ, Columbus, OH 43210 USA.
[Eron, Joseph J.] Univ N Carolina, Chapel Hill, NC USA.
RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, GRJ 504,55 Fruit St, Boston, MA 02114 USA.
EM rgandhi@partners.org
FU NCRR NIH HHS [M01 RR000046, M01 RR000046-48, P20 RR011126, P20
RR011126-049001, UL1 RR025780]; NIAID NIH HHS [P30 AI054907, P30
AI050410, P30 AI054907-01, P30 AI078498, P30 AI078498-01, R01 AI066992,
R01 AI066992-05, U01 AI027665, U01 AI027665-13, U01 AI038855, U01
AI038855-05, U01 AI038858, U01 AI038858-06, U01 AI068634, U01
AI068634-04, U01 AI068636, U01 AI068636-04, U01 AI069415, U01
AI069415-03, U01 AI069423, U01 AI069423-03, U01 AI069450, U01
AI069450-03, U01 AI069472, U01 AI069472-03, U01 AI069474, U01 AI069495,
U01 AI069511, U01 AI069532, UM1 AI068634, UM1 AI068636, UM1 AI069450,
UM1 AI069474, UM1 AI069532]
NR 15
TC 44
Z9 44
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 15
PY 2010
VL 201
IS 2
BP 293
EP 296
DI 10.1086/649569
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 536NN
UT WOS:000273051200016
PM 20001856
ER
PT J
AU Peleg, AY
Pillai, S
Mylonakis, E
Moellering, RC
Eliopoulos, GM
AF Peleg, Anton Y.
Pillai, Satish
Mylonakis, Eleftherios
Moellering, Robert C., Jr.
Eliopoulos, George M.
TI Is High Vancomycin Minimum Inhibitory Concentration a Good Marker to
Predict the Outcome of Methicillin-Resistant Staphylococcus aureus
Bacteremia? Reply
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
ID AGR
C1 [Peleg, Anton Y.; Pillai, Satish; Moellering, Robert C., Jr.; Eliopoulos, George M.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Peleg, Anton Y.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Peleg, Anton Y.; Pillai, Satish; Mylonakis, Eleftherios; Moellering, Robert C., Jr.; Eliopoulos, George M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Peleg, AY (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
EM apeleg@bidmc.harvard.edu
OI Peleg, Anton/0000-0002-2296-2126
NR 9
TC 1
Z9 1
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 15
PY 2010
VL 201
IS 2
BP 312
EP 313
DI 10.1086/649571
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 536NN
UT WOS:000273051200020
ER
PT J
AU Xu, HY
Song, LK
Kim, M
Holmes, MA
Kraft, Z
Sellhorn, G
Reinherz, EL
Stamatatos, L
Strong, RK
AF Xu, Hengyu
Song, Likai
Kim, Mikyung
Holmes, Margaret A.
Kraft, Zane
Sellhorn, George
Reinherz, Ellis L.
Stamatatos, Leonidas
Strong, Roland K.
TI Interactions between Lipids and Human Anti-HIV Antibody 4E10 Can Be
Reduced without Ablating Neutralizing Activity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; MEMBRANE-PROTEINS;
EPITOPE; GP41; 2F5; GLYCOPROTEIN; TRYPTOPHAN; RESIDUES; BINDING
AB Human 4E10 is one of the broadest-specificity, HIV-1-neutralizing monoclonal antibodies known, recognizing a membrane-proximal linear epitope on gp41. The lipid cross-reactivity of 4E10 has been alternately suggested either to contribute to the apparent rarity of 4E10-like antibody responses in HIV infections, through elimination by B-cell tolerance mechanisms to self-antigens, or to contribute to neutralization potency by virus-specific membrane binding outside of the membrane-proximal external region (MPER). To investigate how 4E10 interacts with membrane and protein components, and whether such interactions contribute to neutralization mechanisms, we introduced two mutations into 4E10 Fv constructs, Trp to Ala at position 100 in the heavy chain [W(H100)A] and Gly to Glu at position 50 in the light chain [G(L50)E], selected to disrupt potential lipid interactions via different mechanisms. Wild-type and mutant Fvs all bound with the same affinity to peptides and monomeric and trimeric gp140s, but the affinities for gp140s were uniformly 10-fold weaker than to peptides. 4E10 Fv binding responses to liposomes in the presence or absence of MPER peptides were weak in absolute terms, consistent with prior observations, and both mutations attenuated interactions even further, as predicted. The W(H100) A mutation reduced neutralization efficiency against four HIV-1 isolates, but the G(L50) E mutation increased potency across the same panel. Electron paramagnetic resonance experiments showed that the W(H100) A mutation, but not the G(L50) E mutation, reduced the ability of 4E10 to extract MPER peptides from membranes. These results show that 4E10 nonspecific membrane binding is separable from neutralization, which is achieved through specific peptide/ lipid orientation changes.
C1 [Xu, Hengyu; Holmes, Margaret A.; Strong, Roland K.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
[Song, Likai; Kim, Mikyung; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Kim, Mikyung; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
[Kim, Mikyung; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Song, Likai; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Kraft, Zane; Sellhorn, George; Stamatatos, Leonidas] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Stamatatos, Leonidas] Univ Washington, Dept Global Hlth, Seattle, WA 98109 USA.
RP Strong, RK (reprint author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, 1100 Fairview Ave N,Mail Stop A3-023, Seattle, WA 98109 USA.
EM rstrong@fhcrc.org
FU Bill & Melinda Gates Foundation
FX This research was conducted as part of the Collaboration for AIDS
Vaccine Discovery with support from the Bill & Melinda Gates Foundation.
NR 42
TC 33
Z9 35
U1 3
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JAN 15
PY 2010
VL 84
IS 2
BP 1076
EP 1088
DI 10.1128/JVI.02113-09
PG 13
WC Virology
SC Virology
GA 535TN
UT WOS:000272994300038
PM 19906921
ER
PT J
AU Miura, T
Brumme, CJ
Brockman, MA
Brumme, ZL
Pereyra, F
Block, BL
Trocha, A
John, M
Mallal, S
Harrigan, PR
Walker, BD
AF Miura, Toshiyuki
Brumme, Chanson J.
Brockman, Mark A.
Brumme, Zabrina L.
Pereyra, Florencia
Block, Brian L.
Trocha, Alicja
John, Mina
Mallal, Simon
Harrigan, P. Richard
Walker, Bruce D.
TI HLA-Associated Viral Mutations Are Common in Human Immunodeficiency
Virus Type 1 Elite Controllers (vol 83, pg 3407, 2009)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [Miura, Toshiyuki] Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA.
Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia.
Murdoch Univ, Perth, WA, Australia.
British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada.
Univ British Columbia, Fac Med, Div Aids, Vancouver, BC, Canada.
RP Miura, T (reprint author), Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA.
NR 2
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JAN 15
PY 2010
VL 84
IS 2
BP 1212
EP 1212
DI 10.1128/JVI.02204-09
PG 1
WC Virology
SC Virology
GA 535TN
UT WOS:000272994300053
ER
PT J
AU Malik, S
Jiang, SM
Garee, JP
Verdin, E
Lee, AV
O'Malley, BW
Zhang, M
Belaguli, NS
Oesterreich, S
AF Malik, Simeen
Jiang, Shiming
Garee, Jason P.
Verdin, Eric
Lee, Adrian V.
O'Malley, Bert W.
Zhang, Mao
Belaguli, Narasimhaswamy S.
Oesterreich, Steffi
TI Histone Deacetylase 7 and FoxA1 in Estrogen-Mediated Repression of RPRM
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID BREAST-CANCER CELLS; NUCLEAR RECEPTOR COREPRESSOR; GENOME-WIDE ANALYSIS;
NF-KAPPA-B; GENE-EXPRESSION; ANDROGEN-RECEPTOR; TRANSCRIPTION FACTORS;
RESPONSE ELEMENTS; DOWN-REGULATION; BINDING-SITES
AB Activation of estrogen receptor alpha (ER alpha)results in both induction and repression of gene transcription; while mechanistic details of estrogen induction are well described, details of repression remain largely unknown. We characterized several ER alpha-repressed targets and examined in detail the mechanism for estrogen repression of Reprimo (RPRM), a cell cycle inhibitor. Estrogen repression of RPRM is rapid and robust and requires a tripartite interaction between ER alpha, histone deacetylase 7 (HDAC7), and FoxA1. HDAC7 is the critical HDAC needed for repression of RPRM; it can bind to ER alpha and represses ER alpha's transcriptional activity-this repression does not require HDAC7's deacetylase activity. We further show that the chromatin pioneer factor FoxA1, well known for its role in estrogen induction of genes, is recruited to the RPRM promoter, is necessary for repression of RPRM, and interacts with HDAC7. Like other FoxA1 recruitment sites, the RPRM promoter is characterized by H3K4me1/me2. Estrogen treatment causes decreases in H3K4me1/me2 and release of RNA polymerase II (Pol II) from the RPRM proximal promoter. Overall, these data implicate a novel role for HDAC7 and FoxA1 in estrogen repression of RPRM, a mechanism which could potentially be generalized to many more estrogen-repressed genes and hence be important in both normal physiology and pathological processes.
C1 [Malik, Simeen; Jiang, Shiming; Garee, Jason P.; Lee, Adrian V.; Oesterreich, Steffi] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Malik, Simeen; Garee, Jason P.; Lee, Adrian V.; O'Malley, Bert W.; Oesterreich, Steffi] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Lee, Adrian V.; Oesterreich, Steffi] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Verdin, Eric] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA.
[Verdin, Eric] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
[Zhang, Mao; Belaguli, Narasimhaswamy S.] Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
RP Oesterreich, S (reprint author), 1 Baylor Plaza,MS 600, Houston, TX 77030 USA.
EM steffio@breastcenter.tmc.edu
OI Verdin, Eric/0000-0003-3703-3183
FU Department of Defense Breast Cancer Research Program [BC043880]; NIH
[R01 CA097213, P01030195]; SPORE pilot [CA58183]; Nancy Owen Foundation
FX This work was supported by a Department of Defense Breast Cancer
Research Program grant (BC043880) ( S. Malik), NIH grants R01 CA097213
and P01030195 ( S. Oesterreich), a SPORE pilot grant (CA58183) ( S.
Oesterreich), and a Nancy Owen Foundation grant ( S. Oesterreich).
NR 73
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Z9 31
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JAN 15
PY 2010
VL 30
IS 2
BP 399
EP 412
DI 10.1128/MCB.00907-09
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 535GL
UT WOS:000272955200004
PM 19917725
ER
PT J
AU Feliers, D
Kasinath, BS
AF Feliers, Denis
Kasinath, Balakuntalam S.
TI Mechanism of VEGF expression by high glucose in proximal tubule
epithelial cells
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Article
DE Renin-angiotensin system; VEGF; Glucose; Epithelial cells; Kidney
ID ENDOTHELIAL GROWTH-FACTOR; RENIN-ANGIOTENSIN SYSTEM; MESSENGER-RNA
TRANSLATION; RAT MESANGIAL CELLS; DIABETIC-NEPHROPATHY;
CONVERTING-ENZYME; CARDIAC-HYPERTROPHY; II PRODUCTION; FACTOR-BETA;
ACTIVATION
AB Angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) are important mediators of kidney injury in diabetes. VEGF expression is increased in proximal tubules of mice with type 1 diabetes. In mouse proximal tubular epithelial cells (MCT) cultured with 30 mM glucose (HG) for 24 h, VEGF expression is increased at the protein and the mRNA level, suggesting a transcriptional mechanism. HG stimulation of VEGF synthesis is prevented by captopril, an inhibitor of angiotensin-converting enzyme, and, by losartan, a specific antagonist of angiotensin type 1 receptor (AT1), suggesting that VEGF synthesis is mediated by Ang II. Synthesis of angiotensinogen (AGT), a precursor of angiotensin II, is increased in MCTs cultured in HG. Although synthesis of renin and ACE is not affected by HG, their activity, is increased in the conditioned medium. Concentrations of Ang I and Ang II are also increased in conditioned medium from HG-treated MCTs and captopril prevents increased Ang II, but not Ang 1, synthesis. Finally, AT1 is activated in MCTs treated with HG, and its activation is prevented by captopril and losartan. The ERK pathway is activated by HG within minutes of stimulation and lasting for up to 24 h. The initial phase of ERK activation is due to HG itself and leads to AGT upregulation and the sustained phase is mediated for the most part by Ang II-activated AT1 receptor and leads to increased VEGF synthesis.
These data show that: (1) HG increases AGT synthesis and activation of renin and ACE by MCTs, leading to local production of Ang I and Ang II. (2) Ang II activates endogenous AT1 and stimulates synthesis of VEGF. (3) HG activation of ERK starts within minutes and lasts for up to 24h. Early ERK activation is involved in AGT upregulation and sustained ERK activation, mediated via AT1, is responsible for VEGF synthesis.
In conclusion, our study shows that MCTs express an endogenous renin-angiotensin system that is activated by high glucose to stimulate the synthesis of VEGF, through activation of the ERK pathway. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Feliers, Denis; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Nephrol, OBrien Kidney Res Ctr, San Antonio, TX 78229 USA.
[Kasinath, Balakuntalam S.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Feliers, D (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med Nephrol, OBrien Kidney Res Ctr, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM feliers@uthscsa.edu
FU American Heart Association [RO1 DK077295]; VA Research Service Merit
Review
FX This work was supported by grants from the American Heart Association
(DF), RO1 DK077295 (BSK), and VA Research Service Merit Review Grant
(BSK). We thank Dr. E. Neilson for mouse proximal tubular epithelial
cells.
NR 69
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U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD JAN 15
PY 2010
VL 314
IS 1
BP 136
EP 142
DI 10.1016/j.mce.2009.09.009
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 523VC
UT WOS:000272101700016
PM 19765632
ER
PT J
AU Bader, B
Walker, RH
Vogel, M
Prosiegel, M
McIntosh, J
Danek, A
AF Bader, Benedikt
Walker, Ruth H.
Vogel, Mathias
Prosiegel, Mario
McIntosh, Jacqueline
Danek, Adrian
TI Tongue Protrusion and Feeding Dystonia: A Hallmark of
Chorea-Acanthocytosis
SO MOVEMENT DISORDERS
LA English
DT Letter
C1 [Bader, Benedikt; Danek, Adrian] Univ Munich, Neurol Klin & Poliklin, Munich, Germany.
[Walker, Ruth H.] Mt Sinai Sch Med, New York, NY USA.
[Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA.
[Vogel, Mathias] Klinikum Bogenhausen, Clin Neuropsychol, Munich, Germany.
[Prosiegel, Mario] Ctr Dysphagia, Fachklin Bad Heilbiunn, Bad Heilbrunn, Germany.
[McIntosh, Jacqueline] Wolfson Neurorehabil Ctr, London, England.
RP Bader, B (reprint author), Univ Munich, Neurol Klin & Poliklin, Munich, Germany.
RI Danek, Adrian/G-7339-2011
OI Danek, Adrian/0000-0001-8857-5383
NR 7
TC 18
Z9 23
U1 0
U2 0
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 JAN 15
PY 2010
VL 25
IS 1
BP 127
EP 129
DI 10.1002/mds.22863
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 554HD
UT WOS:000274425200024
PM 19938148
ER
PT J
AU Kremen, WS
Prom-Wormley, E
Panizzon, MS
Eyler, LT
Fischl, B
Neale, MC
Franz, CE
Lyons, MJ
Pacheco, J
Perry, ME
Stevens, A
Schmitt, JE
Grant, MD
Seidman, LJ
Thermenos, HW
Tsuang, MT
Eisen, SA
Dale, AM
Fennema-Notestine, C
AF Kremen, William S.
Prom-Wormley, Elizabeth
Panizzon, Matthew S.
Eyler, Lisa T.
Fischl, Bruce
Neale, Michael C.
Franz, Carol E.
Lyons, Michael J.
Pacheco, Jennifer
Perry, Michele E.
Stevens, Allison
Schmitt, J. Eric
Grant, Michael D.
Seidman, Larry J.
Thermenos, Heidi W.
Tsuang, Ming T.
Eisen, Seth A.
Dale, Anders M.
Fennema-Notestine, Christine
TI Genetic and environmental influences on the size of specific brain
regions in midlife: The VETSA MRI study
SO NEUROIMAGE
LA English
DT Article
DE Heritability; Twins; Magnetic resonance imaging (MRI); Brain structure;
Cortical thickness
ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED
ANALYSIS; CORTICAL THICKNESS; COGNITIVE PERFORMANCE; TWIN DESIGN;
RELIABILITY; SEGMENTATION; MULTIVARIATE; VOLUME
AB The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences oil human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51-59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00-0.75) as compared with subcortical and ventricular ROIs (0.48-0.85). The results did not indicate lateralized heritability differences or greater genetic influences oil the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic Studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Kremen, William S.; Panizzon, Matthew S.; Eyler, Lisa T.; Franz, Carol E.; Perry, Michele E.; Tsuang, Ming T.; Fennema-Notestine, Christine] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Kremen, William S.; Tsuang, Ming T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA.
[Kremen, William S.; Eyler, Lisa T.; Tsuang, Ming T.] VA San Diego Healthcare Syst, La Jolla, CA USA.
[Prom-Wormley, Elizabeth; Neale, Michael C.; Schmitt, J. Eric] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA.
[Prom-Wormley, Elizabeth; Neale, Michael C.; Schmitt, J. Eric] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA.
[Fischl, Bruce; Pacheco, Jennifer; Stevens, Allison] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Fischl, Bruce; Pacheco, Jennifer; Stevens, Allison] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lyons, Michael J.; Grant, Michael D.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Perry, Michele E.] Univ Calif San Diego, Dept Cognit Neurosci, La Jolla, CA 92093 USA.
[Seidman, Larry J.; Thermenos, Heidi W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Eisen, Seth A.] Dept Vet Affairs, Washington, DC USA.
[Eisen, Seth A.] Washington Univ, Dept Med, St Louis, MO USA.
[Eisen, Seth A.] Washington Univ, Dept Psychiat, St Louis, MO USA.
[Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
RP Kremen, WS (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr MC 0738, La Jolla, CA 92093 USA.
EM wkremen@ucsd.edu
RI Lyons, Michael/B-6119-2011; Dale, Anders/A-5180-2010;
OI Lyons, Michael/0000-0001-6516-9219; Fennema-Notestine,
Christine/0000-0002-6527-6361
FU National Institute on Aging [AG022381, AG018384, AG018386, AG022982];
National Center for Research Resources [P41-RR14075]; NCRR BIRN
Morphometric [BIRN002]; National Institute for Biomedical Imaging and
Bioengineering [R01EB006758]; National Institute for Neurological
Disorders and Stroke [R01 NS052585-01]; Mental Illness and Neuroscience
Discovery (MIND) Institute,; National Alliance for Medical Image
Computing (NAMIC); National Institutes of Health through the NIH Roadmap
for Medical Research [U54 EB005149]; Ellison Medical Foundation; U.S.
Department of Veterans Affairs; Vietnam Era Twin (VET) Registry;
Department of Defense; the National Personnel Records Center; National
Archives and Records Administration; Internal Revenue Service; National
Opinion Research Center; National Research Council; National Academy of
Sciences; Institute for Survey Research, Temple University
FX Funded by the National Institute on Aging (AG022381, AG018384, AG018386,
AG022982): the National Center for Research Resources (P41-RR14075; NCRR
BIRN Morphometric Project BIRN002); the National Institute for
Biomedical Imaging and Bioengineering (R01EB006758); the National
Institute for Neurological Disorders and Stroke (R01 NS052585-01); and
the Mental Illness and Neuroscience Discovery (MIND) Institute, part of
the National Alliance for Medical Image Computing (NAMIC), funded by the
National Institutes of Health through the NIH Roadmap for Medical
Research, Grant U54 EB005149. Additional support was provided by The
Autism & Dyslexia Project funded by the Ellison Medical Foundation. The
U.S. Department of Veterans Affairs has provided financial support for
the development and maintenance of the Vietnam Era Twin (VET) Registry.
Numerous organizations have provided invaluable assistance in the
conduct of this study, including the Department of Defense; the National
Personnel Records Center, National Archives and Records Administration;
the Internal Revenue Service; the National Opinion Research Center: the
National Research Council, National Academy of Sciences; and the
Institute for Survey Research, Temple University. Most importantly, the
authors gratefully acknowledge the continued cooperation and
participation of the members of the VET Registry and their families.
Without their contribution this research would not have been possible.
NR 49
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U1 1
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2010
VL 49
IS 2
BP 1213
EP 1223
DI 10.1016/j.neuroimage.2009.09.043
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 533FF
UT WOS:000272808400008
PM 19786105
ER
PT J
AU Takahashi, E
Dai, GP
Wang, RP
Ohki, K
Rosen, GD
Galaburda, AM
Grant, PE
Wedeen, VJ
AF Takahashi, Emi
Dai, Guangping
Wang, Ruopeng
Ohki, Kenichi
Rosen, Glenn D.
Galaburda, Albert M.
Grant, P. Ellen
Wedeen, Van J.
TI Development of cerebral fiber pathways in cats revealed by diffusion
spectrum imaging
SO NEUROIMAGE
LA English
DT Article
DE Diffusion Spectrum Imaging; Tractography; Development; Thalamo-cortical
tracts; Cat
ID WHITE-MATTER DEVELOPMENT; FETAL-BRAIN DEVELOPMENT; MAGNETIC-RESONANCE;
VISUAL-CORTEX; MICROSTRUCTURAL DEVELOPMENT; ANATOMICAL CHARACTERIZATION;
PREMATURE-INFANTS; WATER DIFFUSION; TENSOR MRI; IN-UTERO
AB Examination of the three-dimensional axonal pathways in the developing brain is key to understanding the formation of cerebral connectivity. By tracing fiber pathways throughout the entire brain, diffusion tractography provides information that cannot be achieved by conventional anatomical MR imaging or histology. However, standard diffusion tractography (based on diffusion tensor imaging, or DTI) tends to terminate in brain areas with low water diffusivity, indexed by low diffusion fractional anisotropy (FA), which can be Caused by crossing fibers as well as fibers with less myelin. For this reason, DTI tractography is not effective for delineating the Structural changes that occur in the developing brain, where the process of myelination is incomplete, and where crossing fibers exist in greater numbers than in the adult brain. Unlike DTI, diffusion spectrum imaging (DSI) can define multiple directions of water diffusivity; as such, diffusion tractography based on DSI provides marked flexibility for delineation of fiber tracts in areas where the fiber architecture is complex and multidirectional, even in areas of low FA. In this study, we showed that FA values were lower in the white matter of newborn (postnatal day 0; P0) cat brains than in the white matter of infant (P35) and juvenile (P100) cat brains. These results correlated well with histological myelin stains of the white matter: the newborn kitten brain has much less myelin than that found in cat brains at later stages of development. Using DSI tractography, we successfully identified structural changes in thalamo-cortical and cortico-cortical association tracts in cat brains from one stage of development to another. in newborns, the main body of the thalamo-cortical tract was smooth, and fibers branching from it were almost straight, while the main body became more complex and branching fibers became Curved reflecting gyrification in the older cats. Cortico-cortical tracts in the temporal lobe were smooth in newborns, and they formed a sharper angle in the later stages of development. The cingulum bundle and superior longitudinal fasciculus became more visible with time. Within the first month after birth, structural changes occurred in these tracts that coincided with the formation of the gyri. These results show that DSI tractography has the potential for mapping morphological changes in low FA areas associated with growth and development. The technique may also be applicable to the study of other forms of brain plasticity, including future Studies in vivo. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Takahashi, Emi; Grant, P. Ellen] Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Childrens Hosp Boston, Boston, MA 02115 USA.
[Takahashi, Emi; Dai, Guangping; Grant, P. Ellen; Wedeen, Van J.] Harvard Univ, Dept Radiol, Sch Med, Charlestown, MA USA.
[Takahashi, Emi; Dai, Guangping; Wang, Ruopeng; Grant, P. Ellen; Wedeen, Van J.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Ohki, Kenichi] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Rosen, Glenn D.; Galaburda, Albert M.] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Grant, P. Ellen] Harvard Univ, Dept Radiol, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA.
RP Takahashi, E (reprint author), Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Childrens Hosp Boston, Boston, MA 02115 USA.
EM emi@nmr.mgh.harvard.edu
OI Rosen, Glenn/0000-0001-8281-5446
FU NIH [RO1 MH 64044]; National Science Foundation [PHY 0855161, PHY
0855453]; Ellison Medical Foundation [208556]
FX We greatly appreciate Nichole Eusemann for her helpful editorial
comments. This work was supported by NIH (RO1 MH 64044), the National
Science Foundation PHY 0855161, PHY 0855453 and the Ellison Medical
Foundation #208556.
NR 75
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Z9 34
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2010
VL 49
IS 2
BP 1231
EP 1240
DI 10.1016/j.neuroimage.2009.09.002
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 533FF
UT WOS:000272808400010
PM 19747553
ER
PT J
AU Sinke, CBA
Sorger, B
Goebel, R
de Gelder, B
AF Sinke, C. B. A.
Sorger, B.
Goebel, R.
de Gelder, B.
TI Tease or threat? Judging social interactions from bodily expressions
SO NEUROIMAGE
LA English
DT Article
DE Emotion; Bodily expressions; Threat; fMRI; Social interaction; Attention
ID FUNCTIONAL SPECIALIZATION; SELECTIVE ATTENTION; PREFRONTAL CORTEX; BODY
EXPRESSIONS; FMRI; AMYGDALA; EMOTION; BRAIN; RESPONSES; PERCEPTION
AB We casually observe many interactions that do not really concern us. Yet sometimes we need to be able to rapidly appraise whether an interaction between two people represents a real threat for one of them Father than an innocent tease. Using functional magnetic resonance imaging, we investigated whether small differences in the body language of two interacting people are picked up by the brain even if observers are performing an unrelated task. Fourteen participants were scanned while watching 3-s movies (192 trials and 96 scrambles) showing a male person either threatening or teasing a female one. In one task condition, observers categorized the interaction as threatening or teasing, and in the other, they monitored randomly appearing dots and categorized the color. Our results clearly show that right amygdala responds more to threatening than to teasing situations irrespective of the observers' task. When observers' attention is not explicitly directed to the situation, this heightened amygdala activation goes together with increased activity in body sensitive regions in fusiform gyrus, extrastriate body area-human motion complex and superior temporal sulcus and is associated with a better behavioral performance of the participants during threatening situations. In addition, regions involved in action observation (inferior frontal gyrus, temporoparietal junction, and inferior parietal lobe) and preparation (premotor, putamen) show increased activation for threat videos. Also regions involved in processing moral violations (temporoparietal junction, hypothalamus) reacted selectively to the threatening interactions. Taken together, our results show which brain regions react selectively to witnessing a threatening interaction even if the situation is not attended because the observers perform an unrelated task. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Sinke, C. B. A.; de Gelder, B.] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
[Sinke, C. B. A.; Sorger, B.; Goebel, R.] Maastricht Univ, Dept Cognit Neurosci, Maastricht, Netherlands.
[de Gelder, B.] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA USA.
RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
EM B.deGelder@uvt.nl
FU EU [FDP6-NEST-043403]
FX This project was funded in part by EU project COBOL (FDP6-NEST-043403).
NR 48
TC 40
Z9 41
U1 5
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2010
VL 49
IS 2
BP 1717
EP 1727
DI 10.1016/j.neuroimage.2009.09.065
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 533FF
UT WOS:000272808400055
PM 19804836
ER
PT J
AU Marsolek, CJ
Deason, RG
Ketz, NA
Ramanathan, P
Bernat, EM
Steele, VR
Patrick, CJ
Verfaellie, M
Schnyer, DM
AF Marsolek, Chad J.
Deason, Rebecca G.
Ketz, Nicholas A.
Ramanathan, Pradeep
Bernat, Edward M.
Steele, Vaughn R.
Patrick, Christopher J.
Verfaellie, Mieke
Schnyer, David M.
TI Identifying objects impairs knowledge of other objects: A relearning
explanation for neural repetition effect
SO NEUROIMAGE
LA English
DT Article
ID CORTICAL ACTIVITY; TEMPORAL CORTEX; INFEROTEMPORAL CORTEX; NEUROIMAGING
EVIDENCE; CEREBRAL-CORTEX; MEMORY; SUPPRESSION; MECHANISMS;
REPRESENTATIONS; RECOGNITION
AB Different items in long-term knowledge are stored in the neocortex as partially overlapping representations that can be altered slightly with usage. This encoding scheme affords well-documented benefits, but potential costs have not been well explored. Here we use functional magnetic resonance imaging (fMRI), neurocomputational modeling, and electrophysiological measures to show that strengthening some visual object representations not only enhances the subsequent ability to identify those (repeated) objects-an effect long known as repetition priming-but also impairs the ability to identify other (non-repeated) objects-a new effect labeled antipriming. As a result, the non-repeated objects elicit increased neural activity likely for the purpose of reestablishing their previously weakened representations. These results suggest a novel reevaluation of the ubiquitously observed repetition effect on neural activity, and they indicate that maintenance relearning may be a crucial aspect of preserving overlapping neural representations of visual objects in long-term memory. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Marsolek, Chad J.; Deason, Rebecca G.; Ketz, Nicholas A.; Ramanathan, Pradeep; Bernat, Edward M.; Steele, Vaughn R.; Patrick, Christopher J.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Verfaellie, Mieke] Boston VA Healthcare Syst, Boston, MA USA.
[Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Schnyer, David M.] Univ Texas Austin, Austin, TX 78712 USA.
RP Marsolek, CJ (reprint author), Univ Minnesota, Dept Psychol, 75 E River Rd, Minneapolis, MN 55455 USA.
EM chad.j.marsolek-1@umn.edu
FU Medical Research Service of the Department of Veterans Affairs; Center
for Cognitive Sciences in conjunction with the National Institute of
Health and Human Development; University of Minnesota
FX We thank Chris Azorson, Steve Engel, and Yuhong Jiang for valuable
comments on a previous version of the manuscript; Susan Park Anderson,
Sarah Davis, Sarah Fitch, Luke Kane, Alvina Kittur, Rachel LaNasa,
Mithra Sathishkumar, and Benjamin Spear for help with data collection
and analysis; and Randy O'Reilly for help with the simulation models.
The research was supported by the National Institute of Mental Health
(D.M.S., M.V., and C.J.M.). It was also supported by the Medical
Research Service of the Department of Veterans Affairs and the Center
for Cognitive Sciences in conjunction with the National Institute of
Health and Human Development and the Office of the Vice President for
Research and Dean of the Graduate School of the University of Minnesota.
NR 56
TC 7
Z9 8
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JAN 15
PY 2010
VL 49
IS 2
BP 1919
EP 1932
DI 10.1016/j.neuroimage.2009.08.063
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 533FF
UT WOS:000272808400076
PM 19744565
ER
PT J
AU Kang, JW
Kim, P
Alonzo, CA
Park, H
Yun, SH
AF Kang, Jeon Woong
Kim, Pilhan
Alonzo, Carlo Amadeo
Park, Hyunsung
Yun, Seok H.
TI Two-photon microscopy by wavelength-swept pulses delivered through
single-mode fiber
SO OPTICS LETTERS
LA English
DT Article
ID ENCODED CONFOCAL MICROSCOPY; OPTICAL MICROSCOPY; IN-VIVO; FLUORESCENCE;
LASER
AB Nonlinear microscopy through flexible fiber-optic catheters has potential in clinical diagnostic applications. Here, we demonstrate a new approach based on wavelength-swept narrowband pulses that permits simple fiber-optic delivery without need of the dispersion management and allows nonmechanical beam scanning. Using 0.86 ps pulses rapidly tuned from 789 nm to 822 nm at a sweep rate of 200 Hz, we demonstrate two-photon fluorescence and second-harmonic generation imaging through a 5-m-long standard single-mode fiber. (C) 2010 Optical Society of America
C1 [Kang, Jeon Woong; Kim, Pilhan; Alonzo, Carlo Amadeo; Park, Hyunsung; Yun, Seok H.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Kang, Jeon Woong; Kim, Pilhan; Alonzo, Carlo Amadeo; Park, Hyunsung; Yun, Seok H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Park, Hyunsung; Yun, Seok H.] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon 305701, South Korea.
[Park, Hyunsung; Yun, Seok H.] Korea Adv Inst Sci & Technol, WCU Program, Taejon 305701, South Korea.
RP Yun, SH (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 8, Boston, MA 02114 USA.
EM syun@hms.harvard.edu
RI Kim, Pilhan/C-1836-2011
OI Kim, Pilhan/0000-0001-8388-1840
FU National Science Foundation (NSF) [ECCS-0801412]; National Research
Foundation of Korea [R312008-000-10071-0, KRF-2007-357C00036]; Human
Frontier Science Program
FX The authors acknowledge the support by the National Science Foundation
(NSF) (ECCS-0801412), the National Research Foundation of Korea
(R312008-000-10071-0 and fellowship KRF-2007-357C00036 to J. W. K.), and
Human Frontier Science Program (Cross Disciplinary Fellowship to P. K.).
NR 15
TC 4
Z9 4
U1 0
U2 2
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 JAN 15
PY 2010
VL 35
IS 2
BP 181
EP 183
PG 3
WC Optics
SC Optics
GA 547IA
UT WOS:000273879200030
PM 20081961
ER
PT J
AU Reichmann, WM
Losina, E
Seage, GR
Arbelaez, C
Safren, SA
Katz, JN
Hetland, A
Walensky, RP
AF Reichmann, William M.
Losina, Elena
Seage, George R., III
Arbelaez, Christian
Safren, Steven A.
Katz, Jeffrey N.
Hetland, Adam
Walensky, Rochelle P.
TI Does Modality of Survey Administration Impact Data Quality: Audio
Computer Assisted Self Interview (ACASI) Versus Self-Administered Pen
and Paper?
SO PLOS ONE
LA English
DT Article
ID SEXUALLY-TRANSMITTED-DISEASE; EMERGENCY SEVERITY INDEX;
RANDOMIZED-TRIAL; RISK BEHAVIORS; DRUG-USERS; HIV RISK; IMPLEMENTATION;
MODE; BIAS
AB Background: In the context of a randomized controlled trial (RCT) on HIV testing in the emergency department (ED) setting, we evaluated preferences for survey modality and data quality arising from each modality.
Methods: Enrolled participants were offered the choice of answering a survey via audio computer assisted self-interview (ACASI) or pen and paper self-administered questionnaire (SAQ). We evaluated factors influencing choice of survey modality. We defined unusable data for a particular survey domain as answering fewer than 75% of the questions in the domain. We then compared ACASI and SAQ with respect to unusable data for domains that address sensitive topics.
Results: Of 758 enrolled ED patients, 218 (29%) chose ACASI, 343 chose SAQ (45%) and 197 (26%) opted not to complete either. Results of the log-binomial regression indicated that older (RR = 1.08 per decade) and less educated participants (RR = 1.25) were more likely to choose SAQ over ACASI. ACASI yielded substantially less unusable data than SAQ.
Conclusions: In the ED setting there may be a tradeoff between increased participation with SAQ versus better data quality with ACASI. Future studies of novel approaches to maximize the use of ACASI in the ED setting are needed.
C1 [Reichmann, William M.; Losina, Elena; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Reichmann, William M.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Losina, Elena; Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA.
[Seage, George R., III; Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Arbelaez, Christian; Hetland, Adam] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
RP Reichmann, WM (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA.
EM wreichmann@partners.org
OI Walensky, Rochelle P./0000-0002-8795-379X
FU National Institute of Mental Health [R01 MH073445, R01 MH65869]
FX Funding: This work was supported by the National Institute of Mental
Health [R01 MH073445, R01 MH65869]. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 29
TC 16
Z9 17
U1 1
U2 12
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 JAN 15
PY 2010
VL 5
IS 1
AR e8728
DI 10.1371/journal.pone.0008728
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 545EI
UT WOS:000273714900009
PM 20090953
ER
PT J
AU Rihel, J
Prober, DA
Arvanites, A
Lam, K
Zimmerman, S
Jang, S
Haggarty, SJ
Kokel, D
Rubin, LL
Peterson, RT
Schier, AF
AF Rihel, Jason
Prober, David A.
Arvanites, Anthony
Lam, Kelvin
Zimmerman, Steven
Jang, Sumin
Haggarty, Stephen J.
Kokel, David
Rubin, Lee L.
Peterson, Randall T.
Schier, Alexander F.
TI Zebrafish Behavioral Profiling Links Drugs to Biological Targets and
Rest/Wake Regulation
SO SCIENCE
LA English
DT Article
ID SLEEP; STRATEGIES; INHIBITORS; DISORDERS; DISCOVERY; EMBRYOS; HERG;
MICE; QT
AB A major obstacle for the discovery of psychoactive drugs is the inability to predict how small molecules will alter complex behaviors. We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multidimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors. Behavioral profiling revealed conserved functions of psychotropic molecules and predicted the mechanisms of action of poorly characterized compounds. In addition, behavioral profiling implicated new factors such as ether-a-go-go-related gene ( ERG) potassium channels and immunomodulators in the control of rest and locomotor activity. These results demonstrate the power of high-throughput behavioral profiling in zebrafish to discover and characterize psychotropic drugs and to dissect the pharmacology of complex behaviors.
C1 [Rihel, Jason; Prober, David A.; Zimmerman, Steven; Jang, Sumin; Schier, Alexander F.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Arvanites, Anthony; Lam, Kelvin; Rubin, Lee L.; Schier, Alexander F.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Haggarty, Stephen J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
[Haggarty, Stephen J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kokel, David; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Charlestown, MA 02129 USA.
[Peterson, Randall T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Schier, Alexander F.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02215 USA.
[Schier, Alexander F.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
RP Rihel, J (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM rihel@fas.harvard.edu; schier@fas.harvard.edu
RI Rihel, Jason/G-7106-2011;
OI Rihel, Jason/0000-0003-4067-2066; Haggarty, Stephen
J./0000-0002-7872-168X
FU Life Sciences Research Foundation; Helen Hay Whitney Foundation; NIH
[MH086867, MH085205]; Stanley Medical Research Institute; Harvard Stem
Cell Institute; McKnight Endowment Fund for Neuroscience
FX We thank J. Dowling, D. Milan, and G. Vanderlaan for suggestions and
reagents and D. Schoppik, G. Uhl, and I. Woods for critical reading of
the manuscript. Supported by a Bristol-Myers Squibb postdoctoral
fellowship of the Life Sciences Research Foundation (J. R.), a Helen Hay
Whitney Foundation postdoctoral fellowship (D. A. P.), a NIH Pathway to
Independence grant (D. A. P.), the Stanley Medical Research Institute
(S. J. H.), the Harvard Stem Cell Institute (L. L. R.), NIH grants
MH086867 and MH085205 (R. T. P.), and grants from NIH and the McKnight
Endowment Fund for Neuroscience (A. F. S.). L. L. R. is a founder of
iPierian Inc., a biotechnology company, and is a member of its
scientific advisory board.
NR 19
TC 290
Z9 295
U1 4
U2 51
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 JAN 15
PY 2010
VL 327
IS 5963
BP 348
EP 351
DI 10.1126/science.1183090
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 544CM
UT WOS:000273629700048
PM 20075256
ER
PT J
AU Bose-O'Reilly, S
Drasch, G
Beinhoff, C
Rodrigues-Filho, S
Roider, G
Lettmeier, B
Maydl, A
Maydl, S
Siebert, U
AF Bose-O'Reilly, Stephan
Drasch, Gustav
Beinhoff, Christian
Rodrigues-Filho, Saulo
Roider, Gabriele
Lettmeier, Beate
Maydl, Alexandra
Maydl, Stefan
Siebert, Uwe
TI Health assessment of artisanal gold miners in Indonesia
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE Mercury; Neurotoxic; Artisanal gold mining; Indonesia; Environment;
Health; Amalgam smelting; Mercury vapor
ID BIOLOGICAL MONITORING VALUES; SEYCHELLES CHILD-DEVELOPMENT; 1998
GERES-III; MINING AREAS; ENVIRONMENTAL-POLLUTANTS; MERCURY
CONTAMINATION; GERMAN POPULATION; PRENATAL EXPOSURE; METHYLMERCURY;
PHILIPPINES
AB Small scale miners use mercury to extract gold from ore in many countries. An environmental and health assessment was performed in Indonesia in two regions, Galangan in Central Kalimantan and Talawaan in Northern Sulawesi. The environmental assessment showed severe mercury contamination of the sediments, and increased mercury levels in local fish. For the health investigation 281 volunteers were recruited and examined by a standardized questionnaire, a neurological examination and neuro-psychological tests. A medical score was used consisting of significant factors of mercury intoxication. Mercury exposed workers showed typical symptoms of mercury intoxication, such as movement 'disorders (ataxia, tremor, dyschadochokinesia, etc.). Blood, urine and hair samples were taken from any participant and analyzed for mercury. The mercury concentration in the biomonitors was high, partly extreme high in the working population, increased in the population living in the same habitat and low in the control group. By a standard protocol which includes a combination of threshold values of mercury in the biomonitors and a medical sum score the diagnosis of chronic mercury intoxication was made for highly burdened workers (amalgam smelters) in 55% in Sulawesi and in 62% in Kalimantan. Less exposed mineral processors and the general population in the mining areas were also intoxicated to a high percentage. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Bose-O'Reilly, Stephan; Lettmeier, Beate; Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria.
[Drasch, Gustav; Roider, Gabriele; Lettmeier, Beate; Maydl, Alexandra; Maydl, Stefan] Univ Munich, Inst Forens Med, D-80336 Munich, Germany.
[Rodrigues-Filho, Saulo] Univ Brasilia, CDS, BR-70910900 Brasilia, DF, Brazil.
[Rodrigues-Filho, Saulo] Ctr Mineral Technol, Rio De Janeiro, Brazil.
[Siebert, Uwe] Harvard Univ, Sch Med, Cardiovasc Res Program, Inst Technol Assessment, Boston, MA USA.
[Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA.
RP Bose-O'Reilly, S (reprint author), Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria.
EM stephan.boeseoreilly@umit.at
RI Banks, Tamara/G-3007-2012
NR 35
TC 33
Z9 33
U1 5
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD JAN 15
PY 2010
VL 408
IS 4
BP 713
EP 725
DI 10.1016/j.scitotenv.2009.10.070
PG 13
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 547ZI
UT WOS:000273928000004
PM 19945736
ER
PT J
AU Bose-O'Reilly, S
Drasch, G
Beinhoff, C
Tesha, A
Drasch, K
Roider, G
Taylor, H
Appleton, D
Siebert, U
AF Bose-O'Reilly, Stephan
Drasch, Gustav
Beinhoff, Christian
Tesha, Aloyce
Drasch, Katalin
Roider, Gabriele
Taylor, Helen
Appleton, Don
Siebert, Uwe
TI Health assessment of artisanal gold miners in Tanzania
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE Mercury; Neurotoxic; Artisanal gold mining; Tanzania; Environment;
Health; Amalgam smelting; Mercury vapor
ID 1998 GERES-III; MERCURY CONTAMINATION; MINING AREAS;
ENVIRONMENTAL-POLLUTANTS; GERMAN POPULATION; PHILIPPINES; EXPOSURE;
FISH; METHYLMERCURY; MINDANAO
AB In 2003 UNIDO (United Nations Industrial Development Organization) conducted an environmental and health assessment in a small-scale mining area in Tanzania. BGS (British Geological Survey) per-formed the environmental assessment. The Institute of Forensic Medicine - University of Munich performed the health assessment. The results of the medical, neurological and neuro-psychological examination of 180 participants from the affected area of Rwamagasa and 31 controls were analyzed. Urine. blood and hair samples were analyzed to detect the level of mercury body burden. Mercury concentrations in the bio-monitors urine, blood and hair were statistically significantly higher in the exposed population from Rwamagasa compared to the control group from Katoro. Only amalgam burners showed mercury levels above the toxicological threshold limits. A speciation of mercury in hair indicated that mainly elemental mercury vapor contributed to the high body burden of the artisanal miners. 104 amalgam-burners, the most exposed population group, were examined. 25 of these workers were found to be intoxicated. Small-scale mining is a serious health hazard for amalgam burners. Reduction of the exposure is essential to prevent further damage. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Bose-O'Reilly, Stephan; Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria.
[Drasch, Gustav; Drasch, Katalin; Roider, Gabriele] Univ Munich, Inst Forens Med, D-80636 Munich, Germany.
[Tesha, Aloyce] Minist Energy & Minerals, Dar Es Salaam, Tanzania.
[Tesha, Aloyce] UNIDO, Dar Es Salaam, Tanzania.
[Taylor, Helen; Appleton, Don] British Geol Survey, Kingsley Dunham Ctr, Keyworth NG12 5GG, Notts, England.
[Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Cardiovasc Res Program, Boston, MA USA.
[Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA.
RP Bose-O'Reilly, S (reprint author), Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria.
EM stephan.boeseoreilly@umit.at
RI Banks, Tamara/G-3007-2012
NR 34
TC 31
Z9 32
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD JAN 15
PY 2010
VL 408
IS 4
BP 796
EP 805
DI 10.1016/j.scitotenv.2009.10.051
PG 10
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 547ZI
UT WOS:000273928000014
PM 19945738
ER
PT J
AU Nikolic, B
Onoe, T
Takeuchi, Y
Khalpey, Z
Primo, V
Leykin, I
Smith, RN
Sykes, M
AF Nikolic, Boris
Onoe, Takashi
Takeuchi, Yasuo
Khalpey, Zain
Primo, Valeria
Leykin, Igor
Smith, R. Neal
Sykes, Megan
TI Distinct Requirements for Achievement of Allotolerance Versus Reversal
of Autoimmunity via Nonmyeloablative Mixed Chimerism Induction in NOD
Mice
SO TRANSPLANTATION
LA English
DT Article
DE Tolerance; Immunology; Transplantation
ID BONE-MARROW-TRANSPLANTATION; NONOBESE DIABETIC MICE; STEM-CELL
TRANSPLANTATION; WHOLE-BODY IRRADIATION; HEMATOPOIETIC CHIMERISM;
MONOCLONAL-ANTIBODIES; TOLERANCE INDUCTION; COSTIMULATORY BLOCKADE;
ISLET TRANSPLANTATION; CONDITIONING REGIMEN
AB Objectives. Mixed hematopoietic chimerism is associated with islet allograft tolerance and may reverse auto immunity, We developed low intensity regimens for the induction of mixed chimerism and examined the effects on autoimmunity in prediabetic nonobese diabetic (NOD) mice.
Research Design and Methods. NOD mice received various combinations of total body irradiation, anti-CD154, anti-CD8 alpha, anti-CD4, and anti-Thy1.2 monoclonal antibodies, with or without transplantation of C57BL/6 bone marrow cells and were followed up for development of diabetes, chimerism, and donor skin graft survival. Autoimmunity was assessed by histologic examination of salivary glands and pancreata.
Results. Although conditioning alone prevented or delayed the onset of diabetes, stable mixed chimerism was required for the reversal of isletitis. Mixed chimerism and skin graft tolerance were achieved in NOD mice receiving anti-CD154 with bone marrow transplantation as the means of tolerizing peripheral CD4(+) T cells to alloantigens. However, isletitis was not reversed in allotolerant mixed chimeras prepared with this regimen.
Conclusions. Partial depletion of peripheral autoreactive NOD CD4(+) T cells is needed to achieve full reversal of isletitis by mixed chimerism induction from a protective donor strain, but it is not required for induction of specific tolerance to donor alloantigens. Thus, the requirements for tolerizing alloreactive and autoreactive NOD CD4 cells are distinct.
C1 [Sykes, Megan] Harvard Univ, Bone Marrow Transplantat Sect, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Boston, MA 02129 USA.
[Nikolic, Boris; Primo, Valeria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02129 USA.
[Smith, R. Neal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA.
RP Sykes, M (reprint author), Harvard Univ, Bone Marrow Transplantat Sect, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA.
EM megan.sykes@tbrc.mgh.harvard.edu
FU Juvenile Diabetes Foundation Center for Islet Transplantation at Harvard
Medical School; JDRF Center on Immunological Tolerance in Type I
Diabetes; NIH/NHLBI [R01 HL049915]; NIH/NIDDK [R03 DK067940]; National
Kidney Foundation; Uehara Memorial Foundation
FX This work was supported in part by the Juvenile Diabetes Foundation
Center for Islet Transplantation at Harvard Medical School, the JDRF
Center on Immunological Tolerance in Type I Diabetes, the NIH/NHLBI R01
HL049915, the NIH/NIDDK R03 DK067940, The Patricia Welder Robinson Young
Investigator Grant of the National Kidney Foundation (B.N.), and a
Postdoctoral Fellowship for study abroad from the Uehara Memorial
Foundation (T.O.).
NR 45
TC 6
Z9 6
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD JAN 15
PY 2010
VL 89
IS 1
BP 23
EP 32
DI 10.1097/TP.0b013e3181c4692e
PG 10
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 543DQ
UT WOS:000273551000003
PM 20061915
ER
PT J
AU Osawa, R
Alexander, BD
Lortholary, O
Dromer, F
Forrest, GN
Lyon, GM
Somani, J
Gupta, KL
del Busto, R
Pruett, TL
Sifri, CD
Limaye, AP
John, GT
Klintmalm, GB
Pursell, K
Stosor, V
Morris, MI
Dowdy, LA
Munoz, P
Kalil, AC
Garcia-Diaz, J
Orloff, S
House, AA
Houston, S
Wray, D
Huprikar, S
Johnson, LB
Humar, A
Razonable, RR
Fisher, RA
Husain, S
Wagener, MM
Singh, N
AF Osawa, Ryosuke
Alexander, Barbara D.
Lortholary, Olivier
Dromer, Francoise
Forrest, Graeme N.
Lyon, G. Marshall
Somani, Jyoti
Gupta, Krishan L.
del Busto, Ramon
Pruett, Timothy L.
Sifri, Costi D.
Limaye, Ajit P.
John, George T.
Klintmalm, Goran B.
Pursell, Kenneth
Stosor, Valentina
Morris, Michele I.
Dowdy, Lorraine A.
Munoz, Patricia
Kalil, Andre C.
Garcia-Diaz, Julia
Orloff, Susan
House, Andrew A.
Houston, Sally
Wray, Dannah
Huprikar, Shirish
Johnson, Leonard B.
Humar, Atul
Razonable, Raymund R.
Fisher, Robert A.
Husain, Shahid
Wagener, Marilyn M.
Singh, Nina
TI Identifying Predictors of Central Nervous System Disease in Solid Organ
Transplant Recipients With Cryptococcosis
SO TRANSPLANTATION
LA English
DT Article
DE Cryptococcosis; Solid organ transplant; Central nervous system disease
ID HEMATOPOIETIC STEM-CELL; NEOFORMANS INFECTION; PRACTICE GUIDELINES;
MENINGITIS; MANAGEMENT
AB Background. Cerebrospinal fluid (CSF) analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine whether a subset of solid organ transplant (SOT) recipients with high likelihood of central nervous system (CNS) disease could be identified in whom CSF analysis must be performed.
Methods. Patients comprised a multicenter cohort of SOT recipients with cryptococcosis.
Results. Of 129 (88%) of 146 SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis more than 24 months posttransplantation (late-onset disease), serum cryptococcal antigen titer more than 1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (chi(2) for trend P<0.001).
Conclusions. CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer more than 1:64 even in the presence of normal mental status.
C1 [Osawa, Ryosuke; Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Osawa, Ryosuke; Husain, Shahid; Wagener, Marilyn M.; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA.
[Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA.
[Lortholary, Olivier] Hop Necker Enfants Malad, Fac Med Paris Descartes, Paris, France.
[Lortholary, Olivier; Dromer, Francoise] Inst Pasteur, Paris, France.
[Lyon, G. Marshall; Somani, Jyoti] Emory Univ, Atlanta, GA 30322 USA.
[Gupta, Krishan L.] Postgrad Inst Med Educ & Res, Chandigarh 160012, Punjab, India.
[del Busto, Ramon] Henry Ford Hosp, Detroit, MI 48202 USA.
[Pruett, Timothy L.; Sifri, Costi D.] Univ Virginia, Charlottesville, VA USA.
[Pruett, Timothy L.; Sifri, Costi D.] Univ Minnesota, Minneapolis, MN USA.
[Limaye, Ajit P.] Univ Washington, Seattle, WA 98195 USA.
[John, George T.] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India.
[Klintmalm, Goran B.] Baylor Univ, Med Ctr, Dallas, TX USA.
[Pursell, Kenneth] Univ Chicago, Chicago, IL 60637 USA.
[Stosor, Valentina] Northwestern Univ, Chicago, IL 60611 USA.
[Morris, Michele I.; Dowdy, Lorraine A.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Munoz, Patricia] Hosp Gen Univ Gregorio Maranon, CIBER Enfermedades Resp CIBERES, Madrid, Spain.
[Kalil, Andre C.] Univ Nebraska, Omaha, NE 68182 USA.
[Garcia-Diaz, Julia] Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA.
[Orloff, Susan] Oregon Hlth & Sci Univ, Portland, OR USA.
[House, Andrew A.] Univ Western Ontario, London, ON, Canada.
[Houston, Sally] Tampa Gen Hosp, Tampa, FL 33606 USA.
[Wray, Dannah] Med Univ S Carolina, Charleston, SC 29425 USA.
[Huprikar, Shirish] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Johnson, Leonard B.] St Johns Hosp, Detroit, MI USA.
[Humar, Atul] Toronto Gen Hosp, Univ Hlth Network, Toronto, ON, Canada.
[Forrest, Graeme N.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Razonable, Raymund R.] Mayo Clin, Rochester, MN USA.
[Fisher, Robert A.] Virginia Commonwealth Univ, Richmond, VA USA.
RP Singh, N (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA.
EM nis5@pitt.edu
RI Garcia-Diaz, Julia/D-3555-2011;
OI Munoz Garcia, Patricia Carmen/0000-0001-5706-5583
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases [R01 AI 054719-01]; Astellas; Enzon; Pfizer; Merck;
Basilea; Schering-Plough
FX This work was Supported by National Institutes of Health, National
Institute of Allergy and infectious Diseases (R01 AI 054719-01; N.S.).;
B.D.A. has served on advisory board for Enzon, Basilea, Abbott, and
Schering-Plough, served on the speaker's bureau of Astellas and Pfizer,
and received grant from Astellas, Enzon, and Pfizer; G.N.F. has received
grant from Astellas. G.M.L. has served on advisory board for and
received grant front Merck and Astellas and served on speaker's bureau
of Astellas, Schering-Plough, and Wyeth; K.P. has served on speaker's
bureau of Merck; M.I.M. has served on advisory board for Astellas,
Pfizer, and Merck, received grant from Astellas, Basilea, and Pfizer,
and served on speaker's bureau of Astellas and Pfizer; P.M. has served
on the speaker's bureau of Merck and Novartis and served on advisory
board for Pfizer; L.B.J. has served on speaker's bureau of Pfizer; and
S. Husain has served on consultant board for and received grant from
Pfizer, Astellas, and Schering-Plough; N.S. has received grant from
Pfizer; and the other authors have no conflict of interests.
NR 22
TC 6
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD JAN 15
PY 2010
VL 89
IS 1
BP 69
EP 74
DI 10.1097/TP.0b013e3181bcda41
PG 6
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 543DQ
UT WOS:000273551000009
PM 20061921
ER
PT J
AU Provan, D
Stasi, R
Newland, AC
Blanchette, VS
Bolton-Maggs, P
Bussel, JB
Chong, BH
Cines, DB
Gernsheimer, TB
Godeau, B
Grainger, J
Greer, I
Hunt, BJ
Imbach, PA
Lyons, G
McMillan, R
Rodeghiero, F
Sanz, MA
Tarantino, M
Watson, S
Young, J
Kuter, DJ
AF Provan, Drew
Stasi, Roberto
Newland, Adrian C.
Blanchette, Victor S.
Bolton-Maggs, Paula
Bussel, James B.
Chong, Beng H.
Cines, Douglas B.
Gernsheimer, Terry B.
Godeau, Bertrand
Grainger, John
Greer, Ian
Hunt, Beverley J.
Imbach, Paul A.
Lyons, Gordon
McMillan, Robert
Rodeghiero, Francesco
Sanz, Miguel A.
Tarantino, Michael
Watson, Shirley
Young, Joan
Kuter, David J.
TI International consensus report on the investigation and management of
primary immune thrombocytopenia
SO BLOOD
LA English
DT Review
ID INTRAVENOUS ANTI-D; HIGH-DOSE DEXAMETHASONE; QUALITY-OF-LIFE;
ITP-STUDY-GROUP; THROMBOPOIESIS-STIMULATING PEPTIBODY; NEONATAL
ALLOIMMUNE THROMBOCYTOPENIA; REFRACTORY AUTOIMMUNE CYTOPENIAS; ANTI-CD20
MONOCLONAL-ANTIBODY; RANDOMIZED CONTROLLED-TRIAL;
INFLAMMATORY-BOWEL-DISEASE
AB Previously published guidelines for the diagnosis and management of primary immune thrombocytopenia (ITP) require updating largely due to the introduction of new classes of therapeutic agents, and a greater understanding of the disease pathophysiology. However, treatment-related decisions still remain principally dependent on clinical expertise or patient preference rather than high-quality clinical trial evidence. This consensus document aims to report on new data and provide consensus-based recommendations relating to diagnosis and treatment of ITP in adults, in children, and during pregnancy. The inclusion of summary tables within this document, supported by information tables in the online appendices, is intended to aid in clinical decision making. (Blood. 2010; 115:168-186)
C1 [Provan, Drew; Newland, Adrian C.] Barts & London Queen Marys Sch Med & Dent, Dept Haematol, London E1 2ES, England.
[Stasi, Roberto] NHS Trust, St Georges Healthcare, Dept Haematol, London, England.
[Blanchette, Victor S.] Univ Toronto, Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada.
[Bolton-Maggs, Paula] Manchester Royal Infirm, Dept Clin Haematol, Manchester M13 9WL, Lancs, England.
[Bussel, James B.] New York Hosp, Dept Pediat, New York, NY 10021 USA.
[Chong, Beng H.] Univ New S Wales, St George Clin Sch, Sydney, NSW, Australia.
[Cines, Douglas B.] Hosp Univ Penn, Dept Pathol & Lab, Philadelphia, PA 19104 USA.
[Gernsheimer, Terry B.] Puget Sound Blood Ctr, Seattle, WA 98104 USA.
[Gernsheimer, Terry B.] Univ Washington, Seattle, WA 98195 USA.
[Godeau, Bertrand] Assistance Publ Hop Paris, Serv Med Interne, Paris, France.
[Grainger, John] Royal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, England.
[Greer, Ian] Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England.
[Hunt, Beverley J.] Kings Coll London, London WC2R 2LS, England.
[Hunt, Beverley J.] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Dept Haematol, London, England.
[Hunt, Beverley J.] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Dept Pathol, London, England.
[Hunt, Beverley J.] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Dept Rheumatol, London, England.
[Imbach, Paul A.] Univ Childrens Hosp, Basel, Switzerland.
[Lyons, Gordon] St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England.
[McMillan, Robert] Scripps Res Inst, La Jolla, CA 92037 USA.
[Rodeghiero, Francesco] San Bortolo Hosp, Dept Cell Therapy & Hematol, Vicenza, Italy.
[Sanz, Miguel A.] Hosp Univ La Fe, Dept Haematol, Valencia, Spain.
[Tarantino, Michael] Comprehens Bleeding Disorders Ctr, Peoria, IL USA.
[Watson, Shirley] ITP Support Assoc, Bedford, England.
[Young, Joan] Platelet Disorder Support Assoc, Rockville, MD USA.
[Kuter, David J.] Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA.
[Kuter, David J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Provan, D (reprint author), Barts & London Queen Marys Sch Med & Dent, Dept Haematol, 80 Newark St, London E1 2ES, England.
EM a.b.provan@qmul.ac.uk
FU Amgen Ltd; Baxter Ltd; GlaxoSmithKline Ltd
FX The writing and project management of this consensus document were
supported by an unrestricted grant provided by Amgen Ltd, Baxter Ltd,
and GlaxoSmithKline Ltd. Frances Essex, MSc, Senior Medical Writer,
ScopeMedical Ltd, provided writing assistance throughout the project;
Rebecca Hunt, Account Director, ScopeMedical Ltd, provided project
management; and Keely Jennings BA, Editorial Services Manager,
ScopeMedical Ltd, provided editorial assistance throughout the project.
NR 206
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U1 5
U2 40
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 JAN 14
PY 2010
VL 115
IS 2
BP 168
EP 186
DI 10.1182/blood-2009-06-225565
PG 19
WC Hematology
SC Hematology
GA 544AE
UT WOS:000273622600006
PM 19846889
ER
PT J
AU Schlett, CL
Doll, H
Dahmen, J
Polacsek, O
Federkeil, G
Fischer, MR
Bamberg, F
Butzlaff, M
AF Schlett, Christopher L.
Doll, Hinnerk
Dahmen, Janosch
Polacsek, Ole
Federkeil, Gero
Fischer, Martin R.
Bamberg, Fabian
Butzlaff, Martin
TI Job requirements compared to medical school education: differences
between graduates from problem-based learning and conventional curricula
SO BMC MEDICAL EDUCATION
LA English
DT Article
ID GENERAL COMPETENCES; PHYSICIAN; OUTCOMES
AB Background: Problem-based Learning (PBL) has been suggested as a key educational method of knowledge acquisition to improve medical education. We sought to evaluate the differences in medical school education between graduates from PBL-based and conventional curricula and to what extent these curricula fit job requirements.
Methods: Graduates from all German medical schools who graduated between 1996 and 2002 were eligible for this study. Graduates self-assessed nine competencies as required at their day-to-day work and as taught in medical school on a 6-point Likert scale. Results were compared between graduates from a PBL-based curriculum (University Witten/Herdecke) and conventional curricula.
Results: Three schools were excluded because of low response rates. Baseline demographics between graduates of the PBL-based curriculum (n = 101, 49% female) and the conventional curricula (n = 4720, 49% female) were similar. No major differences were observed regarding job requirements with priorities for "Independent learning/working" and "Practical medical skills". All competencies were rated to be better taught in PBL-based curriculum compared to the conventional curricula (all p < 0.001), except for "Medical knowledge" and "Research competence". Comparing competencies required at work and taught in medical school, PBL was associated with benefits in "Interdisciplinary thinking" (Delta + 0.88), "Independent learning/working" (Delta + 0.57), "Psycho-social competence" (Delta + 0.56), "Teamwork" (Delta + 0.39) and "Problem-solving skills" (Delta + 0.36), whereas "Research competence" (Delta - 1.23) and "Business competence" (Delta - 1.44) in the PBL-based curriculum needed improvement.
Conclusion: Among medical graduates in Germany, PBL demonstrated benefits with regard to competencies which were highly required in the job of physicians. Research and business competence deserve closer attention in future curricular development.
C1 [Butzlaff, Martin] Private Univ Witten Herdecke, Board Directors, Witten, Germany.
[Schlett, Christopher L.; Doll, Hinnerk; Dahmen, Janosch; Polacsek, Ole; Fischer, Martin R.] Private Univ Witten Herdecke, Inst Teaching & Educ Res Hlth Sci, Witten, Germany.
[Schlett, Christopher L.; Bamberg, Fabian] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Schlett, Christopher L.; Bamberg, Fabian] Harvard Univ, Sch Med, Boston, MA USA.
[Federkeil, Gero] Ctr Higher Educ Dev, Gutersloh, Germany.
[Bamberg, Fabian] Univ Munich, Univ Hosp Munich, Dept Clin Radiol, Munich, Germany.
RP Butzlaff, M (reprint author), Private Univ Witten Herdecke, Board Directors, Witten, Germany.
EM butzlaff@uni-wh.de
NR 29
TC 6
Z9 8
U1 3
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6920
J9 BMC MED EDUC
JI BMC Med. Educ.
PD JAN 14
PY 2010
VL 10
AR 1
DI 10.1186/1472-6920-10-1
PG 8
WC Education & Educational Research; Education, Scientific Disciplines
SC Education & Educational Research
GA 688GO
UT WOS:000284838000001
PM 20074350
ER
PT J
AU Kajiwara, Y
Franciosi, S
Takahashi, N
Krug, L
Schmeidler, J
Taddei, K
Haroutunian, V
Fried, U
Ehrlich, M
Martins, RN
Gandy, S
Buxbaum, JD
AF Kajiwara, Yuji
Franciosi, Sonia
Takahashi, Nagahide
Krug, Lisa
Schmeidler, James
Taddei, Kevin
Haroutunian, Vahram
Fried, Ulrik
Ehrlich, Michelle
Martins, Ralph N.
Gandy, Samuel
Buxbaum, Joseph D.
TI Extensive proteomic screening identifies the obesity-related NYGGF4
protein as a novel LRP1-interactor, showing reduced expression in early
Alzheimer's disease
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
ID RECEPTOR-RELATED PROTEIN; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E
RECEPTOR; ISOFORM-SPECIFIC MANNER; CYTOPLASMIC DOMAIN; E GENE;
LIPOPROTEIN; LRP; BINDING; MICE
AB Background: The low-density lipoprotein receptor related protein 1 (LRP1) has been implicated in Alzheimer's disease (AD) but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1.
Results: We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1. The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP), which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b). Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells. Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1. Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression.
Conclusions: These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered early in disease. Genetic and functional studies have implicated both LRP1 and NYGGF4 in obesity and cardiovascular disease and the physical association of these proteins may reflect a common mechanism. This is particularly interesting in light of the dual role of ApoE in both cardiovascular risk and AD. The results support further studies on the functional relationship between NYGGF4 and LRP1.
C1 [Kajiwara, Yuji; Franciosi, Sonia; Takahashi, Nagahide; Krug, Lisa; Fried, Ulrik; Buxbaum, Joseph D.] Mt Sinai Sch Med, Lab Mol Neuropsychiat, New York, NY 10029 USA.
[Kajiwara, Yuji; Franciosi, Sonia; Takahashi, Nagahide; Krug, Lisa; Schmeidler, James; Haroutunian, Vahram; Fried, Ulrik; Gandy, Samuel; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Kajiwara, Yuji; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
[Taddei, Kevin; Martins, Ralph N.] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Ctr Excellence Alzheimers Dis Res Care, Joondalup, WA, Australia.
[Taddei, Kevin] Hollywood Private Hosp, Sir James McCusker Alzheimers Dis Res Unit, Perth, WA, Australia.
[Haroutunian, Vahram] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA.
[Ehrlich, Michelle; Gandy, Samuel] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
[Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
RP Buxbaum, JD (reprint author), Mt Sinai Sch Med, Lab Mol Neuropsychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM joseph.buxbaum@mssm.edu
OI Buxbaum, Joseph/0000-0001-8898-8313
FU National Institute of Aging of the National Institutes of Health
[AG010491, AG005138, AG002219, AG21792]
FX A part of this work was carried out at the Marine Biological Laboratory,
Woods Hole, MA. We thank Dr. Guojun Bu for the mLRP4 construct, Dr.
Eddie Koo for anti-LRP1, and Rebecca Vitale for her help with this
study. This work was supported by grants from the National Institute of
Aging of the National Institutes of Health [AG010491 (SEG, PI; JDB, PL),
AG005138 (Mary Sano, PI; JDB, PL), AG002219 (VH, PI; JDB, PL), and
AG21792 (JDB, PI)]. JDB is the G. Harold and Leila Y. Mathers Professor
of Geriatrics and Adult Development.
NR 51
TC 7
Z9 8
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD JAN 14
PY 2010
VL 5
AR 1
DI 10.1186/1750-1326-5-1
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 559QA
UT WOS:000274839800001
PM 20205790
ER
PT J
AU Pleasance, ED
Cheetham, RK
Stephens, PJ
McBride, DJ
Humphray, SJ
Greenman, CD
Varela, I
Lin, ML
Ordonez, GR
Bignell, GR
Ye, K
Alipaz, J
Bauer, MJ
Beare, D
Butler, A
Carter, RJ
Chen, LN
Cox, AJ
Edkins, S
Kokko-Gonzales, PI
Gormley, NA
Grocock, RJ
Haudenschild, CD
Hims, MM
James, T
Jia, MM
Kingsbury, Z
Leroy, C
Marshall, J
Menzies, A
Mudie, LJ
Ning, ZM
Royce, T
Schulz-Trieglaff, OB
Spiridou, A
Stebbings, LA
Szajkowski, L
Teague, J
Williamson, D
Chin, L
Ross, MT
Campbell, PJ
Bentley, DR
Futreal, PA
Stratton, MR
AF Pleasance, Erin D.
Cheetham, R. Keira
Stephens, Philip J.
McBride, David J.
Humphray, Sean J.
Greenman, Chris D.
Varela, Ignacio
Lin, Meng-Lay
Ordonez, Gonzalo R.
Bignell, Graham R.
Ye, Kai
Alipaz, Julie
Bauer, Markus J.
Beare, David
Butler, Adam
Carter, Richard J.
Chen, Lina
Cox, Anthony J.
Edkins, Sarah
Kokko-Gonzales, Paula I.
Gormley, Niall A.
Grocock, Russell J.
Haudenschild, Christian D.
Hims, Matthew M.
James, Terena
Jia, Mingming
Kingsbury, Zoya
Leroy, Catherine
Marshall, John
Menzies, Andrew
Mudie, Laura J.
Ning, Zemin
Royce, Tom
Schulz-Trieglaff, Ole B.
Spiridou, Anastassia
Stebbings, Lucy A.
Szajkowski, Lukasz
Teague, Jon
Williamson, David
Chin, Lynda
Ross, Mark T.
Campbell, Peter J.
Bentley, David R.
Futreal, P. Andrew
Stratton, Michael R.
TI A comprehensive catalogue of somatic mutations from a human cancer
genome
SO NATURE
LA English
DT Article
ID NUCLEOTIDE EXCISION-REPAIR; ETS TRANSCRIPTION FACTOR; MYELOID-LEUKEMIA
GENOME; SKIN-CANCER; PATHWAYS; MELANOMA; CARCINOGENESIS; EPIDEMIOLOGY;
MECHANISMS; EXPRESSION
AB All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.
C1 [Pleasance, Erin D.; Stephens, Philip J.; McBride, David J.; Greenman, Chris D.; Varela, Ignacio; Lin, Meng-Lay; Ordonez, Gonzalo R.; Bignell, Graham R.; Beare, David; Butler, Adam; Chen, Lina; Edkins, Sarah; Jia, Mingming; Leroy, Catherine; Marshall, John; Menzies, Andrew; Mudie, Laura J.; Ning, Zemin; Stebbings, Lucy A.; Teague, Jon; Campbell, Peter J.; Futreal, P. Andrew; Stratton, Michael R.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
[Cheetham, R. Keira; Humphray, Sean J.; Bauer, Markus J.; Carter, Richard J.; Cox, Anthony J.; Kokko-Gonzales, Paula I.; Gormley, Niall A.; Grocock, Russell J.; Hims, Matthew M.; James, Terena; Kingsbury, Zoya; Schulz-Trieglaff, Ole B.; Spiridou, Anastassia; Szajkowski, Lukasz; Ross, Mark T.; Bentley, David R.] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England.
[Ye, Kai] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2333 ZC Leiden, Netherlands.
[Ye, Kai] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, NL-2333 ZC Leiden, Netherlands.
[Alipaz, Julie; Royce, Tom] Illumina Inc, Corp Headquarters, San Diego, CA 92121 USA.
[Haudenschild, Christian D.; Williamson, David] Illumina Hayward, Hayward, CA 94545 USA.
[Chin, Lynda] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Stratton, Michael R.] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
RP Stratton, MR (reprint author), Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
EM paf@sanger.ac.uk; mrs@sanger.ac.uk
RI Bell, Tiffany/F-4403-2010; Ye, Kai/B-3640-2012; Ning, Zemin/D-2411-2013;
Tang, Macy/B-9798-2014; Varela, Ignacio/G-1699-2016;
OI Varela, Ignacio/0000-0002-0969-506X; Ning, Zemin/0000-0003-4359-776X
FU Wellcome Trust [077012/Z/05/Z]
FX The authors acknowledge the support of C. Henry, S. Kahn, D. Evers, G.
Smith, K. Hall and the technical and administrative support staff at
Illumina. I. V. is supported by the Human Frontiers Science Program and
P.J.C. by the Kay Kendall Leukaemia Fund. We would like to acknowledge
the Wellcome Trust for support under grant reference 077012/Z/05/Z.
NR 41
TC 781
Z9 803
U1 9
U2 103
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JAN 14
PY 2010
VL 463
IS 7278
BP 191
EP U73
DI 10.1038/nature08658
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 543MQ
UT WOS:000273582700027
PM 20016485
ER
PT J
AU McMahon, GT
Blake, MA
Wu, CL
AF McMahon, Graham T.
Blake, Michael A.
Wu, Chin-Lee
TI A Man with Hypertension, Hyperglycemia, and Edema Secondary Cushing's
syndrome due to metastatic small-cell carcinoma of prostatic origin
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ECTOPIC ACTH; ADENOCARCINOMA; THERAPY; MANAGEMENT; CANCER
C1 [McMahon, Graham T.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA.
[Blake, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[McMahon, Graham T.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Blake, Michael A.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA.
[Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP McMahon, GT (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA.
RI McMahon, Graham/D-3740-2009
OI McMahon, Graham/0000-0003-4288-6535
NR 31
TC 4
Z9 5
U1 0
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 14
PY 2010
VL 362
IS 2
BP 156
EP 166
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 543FU
UT WOS:000273558500015
PM 20071706
ER
PT J
AU Sykes, M
AF Sykes, Megan
TI Immune Evasion by Chimeric Trachea
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID TRANSPLANTATION; TOLERANCE; ALLOGRAFTS; RESPONSES; MICE
C1 [Sykes, Megan] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Sykes, Megan] Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02114 USA.
RP Sykes, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
FU NHLBI NIH HHS [R01 HL063474, P01 HL018646]; NIAID NIH HHS [R01 AI055581]
NR 12
TC 8
Z9 9
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 JAN 14
PY 2010
VL 362
IS 2
BP 172
EP 174
DI 10.1056/NEJMe0908366
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 543FU
UT WOS:000273558500018
PM 20071709
ER
PT J
AU Li, JF
Li, L
Sheen, J
AF Li, Jian-Feng
Li, Li
Sheen, Jen
TI Protocol: a rapid and economical procedure for purification of plasmid
or plant DNA with diverse applications in plant biology
SO PLANT METHODS
LA English
DT Article
ID GENE-EXPRESSION ANALYSIS; TRANSFORMATION; ARABIDOPSIS; EXTRACTION;
VECTORS
AB Research in plant molecular biology involves DNA purification on a daily basis. Although different commercial kits enable convenient extraction of high-quality DNA from E. coli cells, PCR and agarose gel samples as well as plant tissues, each kit is designed for a particular type of DNA extraction work, and the cost of purchasing these kits over a long run can be considerable. Furthermore, a simple method for the isolation of binary plasmid from Agrobacterium tumefaciens cells with satisfactory yield is lacking. Here we describe an easy protocol using homemade silicon dioxide matrix and seven simple solutions for DNA extraction from E. coli and A. tumefaciens cells, PCR and restriction digests, agarose gel slices, and plant tissues. Compared with the commercial kits, this protocol allows rapid DNA purification from diverse sources with comparable yield and purity at negligible cost. Following this protocol, we have demonstrated: (1) DNA fragments as small as a MYC-epitope tag coding sequence can be successfully recovered from an agarose gel slice; (2) Miniprep DNA from E. coli can be eluted with as little as 5 mu l water, leading to high DNA concentrations (> 1 mu g/mu l) for efficient biolistic bombardment of Arabidopsis seedlings, polyethylene glycol (PEG)-mediated Arabidopsis protoplast transfection and maize protoplast electroporation; (3) Binary plasmid DNA prepared from A. tumefaciens is suitable for verification by restriction analysis without the need for large scale propagation; (4) High-quality genomic DNA is readily isolated from several plant species including Arabidopsis, tobacco and maize. Thus, the silicon dioxide matrix-based DNA purification protocol offers an easy, efficient and economical way to extract DNA for various purposes in plant research.
C1 [Li, Jian-Feng; Li, Li; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Li, Jian-Feng; Li, Li; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
RP Li, JF (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM jli@molbio.mgh.harvard.edu
RI Li, Jian-Feng/H-4307-2011
FU NIH R01 [GM070567, GM060493]
FX We are grateful to Dr. Andreas Nebenfuh (University of Tennessee) for
the generous gifts of pAN-GFP and pPZP222 vectors. This work was
sponsored by NIH R01 grants GM070567 and GM060493 to J. S.
NR 12
TC 7
Z9 7
U1 5
U2 37
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1746-4811
J9 PLANT METHODS
JI Plant Methods
PD JAN 14
PY 2010
VL 6
AR 1
DI 10.1186/1746-4811-6-1
PG 8
WC Biochemical Research Methods; Plant Sciences
SC Biochemistry & Molecular Biology; Plant Sciences
GA 562HB
UT WOS:000275039700001
ER
PT J
AU Hui, KKS
Marina, O
Claunch, JD
Nixon, EE
Fang, JL
Liu, J
Li, M
Napadow, V
Vangel, M
Makris, N
Chan, ST
Kwong, KK
Rosen, BR
AF Hui, Kathleen K. S.
Marina, Ovidiu
Claunch, Joshua D.
NiXon, Erika E.
Fang, Jiliang
Liu, Jing
Li, Ming
Napadow, Vitaly
Vangel, Mark
Makris, Nikos
Chan, Suk-Tak
Kwong, Kenneth K.
Rosen, Bruce R.
TI Acupuncture mobilizes the brain's default mode and its anti-correlated
network in healthy subjects (vol 1287, pg 84, 2009)
SO BRAIN RESEARCH
LA English
DT Correction
C1 [Hui, Kathleen K. S.; Marina, Ovidiu; Claunch, Joshua D.; NiXon, Erika E.; Fang, Jiliang; Liu, Jing; Li, Ming; Napadow, Vitaly; Vangel, Mark; Chan, Suk-Tak; Kwong, Kenneth K.; Rosen, Bruce R.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Hui, Kathleen K. S.; Marina, Ovidiu; Claunch, Joshua D.; NiXon, Erika E.; Fang, Jiliang; Liu, Jing; Li, Ming; Napadow, Vitaly; Vangel, Mark; Makris, Nikos; Chan, Suk-Tak; Kwong, Kenneth K.; Rosen, Bruce R.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Marina, Ovidiu] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Fang, Jiliang] China Acad Tradit Chinese Med, Dept Radiol, Guang An Men Hosp, Beijing, Peoples R China.
[Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Charlestown, MA 02129 USA.
[Chan, Suk-Tak] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China.
RP Hui, KKS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA.
EM hui@nmr.mgh.harvard.edu
RI Chan, Suk-tak/G-5846-2015
NR 1
TC 0
Z9 0
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 JAN 13
PY 2010
VL 1308
BP 185
EP 185
DI 10.1016/j.brainres.2009.10.017
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 555LT
UT WOS:000274513000019
ER
PT J
AU Goldstein, JM
Jerram, M
Abbs, B
Whitfield-Gabrieli, S
Makris, N
AF Goldstein, Jill M.
Jerram, Matthew
Abbs, Brandon
Whitfield-Gabrieli, Susan
Makris, Nikos
TI Sex Differences in Stress Response Circuitry Activation Dependent on
Female Hormonal Cycle
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID VENTROMEDIAL PREFRONTAL CORTEX; ESTROGEN-RECEPTOR-BETA;
GENDER-DIFFERENCES; PARAVENTRICULAR NUCLEUS; MENSTRUAL-CYCLE;
VISUAL-STIMULI; WOMEN; FMRI; HYPOTHALAMUS; ESTRADIOL
AB Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i. e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.
C1 [Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02120 USA.
[Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02120 USA.
[Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon] Brigham & Womens Hosp, Dept Med, Boston, MA 02120 USA.
[Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA.
Harvard Univ, Sch Med, Boston, MA 02120 USA.
[Goldstein, Jill M.; Abbs, Brandon] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neurosci, Charlestown, MA 02129 USA.
[Goldstein, Jill M.; Abbs, Brandon] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Goldstein, Jill M.; Jerram, Matthew; Makris, Nikos] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Goldstein, Jill M.; Jerram, Matthew; Makris, Nikos] MIT, Charlestown, MA 02129 USA.
[Jerram, Matthew] Suffolk Univ, Dept Psychol, Boston, MA 02108 USA.
[Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Makris, Nikos] Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA 02129 USA.
RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1 Brigham Circle,1620 Tremont St, Boston, MA 02120 USA.
EM jill_goldstein@hms.harvard.edu
FU National Institute of Mental Health [NIMH-ORWH P50MH082679, NIMH
R01MH56956]; Athinoula Martinos Center for Biomedical Imaging at
Massachusetts General Hospital Collaborative Start-up Award
FX This work was supported by grants from the National Institute of Mental
Health to J. M. G. (NIMH-ORWH P50MH082679, NIMH R01MH56956) and the
Athinoula Martinos Center for Biomedical Imaging at Massachusetts
General Hospital Collaborative Start-up Award. Wealso thank Dr. Bernard
Harlow for access to the female population sample, Dr. Russell Poldrack
for statistical help on the design of earlier versions of this study,
Dr. Deborah Walder and Gabe Daly for help on some earlier stages of data
analyses, Sarah Spaeth for help with data acquisition and analysis,
George Papadimitriou for help in image production, Drs. Anne Klibanski
and Stuart Tobet for comments on earlier aspects of the study, and Lisa
Cushman-Daly for manuscript preparation.
NR 48
TC 120
Z9 126
U1 4
U2 15
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 JAN 13
PY 2010
VL 30
IS 2
BP 431
EP 438
DI 10.1523/JNEUROSCI.3021-09.2010
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 543OC
UT WOS:000273586900003
PM 20071507
ER
PT J
AU Rodriguez, E
Nilges, M
Weissleder, R
Chen, JW
AF Rodriguez, Elisenda
Nilges, Mark
Weissleder, Ralph
Chen, John W.
TI Activatable Magnetic Resonance Imaging Agents for Myeloperoxidase
Sensing: Mechanism of Activation, Stability, and Toxicity
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PARAMAGNETIC CONTRAST AGENTS; CORONARY-ARTERY-DISEASE; ENZYME
MYELOPEROXIDASE; ROTATIONAL-DYNAMICS; MULTIPLE-SCLEROSIS; PEROXIDASE;
OXIDATION; MEDIA; EXPRESSION; LESIONS
AB Myeloperoxidase (MPO) is increasingly being recognized as an important factor in many inflammatory diseases, particularly cardiovascular and neurological diseases. MPO-specific imaging agents would thus be highly useful to diagnose early disease, monitor disease progression, and quantify treatment effects. This study reports in vitro and in vivo characterizations of the mechanism of interaction between MPO and paramagnetic enzyme substrates based on physical and biological measurements. We show that these agents are activated through a radical mechanism, which can combine to form oligomers and, in the presence of tyrosine-containing peptide, bind to proteins. We further identified two new imaging agents, which represent the near extremes in either oligomerization (mono-5HT-DTPA-Gd) or protein-binding in their activation mechanism (bis-o-dianisidine-DTPA-Gd). On the other hand, we found that the agent bis-5HT-DTPA-Gd utilizes both mechanisms when activated. These properties yield distinct in vivo pharmacokinetics profiles for each of these agents that may be exploited for different applications. Specificity studies show that only MPO, but not eosinophil peroxidase, can highly activate these agents, and that MPO activity as low as 0.005 U/mg of tissue can be detected. Gd kinetic lability and cytotoxicity studies further confirm stability of the Gd ion and low toxicity for the 5HT-based agents, suggesting that these agents are suitable for translational in vivo studies.
C1 [Rodriguez, Elisenda; Weissleder, Ralph; Chen, John W.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA.
[Nilges, Mark] Univ Illinois, Illinois EPR Res Ctr, Urbana, IL 61801 USA.
[Weissleder, Ralph; Chen, John W.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
RP Chen, JW (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA.
EM jwchen@mgh.harvard.edu
FU EC-Marie Curie [39639]; National Institutes of Health [K08HL081170,
ROI-HL078641]
FX We thank Ben Bautz, Alexy Chudnovsky, Martin Etzrodt, and Christopher N.
LaFratta for experimental assistance and Brian Rutt for helpful
discussions. We also acknowledge Alexei Bogdanov and Manel Querol for
early contributions to the development of MPO sensing agents. E.R. was
supported by the EC-Marie Curie grant OIF (Molecular Imaging 39639).
This work was supported in part by National Institutes of Health Grants
K08HL081170 (J.W.C.) and ROI-HL078641 (R.W.).
NR 43
TC 41
Z9 44
U1 1
U2 18
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JAN 13
PY 2010
VL 132
IS 1
BP 168
EP 177
DI 10.1021/ja905274f
PG 10
WC Chemistry, Multidisciplinary
SC Chemistry
GA 562VW
UT WOS:000275084400047
PM 19968300
ER
PT J
AU Yamodo, IH
Chiara, DC
Cohen, JB
Miller, KW
AF Yamodo, Innocent H.
Chiara, David C.
Cohen, Jonathan B.
Miller, Keith W.
TI Conformational Changes in the Nicotinic Acetylcholine Receptor during
Gating and Desensitization
SO BIOCHEMISTRY
LA English
DT Article
ID GATED ION-CHANNEL; LIPID-PROTEIN INTERFACE; X-RAY-STRUCTURE;
BINDING-SITES; NONCOMPETITIVE INHIBITOR; HYDROPHOBIC INHIBITOR; GLYCINE
RECEPTORS; RESTING STATE; TORPEDO; MECHANISM
AB The nicotinic acetylcholine receptor (nAChR) is a member of the important Cys loop ligand-gated ion channel superfamily that modulates neuronal excitability. After they respond to their agonists, their actions are terminated either by removal of ligand or by fast and slow desensitization, processes that play ail important role in modulating the duration of conducting states and hence of integrated neuronal behavior. We monitored structural changes Occurring during fast and slow desensitization in the transmembrane domain of the Torpedo nAChR using time-resolved photolabeling with the hydrophobic probe 3-(trifluoromethyl)-3-(m-iodophenyl)diazirine (TID). After channel opening, TID photolabels a residue oil the delta-subunit's M2-M3 loop and a cluster of four residues on delta M1 and delta M2, defining all open state pocket [Arevalo, E., et al. (2005) J. Biol. Chem. 280, 13631-13640]. We now find that photolabeling of this pocket persists during the transition to the fact desensitized state, the extent of photoincorporation decreasing only with the transition to the slow desensitized state. In contrast, the extent of photoincorporation in the channel lumen at the conserved 9'-leucines oil the second transmembrane helix (M2-9') decreased successively during the resting to open and open to fast desensitized state transitions, implying that the local conformation is different in each state, a Conclusion consistent with the hypothesis that there are separate gates for channel opening and desensitization. Thus, although during Cast desensitization there is a conformation change in the channel lumen at the level of M2-9', there is none in the regions of the delta-subunit's M2-M3 loop and the interior of its M1-M4 helix bundle until slow desensitization occurs.
C1 [Yamodo, Innocent H.; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02116 USA.
[Chiara, David C.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02116 USA.
RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 32 Fruit St, Boston, MA 02114 USA.
EM k_miller@helix.mgh.harvard.edu
FU National Institutes of Health [GM-58448]; Department of Anesthesia and
Critical Care; Massachusetts General Hospital; Howard Hughes Biomedical
Research Support Program
FX This research was supported by a grant from the National Institutes of
Health (GM-58448), by the Department of Anesthesia and Critical Care,
Massachusetts General Hospital, and by an award to the Harvard Medical
School from the Howard Hughes Biomedical Research Support Program.
NR 47
TC 23
Z9 23
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JAN 12
PY 2010
VL 49
IS 1
BP 156
EP 165
DI 10.1021/bi901550p
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 539PE
UT WOS:000273267300018
PM 19961216
ER
PT J
AU Li, NC
Lee, A
Whitmer, RA
Kivipelto, M
Lawler, E
Kazis, LE
Wolozin, B
AF Li, Nien-Chen
Lee, Austin
Whitmer, Rachel A.
Kivipelto, Miia
Lawler, Elizabeth
Kazis, Lewis E.
Wolozin, Benjamin
TI Use of angiotensin receptor blockers and risk of dementia in a
predominantly male population: prospective cohort analysis
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID ALZHEIMER-DISEASE PROGRESSION; MILD COGNITIVE IMPAIRMENT; ENZYME ACE
INHIBITORS; QUALITY-OF-LIFE; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE;
HYPERTENSIVE PATIENTS; HEART-FAILURE; SYSTEM; LOSARTAN
AB Objective To investigate whether angiotensin receptor blockers protect against Alzheimer's disease and dementia or reduce the progression of both diseases.
Design Prospective cohort analysis.
Setting Administrative database of the US Veteran Affairs, 2002-6.
Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease.
Main outcome measures Time to incident Alzheimer's disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the "cardiovascular comparator") over a four year period (fiscal years 2003-6) using Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer's disease or dementia.
Results Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 (95% confidence interval 0.69 to 0.84) compared with the cardiovascular comparator and 0.81 (0.73 to 0.90) compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer's disease were associated with a significantly lower risk of admission to a nursing home (0.51, 0.36 to 0.72) and death (0.83, 0.71 to 0.97). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54, 0.51 to 0.57) and admission to a nursing home (0.33, 0.22 to 0.49). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer's disease.
Conclusions Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer's disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population.
C1 [Li, Nien-Chen; Lee, Austin; Kazis, Lewis E.; Wolozin, Benjamin] Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Li, Nien-Chen; Kazis, Lewis E.] Boston Univ, Sch Publ Hlth,Management & Policy Program, Ctr Assessment Pharmaceut Practices & Pharmaceut, Dept Hlth Policy & Management, Boston, MA USA.
[Lee, Austin] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Whitmer, Rachel A.] Kaiser Permanente, Div Res Epidemiol Etiol & Prevent, Oakland, CA USA.
[Kivipelto, Miia] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden.
[Lawler, Elizabeth] VA Cooperat Studies Program, MAVERIC, Boston, MA USA.
[Wolozin, Benjamin] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA.
[Wolozin, Benjamin] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
RP Wolozin, B (reprint author), Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
EM bwolozin@bu.edu
OI Kazis, Lewis/0000-0003-1800-5849; Kivipelto, Miia/0000-0003-0992-3875
FU Retirement Research Foundation; Casten Foundation
FX This work was supported by a grant award to BW from the Retirement
Research Foundation and a donation from the Casten Foundation. The
researchers operate independently of the funders of the study.; BW and
RAW received a grant award from the Retirement Research Foundation to
fund this research. BW received a donation from the Casten Foundation to
fund this research.
NR 61
TC 192
Z9 197
U1 3
U2 17
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 JAN 12
PY 2010
VL 340
AR b5465
DI 10.1136/bmj.b5465
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 545CZ
UT WOS:000273711400005
PM 20068258
ER
PT J
AU Ay, H
Gungor, L
Arsava, EM
Rosand, J
Vangel, M
Benner, T
Schwamm, LH
Furie, KL
Koroshetz, WJ
Sorensen, AG
AF Ay, H.
Gungor, L.
Arsava, E. M.
Rosand, J.
Vangel, M.
Benner, T.
Schwamm, L. H.
Furie, K. L.
Koroshetz, W. J.
Sorensen, A. G.
TI A score to predict early risk of recurrence after ischemic stroke
SO NEUROLOGY
LA English
DT Article
ID LONG-TERM RISK; CEREBRAL INFARCTION; SUBTYPE DIAGNOSIS; COMMUNITY
STROKE; ATTACK; SEVERITY; SURVIVAL; LEUKOARAIOSIS; PROGNOSIS; PATTERNS
AB Background: There is currently no instrument to stratify patients presenting with ischemic stroke according to early risk of recurrent stroke. We sought to develop a comprehensive prognostic score to predict 90-day risk of recurrent stroke.
Methods: We analyzed data on 1,458 consecutive ischemic stroke patients using a Cox regression model with time to recurrent stroke as the response and clinical and imaging features typically available to physician at admission as covariates. The 90-day risk of recurrent stroke was calculated by summing up the number of independent predictors weighted by their corresponding beta-coefficients. The resultant score was called recurrence risk estimator at 90 days or RRE-90 score (available at: http://www.nmr.mgh.harvard.edu/RRE-90/).
Results: Sixty recurrent strokes (54 had baseline imaging) occurred during the follow-up period. The risk adjusted for time to follow-up was 6.0%. Predictors of recurrence included admission etiologic stroke subtype, prior history of TIA/stroke, and topography, age, and distribution of brain infarcts. The RRE-90 score demonstrated adequate calibration and good discrimination (area under the ROC curve [AUC] = 0.70-0.80), which was maintained when applied to a separate cohort of 433 patients (AUC = 0.70-0.76). The model's performance was also maintained for predicting early (14-day) risk of recurrence (AUC = 0.80).
Conclusions: The RRE-90 is a Web-based, easy-to-use prognostic score that integrates clinical and imaging information available in the acute setting to quantify early risk of recurrent stroke. The RRE-90 demonstrates good predictive performance, suggesting that, if validated externally, it has promise for use in creating individualized patient management algorithms and improving clinical practice in acute stroke care. Neurology (R) 2010;74:128-135
C1 [Ay, H.; Rosand, J.; Schwamm, L. H.; Furie, K. L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Serv, Boston, MA 02115 USA.
[Ay, H.; Gungor, L.; Arsava, E. M.; Vangel, M.; Benner, T.; Sorensen, A. G.] Harvard Univ, Sch Med, Dept Radiol, AA Martinos Ctr Biomed Imaging,Massachusetts Gen, Boston, MA 02115 USA.
[Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Rosand, J.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Koroshetz, W. J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Ay, H (reprint author), Harvard Univ, AA Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp, 149 13th St,Room 2301, Charlestown, MA 02129 USA.
EM hay@partners.org
RI Arsava, Ethem Murat/I-9197-2013;
OI Arsava, Ethem Murat/0000-0002-6527-4139; Schwamm,
Lee/0000-0003-0592-9145
FU NIH [R01-NS059710, R01-NS059727, NINDS P50 NS051343-01, NINDS U01
NS052220 IMS-3, NCRR 1 UL 1 RR025758-01, DHHS/CDC [5 U13 DP001176-02],
NINDS NS38477, NCI CA137254, NINDS NS063925, NINDS NS061119]; American
Heart Association; Forest Laboratories, Inc; Deane Institute; Millennium
Pharmaceuticals, Inc.; Siemens Medical Solutions; AstraZeneca; Genentech
Inc; Novartis; Merck Serono; Schering Plough Corp
FX Dr. Ay receives research support from the NIH [R01-NS059710 (PI)]. Dr.
Gungor and Dr. Arsava report no disclosures. Dr. Rosand receives
research support from the NIH [R01-NS059727 (PI)] and from the American
Heart Association. Dr. Vangel reports no disclosures. Dr. Benner serves
as a consultant for Siemens Medical Solutions and Bayer Schering Pharma.
Dr. Schwamm serves on scientific advisory boards for CoAxia, Inc. and
Phreesia; has received honoraria and funding for travel for lectures or
educational activities not funded by industry; serves on the editorial
board of Neurocritical Care; may accrue revenue on US Patent 6,542,769
(filed 2003): Imaging system for obtaining quantitative perfusion
indices; his spouse receives royalties from publishing Obstetric
Anesthesia (Cambridge Pocket Clinicians, 2007-2009); serves as a
consultant to Medtronic, Inc./CryoCath, Research Triangle Inc., and the
Massachusetts Department of Public Health; serves on an external
scientific review committee for the Canadian Stroke Network; and
receives research support from Forest Laboratories, Inc., the NIH [NINDS
P50 NS051343-01 (Co-I), NINDS U01 NS052220 IMS-3 (Site PI), and NCRR 1
UL 1 RR025758-01 (CRC Staff)] and the DHHS/CDC [5 U13 DP001176-02 (PI)].
Dr. Furie has served on scientific advisory boards for Novartis and GE
Healthcare and receives research support from the NIH/NINDS
[R01-HS011392 (PI) and P50-NS051343 (PI)], the American Heart
Association, and the Deane Institute. Dr. Koroshetz is a full-time
employee of the NIH and holds stock in NeuroLogica. Dr. Sorensen has
served on scientific advisory boards for Olea Medical and Breakaway
Imaging; has received funding for travel from Genentech, Inc., Siemens
Medical Solutions, Millennium Pharmaceuticals, Inc., AstraZeneca, and
for speaking and educational activities not funded by industry; serves
as a Section Editor of Stroke and on the editorial boards of The
Oncologist and the Journal of Clinical Oncology; may accrue revenue on
US Patent 7020578 (issued 2001): Method for evaluating novel, stroke
treatments using a tissue risk map, US Patent 6542769 (issued 2000):
Imaging system for obtaining quantitative perfusion indices, US Patent
10558343 (issued 2004): Delay-compensated calculation of tissue blood
flow, US Patent 11075990 (issued: 2005): High-flow oxygen delivery
system and methods of use thereof, and US Patent 11417769 (issued:
2006): Magnetic resonance spatial risk map for tissue outcome
prediction; receives royalties from publishing Cerebral MR Perfusion
Imaging (Thieme, 2000); has received honoraria from Siemens Medical
Solutions, Novartis, GE Healthcare, and for speaking and educational
activities not funded by industry; has served as a consultant to
Mitsubishi Tanabe Pharma Corporation, AstraZeneca, and Genentech, Inc.;
receives research support from Millennium Pharmaceuticals, Inc., Siemens
Medical Solutions, AstraZeneca, Genentech Inc., Novartis, Merck Serono,
Schering Plough Corp, the NIH [NINDS NS38477 (PI), NCI CA137254 (PI),
NINDS NS063925 (PI), and NINDS NS061119 (PI)]; and holds stock and stock
options in Epix Pharmaceuticals.
NR 38
TC 44
Z9 46
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JAN 12
PY 2010
VL 74
IS 2
BP 128
EP 135
DI 10.1212/WNL.0b013e3181ca9cff
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 543HC
UT WOS:000273563600007
PM 20018608
ER
PT J
AU VanCott, AC
Cramer, JA
Copeland, LA
Zeber, JE
Steinman, MA
Dersh, JJ
Glickman, ME
Mortensen, EM
Amuan, ME
Pugh, MJ
AF VanCott, Anne C.
Cramer, Joyce A.
Copeland, Laurel A.
Zeber, John E.
Steinman, Michael A.
Dersh, Jeffrey J.
Glickman, Mark E.
Mortensen, Eric M.
Amuan, Megan E.
Pugh, Mary Jo
TI Suicide-related behaviors in older patients with new anti-epileptic drug
use: data from the VA hospital system
SO BMC MEDICINE
LA English
DT Article
ID LEVETIRACETAM THERAPY; CLINICAL-TRIALS; RISK-FACTORS; FOLLOW-UP;
EPILEPSY; DEPRESSION; VETERANS; AGE; DISORDERS; DEMENTIA
AB Background: The U. S. Food and Drug Administration (FDA) recently linked antiepileptic drug (AED) exposure to suicide-related behaviors based on meta-analysis of randomized clinical trials. We examined the relationship between suicide-related behaviors and different AEDs in older veterans receiving new AED monotherapy from the Veterans Health Administration (VA), controlling for potential confounders.
Methods: VA and Medicare databases were used to identify veterans 66 years and older, who received a) care from the VA between 1999 and 2004, and b) an incident AED ( monotherapy) prescription. Previously validated ICD-9-CM codes were used to identify suicidal ideation or behavior (suicide-related behaviors cases), epilepsy, and other conditions previously associated with suicide-related behaviors. Each case was matched to controls based on prior history of suicide-related behaviors, year of AED prescription, and epilepsy status.
Results: The strongest predictor of suicide-related behaviors (N = 64; Controls N = 768) based on conditional logistic regression analysis was affective disorder ( depression, anxiety, or post-traumatic stress disorder (PTSD); Odds Ratio 4.42, 95% CI 2.30 to 8.49) diagnosed before AED treatment. Increased suicide-related behaviors were not associated with individual AEDs, including the most commonly prescribed AED in the US - phenytoin.
Conclusion: Our extensive diagnostic and treatment data demonstrated that the strongest predictor of suicide-related behaviors for older patients newly treated with AED monotherapy was a previous diagnosis of affective disorder. Additional, research using a larger sample is needed to clearly determine the risk of suicide-related behaviors among less commonly used AEDs.
C1 [VanCott, Anne C.] VA Pittsburgh Healthcare Syst, Div Neurol, Pittsburgh, PA USA.
[VanCott, Anne C.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Cramer, Joyce A.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Cramer, Joyce A.] Epilepsy Therapy Project, Orange, CT USA.
[Copeland, Laurel A.; Zeber, John E.; Dersh, Jeffrey J.; Mortensen, Eric M.; Pugh, Mary Jo] S Texas Vet Hlth Care Syst VERDICT, Vet Affairs HSR&D, San Antonio, TX USA.
[Copeland, Laurel A.; Zeber, John E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.
[Glickman, Mark E.; Amuan, Megan E.] Edith Nourse Rogers Mem Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Glickman, Mark E.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Gen Med, San Antonio, TX 78229 USA.
RP VanCott, AC (reprint author), VA Pittsburgh Healthcare Syst, Div Neurol, Pittsburgh, PA USA.
EM Anne.VanCott@va.gov
OI Glickman, Mark/0000-0003-3993-2801; Pugh, Mary Jo/0000-0003-4196-7763;
Mortensen, Eric/0000-0002-3880-5563; Copeland,
Laurel/0000-0002-9478-0209
FU Department of Veterans Affairs, Health Services Research and Development
Service [IIR-02-274]; VA Health Services Research and Development
Service Merit Review Entry [MRP-05-145]; South Texas Veterans Healthcare
System/Audie L. Murphy Division; VERDICT
FX This study was funded by the Department of Veterans Affairs, Health
Services Research and Development Service (IIR-02-274). Dr. Copeland
received funding from VA Health Services Research and Development
Service Merit Review Entry Program Award (MRP-05-145). The authors
acknowledge and appreciate support from the South Texas Veterans
Healthcare System/Audie L. Murphy Division and the VERDICT research
program. The views expressed in this article are those of the authors
and do not necessarily represent the views of the Department of Veterans
Affairs. We thank Alan Ettinger, MD for reviewing and providing comments
regarding this manuscript. We also acknowledge contributions of other
members of the TIGER research team: Dan R. Berlowitz MD, MPH, Janice E.
Knoefel MD, Jeffrey Tabares BA, Francesca Cunningham PharmD, Omotola
Hope MD, Nancy Kressin PhD, Barbara Bokhour PhD, and Marcos Restrepo MD.
NR 31
TC 40
Z9 41
U1 3
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD JAN 11
PY 2010
VL 8
AR 4
DI 10.1186/1741-7015-8-4
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 557OG
UT WOS:000274678200001
PM 20064226
ER
PT J
AU Lee, BJ
Egi, Y
van Leyen, K
Lo, EH
Arai, K
AF Lee, Brian J.
Egi, Yasuhiro
van Leyen, Klaus
Lo, Eng H.
Arai, Ken
TI Edaravone, a free radical scavenger, protects components of the
neurovascular unit against oxidative stress in vitro
SO BRAIN RESEARCH
LA English
DT Article
DE Oxidative stress; Neuron; Astrocyte; Endothelial cell; Neurovascular
unit; Stroke
ID PRIMARY-CULTURED ASTROCYTES; CEREBRAL ENDOTHELIAL-CELLS;
PEROXIDE-INDUCED APOPTOSIS; ACUTE ISCHEMIC-STROKE; MITOCHONDRIAL
DYSFUNCTION; ARTERY OCCLUSION; NEURONAL DEATH; BRAIN EDEMA; MCI-186;
NEUROPROTECTION
AB The concept of the neurovascular unit suggests that to be successful, stroke therapies must protect all neuronal, glial and endothelial components in brain. in this study, we tested the efficacy of the free radical scavenger edaravone in three cellular models of oxidative stress. HT22 neuronal cells were subjected to oxidative stress using the standard glutamate-induced glutathione depletion model. Primary rat astrocytes were exposed to H(2)O(2). Oxidative stress was induced in human brain endothelial cells with sodium nitroprusside (SNP). Edaravone significantly reduced oxidative cell death in both HT22 neuronal cells and primary rat astrocytes in a dose-dependent manner. SNP did not kill brain endothelial cells but instead reduced their production of brain-derived neurotrophic factor (BDNF). Edaravone significantly ameliorated this response. These data suggest that free radical scavengers are effective in all cell types of the neurovascular unit, and should still be considered as a potential therapeutic approach for stroke. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Arai, Ken] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Arai, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA.
EM karai@partners.org
RI van Leyen, Klaus/C-9126-2013
FU Deane Foundation; American Heart Association; NIH
FX Supported in part by the Deane Foundation, American Heart Association
and NIH.
NR 44
TC 31
Z9 36
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 JAN 11
PY 2010
VL 1307
BP 22
EP 27
DI 10.1016/j.brainres.2009.10.026
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 554QZ
UT WOS:000274450800003
PM 19840779
ER
PT J
AU Mehta, DD
Deliyski, DD
Zeitels, SM
Quatieri, TF
Hillman, RE
AF Mehta, Daryush D.
Deliyski, Dimitar D.
Zeitels, Steven M.
Quatieri, Thomas F.
Hillman, Robert E.
TI Voice Production Mechanisms Following Phonosurgical Treatment of Early
Glottic Cancer
SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY
LA English
DT Article; Proceedings Paper
CT 89th Annual Meeting of the American-Broncho-Esophagological-Association
CY MAY 28-29, 2009
CL Phoenix, AZ
SP Amer Broncho Esophagol Assoc
DE acoustic perturbation; glottic cancer; high-speed videoendoscopy; vocal
fold asymmetry; voice production
ID HIGH-SPEED VIDEOENDOSCOPY; VOCAL FOLD; VIDEOKYMOGRAPHY; EVOLUTION
AB Objectives: Although near-normal conversational voices can be achieved with the phonosurgical management of early glottic cancer, there are still acoustic and aerodynamic deficits in vocal function that Must be better understood to help further optimize phonosurgical interventions. Stroboscopic assessment is inadequate for this purpose.
Methods: A newly developed color high-speed videoendoscopy (HSV) system that included time-synchronized recordings of the acoustic signal Was used to perform a detailed examination of voice production mechanisms in 14 Subjects. Digital image processing techniques were used to quantify glottal phonatory function and to delineate relationships between vocal fold vibratory properties and acoustic perturbation measures.
Results: The results for multiple measurements of vibratory asymmetry showed that 31% to 62% of subjects displayed higher-than-normal average values, whereas the mean values for glottal Closure duration (open quotient) and periodicity of vibration fell within normal limits. The average HSV-based measures did not correlate significantly with the acoustic perturbation Measures, but moderate correlations were exhibited between the acoustic measures and the SDs of the HSV-based parameters.
Conclusions: The use of simultaneous, time-synchronized HSV and acoustic recordings can provide new insights into postoperative voice production mechanisms that cannot be obtained with stroboscopic assessment.
C1 [Mehta, Daryush D.; Zeitels, Steven M.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Mehta, Daryush D.; Quatieri, Thomas F.; Hillman, Robert E.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA.
[Mehta, Daryush D.; Quatieri, Thomas F.] MIT, Lincoln Lab, Lexington, MA 02173 USA.
[Zeitels, Steven M.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Deliyski, Dimitar D.] Univ S Carolina, Dept Commun Sci & Disorders, Columbia, SC 29208 USA.
RP Hillman, RE (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA.
FU NIDCD NIH HHS [R01 DC007640, R01 DC007640-01A2, R01 DC007640-02, R01
DC007640-03, T32 DC000038, T32 DC00038]; NIEHS NIH HHS [27304C0002,
27306C0002]
NR 20
TC 40
Z9 41
U1 0
U2 5
PU ANNALS PUBL CO
PI ST LOUIS
PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA
SN 0003-4894
J9 ANN OTO RHINOL LARYN
JI Ann. Otol. Rhinol. Laryngol.
PD JAN 10
PY 2010
VL 119
IS 1
BP 1
EP 9
PG 9
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 544SW
UT WOS:000273680600001
PM 20128179
ER
PT J
AU Scott, AR
Chong, PST
Hartnick, CJ
Randolph, GW
AF Scott, Andrew R.
Chong, Peter Siao Tick
Hartnick, Christopher J.
Randolph, Gregory W.
TI Spontaneous and Evoked Laryngeal Electromyography of the Thyroarytenoid
Muscles: A Canine Model for Intraoperative Recurrent Laryngeal Nerve
Monitoring
SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY
LA English
DT Article; Proceedings Paper
CT 88th Annual Meeting of the American-Broncho-Esophagological-Association
CY MAY 01-02, 2008
CL Orlando, FL
SP Amer Broncho Esophagol Assoc
DE canine recurrent laryngeal nerve model; laryngeal electromyography;
recurrent laryngeal nerve monitoring
ID VOCAL FOLD PARALYSIS
AB Objectives: We sought to determine the feasibility of performing spontaneous and evoked intraoperative laryngeal electromyography (L-EMG) using nerve monitoring equipment and to compare recording electrode configurations and methods of recurrent laryngeal nerve (RLN) stimulation in dogs.
Methods: Four beagles underwent crush injury of the left RLN, and 2 beagles underwent left RLN transection. Serial spontaneous and evoked L-EMG was recorded with the NIM-Response nerve monitoring system under sedation. Transesophageal, percutaneous, and direct open RLN stimulation was performed. Recordings of spontaneous and evoked responses were made with endotracheal tube surface electrodes and bipolar vocal fold needle electrodes. The L-EMG procedures were repeated every 1 to 2 weeks after injury, and intersubject and intertrial differences were evaluated.
Results: Low-amplitude motor unit action potentials, polyphasic potentials, fasciculations, and fibrillations were detected in injured animals with bipolar needle recording electrodes with this system of spontaneous L-EMG. The surface recording electrodes did not detect pathologic waveforms. Percutaneous needle stimulation of the RLN is possible at Currents slightly higher than those used for direct stimulation. Consistent, discrete, transesophageal stimulation of the RLN could not be reliably performed. Recording evoked responses with needle electrodes generated sharper waveforms, facilitating calculation of latency and wave duration. Evoked L-EMG utilizing surface recording electrodes limited the intertrial and intersubject variability of evoked amplitude.
Conclusions: Typical patterns of nerve injury can be detected with this system of intraoperative L-EMG in a canine model. Quantitative measures of amplitude, latency, and wave duration in healthy and injured canine RLNs may be determined with this system.
C1 [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Thyroid & Parathyroid Surg, Boston, MA 02114 USA.
[Scott, Andrew R.; Hartnick, Christopher J.; Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Pediat, Boston, MA 02114 USA.
[Chong, Peter Siao Tick] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Surg Oncol, Boston, MA 02115 USA.
[Randolph, Gregory W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Surg Serv, Boston, MA 02115 USA.
RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Thyroid & Parathyroid Surg, 243 Charles St, Boston, MA 02114 USA.
NR 12
TC 15
Z9 16
U1 0
U2 2
PU ANNALS PUBL CO
PI ST LOUIS
PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA
SN 0003-4894
J9 ANN OTO RHINOL LARYN
JI Ann. Otol. Rhinol. Laryngol.
PD JAN 10
PY 2010
VL 119
IS 1
BP 54
EP 63
PG 10
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 544SW
UT WOS:000273680600011
PM 20128189
ER
PT J
AU Maron, BA
Goldhaber, SZ
Sturzu, AC
Rhee, DK
Ali, BS
Shah, PB
Kirshenbaum, JM
AF Maron, Bradley A.
Goldhaber, Samuel Z.
Sturzu, Anthony C.
Rhee, David K.
Ali, Bilal S.
Shah, Pinak Bipin
Kirshenbaum, James M.
TI Catheter-Directed Thrombolysis for Giant Right Atrial Thrombus
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
C1 [Maron, Bradley A.] Brigham & Womens Hosp, Div Cardiovasc Med, PBB G, Dept Internal Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Sturzu, Anthony C.] Massachusetts Gen Hosp, Dept Internal Med, Div Cardiol, Boston, MA 02114 USA.
RP Maron, BA (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, PBB G, Dept Internal Med, 75 Francis St, Boston, MA 02115 USA.
EM bmaron@partners.org
NR 4
TC 2
Z9 3
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD JAN 10
PY 2010
VL 3
IS 1
BP 126
EP 127
DI 10.1161/CIRCIMAGING.109.906487
PG 2
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 545MI
UT WOS:000273736000016
PM 20086226
ER
PT J
AU Duda, DG
Ancukiewicz, M
Jain, RK
AF Duda, Dan G.
Ancukiewicz, Marek
Jain, Rakesh K.
TI Biomarkers of Antiangiogenic Therapy: How Do We Move From Candidate
Biomarkers to Valid Biomarkers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; VASCULAR NORMALIZATION;
GLIOBLASTOMA PATIENTS; TUMOR ANGIOGENESIS; KINASE INHIBITOR;
BEVACIZUMAB; PACLITAXEL; FLUOROURACIL; CARBOPLATIN
C1 [Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Duda, DG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
FU NCI NIH HHS [P01 CA080124]
NR 24
TC 31
Z9 31
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 JAN 10
PY 2010
VL 28
IS 2
BP 183
EP 185
DI 10.1200/JCO.2009.24.8021
PG 3
WC Oncology
SC Oncology
GA 541LU
UT WOS:000273418000001
PM 19949009
ER
PT J
AU Hanrahan, EO
Lin, HY
Kim, ES
Yan, SY
Du, DZ
McKee, KS
Tran, HT
Lee, JJ
Ryan, AJ
Langmuir, P
Johnson, BE
Heymach, JV
AF Hanrahan, Emer O.
Lin, Heather Y.
Kim, Edward S.
Yan, Shaoyu
Du, Danny Z.
McKee, Kathryn S.
Tran, Hai T.
Lee, J. Jack
Ryan, Anderson J.
Langmuir, Peter
Johnson, Bruce E.
Heymach, John V.
TI Distinct Patterns of Cytokine and Angiogenic Factor Modulation and
Markers of Benefit for Vandetanib and/or Chemotherapy in Patients With
Non-Small-Cell Lung Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; METASTATIC
COLORECTAL-CANCER; COOPERATIVE-ONCOLOGY-GROUP; RANDOMIZED PHASE-II;
FACTOR RECEPTOR; THERAPEUTIC IMPLICATIONS; TUMOR ANGIOGENESIS;
BREAST-CANCER; BEVACIZUMAB
AB Purpose
There is an unmet need for biomarkers for identifying patients likely to benefit from anticancer treatments, selecting dose, and understanding mechanisms of resistance. Plasma vascular endothelial growth factor (VEGF) and soluble VEGF receptor 2 (sVEGFR-2) are known to be modulated by VEGF pathway inhibitors. It is unknown whether chemotherapy or VEGFR inhibitor/chemotherapy combinations induce changes in these or other cytokines and angiogenic factors (CAFs) and whether such changes could be markers of benefit.
Methods
Thirty-five plasma CAFs were analyzed using multiplexed bead arrays and enzyme-linked immunosorbent assays from 123 patients with non-small-cell lung cancer in a randomized phase II study who received vandetanib, a VEGFR and epidermal growth factor receptor inhibitor, monotherapy carboplatin and paclitaxel (CP), or the combination (VCP). Changes in CAFs at days 8, 22, and 43 from baseline were correlated with progression risk.
Results
VEGF increased and sVEGFR-2 decreased by day 43 in the vandetanib arm, whereas a distinct pattern was observed in the CP and VCP arms, with significant decreases in interleukin (IL) -12, IL-1 receptor antagonist, an