FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Copeland, LA
Zeber, JE
Wang, CP
Parchman, ML
Lawrence, VA
Valenstein, M
Miller, AL
AF Copeland, Laurel A.
Zeber, John E.
Wang, Chen-Pin
Parchman, Michael L.
Lawrence, Valerie A.
Valenstein, Marcia
Miller, Alexander L.
TI Patterns of primary care and mortality among patients with schizophrenia
or diabetes: a cluster analysis approach to the retrospective study of
healthcare utilization
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID SERIOUS MENTAL-ILLNESS; OF-VETERANS-AFFAIRS; EXCESS MORTALITY; SYSTEM;
MANAGEMENT; RETENTION; QUALITY; RISK
AB Background: Patients with schizophrenia have difficulty managing their medical healthcare needs, possibly resulting in delayed treatment and poor outcomes. We analyzed whether patients reduced primary care use over time, differentially by diagnosis with schizophrenia, diabetes, or both schizophrenia and diabetes. We also assessed whether such patterns of primary care use were a significant predictor of mortality over a 4-year period.
Methods: The Veterans Healthcare Administration (VA) is the largest integrated healthcare system in the United States. Administrative extracts of the VA's all-electronic medical records were studied. Patients over age 50 and diagnosed with schizophrenia in 2002 were age-matched 1:4 to diabetes patients. All patients were followed through 2005. Cluster analysis explored trajectories of primary care use. Proportional hazards regression modelled the impact of these primary care utilization trajectories on survival, controlling for demographic and clinical covariates.
Results: Patients comprised three diagnostic groups: diabetes only (n = 188,332), schizophrenia only (n = 40,109), and schizophrenia with diabetes (Scz-DM, n = 13,025). Cluster analysis revealed four distinct trajectories of primary care use: consistent over time, increasing over time, high and decreasing, low and decreasing. Patients with schizophrenia only were likely to have low-decreasing use (73% schizophrenia-only vs 54% Scz-DM vs 52% diabetes). Increasing use was least common among schizophrenia patients (4% vs 8% Scz-DM vs 7% diabetes) and was associated with improved survival. Low-decreasing primary care, compared to consistent use, was associated with shorter survival controlling for demographics and case-mix. The observational study was limited by reliance on administrative data.
Conclusion: Regular primary care and high levels of primary care were associated with better survival for patients with chronic illness, whether psychiatric or medical. For schizophrenia patients, with or without comorbid diabetes, primary care offers a survival benefit, suggesting that innovations in treatment retention targeting at-risk groups can offer significant promise of improving outcomes.
C1 [Copeland, Laurel A.; Zeber, John E.; Wang, Chen-Pin; Parchman, Michael L.; Lawrence, Valerie A.] S Texas Vet Hlth Care Syst, VERDICT Res, San Antonio, TX USA.
[Copeland, Laurel A.; Zeber, John E.; Miller, Alexander L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Wang, Chen-Pin] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA.
[Lawrence, Valerie A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Valenstein, Marcia] Vet Adm Ann Arbor Healthcare Syst, SMITREC Res, Ann Arbor, MI USA.
[Valenstein, Marcia] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP Copeland, LA (reprint author), S Texas Vet Hlth Care Syst, VERDICT Res, San Antonio, TX USA.
EM copelandl@uthscsa.edu; zeber@uthscsa.edu; chen-pin.wang@va.gov;
parchman@uthscsa.edu; vlawrence@uthscsa.edu; marciav@umich.edu;
millera@uthscsa.edu
OI Copeland, Laurel/0000-0002-9478-0209
FU Department of Veterans Affairs; Veterans Health Administration, Health
Services Research and Development Service [IIR 05-326]; South Texas
Veterans Health Care System, San Antonio, TX; University of Texas Health
Science Center at San Antonio; Serious Mental Illness Treatment Research
& Evaluation Center; VA Ann Arbor Healthcare System, Ann Arbor, MI;
Merit Review Entry Program [MRP-05145]; VA Health Services Research and
Development program; VA HSRD [IIR05-326]
FX This research was supported by the Department of Veterans Affairs,
Veterans Health Administration, Health Services Research and Development
Service ( IIR 05-326; PI: Copeland). This work was completed with the
additional support of the VERDICT Research Program at the South Texas
Veterans Health Care System, San Antonio, TX, the University of Texas
Health Science Center at San Antonio, and the Serious Mental Illness
Treatment Research & Evaluation Center, VA Ann Arbor Healthcare System,
Ann Arbor, MI. LAC is funded by Merit Review Entry Program grant
MRP-05145 from the VA Health Services Research and Development program.
CPW, VAL, ALM, MV and JEZ are co-investigators on grant VA HSRD
IIR05-326 [Copeland-PI]. The authors gratefully acknowledge the
contributions of Brandon J Hosek in extracting, aggregating, and
managing the data.
NR 30
TC 35
Z9 36
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD JUL 26
PY 2009
VL 9
AR 127
DI 10.1186/1472-6963-9-127
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 490SW
UT WOS:000269525900001
PM 19630997
ER
PT J
AU Raab, MS
Podar, K
Breitkreutz, I
Richardson, PG
Anderson, KC
AF Raab, Marc S.
Podar, Klaus
Breitkreutz, Iris
Richardson, Paul G.
Anderson, Kenneth C.
TI Multiple myeloma
SO LANCET
LA English
DT Review
ID STEM-CELL TRANSPLANTATION; PEGYLATED LIPOSOMAL DOXORUBICIN; THALIDOMIDE
PLUS DEXAMETHASONE; HIGH-DOSE THERAPY; PROTEASOME INHIBITOR BORTEZOMIB;
BONE-MARROW TRANSPLANTATION; PREVIOUSLY TREATED PATIENTS;
NEWLY-DIAGNOSED MYELOMA; NF-KAPPA-B; PHASE-II
AB Multiple myeloma is characterised by clonal proliferation of malignant plasma cells, and mounting evidence indicates that the bone marrow microenvironment of tumour cells has a pivotal role in myeloma pathogenesis. This knowledge has already expanded treatment options for patients with multiple myeloma. Prototypic drugs thalidomide, bortezomib, and lenalidomide have each been approved for the treatment of this disease by targeting both multiple myeloma cells and the bone marrow microenvironment. Although benefit was first shown in relapsed and refractory disease, improved overall response, duration of response, and progression-free and overall survival can be achieved when these drugs are part of first-line regimens. This treatment framework promises to improve outcome not only for patients with multiple myeloma, but also with other haematological malignancies and solid tumours.
C1 [Raab, Marc S.; Podar, Klaus; Breitkreutz, Iris; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
[Raab, Marc S.; Podar, Klaus; Breitkreutz, Iris; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA.
[Raab, Marc S.] Heidelberg Univ, Med Ctr, Dept Med 5, Heidelberg, Germany.
[Raab, Marc S.; Breitkreutz, Iris] Natl Ctr Tumor Dis, Heidelberg, Germany.
[Raab, Marc S.; Breitkreutz, Iris] German Canc Res Ctr, D-6900 Heidelberg, Germany.
RP Anderson, KC (reprint author), Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, 44 Binney St, Boston, MA 02115 USA.
EM Kenneth_Anderson@dfci.harvard.edu
NR 148
TC 347
Z9 370
U1 8
U2 55
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JUL 25
PY 2009
VL 374
IS 9686
BP 324
EP 339
DI 10.1016/S0140-6736(09)60221-X
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA 477GW
UT WOS:000268508200030
PM 19541364
ER
PT J
AU Joussen, AM
Doehmen, S
Le, ML
Koizumi, K
Radetzky, S
Krohne, TU
Poulaki, V
Semkova, I
Kociok, N
AF Joussen, Antonia M.
Doehmen, Sven
Le, Minh L.
Koizumi, Kan
Radetzky, Sven
Krohne, Tim U.
Poulaki, Vassiliki
Semkova, Irina
Kociok, Norbert
TI TNF-alpha mediated apoptosis plays an important role in the development
of early diabetic retinopathy and long-term histopathological
alterations
SO MOLECULAR VISION
LA English
DT Article
ID NF-KAPPA-B; CELL-DEATH; RHEUMATOID-ARTHRITIS; ENDOTHELIAL-CELLS;
TRANSCRIPTIONAL REGULATION; ADHESION MOLECULES; VASCULAR LEAKAGE;
IN-VIVO; EXPRESSION; RETINA
AB Purpose: The pathophysiology of diabetic retinopathy involves leukocyte adhesion to retinal vasculature, early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell death. We investigated the involvement of tumor necrosis factor alpha (TNF-alpha) in diabetes-related histopathological changes in two relevant rodent models.
Methods: In short-term studies, Long-Evans rats with streptozotocin-induced diabetes were treated with or without the TNF-alpha inhibitor, etanercept. For long-term studies, tumor necrosis factor receptor I (TNF-RI)-deficient mice and TNF-RII-deficient mice, as well as C57/Bl6 wild-type mice, were fed 30% galactose for up to 20 months. The retinal histopathological alterations of hypergalactosemia were analyzed in trypsin digest preparations. Endothelial cell injury and apoptosis in rat retinas were evaluated by propidium iodide, TUNEL, CytoDeath staining, and DNA fragmentation ELISA. Caspase 3 and 8 activity was evaluated by immunoblotting and quantitative enzymatic activity assay.
Results: Etanercept suppressed caspase activation, retinal cell injury, and apoptosis in short-term diabetic rats. Pericyte and endothelial cell loss were also reduced in long-term hypergalactosemic mice. Long-term studies demonstrated that pericyte loss and endothelial cell loss were reduced in comparison to wild-type diabetic controls.
Conclusions: Our study identifies an important role for TNF-alpha in the pathogenesis of signature diabetic retinopathy pathologies and demonstrates that etanercept can inhibit retinal cell death and long-term complication of diabetes. Taken together, our results suggest that etanercept could prove beneficial in preventing both early and late vascular diabetic complications.
C1 [Joussen, Antonia M.; Semkova, Irina; Kociok, Norbert] Univ Dusseldorf, Dept Ophthalmol, D-40225 Dusseldorf, Germany.
[Joussen, Antonia M.; Doehmen, Sven; Le, Minh L.; Koizumi, Kan; Radetzky, Sven; Krohne, Tim U.; Semkova, Irina; Kociok, Norbert] Univ Cologne, Dept Vitreoretinal Surg, Ctr Ophthalmol, D-5000 Cologne 41, Germany.
[Joussen, Antonia M.; Doehmen, Sven] Univ Cologne, Ctr Mol Med, D-5000 Cologne 41, Germany.
[Poulaki, Vassiliki] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA.
RP Joussen, AM (reprint author), Univ Dusseldorf, Dept Ophthalmol, Moorenstr 5, D-40225 Dusseldorf, Germany.
EM JoussenA@googlemail.com
RI Krohne, Tim/D-1497-2013
OI Krohne, Tim/0000-0003-2280-925X
FU Deutsche Forschungsgemeinschaft DFG [JO 324/6-1, JO 324/4-1, JO
324/10-1]
FX This study was funded by the Deutsche Forschungsgemeinschaft DFG JO
324/6-1 (ENP), DFG JO 324/4-1, DFG JO 324/10-1, Ernst und Berta Grimmke
Stiftung, Meyer-Schwarting Stiftung, Gertrud und Werner Muller Stiftung,
and the Foundation Fighting Blindness (to V.P.). We thank Christina
Esser, Claudia Gavranic, and Heimke Bucken for professional technical
assistance and Silke Coburger, PhD, Department of Medical Informatics,
University of Cologne for statistical advice. There is no financial or
other connection to the manufacturer of etanercept.
NR 44
TC 108
Z9 115
U1 1
U2 5
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUL 25
PY 2009
VL 15
IS 151
BP 1418
EP 1428
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 493LZ
UT WOS:000269739600001
PM 19641635
ER
PT J
AU Taboada, E
Solanas, R
Rodriguez, E
Weissleder, R
Roig, A
AF Taboada, Elena
Solanas, Raul
Rodriguez, Elisenda
Weissleder, Ralph
Roig, Anna
TI Supercritical-Fluid-Assisted One-Pot Synthesis of Biocompatible
Core(gamma-Fe2O3)/Shell(SiO2) Nanoparticles as High Relaxivity
T-2-Contrast Agents for Magnetic Resonance Imaging
SO ADVANCED FUNCTIONAL MATERIALS
LA English
DT Article
ID SILICA PARTICLES; DELIVERY-SYSTEM; MRI; AEROGELS
AB Monodisperse iron oxide/microporous silica core/shell composite nanoparticles, core(gamma-Fe2O3)/shell(SiO2), with a diameter of approximately 100 nm and a high magnetization are synthesized by combining sol-gel chemistry and supercritical fluid technology. This one-step processing method, which is easily scalable, allows quick fabrication of materials with controlled properties and in high yield. The particles have a specific magnetic moment (per kg of iron) comparable to that of the bulk maghemite and show superparamagnetic behavior at room temperature. The nanocomposites are proven to be useful as T-2 MRI imaging agent. They also have potential to be used in NMR proximity sensing, theranostic drug delivery, and bioseparation.
C1 [Taboada, Elena; Solanas, Raul; Roig, Anna] CSIC, ICMAB, Bellaterra 08193, Spain.
[Solanas, Raul] MATGAS 2000 AIE, Bellaterra 08193, Spain.
[Rodriguez, Elisenda; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA.
[Rodriguez, Elisenda; Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Taboada, E (reprint author), CSIC, ICMAB, Campus UAB, Bellaterra 08193, Spain.
EM roig@icmab.es
RI ROIG, ANNA/E-7616-2011
OI ROIG, ANNA/0000-0001-6464-7573
FU Ministerio de Ciencia e Innovacion [MAT2006-13572-C02-01];
CONSOLIDER-NANOSELECT [CSD2007-00041]; Fundacion Domingo Martinez
(2009); EC-NoE FAME; CNRS
FX This work has been partially financed by the Ministerio de Ciencia e
Innovacion (MAT2006-13572-C02-01 and
CONSOLIDER-NANOSELECT-CSD2007-00041), the Fundacion Domingo Martinez
(2009), and the EC-NoE FAME. We thank M.-H. Delville from CNRS Bordeaux
for early discussions on the materials and D. X. Chen (ICREA-UAB), A.
Goni (ICREA-CSIC), and A. Slawska-Waniewska (I F-PAS) for fruitful
discussions on the magnetic properties. E. R. kindly acknowledges the
EC-Marie Curie grant OIF (Molecular Imaging 39639).
NR 33
TC 82
Z9 82
U1 5
U2 46
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1616-301X
J9 ADV FUNCT MATER
JI Adv. Funct. Mater.
PD JUL 24
PY 2009
VL 19
IS 14
BP 2319
EP 2324
DI 10.1002/adfm.200801681
PG 6
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 478RR
UT WOS:000268606500018
ER
PT J
AU Kelly, TJ
Lerin, C
Haas, W
Gygi, SP
Puigserver, P
AF Kelly, Timothy J.
Lerin, Carles
Haas, Wilhelm
Gygi, Steven P.
Puigserver, Pere
TI GCN5-mediated Transcriptional Control of the Metabolic Coactivator PGC-1
beta through Lysine Acetylation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PPAR-GAMMA COACTIVATOR-1; FATTY-ACID OXIDATION; MITOCHONDRIAL
BIOGENESIS; SKELETAL-MUSCLE; RECEPTOR-ALPHA; ERR-ALPHA;
ENERGY-EXPENDITURE; INSULIN-RESISTANCE; PGC-1-ALPHA; ACTIVATION
AB Changes in expression levels of genes encoding for proteins that control metabolic pathways are essential to maintain nutrient and energy homeostasis in individual cells as well as in organisms. An important regulated step in this process is accomplished through covalent chemical modifications of proteins that form complexes with the chromatin of gene promoters. The peroxisome proliferators gamma co-activator 1 (PGC-1) family of transcriptional co-activators comprises important components of a number of these complexes and participates in a large array of glucose and lipid metabolic adaptations. Here, we show that PGC-1 beta is acetylated on at least 10 lysine residues distributed along the length of the protein by the acetyl transferase general control of amino-acid synthesis (GCN5) and that this acetylation reaction is reversed by the deacetylase sirtuin 1 (SIRT1). GCN5 strongly interacts with PGC-1 beta and represses its transcriptional activity associated with transcription factors such as ERR alpha, NRF-1, and HNF4 alpha, however acetylation and transcriptional repression do not occur when a catalytically inactive GCN5 is co-expressed. Transcriptional repression coincides with PGC-1 beta redistribution to nuclear foci where it co-localizes with GCN5. Furthermore, knockdown of GCN5 ablates PGC-1 beta acetylation and increases transcriptional activity. In primary skeletal muscle cells, PGC-1 beta induction of endogenous target genes, including MCAD and GLUT4, is largely repressed by GCN5. Functionally, this translates to a blunted response to PGC-1 beta-induced insulin-mediated glucose transport. These results suggest that PGC-1 beta acetylation by GCN5 might be an important step in the control of glucose and lipid pathways and its dysregulation could contribute to metabolic diseases.
C1 [Puigserver, Pere] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Kelly, Timothy J.; Lerin, Carles; Haas, Wilhelm; Gygi, Steven P.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kelly, Timothy J.] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA.
RP Puigserver, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 1 Jimmy Fund Way,Smith 932C, Boston, MA 02115 USA.
EM pere_puigserver@dfci.harvard.edu
FU National Institutes of Health [RO1 DK069966]; Ellison Medical Foundation
New Scholar Award; American Diabetes Association; U.S. Dept. of Defense
FX This work was supported, in whole or in part, by National Institutes of
Health Grant RO1 DK069966 (to P. P.). This work was also supported by an
Ellison Medical Foundation New Scholar Award, by the American Diabetes
Association, and by the U.S. Dept. of Defense.
NR 46
TC 52
Z9 55
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 24
PY 2009
VL 284
IS 30
BP 19945
EP 19952
DI 10.1074/jbc.M109.015164
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 471ZO
UT WOS:000268097400021
PM 19491097
ER
PT J
AU Bains, M
Florez-McClure, ML
Heidenreich, KA
AF Bains, Mona
Florez-McClure, Maria L.
Heidenreich, Kim A.
TI Insulin-like Growth Factor-I Prevents the Accumulation of Autophagic
Vesicles and Cell Death in Purkinje Neurons by Increasing the Rate of
Autophagosome-to-lysosome Fusion and Degradation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CHAPERONE-MEDIATED AUTOPHAGY; CEREBELLAR GRANULE NEURONS;
PROTEIN-KINASE; ALZHEIMERS-DISEASE; SIGNALING PATHWAYS;
GLUTAMATE-RECEPTOR; TRANSGENIC MICE; LURCHER MICE; APOPTOSIS;
MACROAUTOPHAGY
AB Continuous macroautophagic activity is critical for the maintenance of neuronal homeostasis; however, unchecked or dysregulated autophagy can lead to cell death. Cultured Purkinje neurons die by an autophagy-associated cell death mechanism when deprived of trophic support. Here, we report that insulin-like growth factor-I ( IGF-I) completely blocked the autophagy-associated cell death of Purkinje neurons. To examine the mechanism by which IGF-I influences autophagy, neurons were infected with adeno-RFP-LC3 and subjected to trophic factor withdrawal, and the size and number of autophagosomes were analyzed by live-cell fluorescence imaging. In control neurons, autophagy occurred at a constitutive low level with most autophagosomes measuring less than 0.75 mu m. Trophic factor withdrawal increased the number and size of autophagosomes with most autophagosomes ranging between 0.75 and 1.5 mu m and some reaching 1.5-2.25 mu m. IGF-I added at the time of trophic factor withdrawal prevented the accumulation of the larger autophagosomes; however, it had no effect on the conversion of LC3, an indicator of autophagy induction. Instead, the rate of autophagosome-to-lysosome fusion measured by colocalization of RFP-LC3 and LysoSensor Green was accelerated by IGF-I. Treating the neurons with bafilomycin A(1) in the presence of IGF-I led to the accumulation of autophagosomes even larger than those induced by trophic factor withdrawal alone, indicating that IGF-I regulates autophagic vesicle turnover. Finally, the effect of IGF-I on autophagy was mediated by an Akt/mTOR-dependent and an ERK-independent pathway. These data suggest a novel role for IGF-I in protecting Purkinje neurons from autophagy-associated cell death by increasing autophagy efficiency downstream of autophagy induction.
C1 [Bains, Mona; Heidenreich, Kim A.] Univ Colorado Denver, Dept Pharmacol, Aurora, CO 80045 USA.
[Florez-McClure, Maria L.] Discovery Martek Biosci Corp, Neurosci Res, Boulder, CO 80301 USA.
[Heidenreich, Kim A.] Denver Vet Affairs Med Ctr, Denver, CO 80262 USA.
RP Heidenreich, KA (reprint author), Univ Colorado Denver, Dept Pharmacol, MS 8303,POB 6511, Aurora, CO 80045 USA.
EM Kim.Heidenreich@ucdenver.edu
FU National Institutes of Health [NS045560, 1F32NS062534-01A1]; Department
of Veterans Affairs merit awards; Department of Defense [03281009]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants NS045560 and 1F32NS062534-01A1 (NINDS). This work was also
supported by a Department of Veterans Affairs merit awards and
Department of Defense Grant 03281009 (United States Army Medical
Research and Material Command).
NR 55
TC 31
Z9 32
U1 3
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 24
PY 2009
VL 284
IS 30
BP 20398
EP 20407
DI 10.1074/jbc.M109.011791
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 471ZO
UT WOS:000268097400065
PM 19509289
ER
PT J
AU Barabasi, AL
AF Barabasi, Albert-Laszlo
TI Scale-Free Networks: A Decade and Beyond
SO SCIENCE
LA English
DT Editorial Material
ID SMALL-WORLD NETWORKS; COMPLEX NETWORKS; INTERNET
AB For decades, we tacitly assumed that the components of such complex systems as the cell, the society, or the Internet are randomly wired together. In the past decade, an avalanche of research has shown that many real networks, independent of their age, function, and scope, converge to similar architectures, a universality that allowed researchers from different disciplines to embrace network theory as a common paradigm. The decade-old discovery of scale-free networks was one of those events that had helped catalyze the emergence of network science, a new research field with its distinct set of challenges and accomplishments.
C1 [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Biol & Comp Sci, Ctr Complex Network Res, Boston, MA 02115 USA.
[Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
RP Barabasi, AL (reprint author), Northeastern Univ, Dept Phys Biol & Comp Sci, Ctr Complex Network Res, Boston, MA 02115 USA.
EM alb@neu.edu
RI Xie, Jianjun/D-9838-2012
NR 26
TC 547
Z9 597
U1 12
U2 156
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 JUL 24
PY 2009
VL 325
IS 5939
BP 412
EP 413
DI 10.1126/science.1173299
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474AR
UT WOS:000268255100038
PM 19628854
ER
PT J
AU Richardson, P
Jagannath, S
Hussein, M
Berenson, J
Singhal, S
Irwin, D
Williams, SF
Bensinger, W
Badros, AZ
Vescio, R
Kenvin, L
Yu, ZN
Olesnyckyj, M
Zeldis, J
Knight, R
Anderson, KC
AF Richardson, Paul
Jagannath, Sundar
Hussein, Mohamad
Berenson, James
Singhal, Seema
Irwin, David
Williams, Stephanie F.
Bensinger, William
Badros, Ashraf Z.
Vescio, Robert
Kenvin, Laurie
Yu, Zhinuan
Olesnyckyj, Marta
Zeldis, Jerome
Knight, Robert
Anderson, Kenneth C.
TI Safety and efficacy of single-agent lenalidomide in patients with
relapsed and refractory multiple myeloma
SO BLOOD
LA English
DT Article
ID EXTENDED FOLLOW-UP; PLUS DEXAMETHASONE; DRUG-RESISTANCE; THALIDOMIDE;
CANCER; THROMBOEMBOLISM; BORTEZOMIB; THERAPY; PHASE-2; TRIAL
AB Lenalidomide plus dexamethasone is effective for the treatment of relapsed and refractory multiple myeloma (MM); however, toxicities from dexamethasone can be dose limiting. We evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed and refractory MM. Patients (N = 222) received lenalidomide 30 mg/day once daily (days 1-21 every 28 days) until disease progression or intolerance. Response, progression-free survival (PFS), overall survival (OS), time to progression (TTP), and safety were assessed. Overall, 67% of patients had received 3 or more prior treatment regimens. Partial response or better was reported in 26% of patients, with minimal response 18%. There was no difference between patients who had received 2 or fewer versus 3 or more prior treatment regimens (45% vs 44%, respectively). Median values for TTP, PFS, and OS were 5.2, 4.9, and 23.2 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which proved manageable with dose reduction. Grade 3 or 4 febrile neutropenia occurred in 4% of patients. Lenalidomide monotherapy is active in relapsed and refractory MM with acceptable toxicities. These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351. (Blood. 2009; 114: 772-778)
C1 [Richardson, Paul] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Jagannath, Sundar] St Vincents Comprehens Canc Ctr, New York, NY USA.
[Hussein, Mohamad] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Hussein, Mohamad] Res Inst, Tampa, FL USA.
[Berenson, James] Inst Myeloma & Bone Canc Res, W Hollywood, CA USA.
[Singhal, Seema] Robert H Lurie Canc Ctr, Chicago, IL USA.
[Irwin, David] Alta Bates Canc Ctr, Berkeley, CA USA.
[Williams, Stephanie F.] Hematol Oncol Associates Illinois, Chicago, IL USA.
[Bensinger, William] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Badros, Ashraf Z.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Vescio, Robert] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Kenvin, Laurie; Yu, Zhinuan; Olesnyckyj, Marta; Zeldis, Jerome; Knight, Robert] Hoechst Celanese Corp, Summit, NJ 07901 USA.
RP Richardson, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA.
EM paul_richardson@dfci.harvard.edu
FU Celgene Corporation
FX The authors gratefully acknowledge the work performed by individual
research teams at all participating study sites; Caitlin Conant and
Nicole Carreau for their administrative support with the paper; and a
special thank you to all of our patients and their families for their
participation.; This study was supported by research funding from
Celgene Corporation. The authors received editorial support in the
preparation of this paper funded by Celgene; the authors were fully
responsible for all content and editorial decisions, and received no
financial support or other form of compensation related to the
development of the paper.
NR 28
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U1 1
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 JUL 23
PY 2009
VL 114
IS 4
BP 772
EP 778
DI 10.1182/blood-2008-12-196238
PG 7
WC Hematology
SC Hematology
GA 474BO
UT WOS:000268257400010
PM 19471019
ER
PT J
AU Wang, QB
Li, W
Zhang, Y
Yuan, X
Xu, KX
Yu, JD
Chen, Z
Beroukhim, R
Wang, HY
Lupien, M
Wu, T
Regan, MM
Meyer, CA
Carroll, JS
Manrai, AK
Janne, OA
Balk, SP
Mehra, R
Han, B
Chinnaiyan, AM
Rubin, MA
True, L
Fiorentino, M
Fiore, C
Loda, M
Kantoff, PW
Liu, XS
Brown, M
AF Wang, Qianben
Li, Wei
Zhang, Yong
Yuan, Xin
Xu, Kexin
Yu, Jindan
Chen, Zhong
Beroukhim, Rameen
Wang, Hongyun
Lupien, Mathieu
Wu, Tao
Regan, Meredith M.
Meyer, Clifford A.
Carroll, Jason S.
Manrai, Arjun Kumar
Janne, Olli A.
Balk, Steven P.
Mehra, Rohit
Han, Bo
Chinnaiyan, Arul M.
Rubin, Mark A.
True, Lawrence
Fiorentino, Michelangelo
Fiore, Christopher
Loda, Massimo
Kantoff, Philip W.
Liu, X. Shirley
Brown, Myles
TI Androgen Receptor Regulates a Distinct Transcription Program in
Androgen-Independent Prostate Cancer
SO CELL
LA English
DT Article
ID KALLIKREIN 2; HUMAN GENOME; HISTONE H3; CHIP-CHIP; CYCLIN-A; COMPLEX;
PROGRESSION; EXPRESSION; SIGNATURES; MODEL
AB The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer cells by generating AR-dependent gene expression profiles and AR cistromes. In contrast to what is found in androgen-dependent cells, AR selectively upregulates M-phase cell-cycle genes in androgen-independent cells, including UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation. Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth.
C1 [Wang, Qianben; Xu, Kexin; Beroukhim, Rameen; Lupien, Mathieu; Fiorentino, Michelangelo; Fiore, Christopher; Loda, Massimo; Kantoff, Philip W.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wu, Tao] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Wang, Qianben; Chen, Zhong] Ohio State Univ, Coll Med, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA.
[Wang, Qianben; Chen, Zhong] Ohio State Univ, Coll Med, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Li, Wei] Baylor Coll Med, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA.
[Li, Wei] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Zhang, Yong; Regan, Meredith M.; Meyer, Clifford A.; Manrai, Arjun Kumar; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Zhang, Yong; Regan, Meredith M.; Meyer, Clifford A.; Manrai, Arjun Kumar; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Yuan, Xin; Wang, Hongyun; Balk, Steven P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA.
[Yu, Jindan; Mehra, Rohit; Han, Bo; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Beroukhim, Rameen] Harvard & MIT, Broad Inst, Cambridge, MA 02139 USA.
[Carroll, Jason S.] Cambridge Res Inst, Canc Res UK, Cambridge CB2 0RE, England.
[Janne, Olli A.] Univ Helsinki, Inst Biomed Physiol, Biomedicum, FI-00014 Helsinki, Finland.
[Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA.
[True, Lawrence] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
RP Wang, QB (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM qianben.wang@osumc.edu; xsliu@jimmy.harvard.edu;
myles_brown@dfci.harvard.edu
RI Li, Wei/A-8544-2009; Zhang, Yong/B-4838-2011; Wang, Qianben/E-4267-2011;
Wu, Tao/C-7533-2013;
OI Zhang, Yong/0000-0001-6316-2734; Brown, Myles/0000-0002-8213-1658;
Rubin, Mark/0000-0002-8321-9950
FU National Institutes of Health [P50 CA090381, K99 CA126160, R01 HG004069,
K99 CA129565]; The Prostate Cancer Foundation; Department of Defense
[W81XWH-07-1-0037, PC080665]
FX This work was supported by grants from National Institutes of Health
(P50 CA090381 to M. B., K99 CA126160 to Q. W., and R01 HG004069 to X. S.
L., and K99 CA129565 to J.Y., The Prostate Cancer Foundation (to M. B),
and Department of Defense (W81XWH-07-1-0037 to X. S. L., and PC080665 to
J.Y.). We thank Drs. Roland Schule for providing KDM1 constructs; and
Michael Rape for UBE2C constructs. We also thank Drs. James DeCaprio,
Gustavo Leone, Tim Huang, Yun Li, and Shengjun Ren for helpful
discussions; and Dr. Chunpeng Zhang and Anna Rorick for technical
assistance.
NR 48
TC 418
Z9 428
U1 4
U2 34
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 23
PY 2009
VL 138
IS 2
BP 245
EP 256
DI 10.1016/j.cell.2009.04.056
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 474IM
UT WOS:000268277000008
PM 19632176
ER
PT J
AU Kalaszczynska, I
Geng, Y
Iino, T
Mizuno, SI
Choi, Y
Kondratiuk, I
Silver, DP
Wolgemuth, DJ
Akashi, K
Sicinski, P
AF Kalaszczynska, Ilona
Geng, Yan
Iino, Tadafumi
Mizuno, Shin-ichi
Choi, Yoon
Kondratiuk, Ilona
Silver, Daniel P.
Wolgemuth, Debra J.
Akashi, Koichi
Sicinski, Piotr
TI Cyclin A Is Redundant in Fibroblasts but Essential in Hematopoietic and
Embryonic Stem Cells
SO CELL
LA English
DT Article
ID DEPENDENT KINASES; C-MYC; EXPRESSION; PROGRESSION; GENE; MICE; MOUSE;
PROLIFERATION; ACCUMULATION; PROGENITOR
AB Cyclins are regulatory subunits of cyclin-dependent kinases. Cyclin A, the first cyclin ever cloned, is thought to be an essential component of the cell-cycle engine. Mammalian cells encode two A-type cyclins, testis-specific cyclin A1 and ubiquitously expressed cyclin A2. Here, we tested the requirement for cyclin A function using conditional knockout mice lacking both A-type cyclins. We found that acute ablation of cyclin A in fibroblasts did not affect cell proliferation, but led to prolonged expression of another cyclin, cyclin E, across the cell cycle. However, combined ablation of all A- and E-type cyclins extinguished cell division. In contrast, cyclin A function was essential for cell-cycle progression of hematopoietic and embryonic stem cells. Expression of cyclin A is particularly high in these compartments, which might render stem cells dependent on cyclin A, whereas in fibroblasts cyclins A and E play redundant roles in cell proliferation.
C1 [Kalaszczynska, Ilona; Geng, Yan; Choi, Yoon; Kondratiuk, Ilona; Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Iino, Tadafumi; Mizuno, Shin-ichi; Akashi, Koichi] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Silver, Daniel P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kalaszczynska, Ilona; Geng, Yan; Iino, Tadafumi; Mizuno, Shin-ichi; Choi, Yoon; Kondratiuk, Ilona; Akashi, Koichi; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Silver, Daniel P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Wolgemuth, Debra J.] Columbia Univ, Ctr Med, Dept Genet & Dev, New York, NY 10032 USA.
[Wolgemuth, Debra J.] Columbia Univ, Ctr Med, Dept Obstet & Gynecol, New York, NY 10032 USA.
RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM peter_sicinski@dfci.harvard.edu
OI Kalaszczynska, Ilona/0000-0001-6698-1372
FU National Institutes of Health [R01CA132740, R01CA108950, R01 HD34915]
FX We thank members of the Sicinski lab, R. Bronson, E. Sicinska, M. A.
Ciemerych-Litwinienko, A. Minamishima, S. Kobayashi, and B. Will for
help and advice, B. Clurman for anti-cyclin E1 antibody, and F. Liu for
anti-phospho Smad3 antibodies. This work was supported by R01CA132740
and R01CA108950 grants from the National Institutes of Health (to P. S.)
and R01 HD34915 (to D. J. W.). P. S. is a Scholar of The Leukemia and
Lymphoma Society.
NR 48
TC 101
Z9 104
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 23
PY 2009
VL 138
IS 2
BP 352
EP 365
DI 10.1016/j.cell.2009.04.062
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 474IM
UT WOS:000268277000016
PM 19592082
ER
PT J
AU Vlopp, KG
Das, A
AF Vlopp, Kevin G.
Das, Anup
TI Comparative Effectiveness - Thinking beyond Medication A versus
Medication B
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID SMOKING-CESSATION
C1 [Vlopp, Kevin G.; Das, Anup] Univ Penn, Philadelphia, PA 19104 USA.
[Vlopp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Vlopp, KG (reprint author), Univ Penn, Philadelphia, PA 19104 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 23
PY 2009
VL 361
IS 4
BP 331
EP 333
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 473DC
UT WOS:000268184500003
ER
PT J
AU Plotkin, SR
Stemmer-Rachamimov, AO
Barker, FG
Halpin, C
Padera, TP
Tyrrell, A
Sorensen, AG
Jain, RK
di Tomaso, E
AF Plotkin, Scott R.
Stemmer-Rachamimov, Anat O.
Barker, Fred G., II
Halpin, Chris
Padera, Timothy P.
Tyrrell, Alex
Sorensen, A. Gregory
Jain, Rakesh K.
di Tomaso, Emmanuelle
TI Hearing Improvement after Bevacizumab in Patients with Neurofibromatosis
Type 2
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; FACIAL-NERVE FUNCTION; PHASE-II TRIAL;
VESTIBULAR-SCHWANNOMA; TUMOR VASCULATURE; ACOUSTIC NEUROMAS; KINASE
INHIBITOR; ANGIOGENESIS; EXPRESSION; MANAGEMENT
AB Background
Profound hearing loss is a serious complication of neurofibromatosis type 2, a genetic condition associated with bilateral vestibular schwannomas, benign tumors that arise from the eighth cranial nerve. There is no medical treatment for such tumors.
Methods
We determined the expression pattern of vascular endothelial growth factor (VEGF) and three of its receptors, VEGFR-2, neuropilin-1, and neuropilin-2, in paraffin-embedded samples from 21 vestibular schwannomas associated with neurofibromatosis type 2 and from 22 sporadic schwannomas. Ten consecutive patients with neurofibromatosis type 2 and progressive vestibular schwannomas who were not candidates for standard treatment were treated with bevacizumab, an anti-VEGF monoclonal antibody. An imaging response was defined as a decrease of at least 20% in tumor volume, as compared with baseline. A hearing response was defined as a significant increase in the word-recognition score, as compared with baseline.
Results
VEGF was expressed in 100% of vestibular schwannomas and VEGFR-2 in 32% of tumor vessels on immunohistochemical analysis. Before treatment, the median annual volumetric growth rate for 10 index tumors was 62%. After bevacizumab treatment in the 10 patients, tumors shrank in 9 patients, and 6 patients had an imaging response, which was maintained in 4 patients during 11 to 16 months of follow-up. The median best response to treatment was a volumetric reduction of 26%. Three patients were not eligible for a hearing response; of the remaining seven patients, four had a hearing response, two had stable hearing, and one had progressive hearing loss. There were 21 adverse events of grade 1 or 2.
Conclusions
VEGF blockade with bevacizumab improved hearing in some, but not all, patients with neurofibromatosis type 2 and was associated with a reduction in the volume of most growing vestibular schwannomas.
C1 [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Padera, Timothy P.; Tyrrell, Alex; Jain, Rakesh K.; di Tomaso, Emmanuelle] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
[Sorensen, A. Gregory] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Halpin, Chris] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA.
RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA.
EM splotkin@partners.org
RI Tyrrell, James/A-6359-2010;
OI Padera, Timothy/0000-0002-3453-9384
FU Harvard Medical School Center for Neurofibromatosis and Allied
Disorders; Neurofibromatosis, Inc., New England; Children's Tumor
Foundation [NF050202]; Neurofibromatosis Research Program of the
Department of Defense [P01NS024279, P01CA80124]; National Institutes of
Health; Federal Share/National Cancer Institute Proton Beam Program
FX Supported by the Harvard Medical School Center for Neurofibromatosis and
Allied Disorders; Neurofibromatosis, Inc., New England; the Children's
Tumor Foundation; a grant (NF050202, to Dr. Plotkin) from the
Neurofibromatosis Research Program of the Department of Defense; a
Claflin Award (to Dr. di Tomaso); grants (P01NS024279, to Dr. Stemmer-
Rachamimov; and P01CA80124, to Dr. Jain) from the National Institutes of
Health; and grants from the Federal Share/National Cancer Institute
Proton Beam Program (to Drs. di Tomaso and Jain).
NR 30
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Z9 168
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 JUL 23
PY 2009
VL 361
IS 4
BP 358
EP 367
DI 10.1056/NEJMoa0902579
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 473DC
UT WOS:000268184500006
PM 19587327
ER
PT J
AU Somers, MJG
Sharma, A
Grant, PE
Guimaraes, AR
Schneeberger, EE
AF Somers, Michael J. G.
Sharma, Amita
Grant, P. Ellen
Guimaraes, Alexander R.
Schneeberger, Eveline E.
TI A Boy with Headache, Nausea, Seizures, and Hypertension Atypical
hemolytic-uremic syndrome with complement factor H mutation
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CRESCENTIC GLOMERULONEPHRITIS; THROMBOTIC MICROANGIOPATHY;
THROMBOCYTOPENIC PURPURA; MALIGNANT HYPERTENSION; CHILDREN; SURFACE
C1 [Somers, Michael J. G.] Childrens Hosp, Div Nephrol, Boston, MA 02115 USA.
[Sharma, Amita] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Grant, P. Ellen; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Schneeberger, Eveline E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Somers, Michael J. G.; Sharma, Amita] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Grant, P. Ellen; Guimaraes, Alexander R.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Schneeberger, Eveline E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Somers, MJG (reprint author), Childrens Hosp, Div Nephrol, Boston, MA 02115 USA.
FU AstraZeneca
FX Dr. Guimaraes reports receiving grant support from AstraZeneca. No other
potential conflict of interest relevant to this article was reported.
NR 25
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 23
PY 2009
VL 361
IS 4
BP 389
EP 400
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 473DC
UT WOS:000268184500011
PM 19625720
ER
PT J
AU Budin, I
Bruckner, RJ
Szostak, JW
AF Budin, Itay
Bruckner, Raphael J.
Szostak, Jack W.
TI Formation of Protocell-like Vesicles in a Thermal Diffusion Column
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID TEMPERATURE; SEPARATION
C1 [Budin, Itay; Bruckner, Raphael J.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Budin, Itay; Bruckner, Raphael J.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA.
[Budin, Itay] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Bruckner, Raphael J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU Harvard Origins Initiative [EXB02-0031-0018]
FX R.J.B. was supported by a fellowship from the Harvard Origins
Initiative. This work was supported in part by Grant EXB02-0031-0018
from the NASA Exobiology Program. J.W.S. is an Investigator of the
Howard Hughes Medical Institute. The authors thank Dr. H. Stone, Dr. J.
Higgins, and S. Tobe for helpful discussions and Dr. A. Ricardo, M.
Elenko. T. Zhu. and Q. Dufton for comments on the manuscript.
NR 13
TC 54
Z9 56
U1 5
U2 38
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 JUL 22
PY 2009
VL 131
IS 28
BP 9628
EP 9629
DI 10.1021/ja9029818
PG 2
WC Chemistry, Multidisciplinary
SC Chemistry
GA 475XG
UT WOS:000268399800014
PM 19601679
ER
PT J
AU Volberding, P
AF Volberding, Paul
TI Cohorts, Trials, and Evidence: Expanding Our Confidence in Guidelines
for Antiretroviral Resistance Testing
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID HIV-INFECTED PATIENTS; SOCIETY-USA PANEL; 2008 RECOMMENDATIONS;
DRUG-RESISTANCE; THERAPY
C1 [Volberding, Paul] Univ Calif San Francisco, San Francisco, CA 94121 USA.
[Volberding, Paul] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Volberding, P (reprint author), Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA.
EM paul.volberding@med.va.gov
NR 13
TC 1
Z9 1
U1 0
U2 1
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 21
PY 2009
VL 151
IS 2
BP 135
EP 136
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 478RH
UT WOS:000268605300008
PM 19620166
ER
PT J
AU Schlueter, PJ
Peterson, RT
AF Schlueter, Peter J.
Peterson, Randall T.
TI Systematizing Serendipity for Cardiovascular Drug Discovery
SO CIRCULATION
LA English
DT Article
ID ZINC-FINGER NUCLEASES; EMBRYONIC STEM-CELLS; SMALL MOLECULES;
GENE-EXPRESSION; IN-VIVO; CAENORHABDITIS-ELEGANS; TRANSGENIC ZEBRAFISH;
CHEMICAL GENETICS; SIGNALING PATHWAY; CONNECTIVITY MAP
C1 [Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
Broad Inst, Cambridge, MA USA.
RP Peterson, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA.
EM peterson@cvrc.mgh.harvard.edu
FU NHLBI NIH HHS [T32 HL007208-32, R01 HL079267, T32 HL07208, R01
HL079267-03, T32 HL007208]
NR 82
TC 6
Z9 6
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 21
PY 2009
VL 120
IS 3
BP 255
EP 263
DI 10.1161/CIRCULATIONAHA.108.824177
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 472EA
UT WOS:000268110900011
PM 19620524
ER
PT J
AU Pagani, FD
Miller, LW
Russell, SD
Aaronson, KD
John, R
Boyle, AJ
Conte, JV
Bogaev, RC
MacGillivray, TE
Naka, Y
Mancini, D
Massey, HT
Chen, L
Klodell, CT
Aranda, JM
Moazami, N
Ewald, GA
Farrar, DJ
Frazier, OH
AF Pagani, Francis D.
Miller, Leslie W.
Russell, Stuart D.
Aaronson, Keith D.
John, Ranjit
Boyle, Andrew J.
Conte, John V.
Bogaev, Roberta C.
MacGillivray, Thomas E.
Naka, Yoshifumi
Mancini, Donna
Massey, H. Todd
Chen, Leway
Klodell, Charles T.
Aranda, Juan M.
Moazami, Nader
Ewald, Gregory A.
Farrar, David J.
Frazier, O. Howard
CA HeartMate II Investigators
TI Extended Mechanical Circulatory Support With a Continuous-Flow Rotary
Left Ventricular Assist Device
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE heart failure; left ventricular assist device; heart transplantation
ID AWAITING HEART-TRANSPLANTATION; DESTINATION THERAPY; CLINICAL-TRIAL;
BLOOD-PUMPS; SYSTEM; BRIDGE; RELIABILITY; CANDIDATES
AB Objectives
This study sought to evaluate the use of a continuous-flow rotary left ventricular assist device (LVAD) as a bridge to heart transplantation.
Background
LVAD therapy is an established treatment modality for patients with advanced heart failure. Pulsatile LVADs have limitations in design precluding their use for extended support. Continuous-flow rotary LVADs represent an innovative design with potential for small size and greater reliability by simplification of the pumping mechanism.
Methods
In a prospective, multicenter study, 281 patients urgently listed (United Network of Organ Sharing status 1A or 1B) for heart transplantation underwent implantation of a continuous-flow LVAD. Survival and transplantation rates were assessed at 18 months. Patients were assessed for adverse events throughout the study and for quality of life, functional status, and organ function for 6 months.
Results
Of 281 patients, 222 (79%) underwent transplantation, LVAD removal for cardiac recovery, or had ongoing LVAD support at 18-month follow-up. Actuarial survival on support was 72% (95% confidence interval: 65% to 79%) at 18 months. At 6 months, there were significant improvements in functional status and 6-min walk test (from 0% to 83% of patients in New York Heart Association functional class I or II and from 13% to 89% of patients completing a 6-min walk test) and in quality of life (mean values improved 41% with Minnesota Living With Heart Failure and 75% with Kansas City Cardiomyopathy questionnaires). Major adverse events included bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in 4 patients.
Conclusions
A continuous-flow LVAD provides effective hemodynamic support for at least 18 months in patients awaiting transplantation, with improved functional status and quality of life. (Thoratec HeartMate II Left Ventricular Assist System [LVAS] for Bridge to Cardiac Transplantation; NCT00121472) (J Am Coll Cardiol 2009; 54: 312-21) (C) 2009 by the American College of Cardiology Foundation
C1 [Pagani, Francis D.; Aaronson, Keith D.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Miller, Leslie W.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Russell, Stuart D.; Conte, John V.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[John, Ranjit; Boyle, Andrew J.] Univ Minnesota, Minneapolis, MN USA.
[Bogaev, Roberta C.; Frazier, O. Howard] Texas Heart Inst, Houston, TX 77025 USA.
[MacGillivray, Thomas E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Naka, Yoshifumi; Mancini, Donna] Columbia Univ, New York, NY USA.
[Massey, H. Todd; Chen, Leway] Univ Rochester, Rochester, NY USA.
[Klodell, Charles T.; Aranda, Juan M.] Univ Florida, Gainesville, FL USA.
[Moazami, Nader; Ewald, Gregory A.] Barnes Jewish Hosp, St Louis, MO 63110 USA.
[Farrar, David J.] Thoratec Corp, Pleasanton, CA USA.
RP Pagani, FD (reprint author), Univ Michigan Hlth Syst, Sect Cardiac Surg, Ctr Cardiovasc, Room 5161,1500 E Med Ctr Dr,SPC 5864, Ann Arbor, MI 48109 USA.
EM fpagani@umich.edu
NR 24
TC 452
Z9 457
U1 2
U2 18
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 JUL 21
PY 2009
VL 54
IS 4
BP 312
EP 321
DI 10.1016/j.jacc.2009.03.055
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 471AW
UT WOS:000268025200004
PM 19608028
ER
PT J
AU Barnes, DE
Covinsky, KE
Whitmer, RA
Kuller, LH
Lopez, OL
Yaffe, K
AF Barnes, D. E.
Covinsky, K. E.
Whitmer, R. A.
Kuller, L. H.
Lopez, O. L.
Yaffe, K.
TI Predicting risk of dementia in older adults The late-life dementia risk
index
SO NEUROLOGY
LA English
DT Article
ID CARDIOVASCULAR HEALTH COGNITION; INCIDENT ALZHEIMER-DISEASE; PROGNOSTIC
INDEX; BREAST-CANCER; PREVALENCE; VALIDATION; MORTALITY; PEOPLE; SCORE
AB Objective: To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years.
Methods: Subjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients.
Results: Subjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), >= 1 apolipoprotein E epsilon 4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores.
Conclusions: The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals. Neurology (R) 2009; 73: 173-179
C1 [Barnes, D. E.; Yaffe, K.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Covinsky, K. E.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA.
[Yaffe, K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Yaffe, K.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA.
San Francisco VA Med Ctr, San Francisco, CA USA.
[Barnes, D. E.; Covinsky, K. E.; Whitmer, R. A.; Yaffe, K.] Kaiser Div Res, Oakland, CA USA.
[Kuller, L. H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Lopez, O. L.] Univ Pittsburgh, Dept Neurol & Psychiat, Pittsburgh, PA 15260 USA.
RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,151R, San Francisco, CA 94121 USA.
EM Deborah.Barnes@ucsf.edu
FU National Heart, Lung, and Blood Institute [N01-HC85079, N01-HC-85086,
N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295]; National Institute on Aging [AG15928]; National Institute
of Neurological Disorders and Stroke; NIH [K01 AG024069]; NIH/NCRR [UL1
RR024131]
FX The research reported in this article was supported by contracts
N01-HC85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103,
N01-HC-55222, N01-HC-75150, N01-HC-45133, grant U01 HL080295 from the
National Heart, Lung, and Blood Institute, and grant AG15928 from the
National Institute on Aging 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. Dr. Barnes is funded through a K01
Career Development Award (K01 AG024069) from the NIH. This project also
was supported by NIH/NCRR UCSF-CTSI grant UL1 RR024131. The
Biostatistics, Research Design, Ethics and Data Management program of
UCSF's Clinical and Translational Sciences Institute (NIH/NCRR UCSF-CTSI
grant UL1 RR024131) provided preliminary data analyses and statistical
advice.
NR 35
TC 86
Z9 88
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL 21
PY 2009
VL 73
IS 3
BP 173
EP 179
DI 10.1212/WNL.0b013e3181a81636
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 472QO
UT WOS:000268147100004
PM 19439724
ER
PT J
AU Paganetti, H
AF Paganetti, Harald
TI Dose to water versus dose to medium in proton beam therapy
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID MONTE-CARLO SIMULATIONS; STOPPING POWERS; CT NUMBERS;
NUCLEAR-INTERACTIONS; HOUNSFIELD UNITS; CROSS-SECTIONS; DISTRIBUTIONS;
DOSIMETRY; ENERGY; VERIFICATION
AB Dose in radiation therapy is traditionally reported as the water-equivalent dose, or dose to water. Monte Carlo dose calculations report dose to medium and thus a methodology is needed to convert dose to medium into dose to water (or vice versa) for comparison of Monte Carlo results with results from planning systems. This paper describes the development of a formalism to convert dose to medium into dose to water for proton fields when simulating the dose with Monte Carlo techniques. The conversion is based on relative stopping power but also considers energy transferred via nuclear interactions. The influence of different interaction mechanisms of proton beams (electromagnetic versus nuclear) is demonstrated. Further, an approximate method for converting doses retroactively is presented. Based on the outlined formalism, five proton therapy patients with a total of 33 fields were analyzed. Dose distributions, dose volume histograms and absolute doses to assess the clinical significance of differences between dose to medium and dose to water are presented. We found that the difference between the two dose reporting definitions can be up to 10% for high CT numbers if analyzing the mean dose to the target. The difference is clinically insignificant for soft tissues. For the structures analyzed, the mean dose to water could be converted to dose to medium by applying a correction factor increasing linearly with increasing average CT number in the volume. We determined that an approximate conversion method, done retroactively with an energy-independent stopping power ratio and without considering nuclear interaction events separately (as compared to on-the-fly conversion during simulation), is sufficiently accurate to compute mean doses. It is insufficient, however, when analyzing the beam range. For proton beams stopping in bony anatomy, the predicted beam range can differ by 2-3 mm when comparing dose to tissue and dose to water.
C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM hpaganetti@partners.org
FU [NIH/NCI6-PO1 CA 21239]
FX This work was supported by NIH/NCI6-PO1 CA 21239 ('Proton Therapy
Research').
NR 32
TC 42
Z9 43
U1 0
U2 10
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 JUL 21
PY 2009
VL 54
IS 14
BP 4399
EP 4421
DI 10.1088/0031-9155/54/14/004
PG 23
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 467VB
UT WOS:000267770100004
PM 19550004
ER
PT J
AU Seco, J
Robertson, D
Trofimov, A
Paganetti, H
AF Seco, Joao
Robertson, Daniel
Trofimov, Alexei
Paganetti, Harald
TI Breathing interplay effects during proton beam scanning: simulation and
statistical analysis
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID ORGAN MOTION; IMRT TREATMENTS; RADIOTHERAPY; LUNG
AB Treatment delivery with active beam scanning in proton radiation therapy introduces the problem of interplay effects when pencil beam motion occurs on a similar time scale as intra-fractional tumor motion. In situations where fractionation may not provide enough repetition to blur the effects of interplay, repeated delivery or 'repainting' of each field several times within a fraction has been suggested. The purpose of this work was to investigate the effectiveness of different repainting strategies in proton beam scanning. To assess the dosimetric impact of interplay effects, we performed a series of simulations considering the following parameters: tumor motion amplitude, breathing period, asymmetry in the motion trajectory for the target and time required to change the beam energy for the delivery system. Several repainting strategies were compared in terms of potential vulnerability to a dose delivery error. Breathing motion perpendicular to the beam direction (representing superior-inferior type tumor motion in patients) was considered and modeled as an asymmetric sine function with a peak-to-peak amplitude of between 10 and 30 mm. The results show that motion effects cause a narrowing of the high-dose profile and widening of the penumbra. The 90% isodose area was reduced significantly when considering a large motion amplitude of 3 cm. The broadening of the penumbra appears to depend only on the amplitude of tumor motion (assuming harmonic motion). The delivered dose exhibits a shift of 10-15% of the tumor amplitude (or 1-5 mm) in the caudal direction due to breathing asymmetry observed for both sin(4)(x) and sin(6)(x) motion. Of the five repainting techniques studied, so-called 'breath sampling' turned out to be most effective in reducing dose errors with a minimal increase in treatment time. In this method, each energy level is repainted at several evenly spaced times within one breathing period. To keep dose delivery errors below 5% while minimizing treatment time, it is recommended that breath sampling repainting be employed using 5-10 paintings per field for an assumed tumor volume of 8.5 x 8.5 x 10 cm(3).For smaller tumor volumes more repaintings will be required, while for larger volumes five repaintings should be sufficient to achieve the required dose accuracy.
C1 [Seco, Joao; Robertson, Daniel; Trofimov, Alexei; Paganetti, Harald] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA.
[Seco, Joao; Robertson, Daniel; Trofimov, Alexei; Paganetti, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Robertson, Daniel] Brigham Young Univ, Dept Phys & Astron, Provo, UT 84602 USA.
RP Seco, J (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA.
RI Seco, Joao/J-4451-2012
FU NIH [P01 CA021239- 29A1]; American Association of Physicists in Medicine
(AAPM)
FX This work was sponsored by NIH grant P01 CA021239- 29A1. One of the
authors (DR) was supported by the Summer Undergraduate Fellowship
Program of the American Association of Physicists in Medicine (AAPM).
NR 14
TC 54
Z9 56
U1 0
U2 10
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 JUL 21
PY 2009
VL 54
IS 14
BP N283
EP N294
DI 10.1088/0031-9155/54/14/N01
PG 12
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 467VB
UT WOS:000267770100016
PM 19550002
ER
PT J
AU Britschgi, M
Olin, CE
Johns, HT
Takeda-Uchimura, Y
LeMieux, MC
Rufibach, K
Rajadas, J
Zhang, H
Tomooka, B
Robinson, WH
Clark, CM
Fagan, AM
Galasko, DR
Holtzman, DM
Jutel, M
Kaye, JA
Lemere, CA
Leszek, J
Li, G
Peskind, ER
Quinn, JF
Yesavage, JA
Ghiso, JA
Wyss-Coray, T
AF Britschgi, M.
Olin, C. E.
Johns, H. T.
Takeda-Uchimura, Y.
LeMieux, M. C.
Rufibach, K.
Rajadas, J.
Zhang, H.
Tomooka, B.
Robinson, W. H.
Clark, C. M.
Fagan, A. M.
Galasko, D. R.
Holtzman, D. M.
Jutel, M.
Kaye, J. A.
Lemere, C. A.
Leszek, J.
Li, G.
Peskind, E. R.
Quinn, J. F.
Yesavage, J. A.
Ghiso, J. A.
Wyss-Coray, T.
TI Neuroprotective natural antibodies to assemblies of amyloidogenic
peptides decrease with normal aging and advancing Alzheimer's disease
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID A-BETA ANTIBODIES; MOUSE MODEL; IN-VITRO; PROTEIN; AUTOANTIBODIES;
OLIGOMERS; PLAQUES; IMMUNOTHERAPY; MICROARRAYS; DEPOSITION
AB A number of distinct beta-amyloid (A beta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural A beta-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic A beta and amyloidogenic non-A beta species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of A beta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of A beta 1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant A beta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from A beta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with A beta the monkeys developed high titers not only against A beta peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of A beta antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.
C1 [Britschgi, M.; Olin, C. E.; Johns, H. T.; Takeda-Uchimura, Y.; Rajadas, J.; Zhang, H.; Yesavage, J. A.; Wyss-Coray, T.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
[LeMieux, M. C.] Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA.
[Rufibach, K.] Univ Zurich, Biostat Unit, Inst Social & Prevent Med, CH-8001 Zurich, Switzerland.
[Robinson, W. H.; Yesavage, J. A.; Wyss-Coray, T.] Vet Affairs Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA 94304 USA.
[Clark, C. M.] Univ Penn, Alzheimers Dis Ctr, Dept Neurol, Philadelphia, PA 19104 USA.
[Clark, C. M.] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA.
[Fagan, A. M.; Holtzman, D. M.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
[Galasko, D. R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Jutel, M.] Wroclaw Med Univ, Dept Internal Med & Allergol, PL-50417 Wroclaw, Poland.
[Kaye, J. A.; Quinn, J. F.] Oregon Hlth & Sci Univ, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA.
[Lemere, C. A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lemere, C. A.] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
[Leszek, J.] Wroclaw Med Univ, Dept Psychiat, PL-51622 Wroclaw, Poland.
[Li, G.; Peskind, E. R.] Univ Washington, Alzheimers Dis Res Ctr, Seattle, WA 98108 USA.
[Li, G.; Peskind, E. R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Ghiso, J. A.] NYU, Langone Med Ctr, Dept Pathol, New York, NY 10016 USA.
[Ghiso, J. A.] NYU, Langone Med Ctr, Dept Psychiat, New York, NY 10016 USA.
RP Wyss-Coray, T (reprint author), Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
EM twc@stanford.edu
RI Rufibach, Kaspar/F-1163-2010
OI Kaye, Jeffrey/0000-0002-9971-3478;
FU John Douglas French Alzheimer's Foundation; Department of Veterans
Affairs; National Institute on Aging [AG20603, AG10491, AG030539, P50
AG005136, AG08017]
FX We thank the patients who participated in this study; M. BenBarak and P.
Chandra for assistance with the peptide array; J. Frost for technical
assistance with the vervet samples; R. Palmour and F. Ervin for housing
the vervets at the Behavioral Science Foundation, St. Kitts, Eastern
Caribbean, and numerous unnamed staff at our institutions for their
effort in patient recruitment, clinical assessment, and sample
preparation. This work was supported by the John Douglas French
Alzheimer's Foundation (T. W.-C.), the Department of Veterans Affairs
(T. W.-C., E. R. P., G. L., and J. A. Y.), and National Institute on
Aging Grants AG20603 (to T. W.-C.), AG10491, AG030539 (to J. A. G.), P50
AG005136 (to E. R. P.), and AG08017 (to J. F. Q. and J. A. K.).
NR 62
TC 88
Z9 89
U1 2
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 21
PY 2009
VL 106
IS 29
BP 12145
EP 12150
DI 10.1073/pnas.0904866106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 473BI
UT WOS:000268178400059
PM 19581601
ER
PT J
AU Cheng, HL
Liu, PX
Wang, ZGC
Zou, LH
Santiago, S
Garbitt, V
Gjoerup, OV
Iglehart, JD
Miron, A
Richardson, AL
Hahn, WC
Zhao, JJ
AF Cheng, Hailing
Liu, Pixu
Wang, Zhigang C.
Zou, Lihua
Santiago, Stephanie
Garbitt, Victoria
Gjoerup, Ole V.
Iglehart, J. Dirk
Miron, Alexander
Richardson, Andrea L.
Hahn, William C.
Zhao, Jean J.
TI SIK1 Couples LKB1 to p53-Dependent Anoikis and Suppresses Metastasis
SO SCIENCE SIGNALING
LA English
DT Article
ID FOCAL ADHESION KINASE; MAMMARY EPITHELIAL-CELLS; HUMAN BREAST-CANCER;
PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; HEPATOCELLULAR-CARCINOMA;
SURVIVAL SIGNALS; P53; APOPTOSIS; TUMOR
AB Resistance to anoikis, the subtype of apoptosis triggered by lack of adhesion, contributes to malignant transformation and the development of metastasis. Although several lines of evidence suggest that p53 plays a critical role in anoikis, the pathway(s) that connect cell detachment to p53 remain undefined. Here, through the use of a kinome-wide loss-of-function screen, we identify the serine-threonine kinase SIK1 (salt-inducible kinase 1) as a regulator of p53-dependent anoikis. Inactivation of SIK1 compromised p53 function in anoikis and allowed cells to grow in an anchorage-independent manner. In vivo, SIK1 loss facilitated metastatic spread and survival of disseminated cells as micrometastases in lungs. The presence of functional SIK1 was required for the activity of the kinase LKB1 in promoting p53-dependent anoikis and suppressing anchorage-independent growth, Matrigel invasion, and metastatic potential. In human cancers, decreased expression of the gene encoding SIK1 closely correlated with development of distal metastases in breast cancers from three independent cohorts. Together, these findings indicate that SIK1 links LKB1 to p53-dependent anoikis and suppresses metastasis.
C1 [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Cheng, Hailing; Liu, Pixu; Wang, Zhigang C.; Zou, Lihua; Santiago, Stephanie; Garbitt, Victoria; Iglehart, J. Dirk; Miron, Alexander; Richardson, Andrea L.; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Cheng, Hailing; Liu, Pixu; Santiago, Stephanie; Garbitt, Victoria; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Wang, Zhigang C.; Zou, Lihua; Iglehart, J. Dirk; Miron, Alexander; Richardson, Andrea L.; Zhao, Jean J.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Gjoerup, Ole V.] Univ Pittsburgh, Inst Canc, Mol Virol Program, Pittsburgh, PA 15213 USA.
[Hahn, William C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Hahn, William C.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
[Hahn, William C.] MIT, Cambridge, MA 02142 USA.
RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM william_hahn@dfci.harvard.edu; jean_zhao@dfci.harvard.edu
FU NCI NIH HHS [R01 CA134502, BC051565, P50 CA089393, P50 CA089393-09, R01
CA134502-02]; PHS HHS [W81XWH-07-1-0408]
NR 71
TC 59
Z9 62
U1 2
U2 11
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD JUL 21
PY 2009
VL 2
IS 80
AR ra35
DI 10.1126/scisignal.2000369
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 569MK
UT WOS:000275601000004
PM 19622832
ER
PT J
AU Zhang, P
Cantiello, HF
AF Zhang, Peng
Cantiello, Horacio F.
TI Measurement of charge distribution in actin bundles by surface potential
microscopy
SO APPLIED PHYSICS LETTERS
LA English
DT Article
DE atomic force microscopy; bioelectric potentials; biological techniques;
feature extraction; gold; image segmentation; molecular biophysics;
proteins; surface potential
ID ELECTROSTATIC FORCE MICROSCOPY; F-ACTIN; FILAMENTS
AB Bundles of filamentous actin (F-actin) deposited on a gold-plated surface were concurrently imaged using atomic force microscopy (AFM) and surface potential microscopy (SPM). The surface potential was mapped as a function of tip distance to surface using a constant bias potential. There was an uneven spatial distribution of charges detected by SPM, consistent with the segmented topological features shown by AFM of the actin bundles. SPM analysis showed localized changes in surface potential between the axial and transversal sections of the bundles, which are consistent with nonuniform charge distributions of adsorbed salt ions on F-actin.
C1 [Zhang, Peng] Massachusetts Gen Hosp, Nephrol Div & Electrophysiol Core, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Zhang, P (reprint author), Massachusetts Gen Hosp, Nephrol Div & Electrophysiol Core, 149 13th St, Charlestown, MA 02129 USA.
EM cantiello@helix.mgh.harvard.edu
NR 21
TC 6
Z9 6
U1 0
U2 6
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0003-6951
J9 APPL PHYS LETT
JI Appl. Phys. Lett.
PD JUL 20
PY 2009
VL 95
IS 3
AR 033701
DI 10.1063/1.3167281
PG 3
WC Physics, Applied
SC Physics
GA 475ZA
UT WOS:000268405300089
ER
PT J
AU Lang, JE
Magbanua, MJM
Scott, JH
Makrigiorgos, GM
Wang, G
Federman, S
Esserman, LJ
Park, JW
Haqq, CM
AF Lang, Julie E.
Magbanua, Mark Jesus M.
Scott, Janet H.
Makrigiorgos, G. Mike
Wang, Gang
Federman, Scot
Esserman, Laura J.
Park, John W.
Haqq, Christopher M.
TI A comparison of RNA amplification techniques at sub-nanogram input
concentration
SO BMC GENOMICS
LA English
DT Article
ID GENE-EXPRESSION PROFILES; BREAST-CANCER; LINEAR AMPLIFICATION; NANOGRAM
AMOUNTS; MESSENGER-RNA; MICROARRAY EXPERIMENTS; CDNA MICROARRAYS;
PATTERNS; BIOPSIES; SAMPLES
AB Background: Gene expression profiling of small numbers of cells requires high-fidelity amplification of sub-nanogram amounts of RNA. Several methods for RNA amplification are available; however, there has been little consideration of the accuracy of these methods when working with very low-input quantities of RNA as is often required with rare clinical samples. Starting with 250 picograms-3.3 nanograms of total RNA, we compared two linear amplification methods 1) modified T7 and 2) Arcturus RiboAmp HS and a logarithmic amplification, 3) Balanced PCR. Microarray data from each amplification method were validated against quantitative real-time PCR (QPCR) for 37 genes.
Results: For high intensity spots, mean Pearson correlations were quite acceptable for both total RNA and low-input quantities amplified with each of the 3 methods. Microarray filtering and data processing has an important effect on the correlation coefficient results generated by each method. Arrays derived from total RNA had higher Pearson's correlations than did arrays derived from amplified RNA when considering the entire unprocessed dataset, however, when considering a gene set of high signal intensity, the amplified arrays had superior correlation coefficients than did the total RNA arrays.
Conclusion: Gene expression arrays can be obtained with sub-nanogram input of total RNA. High intensity spots showed better correlation on array-array analysis than did unfiltered data, however, QPCR validated the accuracy of gene expression array profiling from low-input quantities of RNA with all 3 amplification techniques. RNA amplification and expression analysis at the sub-nanogram input level is both feasible and accurate if data processing is used to focus attention to high intensity genes for microarrays or if QPCR is used as a gold standard for validation.
C1 [Lang, Julie E.; Esserman, Laura J.] Univ Calif San Francisco, Dept Surg, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
[Magbanua, Mark Jesus M.; Scott, Janet H.; Federman, Scot; Park, John W.; Haqq, Christopher M.] Univ Calif San Francisco, Dept Med Oncol, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
[Haqq, Christopher M.] Univ Calif San Francisco, Dept Urol, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
[Makrigiorgos, G. Mike; Wang, Gang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lang, Julie E.] Univ Arizona, Arizona Canc Ctr, Dept Surg, Tucson, AZ 85724 USA.
RP Lang, JE (reprint author), Univ Calif San Francisco, Dept Surg, Ctr Comprehens Canc, 1500 Divisadero St, San Francisco, CA 94143 USA.
EM jlang@azcc.arizona.edu; mmmagbanua@cc.ucsf.edu; jscott@cc.ucsf.edu;
mmakrigiorgos@lroc.harvard.edu; gwang@lroc.harvard.edu;
sfederman@cc.ucsf.edu; laura.esserman@ucsfmedctr.org; jpark@cc.ucsf.edu;
chaqq@cougarbiotechnology.com
FU National Cancer Institute [P50 CA89520, R01 CA101042-01]; NCI; UC
Discovery [S97-49, 99-10055]; DOD [BC020504]
FX Research was supported by National Cancer Institute Grants P50 CA89520,
R01 CA101042-01 and NCI Interdisciplinary Research Teams for Molecular
Target Assessment (U54 CA90788); UC Discovery (S97-49, 99-10055); and a
gift from Bank of the West. G. M. M was supported by DOD grant BC020504.
We wish to thank Dr. Joe De Risi (UCSF) for providing protocols and
training to our group. We acknowledge Daniel B. Khodabakhsh and Julia
Crothers (UCSF) for their contributions. We wish to thank Pamela Derrish
(UCSF) for her editorial assistance. Many thanks to Dr. George Watts
(University of Arizona Genomics Core) for advice in preparation of this
manuscript.
NR 35
TC 14
Z9 15
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 20
PY 2009
VL 10
AR 326
DI 10.1186/1471-2164-10-326
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 490NN
UT WOS:000269507800001
PM 19619282
ER
PT J
AU Harris, LN
Broadwater, G
Abu-Khalaf, M
Cowan, D
Thor, AD
Budman, D
Cirrincione, CT
Berry, DA
Winer, EP
Hudis, CA
Hayes, DF
Friedman, P
Ellis, M
Dressler, L
AF Harris, Lyndsay N.
Broadwater, Gloria
Abu-Khalaf, Maysa
Cowan, David
Thor, Ann D.
Budman, Daniel
Cirrincione, Constance T.
Berry, Donald A.
Winer, Eric P.
Hudis, Clifford A.
Hayes, Daniel F.
Friedman, Paula
Ellis, Matthew
Dressler, Lynn
TI Topoisomerase II alpha Amplification Does Not Predict Benefit From
Dose-Intense Cyclophosphamide, Doxorubicin, and Fluorouracil Therapy in
HER2-Amplified Early Breast Cancer: Results of CALGB 8541/150013
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TRIAL COMPARING DOXORUBICIN; IN-SITU HYBRIDIZATION; ADJUVANT
CHEMOTHERAPY; PROTEIN OVEREXPRESSION; GENE AMPLIFICATION; ERBB-2;
SENSITIVITY; ACTIVATION; HER2; METHOTREXATE
AB Purpose We have demonstrated that patients with HER2-amplified tumors derive more benefit from higher doses of doxorubicin-containing chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil [CAF]). Because topoisomerase II alpha(Topo-II alpha) is a target for doxorubicin and is coamplified in 20% to 50% of HER2-amplified tumors, we postulated that Topo-II alpha copy number might account for the benefit from CAF dose escalation in HER2-positive tumors. To address this hypothesis, we examined Topo-II alpha and HER2 copy number, CAF dose, and clinical outcomes in Cancer and Leukemia Group B (CALGB) 8541.
Patients and Methods Topo-II alpha and HER2 copy number were measured by fluorescent in situ hybridization (FISH) using a triple-probe system, which includes Topo-II alpha, HER2, and chromosome 17 (CEP17). Topo-II alpha and/or HER2 were classified as amplified (>= two copies/CEP17, deleted (<= 0.67 copies/CEP17) and normal copy number (> .67 to < 2.0 copies/CEP17).
Results Topo-II alpha/HER2/CEP17 measurement was successful in 624 of 687 cases. HER2 was amplified in 117 cases (19%). Topo-II alpha was amplified in 41 cases (7%) and deleted in 69 cases (11%). Topo-II alpha amplification was highly correlated with HER2 amplification (39 of 41; P < .0001), HER2 by immunohistochemistry, and by dual-probe FISH. Topo-II alpha was deleted in both the HER2-amplified (30 of 69; 43%), normal (22 of 69; 32%) and HER2-deleted tumors (17 of 69; 25%). Although Topo-II alpha-amplified tumors were nearly always HER2 amplified, these tumors did not receive benefit from increasing the dose of CAF (P = .15).
Conclusion The correlative companion study CALGB 8541-150013 does not support the hypothesis that Topo-II alpha amplification is the mechanism behind benefit from increased dose of anthracyclines in HER2-positive breast cancer.
C1 Yale Canc Ctr, New Haven, CT USA.
Univ N Carolina, Chapel Hill, NC USA.
Duke Univ, Durham, NC 27706 USA.
Univ Colorado, Denver, CO 80202 USA.
N Shore Hosp Ctr, Long Isl City, NY USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Cent Off, Canc & Leukemia Grp B, Chicago, IL USA.
Washington Univ, St Louis, MO USA.
RP Harris, LN (reprint author), Yale Univ, 333 Cedar St,WWW 213, New Haven, CT 06850 USA.
EM lyndsay.harris@yale.edu
FU NCI NIH HHS [P30 CA016672]
NR 34
TC 34
Z9 36
U1 0
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2009
VL 27
IS 21
BP 3430
EP 3436
DI 10.1200/JCO.2008.18.4085
PG 7
WC Oncology
SC Oncology
GA 471II
UT WOS:000268049100006
PM 19470942
ER
PT J
AU Stark, JR
Perner, S
Stampfer, MJ
Sinnott, JA
Finn, S
Eisenstein, AS
Ma, J
Fiorentino, M
Kurth, T
Loda, M
Giovannucci, EL
Rubin, MA
Mucci, LA
AF Stark, Jennifer R.
Perner, Sven
Stampfer, Meir J.
Sinnott, Jennifer A.
Finn, Stephen
Eisenstein, Anna S.
Ma, Jing
Fiorentino, Michelangelo
Kurth, Tobias
Loda, Massimo
Giovannucci, Edward L.
Rubin, Mark A.
Mucci, Lorelei A.
TI Gleason Score and Lethal Prostate Cancer: Does 3+4=4+3?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RADICAL PROSTATECTOMY; PROGNOSTIC-SIGNIFICANCE; CARDIOVASCULAR-DISEASE;
PHYSICIANS HEALTH; RADIATION-THERAPY; RANDOMIZED-TRIAL; GRADING SYSTEM;
NEEDLE-BIOPSY; BETA-CAROTENE; PROGRESSION
AB Purpose Gleason grading is an important predictor of prostate cancer (PCa) outcomes. Studies using surrogate PCa end points suggest outcomes for Gleason score (GS) 7 cancers vary according to the predominance of pattern 4. These studies have influenced clinical practice, but it is unclear if rates of PCa mortality differ for 3 + 4 and 4 + 3 tumors. Using PCa mortality as the primary end point, we compared outcomes in Gleason 3 + 4 and 4 + 3 cancers, and the predictive ability of GS from a standardized review versus original scoring.
Patients and Methods Three study pathologists conducted a blinded standardized review of 693 prostatectomy and 119 biopsy specimens to assign primary and secondary Gleason patterns. Tumor specimens were from PCa patients diagnosed between 1984 and 2004 from the Physicians' Health Study and Health Professionals Follow-Up Study. Lethal PCa (n = 53) was defined as development of bony metastases or PCa death. Hazard ratios (HR) were estimated according to original GS and standardized GS. We compared the discrimination of standardized and original grading with C-statistics from models of 10-year survival.
Results For prostatectomy specimens, 4 + 3 cancers were associated with a three-fold increase in lethal PCa compared with 3 + 4 cancers (95% CI, 1.1 to 8.6). The discrimination of models of standardized scores from prostatectomy (C-statistic, 0.86) and biopsy (C-statistic, 0.85) were improved compared to models of original scores (prostatectomy C-statistic, 0.82; biopsy C-statistic, 0.72).
Conclusion Ignoring the predominance of Gleason pattern 4 in GS 7 cancers may conceal important prognostic information. A standardized review of GS can improve prediction of PCa survival.
C1 [Stark, Jennifer R.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA.
Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA.
RP Stark, JR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM stark@hsph.harvard.edu
RI Rider, Jennifer/A-5371-2011; Kurth, Tobias/A-9243-2012;
OI Kurth, Tobias/0000-0001-7169-2620; Rubin, Mark/0000-0002-8321-9950;
Rider, Jennifer/0000-0002-2637-6036; Finn, Stephen/0000-0002-8628-5814
FU National Cancer Institute [5R01CA058684-13, 5R01CA042182-20, CA34944,
CA40360, CA097193]; Department of Defense [W81XWH-05-1-0562]; National
Research Service Award Training Program in Cancer Epidemiology and a
Dana-Farber/Harvard Cancer Center [T32 CA009001-32]; National Heart,
Lung, and Blood Institute [HL-26490, HL-34595]
FX Supported by Grants No. 5R01CA058684-13 and 5R01CA042182-20 from the
National Cancer Institute; Grant No. W81XWH-05-1-0562 from the
Department of Defense; and Grant No. T32 CA009001-32 from the National
Research Service Award Training Program in Cancer Epidemiology and a
Dana-Farber/Harvard Cancer Center SPORE Career Development Award (J. R.
S.). The Physicians Health Study is supported by Grants No. CA34944,
CA40360, and CA097193 from the National Cancer Institute and Grants No.
HL-26490 and HL-34595 from the National Heart, Lung, and Blood
Institute.
NR 33
TC 158
Z9 162
U1 1
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2009
VL 27
IS 21
BP 3459
EP 3464
DI 10.1200/JCO.2008.20.4669
PG 6
WC Oncology
SC Oncology
GA 471II
UT WOS:000268049100010
PM 19433685
ER
PT J
AU Apperley, JF
Cortes, JE
Kim, DW
Roy, L
Roboz, GJ
Rosti, G
Bullorsky, EO
Abruzzese, E
Hochhaus, A
Heim, D
de Souza, CA
Larson, RA
Lipton, JH
Khoury, HJ
Kim, HJ
Sillaber, C
Hughes, TP
Erben, P
Van Tornout, J
Stone, RM
AF Apperley, Jane F.
Cortes, Jorge E.
Kim, Dong-Wook
Roy, Lydia
Roboz, Gail J.
Rosti, Gianantonio
Bullorsky, Eduardo O.
Abruzzese, Elisabetta
Hochhaus, Andreas
Heim, Dominik
de Souza, Carmino A.
Larson, Richard A.
Lipton, Jeffrey H.
Khoury, H. Jean
Kim, Hyeoung-Joon
Sillaber, Christian
Hughes, Timothy P.
Erben, Philipp
Van Tornout, Jan
Stone, Richard M.
TI Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated
Phase After Imatinib Failure: The START A Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 48th Annual Meeting of the American-Society-of-Hematology
CY DEC 09-12, 2006
CL Orlando, FL
SP Amer Soc Hematol
ID CHRONIC MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; CYTOGENETIC
RESPONSES; BCR-ABL; BLAST CRISIS; FOLLOW-UP; RESISTANCE; THERAPY; LYN;
INDEPENDENCE
AB Purpose
Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population.
Patients and Methods
Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily.
Results
At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%).
Conclusion
Dasatinib is effective in patients with CML-AP after imatinib treatment failure.
C1 [Apperley, Jane F.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Med, London W12 0NN, England.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Catholic Univ Korea, St Marys Hosp, Seoul, South Korea.
Chonnam Natl Univ, Hwasun Gun, Jeollanam Do, South Korea.
CHU Poitiers, Clin Res Ctr, Poitiers, France.
Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA.
S Orsola Malpighi Univ Hosp, Bologna, Italy.
Osped S Eugenio, Rome, Italy.
British Hosp Buenos Aires, Buenos Aires, DF, Argentina.
Univ Heidelberg, Med Fak Mannheim, D-6800 Mannheim, Germany.
Univ Basel Hosp, CH-4031 Basel, Switzerland.
Univ Estadual Campinas, Campinas, SP, Brazil.
Univ Chicago, Chicago, IL 60637 USA.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
Emory Univ, Sch Med, Atlanta, GA USA.
Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, Vienna, Austria.
Univ Adelaide, Adelaide, SA, Australia.
Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Apperley, JF (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Med, Du Cane Rd, London W12 0NN, England.
EM j.apperley@imperial.ac.uk
RI Sangue, Inct/I-1919-2013;
OI Larson, Richard/0000-0001-9168-3203; Hochhaus,
Andreas/0000-0003-0626-0834
FU NCI NIH HHS [P30 CA016672]
NR 30
TC 115
Z9 119
U1 0
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2009
VL 27
IS 21
BP 3472
EP 3479
DI 10.1200/JCO.2007.14.3339
PG 8
WC Oncology
SC Oncology
GA 471II
UT WOS:000268049100012
PM 19487385
ER
PT J
AU Angelov, L
Doolittle, ND
Kraemer, DF
Siegal, T
Barnett, GH
Peereboom, DM
Stevens, G
McGregor, J
Jahnke, K
Lacy, CA
Hedrick, NA
Shalom, E
Ference, S
Bell, S
Sorenson, L
Tyson, RM
Haluska, M
Neuwelt, EA
AF Angelov, Lilyana
Doolittle, Nancy D.
Kraemer, Dale F.
Siegal, Tali
Barnett, Gene H.
Peereboom, David M.
Stevens, Glen
McGregor, John
Jahnke, Kristoph
Lacy, Cynthia A.
Hedrick, Nancy A.
Shalom, Edna
Ference, Sandra
Bell, Susan
Sorenson, Lisa
Tyson, Rose Marie
Haluska, Marianne
Neuwelt, Edward A.
TI Blood-Brain Barrier Disruption and Intra-Arterial Methotrexate-Based
Therapy for Newly Diagnosed Primary CNS Lymphoma: A Multi-Institutional
Experience
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology
CY JUN 01-05, 2007
CL Chicago, IL
SP Amer Soc Clin Oncol
ID CENTRAL-NERVOUS-SYSTEM; HIGH-DOSE METHOTREXATE; ENHANCED CHEMOTHERAPY
DELIVERY; TERM-FOLLOW-UP; PHASE-II; DEFERRED RADIOTHERAPY; EUROPEAN
ORGANIZATION; COGNITIVE FUNCTIONS; MULTICENTER; SURVIVAL
AB Purpose Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved.
Patients and Methods This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age >= 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis.
Results The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age >= 60 years and KPS >= 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae.
Conclusion This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.
C1 Cleveland Clin, Brain Tumor & Neuro Oncol Ctr, Cleveland, OH USA.
Cleveland Clin, Dept Neurosurg, Cleveland, OH USA.
Cleveland Clin, Dept Hematol, Cleveland, OH USA.
Cleveland Clin, Dept Med Oncol, Cleveland, OH USA.
Ohio State Univ, Med Ctr, Dept Neurosurg, Columbus, OH 43210 USA.
Oregon Hlth & Sci Univ, Dept Neurol, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA.
Oregon Hlth & Sci Univ, Dept Publ Hlth, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA.
Oregon Hlth & Sci Univ, Dept Prevent Med, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA.
Oregon State Univ, Dept Pharm Practice, Corvallis, OR 97331 USA.
Portland VA Med Ctr, Portland, OR USA.
Hadassah Hebrew Univ Hosp, Leslie & Michael Gaffin Ctr Neurooncol, Jerusalem, Israel.
RP Neuwelt, EA (reprint author), 3181 SW Sam Jackson Pk Rd,Mailcode L603, Portland, OR 97239 USA.
EM neuwelte@ohsu.edu
RI McGregor, John/K-6870-2013
FU NCI NIH HHS [R01 CA137488, CA137488, R01 CA137488-15, R13 CA086959, R13
CA086959-10]; NINDS NIH HHS [NS34608, NS44687, R37 NS044687, R01
NS034608, R01 NS044687]
NR 47
TC 82
Z9 84
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 JUL 20
PY 2009
VL 27
IS 21
BP 3503
EP 3509
DI 10.1200/JCO.2008.19.3789
PG 7
WC Oncology
SC Oncology
GA 471II
UT WOS:000268049100016
PM 19451444
ER
PT J
AU Richardson, PG
Xie, WL
Mitsiades, C
Chanan-Khan, AA
Lonial, S
Hassoun, H
Avigan, DE
Oaklander, AL
Kuter, DJ
Wen, PY
Kesari, S
Briemberg, HR
Schlossman, RL
Munshi, NC
Heffner, LT
Doss, D
Esseltine, DL
Weller, E
Anderson, KC
Amato, AA
AF Richardson, Paul G.
Xie, Wanling
Mitsiades, Constantine
Chanan-Khan, Asher A.
Lonial, Sagar
Hassoun, Hani
Avigan, David E.
Oaklander, Anne Louise
Kuter, David J.
Wen, Patrick Y.
Kesari, Santosh
Briemberg, Hannah R.
Schlossman, Robert L.
Munshi, Nikhil C.
Heffner, L. Thompson
Doss, Deborah
Esseltine, Dixie-Lee
Weller, Edie
Anderson, Kenneth C.
Amato, Anthony A.
TI Single-Agent Bortezomib in Previously Untreated Multiple Myeloma:
Efficacy, Characterization of Peripheral Neuropathy, and Molecular
Correlations With Response and Neuropathy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; PLUS DEXAMETHASONE; PHASE-II; REFRACTORY
MYELOMA; INDUCTION THERAPY; ONCOLOGY-GROUP; APEX TRIAL; FOLLOW-UP;
THALIDOMIDE; MULTICENTER
AB Purpose To assess efficacy and safety of single-agent bortezomib in previously untreated patients with multiple myeloma, investigate prevalence of baseline and treatment-emergent polyneuropathy, and identify molecular markers associated with response and neuropathy.
Patients and Methods Patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11, for up to eight 21-day cycles. A subset of patients underwent neurophysiologic evaluation pre- and post-treatment. Bone marrow aspirates were performed at baseline for exploratory whole-genome analyses.
Results Among 64 patients, 41% had partial response or better, including 9% complete/near-complete responses; median duration of response was 8.4 months. Response rates did not differ in the presence or absence of adverse cytogenetics. After median follow-up of 29 months, median time to progression was 17.3 months. Median overall survival had not been reached; estimated 1-year survival was 92%. Thirty-two patients successfully underwent optional stem-cell transplantation. Bortezomib treatment was generally well tolerated. At baseline, 20% of patients had sensory polyneuropathy. Sensory polyneuropathy developed during treatment in 64% of patients ( grade 3 in 3%), but proved manageable and resolved in 85% within a median of 98 days. Neurologic examination, neurophysiologic testing, and measurements of epidermal nerve fiber densities in 35 patients confirmed pretreatment sensory neuropathy in 20% and new or worsening neuropathy in 63%. Pharmacogenomic analyses identified molecular markers of response and treatment-emergent neuropathy, which will require future study.
Conclusion Single-agent bortezomib is effective in previously untreated myeloma. Baseline myelomaassociated neuropathy seems more common than previously reported, and bortezomib-associated neuropathy, although a common toxicity, is reversible in most patients.
C1 [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Millennium Pharmaceut Inc, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA.
EM richardson@dfci.harvard.edu
RI Kesari, Santosh/E-8461-2013
FU Public Health Service [NINDS R01NS42866, P30 EY 12196]; Millennium
Pharmaceuticals; Johnson & Johnson Pharmaceuticals Research &
Development, LLC
FX Supported in part by the Public Health Service (Grant No. NINDS
R01NS42866, P30 EY 12196) and by Millennium Pharmaceuticals and Johnson
& Johnson Pharmaceuticals Research & Development, LLC.
NR 55
TC 138
Z9 146
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 JUL 20
PY 2009
VL 27
IS 21
BP 3518
EP 3525
DI 10.1200/JCO.2008.18.3087
PG 8
WC Oncology
SC Oncology
GA 471II
UT WOS:000268049100018
PM 19528374
ER
PT J
AU Park, Y
Choi, W
Yaqoob, Z
Dasari, R
Badizadegan, K
Feld, MS
AF Park, YongKeun
Choi, Wonshik
Yaqoob, Zahid
Dasari, Ramachandra
Badizadegan, Kamran
Feld, Michael S.
TI Speckle-field digital holographic microscopy
SO OPTICS EXPRESS
LA English
DT Article
ID DIFFRACTION PHASE MICROSCOPY; FLUORESCENCE MICROSCOPY; REFRACTIVE-INDEX;
DYNAMICS; ILLUMINATION; CELLS
AB The use of coherent light in conventional holographic phase microscopy (HPM) poses three major drawbacks: poor spatial resolution, weak depth sectioning, and fixed pattern noise due to unwanted diffraction. Here, we report a technique which can overcome these drawbacks, but maintains the advantage of phase microscopy - high contrast live cell imaging and 3D imaging. A speckle beam of a complex spatial pattern is used for illumination to reduce fixed pattern noise and to improve optical sectioning capability. By recording of the electric field of speckle, we demonstrate high contrast 3D live cell imaging without the need for axial scanning - neither objective lens nor sample stage. This technique has great potential in studying biological samples with improved sensitivity, resolution and optical sectioning capability. (C) 2009 Optical Society of America
C1 [Park, YongKeun; Choi, Wonshik; Yaqoob, Zahid; Dasari, Ramachandra; Badizadegan, Kamran; Feld, Michael S.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA.
[Park, YongKeun] Harvard MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Choi, Wonshik] Korea Univ, Dept Phys, Seoul 136701, South Korea.
[Badizadegan, Kamran] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Badizadegan, Kamran] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Park, Y (reprint author), MIT, George R Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM wonshik@mit.edu
RI Park, YongKeun/B-9017-2009
FU National Institutes of Health [P41-RR02594]; National Science Foundation
[DBI-0754339]; Hamamatsu Corporation; Samsung Scholarship; Whitaker
Health Science Fellowship
FX This work was funded by the National Center for Research Resources of
the National Institutes of Health (P41-RR02594), the National Science
Foundation (DBI-0754339) and Hamamatsu Corporation. Y.-K. Park was
supported by Samsung Scholarship and Whitaker Health Science Fellowship.
NR 21
TC 61
Z9 62
U1 1
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 JUL 20
PY 2009
VL 17
IS 15
BP 12285
EP 12292
DI 10.1364/OE.17.012285
PG 8
WC Optics
SC Optics
GA 475XE
UT WOS:000268399500009
PM 19654630
ER
PT J
AU Dunfee, RL
Thomas, ER
Gabuzda, D
AF Dunfee, Rebecca L.
Thomas, Elaine R.
Gabuzda, Dana
TI Enhanced macrophage tropism of HIV in brain and lymphoid tissues is
associated with sensitivity to the broadly neutralizing CD4 binding site
antibody b12
SO RETROVIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTION; GP120; ENVELOPE; ENTRY;
DEMENTIA; CONFORMATION; PATHOGENESIS; SPECIFICITY; CORECEPTORS
AB Macrophages in the central nervous system (CNS) and other tissues are an important cellular reservoir for human immunodeficiency virus type 1 (HIV) infection, particularly in the later stages of disease. Macrophage-tropic HIV strains have an enhanced capacity to enter cells expressing low levels of CD4 through mechanisms that are not well understood. Here, we use a panel of primary HIV envelopes from brain and lymphoid tissues to examine the relationship between neutralization sensitivity to reagents targeting the CD4 binding site and virus entry into macrophages. Neutralization assays using pseudotyped viruses showed an association between the capacity of HIV to enter macrophages and increased sensitivity to the broadly neutralizing monoclonal antibody (mAb) b12, which recognizes a conserved epitope overlapping the CD4 binding site, but not sensitivity to soluble CD4 (sCD4) or b6, a non-neutralizing CD4 binding site mAb. Furthermore, loss of an N-linked glycosylation site at position 386 in the V4 region of Env enhanced macrophage tropism together with b12 sensitivity, but not neutralization by sCD4, b6, or a broadly neutralizing AIDS patient serum. These findings suggest that exposure of the b12 epitope, rather than exposure of the CD4 binding site per se, enhances HIV macrophage tropism, possibly by exposing a region on the outer domain of gp120 that is initially recognized by CD4. These findings suggest overlap between specific gp120 determinants in or near the b12 epitope and those conferring macrophage tropism.
C1 [Dunfee, Rebecca L.; Thomas, Elaine R.; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Dunfee, Rebecca L.; Thomas, Elaine R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM dunfeer@niaid.nih.gov; EThomas@arrowt.co.uk;
dana_gabuzda@dfci.harvard.edu
FU NIH [MH83588]; Harvard University Center for AIDS Research and
DFCI/Harvard Cancer Center
FX We thank Dennis Burton (Scripps) for providing the b12 and b6
antibodies. This work was supported by NIH grant MH83588. Core
facilities were supported by Harvard University Center for AIDS Research
and DFCI/Harvard Cancer Center grants.
NR 37
TC 27
Z9 28
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JUL 20
PY 2009
VL 6
AR 69
DI 10.1186/1742-4690-6-69
PG 7
WC Virology
SC Virology
GA 487TX
UT WOS:000269300500001
PM 19619305
ER
PT J
AU Pryaslova, JP
Lyamin, OI
Siegel, JM
Mukhametov, LM
AF Pryaslova, Julia P.
Lyamin, Oleg I.
Siegel, Jerome M.
Mukhametov, Lev M.
TI Behavioral sleep in the walrus
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Quiet sleep; REM sleep; Behavioral sleep; Sleep variability; Continuous
swimming; Breathing pattern; Walrus; Pinnipeds
ID SEAL PAGOPHILUS-GROENLANDICA; MAMMALIAN SLEEP; FUR-SEAL; PATTERNS; PUPS;
WAKEFULNESS; ASYMMETRY; WAKE; EEG
AB In this study we examined behavioral sleep in the walrus, the only living species of the family Odobenidae. The behavior of four 1.5-2-year-old captive walruses was videotaped continuously for 7-17 days and scored in 1-min epochs. When walruses had access to water and land, behavioral sleep, the combined amount of quiet and rapid eye movement (REM) sleep, occupied on average 17 +/- 4% of 24 h (n = 4) with the majority of sleep occurring on land. All walruses alternated periods of almost continuous swimming lasting for 40-84 h with periods of rest on land lasting for 2-19 h. When in water they were predominantly awake (88-99% of the time). On land walruses were asleep on average 40-74% of the time. The total sleep time varied between 0 and 60% of 24 h with the daily amount of REM sleep ranging from 0 to 5% of 24 h. In water, walruses slept while floating at the surface, lying on the bottom or standing and leaning against the pool wall. REM sleep in water occurred in all positions. On land the breathing pattern was regular during quiet sleep (most pauses were <30s) and arrhythmic in REM sleep (apneas lasted up to 160s). While in water the irregularity of breathing further increased (apneas were >4 min) and all REM sleep episodes occurred during a single apnea. Data indicate that the pattern of sleep and breathing in walruses is similar to the Otariidae seats while on land and the Phocidae seats while in water. Published by Elsevier B.V.
C1 [Lyamin, Oleg I.; Siegel, Jerome M.] Vet Affairs Greater Los Angeles Healthcare Syst S, Neurobiol Res 151A3, North Hills, CA 91343 USA.
[Pryaslova, Julia P.; Lyamin, Oleg I.; Mukhametov, Lev M.] Utrish Dolphinarium Ltd, Moscow 119071, Russia.
[Lyamin, Oleg I.; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat, Sch Med, Los Angeles, CA USA.
RP Lyamin, OI (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst S, Neurobiol Res 151A3, 16111 Plummer St, North Hills, CA 91343 USA.
EM olyamin@ucla.edu
FU Utrish Dolphinarium Ltd. (Moscow, Russia); The Medical Research Service
of the Department of Veterans Affairs (USA)
FX This research was supported by Utrish Dolphinarium Ltd. (Moscow, Russia)
and The Medical Research Service of the Department of Veterans Affairs
(USA). The authors wish to thank the staff of the Utrish Dolphinarium
and the Utrish Marine Station (Severtsov Institute of the Russian
Academy of Sciences, Novorossiysk, Russia), for their help and
assistance during the observations. We are also thankful to J. Lapierre
for valuable comments on this manuscript.
NR 40
TC 5
Z9 5
U1 3
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD JUL 19
PY 2009
VL 201
IS 1
BP 80
EP 87
DI 10.1016/j.bbr.2009.01.033
PG 8
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 447ZV
UT WOS:000266231800012
PM 19428620
ER
PT J
AU Smolen, JS
Kay, J
Doyle, MK
Landewe, R
Matteson, EL
Wollenhaupt, J
Gaylis, N
Murphy, FT
Neal, JS
Zhou, YY
Visvanathan, S
Hsia, EC
Rahman, MU
AF Smolen, Josef S.
Kay, Jonathan
Doyle, Mittie K.
Landewe, Robert
Matteson, Eric L.
Wollenhaupt, Juergen
Gaylis, Norman
Murphy, Frederick T.
Neal, Jeffrey S.
Zhou, Yiying
Visvanathan, Sudha
Hsia, Elizabeth C.
Rahman, Mahboob U.
CA GO-AFTER Study Investigators
TI Golimumab inpatients with active rheumatoid arthritis after treatment
with tumour necrosis factor alpha inhibitors (GO-AFTER study): a
multicentre, randomised, double-blind, placebo-controlled, phase III
trial
SO LANCET
LA English
DT Article
ID DISEASE-ACTIVITY; MONOCLONAL-ANTIBODY; CLINICAL-TRIALS; CONCOMITANT
METHOTREXATE; EFFICACY; ETANERCEPT; THERAPY; SAFETY; INFLIXIMAB;
ADALIMUMAB
AB Background Turnout necrosis factor a (TNF alpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNF alpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNF alpha inhibitor golimumab in patients with active rheumatoid arthritis who had previously received one or more TNF alpha inhibitors.
Methods 461 patients with active rheumatoid arthritis from 82 sites in 10 countries were randomly allocated by interactive voice response system, stratified by study site and methotrexate use, to receive subcutaneous injections of placebo (n=155), 50 mg golimumab (n=153), or 100 mg golimumab (n=153) every 4 weeks between Feb 21, 2006, and Sept 26, 2007. Allocation was double-blind. Eligible patients had been treated with at least one dose of a TNF alpha inhibitor previously. Patients continued stable doses of methotrexate, sulfasalazine, hydroxychloroquine, oral corticosteroids, and non-steroidal anti-inflammatory drugs. The primary endpoint was achievement at week 14 of 20% or higher improvement in American College of Rheumatology criteria for assessment of rheumatoid arthritis (ACR20). At week 16, patients who had less than 20% improvement in tender and swollen joint counts were given rescue therapy and changed treatment from placebo to 50 mg golimumab, or from 50 mg to 100 mg golimumab. Drug efficacy was assessed by intention to treat and safety was assessed according to the study drug given. This study is registered with ClinicalTrials.gov, number NCT00299546.
Findings Patients had discontinued previous TNF alpha inhibitors because of lack of effectiveness (269 [58%] patients) or reasons unrelated to effectiveness (246 [53%] patients), such as intolerance and accessibility issues. Patients had active disease, which was indicated by a median of 14.0 (IQR 9.0-22.0) swollen and 26.0 (16.0-41.0) tender joints for the whole group. 28 (18%) patients on placebo, 54 (35%) patients on 50 mg golimumab (odds ratio 2.5 [95% Cl 1.5-4.2], p=0.0006), and 58 (38%) patients on 100 mg golimumab (2.8 [1.6-4.7], p=0.0001) achieved ACR20 at week 14. Two patients were never treated, and 57 patients did not complete the study because of adverse events, unsatisfactory treatment effect, loss to follow-up, death, or other reasons. 155 patients on placebo, 153 on 50 mg golimumab, and 153 on 100 mg golimumab were assessed for drug efficacy. For weeks 1-16, serious adverse events were recorded in 11 (7%) patients on placebo, 8 (5%) on 50 mg golimumab, and 4 (3%) on 100 mg golimumab. For weeks 1-24, after some patients were given rescue therapy, serious adverse events were recorded in 15 (10%) patients on placebo, 14 (5%) on 50 mg golimumab, and 8 (4%) on 100 mg golimumab.
Interpretation Golimumab reduced the signs and symptoms of rheumatoid arthritis in patients with active disease who had previously received one or more TNF alpha inhibitors.
C1 [Smolen, Josef S.] Med Univ Vienna, A-1090 Vienna, Austria.
[Smolen, Josef S.] Hietzing Hosp, Vienna, Austria.
[Kay, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kay, Jonathan] Havard Med Sch, Boston, MA USA.
[Doyle, Mittie K.; Zhou, Yiying; Visvanathan, Sudha; Hsia, Elizabeth C.; Rahman, Mahboob U.] Centocor Researc & Dev, Malvern, PA USA.
[Doyle, Mittie K.; Murphy, Frederick T.; Hsia, Elizabeth C.; Rahman, Mahboob U.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Landewe, Robert] Univ Hosp Maastricht, Maastricht, Netherlands.
[Matteson, Eric L.] Mayo Clin, Rochester, MN USA.
[Wollenhaupt, Juergen] Klin Eibek, Hamburg, Germany.
[Gaylis, Norman] Arthrit & Rheumat Dis Specialties, Aventura, FL USA.
[Murphy, Frederick T.] Altoona Ctr Clin Res, Duncansville, PA USA.
[Neal, Jeffrey S.] Bluegrass Community Res, Lexington, KY USA.
RP Smolen, JS (reprint author), Med Univ Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM josef.smolen@wienkav.at
OI Kay, Jonathan/0000-0002-8970-4260
FU Centocor Research and Development and Schering-Plough Research Institute
FX This study was sponsored by Centocor Research and Development and
Schering-Plough Research Institute. We thank the patients,
investigators, and study personnel who made the trial possible; and
Scott Newcomer, medical writer for Centocor Ortho Biotech Services, a
wholly owned subsidiary of Johnson & Johnson, for his assistance in the
preparation of this report.
NR 39
TC 248
Z9 264
U1 1
U2 14
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 JUL 18
PY 2009
VL 374
IS 9685
BP 210
EP 221
DI 10.1016/S0140-6736(09)60506-7
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 474DP
UT WOS:000268263000029
PM 19560810
ER
PT J
AU Kaufman, DS
Shipley, WU
Feldman, AS
AF Kaufman, Donald S.
Shipley, William U.
Feldman, Adam S.
TI Bladder cancer
SO LANCET
LA English
DT Review
ID TRANSITIONAL-CELL-CARCINOMA; PHASE-II TRIAL; BACILLUS-CALMETTE-GUERIN;
METASTATIC UROTHELIAL CANCER; COOPERATIVE-ONCOLOGY-GROUP;
CISPLATIN-BASED CHEMOTHERAPY; 2ND TRANSURETHRAL RESECTION; GEMCITABINE
PLUS CISPLATIN; RANDOMIZED CLINICAL-TRIALS; MOLECULAR TARGETED THERAPY
AB Bladder cancer is a heterogeneous disease, with 70% of patients presenting with superficial tumours, which tend to recur but are generally not life threatening, and 30% presenting as muscle-invasive disease associated with a high risk of death from distant metastases. The main presenting symptom of all bladder cancers is painless haematuria, and the diagnosis is established by urinary cytology and transurethral tumour resection. Intravesical treatment is used for carcinoma in situ and other high grade non-muscle-invasive tumours. The standard of care for muscle-invasive disease is radical cystoprostatectomy, and several types of urinary diversions are offered to patients, with quality of life as an important consideration. Bladder preservation with transurethral tumour resection, radiation, and chemotherapy can in some cases be equally curative. Several chemotherapeutic agents have proven to tie useful as neoadjuvant or adjuvant treatment and in patients with metastatic disease. We discuss bladder preserving approaches, combination chemotherapy including new agents, targeted therapies, and advances in molecular biology.
C1 [Kaufman, Donald S.] Massachusetts Gen Hosp, Claire & John Bertucci Ctr Genitourinary Canc, Dept Med, Boston, MA 02114 USA.
[Shipley, William U.] Massachusetts Gen Hosp, Claire & John Bertucci Ctr Genitourinary Canc, Dept Radiat Oncol, Boston, MA 02114 USA.
[Feldman, Adam S.] Massachusetts Gen Hosp, Claire & John Bertucci Ctr Genitourinary Canc, Dept Urol, Boston, MA 02114 USA.
RP Kaufman, DS (reprint author), Massachusetts Gen Hosp, Claire & John Bertucci Ctr Genitourinary Canc, Dept Med, Yawkey Bldg,Fruit St, Boston, MA 02114 USA.
EM dskaufman@partners.org
NR 129
TC 405
Z9 430
U1 8
U2 61
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 JUL 18
PY 2009
VL 374
IS 9685
BP 239
EP 249
DI 10.1016/S0140-6736(09)60491-8
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 474DP
UT WOS:000268263000033
PM 19520422
ER
PT J
AU Stanley, TL
Joy, T
Hadigan, CM
Liebau, JG
Makimura, H
Chen, CY
Thomas, BJ
Weise, SB
Robbins, GK
Grinspoon, SK
AF Stanley, Takara L.
Joy, Tisha
Hadigan, Colleen M.
Liebau, James G.
Makimura, Hideo
Chen, Cindy Y.
Thomas, Bijoy J.
Weise, Steven B.
Robbins, Gregory K.
Grinspoon, Steven K.
TI Effects of switching from lopinavir/ritonavir to atazanavir/ritonavir on
muscle glucose uptake and visceral fat in HIV-infected patients
SO AIDS
LA English
DT Article
DE atazanavir; glucose; HIV; intra-abdominal fat; lipids; lipodystrophy;
lopinavir
ID TWICE-DAILY LOPINAVIR/RITONAVIR; ONCE-DAILY ATAZANAVIR/RITONAVIR;
HORMONE-RELEASING FACTOR; PROTEASE INHIBITORS; INSULIN-RESISTANCE;
GROWTH-HORMONE; ADIPOCYTE DIFFERENTIATION; HIV-1-INFECTED PATIENTS;
ANTIRETROVIRAL THERAPY; SKELETAL-MUSCLE
AB Objective: To determine the effects of switching from lopinavir/ritonavir (LPV/r) to atazanavir/ritonavir (ATV/r) on muscle glucose uptake, glucose homeostasis, lipids, and body composition.
Methods: Fifteen HIV-infected men and women on a regimen containing LPV/r and with evidence of hyperinsulinemia and/or dyslipidemia were randomized to continue LPV/r or to switch to ATV/r (ATV 300 mg and ritonavir 100 mg daily) for 6 months. The primary endpoint was change in thigh muscle glucose uptake as measured by positron emission tomography. Secondary endpoints included abdominal visceral adipose tissue, fasting lipids, and safety parameters. The difference over time between treatment groups (treatment effect of ATV/r relative to LPV/r) was determined by repeated measures ANCOVA.
Results: After 6 months, anterior thigh muscle glucose uptake increased significantly (treatment effect +18.2 +/- 5.9 mu mol/kg per min, ATV/r vs. LPV/r, P=0.035), and visceral adipose tissue area decreased significantly in individuals who switched to ATV/r (treatment effect -31 +/- 11 cm(2), ATV/r vs. LPV/r, P=0.047). Switching to ATV/r significantly decreased triglyceride (treatment effect -182 +/- 64 mg/dl, ATV/r vs. LPV/r, P=0.02) and total cholesterol (treatment effect -23 +/- 8 mg/dl, ATV/r vs. LPV/r, P=0.01), whereas high-density lipoprotein and low-density lipoprotein did not change significantly. Fasting glucose also decreased significantly following switch to ATV/r (treatment effect -15 +/- 4 mg/dl, ATV/r vs. LPV/r, P=0.002).
Conclusion: Switching from LPV/r to ATV/r significantly increases glucose uptake by muscle, decreases abdominal visceral adipose tissue, improves lipid parameters, and decreases fasting glucose over 6 months. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Stanley, Takara L.; Joy, Tisha; Liebau, James G.; Makimura, Hideo; Chen, Cindy Y.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
[Robbins, Gregory K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Thomas, Bijoy J.; Weise, Steven B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Thomas, Bijoy J.; Weise, Steven B.] Harvard Univ, Sch Med, Boston, MA USA.
[Hadigan, Colleen M.] NIH, Bethesda, MD 20892 USA.
RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
EM sgrinspoon@partners.org
FU NIH [M01-RR01066, 1 ULI RR025758-01, T32 HID052961-03, K01 AI062435, K24
DK064545-06]; Harvard Clinical and Translational Science Center;
National Center for Research Resources; Boehringer Ingelheim, Gilead;
Schering-Plough; Bristol Myers Squibb and Theratechnologies
FX Funding was provided by BMS in the form of an investigator initiated
research grant and NIH M01-RR01066 and 1 ULI RR025758-01, Harvard
Clinical and Translational Science Center, from the National Center for
Research Resources. NIH funding also provided by T32 HID052961-03
trainee support to TS., K01 AI062435 to G.R., and K24 DK064545-06 to
S.G. G.R. has received grant support from Boehringer Ingelheim, Gilead,
and Schering-Plough, and has been a consultant for Abbott Laboratories.
S.G. has received research support from Bristol Myers Squibb and
Theratechnologies and served as a consultant for Theratechnologies and
Serono, Inc.
NR 40
TC 31
Z9 32
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 17
PY 2009
VL 23
IS 11
BP 1349
EP 1357
DI 10.1097/QAD.0b013e32832ba904
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 470GJ
UT WOS:000267962900007
PM 19474651
ER
PT J
AU Barth, MC
Ahluwalia, N
Anderson, TJT
Hardy, GJ
Sinha, S
Alvarez-Cardona, JA
Pruitt, IE
Rhee, EP
Colvin, RA
Gerszten, RE
AF Barth, Marita C.
Ahluwalia, Neil
Anderson, Thomas J. T.
Hardy, Gregory J.
Sinha, Sumita
Alvarez-Cardona, Jose A.
Pruitt, Ivy E.
Rhee, Eugene P.
Colvin, Richard A.
Gerszten, Robert E.
TI Kynurenic Acid Triggers Firm Arrest of Leukocytes to Vascular
Endothelium under Flow Conditions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED-RECEPTOR; INFLAMMATORY-BOWEL-DISEASE; FUNCTIONAL
EXPRESSION; CHEMOTACTIC FACTORS; PATHWAY METABOLISM; MOLECULAR-CLONING;
DENDRITIC CELLS; MICE REVEALS; ADHESION; TRYPTOPHAN
AB Recent studies have demonstrated that kynurenic acid (KYNA), a compound produced endogenously by the interferon-gamma-induced degradation of tryptophan by indoleamine 2,3-dioxygenase, activates the previously orphaned G protein-coupled receptor, GPR35. This receptor is expressed in immune tissues, although its potential function in immunomodulation remains to be explored. We determined that GPR35 was most highly expressed on human peripheral monocytes. In an in vitro vascular flow model, KYNA triggered the firm arrest of monocytes to both fibronectin and ICAM-1, via beta(1) integrin- and beta(2) integrin-mediated mechanisms, respectively. Incubation of monocytes with pertussis toxin prior to use in flow experiments significantly reduced the KYNA-induced monocyte adhesion, suggesting that adhesion is triggered by a G(i)-mediated process. Furthermore, KYNA-triggered adhesion of monocytic cells was reduced by short hairpin RNA-mediated silencing of GPR35. Although GPR35 is expressed at slightly lower levels on neutrophils, KYNA induced firm adhesion of these cells to an ICAM-1-expressing monolayer as well. KYNA also elicited neutrophil shedding of surface L-selectin, another indicator of leukocyte activation. Taken together, these data suggest that KYNA could be an important early mediator of leukocyte recruitment.
C1 [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA.
Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA.
EM Gerszten.Robert@mgh.harvard.edu
OI Anderson, Thomas/0000-0002-2762-6703
FU NHLBI NIH HHS [HL65584, R01 HL065584]
NR 41
TC 58
Z9 60
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 17
PY 2009
VL 284
IS 29
BP 19189
EP 19195
DI 10.1074/jbc.M109.024042
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 469OE
UT WOS:000267908300008
PM 19473985
ER
PT J
AU Kao, SY
AF Kao, Shyan-Yuan
TI DNA damage induces nuclear translocation of parkin
SO JOURNAL OF BIOMEDICAL SCIENCE
LA English
DT Article
ID RECESSIVE JUVENILE PARKINSONISM; VIRUS TYPE-1 TAX; SUBSTANTIA-NIGRA;
OXIDATIVE DAMAGE; ALPHA-SYNUCLEIN; HUMAN BRAIN; DISEASE; PROTEIN; GENE;
REPAIR
AB Parkinson's disease (PD) is the second most common form of human degenerative disorder. Mutation of parkin is one of the most prevalent causes of autosomal recessive PD. Parkin is an E3 ubiquitin ligase that acts on a variety of substrates, resulting in polyubiquitination and degradation by the proteasome or monoubiquitination and regulation of biological activity. However, the cellular functions of parkin that relate to its pathological involvement in PD are not well understood. Here I show that parkin translocates into nucleus upon DNA damage. Nuclear translocation of parkin appears to be required to promote DNA repair. These findings suggest that DNA damage induces nuclear translocation of parkin leading to the PCNA interaction and possibly other nuclear proteins involved in DNA repair. These results suggest that parkin promotes DNA repair and protects against genotoxicity, and implicate DNA damage as a potential pathogenic mechanism in parkinsonism.
C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
RP Kao, SY (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM shyan-yuan_kao@meei.harvard.edu
NR 29
TC 14
Z9 14
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1021-7770
J9 J BIOMED SCI
JI J. Biomed. Sci.
PD JUL 17
PY 2009
VL 16
AR 67
DI 10.1186/1423-0127-16-67
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 482MX
UT WOS:000268894100001
PM 19615059
ER
PT J
AU Sundrud, MS
Mazitschek, R
Whitman, M
AF Sundrud, M. S.
Mazitschek, Ralph
Whitman, Malcolm
TI Halofuginone inhibits T(H)17 cell differentiation by activating the
amino acid starvation response (vol 324, pg 1334, 2009)
SO SCIENCE
LA English
DT Correction
C1 [Mazitschek, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Mazitschek, Ralph] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02142 USA.
[Mazitschek, Ralph] Broad Inst, Chem Biol Program, Cambridge, MA 02142 USA.
EM mwhitman@hms.harvard.edu
RI Mazitschek, Ralph/E-3741-2013
OI Mazitschek, Ralph/0000-0002-1105-689X
NR 1
TC 0
Z9 0
U1 0
U2 6
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 JUL 17
PY 2009
VL 325
IS 5938
BP 267
EP 267
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 471DZ
UT WOS:000268036600017
ER
PT J
AU Alousi, AM
Weisdorf, DJ
Logan, BR
Bolanos-Meade, J
Carter, S
DiFronzo, N
Pasquini, M
Goldstein, SC
Ho, VT
Hayes-Lattin, B
Wingard, JR
Horowitz, MM
Levine, JE
AF Alousi, Amin M.
Weisdorf, Daniel J.
Logan, Brent R.
Bolanos-Meade, Javier
Carter, Shelly
DiFronzo, Nancy
Pasquini, Marcelo
Goldstein, Steven C.
Ho, Vincent T.
Hayes-Lattin, Brandon
Wingard, John R.
Horowitz, Mary M.
Levine, John E.
CA Blood & Marrow Transplant Clin Tri
TI Etanercept, mycophenolate, denileukin, or pentostatin plus
corticosteroids for acute graft-versus-host disease: a randomized phase
2 trial from the Blood and Marrow Transplant Clinical Trials Network
SO BLOOD
LA English
DT Article; Proceedings Paper
CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint
Symposium
CY DEC 06-09, 2008
CL San Francisco, CA
SP Amer Soc Hematol (ASH), Sanofi Aventis U.S.
ID INITIAL THERAPY; CHRONIC GVHD; METHOTREXATE; CYCLOSPORINE; PROPHYLAXIS;
PREDNISONE; DIFTITOX; EFFICACY; STEROIDS; MODERATE
AB Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard initial therapy, yet only 25% to 41% of patients completely respond. This randomized, 4-arm, phase 2 trial was designed to identify the most promising agent(s) for initial therapy for aGVHD. Patients were randomized to receive methylprednisolone 2 mg/kg per day plus etanercept, mycophenolate mofetil (MMF), denileukin diftitox (denileukin), or pentostatin. Patients (n = 180) were randomized; their median age was 50 years (range, 7.5-70 years). Myeloablative conditioning represented 66% of transplants. Grafts were peripheral blood (61%), bone marrow (25%), or umbilical cord blood (14%); 53% were from unrelated donors. Patients who received MMF for prophylaxis (24%) were randomized to a non-MMF arm. At randomization, aGVHD was grade I to II (68%), III to IV (32%), and (53%) had visceral organ involvement. Day 28 complete response rates were etanercept 26%, MMF 60%, denileukin 53%, and pentostatin 38%. Corresponding 9-month overall survival was 47%, 64%, 49%, and 47%, respectively. Cumulative incidences of severe infections were as follows: etanercept 48%, MMF 44%, denileukin 62%, and pentostatin 57%. Efficacy and toxicity data suggest the use of MMF plus corticosteroids is the most promising regimen to compare against corticosteroids alone in a definitive phase 3 trial. This study is registered at http://www. clinicaltrials.gov as NCT00224874. (Blood. 2009; 114: 511-517)
C1 [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Weisdorf, Daniel J.] Univ Minnesota, Dept Bone Marrow Transplant, Minneapolis, MN USA.
[Logan, Brent R.] Med Coll Wisconsin, Dept Populat Hlth, Milwaukee, WI 53226 USA.
[Bolanos-Meade, Javier] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
[Carter, Shelly] EMMES Corp, Rockville, MD USA.
[DiFronzo, Nancy] NHLBI, Transfus Med & Cellular Therapeut Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Pasquini, Marcelo] Med Coll Wisconsin, Dept Med, Div Neoplast Dis & Related Disorders, CIBMTR, Milwaukee, WI 53226 USA.
[Goldstein, Steven C.] Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Ho, Vincent T.] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA.
[Hayes-Lattin, Brandon] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA.
[Wingard, John R.] Univ Florida, Dept Med, Shands Canc Ctr, Gainesville, FL USA.
[Levine, John E.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
[Horowitz, Mary M.] Froedtert & Med Coll Wisconsin, Dept Med, Div Neoplast Dis & Related Disorders, Milwaukee, WI USA.
[Horowitz, Mary M.] Froedtert & Med Coll Wisconsin, CIBMTR, Milwaukee, WI USA.
RP Alousi, AM (reprint author), 1515 Holcombe Blvd,Unit 423, Houston, TX 77030 USA.
EM aalousi@mdanderson.org
OI Levine, John/0000-0002-9133-0800
FU NCI NIH HHS [U24 CA076518]; NHLBI NIH HHS [U10 HL069249, U10 HL069286,
U10 HL069294, U10 HL069301, U10 HL069330, U10 HL069348]
NR 24
TC 110
Z9 114
U1 0
U2 1
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 JUL 16
PY 2009
VL 114
IS 3
BP 511
EP 517
DI 10.1182/blood-2009-03-212290
PG 7
WC Hematology
SC Hematology
GA 471ML
UT WOS:000268061800008
PM 19443659
ER
PT J
AU Azab, AK
Azab, F
Blotta, S
Pitsillides, CM
Thompson, B
Runnels, JM
Roccaro, AM
Ngo, HT
Melhem, MR
Sacco, A
Jia, XY
Anderson, KC
Lin, CP
Rollins, BJ
Ghobrial, IM
AF Azab, Abdel Kareem
Azab, Feda
Blotta, Simona
Pitsillides, Costas M.
Thompson, Brian
Runnels, Judith M.
Roccaro, Aldo M.
Ngo, Hai T.
Melhem, Molly R.
Sacco, Antonio
Jia, Xiaoying
Anderson, Kenneth C.
Lin, Charles P.
Rollins, Barrett J.
Ghobrial, Irene M.
TI RhoA and Rac1 GTPases play major and differential roles in stromal
cell-derived factor-1-induced cell adhesion and chemotaxis in multiple
myeloma
SO BLOOD
LA English
DT Article
ID BONE-MARROW; ACTIN CYTOSKELETON; IN-VIVO; MIGRATION; FACTOR-1-ALPHA;
INHIBITION; LOCOMOTION; BIOLOGY; KINASE; VLA-4
AB The interaction of multiple myeloma (MM) cells with the bone marrow (BM) milieu plays a crucial role in MM pathogenesis. Stromal cell-derived factor-1 (SDF1) regulates homing of MM cells to the BM. In this study, we examined the role of RhoA and Rac1 GTPases in SDF1-induced adhesion and chemotaxis of MM. We found that both RhoA and Rac1 play key roles in SDF1-induced adhesion of MM cells to BM stromal cells, whereas RhoA was involved in chemotaxis and motility. Furthermore, both ROCK and Rac1 inhibitors reduced SDF1-induced polymerization of actin and activation of LIMK, SRC, FAK, and cofilin. Moreover, RhoA and Rac1 reduced homing of MM cells to BM niches. In conclusion, we characterized the role of RhoA and Rac1 GTPases in SDF1-induced adhesion, chemotaxis, and homing of MM cells to the BM, providing the framework for targeting RhoA and Rac1 GTPases as novel MM therapy. (Blood. 2009; 114: 619-629)
C1 [Azab, Abdel Kareem; Azab, Feda; Blotta, Simona; Runnels, Judith M.; Roccaro, Aldo M.; Ngo, Hai T.; Melhem, Molly R.; Sacco, Antonio; Jia, Xiaoying; Anderson, Kenneth C.; Rollins, Barrett J.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pitsillides, Costas M.; Thompson, Brian; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA.
RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, 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; Roccaro, Aldo/0000-0002-1872-5128
FU NIH [R01CA125690, EB000664]; Leukemia & Lymphoma Society
FX This study is supported in part by R01CA125690, NIH EB000664 (Bethesda,
MD), and the Leukemia & Lymphoma Society (White Plains, NY) to I. M. G.
NR 34
TC 63
Z9 66
U1 0
U2 10
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 16
PY 2009
VL 114
IS 3
BP 619
EP 629
DI 10.1182/blood-2009-01-199281
PG 11
WC Hematology
SC Hematology
GA 471ML
UT WOS:000268061800022
PM 19443661
ER
PT J
AU Gutierrez, A
Sanda, T
Grebliunaite, R
Carracedo, A
Salmena, L
Ahn, YB
Dahlberg, S
Neuberg, D
Moreau, LA
Winter, SS
Larson, R
Zhang, JH
Protopopov, A
Chin, L
Pandolfi, PP
Silverman, LB
Hunger, SP
Sallan, SE
Look, AT
AF Gutierrez, Alejandro
Sanda, Takaomi
Grebliunaite, Ruta
Carracedo, Arkaitz
Salmena, Leonardo
Ahn, Yebin
Dahlberg, Suzanne
Neuberg, Donna
Moreau, Lisa A.
Winter, Stuart S.
Larson, Richard
Zhang, Jianhua
Protopopov, Alexei
Chin, Lynda
Pandolfi, Pier Paolo
Silverman, Lewis B.
Hunger, Stephen P.
Sallan, Stephen E.
Look, A. Thomas
TI High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute
lymphoblastic leukemia
SO BLOOD
LA English
DT Article
ID HUMAN CANCERS; MUTATIONS; GENE; PATHWAY; RESISTANCE; ONCOGENE; THERAPY;
NOTCH1; TUMORS
AB To more comprehensively assess the pathogenic contribution of the PTEN-PI3K-AKT pathway to T-cell acute lymphoblastic leukemia (T-ALL), we examined diagnostic DNA samples from children with T-ALL using array comparative genomic hybridization and sequence analysis. Alterations of PTEN, PI3K, or AKT were identified in 47.7% of 44 cases. There was a striking clustering of PTEN mutations in exon 7 in 12 cases, all of which were predicted to truncate the C2 domain without disrupting the phosphatase domain of PTEN. Induction chemotherapy failed to induce remission in 3 of the 4 patients whose lymphoblasts harbored PTEN deletions at the time of diagnosis, compared with none of the 12 patients with mutations of PTEN exon 7 (P = .007), suggesting that PTEN deletion has more adverse therapeutic consequences than mutational disruptions that preserve the phosphatase domain. These findings add significant support to the rationale for the development of therapies targeting the PTEN-PI3K-AKT pathway in T-ALL. (Blood. 2009; 114: 647-650)
C1 [Gutierrez, Alejandro; Sanda, Takaomi; Grebliunaite, Ruta; Ahn, Yebin; Moreau, Lisa A.; Silverman, Lewis B.; Sallan, Stephen E.; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Gutierrez, Alejandro; Silverman, Lewis B.; Sallan, Stephen E.; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Carracedo, Arkaitz; Salmena, Leonardo; Pandolfi, Pier Paolo] Beth Israel Deaconess Canc Ctr, Canc Genet Program, Boston, MA USA.
[Dahlberg, Suzanne; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Winter, Stuart S.] Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA.
[Winter, Stuart S.] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA.
[Zhang, Jianhua; Protopopov, Alexei; Chin, Lynda] Belfer Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA USA.
[Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hunger, Stephen P.] Univ Colorado, Sch Med, Aurora, CO USA.
[Hunger, Stephen P.] Childrens Hosp, Ctr Canc & Blood Disorders, Aurora, CO USA.
RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM Thomas_look@dfci.harvard.edu
RI Carracedo, Arkaitz/F-7029-2011;
OI Carracedo, Arkaitz/0000-0001-5957-1260; Gutierrez,
Alejandro/0000-0002-0249-9007; Larson, Richard/0000-0001-9168-3203
FU National Institutes of Health [5P01CA68484, 1K08CA133103]; Community
Foundation of the National Capital Region; Children's Oncology Group
[CA98543, CA114766]; William Lawrence Foundation; American Society of
Hematology-Amos Medical Faculty Development program; University of
Colorado; Center for Applied Cancer Science
FX This work was supported by the National Institutes of Health (grant
5P01CA68484; S. E. S., A. T. L.) and by an award from the Wine Advocate
Fund for Philanthropy of the Community Foundation of the National
Capital Region. Children's Oncology Group cell banking and sample
distribution were supported by the Children's Oncology Group 9900 cell
biology study and grants CA98543 and CA114766. A. G. is supported by the
William Lawrence Foundation, the American Society of Hematology-Amos
Medical Faculty Development program, and by the National Institutes of
Health (grant 1K08CA133103). S. P. H. is the Ergen Family Chair in
Pediatric Cancer at the University of Colorado. The array CGH analyses
were performed and supported in part by the Center for Applied Cancer
Science of the Robert A. and Renee
NR 23
TC 203
Z9 208
U1 5
U2 15
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 JUL 16
PY 2009
VL 114
IS 3
BP 647
EP 650
DI 10.1182/blood-2009-02-206722
PG 4
WC Hematology
SC Hematology
GA 471ML
UT WOS:000268061800025
PM 19458356
ER
PT J
AU Patterson, TF
Mackool, BT
Gilman, MD
Piris, A
AF Patterson, Thomas F.
Mackool, Bonnie T.
Gilman, Matthew D.
Piris, Adriano
TI A Man with Skin and Pulmonary Lesions after Bone Marrow Transplantation
Disseminated fusarium infection involving the lungs and skin
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article; Proceedings Paper
CT Annual Conference on Infectious Diseases of Adults
CY APR 16, 2008
CL Boston, MA
ID INVASIVE FUNGAL-INFECTIONS; CARE CANCER CENTER; HEMATOLOGIC
MALIGNANCIES; NEUTROPENIC PATIENTS; RISK-FACTORS; ASPERGILLOSIS;
EPIDEMIOLOGY; ZYGOMYCOSIS; EXPERIENCE; MANAGEMENT
C1 [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, San Antonio, TX 78229 USA.
[Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Mackool, Bonnie T.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Gilman, Matthew D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Piris, Adriano] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Patterson, TF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, San Antonio, TX 78229 USA.
NR 26
TC 7
Z9 7
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 16
PY 2009
VL 361
IS 3
BP 287
EP 296
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 470LL
UT WOS:000267976100012
PM 19605834
ER
PT J
AU Zahid, M
Good, CB
Singla, I
Sonel, AF
AF Zahid, Maliha
Good, Chester B.
Singla, Ish
Sonel, Ali F.
TI Clinical Significance of Borderline Elevated Troponin I Levels Across
Different Assays in Patients With Suspected Acute Coronary Syndrome
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CARDIAC TROPONIN; MYOCARDIAL-INFARCTION; MORTALITY; RISK; TERM
AB We aimed to elucidate the clinical significance of borderline troponin I (TnI) increases and see if such increases are of similar significance across different assays. Markedly increased TnI is a strong predictor of adverse cardiac events. It is not clear if borderline increases with different commercially available TnI assays provide similar prognostic information. From January 2001 to February 2004, 3 different TnI assays (Beckman Access TnI, Beckman Access AccuTnI, and Vitros ECI Troponin) were used to evaluate the peak TO value in 1,152 consecutive patients admitted with suspected acute coronary syndrome/non-ST-elevation myocardial infarction (MI). Recommended cutoffs were used to differentiate borderline from marked increases reported as consistent with MI. Clinical data and 30-day death/new MIs were determined by chart abstraction. Demographics and cardiac risk factors were similar for the 3 groups. Frequency of borderline TnI ranged widely among assays (18.7% to 42.1%) but was significantly less with the Vitros ECI Troponin assay (p < 0.0001). Prognostic significance of borderline increased TnI values also varied greatly by assay, with borderline Beckman Access AccuTnI increases being predictive of adverse 30-day outcomes (odds ratio 4.0, 95% confidence interval 1.46 to 10.97, p = 0.007), but not with the other 2 assays. Borderline increases were significantly associated with chronic renal insufficiency (CRI; serum creatine > 1.5); the relation to adverse 30-day outcomes and borderline increases persisted after correcting for CRI in a multivariate logistic regression model. In conclusion, although borderline increased TnI levels are common and significantly associated with CRI, they do not all portend the same clinical prognosis. This study highlights the need for standardization of TnI levels across different assays. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;104:164-168)
C1 [Zahid, Maliha; Good, Chester B.; Singla, Ish; Sonel, Ali F.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Good, Chester B.; Sonel, Ali F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Good, Chester B.; Sonel, Ali F.] Ctr Healthy Equ & Res Promot, Pittsburgh, PA USA.
RP Zahid, M (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA.
EM maz7@pitt.edu
NR 11
TC 10
Z9 10
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 JUL 15
PY 2009
VL 104
IS 2
BP 164
EP 168
DI 10.1016/j.amjcard.2009.03.012
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 477TB
UT WOS:000268540500003
PM 19576340
ER
PT J
AU Melloni, C
Alexander, KP
Ou, FS
LaPointe, NMA
Roe, MT
Newby, LK
Baloch, K
Ho, PM
Rumsfeld, JS
Peterson, ED
AF Melloni, Chiara
Alexander, Karen P.
Ou, Fang-Shu
LaPointe, Nancy M. Allen
Roe, Matthew T.
Newby, L. Kristin
Baloch, Khaula
Ho, P. Michael
Rumsfeld, John S.
Peterson, Eric D.
TI Predictors of Early Discontinuation of Evidence-Based Medicine After
Acute Coronary Syndrome
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; MEDICATION ADHERENCE; PATIENT
COMMUNICATION; SECONDARY PREVENTION; ADVERSE OUTCOMES; ARTERY-DISEASE;
THERAPY; MORTALITY; NONADHERENCE; ASSOCIATION
AB Use of evidence-based medicine (EBM) improves outcomes after acute coronary syndromes (ACS), yet patients often discontinue prescribed therapies after discharge. Although such discontinuation is well documented, patients' reasons for medication discontinuation have not been reported. MAINTAIN is a longitudinal follow-up registry of CRUSADE/ACTION, which enrolled patients during an ACS hospitalization from January 2006 to September 2007. All discharge medications were obtained from hospital charts. Patients were interviewed by telephone 3 months after discharge to determine if EBM classes prescribed at discharge were continued (aspirin, clopidogrel, beta blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and lipid-lowering medications). If discontinuation occurred, patients were asked if it was with provider knowledge/input or not (self-discontinuation). A multivariable logistic regression model was performed to identify factors associated with self-discontinuation of prescribed EBM. Of the 1,077 patients interviewed, 1,006 (93.4%) were discharged on aspirin, 816 (75.8%) on clopidogrel, 982 (91.2%) on beta blockers, 745 (69.2%) on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 968 (89.9%) on lipid-lowering medications. At 3-month follow-up, 304 patients (28.2%) had discontinued >= 1 of these prescribed EBM classes. Although many reported provider involvement, most discontinuation (61.5%) was self-determined. Factors independently associated with self-discontinuation were no pharmacy coinsurance, increasing number of medications, not using reminder tools (e.g., pillbox), lower education, and dialysis. In conclusion, 1/3 of patients with ACS discontinue >= 1 of their prescribed EBMs within 3 months of hospital discharge, and most of this discontinuation is without provider involvement. Patient education, better prescription drug coverage, and reminder strategies may improve use of EBMs at 3 months after discharge from ACS admission. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;104:175-181)
C1 [Melloni, Chiara; Alexander, Karen P.; Ou, Fang-Shu; Roe, Matthew T.; Newby, L. Kristin; Baloch, Khaula; Peterson, Eric D.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
[Melloni, Chiara; Alexander, Karen P.; Ou, Fang-Shu; Roe, Matthew T.; Newby, L. Kristin; Baloch, Khaula; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA.
[LaPointe, Nancy M. Allen] Duke Univ, Med Ctr, Div Clin Pharmacol, Durham, NC 27710 USA.
[Ho, P. Michael; Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Ho, P. Michael; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
RP Melloni, C (reprint author), Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
EM mello004@mc.duke.edu
FU Bristol-Myers Squibb/Sanoti-Aventis Pharmaceuticals; Merck
Schering-Plough Pharmaceutical
FX MAINTAIN is funded by Bristol-Myers Squibb/Sanoti-Aventis
Pharmaceuticals partnership and by Merck Schering-Plough Pharmaceutical.
NR 28
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Z9 56
U1 0
U2 4
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 15
PY 2009
VL 104
IS 2
BP 175
EP 181
DI 10.1016/j.amjcard.2009.03.013
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 477TB
UT WOS:000268540500005
PM 19576342
ER
PT J
AU Dhaliwal, AS
Habib, G
Deswal, A
Verduzco, M
Souchek, J
Ramasubbu, K
Aguilar, D
Ma, TS
Jneid, HM
Bolos, M
Bozkurt, B
AF Dhaliwal, Amandeep S.
Habib, Gabriel
Deswal, Anita
Verduzco, Melinda
Souchek, Julianne
Ramasubbu, Kumudha
Aguilar, David
Ma, Tony S.
Jneid, Hani M.
Bolos, Mariana
Bozkurt, Biykem
TI Impact of Alpha 1-Adrenergic Antagonist Use for Benign Prostatic
Hypertrophy on Outcomes in Patients With Heart Failure
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LEFT-VENTRICULAR DYSFUNCTION; DOUBLE-BLIND; ALPHA(1)-ADRENERGIC
RECEPTORS; PLASMA NOREPINEPHRINE; HYPERTENSIVE PATIENTS;
ALPHA-ADRENOCEPTOR; PRAZOSIN THERAPY; CARVEDILOL; DOXAZOSIN; TRIAL
AB Previous clinical trials have shown that alpha(1)-adrenergic antagonists are not effective in subjects with heart failure (HF) and might increase HF rates when used for hypertension. However, alpha(1)-adrenergic antagonists may be prescribed to subjects with HF who have symptomatic benign prostatic hyperplasia. We sought to determine any association between alpha(1)-adrenergic antagonist use, commonly prescribed for benign prostatic hyperplasia, and the clinical outcomes of subjects with HF receiving contemporary therapy. An existing database of 388 subjects with decompensated HF admissions from 2002 to 2004 at the Veterans Affairs Hospital was analyzed according to the use of alpha(1)-adrenergic antagonists at discharge. Covariate-adjusted Cox proportional hazard models were used to examine any association with future admissions for decompensated HF and total mortality. Alpha-1-adrenergic antagonist therapy was prescribed in 25% of our HF population, predominantly for benign prostatic hyperplasia, and was not associated with significant increases in the combined risk of all-cause mortality and rehospitalization for HF (hazard ratio 1.24, 95% confidence interval 0.93 to 1.65, p = 0.14), HF hospitalization (hazard ratio 1.20, 95% confidence interval 0.85 to 1.70, p 0.31), or all-cause mortality (hazard ratio 1.10, 95% confidence interval 0.78 to 1.56, p 0.57). In patients not receiving beta-blocker therapy, alpha(1)-adrenergic antagonist therapy was significantly associated with increased HF hospitalizations (hazard ratio 1.94, 95% confidence interval 1.14 to 3.32, p = 0.015). In conclusion, in patients with chronic HF, the use of alpha(1)-adrenergic antagonists was significantly associated with more HF hospitalizations when prescribed without concomitant beta blockade. Thus, background beta-blocker therapy appears to be protective against the potential harmful effects of alpha(1)-adrenergic antagonist therapy in patients with HF. Published by Elsevier Inc. (Am J Cardiol 2009;104:270-275)
C1 [Dhaliwal, Amandeep S.; Habib, Gabriel; Deswal, Anita; Verduzco, Melinda; Souchek, Julianne; Ramasubbu, Kumudha; Ma, Tony S.; Jneid, Hani M.; Bozkurt, Biykem] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Cardiol Sect, Houston, TX USA.
[Deswal, Anita; Ramasubbu, Kumudha; Aguilar, David; Bolos, Mariana; Bozkurt, Biykem] Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA.
RP Bozkurt, B (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Cardiol Sect, Houston, TX USA.
EM bbozkurt@bcm.tmc.edu
FU Veterans Affairs Medical Research Service; National Institutes of
Health, Bethesda, Maryland [NIH-K12]
FX Dr. Bozkurt is a recipient of a Merit Entry Level grant support from the
Veterans Affairs Medical Research Service. Dr. Aguilar is a recipient of
the Mentored Clinical Scientist Development Program (NIH-K12 Award)
award from the National Institutes of Health, Bethesda, Maryland.
NR 29
TC 7
Z9 10
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 JUL 15
PY 2009
VL 104
IS 2
BP 270
EP 275
DI 10.1016/j.amjcard.2009.03.030
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 477TB
UT WOS:000268540500022
PM 19576359
ER
PT J
AU Jensen, JK
Atar, D
Kristensen, SR
Mickley, H
Januzzi, JL
AF Jensen, Jesper K.
Atar, Dan
Kristensen, Soren R.
Mickley, Hans
Januzzi, James L., Jr.
TI Usefulness of Natriuretic Peptide Testing for Long-Term Risk Assessment
Following Acute Ischemic Stroke
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID HEART-FAILURE; PROGNOSTIC VALUE; PLASMA-LEVELS; NT-PROBNP; MORTALITY;
TRIAL; DISEASE; DIAGNOSIS; SUBTYPES; TIME
AB Acute-phase levels of B-type natriuretic peptide (BNP) and the N-terminal fragment of the BNP prohormone (NT-pro-BNP) have been associated with mortality when measured in patients with an acute ischemic stroke; however, data regarding the longer-term value of NT-pro-BNP for long-term prognostication after ischemic stroke are limited. Two hundred sixteen patients (mean age 67 +/- 13 years) with acute ischemic stroke were seen 6 months after index admission at which time a structured evaluation including measurement of plasma NT-pro-BNP was performed. Patients were followed for 45 months, with all-cause mortality as the clinical end point. Median NT-pro-BNP concentration for the entire group was 147 pg/ml (10th to 90th percentiles 37 to 869). At follow-up 45 patients (21%) had died. NT-pro-BNP concentrations were significantly higher in decedents (308 pg/ml, 10th to 90th percentiles 74 to 2,279) than in the 171 survivors (132 pg/ml, 10th to 90th percentiles 35 to 570, p < 0.001). Patients with NT-pro-BNP <= 147 pg/ml had a significantly improved survival rate on univariate analysis (p < 0.001). In multivariate analysis after adjustment for age, stroke severity, heart and renal failures, levels of NT-pro-BNP were an independent predictor of mortality > 6 months after stroke (adjusted hazard ratio 1.5, 95% confidence interval 1.1 to 1.9, p = 0.005). In conclusion, NT-pro-BNP concentrations measured during the stable phase after acute ischemic stroke are strongly predictive of long-term mortality. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;104:287-291)
C1 [Jensen, Jesper K.; Mickley, Hans] Odense Univ Hosp, Dept Cardiol, DK-5000 Odense, Denmark.
[Atar, Dan] Aarhus Univ Hosp, Aalborg Hosp, Cardiovasc Res Ctr, Dept Clin Biochem, Aalborg, Denmark.
[Kristensen, Soren R.] Univ Oslo, Aker Univ Hosp, Div Cardiol, Oslo, Norway.
[Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Jensen, JK (reprint author), Odense Univ Hosp, Dept Cardiol, DK-5000 Odense, Denmark.
EM jesperkjensen@dadlnet.dk
RI Kristensen, Soren/D-4440-2013
OI Kristensen, Soren/0000-0002-2649-506X
FU Klinisk Institut at Odense University Hospital, Odense, Denmark; Novo
Nordisk Foundation, Copenhagen, Denmark; Danish Heart Foundation
FX This study was supported by a grant front the Klinisk Institut at Odense
University Hospital, Odense, Denmark, and the Novo Nordisk Foundation,
Copenhagen, Denmark. Dr. Jensen was supported by a grant from the Danish
Heart Foundation.
NR 28
TC 17
Z9 19
U1 0
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 15
PY 2009
VL 104
IS 2
BP 287
EP 291
DI 10.1016/j.amjcard.2009.03.029
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 477TB
UT WOS:000268540500025
PM 19576362
ER
PT J
AU Hernandez, JO
Norstrom, J
Wysock, G
AF Hernandez, Jovino Ocasio
Norstrom, Jeni
Wysock, Glenn
TI Acyclovir-induced renal failure in an obese patient
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
DE Acyclovir; Antivirals; Doxycycline; Kidney failure; Moxifloxacin;
Obesity; Toxicity
ID INTRAVENOUS ACYCLOVIR; NEPHROTOXICITY
AB Purpose. A case of acyclovir-induced acute renal failure in an obese patient is described.
Summary. A 60-year-old white man arrived at the emergency department complaining of confusion and disorientation. He was 5 ft 7 in tall and weighed 108.9 kg. His medical and surgical histories included chronic obstructive pulmonary disease (COPD), sleep apnea not requiring biphasic positive airway pressure, obesity, oxygen supplementation, and appendectomy. He also had a history of cyst drainage on the back of his neck, with recent drainage emitting a foul odor, and suffered recurrent herpes cold sores on his chin. A lumbar puncture revealed abnormal cerebral spinal fluid. A diagnosis of herpes encephalitis was considered, and the patient was empirically treated with i.v. acyclovir 1 g over 60 minutes every eight hours, with the dosage based on actual body weight. He was also given moxifloxacin 400 mg i.v. daily for possible COPD exacerbation and doxycycline 100 mg i.v. twice daily for possible leptospirosis meningitis. On hospital day 3, his serum creatinine (SCr) and blood urea nitrogen (BUN) concentrations rose to 2.8 g/dL and 32 mg/dL, respectively. Acyclovir was subsequently discontinued, as were all i.v. antibiotics. On day 7, hydration therapy was initiated, as was therapy to alkalinize the urine, and his neurologic status began to improve. At discharge, the patient's SCr and BUN levels were 3.1 g/dL and 38 mg/dL, respectively. His discharge diagnoses included encephalitis with possible viral origin and acyclovir-induced nephrotoxicity.
Conclusion. An obese man receiving excessive doses of i.v. acyclovir developed acute but reversible renal failure.
C1 [Hernandez, Jovino Ocasio] Winter Haven Hosp, Serv Pharm, Winter Haven, FL 33881 USA.
[Norstrom, Jeni] VA Boston Healthcare Syst, Boston, MA USA.
[Norstrom, Jeni] Univ Florida, Sch Pharm, Gainesville, FL USA.
RP Hernandez, JO (reprint author), Winter Haven Hosp, Serv Pharm, 200 Ave F NE, Winter Haven, FL 33881 USA.
EM jovino.hernandez@mfms.com
NR 22
TC 8
Z9 8
U1 2
U2 2
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD JUL 15
PY 2009
VL 66
IS 14
BP 1288
EP 1291
DI 10.2146/ajhp080307
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 467UW
UT WOS:000267769600015
PM 19574603
ER
PT J
AU Hung, WW
Wisnivesky, JP
Siu, AL
Ross, JS
AF Hung, William W.
Wisnivesky, Juan P.
Siu, Albert L.
Ross, Joseph S.
TI Cognitive Decline among Patients with Chronic Obstructive Pulmonary
Disease
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE chronic obstructive pulmonary disease; cognitive impairment;
longitudinal survey
ID IMPAIRMENT; DEFICITS; COPD
AB Rationale: Prior research has suggested an association between chronic obstructive pulmonary disease (COPD) and the development of cognitive decline; however, these studies have been cross-sectional or small case series.
Objectives: To determine whether COPD increases the risk of cognitive decline among older adults surveyed in a large, population-based longitudinal cohort.
Methods: We included data from the 1996 to 2002 waves of the Health and Retirement Study, a biennial nationally representative survey. We studied respondents who completed cognitive testing in 1996 and at least one subsequent survey, and excluded those with unknown history of COPD. Clinical history of COPD was based on self-report; severity was categorized based on use of oxygen or disease-related activity limitations. Our primary outcome was cognitive performance, measured using a validated 35-point scale. We examined the effect of COPD on cognition using multivariable mixed linear models accounting for repeated measurements, adjusted for sociodemographic and clinical characteristics.
Measurements and Main Results: A total of 4,150 adults were included in our study. Among them, 12% reported a history of COPD (29% severe, 71% nonsevere disease). On repeated measurement, mean cognition scores of older adults with both severe and nonsevere COPD were significantly lower when compared with adults without COPD (2.6 points [P < 0.001] and 0.9 points [P < 0,001], respectively). After multivariable adjustment, mean scores of adults with severe COPD remained lower (0.9 point [P < 0.001]), whereas mean score of adults with nonsevere COPD was no longer different (P = 0.39) when compared with adults without COPD.
Conclusions. Severe COPD was associated with lower cognitive performance on standardized measurement over time.
C1 [Hung, William W.; Siu, Albert L.; Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA.
[Wisnivesky, Juan P.] Mt Sinai Sch Med, Dept Med, Div Gen Internal Med, New York, NY 10029 USA.
[Wisnivesky, Juan P.] Mt Sinai Sch Med, Dept Med, Div Pulm Crit Care & Sleep Med, New York, NY 10029 USA.
[Hung, William W.; Siu, Albert L.; Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
[Hung, William W.; Siu, Albert L.; Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Hlth Serv Res & Dev, Serv Res Enhancement Award Program, Bronx, NY USA.
RP Hung, WW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA.
EM william.hung@mssm.edu
NR 23
TC 57
Z9 61
U1 0
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUL 15
PY 2009
VL 180
IS 2
BP 134
EP 137
DI 10.1164/rccm.200902-0276OC
PG 4
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 472EP
UT WOS:000268112500007
PM 19423714
ER
PT J
AU Wong, K
Lyddon, R
Dracheva, S
AF Wong, Kevin
Lyddon, Rebecca
Dracheva, Stella
TI TaqMan-based, real-time quantitative polymerase chain reaction method
for RNA editing analysis
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE RNA editing; GluR5; Multiplex qPCR; Taqman
ID SEROTONIN 2C RECEPTOR; PCR DATA-ANALYSIS; MESSENGER-RNA; ADENOSINE;
TRANSMISSION; DEAMINASES; MECHANISM; CORTEX; GLUR2; BRAIN
AB Abnormal adenosine to inosine (A-to-1) messenger RNA (mRNA) editing has been linked to several disease states afflicting the central nervous system. Here we report an assay to determine RNA editing frequencies at specific sites that is based on quantitative polymerase chain reaction (qPCR) with TaqMan probes. The assay was tested by measuring the frequency of the A-to-1 mRNA editing at the Q/R site of the human kainate receptor Subunit GluR5 and was compared with two established methods of assessing RNA editing: sequencing of individual clones and restriction analysis. The qPCR assay displayed high sensitivity and reproducibility, demonstrated exceptional discrimination between edited and Unedited transcript variants, and proved to have several advantages over the other editing methods. Due to the fact that TaqMan-based qPCR technology can be easily adapted to different editing targets, the increased capabilities afforded by this new technique should facilitate various RNA editing studies that aim to elucidate the role of this process in normal physiology and in disease. Published by Elsevier Inc. Published by Elsevier Inc.
C1 [Wong, Kevin; Dracheva, Stella] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA.
[Lyddon, Rebecca; Dracheva, Stella] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
RP Dracheva, S (reprint author), Bronx VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM stella.dracheva@mssm.edu
FU VA Merit award; American Foundation for Suicide Prevention; VISN3 Mental
Illness Research and Education Clinical Center (MIRECC)
FX Postmortem brain tissue was donated by the Stanley Medical Research
Institute's array Collection Courtesy of Michael B. Knable, E. Fuller
Torrey, Maree J Webster, and Robert H. Yolken. This Study was supported
by a VA Merit award (S.D.), a grant from the American Foundation for
Suicide Prevention (S.D.), and the VISN3 Mental Illness Research and
Education Clinical Center (MIRECC).
NR 28
TC 6
Z9 6
U1 2
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD JUL 15
PY 2009
VL 390
IS 2
BP 173
EP 180
DI 10.1016/j.ab.2009.04.011
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 457QB
UT WOS:000266946000011
PM 19371717
ER
PT J
AU Daniel, KD
Kim, GY
Vassiliou, CC
Galindo, M
Guimaraes, AR
Weissleder, R
Charest, A
Langer, R
Cima, MJ
AF Daniel, Karen D.
Kim, Grace Y.
Vassiliou, Christophoros C.
Galindo, Marilyn
Guimaraes, Alexander R.
Weissleder, Ralph
Charest, Al
Langer, Robert
Cima, Michael J.
TI Implantable diagnostic device for cancer monitoring
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Magnetic nanoparticle; Cancer biomarker; In vivo sensor; Human chorionic
gonadotrophin
ID HUMAN CHORIONIC-GONADOTROPIN; FREE BETA-SUBUNIT; PARATHYROID-HORMONE;
SERUM; NANOPARTICLES; RECURRENCE; BIOMARKERS; ACCURACY; ASCITES; MARKERS
AB Biopsies provide required information to diagnose cancer but, because of their invasiveness, they are difficult to use for managing cancer therapy. The ability to repeatedly sample the local environment for tumor biomarker, chemotherapeutic agent, and tumor metabolite concentrations could improve early detection of metastasis and personalized therapy. Here we describe an implantable diagnostic device that senses the local in vivo environment. This device, which could be left behind during biopsy, uses a semi-permeable membrane to contain nanoparticle magnetic relaxation switches. A cell line secreting a model cancer biomarker produced ectopic tumors in mice. The transverse relaxation time (T(2)) of devices in tumor-bearing mice was 20 +/- 10% lower than devices in control mice after 1 day by magnetic resonance imaging (p < 0.01). Short term applications for this device are numerous, including verification of successful tumor resection. This may represent the first continuous monitoring device for soluble cancer biomarkers; in vivo. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Kim, Grace Y.; Cima, Michael J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
[Langer, Robert; Cima, Michael J.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Langer, Robert] MIT, Div Biol Engn, Cambridge, MA 02139 USA.
[Charest, Al] Tufts Med Ctr, Dept Neurosurg, Boston, MA USA.
[Charest, Al] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Charest, Al] MIT, Ctr Canc Res, Cambridge, MA 02139 USA.
[Guimaraes, Alexander R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Guimaraes, Alexander R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA.
[Vassiliou, Christophoros C.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Kim, Grace Y.; Langer, Robert] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA.
[Daniel, Karen D.; Galindo, Marilyn; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
RP Cima, MJ (reprint author), MIT, Dept Mat Sci & Engn, 77 Massachusetts Ave,Room 12-011, Cambridge, MA 02139 USA.
EM mjcima@mit.edu
FU NCI Centers of Cancer Nanotechnology Excellence [5 U54 CA119349-12]; NSF
Division of Materials Research Award [0746264]
FX This work was supported by NCI Centers of Cancer Nanotechnology
Excellence No. 5 U54 CA119349-12 grant and NSF Division of Materials
Research Award No. 0746264. We would like to acknowledge Stephen
Woolfenden for assistance with in vivo studies and Lee Josephson at CMIR
for assistance with MRSw.
NR 28
TC 27
Z9 28
U1 0
U2 26
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD JUL 15
PY 2009
VL 24
IS 11
BP 3252
EP 3257
DI 10.1016/j.bios.2009.04.010
PG 6
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA 465IY
UT WOS:000267577900012
PM 19442510
ER
PT J
AU Fujiwara, N
Murata, Y
Arai, K
Egi, Y
Lu, J
Wu, O
Singhal, AB
Lo, EH
AF Fujiwara, Norio
Murata, Yoshihiro
Arai, Ken
Egi, Yasuhiro
Lu, Jie
Wu, Ona
Singhal, Aneesh B.
Lo, Eng H.
TI Combination therapy with normobaric oxygen (NBO) plus thrombolysis in
experimental ischemic stroke
SO BMC NEUROSCIENCE
LA English
DT Article
ID FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; HYPERBARIC
OXYGENATION; TIME WINDOW; RAT MODEL; HYPEROXIA; BRAIN; NEUROPROTECTION;
REPERFUSION; FUTURE
AB Background: The widespread use of tissue plasminogen activator (tPA), the only FDA-approved acute stroke treatment, remains limited by its narrow therapeutic time window and related risks of brain hemorrhage. Normobaric oxygen therapy (NBO) may be a useful physiological strategy that slows down the process of cerebral infarction, thus potentially allowing for delayed or more effective thrombolysis. In this study we investigated the effects of NBO started simultaneously with intravenous tPA, in spontaneously hypertensive rats subjected to embolic middle cerebral artery (MCA) stroke. After homologous clot injection, animals were randomized into different treatment groups: saline injected at 1 hour; tPA at 1 hour; saline at 1 hour plus NBO; tPA at 1 hour plus NBO. NBO was maintained for 3 hours. Infarct volume, brain swelling and hemorrhagic transformation were quantified at 24 hours. Outcome assessments were blinded to therapy.
Results: Upon clot injection, cerebral perfusion in the MCA territory dropped below 20% of pre-ischemic baselines. Both tPA-treated groups showed effective thrombolysis (perfusion restored to nearly 100%) and smaller infarct volumes (379 +/- 57 mm(3) saline controls; 309 +/- 58 mm(3) NBO; 201 +/- 78 mm(3) tPA; 138 +/- 30 mm(3) tPA plus NBO), showing that tPA-induced reperfusion salvages ischemic tissue and that NBO does not significantly alter this neuroprotective effect. NBO had no significant effect on hemorrhagic conversion, brain swelling, or mortality.
Conclusion: NBO can be safely co-administered with tPA. The efficacy of tPA thrombolysis is not affected and there is no induction of brain hemorrhage or edema. These experimental results require clinical confirmation.
C1 [Singhal, Aneesh B.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Neuroprotect Res Lab, Boston, MA 02115 USA.
[Fujiwara, Norio; Murata, Yoshihiro; Arai, Ken; Egi, Yasuhiro; Lu, Jie; Wu, Ona; Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Neuroprotect Res Lab, Boston, MA 02115 USA.
RP Singhal, AB (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Neuroprotect Res Lab, Boston, MA 02115 USA.
EM nfujiwara@partners.org; asinghal2@gmail.com; karai@partners.org;
yasu.egi@gmail.com; lucy_lj1124@yahoo.com; onawu@partners.org;
asinghal@partners.org; Lo@helix.mgh.harvard.edu
FU NIH [R01-NS51412, P50-NS51343, P50-NS10828, R01-NS48422, R01-NS56458,
R37-NS37074]
FX The authors gratefully thank Dr. Xiaoying Wang and our SPOTRIAS
co-investigators for helpful discussions. Supported in part by NIH
grants R01-NS51412, P50-NS51343, P50-NS10828, R01-NS48422, R01-NS56458,
and R37-NS37074.
NR 31
TC 26
Z9 28
U1 0
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2202
J9 BMC NEUROSCI
JI BMC Neurosci.
PD JUL 15
PY 2009
VL 10
AR 79
DI 10.1186/1471-2202-10-79
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 480AH
UT WOS:000268703300003
PM 19604385
ER
PT J
AU Saphner, T
Triest-Robertson, S
Li, HL
Holzman, P
AF Saphner, Tom
Triest-Robertson, Shirley
Li, Hailun
Holzman, Paul
TI The Association of Nonalcoholic Steatohepatitis and Tamoxifen in
Patients With Breast Cancer
SO CANCER
LA English
DT Article
DE body mass index; cirrhosis; diabetes; fatty liver disease;
tamoxifen-induced hepatic steatosis; tamoxifen; nonalcoholic
steatohepatitis; NASH; fatty liver disease
ID NON-ALCOHOLIC STEATOHEPATITIS; ADJUVANT TAMOXIFEN; HEPATIC STEATOSIS;
FATTY LIVER; THERAPY; BEZAFIBRATE; CIRRHOSIS; WOMEN; NASH
AB BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver damage that can progress to cirrhosis. NASH is associated with obesity and diabetes. The condition also may be associated with some medications, including tamoxifen. Early case reports and small series have documented NASH in patients who received tamoxifen. METHODS: The records of patients registered in the St. Vincent Hospital Cancer Registry of Green Bay Wisconsin from January 1, 1992 to December 31, 2000 were reviewed. RESULTS: In total, 1105 patients with breast cancer were evaluated for NASH, and 24 cases of NASH were documented (2.2%). Seven patients had NASH before their diagnosis of breast cancer, and 17 patients developed NASH after their diagnosis of breast cancer. In multivariate analysis, the factors associated with NASH were tamoxifen use (odds ratio [OR], 8.2; 95% confidence interval [CI], 1.06-63.72), body mass index (BMI) (OR, 1.13; 95% CI, 1.06-1.20), and age (OR, 95% CI, 0.91-0.99). NASH improved after tamoxifen was stopped. After discontinuation of tamoxifen, transaminase levels returned to normal in 14 of 16 patients. CONCLUSIONS: NASH was present in 24 of 1105 patients with breast cancer (2.2%). Seven patients had NASH before they were diagnosed with breast cancer, and 17 patients developed NASH after their diagnosis. NASH was associated with the use of tamoxifen and improved when tamoxifen was stopped. Cancer 2009;115:3189-95. (C) 2009 American Cancer Society.
C1 [Saphner, Tom] St Marys Hosp, Dept Oncol, Green Bay, WI USA.
[Triest-Robertson, Shirley] St Vincents Hosp, Dept Oncol, Green Bay, WI USA.
[Li, Hailun] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Holzman, Paul] St Marys Hosp, Dept Pathol, Green Bay, WI USA.
RP Saphner, T (reprint author), Green Bay Oncol, POB 13453, Green Bay, WI 54307 USA.
EM tsaphner@gboncology.com
NR 36
TC 25
Z9 29
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 JUL 15
PY 2009
VL 115
IS 14
BP 3189
EP 3195
DI 10.1002/cncr.24374
PG 7
WC Oncology
SC Oncology
GA 468JM
UT WOS:000267813700006
PM 19484789
ER
PT J
AU Donelan, K
Hobrecker, K
Schapira, L
Mailhot, JR
Goulart, BH
Chabner, BA
AF Donelan, Karen
Hobrecker, Karin
Schapira, Lidia
Mailhot, Johanna R.
Goulart, Bernardo H.
Chabner, Bruce A.
TI Medical Interpreter Knowledge of Cancer and Cancer Clinical Trials
SO CANCER
LA English
DT Article
DE cancer; clinical trials; disparities; limited English proficiency
ID CARE; COMMUNICATION; SERVICES
AB BACKGROUND: Cancer patients with limited English proficiency may need specialized assistance to communicate with health professionals about cancer and clinical trials. METHODS: Medical interpreters working in several Boston-area hospitals were invited to participate in training sessions about cancer and cancer clinical trials. We did a pre and post survey-based assessment of knowledge of basic concepts in cancer and clinical trials, and post assessment of satisfaction, among 97 interpreters in cancer training and education sessions and 79 participants in clinical trial training and education sessions. RESULTS: Participants had a range of prior experience with interpretation in the context of cancer and clinical trials. Training increased mean accuracy from 49% to 72% in knowledge items about cancer, and from 72% to 78% in knowledge about clinical trials. Interpreters reported several areas of concern with respect to standards of practice. CONCLUSIONS: Pretest surveys of medical interpreters revealed several areas of important knowledge gaps about cancer and clinical trials. Posttest assessment showed that training can be useful to improving short-term accuracy, but that more work is needed to develop curricula and testing measures to address these knowledge gaps. Cancer 2009;115:3283-92. (C) 2009 American Cancer Society.
C1 [Donelan, Karen] Massachusetts Gen Hosp, Inst Technol Assessment, Patient Care Serv, Boston, MA 02114 USA.
[Donelan, Karen; Mailhot, Johanna R.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Schapira, Lidia; Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Goulart, Bernardo H.] Univ Washington, Div Hematol, Med Ctr, Seattle, WA 98195 USA.
RP Donelan, K (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Patient Care Serv, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM kdonelan@partners.org
FU National Cancer Institute award to Massachusetts General Hospital [5 R21
CA101712-02]
FX Funding for interpreter participation in training sessions was provided
by the National Cancer Institute award to Massachusetts General
Hospital, 5 R21 CA101712-02 (Bruce A Chabner, principal Investigator).
NR 24
TC 5
Z9 5
U1 2
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD JUL 15
PY 2009
VL 115
IS 14
BP 3283
EP 3292
DI 10.1002/cncr.24377
PG 10
WC Oncology
SC Oncology
GA 468JM
UT WOS:000267813700016
PM 19484791
ER
PT J
AU Mack, JW
Block, SD
Nilsson, M
Wright, A
Trice, E
Friedlander, R
Paulk, E
Prigerson, HG
AF Mack, Jennifer W.
Block, Susan D.
Nilsson, Matthew
Wright, Alexi
Trice, Elizabeth
Friedlander, Robert
Paulk, Elizabeth
Prigerson, Holly G.
TI Measuring Therapeutic Alliance Between Oncologists and Patients With
Advanced Cancer The Human Connection Scale
SO CANCER
LA English
DT Article
DE end-of-life care; health-related quality of life; patient-physician
relationship; peaceful acceptance; terminal illness; trust
ID QUALITY-OF-LIFE; PALLIATIVE CARE; COMMUNICATION-SKILLS; TERMINAL
ILLNESS; WORKING ALLIANCE; DYING PATIENTS; END; PERSPECTIVES; PROGNOSIS;
DISEASE
AB BACKGROUND: Patients consider their human connection with a physician an important aspect of end-of-life (EOL) care. In this study, the authors sought to develop and validate a measure of therapeutic alliance between patients with advanced cancer and their physicians and to evaluate the effects of therapeutic alliance on EOL experiences and care. METHODS: The Human Connection (THC) scale was developed to measure the extent to which patients felt a sense of mutual understanding, caring, and trust with their physicians. The scale was administered to 217 patients with advanced cancer along with measures of attributes that have been related hypothetically to therapeutic alliance, including emotional acceptance of terminal illness. EOL outcomes in 90 patients who died during the study also were examined. RESULTS: The 16-item THC questionnaire was consistent internally (Cronbach alpha = .90) and valid based on its expected positive association with emotional acceptance of terminal illness (r = .31; P < .0001). THC scores were related inversely to symptom burden (r = -.19; P = .006), functional status (Karnofsky performance status; r = .22; P = .001), and mental illness (THC score: 50.69 for patients with any Diagnostic and Statistical Manual [DSM] diagnosis vs 55.22 for patients with no DSM diagnosis; P = .03). THC scores were not associated significantly with EOL discussions (P = .68). Among the patients who died, EOL intensive care unit (ICU) care was associated inversely with therapeutic alliance (THC score: 46.5 for patients who received ICU care vs 55.5 for patients without ICU care; P = .002), so that patients with higher THC scores were less likely to spend time in the ICU during the last week of life. CONCLUSIONS: The THC scale is a valid and reliable measure of therapeutic alliance between patients with advanced cancer and their physicians. In addition, there was no evidence to suggest that EOL discussions harm patients' therapeutic alliance. A strong therapeutic alliance was associated with emotional acceptance of a terminal illness and with decreased ICU care at the EOL among patients with advanced cancer. Cancer 2009;115:3302-11. (C) 2009 American Cancer Society.
C1 [Mack, Jennifer W.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Mack, Jennifer W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Mack, Jennifer W.] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[Block, Susan D.; Nilsson, Matthew; Wright, Alexi; Trice, Elizabeth; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA.
[Wright, Alexi; Trice, Elizabeth] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Friedlander, Robert] New Hampshire Oncol Hematol PA, Hooksett, NH USA.
[Paulk, Elizabeth] Univ Texas SW Med Ctr Dallas, Palliat Care Serv, Dallas, TX 75390 USA.
RP Mack, JW (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM jennifer_mack@dfci.harvard.edu
FU National Institute of Mental Health [MH63892]; National Cancer Institute
[CA106370]; Center for Psycho-Oncology and Palliative Care Research,
Dana-Farber Cancer Institute; American Cancer Society Mentored Research
Scholar Grant
FX Dr. Mack was Supported by an American Cancer Society Mentored Research
Scholar Grant.
NR 48
TC 45
Z9 45
U1 3
U2 16
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD JUL 15
PY 2009
VL 115
IS 14
BP 3302
EP 3311
DI 10.1002/cncr.24360
PG 10
WC Oncology
SC Oncology
GA 468JM
UT WOS:000267813700018
PM 19484795
ER
PT J
AU Ho-Tin-Noe, B
Goerge, T
Wagner, DD
AF Ho-Tin-Noe, Benoit
Goerge, Tobias
Wagner, Denisa D.
TI Platelets: Guardians of Tumor Vasculature
SO CANCER RESEARCH
LA English
DT Review
ID ENDOTHELIAL INTERACTION; P-SELECTIN; ANGIOGENESIS; HEMORRHAGE; CANCER;
MICROVASCULATURE; THROMBOCYTOPENIA; ANGIOPOIETIN-1; PRESERVATION;
INTEGRITY
AB Solid tumors generate a prothrombotic environment capable of platelet activation. Recent findings indicate that the activated platelets are crucial regulators of tumor vascular homeostasis in that they prevent tumor hemorrhage. Surprisingly, this effect is independent of platelets' capacity to form thrombi and instead relies on the secretion of their granule content. Thus, targeting platelet secretory activities may represent a new approach to specifically destabilize tumor vasculature. [Cancer Res 2009;69(14):5623-6]
C1 [Ho-Tin-Noe, Benoit; Goerge, Tobias; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Ho-Tin-Noe, Benoit; Goerge, Tobias; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Ho-Tin-Noe, Benoit] Hop Xavier Bichat, INSERM, U698, Paris, France.
[Goerge, Tobias] Univ Munster, Dept Dermatol, D-4400 Munster, Germany.
RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA.
EM wagner@idi.harvard.edu
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health [P01 HL066105, R37 HL041002]
FX Grant support: National Heart, Lung, and Blood Institute of the National
Institutes of Health grants P01 HL066105 and R37 HL041002 (to D.D.
Wagner).
NR 31
TC 35
Z9 35
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 JUL 15
PY 2009
VL 69
IS 14
BP 5623
EP 5626
DI 10.1158/0008-5472.CAN-09-1370
PG 4
WC Oncology
SC Oncology
GA 475LJ
UT WOS:000268360300002
PM 19584268
ER
PT J
AU Rebbeck, TR
Mitra, N
Domchek, SM
Wan, F
Chuai, S
Friebel, TM
Panossian, S
Spurdle, A
Chenevix-Trench, G
Singer, CF
Pfeiler, G
Neuhausen, SL
Lynch, HT
Garber, JE
Weitzel, JN
Isaacs, C
Couch, F
Narod, SA
Rubinstein, WS
Tomlinson, GE
Ganz, PA
Olopade, OI
Tung, N
Blum, JL
Greenberg, R
Nathanson, KL
Daly, MB
AF Rebbeck, Timothy R.
Mitra, Nandita
Domchek, Susan M.
Wan, Fei
Chuai, Shannon
Friebel, Tara M.
Panossian, Saarene
Spurdle, Amanda
Chenevix-Trench, Georgia
Singer, Christian F.
Pfeiler, Georg
Neuhausen, Susan L.
Lynch, Henry T.
Garber, Judy E.
Weitzel, Jeffrey N.
Isaacs, Claudine
Couch, Fergus
Narod, Steven A.
Rubinstein, Wendy S.
Tomlinson, Gail E.
Ganz, Patricia A.
Olopade, Olufunmilayo I.
Tung, Nadine
Blum, Joanne L.
Greenberg, Roger
Nathanson, Katherine L.
Daly, Mary B.
CA kConFab
TI Modification of Ovarian Cancer Risk by BRCA1/2-interacting Genes in a
Multicenter Cohort of BRCA1/2 Mutation Carriers
SO CANCER RESEARCH
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISM; MODIFIES BREAST-CANCER; DNA-DAMAGE
RESPONSE; UNKNOWN CLINICAL-SIGNIFICANCE; NBS1 GENE; HAPLOTYPE
FREQUENCIES; SEQUENCE VARIANTS; 657DEL5 MUTATION; FANCONI-ANEMIA; REPAIR
AB Inherited BRCA1/2 mutations confer elevated ovarian cancer risk. Knowledge of factors that can improve ovarian cancer risk assessment in BRCA1/2 mutation carriers is important because no effective early detection for ovarian cancers exists. A cohort of 1,575 BRCA1 and 856 BRCA2 mutation carriers was used to evaluate haplotypes at ATM, BARD1, BRIP1, CTIP, MRE11, NBS1, RAD50, RAD51, and TOPBP1 in ovarian cancer risk. In BRCA1 carriers, no associations were observed with ATM, BARD1, CTIP, RAD50, RAD51, or TOPBP1. At BRIP1, an association was observed for one haplotype with a multiple testing corrected P (P(corr)) = 0.012, although no individual haplotype was significant. At MRE11, statistically significant associations were observed for one haplotype (P(corr) = 0.007). At NBS1, we observed a P(corr) = 0.024 for haplotypes. In BRCA2 carriers, no associations were observed with CTIP, NBS1, RAD50, or TOPBP1. Rare haplotypes at ATM (P(corr) = 0.044) and BARD1 (P(corr) = 0.012) were associated with ovarian cancer risk. At BNP1, two common haplotypes were significantly associated with ovarian cancer risk (P(corr) = 0.011). At MRE11, we observed a significant haplotype association (P(corr) = 0.012). and at RAD51, one common haplotype was significantly associated with ovarian cancer risk (P(corr) = 0.026). Variants in genes that interact biologically with BRCA1 and/or BRCA2 may be associated with modified ovarian cancer risk in women who carry BRCA1/2 mutations. [Cancer Res 2009;69(14):5801-10]
C1 [Rebbeck, Timothy R.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.; Mitra, Nandita; Wan, Fei; Chuai, Shannon; Friebel, Tara M.; Panossian, Saarene] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Domchek, Susan M.; Greenberg, Roger; Nathanson, Katherine L.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Daly, Mary B.] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA.
[Spurdle, Amanda; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Singer, Christian F.; Pfeiler, Georg] Med Univ Vienna, Dept Obstet & Gynaecol, Vienna, Austria.
[Neuhausen, Susan L.] Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA.
[Lynch, Henry T.] Creighton Univ, Dept Med, Omaha, NE 68178 USA.
[Lynch, Henry T.] Creighton Univ, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA.
[Garber, Judy E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Weitzel, Jeffrey N.] City Hope Comprehens Canc Ctr, Duarte, CA USA.
[Isaacs, Claudine] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA.
[Couch, Fergus] Mayo Clin, Coll Med, Rochester, MN USA.
[Narod, Steven A.] Womens Coll Hosp, Toronto, ON M5S 1B2, Canada.
[Rubinstein, Wendy S.] NorthShore Univ HealthSyst, Evanston, IL USA.
[Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA.
[Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA.
[Tomlinson, Gail E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Olopade, Olufunmilayo I.] Univ Chicago, Chicago, IL 60637 USA.
RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Abramson Canc Ctr, 217 Blockley Hall, Philadelphia, PA 19104 USA.
EM rebbeck@mail.med.upenn.edu
RI Spurdle, Amanda/A-4978-2011;
OI Spurdle, Amanda/0000-0003-1337-7897; Nathanson,
Katherine/0000-0002-6740-0901
FU NIH [5UO1 CA86389, R01-CA083855, R01-CA74115, P30-CA51008-19,
R01-CA102776, M01 RR00043]; National Breast Cancer Foundation; National
Health and Medical Research Council; Queensland Cancer Fund; Cancer
Councils of New South Wales, Victoria, Tasmania, and South Australia;
Cancer Foundation of Western Australia
FX Revenue from Nebraska cigarette taxes awarded to Creighton University by
the Nebraska Department of Death and Human Services. NIH grants 5UO1
CA86389 (H.T. Lynch), R01-CA083855 and R01-CA74115 (S.L. Neuhausen),
P30-CA51008-19 (C. Isaacs), and R01-CA102776 and R01-CA083855 (T.R.
Rebbeck) and NIH General Clinical Research Center grant M01 RR00043
awarded to the City of Hope National Medical Center (J.N. Weitzel). The
Kathleen Cunningham Consortium for Research into Familial Breast Cancer
is supported by grants from the National Breast Cancer Foundation, the
National Health and Medical Research Council, the Queensland Cancer
Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and
South Australia, and the Cancer Foundation of Western Australia.
NR 46
TC 21
Z9 21
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 JUL 15
PY 2009
VL 69
IS 14
BP 5801
EP 5810
DI 10.1158/0008-5472.CAN-09-0625
PG 10
WC Oncology
SC Oncology
GA 475LJ
UT WOS:000268360300026
PM 19584272
ER
PT J
AU McMillin, DW
Ooi, M
Delmore, J
Negri, J
Hayden, P
Mitsiades, N
Jakubikova, J
Maira, SM
Garcia-Echeverria, C
Schlossman, R
Munshi, NC
Richardson, PG
Anderson, KC
Mitsiades, CS
AF McMillin, Douglas W.
Ooi, Melissa
Delmore, Jake
Negri, Joseph
Hayden, Patrick
Mitsiades, Nicolas
Jakubikova, Jana
Maira, Sauveur-Michel
Garcia-Echeverria, Carlos
Schlossman, Robert
Munshi, Nikhil C.
Richardson, Paul G.
Anderson, Kenneth C.
Mitsiades, Constantine S.
TI Antimyeloma Activity of the Orally Bioavailable Dual
Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor
NVP-BEZ235
SO CANCER RESEARCH
LA English
DT Article
ID MULTIPLE-MYELOMA CELLS; SET ENRICHMENT ANALYSIS; GENE-EXPRESSION;
THERAPEUTIC APPLICATIONS; IDENTIFICATION; SIGNATURE; GROWTH; CANCER;
ACTIVATION; IDENTIFY
AB The phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway mediates proliferation, survival, and drug resistance in multiple myeloma (MM) cells. Here, we tested the anti-MM activity of NVP-BEZ235 (BEZ235), which inhibits PI3K/Akt/mTOR signaling at the levels of PI3K and mTOR. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric survival assays showed that MM cell lines exhibited dose- and time-dependent decreased viability after exposure to BEZ235 (IC(50), 25-800 nmol/L or 48 hours). MM cells highly sensitive (IC(50), <25 nmol/L) to BEZ235 (e.g., MM.1S, MM.1R, Dox40, and KMS-12-PE) included both lines sensitive and resistant to conventional (dexamethasone, cytotoxic chemotherapeutics) agents. Pharmacologically relevant BEZ235 concentrations (25-400 nmol/L,) induced rapid commitment to and induction of MM.1S and OPM-2 cell death. Furthermore, normal donor peripheral blood mononuclear cells were less sensitive (IC(50), >800 nmol/L) than the majority of MM cell lines tested, suggesting a favorable therapeutic index. In addition, BEZ235 was able to target MM cells in the presence of exogenous interleukin-6, insulin-like growth factor-1, stromal cells, or osteoclasts, which are known to protect against various anti-MM agents. Molecular profiling revealed that BEZ235 treatment decreased the amplitude of transcriptional signatures previously associated with myc, ribosome, and proteasome function, as well as high-risk MM and undifferentiated human embryonic stem cells. In vivo xenograft studies revealed significant reduction in tumor burden (P = 0.011) and survival (P = 0.028) in BEZ235-treated human MM tumor-bearing mice. Combinations of BEZ235 with conventional (e.g., dexamethasone and doxorubicin) or novel (e.g., bortezomib) anti-MM agents showed lack of antagonism. These results indicate that BEZ235 merits clinical testing, alone and in combination with other agents, in MM. [Cancer Res 2009;69(14):5835-42]
C1 [McMillin, Douglas W.; Ooi, Melissa; Delmore, Jake; Negri, Joseph; Hayden, Patrick; Mitsiades, Nicolas; Jakubikova, Jana; Schlossman, Robert; Munshi, Nikhil C.; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA.
[McMillin, Douglas W.; Ooi, Melissa; Delmore, Jake; Negri, Joseph; Hayden, Patrick; Mitsiades, Nicolas; Jakubikova, Jana; Anderson, Kenneth C.; Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Maira, Sauveur-Michel; Garcia-Echeverria, Carlos] Novartis Inst Biomed Res, Basel, Switzerland.
RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM Constantine_Mitsiades@dfci.harvard.edu
FU "Dunkin Donuts Rising Stars" Program at the Dana-Farber Cancer
Institute; Chambers Medical Foundation; Cobb Family Fellowship; NIH
[R01CA050947, PO-1-78378]
FX "Dunkin Donuts Rising Stars" Program at the Dana-Farber Cancer Institute
(C.S. Mitsiades), Chambers Medical Foundation (P.G. Richardson and C.S.
Mitsiades), Cobb Family Fellowship (D.W. McMillin), and NIH grants
R01CA050947 (K.C. Anderson and C.S. Mitsiades) and PO-1-78378 (K.C.
Anderson).
NR 31
TC 90
Z9 94
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2009
VL 69
IS 14
BP 5835
EP 5842
DI 10.1158/0008-5472.CAN-08-4285
PG 8
WC Oncology
SC Oncology
GA 475LJ
UT WOS:000268360300030
PM 19584292
ER
PT J
AU Sicard, P
Jacquet, S
Kobayashi, KS
Flavell, RA
Marber, MS
AF Sicard, Pierre
Jacquet, Sebastien
Kobayashi, Koichi S.
Flavell, Richard A.
Marber, Michael S.
TI Pharmacological postconditioning effect of muramyl dipeptide is mediated
through RIP2 and TAK1
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Postconditioning; TAK1; RIP2; MDP; Ischaemia-reperfusion
ID ISCHEMIA-REPERFUSION INJURY; PERMEABILITY TRANSITION PORE;
MYOCARDIAL-INFARCTION; TRANSGENIC MICE; TNF-ALPHA; ACTIVATION; HEART;
MECHANISMS; PROTECTION; ENDOTOXIN
AB Despite their ability to cause septic shock and myocardial dysfunction, components of Gram-negative bacterial cell walls, like lipopolysaccharide, have been shown in numerous studies to induce myocardial protection during ischaemia-reperfusion injury. Muramyl dipeptide (MDP) is another such component recognized by an intracellular receptor, nucleotide-binding oligomerization domain 2. Receptor activation leads to intracellular signals through receptor interacting protein-2 (RIP2) and tumour growth factor-beta-activated kinase-1 (TAK1). However, little is known about the RIP2/TAK1 pathway in the heart. The aim of this study was to determine whether the RIP2/TAK1 pathway has a cardioprotective role in a mouse model of myocardial infarction.
We isolated and subjected wild-type (WT) and RIP2(-/-) mouse hearts to 30 min of global ischaemia and 120 min of reperfusion with or without perfusion of MDP (10 mu g/mL) before or after the ischaemic period and determined the infarct size. We examined activation of the TAK1/nuclear factor kappa B (NF kappa B) signalling pathway. The effect of TAK1 inhibition on MDP-induced cardioprotection was also evaluated. Exposure to MDP during reperfusion significantly reduced infarct size in WT hearts (from 51.7 +/- 5.6% in control to 38.1 +/- 6.7%, P < 0.05), but not in RIP2(-/-) hearts or in WT hearts with coincident pharmacological inhibition of TAK1. MDP treatment significantly increased the levels of p-TAK1 and p-JNK (Jun N-terminal kinase) and led to NF kappa B activation via phosphorylation and degradation of IkappaB in the WT, but not in the RIP2(-/-), myocardium.
These results indicate that MDP at reperfusion induced cardioprotection through an RIP2/TAK1-dependent mechanism.
C1 [Sicard, Pierre; Jacquet, Sebastien; Marber, Michael S.] Kings Coll London, British Heart Fdn Ctr Res Excellence, Div Cardiovasc, Rayne Inst,St Thomas Hosp, London SE1 7EH, England.
[Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Flavell, Richard A.] Yale Univ, Dept Immunobiol, Howard Hughes Med Inst, Sch Med, New Haven, CT 06520 USA.
RP Jacquet, S (reprint author), Kings Coll London, British Heart Fdn Ctr Res Excellence, Div Cardiovasc, Rayne Inst,St Thomas Hosp, Lambeth Palace Rd, London SE1 7EH, England.
EM sebastien.jacquet@kcl.ac.uk
RI Sicard, Pierre/B-1637-2010;
OI Sicard, Pierre/0000-0001-8100-9792; Sicard, Pierre/0000-0001-5837-3916
FU British Heart Foundation [07/073/23432]; Department of Health; NIDDK NIH
HHS [R01 DK074738, R01 DK074738-05]
NR 30
TC 6
Z9 9
U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD JUL 15
PY 2009
VL 83
IS 2
BP 277
EP 284
DI 10.1093/cvr/cvp055
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 463OF
UT WOS:000267440800013
PM 19213760
ER
PT J
AU Wu, CJ
Ritz, J
AF Wu, Catherine J.
Ritz, Jerome
TI Revealing Tumor Immunity after Hematopoietic Stem Cell Transplantation
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID CHRONIC MYELOGENOUS LEUKEMIA; GRAFT; RECIPIENTS; INDUCTION; HLA
AB Allogeneic hematopoietic stem cell transplantation is currently the most effective method for inducing tumor immunity. However, the diversity of target antigens recognized by donor T cells has not been established. New studies show that tumor-reactive T cells are directed against diverse tumor-specific targets as well as minor histocompatibility antigens.
C1 [Wu, Catherine J.; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr,Harvard Stem Cell Inst, Boston, MA 02115 USA.
RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr,Harvard Stem Cell Inst, M530,44 Binney St, Boston, MA 02115 USA.
EM jerome_ritz@dfci.harvard.edu
OI Ritz, Jerome/0000-0001-5526-4669
NR 12
TC 7
Z9 7
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2009
VL 15
IS 14
BP 4515
EP 4517
DI 10.1158/1078-0432.CCR-09-0873
PG 3
WC Oncology
SC Oncology
GA 482SG
UT WOS:000268908400001
PM 19584145
ER
PT J
AU Yip, S
Miao, JY
Cahill, DP
Iafrate, AJ
Aldape, K
Nutt, CL
Louis, DN
AF Yip, Stephen
Miao, Jiangyong
Cahill, Daniel P.
Iafrate, A. John
Aldape, Ken
Nutt, Catherine L.
Louis, David N.
TI MSH6 Mutations Arise in Glioblastomas during Temozolomide Therapy and
Mediate Temozolomide Resistance
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MISMATCH-REPAIR SYSTEM; COLORECTAL-CANCER; MALIGNANT GLIOMAS;
DNA-REPAIR; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; MICROSATELLITE
INSTABILITY; ALKYLATING-AGENTS; MGMT; O-6-BENZYLGUANINE; RECURRENT
AB Purpose: Over the past few years, the alkylating agent temozolomide has become the standard-of-care therapy for patients with glioblastoma, the most common brain tumor. Recently, large-scale cancer genome sequencing efforts have identified a hypermutation phenotype and inactivating MSH6 mismatch repair gene mutations in recurrent, post-temozolomide glioblastomas, particularly those growing more rapidly during temozolomide treatment. This study aimed to clarify the timing and role of MSH6 mutations in mediating glioblastoma temozolomide resistance.
Experimental Design: MSH6 sequence and microsatellite instability (MSI) status were determined in matched prechemotherapy and postchemotherapy glioblastomas identified by The Cancer Genome Atlas (TCGA) as having posttreatment MSH6 mutations. Temozolomide-resistant lines were derived in vitro through selective growth under temozolomide, and the MSH6 gene was sequenced in resistant clones. The role of MSH6 inactivation in mediating resistance was explored using lentiviral short hairpin RNA knockdown and MSH6 reconstitution.
Results: MSH6 mutations were confirmed in posttreatment TCGA glioblastomas but absent in matched pretreatment tumors. The posttreatment hypermutation phenotype displayed a signature bias toward CpC transitions and was not associated with MSI. In vitro modeling through exposure of an MSH6 wild-type glioblastoma line to temozolomide resulted in resistant clones; one clone showed an MSH6 mutation,Thr(1219)lle, that had been independently noted in two treated TCGA glioblastomas. Knockdown of MSH6 in the glioblastoma line U251 increased resistance to temozolomide cytotoxicity and reconstitution restored cytotoxicity in MSH6-null glioma cells.
Conclusions: MSH6 mutations are selected in glioblastomas during temozolomide therapy both in vitro and in vivo and are causally associated with temozolomide resistance.
C1 [Yip, Stephen; Miao, Jiangyong; Cahill, Daniel P.; Iafrate, A. John; Nutt, Catherine L.; Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv, Boston, MA 02114 USA.
[Cahill, Daniel P.; Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA.
[Iafrate, A. John; Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
[Yip, Stephen; Miao, Jiangyong; Iafrate, A. John; Nutt, Catherine L.; Louis, David N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Aldape, Ken] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
RP Louis, DN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv, WRN225, Boston, MA 02114 USA.
EM louis@helix.mgh.harvard.edu
RI Nutt, Catherine/K-8794-2012;
OI Cahill, Daniel/0000-0003-2552-6546
FU NIH [CA57683]; Royal College of Physicians and Surgeons of Canada;
Burroughs-Wellcome Career Award
FX NIH CA57683 (C.L. Nutt and D.N. Louis) and Clinician Investigator
Fellowship from The Royal College of Physicians and Surgeons of Canada
(S. Yip), and a Burroughs-Wellcome Career Award in the Medical Sciences
(D.P. Cahill). The costs of publication of this article were defrayed in
part by the payment of page charges. This article must therefore be
hereby marked advertisement in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
NR 37
TC 117
Z9 123
U1 5
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2009
VL 15
IS 14
BP 4622
EP 4629
DI 10.1158/1078-0432.CCR-08-3012
PG 8
WC Oncology
SC Oncology
GA 482SG
UT WOS:000268908400015
PM 19584161
ER
PT J
AU Baba, Y
Nosho, K
Shima, K
Freed, E
Irahara, N
Philips, J
Meyerhardt, JA
Hornick, JL
Shivdasani, RA
Fuchs, CS
Ogino, S
AF Baba, Yoshifumi
Nosho, Katsuhiko
Shima, Kaori
Freed, Ellen
Irahara, Natsumi
Philips, Juliet
Meyerhardt, Jeffrey A.
Hornick, Jason L.
Shivdasani, Ramesh A.
Fuchs, Charles S.
Ogino, Shuji
TI Relationship of CDX2 Loss with Molecular Features and Prognosis in
Colorectal Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; HOMEOBOX GENE-EXPRESSION; POPULATION-BASED
SAMPLE; MICROSATELLITE INSTABILITY; COLON-CANCER; FAMILY-HISTORY;
IMMUNOHISTOCHEMICAL SURVEY; LINE-1 HYPOMETHYLATION; BRAF MUTATION;
MUTANT MICE
AB Purpose: The homeodomain transcription factor CDX2 is a relatively specific immunchistochemical marker for gastrointestinal carcinoma. However, no study has comprehensively examined the relationship between CDX2 expression in colon cancer and clinical, pathologic, prognostic, and molecular features, including microsatellite instability and CpG island methylator phenotype (CIMP).
Experimental Design: Utilizing 621 colorectal cancers with clinical outcome and molecular data, CDX2 loss was detected in 183 (29%) tumors by immunohistochemistry.
Results: In multivariate logistic regression analysis, CDX2 loss was associated with female gender [odds ratio (OR), 3.32; P < 0.0001], CIMP-high (OR, 4.42; P = 0.0003), high tumor grade (OR, 2.69; P = 0.0085), stage IV disease (OR, 2.03; P = 0.019), and inversely with LINE-1 hypomethylation (for a 30% decline; OR, 0.33; P = 0.0031), p53 expression (OR, 0.55; P = 0.011), and beta-catenin activation (OR, 0.60; P = 0.037), but not with body mass index, tumor location, microsatellite instability, BRAF, KRAS, PIK3CA, p21, or cyclooxygenase-2. CDX2 loss was not independently associated with patient survival. However, the prognostic effect of CDX2 loss seemed to differ according to family history of colorectal cancer (P-interaction = 0.0094). CDX2 loss was associated with high overall mortality (multivariate hazard ratio, 2.40; 95% Cl, 1.28-4.51) among patients with a family history of colorectal cancer; no such association was present (multivariate hazard ratio, 0.97; 95% Cl, 0.66-1.41) among patients without a family history of colorectal cancer.
Conclusions: CDX2 loss in colorectal cancer is independently associated with female gender, CIMP-high, high-level LINE-1 methylation, high tumor grade, and advanced stage. CDX2 loss may be associated with poor prognosis among patients with a family history of colorectal cancer.
C1 [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Baba, Yoshifumi; Nosho, Katsuhiko; Shima, Kaori; Freed, Ellen; Irahara, Natsumi; Philips, Juliet; Meyerhardt, Jeffrey A.; Shivdasani, Ramesh A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, 44 Binney St,Room JF 215C, Boston, MA 02115 USA.
EM shuji.ogino@dfci.harvard.edu
FU U.S. NIH [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826, K07
CA97992]; Entertainment Industry Foundation National Colorectal Cancer
Research Alliance; Japan Society for Promotion of Science
FX U.S. NIH grants P01 CA87969 (S. Hankinson), P01 CA55075 (W. Willett),
P50 CA127003 (C.S. Fuchs), K07 CA122826 (S. Ogino), and K07 CA97992
(J.A. Meyerhardt); and in part by grants from the Bennett Family Fund
and from the Entertainment Industry Foundation National Colorectal
Cancer Research Alliance. K. Nosho was supported by a fellowship grant
from the Japan Society for Promotion of Science. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of National Cancer Institute or NIH. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript. The costs of publication of this
article were defrayed in part by the payment of page charges. This
article must therefore be hereby marked advertisement in accordance with
18 U.S.C. section 1734 solely to indicate this fact.
NR 51
TC 60
Z9 67
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2009
VL 15
IS 14
BP 4665
EP 4673
DI 10.1158/1078-0432.CCR-09-0401
PG 9
WC Oncology
SC Oncology
GA 482SG
UT WOS:000268908400019
PM 19584150
ER
PT J
AU Bradbury, PA
Zhai, RH
Ma, C
Xu, W
Hopkins, J
Kulke, MJ
Asomaning, K
Wang, ZX
Su, L
Heist, RS
Lynch, TJ
Wain, JC
Christiani, D
Liu, G
AF Bradbury, Penelope A.
Zhai, Rihong
Ma, Clement
Xu, Wei
Hopkins, Jessica
Kulke, Matthew J.
Asomaning, Kofi
Wang, Zhaoxi
Su, Li
Heist, Rebecca S.
Lynch, Thomas J.
Wain, John C.
Christiani, David
Liu, Geoffrey
TI Vascular Endothelial Growth Factor Polymorphisms and Esophageal Cancer
Prognosis
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; FACTOR GENE POLYMORPHISMS; TUMOR ANGIOGENESIS;
FACTOR EXPRESSION; CONTINUOUS TRAITS; GASTRIC-CANCER; BREAST-CANCER;
VEGF GENE; ASSOCIATION; ADENOCARCINOMA
AB Purpose: Vascular endothelial growth factor (VEGF) promotes angiogenesis and vascular permeability. The VEGF gene is polymorphic. We investigated the prognostic significance of three VEGF single nucleotide polymorphisms (SNP) in esophageal cancer.
Experimental Design: Three hundred sixty-one patients were genotyped for three VEGF SNPs (-460T/C, 405G/C, and 936C/T) using DNA extracted from prospectively collected blood samples. The association of each individual SNP, and haplotypes of the three SNPs, on overall survival (OS) was investigated.
Results: The variant allele of 936C/T was associated with improved OS compared with the wildtype genotype (log-rank P < 0.001). This association remained significant for OS after adjustments for age, gender, performance status, and disease stage [VEGF 936C/T: adjusted hazard ratio (AHR), 0.70; 95% confidence interval (95% CI), 0.49-0.99; P = 0.04; VEGF 936T/T: AHR, 0.11; 95% Cl, 0.02-0.82; P = 0.03]. No independent associations were found for VEGF -460T/C and VEGF 405G/C. The CGC haplotype of the three VEGF SNPs (-460T/C, 405G/C, and 936C/T) combined was associated with reduced OS compared with all other patients (CGC/CGC: AHR, 1.51; 95% Cl, 1.00-2.30; P = 0.05).
Conclusions: VEGF 936C/T, and a haplotype of 460T/C, 405G/C, and 936C/T combined, has potential prognostic significance in esophageal cancer.
C1 [Bradbury, Penelope A.; Ma, Clement; Xu, Wei; Hopkins, Jessica; Liu, Geoffrey] Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp, Dept Med, Toronto, ON M5G 2M9, Canada.
[Liu, Geoffrey] Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2M9, Canada.
[Zhai, Rihong; Asomaning, Kofi; Wang, Zhaoxi; Su, Li; Heist, Rebecca S.; Christiani, David; Liu, Geoffrey] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA.
[Kulke, Matthew J.] Dana Farber Canc Inst, Dept Adult Oncol Med Oncol, Boston, MA USA.
[Heist, Rebecca S.; Lynch, Thomas J.; Liu, Geoffrey] Harvard Univ, Sch Med, Dept Med, MGH Canc Ctr, Boston, MA USA.
[Wain, John C.] Harvard Univ, Sch Med, Thorac Surg Unit, Boston, MA USA.
[Christiani, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA.
[Hopkins, Jessica] McMaster Univ, Community Hlth Family Med, Hamilton, ON, Canada.
RP Liu, G (reprint author), Univ Toronto, Ontario Canc Inst, Princess Margaret Hosp, Dept Med, 610 Univ Ave,Suite 7-124, Toronto, ON M5G 2M9, Canada.
EM Geoffrey.Liu@uhn.on.ca
RI Liu, Geoffrey/N-4421-2016
FU NIH [R01 CA109193, RO3 CA110822, R01 CA074386, R01 CA092824]; Doris Duke
Charitable Foundation; Kevin Jackson Memorial Fund; Alan B. Brown Chair
in Molecular Genomics; Flight Attendant Medical Research Institute
[062409_YCSA]; Ontario Cancer Research Network Fellowship
FX NIH grants R01 CA109193, RO3 CA110822, R01 CA074386, and R01 CA092824;
Doris Duke Charitable Foundation; Kevin Jackson Memorial Fund; Alan B.
Brown Chair in Molecular Genomics; Flight Attendant Medical Research
Institute grant 062409_YCSA, and Ontario Cancer Research Network
Fellowship. The costs of publication of this article were defrayed in
part by the payment of page charges. This article must therefore be
hereby marked advertisement in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
NR 29
TC 36
Z9 38
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2009
VL 15
IS 14
BP 4680
EP 4685
DI 10.1158/1078-0432.CCR-09-0192
PG 6
WC Oncology
SC Oncology
GA 482SG
UT WOS:000268908400021
PM 19584152
ER
PT J
AU Mosquera, JM
Mehra, R
Regan, MM
Perner, S
Genega, EM
Bueti, G
Shah, RB
Gaston, S
Tomlins, SA
Wei, JT
Kearney, MC
Johnson, LA
Tang, JM
Chinnaiyan, AM
Rubin, MA
Sanda, MG
AF Mosquera, Juan-Miguel
Mehra, Rohit
Regan, Meredith M.
Perner, Sven
Genega, Elizabeth M.
Bueti, Gerri
Shah, Rajal B.
Gaston, Sandra
Tomlins, Scott A.
Wei, John T.
Kearney, Michael C.
Johnson, Laura A.
Tang, Jeffrey M.
Chinnaiyan, Arul M.
Rubin, Mark A.
Sanda, Martin G.
TI Prevalence of TMPRSS2-ERG Fusion Prostate Cancer among Men Undergoing
Prostate Biopsy in the United States
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GENE FUSION; HETEROGENEITY; TRANSCRIPTS; EXPRESSION; URINE
AB Purpose: Fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is a putatively oncogenic gene rearrangement that is commonly found in prostate cancer tissue from men undergoing prostatectomy. However, the prevalence of the fusion was less common in samples of transurethral resection of the prostate from a Swedish cohort of patients with incidental prostate cancer followed by watchful waiting, raising the question as to whether the high prevalence in prostatectomy specimens reflects selection bias. We sought to determine the prevalence of TMPRSS2-ERG gene fusion among prostate-specific antigen - screened men undergoing prostate biopsy in the United States.
Experimental Design: We studied 140 prostate biopsies from the same number of patients for TMPRSS2-ERG fusion status with a fluorescent in situ hybridization assay. One hundred and thirty-four samples (100 cancer and 34 benign) were assessable.
Results: ERG gene rearrangement was detected in 46% of prostate biopsies that were found to have prostate cancer and in 0% of benign prostate biopsies (P < 0.0001). Evaluation of morphologic features showed that cribriform growth, blue-tinged mucin, macronucleoli, and collagenous micronodules were significantly more frequent in TMPRSS2-ERG fusion - positive prostate cancer biopsies than gene fusion - negative prostate cancer biopsies (P <= 0.04). No significant association with Gleason score was detected. In addition, non-Caucasian patients were less likely to have positive fusion status (P = 0.02).
Conclusions: This is the first prospective North American multicenter study to characterize TMPRSS2-ERG prostate cancer prevalence in a cohort of patients undergoing needle biopsy irrespective of whether or not they subsequently undergo prostatectomy. Our results show that this gene rearrangement is common among North American men who have prostate cancer on biopsy, is absent in benign prostate biopsy, and is associated with specific morphologic features. These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.
C1 [Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02115 USA.
[Mosquera, Juan-Miguel; Perner, Sven; Johnson, Laura A.; Tang, Jeffrey M.; Rubin, Mark A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Mosquera, Juan-Miguel; Regan, Meredith M.; Perner, Sven; Genega, Elizabeth M.; Gaston, Sandra; Kearney, Michael C.; Rubin, Mark A.; Sanda, Martin G.] Harvard Univ, Sch Med, Boston, MA USA.
[Shah, Rajal B.; Wei, John T.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Shah, Rajal B.; Chinnaiyan, Arul M.] Univ Michigan, Sch Med, Michigan Urol Ctr, Ann Arbor, MI 48109 USA.
[Genega, Elizabeth M.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA.
[Gaston, Sandra] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA.
[Perner, Sven] Univ Ulm, Dept Pathol, Ulm, Germany.
[Rubin, Mark A.] MIT, Broad Inst, Cambridge, MA 02139 USA.
[Rubin, Mark A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Regan, Meredith M.; Rubin, Mark A.] Dana Farber Harvard Comprehens Canc Ctr, Boston, MA USA.
RP Sanda, MG (reprint author), Beth Israel Deaconess Med Ctr, Div Urol, 330 Brookline Ave,Rabb 440, Boston, MA 02115 USA.
EM msanda@bidmc.harvard.edu
RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Wei,
John/E-8967-2012;
OI Rubin, Mark/0000-0002-8321-9950
FU NIH [P50 CA090381, R01AG21404, U01 CA113913, P50 CA69568]; German
Research Foundation Deutsche Forschungsgemeinschaft DFG [PE1179/1-2];
Department of Defense [PC061474]; ERDN [U01 CA111275]
FX NIH Prostate Specialized Programs of Research Excellence (SPORE) at the
Dana-Farber/Harvard Cancer Center NCI P50 CA090381 (M.A. Rubin),
R01AG21404 (M.A. Rubin), German Research Foundation Deutsche
Forschungsgemeinschaft DFG no. PE1179/1-2 (S. Perner), Department of
Defense Prostate Cancer Training Award PC061474, NIH grant U01 CA113913
for the Beth Israel Deaconess Early Detection Research Network (ERDN;
Harvard/Michigan Prostate Cancer Clinical Center; M. Sanda), ERDN U01
CA111275 and SPORE P50 CA69568 (A.M. Chinnaiyan); A.M. Chinnaiyan is a
Howard Hughes Medical Institute Investigator.; The costs of publication
of this article were defrayed in part by the payment of page charges.
This article must therefore be hereby marked advertisement in accordance
with 18 U.S.C. Section 1734 solely to indicate this fact.
NR 20
TC 121
Z9 126
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2009
VL 15
IS 14
BP 4706
EP 4711
DI 10.1158/1078-0432.CCR-08-2927
PG 6
WC Oncology
SC Oncology
GA 482SG
UT WOS:000268908400025
PM 19584163
ER
PT J
AU Butt, AA
Wang, XQ
Budoff, M
Leaf, D
Kuller, LH
Justice, AC
AF Butt, Adeel A.
Wang Xiaoqiang
Budoff, Matthew
Leaf, David
Kuller, Lewis H.
Justice, Amy C.
TI Hepatitis C Virus Infection and the Risk of Coronary Disease
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID FATTY LIVER-DISEASE; ARTERY-DISEASE; HEPATOCELLULAR-CARCINOMA;
HEMODIALYSIS-PATIENTS; ATHEROSCLEROSIS; VETERANS; HIV; INFLAMMATION;
ASSOCIATION; COCAINE
AB Background. The association between hepatitis C virus (HCV) infection and coronary artery disease (CAD) is controversial. We conducted this study to determine and quantify this association.
Methods. We used an established, national, observational cohort of all HCV-infected veterans receiving care at all Veterans Affairs facilities, the Electronically Retrieved Cohort of HCV Infected Veterans, to identify HCV-infected subjects and HCV-uninfected control subjects. We used the Cox proportional-hazards model to determine the risk of CAD among HCV-infected subjects and control subjects.
Results. We identified 82,083 HCV-infected and 89,582 HCV-uninfected subjects. HCV-infected subjects were less likely to have hypertension, hyperlipidemia, and diabetes but were more likely to abuse alcohol and drugs and to have renal failure and anemia. HCV-infected subjects had lower mean (+/- standard deviation) total plasma cholesterol (175 +/- 40.8 mg/dL vs. 198 +/- 41.0 mg/dL), low-density lipoprotein cholesterol (102 +/- 36.8 mg/dL vs. 119 +/- 38.2 mg/dL), and triglyceride (144 +/- 119 mg/dL vs. 179 +/- 151 mg/dL) levels, compared with HCV-uninfected subjects (P < .001 for all comparisons). In multivariable analysis, HCV infection was associated with a higher risk of CAD (hazard ratio, 1.25; 95% confidence interval, 1.20-1.30). Traditional risk factors (age, hypertension, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia) were associated with a higher risk of CAD in both groups, whereas minority race and female sex were associated with a lower risk of CAD.
Conclusions. HCV-infected persons are younger and have lower lipid levels and a lower prevalence of hypertension. Despite a favorable risk profile, HCV infection is associated with a higher risk of CAD after adjustment for traditional risk factors.
C1 [Butt, Adeel A.] Univ Pittsburgh, Med Ctr, Sch Med, Pittsburgh, PA 15213 USA.
[Justice, Amy C.] Yale Univ, Sch Med & Publ Hlth, New Haven, CT USA.
[Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Butt, Adeel A.; Wang Xiaoqiang] Univ Pittsburgh, Grad Sch Publ Hlth, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA.
[Butt, Adeel A.; Wang Xiaoqiang] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15213 USA.
[Leaf, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Leaf, David] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Los Angeles, CA USA.
RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, 3601 5th Ave,Ste 3A, Pittsburgh, PA 15213 USA.
EM butta@dom.pitt.edu
FU National Institutes of Health, National Institute on Drug Abuse [K23
DA016175-01A1]
FX National Institutes of Health, National Institute on Drug Abuse (K23
DA016175-01A1 to A. A. B.).
NR 44
TC 114
Z9 120
U1 1
U2 4
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 JUL 15
PY 2009
VL 49
IS 2
BP 225
EP 232
DI 10.1086/599371
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 460XU
UT WOS:000267226900011
PM 19508169
ER
PT J
AU Beppu, H
Malhotra, R
Beppu, Y
Lepore, JJ
Parmacek, MS
Bloch, KD
AF Beppu, Hideyuki
Malhotra, Rajeev
Beppu, Yuko
Lepore, John J.
Parmacek, Michael S.
Bloch, Kenneth D.
TI BMP type II receptor regulates positioning of outflow tract and
remodeling of atrioventricular cushion during cardiogenesis
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Cardiogenesis; Bone morphogenetic protein; Cre-loxP; Endocardial
cushion; Valvulogenesis; Cardiac outflow tract
ID MORPHOGENETIC PROTEIN-RECEPTOR; SMOOTH-MUSCLE-CELLS; NEURAL CREST CELLS;
ENDOCARDIAL CUSHION; CARDIAC MORPHOGENESIS; MOUSE EMBRYOGENESIS; HEART;
MICE; GASTRULATION; DELETION
AB Signaling of bone morphogenetic protein (BMP) via type I and type II receptors is involved in multiple processes contributing to cardiogenesis. To investigate the role of the BMP type II receptor (BMPRII) in heart development, the BMPRII gene was deleted throughout the embryo during gastrulation using a Mox2-Cre transgene. BMPR(flox/-);Mox2-Cre mice exhibited cardiac defects including double-outlet right ventricle, ventricular septal defect (VSD), atrioventricular (AV) cushion defects, and thickened valve leaflets. To characterize the tissue-specific functions of BMPRII in cardiogenesis, a series of Cre transgenes (alpha MHC-, Tie2-, Wnt1-, and SM22 alpha-Cre) was employed. Interestingly, myocardial development was normal when the BMPRII gene was deleted in myocardial cells using Mox2-Cre, alpha MHC-Cre, or SM22 alpha-Cre transgenes, suggesting that signaling by other BMP type II receptors may compensate for the absence of BMPRII in the myocardial cells. AV cushion defects including atrial septal defect, membranous VSD, and thickened valve leaflets were found in BMPR(flox/-);Tie2-Cre mice. Abnormal positioning of the aorta was observed in BMPRII(flox/-);Wnt1-Cre and BMPRII(flox/-);SM22 alpha-Cre mice. Taken together, these results demonstrate that endocardial BMPRII expression is required for septal formation and valvulogenesis. Moreover, mesenchymal BMPRII expression in the outflow tract cushion is required for proper positioning of the aorta. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Beppu, Hideyuki; Beppu, Yuko; Bloch, Kenneth D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Beppu, Hideyuki; Malhotra, Rajeev; Beppu, Yuko; Bloch, Kenneth D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Res Ctr, Charlestown, MA 02129 USA.
[Lepore, John J.; Parmacek, Michael S.] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
RP Beppu, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, 55 Fruit St, Boston, MA 02114 USA.
EM beppu-ind@umin.ac.jp
OI Parmacek, Michael/0000-0003-1449-4665; Malhotra,
Rajeev/0000-0003-0120-4630
FU American Heart Association Scientist Development [0535079N]; NIH [5R01
HL074352]
FX The authors thank Drs. Calum MacRae and Donald B. Bloch for valuable
discussions and experimental advice, and Dr. E. Dale Abel for alpha
MHC-Cre transgenic mice. This work was supported by American Heart
Association Scientist Development Grant 0535079N (HB) and a NIH grant
5R01 HL074352 (KDB).
NR 39
TC 34
Z9 36
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 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
BP 167
EP 175
DI 10.1016/j.ydbio.2009.04.032
PG 9
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900006
PM 19409885
ER
PT J
AU Mayack, SR
Shadrach, J
Schepers, K
Passegue, E
Wagers, AJ
AF Mayack, Shane R.
Shadrach, Jennifer
Schepers, Koen
Passegue, Emmanuelle
Wagers, Amy J.
TI Blood stem cells: Regulation by the niche
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Mayack, Shane R.; Shadrach, Jennifer; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Schepers, Koen; Passegue, Emmanuelle] Univ Calif San Francisco, San Francisco, CA 94143 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 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 32
BP 395
EP 395
DI 10.1016/j.ydbio.2009.05.041
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900055
ER
PT J
AU Wood, AW
Brown, YA
AF Wood, Antony W.
Brown, Yvonne A.
TI Intraembryonic functions of IGF2 signaling in zebrafish
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Wood, Antony W.; Brown, Yvonne A.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 312
BP 477
EP 477
DI 10.1016/j.ydbio.2009.05.340
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900333
ER
PT J
AU Blackiston, DJ
Levin, M
AF Blackiston, Douglas J.
Levin, Michael
TI Control of embryonic stem cell proliferation and migration can be
controlled in vivo by pharmacological modulation of endogenous ion
channels
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Blackiston, Douglas J.; Levin, Michael] Forsyth Inst, Ctr Regenerat & Dev Biol, Boston, MA USA.
[Levin, Michael] Tufts Univ, Dept Biol, Medford, MA 02155 USA.
NR 0
TC 0
Z9 0
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 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 419
BP 506
EP 506
DI 10.1016/j.ydbio.2009.05.561
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900437
ER
PT J
AU Green, JB
Tabler, JM
Ossipova, OM
Yamanaka, H
Panousopoulou, E
AF Green, Jeremy B.
Tabler, Jacqueline M.
Ossipova, Olga M.
Yamanaka, Hiroaki
Panousopoulou, Eleni
TI Control of cell and tissue polarity in neurectoderm by the PAR-1 (MARK)
proteins in Xenopus
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Green, Jeremy B.; Tabler, Jacqueline M.; Yamanaka, Hiroaki; Panousopoulou, Eleni] Kings Coll London, Dept Craniofacial Dev, London WC2R 2LS, England.
[Ossipova, Olga M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 420
BP 507
EP 507
DI 10.1016/j.ydbio.2009.05.447
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900438
ER
PT J
AU Huett, A
Leong, JM
Podolsky, DK
Xavier, RJ
AF Huett, Alan
Leong, John M.
Podolsky, Daniel K.
Xavier, Ramnik J.
TI The cytoskeletal scaffold Shank3 is recruited to pathogen-induced actin
rearrangements
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Bacterial infection; Attaching and effacing; Actin; Cytoskeleton;
Synapse
ID ESCHERICHIA-COLI TIR; POSTSYNAPTIC DENSITY PROTEINS; NCK SH2/SH3
ADAPTERS; PEDESTAL FORMATION; HOST-CELLS; ENTEROCYTE EFFACEMENT;
TYROSINE KINASES; DENDRITIC SPINES; SUBSTRATE IRSP53; RECEPTOR
AB The common gastrointestinal pathogens enteropathogenic Escherichia coli (EPEC) and Salmonella typhimurium both reorganize the gut epithelial cell actin cytoskeleton to mediate pathogenesis, utilizing mimicry of the host signaling apparatus. The PDZ domain-containing protein Shank3, is a large cytoskeletal scaffold protein with known functions in neuronal morphology and synaptic signaling, and is also capable of acting as a scaffolding adaptor during Ret tyrosine kinase signaling in epithelial cells. Using immunofluorescent and functional RNA-interference approaches we show that Shank3 is present in both EPEC- and S. typhimurium-induced actin rearrangements and is required for optimal EPEC pedestal formation. We propose that Shank3 is one of a number of host synaptic proteins likely to play key roles in bacteria-host interactions. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Huett, Alan; Podolsky, Daniel K.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis,Sch Med, Boston, MA 02115 USA.
[Huett, Alan; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA.
[Leong, John M.] Univ Massachusetts, Med Ctr, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA.
RP Xavier, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis,Sch Med, Boston, MA 02115 USA.
EM xavier@molbio.mgh.harvard.edu
FU National Institutes of Health [AI062773, AI46454, DK060049, DK043351]
FX We would like to thank Tony Pawson (Mount Sinai Hospital, Toronto
Canada) for his kind gift of Nck 1 and 2 double knockout and isogenic
wild-type MEFs. Salmonella typhimurium Sl1344 DsRed2 was a gift from Dr
HC Reinecker (Massachusetts General Hospital, Boston), and EPEC E2348/69
was obtained from Dr S Snapper (Massachusetts General Hospital). This
work was supported by grants from the National Institutes of Health to
RJX (NIH AI062773), JML (AI46454) and DKP (DK060049 and DK043351).
NR 51
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Z9 5
U1 1
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD JUL 15
PY 2009
VL 315
IS 12
BP 2001
EP 2011
DI 10.1016/j.yexcr.2009.04.003
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 457TL
UT WOS:000266956200001
PM 19371741
ER
PT J
AU Johnson, AD
Kavousi, M
Smith, AV
Chen, MH
Dehghan, A
Aspelund, T
Lin, JP
van Duijn, CM
Harris, TB
Cupples, LA
Uitterlinden, AG
Launer, L
Hofman, A
Rivadeneira, F
Stricker, B
Yang, Q
O'Donnell, CJ
Gudnason, V
Witteman, JC
AF Johnson, Andrew D.
Kavousi, Maryam
Smith, Albert V.
Chen, Ming-Huei
Dehghan, Abbas
Aspelund, Thor
Lin, Jing-Ping
van Duijn, Cornelia M.
Harris, Tamara B.
Cupples, L. Adrienne
Uitterlinden, Andre G.
Launer, Lenore
Hofman, Albert
Rivadeneira, Fernando
Stricker, Bruno
Yang, Qiong
O'Donnell, Christopher J.
Gudnason, Vilmundur
Witteman, Jacqueline C.
TI Genome-wide association meta-analysis for total serum bilirubin levels
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CORONARY-HEART-DISEASE; ORGANIC CATION TRANSPORTER; UGT1A1-ASTERISK-28
ALLELE; OATP-C; GENE; POLYMORPHISMS; EXPRESSION; INHERITANCE; ROTTERDAM;
DESIGN
AB Variation in serum bilirubin is associated with altered cardiovascular disease risk and drug metabolism. We aimed to identify genetic contributors to variability in serum bilirubin levels by combining results from three genome-wide association studies (Framingham heart study, n = 3424; Rotterdam study, n = 3847; Age, Gene, Environment and Susceptibility-Reykjavik, n = 2193). Meta-analysis showed strong replication for a genetic influence on serum bilirubin levels of the UGT1A1 locus (P < 5 x 10(-324)) and a 12p12.2 locus. The peak signal in the 12p12.2 region was a non-synonymous SNP in SLCO1B1 (rs4149056, P = 6.7 x 10(-13)), which gives rise to a valine to alanine amino acid change leading to reduced activity for a hepatic transporter with known affinity for bilirubin. There were also suggestive associations with several other loci. The top variants in UGT1A1 and SLCO1B1 explain similar to 18.0 and similar to 1.0% of the variation in total serum bilirubin levels, respectively. In a conditional analysis adjusted for individual genotypes for the top UGT1A1 variant, the top SLCO1B1 variant remained highly significant (P = 7.3 x 10(-13)), but no other variants achieved genome-wide significance. In one of the largest genetic studies of bilirubin to date (n = 9464), we confirm the substantial genetic influence of UGT1A1 variants, consistent with past linkage and association studies, and additionally provide strong evidence of a role for allelic variation in SLCO1B1. Given the involvement of bilirubin in a number of physiological and disease processes, and the roles for UGT1A1 and SLCO1B1 in drug metabolism, these genetic findings have potential clinical importance. In analyses for association with gallbladder disease or gallstones, top bilirubin SNPs in UGT1A1 and SLCO1B1 were not associated.
C1 [Johnson, Andrew D.; Chen, Ming-Huei; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Kavousi, Maryam; Dehghan, Abbas; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Rivadeneira, Fernando; Stricker, Bruno; Witteman, Jacqueline C.] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.; Rivadeneira, Fernando; Stricker, Bruno] Erasmus MC Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Reykjavik, Iceland.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Lin, Jing-Ping] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Harris, Tamara B.; Launer, Lenore] Natl Inst Agings Age, Gene Environm Susceptibil Study, Reykjavik, Iceland.
[Cupples, L. Adrienne; Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Stricker, Bruno] Inspectorate Hlth Care, The Hague, Netherlands.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM codonnell@nih.gov
RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Johnson,
Andrew/G-6520-2013; Yang, Qiong/G-5438-2014; Gudnason,
Vilmundur/K-6885-2015; Rivadeneira, Fernando/O-5385-2015; Smith,
Albert/K-5150-2015;
OI Dehghan, Abbas/0000-0001-6403-016X; Aspelund, Thor/0000-0002-7998-5433;
Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845;
Cupples, L. Adrienne/0000-0003-0273-7965
FU NHLBI NIH HHS [N01-HC-25195, N02-HL-6-4278]; NIA NIH HHS [N01-AG-12100]
NR 39
TC 113
Z9 115
U1 2
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 15
PY 2009
VL 18
IS 14
BP 2700
EP 2710
DI 10.1093/hmg/ddp202
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 463OJ
UT WOS:000267441200017
PM 19414484
ER
PT J
AU Wark, PA
Wu, K
van 't Veer, P
Fuchs, CF
Giovannucci, EL
AF Wark, Petra A.
Wu, Kana
van 't Veer, Pieter
Fuchs, Charles F.
Giovannucci, Edward L.
TI Family history of colorectal cancer: A determinant of advanced adenoma
stage or adenoma multiplicity?
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE family history; cohort study; colorectal neoplasm; colorectal adenomas;
colorectal cancer
ID COLON-CANCER; 1ST-DEGREE RELATIVES; RISK-FACTORS; POLYPS; DYSPLASIA;
CARCINOMA; CLASSIFICATION; SURVEILLANCE; METAANALYSIS; INDIVIDUALS
AB A family history of colorectal cancer may increase colorectal cancer risk by influencing adenoma growth or enhancing the formation of new lesions. Data of men from the prospective Health Professionals Follow-Up Study who underwent an endoscopy between 1986 and 2004 were used to evaluate whether a family history of colorectal cancer is associated with adenoma multiplicity or advanced adenoma stage (>= 1 cm, histology with villous component or carcinoma in situ). 21.4% of the 3,881 adenoma patients and 13.9% of the 24,959 adenoma-free men had a first-degree relative with colorectal cancer. Thousand four hundred and ninety-six men were classified as having advanced and 1,507 as having nonadvanced adenomas. Six hundred and twenty-two men had multiple and 1,985 had single adenomas in the distal colon and rectum. A family history of colorectal cancer was similarly associated with advanced and nonadvanced adenomas [multivariable odds ratio (OR) (95% confidence interval): advanced vs. nonadvanced, 0.98 (0.82-1.17), advanced vs. adenoma-free: 1.67 (1.47-1.91), nonadvanced vs. adenoma-free: 1.70 (1.49-1.94)], although potential differences according to adenoma location were seen. A family history of colorectal cancer was more strongly associated with multiple distally located adenomas [odds ratio (95% confidence interval): multiple vs. single, 1.35 (1.09-1.68), multiple vs. no distally located adenomas: 2.02 (1.67-2.44), single vs. no distally located adenomas: 1.49 (1.32-1.68)]. The number of adenomas was also positively associated with a family history of colorectal cancer. Our findings suggest that at the population level, heritable factors may be more important in earlier stages of adenoma formation than at stages of adenoma advancement for at least distally located adenomas. (C) 2009 UICC
C1 [Wark, Petra A.] London Sch Hyg & Trop Med, Canc Res UK Epidemiol & Genet Grp, Dept Epidemiol & Populat Hlth, London WC1, England.
[Wark, Petra A.; van 't Veer, Pieter] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
[Wu, Kana; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Fuchs, Charles F.] Harvard Ctr Canc Prevent, Boston, MA USA.
[Fuchs, Charles F.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Giovannucci, EL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA.
EM edward.giovannucci@channing.harvard.edu
OI Wark, Petra/0000-0003-1020-4640
FU NCI [CA 55075]; Dutch Cancer Society; Netherlands Organisation for
Health Research and Development; Cancer Research UK
FX The HPFS is supported by NCI Research Grant CA 55075. Dr. Petra Wark's
visit to the Harvard School of Public Health was made possible with
support from the Dutch Cancer Society, and she was further supported by
the Netherlands Organisation for Health Research and Development and
Cancer Research UK. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Cancer Institute or the National Institutes of Health.
NR 41
TC 18
Z9 18
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2009
VL 125
IS 2
BP 413
EP 420
DI 10.1002/ijc.24288
PG 8
WC Oncology
SC Oncology
GA 460ZJ
UT WOS:000267231600021
PM 19358277
ER
PT J
AU Whitson, JM
Noonan, EJ
Pookot, D
Place, RF
Dahiya, R
AF Whitson, Jared M.
Noonan, Emily J.
Pookot, Deepa
Place, Robert F.
Dahiya, Rajvir
TI Double stranded-RNA-mediated activation of P21 gene induced apoptosis
and cell cycle arrest in renal cell carcinoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE renal cell carcinoma; RNAa; saRNA; p21WAF1/CIP1; apoptosis;
survivin/Birc5
ID BLADDER-CANCER CELLS; SURVIVIN EXPRESSION; DEPENDENT KINASE;
MAMMALIAN-CELLS; IN-VIVO; P21(WAF1/CIP1); INTERFERENCE; INHIBITION;
SIRNAS; DRUGS
AB Small double stranded RNAs (dsRNA) are a new class of molecules which regulate gene expression. Accumulating data suggest that some dsRNA can function as tumor suppressors. Here, we report further evidence on the potential of dsRNA mediated p21 induction. Using the human renal cell carcinoma cell line A498, we found that dsRNA targeting the p21 promoter significantly induced the expression of p21 mRNA and protein levels. As a result, dsP21 transfected cells had a significant decrease in cell viability with a concomitant G1 arrest. We also observed a significant increase in apoptosis. These findings were associated with a significant decrease in survivin mRNA and protein levels. This is the first report that demonstrates dsRNA mediated gene activation in renal cell carcinoma and suggests that forced over-expression of p21 may lead to an increase in apoptosis through a survivin dependent mechanism. (C) 2009 UICC
C1 [Whitson, Jared M.; Dahiya, Rajvir] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA.
[Noonan, Emily J.; Pookot, Deepa; Place, Robert F.; Dahiya, Rajvir] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Urol Res Ctr 112F, 4150 Clement St, San Francisco, CA 94121 USA.
EM rdahiya@urology.ucsf.edu
FU NIH [RO1CA111470, RO1CA101844, RO1CA130860, T32DK007790]
FX Grant sponsor: NIH; Grant numbers: RO1CA111470, RO1CA101844,
RO1CA130860. T32DK007790.
NR 33
TC 19
Z9 26
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2009
VL 125
IS 2
BP 446
EP 452
DI 10.1002/ijc.24370
PG 7
WC Oncology
SC Oncology
GA 460ZJ
UT WOS:000267231600026
PM 19384944
ER
PT J
AU Smith, BD
Arthur, DW
Buchholz, TA
Haffty, BG
Hahn, CA
Hardenbergh, PH
Julian, TB
Marks, LB
Todor, DA
Vicini, FA
Whelan, TJ
White, J
Wo, JY
Harris, JR
AF Smith, Benjamin D.
Arthur, Douglas W.
Buchholz, Thomas A.
Haffty, Bruce G.
Hahn, Carol A.
Hardenbergh, Patricia H.
Julian, Thomas B.
Marks, Lawrence B.
Todor, Dorin A.
Vicini, Frank A.
Whelan, Timothy J.
White, Julia
Wo, Jennifer Y.
Harris, Jay R.
TI ACCELERATED PARTIAL BREAST IRRADIATION CONSENSUS STATEMENT FROM THE
AMERICAN SOCIETY FOR RADIATION ONCOLOGY (ASTRO)
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Accelerated partial-breast irradiation; Breast cancer; Consensus
statement
ID DOSE-RATE BRACHYTHERAPY; PHASE-II TRIAL; MULTICATHETER INTERSTITIAL
BRACHYTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; MAMMOSITE BALLOON
BRACHYTHERAPY; INITIAL DOSIMETRIC EXPERIENCE; EXTERNAL-BEAM
RADIOTHERAPY; AUSTRIAN MULTICENTER TRIAL; SURGICAL ADJUVANT BREAST;
CARCINOMA-IN-SITU
AB Purpose: To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation (APBI), based on current published evidence complemented by expert opinion.
Methods and Materials: A systematic search of the National Library of Medicine's PubMed database yielded 645 candidate original research articles potentially applicable to APBI. Of these, 4 randomized trials and 38 prospective single-arm studies were identified. A Task Force composed of all authors synthesized the published evidence and, through a series of meetings, reached consensus regarding the recommendations contained herein.
Results: The Task Force proposed three patient groups: (1) a "suitable: group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety.
Conclusion: Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer. (C) 2009 American Society for Radiation Oncology
C1 [Smith, Benjamin D.] Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA.
[Smith, Benjamin D.; Buchholz, Thomas A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Arthur, Douglas W.; Todor, Dorin A.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA.
[Haffty, Bruce G.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiat Oncol, New Brunswick, NJ USA.
[Hahn, Carol A.] Duke Univ, Sch Med, Dept Radiat Oncol, Durham, NC USA.
[Hardenbergh, Patricia H.] Shaw Reg Canc Ctr, Veil, CO USA.
[Julian, Thomas B.] Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA 15212 USA.
[Marks, Lawrence B.] Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA.
[Vicini, Frank A.] William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI 48072 USA.
[Whelan, Timothy J.] Juravinski Canc Ctr, Dept Radiat Oncol, Hamilton, ON, Canada.
[White, Julia] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA.
[Wo, Jennifer Y.] Harvard Radiat Oncol Residency Program, Boston, MA USA.
[Harris, Jay R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Harris, Jay R.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
RP Smith, BD (reprint author), 2200 Bergquist Dr,Suite 1, Lackland AFB, TX 78236 USA.
EM benjamin.smith@lackland.af.mil
RI Whelan, Timothy/D-3185-2017;
OI Smith, Benjamin/0000-0001-7866-1093
NR 99
TC 419
Z9 439
U1 3
U2 26
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2009
VL 74
IS 4
BP 987
EP 1001
DI 10.1016/j.ijrobp.2009.02.031
PG 15
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 464KY
UT WOS:000267505000003
PM 19545784
ER
PT J
AU Yoon, SS
Stangenberg, L
Lee, YJ
Rothrock, C
Dreyfuss, JM
Baek, KH
Waterman, PR
Nielsen, GP
Weissleder, R
Mahmood, U
Park, PJ
Jacks, T
Dodd, RD
Fisher, CJ
Ryeom, S
Kirsch, DG
AF Yoon, Sam S.
Stangenberg, Lars
Lee, Yoon-Jin
Rothrock, Courtney
Dreyfuss, Jonathan M.
Baek, Kwan-Hyuck
Waterman, Peter R.
Nielsen, G. Petur
Weissleder, Ralph
Mahmood, Umar
Park, Peter J.
Jacks, Tyler
Dodd, Rebecca D.
Fisher, Carolyn J.
Ryeom, Sandra
Kirsch, David G.
TI EFFICACY OF SUNITINIB AND RADIOTHERAPY IN GENETICALLY ENGINEERED MOUSE
MODEL OF SOFT-TISSUE SARCOMA
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Sarcoma; radiotherapy; angiogenesis; sunitinib
ID IONIZING-RADIATION; GENE-EXPRESSION; RECTAL-CANCER; GROWTH-FACTOR;
TUMOR; SU11248; ANGIOGENESIS; IRRADIATION; AGENTS
AB Purpose: Sunitinib (SU) is a multitargeted receptor tyrosine kinase inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors. The present study examined SU and radiotherapy (RT) in a genetically engineered mouse model of soft tissue sarcoma (STS).
Methods and Materials: Primary extremity STSs were generated in genetically engineered mice. The mice were randomized to treatment with SU, RT (10 Gy x 2), or both (SU+RT). Changes in the tumor vasculature before and after treatment were assessed in vivo using fluorescence-mediated tomography. The control and treated tumors were harvested and extensively analyzed.
Results: The mean fluorescence in the tumors was not decreased by RT but decreased 38-44% in tumors treated with SU or SU+RT. The control tumors grew to a mean of 1378 mm(3) after 12 days. SU alone or RT alone delayed tumor growth by 56% and 41%, respectively, but maximal growth inhibition (71%) was observed with the combination therapy. SU target effects were confirmed by loss of target receptor phosphorylation and alterations in SU-related gene expression. Cancer cell proliferation was decreased and apoptosis increased in the SU and RT groups, with a synergistic effect on apoptosis observed in the SU+RT group. RT had a minimal effect on the tumor microvessel density and endothelial cell-specific apoptosis, but SU alone or SU+RT decreased the microvessel density by >66% and induced significant endothelial cell apoptosis.
Conclusion: SU inhibited STS growth by effects on both cancer cells and tumor vasculature. SU also augmented the efficacy of RT, suggesting that this combination strategy could improve local control of STS. (C) 2009 Elsevier Inc.
C1 [Yoon, Sam S.; Lee, Yoon-Jin; Rothrock, Courtney] Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA.
[Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Stangenberg, Lars; Waterman, Peter R.; Weissleder, Ralph; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA.
[Waterman, Peter R.; Weissleder, Ralph; Mahmood, Umar] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Dreyfuss, Jonathan M.; Baek, Kwan-Hyuck; Waterman, Peter R.; Weissleder, Ralph; Mahmood, Umar; Park, Peter J.; Ryeom, Sandra] Harvard Univ, Sch Med, Boston, MA USA.
[Dreyfuss, Jonathan M.; Park, Peter J.] Brigham & Womens Hosp, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA.
[Baek, Kwan-Hyuck; Ryeom, Sandra] Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA.
[Baek, Kwan-Hyuck; Ryeom, Sandra] Boston Childrens Hosp, Dept Surg, Boston, MA USA.
[Jacks, Tyler] MIT, Ctr Canc Res, Dept Biol, Boston, MA USA.
[Jacks, Tyler] MIT, Howard Hughes Med Inst, Boston, MA USA.
[Dodd, Rebecca D.; Fisher, Carolyn J.; Kirsch, David G.] Duke Univ, Sch Med, Dept Radiat Oncol, Durham, NC USA.
[Dodd, Rebecca D.; Fisher, Carolyn J.; Kirsch, David G.] Duke Univ, Sch Med, Dept Pharmacol, Durham, NC USA.
[Dodd, Rebecca D.; Fisher, Carolyn J.; Kirsch, David G.] Duke Univ, Sch Med, Dept Canc Biol, Durham, NC USA.
RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Yawkey 7B-7926,55 Fruit St, Boston, MA 02114 USA.
EM syoon@partners.org
FU NCI NIH HHS [P30 CA014051, K08 CA114176, K12 CA 87723-03, K12 CA087723,
KO8 CA 114176, L30 CA109410, L30 CA109410-01, P30-CA14051, P50 CA086355,
P50 CA086355-07, P50 CA86355, R21 CA117128, R21 CA117128-02, U24
CA092782, U24 CA092782-08, U24 CA92782, U54 CA119349, U54
CA119349-040003]
NR 23
TC 28
Z9 29
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2009
VL 74
IS 4
BP 1207
EP 1216
DI 10.1016/j.ijrobp.2009.02.052
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 464KY
UT WOS:000267505000034
PM 19545786
ER
PT J
AU Bei, M
AF Bei, Marianna
TI Molecular Genetics of Ameloblast Cell Lineage
SO JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL
EVOLUTION
LA English
DT Article
ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; LINKED AMELOGENESIS IMPERFECTA;
ALPHA-3 CHAIN GENE; HOMOZYGOUS NONSENSE MUTATION; TOOTH DEVELOPMENT;
TISSUE INTERACTIONS; LAMININ-5 SUBUNITS; MATURATION STAGE; ENAMEL
FORMATION; MICE DISPLAY
AB Late tooth morphogenesis is characterized by a series of events that determine crown morphogenesis and the histodifferentiation of epithelial cells into enamel-secreting ameloblasts and of mesenchymal cells into dentin-secreting odontoblasts. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete a number of enamel-specific proteins. After depositing the full thickness of enamel matrix, ameloblasts shrink in size and regulate enamel maturation. Amelogenesis imperfecta (AI) is a heterogeneous group of inherited defects in enamel formation. Clinically, AI presents as a spectrum of enamel malformations that are categorized as hypoplastic, hypocalcified, or hypomaturation types, based upon the thickness and hardness of the enamel. The different types of AI are inherited, either as X-linked, autosomal-dominant, or autosomal-recessive traits. Recently, several gene mutations have been identified to cause the subtypes of AI. How these genes, however, coordinate their function to control amelogenesis is not understood. In this review, we discuss the role of genes that play definitive role on the determination of ameloblast cell fate and life cycle based on studies in transgenic animals. J. Exp. Zool. (Mol. Dev. Evol.) 312B:437-444, 2009. (C) 2008 Wiley-Liss, Inc.
C1 [Bei, Marianna] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Bei, Marianna] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Bei, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St,Rm 3-214, Charlestown, MA 02129 USA.
EM mbei@partners.org
FU NIH [RO3 DE 018415]; Shiseido Inc; Harvard Medical School
FX Grant sponsor: NIH; Grant number: RO3 DE 018415; Grant sponsor: Shiseido
Inc.; Grant sponsor: Harvard Medical School.
NR 62
TC 26
Z9 26
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-5007
J9 J EXP ZOOL PART B
JI J. Exp. Zool. Part B
PD JUL 15
PY 2009
VL 312B
IS 5
BP 437
EP 444
DI 10.1002/jez.b.21261
PG 8
WC Evolutionary Biology; Developmental Biology; Zoology
SC Evolutionary Biology; Developmental Biology; Zoology
GA 462JF
UT WOS:000267347300006
PM 19090561
ER
PT J
AU Fiorina, P
Jurewicz, M
Augello, A
Vergani, A
Dada, S
La Rosa, S
Selig, M
Godwin, J
Law, K
Placidi, C
Smith, RN
Capella, C
Rodig, S
Adra, CN
Atkinson, M
Sayegh, MH
Abdi, R
AF Fiorina, Paolo
Jurewicz, Mollie
Augello, Andrea
Vergani, Andrea
Dada, Shirine
La Rosa, Stefano
Selig, Martin
Godwin, Jonathan
Law, Kenneth
Placidi, Claudia
Smith, R. Neal
Capella, Carlo
Rodig, Scott
Adra, Chaker N.
Atkinson, Mark
Sayegh, Mohamed H.
Abdi, Reza
TI Immunomodulatory Function of Bone Marrow-Derived Mesenchymal Stem Cells
in Experimental Autoimmune Type 1 Diabetes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; VERSUS-HOST-DISEASE; NOD MICE; IN-VITRO;
LYMPHOCYTE-PROLIFERATION; GRAFT-SURVIVAL; THERAPY; VIVO; ARTHRITIS;
INFUSION
AB Human clinical trials in type 1 diabetes (T1D) patients using mesenchymal stem cells (MSC) are presently underway without prior validation in a mouse model for the disease. In response to this void, we characterized bone marrow-derived murine MSC for their ability to modulate immune responses in the context of T1D, as represented in NOD mice. In comparison to NOD mice, BALB/c-MSC mice were found to express higher levels of the negative costimulatory molecule PD-L1 and to promote a shift toward Th2-like responses in treated NOD mice. In addition, transfer of MSC from resistant strains (i.e., nonobese resistant mice or BALB/c), but not from NOD mice, delayed the onset of diabetes when administered to prediabetic NOD mice. The number of BALB/c-MSC trafficking to the pancreatic lymph nodes of NOD mice was higher than in NOD mice provided autologous NOD-MSC. Administration of BALB/c-MSC temporarily resulted in reversal of hyperglycemia in 90% of NOD mice (p = 0.002). Transfer of autologous NOD-MSC imparted no such therapeutic benefit. We also noted soft tissue and visceral tumors in NOD-MSC-treated mice, which were uniquely observed in this setting (i.e., no tumors were present with BALB/c- or nonobese resistant mice-MSC transfer). The importance of this observation remains to be explored in humans, as inbred mice such as NOD may be more susceptible to tumor formation. These data provide important preclinical data supporting the basis for further development of allogeneic MSC-based therapies for T1D and, potentially, for other autoimmune disorders. The Journal of Immunology, 2009, 183: 993-1004.
C1 [Abdi, Reza] Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr,Div Nephrol, Boston, MA 02115 USA.
[Fiorina, Paolo; Jurewicz, Mollie; Vergani, Andrea; Dada, Shirine; Godwin, Jonathan; Adra, Chaker N.; Sayegh, Mohamed H.; Abdi, Reza] Harvard Univ, Sch Med, Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA.
[Fiorina, Paolo; Vergani, Andrea] Ist Sci San Raffaele, Dept Med, I-20132 Milan, Italy.
[Augello, Andrea; La Rosa, Stefano; Placidi, Claudia; Capella, Carlo] Univ Insubria, Dept Pathol, Osped Circolo, Varese, Italy.
[Augello, Andrea; La Rosa, Stefano; Placidi, Claudia; Capella, Carlo] Univ Insubria, Dept Human Morphol, Varese, Italy.
[Law, Kenneth; Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, Div Hematopathol, Boston, MA 02115 USA.
[Selig, Martin; Smith, R. Neal] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Adra, Chaker N.] King Faisal Specialist Hosp & Res Ctr, Stem Cell Therapy Program, Riyadh 11211, Saudi Arabia.
[Atkinson, Mark] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA.
RP Abdi, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr,Div Nephrol, 221 Longwood Ave, Boston, MA 02115 USA.
EM paolo.fiorina@childrens.harvard.edu; rabdi@rics.bwh.harvard.edu
RI Augello, Andrea/C-7321-2013
OI Augello, Andrea/0000-0001-5959-7989
FU National Institutes of Health [P01 AI-41521]; Juvenile Diabetes Research
Foundation (JDRF) [4-2007-1065]; Scott and Heidi Schuster Foundation;
American Society of Transplantation-JDRF Faculty Grant; JDRF-Career
Development Award
FX This work is supported in part by National Institutes of Health P01
AI-41521, Juvenile Diabetes Research Foundation (JDRF) Grant
4-2007-1065, JDRF R&D Grant 4-2007-1065, and by the Scott and Heidi
Schuster Foundation (M.H.S.). P.F. is the recipient of an American
Society of Transplantation-JDRF Faculty Grant and a JDRF-Career
Development Award. R.A. is the recipient of a JDRF Regular Grant.
NR 48
TC 188
Z9 197
U1 3
U2 22
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2009
VL 183
IS 2
BP 993
EP 1004
DI 10.4049/jimmunol.0900803
PG 12
WC Immunology
SC Immunology
GA 468JD
UT WOS:000267812600025
PM 19561093
ER
PT J
AU Kasorn, A
Alcaide, P
Jia, YH
Subramanian, KK
Sarraj, B
Li, YT
Loison, F
Hattori, H
Silberstein, LE
Luscinskas, WF
Luo, HR
AF Kasorn, Anongnard
Alcaide, Pilar
Jia, Yonghui
Subramanian, Kulandayan K.
Sarraj, Bara
Li, Yitang
Loison, Fabien
Hattori, Hidenori
Silberstein, Leslie E.
Luscinskas, William F.
Luo, Hongbo R.
TI Focal Adhesion Kinase Regulates Pathogen-Killing Capability and Life
Span of Neutrophils via Mediating Both Adhesion-Dependent and
-Independent Cellular Signals
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TYROSINE PHOSPHORYLATION; RESPIRATORY BURST; LEUKOCYTE RECRUITMENT;
BIOLOGICAL SURFACES; NADPH OXIDASE; P-SELECTIN; ACTIVATION; PROTEIN;
MIGRATION; PHAGOCYTOSIS
AB Various neutrophil functions such as phagocytosis, superoxide production, and survival are regulated by integrin signaling. Despite the essential role of focal adhesion kinase (FAK) in mediating this signaling pathway, its exact function in neutrophils is ill defined. In this study, we investigated the role of FAK in neutrophils using a myeloid-specific conditional FAK knockout mouse. As reported in many other cell types, FAK is required for regulation of focal adhesion dynamics when neutrophils adhere to fibronectin or ICAM-1. Adhesion on VCAM-1-coated surfaces and chemotaxis after adhesion were not altered in FAK null neutrophils. In addition, we observed significant reduction in NADPH oxidase-mediated superoxide production and complement-mediated phagocytosis in FAK null neutrophils. As a result, these neutrophils displayed decreased pathogen killing capability both in vitro and in vivo in a mouse peritonitis model. In adherent cells, the defects associated with FAK deficiency are likely due to suppression of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) signaling and chemoattractant-elicited calcium signaling. Disruption of FAK also reduced chemoattractant-elicited superoxide production in suspended neutrophils in the absence of cell adhesion. This may be solely caused by suppression of PtdIns(3,4,5)P3 signaling in these cells, because the fMLP-elicited calcium signal was not altered. Consistent with decreased PtdIns(3,4,5)P3/Akt signaling in FAK null neutrophils, we also observed accelerated spontaneous death in these cells. Taken together, our results revealed previously unrecognized roles of FAK in neutrophil function and provided a potential therapeutic target for treatment of a variety of infectious and inflammatory diseases. The Journal of Immunology, 2009, 183: 1032-1043.
C1 [Kasorn, Anongnard] Srinakharinwirot Univ, Fac Med, Dept Community Med, Bangkok, Thailand.
[Jia, Yonghui; Subramanian, Kulandayan K.; Li, Yitang; Loison, Fabien; Hattori, Hidenori; Silberstein, Leslie E.; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA.
[Jia, Yonghui; Subramanian, Kulandayan K.; Li, Yitang; Loison, Fabien; Hattori, Hidenori; Silberstein, Leslie E.; Luo, Hongbo R.] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
[Alcaide, Pilar; Luscinskas, William F.] Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Dept Pathol, Boston, MA 02115 USA.
[Sarraj, Bara] Northwestern Univ, Div Organ Transplant, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Luo, HR (reprint author), Karp Family Res Bldg,Room 10214, Boston, MA 02115 USA.
EM Hongbo.Luo@childrens.harvard.edu
RI Loison, Fabien/G-3385-2014
OI Loison, Fabien/0000-0002-6678-1730
FU National Institutes of Health Training [HL066987]
FX B.S. is supported by National Institutes of Health Training Grant
HL066987, and H.L. is supported by National Institutes of Health Grants
HL085100, A1076471, and GM076084 and a Research Scholar Grant from
American Cancer Society.
NR 69
TC 21
Z9 23
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2009
VL 183
IS 2
BP 1032
EP 1043
DI 10.4049/jimmunol.0802984
PG 12
WC Immunology
SC Immunology
GA 468JD
UT WOS:000267812600029
PM 19561112
ER
PT J
AU Lazaro, E
Godfrey, SB
Stamegna, P
Ogbechie, T
Kerrigan, C
Zhang, M
Walker, BD
Le Gall, S
AF Lazaro, Estibaliz
Godfrey, Sasha Blue
Stamegna, Pamela
Ogbechie, Tobi
Kerrigan, Christopher
Zhang, Mei
Walker, Bruce D.
Le Gall, Sylvie
TI Differential HIV Epitope Processing in Monocytes and CD4 T Cells Affects
Cytotoxic T Lymphocyte Recognition
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 15th Conference on Retroviruses and Opportunistic Infections
CY FEB 03-06, 2008
CL Boston, MA
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; CLASS-I
MOLECULES; VIRAL LOAD; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION;
TRIMS PRECURSORS; DENDRITIC CELLS; MHC; PEPTIDE
AB The ability of cytotoxic T lymphocytes (CTLs) to clear virus-infected cells is dependent on the presentation of viral peptides processed intracellularly and displayed by major histocompatibility complex class I. Most CTL functional assays use exogenously added peptides, a practice that does not account for the kinetics and quantity of antigenic peptides produced by infectable cells. Here, we examined the relative ability of 2 major human immunodeficiency virus-infectable cell subsets-CD4 T lymphocytes and monocytes-to produce antigenic peptides, using cytosol as a source of peptidases and mass spectrometry to define the degradation products. We show clear subset-specific differences in the kinetics of peptide production and the ability of the peptides produced to sensitize cells for lysis by CTLs, with primary CD4 T lymphocytes having significantly lower proteolytic activity than monocytes. These differences in epitope processing by cell subsets may affect the efficiency of CTL-mediated clearance of infected subsets and contribute to the establishment of chronic infection.
C1 [Le Gall, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard,AIDS Res Ctr, Boston, MA 02129 USA.
[Lazaro, Estibaliz; Godfrey, Sasha Blue; Stamegna, Pamela; Ogbechie, Tobi; Kerrigan, Christopher; Zhang, Mei; Walker, Bruce D.; Le Gall, Sylvie] Harvard Univ, Sch Med, Boston, MA USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Le Gall, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard,AIDS Res Ctr, CNY149 13th St, Boston, MA 02129 USA.
EM sylvie_legall@hms.harvard.edu
OI Godfrey, Sasha Blue/0000-0001-9992-5975
FU Howard Hughes Medical Institute; NIAID NIH HHS [AI60502, P30 AI060354,
R01 AI028568, AI28568, R01 AI084753, R01 AI084753-01, R21 AI060502, R37
AI028568]
NR 44
TC 18
Z9 19
U1 1
U2 2
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 JUL 15
PY 2009
VL 200
IS 2
BP 236
EP 243
DI 10.1086/599837
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 458RD
UT WOS:000267040300011
PM 19505257
ER
PT J
AU Ma, QL
Yang, FS
Rosario, ER
Ubeda, OJ
Beech, W
Gant, DJ
Chen, PP
Hudspeth, B
Chen, CR
Zhao, YL
Vinters, HV
Frautschy, SA
Cole, GM
AF Ma, Qiu-Lan
Yang, Fusheng
Rosario, Emily R.
Ubeda, Oliver J.
Beech, Walter
Gant, Dana J.
Chen, Ping Ping
Hudspeth, Beverly
Chen, Cory
Zhao, Yongle
Vinters, Harry V.
Frautschy, Sally A.
Cole, Greg M.
TI beta-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of
Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling:
Suppression by Omega-3 Fatty Acids and Curcumin
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GLYCOGEN-SYNTHASE KINASE-3-BETA; POLYUNSATURATED FATTY-ACIDS; DEPENDENT
DIABETES-MELLITUS; APOLIPOPROTEIN-E GENOTYPE; GROWTH-FACTOR EXPRESSION;
TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE AD; DOCOSAHEXAENOIC ACID;
OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES
AB Both insulin resistance (type II diabetes) and beta-amyloid (A beta) oligomers are implicated in Alzheimer's disease (AD). Here, we investigate the role of A beta oligomer-induced c-Jun N-terminal kinase (JNK) activation leading to phosphorylation and degradation of the adaptor protein insulin receptor substrate-1 (IRS-1). IRS-1 couples insulin and other trophic factor receptors to downstream kinases and neuroprotective signaling. Increased phospho-IRS-1 is found in AD brain and insulin-resistant tissues from diabetics. Here, we report A beta oligomers significantly increased active JNK and phosphorylation of IRS-1 (Ser616) and tau (Ser422) in cultured hippocampal neurons, whereas JNK inhibition blocked these responses. The omega-3 fatty acid docosahexaenoic acid (DHA) similarly inhibited JNK and the phosphorylation of IRS-1 and tau in cultured hippocampal neurons. Feeding 3xTg-AD transgenic mice a diet high in saturated and omega-6 fat increased active JNK and phosphorylated IRS-1 and tau. Treatment of the 3xTg-AD mice on high-fat diet with fish oil or curcumin or a combination of both for 4 months reduced phosphorylated JNK, IRS-1, and tau and prevented the degradation of total IRS-1. This was accompanied by improvement in Y-maze performance. Mice fed with fish oil and curcumin for 1 month had more significant effects on Y-maze, and the combination showed more significant inhibition of JNK, IRS-1, and tau phosphorylation. These data indicate JNK mediates A beta oligomer inactivation of IRS-1 and phospho-tau pathology and that dietary treatment with fish oil/DHA, curcumin, or a combination of both has the potential to improve insulin/trophic signaling and cognitive deficits in AD.
C1 [Ma, Qiu-Lan; Yang, Fusheng; Rosario, Emily R.; Ubeda, Oliver J.; Beech, Walter; Gant, Dana J.; Chen, Ping Ping; Hudspeth, Beverly; Chen, Cory; Zhao, Yongle; Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA.
[Vinters, Harry V.; Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA.
[Vinters, Harry V.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Ma, Qiu-Lan; Yang, Fusheng; Rosario, Emily R.; Ubeda, Oliver J.; Beech, Walter; Gant, Dana J.; Chen, Ping Ping; Hudspeth, Beverly; Chen, Cory; Zhao, Yongle; Frautschy, Sally A.; Cole, Greg M.] Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res & Clin Ctr, Vet Affairs Med Ctr, North Hills, CA 91343 USA.
RP Cole, GM (reprint author), Greater Los Angeles Healthcare Syst Res 151, Vet Affairs, Bldg 7,Room A101,16111 Plummer St, North Hills, CA 91343 USA.
EM gmcole@ucla.edu
FU National Institutes of Health (NIH) [R01 AT003008]; National Institute
on Aging-NIH [R01 AG16570, AG13471, U01 AG028583, R01 AG021975];
Alzheimer's Association [NIRG-07-59659]; Daljit S. and Elaine Sarkaria
Chair in Diagnostic Medicine
FX This work was supported by National Institutes of Health (NIH) Grant R01
AT003008 (G. M. C.); National Institute on Aging-NIH Grants R01 AG16570
(G. M. C., H. V. V.), AG13471 (G. M. C.), U01 AG028583 (S. A. F.), and
R01 AG021975 (S. A. F.); and Alzheimer's Association Grant NIRG-07-59659
(Q.-L. M.). H. V. V. was supported in part by the Daljit S. and Elaine
Sarkaria Chair in Diagnostic Medicine.
NR 99
TC 227
Z9 240
U1 3
U2 31
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 JUL 15
PY 2009
VL 29
IS 28
BP 9078
EP 9089
DI 10.1523/JNEUROSCI.1071-09.2009
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 470YI
UT WOS:000268018000022
PM 19605645
ER
PT J
AU Mizumori, M
Ham, M
Guth, PH
Engel, E
Kaunitz, JD
Akiba, Y
AF Mizumori, Misa
Ham, Maggie
Guth, Paul H.
Engel, Eli
Kaunitz, Jonathan D.
Akiba, Yasutada
TI Intestinal alkaline phosphatase regulates protective surface
microclimate pH in rat duodenum
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID MUCUS-BICARBONATE BARRIER; CYSTIC-FIBROSIS; BRUSH-BORDER; ATP RELEASE;
ADENOSINE-TRIPHOSPHATASE; CARBONIC-ANHYDRASES; MOUSE DUODENUM; KNOCKOUT
MICE; P2X RECEPTORS; ACID
AB Regulation of localized extracellular pH (pH(o)) maintains normal organ function. An alkaline microclimate overlying the duodenal enterocyte brush border protects the mucosa from luminal acid. We hypothesized that intestinal alkaline phosphatase (IAP) regulates pH(o) due to pH-sensitive ATP hydrolysis as part of an ecto-purinergic pH regulatory system, comprised of cell-surface P2Y receptors and ATP-stimulated duodenal bicarbonate secretion (DBS). To test this hypothesis, we measured DBS in a perfused rat duodenal loop, examining the effect of the competitive alkaline phosphatase inhibitor glycerol phosphate (GP), the ecto-nucleoside triphosphate diphosphohydrolase inhibitor ARL67156, and exogenous nucleotides or P2 receptor agonists on DBS. Furthermore, we measured perfusate ATP concentration with a luciferin-luciferase bioassay. IAP inhibition increased DBS and luminal ATP output. Increased luminal ATP output was partially CFTR dependent, but was not due to cellular injury. Immunofluorescence localized the P2Y(1) receptor to the brush border membrane of duodenal villi. The P2Y(1) agonist 2-methylthio-ADP increased DBS, whereas the P2Y(1) antagonist MRS2179 reduced ATP- or GP-induced DBS. Acid perfusion augmented DBS and ATP release, further enhanced by the IAP inhibitor l-cysteine, and reduced by the exogenous ATPase apyrase. Furthermore, MRS2179 or the highly selective P2Y(1) antagonist MRS2500 co-perfused with acid induced epithelial injury, suggesting that IAP/ATP/P2Y signalling protects the mucosa from acid injury. Increased DBS augments IAP activity presumably by raising pH(o), increasing the rate of ATP degradation, decreasing ATP-mediated DBS, forming a negative feedback loop. The duodenal epithelial brush border IAP-P2Y-HCO3- surface microclimate pH regulatory system effectively protects the mucosa from acid injury.
C1 [Mizumori, Misa; Ham, Maggie; Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Dept Med, Sch Med, Los Angeles, CA 90073 USA.
[Engel, Eli] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90073 USA.
[Guth, Paul H.; Kaunitz, Jonathan D.; Akiba, Yasutada] Greater Los Angles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA.
[Kaunitz, Jonathan D.; Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA.
RP Kaunitz, JD (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM jake@ucla.edu
FU Department of Veterans Affairs Merit Review Award; NIH-NIDDK [R01
DK54221, P30 DK0413]
FX We thank Jenifer Kugler for her assistance with manuscript preparation.
This work was supported by a Department of Veterans Affairs Merit Review
Award, NIH-NIDDK R01 DK54221 (J.D.K.), and the animal core of NIH-NIDDK
P30 DK0413 (J. E. Rozengurt).
NR 51
TC 48
Z9 48
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD JUL 15
PY 2009
VL 587
IS 14
BP 3651
EP 3663
DI 10.1113/jphysiol.2009.172270
PG 13
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 471FF
UT WOS:000268040500029
PM 19451200
ER
PT J
AU Wolpin, BM
Stampfer, MJ
AF Wolpin, Brian M.
Stampfer, Meir J.
TI Defining Determinants of Pancreatic Cancer Risk: Are We Making Progress?
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID MALE SMOKERS; MEAT; CONSUMPTION; GLUCOSE; COHORT; FAT
C1 [Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Wolpin, Brian M.; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA USA.
[Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, 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
FU NCI NIH HHS [R01 CA124908]
NR 12
TC 2
Z9 2
U1 0
U2 0
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 JUL 15
PY 2009
VL 101
IS 14
BP 972
EP 973
DI 10.1093/jnci/djp182
PG 2
WC Oncology
SC Oncology
GA 472FE
UT WOS:000268114300004
PM 19561317
ER
PT J
AU Brainard, DM
Seung, E
Frahm, N
Cariappa, A
Bailey, CC
Hart, WK
Shin, HS
Brooks, SF
Knight, HL
Eichbaum, Q
Yang, YG
Sykes, M
Walker, BD
Freeman, GJ
Pillai, S
Westmoreland, SV
Brander, C
Luster, AD
Tager, AM
AF Brainard, Diana M.
Seung, Edward
Frahm, Nicole
Cariappa, Annaiah
Bailey, Charles C.
Hart, William K.
Shin, Hae-Sook
Brooks, Sarah F.
Knight, Heather L.
Eichbaum, Quentin
Yang, Yong-Guang
Sykes, Megan
Walker, Bruce D.
Freeman, Gordon J.
Pillai, Shiv
Westmoreland, Susan V.
Brander, Christian
Luster, Andrew D.
Tager, Andrew M.
TI Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune
Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SCID-HU MOUSE; HUMAN B-CELLS; HIV-1 INFECTION; T-CELLS; BONE-MARROW;
HEMATOPOIETIC STEM; IN-VIVO; DISEASE PROGRESSION; TYPE-1 INFECTION;
PROGENITOR CELLS
AB The generation of humanized BLT mice by the cotransplantation of human fetal thymus and liver tissues and CD34(+) fetal liver cells into nonobese diabetic/severe combined immunodeficiency mice allows for the long-term reconstitution of a functional human immune system, with human T cells, B cells, dendritic cells, and monocytes/macrophages repopulating mouse tissues. Here, we show that humanized BLT mice sustained high-level disseminated human immunodeficiency virus (HIV) infection, resulting in CD4(+) T-cell depletion and generalized immune activation. Following infection, HIV-specific humoral responses were present in all mice by 3 months, and HIV-specific CD4(+) and CD8(+) T-cell responses were detected in the majority of mice tested after 9 weeks of infection. Despite robust HIV-specific responses, however, viral loads remained elevated in infected BLT mice, raising the possibility that these responses are dysfunctional. The increased T-cell expression of the negative costimulator PD-1 recently has been postulated to contribute to T-cell dysfunction in chronic HIV infection. As seen in human infection, both CD4(+) and CD8(+) T cells demonstrated increased PD-1 expression in HIV-infected BLT mice, and PD-1 levels in these cells correlated positively with viral load and inversely with CD4(+) cell levels. The ability of humanized BLT mice to generate both cellular and humoral immune responses to HIV will allow the further investigation of human HIV-specific immune responses in vivo and suggests that these mice are able to provide a platform to assess candidate HIV vaccines and other immunotherapeutic strategies.
C1 [Brainard, Diana M.; Seung, Edward; Hart, William K.; Shin, Hae-Sook; Brooks, Sarah F.; Luster, Andrew D.; Tager, Andrew M.] Harvard Univ, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA.
[Brainard, Diana M.; Frahm, Nicole; Knight, Heather L.; Eichbaum, Quentin; Walker, Bruce D.; Brander, Christian] Harvard Univ, Sch Med, Div Aids, Charlestown, MA 02129 USA.
[Brainard, Diana M.; Frahm, Nicole; Knight, Heather L.; Eichbaum, Quentin; Walker, Bruce D.; Brander, Christian] MGH MIT & Harvard, Ragon Inst, Charlestown, MA 02129 USA.
[Frahm, Nicole] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98109 USA.
[Cariappa, Annaiah; Pillai, Shiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res, Charlestown, MA 02129 USA.
[Bailey, Charles C.; Westmoreland, Susan V.] Harvard Univ, Div Comparat Pathol, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA.
[Yang, Yong-Guang; Sykes, Megan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Brander, Christian] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain.
[Brander, Christian] Irsicaixa Fdn, Badalona, Spain.
RP Luster, AD (reprint author), Harvard Univ, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp,Sch Med, Bldg 149-8301,149 13th St, Charlestown, MA 02129 USA.
EM aluster@mgh.harvard.edu; amtager@partners.org
OI Brander, Christian/0000-0002-0548-5778
FU Harvard University CFAR (HU CFAR) Scholar Award; HU CFAR Collaborative
Feasibility Study Award; National Institutes of Health [K08 AI058857,
R01 A1067077, AI064930, AI069458, P30 AI060354, P51 RR00168, T32
RR07000, P01 AI078897]
FX This work was supported by a Harvard University CFAR (HU CFAR) Scholar
Award and an HU CFAR Collaborative Feasibility Study Award to A. T. and
by National Institutes of Health grants K08 AI058857 to D. B., R01
A1067077 to C. B., AI064930 and AI069458 to S. P., P30 AI060354 to B.
W., P51 RR00168 and T32 RR07000 to S. V. W., and P01 AI078897 (Project
4) to A. L.
NR 67
TC 124
Z9 125
U1 2
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL 15
PY 2009
VL 83
IS 14
BP 7305
EP 7321
DI 10.1128/JVI.02207-08
PG 17
WC Virology
SC Virology
GA 462LO
UT WOS:000267354300033
PM 19420076
ER
PT J
AU Kumar, D
Shadrach, JL
Wagers, AJ
Lassar, AB
AF Kumar, Deepak
Shadrach, Jennifer L.
Wagers, Amy J.
Lassar, Andrew B.
TI Id3 Is a Direct Transcriptional Target of Pax7 in Quiescent Satellite
Cells
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID MUSCLE PROGENITOR CELLS; SKELETAL-MUSCLE; STEM-CELLS; FATE
DETERMINATION; SOMITIC ORIGIN; SELF-RENEWAL; GENE; POPULATION;
EXPRESSION; MYOGENESIS
AB Pax7 is a key regulator of skeletal muscle stem cells and is required along with Pax3 to generate skeletal muscle precursors. We have identified a collection of genes induced by either Pax3 or Pax7 in C2C12 muscle cells. Two notable Pax3/7 targets are the inhibitory helix-loop-helix (HLH) proteins inhibitor of DNA binding (Id) 2 and Id3, both of which are coordinately expressed with Pax7 in quiescent satellite cells and are induced in quiescent C2C12 myogenic cells after ectopic expression of either Pax3 or Pax7. Ectopic Pax7 activates expression of a luciferase reporter driven by the Id3 promoter, and maximal induction of this reporter requires a conserved Pax7 binding site located upstream of the Id3 gene. Chromatin immunoprecipitation indicated that Pax7 is bound upstream of the Id3 promoter in quiescent satellite cells. In addition, short hairpin RNA-mediated knockdown of Pax7 expression in cultured satellite cells coordinately decreased both Id2 and Id3 expression. Together, these findings indicate that Id3 is a direct transcriptional target for Pax7 in quiescent satellite cells, and they suggest that Pax7 acts to block premature differentiation of quiescent satellite cells by inducing the expression of Id2 and Id3, which in turn may act to block either the precocious induction of myogenic basic (b) HLH proteins, the activity of myogenic bHLH proteins, or both.
C1 [Kumar, Deepak; Lassar, Andrew B.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Shadrach, Jennifer L.; Wagers, Amy J.] Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02115 USA.
[Shadrach, Jennifer L.; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Shadrach, Jennifer L.; Wagers, Amy J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Lassar, AB (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM andrew_lassar@hms.harvard.edu
FU National Institutes of Health [GM-054879]; Harvard Stem Cell Institute;
Jain Foundation; Beckman Foundation; Muscular Dystrophy Association
FX We thank Robert Lim for generously supplying the Id3 promoter; Michael
Rudnicki for the Pax7 cDNA; Hyung-song Nam, Yvette Chin, and Robert
Benezra for characterizing and supplying the anti-Id3 rabbit monoclonal
antibody (now available from CalBioreagents, San Mateo, CA); and Robert
Benezra for thoughtful comments on our work. This work was funded by
National Institutes of Health grant GM-054879 (to A. B. L.) and grants
from the Harvard Stem Cell Institute, Jain Foundation, and Beckman
Foundation (to A. J. W.). D. K. was funded by a fellowship from the
Muscular Dystrophy Association.
NR 35
TC 56
Z9 58
U1 0
U2 3
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JUL 15
PY 2009
VL 20
IS 14
BP 3170
EP 3177
DI 10.1091/mbc.E08-12-1185
PG 8
WC Cell Biology
SC Cell Biology
GA 470NL
UT WOS:000267981600001
PM 19458195
ER
PT J
AU Bourgo, RJ
Siddiqui, H
Fox, S
Solomon, D
Sansam, CG
Yaniv, M
Muchardt, C
Metzger, D
Chambon, P
Roberts, CWM
Knudsen, ES
AF Bourgo, Ryan J.
Siddiqui, Hasan
Fox, Sejal
Solomon, David
Sansam, Courtney G.
Yaniv, Moshe
Muchardt, Christian
Metzger, Daniel
Chambon, Pierre
Roberts, Charles W. M.
Knudsen, Erik S.
TI SWI/SNF Deficiency Results in Aberrant Chromatin Organization, Mitotic
Failure, and Diminished Proliferative Capacity
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID REMODELING COMPLEX; CHROMOSOME SEGREGATION; CANCER; GENE; BRG1;
HETEROCHROMATIN; GENOME; BRM; HAPLOINSUFFICIENCY; TRANSCRIPTION
AB Switch (SWI)/sucrose nonfermentable (SNF) is an evolutionarily conserved complex with ATPase function, capable of regulating nucleosome position to alter transcriptional programs within the cell. It is known that the SWI/SNF complex is responsible for regulation of many genes involved in cell cycle control and proliferation, and it has recently been implicated in cancer development. The ATPase action of SWI/SNF is conferred through either the brahma-related gene 1 (Brg1) or brahma (Brm) subunit of the complex, and it is of central importance to the modification of nucleosome position. In this study, the role of the Brg1 and Brm subunits were examined as they relate to chromatin structure and organization. Deletion of the Brg1 ATPase results in dissolution of pericentromeric heterochromatin domains and a redistribution of histone modifications associated with these structures. This effect was highly specific to Brg1 and is not reproduced by the loss of Brm or SNF5/BAF47/INI1. Brg1 deficiency is associated with the appearance of micronuclei and aberrant mitoses that are a by-product of dissociated chromatin structure. Thus, Brg1 plays a critical role in maintaining chromatin structural integrity.
C1 [Bourgo, Ryan J.; Knudsen, Erik S.] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA.
[Siddiqui, Hasan] Ohio State Univ, Coll Med & Publ Hlth, Ctr Comprehens Canc, Human Canc Genet Program,Dept Mol Virol Immunol &, Columbus, OH 43210 USA.
[Fox, Sejal] Univ Cincinnati, Coll Med, Dept Cell & Canc Biol, Cincinnati, OH 45267 USA.
[Solomon, David] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Yaniv, Moshe; Muchardt, Christian] Inst Pasteur, Dept Dev Biol, CNRS, F-75724 Paris, France.
[Metzger, Daniel; Chambon, Pierre] Inst Genet & Biol Mol & Cellulaire, Dept Funct Genom, F-67400 Illkirch Graffenstaden, France.
[Metzger, Daniel; Chambon, Pierre] INSERM, U596, F-67400 Illkirch Graffenstaden, France.
[Metzger, Daniel; Chambon, Pierre] CNRS, UMR 7104, F-67400 Illkirch Graffenstaden, France.
[Metzger, Daniel; Chambon, Pierre] Univ Strasbourg, F-67000 Strasbourg, France.
[Metzger, Daniel; Chambon, Pierre] Coll France, F-67400 Illkirch Graffenstaden, France.
[Sansam, Courtney G.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Bourgo, RJ (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA.
EM ryan.bourgo@jefferson.edu
FU National Cancer Institute [CA 104213]
FX We thank members of the Erik and Karen Knudsen's laboratories for
critical review of the manuscript and insightful discussion. We also
thank Drs. Christian Muchardt and Moshe Yaniv for providing Brm
nullizygous mice, Drs. Daniel Metzger and Pierre Chambon for providing
Brg1f/f mice, and to Dr. Charles Roberts for providing
SNF5f/f mouse embryonic fibroblasts and the pBABE-Puro and
pBABE-Puro-Cre plasmids. Finally, we thank Dr. A. Kathleen McClendon for
providing the p53DD retrovirus. E. S. K. is supported by National Cancer
Institute grant CA 104213.
NR 32
TC 37
Z9 38
U1 0
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JUL 15
PY 2009
VL 20
IS 14
BP 3192
EP 3199
DI 10.1091/mbc.E08-12-1224
PG 8
WC Cell Biology
SC Cell Biology
GA 470NL
UT WOS:000267981600003
PM 19458193
ER
PT J
AU Gao, DM
Inuzuka, H
Korenjak, M
Tseng, A
Wu, T
Wan, LX
Kirschner, M
Dyson, N
Wei, WY
AF Gao, Daming
Inuzuka, Hiroyuki
Korenjak, Michael
Tseng, Alan
Wu, Tao
Wan, Lixin
Kirschner, Marc
Dyson, Nicholas
Wei, Wenyi
TI Cdh1 Regulates Cell Cycle through Modulating the Claspin/Chk1 and the
Rb/E2F1 Pathways
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID ANAPHASE-PROMOTING COMPLEX; ONCOGENE-INDUCED SENESCENCE; DNA-DAMAGE;
UBIQUITIN LIGASE; HUMAN FIBROBLASTS; BINDING-PROTEIN; G(1) ARREST;
CHECKPOINT; P53; DEGRADATION
AB APC/Cdh1 is a major cell cycle regulator and its function has been implicated in DNA damage repair; however, its exact role remains unclear. Using affinity purification coupled with mass spectrometry, we identified Claspin as a novel Cdh1-interacting protein and further demonstrated that Claspin is a novel Cdh1 ubiquitin substrate. As a result, inactivation of Cdh1 leads to activation of the Claspin/Chk1 pathway. Previously, we demonstrated that Rb interacts with Cdh1 to influence its ability to degrade Skp2. Here, we report that Cdh1 reciprocally regulates the Rb pathway through competing with E2F1 to bind the hypophosphorylated form of Rb. Although inactivation of Cdh1 in HeLa cells, with defective p53/Rb pathways, led to premature S phase entry, acute depletion of Cdh1 in primary human fibroblasts resulted in premature senescence. Acute loss of many other major tumor suppressors, including PTEN and VHL, also induces premature senescence in a p53- or Rb-dependent manner. Similarly, we showed that inactivation of the p53/Rb pathways by overexpression of SV40 LT-antigen partially reversed Cdh1 depletion-induced growth arrest. Therefore, loss of Cdh1 is only beneficial to cells with abnormal p53 and Rb pathways, which helps explain why Cdh1 loss is not frequently found in many tumors.
C1 [Gao, Daming; Inuzuka, Hiroyuki; Tseng, Alan; Wan, Lixin; Wei, Wenyi] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Wu, Tao; Kirschner, Marc] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02215 USA.
[Korenjak, Michael; Dyson, Nicholas] Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Korenjak, Michael; Dyson, Nicholas] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Wei, WY (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
EM wwei2@bidmc.harvard.edu
RI Wan, Lixin/F-2124-2011; Wu, Tao/C-7533-2013
FU Harvard Medical School Milton Fund; Beth Israel Deaconess Medical
Center; National Institutes of Health [R01 GM89763, R01 GM53203]
FX We thank Alex Toker, Christoph Schorl, Shavali Shaik, and Susan Glueck
for critical reading of the manuscript; James DeCaprio (Dana-Farber
Cancer Institute, Boston, MA), Christoph Geisen (Dana-Farber Cancer
Institute, Boston, MA), William Hahn, Bert Vogelstein (Johns Hopkins
University, Baltimore, MD), Michele Pagano, and Peter Jackson for
providing reagents; Michele Pagano for sharing unpublished data, and
members of the Wei and Dyson labs for useful discussions. W. W. is V
Scholar and Kimmel Scholar. M. K. is supported by the postdoctoral
fellowship from the Deutsche Forschungsgemeinschaft (German Research
Foundation). This work is supported in part by the Harvard Medical
School Milton Fund, the start-up package provided by the Beth Israel
Deaconess Medical Center, and National Institutes of Health Grant R01
GM89763 to W. W, and National Institutes of Health Grant R01 GM53203 to
N. D.
NR 61
TC 35
Z9 35
U1 0
U2 8
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JUL 15
PY 2009
VL 20
IS 14
BP 3305
EP 3316
DI 10.1091/mbc.E09-01-0092
PG 12
WC Cell Biology
SC Cell Biology
GA 470NL
UT WOS:000267981600013
PM 19477924
ER
PT J
AU Simon, KC
Chen, HL
Gao, X
Schwarzschild, MA
Ascherio, A
AF Simon, Kelly Claire
Chen, Honglei
Gao, Xiang
Schwarzschild, Michael A.
Ascherio, Alberto
TI Reproductive Factors, Exogenous Estrogen Use, and Risk of Parkinson's
Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; estrogen; epidemiology; reproductive factors
ID POSTMENOPAUSAL HORMONE USE; BREAST-CANCER; INDUCED NEUROPROTECTION;
PREMENOPAUSAL WOMEN; CIGARETTE-SMOKING; AGE; GENDER; REPRODUCIBILITY;
PROGESTERONE; CAFFEINE
AB To determine if reproductive factors or exogenous estrogen are associated with risk of Parkinson's disease (PD), we conducted a prospective study with 22 years of follow-up among postmenopausal participants in the Nurses' Health Study. Relative risks (RRs) and 95% confidence intervals (CIs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. Risk of PD was not significantly associated with any of the reproductive factors measured or exogenous estrogen use. Use of postmenopausal hormones, however, may modify the associations of smoking and caffeine intake with PD risk. The inverse relation between smoking and PD risk was attenuated among ever users of post-menopausal hormones (P for interaction = 0.05). Similar results were obtained for caffeine (P for interaction = 0.09). In exploratory analyses, women using progestin-only hormones were found to have an increased PD risk, but this result was based on a very small number of cases (n = 4). In this large longitudinal study, we found no evidence of a beneficial effect of exogenous or endogenous estrogens on risk of PD. The use of postmenopausal hormone use may interact with other risk factors, but findings are preliminary and need confirmation in other populations. (C) 2009 Movement Disorder Society
C1 [Simon, Kelly Claire; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Simon, KC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,3rd Floor, Boston, MA 02115 USA.
EM ksimon@hsph.harvard.edu
OI Chen, Honglei/0000-0003-3446-7779
FU NIH/NINDS [ROI NS048517, T32 ES07069-26]; Intramural Research Program of
the National Institute of Environmental Health Sciences, the National
Institute of Health [ZOIES1019]; DOD [W81XWH-091-0881]
FX This work was funded by grant NIH/NINDS ROI NS048517 and training grant
T32 ES07069-26 and was in part supported by the Intramural Research
Program of the National Institute of Environmental Health Sciences, the
National Institute of Health (ZOIES1019) and DOD grant W81XWH-091-0881.
We thank Eilis O'Reilly for technical support. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 43
TC 30
Z9 30
U1 0
U2 4
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 JUL 15
PY 2009
VL 24
IS 9
BP 1359
EP 1365
DI 10.1002/mds.22619
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 478UH
UT WOS:000268613300015
PM 19424986
ER
PT J
AU Gass, N
Porkka-Heiskanen, T
Kalinchuk, AV
AF Gass, Natalia
Porkka-Heiskanen, Tarja
Kalinchuk, Anna V.
TI The role of the basal forebrain adenosine receptors in sleep homeostasis
SO NEUROREPORT
LA English
DT Article
DE adenosine; electrophysiology; in vivo microdialysis; sleep deprivation
ID CENTRAL-NERVOUS-SYSTEM; BEHAVIORAL STATE; A(2A) RECEPTOR; A(1) RECEPTOR;
NEURONS; RAT; MICRODIALYSIS; DEPRIVATION; WAKEFULNESS; MODULATION
AB Multiple studies indicate that adenosine released in the basal forebrain during prolonged wakefulness could affect recovery sleep. It is still unclear which of adenosine receptors provide its sleep-modulating effects in the basal forebrain. We infused adenosine A(1) and A(2A) receptors antagonists into the rat basal forebrain during sleep deprivation and compared characteristics of recovery non-rapid eye movement (non-REM) sleep (its amount and non-REM sleep delta power) after sleep deprivation, and after sleep deprivation combined with perfusion of antagonists. A(1) receptor antagonist significantly reduced recovery sleep amount and delta power, whereas A(2A) receptor antagonist had no effect on recovery sleep. We conclude that adenosine can promote recovery non-REM sleep when acting through A(1) receptors in the basal forebrain. NeuroReport 20:1013-1018 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Kalinchuk, Anna V.] Harvard Univ, Sch Med, Dept Psychiat, Neurosci Lab, W Roxbury, MA 02132 USA.
[Gass, Natalia; Porkka-Heiskanen, Tarja] Univ Helsinki, Dept Physiol, Inst Biomed, Helsinki, Finland.
[Kalinchuk, Anna V.] VA Boston Healthcare Syst, W Roxbury, MA 02132 USA.
RP Kalinchuk, AV (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Neurosci Lab, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM anna_kalinchuk@hms.harvard.edu
OI Stenberg, Tarja/0000-0003-1843-7625
FU Center for International Mobility (CIMO); Finnish Graduate School of
Neuroscience and Academy of Finland
FX The authors thank Mr Ernst Mecke, Mrs Pirjo Saarelainen, and Mrs Sari
Levo-Siitari for their excellent technical assistance. This study was
supported by grants from Center for International Mobility (CIMO),
Finnish Graduate School of Neuroscience and Academy of Finland.
NR 24
TC 13
Z9 13
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD JUL 15
PY 2009
VL 20
IS 11
BP 1013
EP 1018
DI 10.1097/WNR.0b013e32832d5859
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 468LQ
UT WOS:000267820400008
PM 19491711
ER
PT J
AU Yeh, PH
Simpson, K
Durazzo, TC
Gazdzinski, S
Meyerhoff, DJ
AF Yeh, Ping-Hong
Simpson, Ken
Durazzo, Timothy C.
Gazdzinski, Stefan
Meyerhoff, Dieter J.
TI Tract-based spatial statistics (TBSS) of diffusion tensor imaging data
in alcohol dependence: Abnormalities of the motivational neurocircuitry
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Alcohol use disorder; Cognition; Brain MRI; Diffusion tensor imaging,
DTI; Tract-based spatial statistics, TBSS; Probabilistic tractography
ID NATIONAL EPIDEMIOLOGIC SURVEY; CHRONIC CIGARETTE-SMOKING; DSM-IV
ALCOHOL; WHITE-MATTER; WATER DIFFUSION; DRUG-ADDICTION; NEUROPSYCHIATRIC
DISORDERS; MULTIPLE-SCLEROSIS; GENE-EXPRESSION; UNITED-STATES
AB Previous diffusion tensor imaging (DTI) studies indicated microstructural disruption of white matter in alcohol dependence. To investigate the microstructure of primary neurocircuitry involved in alcohol use disorders, the present study used Tract-Based Spatial Statistics (TBSS) of DTI measures as well as probabilistic tractography. Eleven recovering alcoholics in their first week of abstinence from alcohol were compared with 10 light-drinking controls; diffusion measures were correlated with measures of neurocognition and drinking severity. Regions characterized by low fractional anisotropy and high mean diffusivity included cortico-striatal fibers and those in frontal white matter and limbic pathways. Greater diffusion abnormalities in sections of commissural fibers (inter-hemispheric connections) were associated with greater drinking severity, and lower fractional anisotropy measures in frontal and limbic fiber tracts correlated with lower visuospatial memory performance. These study findings provide direct evidence of compromised integrity of the motivational brain circuitry in alcohol use disorders. These abnormalities in fiber connections could be partially responsible for deficiencies in executive functions, behavioral regulation, and impulse control commonly described in alcohol dependence. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Yeh, Ping-Hong; Simpson, Ken; Durazzo, Timothy C.; Gazdzinski, Stefan; Meyerhoff, Dieter J.] San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA.
[Durazzo, Timothy C.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
RP Yeh, PH (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, 4150 Clement St 114M, San Francisco, CA 94121 USA.
EM ping-hong_yeh@med.unc.edu
FU NIH [AA10788]
FX NIH AA10788 (DJM) and the Veteran's Administration research service
supported this project We thank Mary Rebecca Young and Bill Clift of the
San Francisco VA Substance Abuse Day Hospital, and Dr. David Pating,
Karen Moise, and their colleagues at the San Francisco Kaiser Permanente
Chemical Dependency Recovery Program for their valuable assistance in
recruiting research participants. We also thank Dr. Hemanth
Thayyullathil for assistance with data analyses, as well as Drs. Michael
W. Weiner, Norbert Schuff, Wang Zhan, and Yu Zhang for valuable
discussions. Last but not least, we thank our study volunteers, who made
this research possible.
NR 72
TC 50
Z9 52
U1 1
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD JUL 15
PY 2009
VL 173
IS 1
BP 22
EP 30
DI 10.1016/j.pscychresns.2008.07.012
PG 9
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 463YF
UT WOS:000267469400004
PM 19442492
ER
PT J
AU van Tulder, MW
Suttorp, M
Morton, S
Bouter, LM
Shekelle, P
AF van Tulder, Maurits W.
Suttorp, Marika
Morton, Sally
Bouter, Lex M.
Shekelle, Paul
TI Empirical Evidence of an Association Between Internal Validity and
Effect Size in Randomized Controlled Trials of Low-Back Pain
SO SPINE
LA English
DT Article
DE Cochrane collaboration; randomized trials; low back pain; bias; effect
size
ID CLINICAL-TRIALS; SYSTEMATIC REVIEWS; QUALITY ASSESSMENT; METHOD
GUIDELINES; CRITERIA LIST; METAANALYSES
AB Study Design. We conducted a methodologic study. Objective. The objective of this study was to assess the validity of the criteria list recommended by the Cochrane Back Review Group Editorial Board by evaluating whether individual items and a total score are associated with effect sizes in randomized controlled trials of back-pain interventions.
Summary of Background Data. There is concern that studies of low methodologic quality may exaggerate the effectiveness of treatments for low back pain. We performed this study to examine the association between a common measure of internal validity and the reported magnitude of treatment effects.
Methods. We assessed the relationship between the 11 items contained in the Cochrane Back Review Group Internal Validity checklist and effect size in randomized trials of interventions for back pain. Of 267 trials in 15 Cochrane reviews that were eligible for inclusion, 51 were excluded, leaving 216 trials included in the analysis. The scores on the 11 items for each trial were taken from the original review. We extracted effect sizes from each low back pain trial.
Results. We found that trials that fulfilled a specific item had smaller effect sizes compared with trials that did not fulfill that item for 10 of the 11 items, and for 6 of the criteria, the absolute difference in effect sizes was 0.10 or greater. The 95% confidence interval of the difference in effect sizes crossed the null value in each case. The number of items fulfilled showed that trials with higher scores consistently reported smaller effect sizes than trials with lower scores. At the thresholds of 5 or 6 items fulfilled, the difference in effect sizes was 0.20 in each case (95% confidence intervals 0.05-0.35 and 0.06-0.34, respectively). Stratified analyses did not support confounding by intervention.
Conclusion. We conclude that the 11-item Internal Validity Checklist is associated with effect size in randomized trials of interventions for back pain, and that our data support the use of a sum score of the number of fulfilled items in this list.
C1 [van Tulder, Maurits W.] Vrije Univ Amsterdam, Dept Hlth Sci, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[van Tulder, Maurits W.; Bouter, Lex M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.
[Suttorp, Marika; Shekelle, Paul] RAND Hlth, Santa Monica, CA USA.
[Morton, Sally] RTI Int, Res Triangle Pk, NC USA.
[Shekelle, Paul] W Los Angeles VA Med Ctr, Los Angeles, CA USA.
RP van Tulder, MW (reprint author), Vrije Univ Amsterdam, Dept Hlth Sci, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
EM maurits.van.tulder@falw.vu.nl
OI Bouter, Lex/0000-0002-2659-5482; van Tulder, Maurits/0000-0002-7589-8471
NR 39
TC 73
Z9 73
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
J9 SPINE
JI SPINE
PD JUL 15
PY 2009
VL 34
IS 16
BP 1685
EP 1692
PG 8
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 527TX
UT WOS:000272390900004
PM 19770609
ER
PT J
AU Hanekamp, JS
Okumi, M
Tena, A
Arn, S
Yamada, K
Sachs, DH
AF Hanekamp, John S.
Okumi, Masayoshi
Tena, Aseda
Arn, Scott
Yamada, Kazuhiko
Sachs, David H.
TI Cytoplasmic Inheritance of Transplantation Antigens in Animals Produced
by Nuclear Transfer
SO TRANSPLANTATION
LA English
DT Article
DE Transplantation; Mitochondria; Transplantation antigens; Tolerance;
Rejection
ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; MITOCHONDRIAL-DNA;
ALLOGRAFTS; TOLERANCE; INDUCTION; PIGS
AB Background. Nuclear transfer has been used as a means of selectively modifying the mammalian genome. One possible consequence of this technology is that the oocytes used in nuclear transfer may provide additional antigens by cytoplasmic inheritance of maternally derived, mitochondrial DNA (mtDNA). These studies examine the potential consequences of such inheritance in a large animal transplantation model.
Methods. Renal transplants were performed between major histocompatibility complex (MHC)-identical animals differing only in the source of their maternally derived cytoplasmic DNA, using a protocol, which uniformly leads to tolerance within standard MFIC-inbred lines. In an attempt to correlate transplant results with a putative marker for disparities in cytoplasmically inherited minor histocompatibility antigens, we examined one hypervariable region of mtDNA, designated hypervariable region 1 (HV1).
Results. The mtDNA sequence of the HV1 region was found to be invariant among MGH miniature swine of different haplotypes, despite 25 years of selective breeding of the sublines of this colony. In contrast, swine derived by nuclear transfer into outbred oocytes differed in the HV1 region sequence from each other and from MGH swine. Renal transplants from standard, inbred. MGH swine to their MHC-identical knockout counterparts derived from outbred oocytes were rejected within 2 weeks, whereas transplants in the reverse direction were accepted for over 30 days.
Conclusions. The HV1 sequence of mtDNA may serve as a marker for the level of diversity of mtDNA. These transplant data are consistent with the existence of mtDNA-encoded mitochondrial minor antigens with a level of diversity that can influence the outcome of renal transplantation.
C1 [Hanekamp, John S.; Tena, Aseda; Arn, Scott; Yamada, Kazuhiko; Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
[Hanekamp, John S.; Tena, Aseda; Arn, Scott; Yamada, Kazuhiko; Sachs, David H.] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Okumi, Masayoshi] Osaka Univ, Grad Sch Med, Dept Urol, Osaka, Japan.
RP Hanekamp, JS (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East,Bldg 149,13th St, Boston, MA 02129 USA.
EM John.hanekamp@tbrc.mgh.harvard.edu
FU NIAID NIH HHS [R37 AI031046, R37 AI031046-19, R01 AI031046-10]
NR 21
TC 5
Z9 5
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 JUL 15
PY 2009
VL 88
IS 1
BP 30
EP 37
DI 10.1097/TP.0b013e3181a9ed5b
PG 8
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 468UJ
UT WOS:000267848000006
PM 19584677
ER
PT J
AU Thinda, S
Tomlinson, JS
AF Thinda, Sumeer
Tomlinson, James S.
TI Mesenteric rheumatoid nodules masquerading as an intra-abdominal
malignancy: a case report and review of the literature
SO WORLD JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
ID ACCELERATED NODULOSIS; ARTHRITIS; THERAPY
AB Background: Rheumatoid nodules are the most common extra-articular findings in patients with rheumatoid arthritis. They occur most commonly at pressure points such as the extensor surfaces of the forearms, fingers, and occiput, but have also been reported to occur in unusual locations including the central nervous system, pericardium, pleura, and sclera. We present the unusual case of rheumatoid nodules in the small bowel mesentery masquerading as an intra-abdominal malignancy.
Case presentation: A 65-year-old-male with a known history of longstanding erosive, nodular, seropositive rheumatoid arthritis was incidentally found to have a mesenteric mass on computed tomography (CT) exam of the abdomen. This mass had not been present on prior imaging studies and was worrisome for a malignancy. Attempts at noninvasive biopsy were nondiagnostic but consistent with a "spindle" cell neoplasm. Laparotomy revealed extensive thickening and fibrosis of the small bowel mesentery along with large, firm nodules throughout the mesentery. A limited bowel resection including a large, partially obstructing, nodule was performed. Pathology was consistent with an unusual presentation of rheumatoid nodules in the mesentery of the small bowel.
Conclusion: Rheumatoid nodules should be considered in the differential diagnosis of a patient who presents with an intra-abdominal mass and a history of rheumatoid arthritis. Currently, no tests or imaging modality can discriminate with sufficient accuracy to rule out a malignancy in this difficult diagnostic delimma. Hopefully, this case will serve as impetus for further study and biomarker discovery to allow for improved diagnostic power.
C1 [Tomlinson, James S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Thinda, Sumeer; Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA.
RP Tomlinson, JS (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
EM sumeer.thinda@ucla.edu; jtomlinson@mednet.ucla.edu
NR 13
TC 0
Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7819
J9 WORLD J SURG ONCOL
JI World J. Surg. Oncol.
PD JUL 15
PY 2009
VL 7
AR 59
DI 10.1186/1477-7819-7-59
PG 5
WC Oncology; Surgery
SC Oncology; Surgery
GA 488DP
UT WOS:000269329600001
PM 19604347
ER
PT J
AU Drachman, DE
AF Drachman, Douglas E.
TI Drug-Eluting Stents in Animals and Patients Where Do We Stand Today?
SO CIRCULATION
LA English
DT Editorial Material
DE Editorials; animal model; paclitaxel; restenosis; sirolimus; stents;
thrombosis
ID INTRAVASCULAR ULTRASOUND; FOLLOW-UP; PACLITAXEL; IMPLANTATION;
THROMBOSIS; MODEL
C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA.
RP Drachman, DE (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA.
EM ddrachman@partners.org
NR 19
TC 10
Z9 10
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 14
PY 2009
VL 120
IS 2
BP 101
EP 103
DI 10.1161/CIRCULATIONAHA.109.872473
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 469XI
UT WOS:000267934700002
PM 19564555
ER
PT J
AU Yan, BP
Kiernan, TJ
Rosenfield, K
Garasic, JM
de Moor, M
AF Yan, Bryan P.
Kiernan, Thomas J.
Rosenfield, Kenneth
Garasic, Joseph M.
de Moor, Michael
TI Dynamic Left Main Coronary Artery Obstruction Associated With Williams
Syndrome
SO CIRCULATION
LA English
DT Editorial Material
C1 [Yan, Bryan P.; Kiernan, Thomas J.; Rosenfield, Kenneth; Garasic, Joseph M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Sect Vasc Med, Boston, MA USA.
[de Moor, Michael] Harvard Univ, Massachusetts Gen Hosp Children, Sch Med, Div Pediat Cardiol, Boston, MA USA.
RP de Moor, M (reprint author), Massgen Hosp Children, CRP510,175 Cambridge St, Boston, MA 02114 USA.
EM mdemoor@partners.org
RI Yan, Bryan/P-5928-2015
NR 2
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 14
PY 2009
VL 120
IS 2
BP 181
EP 182
DI 10.1161/CIRCULATIONAHA.108.831941
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 469XI
UT WOS:000267934700012
PM 19597063
ER
PT J
AU Meeker, JD
Missmer, SA
Altshul, L
Vitonis, AF
Ryan, L
Cramer, DW
Hauser, R
AF Meeker, John D.
Missmer, Stacey A.
Altshul, Larisa
Vitonis, Allison F.
Ryan, Louise
Cramer, Daniel W.
Hauser, Russ
TI Serum and follicular fluid organochlorine concentrations among women
undergoing assisted reproduction technologies
SO ENVIRONMENTAL HEALTH
LA English
DT Article
ID POLYCHLORINATED-BIPHENYLS; MATERNAL SERUM; CRITICAL WINDOWS;
UNITED-STATES; EXPOSURE; PREGNANCY; BLOOD; PLASMA; DDT; PCB
AB Background: Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error.
Methods: The present study was conducted to assess the correlation between concentrations of organochlorines in serum and follicular fluid samples collected from a subset of women undergoing ART in a large study that took place between 1994 and 2003, as well as the temporal reliability of serum organochlorine concentrations among women undergoing multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p, p'-DDT), the DDT metabolite p, p'-DDE, hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in 72 follicular fluid samples and 265 serum samples collected from 110 women.
Results: Organochlorine concentrations in paired serum and follicular fluid samples were correlated, with Pearson and Spearman coefficients ranging from 0.60 to 0.92. Serum organochlorine concentrations were two- to three-fold greater than in follicular fluid, and a significant inverse trend was observed in the distribution of follicular fluid: serum ratios with increasing molecular weight of the compound (p-value for trend < 0.0001). Serum organochlorine concentrations were highly reliable over the course of several months, with intraclass correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence for a declining trend in organochlorine concentrations between samples collected between years 1994-1998 and those collected in 1999-2003.
Conclusion: Our results support the use of a single serum sample to adequately represent a more biologically relevant dose (concentrations in follicular fluid), as well as exposure levels over time, in epidemiological studies of ART outcomes in relation to organochlorine exposure.
C1 [Meeker, John D.] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Missmer, Stacey A.; Vitonis, Allison F.; Cramer, Daniel W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Altshul, Larisa; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Ryan, Louise] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA.
[Hauser, Russ] Massachusetts Gen Hosp, Vitro Fertilizat Unit, Boston, MA 02114 USA.
RP Meeker, JD (reprint author), Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
EM meekerj@umich.edu; smissmer@hsph.harvard.edu; LALTSHUL@hsph.harvard.edu;
avitonis@partners.org; lryan@hsph.harvard.edu; dcramer@partners.org;
rhauser@hohp.harvard.edu
RI Ryan, Louise/A-4562-2009;
OI Ryan, Louise/0000-0001-5957-2490; Meeker, John/0000-0001-8357-5085
FU National Institute of Environmental Health Sciences [R01-ES013967];
National Institute of Child Health and Human Development [R01-HD32153]
FX Work supported by grant R01-ES013967 from the National Institute of
Environmental Health Sciences and grant R01-HD32153 from the National
Institute of Child Health and Human Development.
NR 42
TC 22
Z9 22
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD JUL 14
PY 2009
VL 8
AR 32
DI 10.1186/1476-069X-8-32
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 482AS
UT WOS:000268856200001
PM 19594949
ER
PT J
AU Helfrich, CD
Li, YF
Sharp, ND
Sales, AE
AF Helfrich, Christian D.
Li, Yu-Fang
Sharp, Nancy D.
Sales, Anne E.
TI Organizational readiness to change assessment (ORCA): Development of an
instrument based on the Promoting Action on Research in Health Services
(PARIHS) framework
SO IMPLEMENTATION SCIENCE
LA English
DT Article
ID TOTAL-QUALITY-MANAGEMENT; THEORETICAL PERSPECTIVES;
CONCEPTUAL-FRAMEWORK; IMPLEMENTATION; VETERANS; CONTEXT; IMPACT; CARE;
FACILITATION; IMPROVEMENT
AB Background: The Promoting Action on Research Implementation in Health Services, or PARIHS, framework is a theoretical framework widely promoted as a guide to implement evidence-based clinical practices. However, it has as yet no pool of validated measurement instruments that operationalize the constructs defined in the framework. The present article introduces an Organizational Readiness to Change Assessment instrument (ORCA), organized according to the core elements and sub-elements of the PARIHS framework, and reports on initial validation.
Methods: We conducted scale reliability and factor analyses on cross-sectional, secondary data from three quality improvement projects (n = 80) conducted in the Veterans Health Administration. In each project, identical 77-item ORCA instruments were administered to one or more staff from each facility involved in quality improvement projects. Items were organized into 19 subscales and three primary scales corresponding to the core elements of the PARIHS framework: (1) Strength and extent of evidence for the clinical practice changes represented by the QI program, assessed with four subscales, (2) Quality of the organizational context for the QI program, assessed with six subscales, and (3) Capacity for internal facilitation of the QI program, assessed with nine subscales.
Results: Cronbach's alpha for scale reliability were 0.74, 0.85 and 0.95 for the evidence, context and facilitation scales, respectively. The evidence scale and its three constituent subscales failed to meet the conventional threshold of 0.80 for reliability, and three individual items were eliminated from evidence subscales following reliability testing. In exploratory factor analysis, three factors were retained. Seven of the nine facilitation subscales loaded onto the first factor; five of the six context subscales loaded onto the second factor; and the three evidence subscales loaded on the third factor. Two subscales failed to load significantly on any factor. One measured resources in general (from the context scale), and one clinical champion role (from the facilitation scale).
Conclusion: We find general support for the reliability and factor structure of the ORCA. However, there was poor reliability among measures of evidence, and factor analysis results for measures of general resources and clinical champion role did not conform to the PARIHS framework. Additional validation is needed, including criterion validation.
C1 [Helfrich, Christian D.; Li, Yu-Fang; Sharp, Nancy D.] VA Puget Sound Healthcare Syst, NW HSR&D Ctr Excellence, Seattle, WA USA.
[Helfrich, Christian D.; Sharp, Nancy D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA.
[Helfrich, Christian D.; Sharp, Nancy D.] Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA.
[Sales, Anne E.] Univ Alberta, Fac Nursing, Edmonton, AB, Canada.
RP Helfrich, CD (reprint author), VA Puget Sound Healthcare Syst, NW HSR&D Ctr Excellence, Seattle, WA USA.
EM christian.helfrich@va.gov; yufang.li@va.gov; nancy.sharp@va.gov;
anne.sales@ualberta.ca
RI Sales, Anne/D-9678-2012; Helfrich, Christian/D-2382-2016;
OI Helfrich, Christian/0000-0002-9827-4768; Sales, Anne/0000-0001-9360-3334
FU Department of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development Service [RRP 07-280]
FX The views expressed in this article are the authors' and do not
necessarily reflect the position or policy of the Department of Veterans
Affairs.
NR 41
TC 93
Z9 95
U1 1
U2 27
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD JUL 14
PY 2009
VL 4
AR 38
DI 10.1186/1748-5908-4-38
PG 13
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 482LY
UT WOS:000268891600001
PM 19594942
ER
PT J
AU Maron, BJ
Maron, MS
Wigle, ED
Braunwald, E
AF Maron, Barry J.
Maron, Martin S.
Wigle, E. Douglas
Braunwald, Eugene
TI The 50-Year History, Controversy, and Clinical Implications of Left
Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy
From Idiopathic Hypertrophic Subaortic Stenosis to Hypertrophic
Cardiomyopathy
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Review
DE cardiomyopathies; hypertrophic; cardiac surgery; heart catheterization;
heart failure; heart failure treatment; hypertrophy
ID SYSTOLIC ANTERIOR MOTION; DIMENSIONAL ECHOCARDIOGRAPHIC ASSESSMENT;
SURGICAL SEPTAL MYECTOMY; MITRAL-VALVE; PRESSURE-GRADIENT;
DOPPLER-ECHOCARDIOGRAPHY; SUDDEN-DEATH; MYOCARDIAL-METABOLISM; OPERATIVE
TREATMENT; MYOTOMY-MYECTOMY
AB Dynamic obstruction to left ventricular (LV) outflow was recognized from the earliest (50 years ago) clinical descriptions of hypertrophic cardiomyopathy (HCM) and has proved to be a complex phenomenon unique in many respects, as well as arguably the most visible and well-known pathophysiologic component of this heterogeneous disease. Over the past 5 decades, the clinical significance attributable to dynamic LV outflow tract gradients in HCM has triggered a periodic and instructive debate. Nevertheless, only recently has evidence emerged from observational analyses in large patient cohorts that unequivocally supports subaortic pressure gradients (and obstruction) both as true impedance to LV outflow and independent determinants of disabling exertional symptoms and cardiovascular mortality. Furthermore, abolition of subaortic gradients by surgical myectomy (or percutaneous alcohol septal ablation) results in profound and consistent symptomatic benefit and restoration of quality of life, with myectomy providing a long-term survival similar to that observed in the general population. These findings resolve the long-festering controversy over the existence of obstruction in HCM and whether outflow gradients are clinically important elements of this complex disease. These data also underscore the important principle, particularly relevant to clinical practice, that heart failure due to LV outflow obstruction in HCM is mechanically reversible and amenable to invasive septal reduction therapy. Finally, the recent observation that the vast majority of patients with HCM have the propensity to develop outflow obstruction (either at rest or with exercise) underscores a return to the characterization of HCM in 1960 as a predominantly obstructive disease. (J Am Coll Cardiol 2009; 54: 191-200) (C) 2009 by the American College of Cardiology Foundation
C1 [Maron, Barry J.] Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN 55407 USA.
[Maron, Martin S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Hypertroph Cardiomyopathy Ctr,Tufts Med Ctr, Boston, MA 02115 USA.
[Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp, Boston, MA 02115 USA.
[Wigle, E. Douglas] Toronto Gen Hosp, Div Cardiol, Toronto, ON, Canada.
RP Maron, BJ (reprint author), Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, 920 E 28th St,Suite 620, Minneapolis, MN 55407 USA.
EM hcm.maron@mhif.org
NR 101
TC 115
Z9 124
U1 0
U2 13
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 JUL 14
PY 2009
VL 54
IS 3
BP 191
EP 200
DI 10.1016/j.jacc.2008.11.069
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 467SJ
UT WOS:000267762400001
PM 19589431
ER
PT J
AU Khalil, AM
Guttman, M
Huarte, M
Garber, M
Raj, A
Morales, DR
Thomas, K
Presser, A
Bernstein, BE
van Oudenaarden, A
Regev, A
Lander, ES
Rinn, JL
AF Khalil, Ahmad M.
Guttman, Mitchell
Huarte, Maite
Garber, Manuel
Raj, Arjun
Morales, Dianali Rivea
Thomas, Kelly
Presser, Aviva
Bernstein, Bradley E.
van Oudenaarden, Alexander
Regev, Aviv
Lander, Eric S.
Rinn, John L.
TI Many human large intergenic noncoding RNAs associate with
chromatin-modifying complexes and affect gene expression
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE histone modifications; epigenetic regulation; polycomb
ID HUMAN GENOME; DIFFERENTIATION; HETEROCHROMATIN; CELLS; FATE
AB We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc) RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, weexpand the catalog of human lincRNAs to approximate to 3,300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR binds the polycomb repressive complex (PRC) 2, we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that approximate to 20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Also, we show that siRNA-mediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression, and that the up-regulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatin-modifying complexes to specific genomic loci to regulate gene expression.
C1 [Khalil, Ahmad M.; Guttman, Mitchell; Huarte, Maite; Garber, Manuel; Morales, Dianali Rivea; Thomas, Kelly; Presser, Aviva; Bernstein, Bradley E.; Regev, Aviv; Lander, Eric S.; Rinn, John L.] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Khalil, Ahmad M.; Guttman, Mitchell; Huarte, Maite; Garber, Manuel; Morales, Dianali Rivea; Thomas, Kelly; Presser, Aviva; Bernstein, Bradley E.; Regev, Aviv; Lander, Eric S.; Rinn, John L.] MIT, Cambridge, MA 02142 USA.
[Khalil, Ahmad M.; Huarte, Maite; Morales, Dianali Rivea; Thomas, Kelly; Rinn, John L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Guttman, Mitchell; Regev, Aviv; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Raj, Arjun; van Oudenaarden, Alexander] MIT, Dept Phys, Cambridge, MA 02139 USA.
[Bernstein, Bradley E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.
[Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
[Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA.
RP Lander, ES (reprint author), Broad Inst Harvard, Cambridge, MA 02142 USA.
EM lander@broad.mit.edu; jrinn@broad.mit.edu
RI Huarte, Maite/J-6903-2014; jia, xu/A-8386-2016;
OI Huarte, Maite/0000-0003-3753-6493; Raj, Arjun/0000-0002-2915-6960
FU National Institutes of Health [HL007893]; National Human Genome Research
Institute; Broad Institute of MIT and Harvard.
FX We thank Yang Shi and Shigeki Iwase (Harvard Medical School) for
antibodies to SMCX and their input on the manuscript; J. P. Mesirov and
Pablo Tamayo [The Broad Institute of Harvard and Massachusetts Institute
of Technology ( MIT)] for discussions and statistical insights; and
Miguel Rivera for access to hEK ChIP-Seq data. A. M. K. is supported by
National Institutes of Health Training Grant HL007893. M. Guttman is a
Vertex scholar. J. L. R is a Damon Runyon-Rachleff Innovation and Smith
Family Foundation Scholar. J. L. R. and A. Regev are Investigators of
the Richard Merkin Foundation for Stem Cell Research at the Broad
Institute. A. R. is supported by the Pioneer award and by the Burroughs
Wellcome Fund. This work was supported by the National Human Genome
Research Institute, and the Broad Institute of MIT and Harvard.
NR 27
TC 1228
Z9 1292
U1 13
U2 128
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 JUL 14
PY 2009
VL 106
IS 28
BP 11667
EP 11672
DI 10.1073/pnas.0904715106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470KD
UT WOS:000267972700045
PM 19571010
ER
PT J
AU Chan, YM
de Guillebon, A
Lang-Muritano, M
Plummer, L
Cerrato, F
Tsiaras, S
Gaspert, A
Lavoie, HB
Wu, CH
Crowley, WF
Amory, JK
Pitteloud, N
Seminara, SB
AF Chan, Yee-Ming
de Guillebon, Adelaide
Lang-Muritano, Mariarosaria
Plummer, Lacey
Cerrato, Felecia
Tsiaras, Sarah
Gaspert, Ariana
Lavoie, Helene B.
Wu, Ching-Hui
Crowley, William F., Jr.
Amory, John K.
Pitteloud, Nelly
Seminara, Stephanie B.
TI GNRH1 mutations in patients with idiopathic hypogonadotropic
hypogonadism
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE GnRH; luteinizing hormone-releasing hormone; LHRH
ID GONADOTROPIN-RELEASING-HORMONE; KALLMANN-SYNDROME; LUTEINIZING-HORMONE;
MESSENGER-RNA; GENE; RECEPTOR; DEFICIENCY; PROTEIN; MOUSE;
PROKINETICIN-2
AB Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by failure to undergo puberty in the setting of low sex steroids and low gonadotropins. IHH is due to abnormal secretion or action of the master reproductive hormone gonadotropin-releasing hormone (GnRH). Several genes have been found to be mutated in patients with IHH, yet to date no mutations have been identified in the most obvious candidate gene, GNRH1 itself, which encodes the preprohormone that is ultimately processed to produce GnRH. We screened DNA from 310 patients with normosmic IHH (nIHH) and 192 healthy control subjects for sequence changes in GNRH1. In 1 patient with severe congenital nIHH (with micropenis, bilateral cryptorchidism, and absent puberty), a homozygous frameshift mutation that is predicted to disrupt the 3 C-terminal amino acids of the GnRH decapeptide and to produce a premature stop codon was identified. Heterozygous variants not seen in controls were identified in 4 patients with nIHH: 1 nonsynonymous missense mutation in the eighth amino acid of the GnRH decapeptide, 1 nonsense mutation that causes premature termination within the GnRH-associated peptide (GAP), which lies C-terminal to the GnRH decapeptide within the GnRH precursor, and 2 sequence variants that cause nonsynonymous amino-acid substitutions in the signal peptide and in GnRH-associated peptide. Our results establish mutations in GNRH1 as a genetic cause of nIHH.
C1 [Chan, Yee-Ming; de Guillebon, Adelaide; Plummer, Lacey; Cerrato, Felecia; Tsiaras, Sarah; Crowley, William F., Jr.; Pitteloud, Nelly; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Boston, MA 02114 USA.
[Chan, Yee-Ming; de Guillebon, Adelaide; Plummer, Lacey; Cerrato, Felecia; Tsiaras, Sarah; Crowley, William F., Jr.; Pitteloud, Nelly; Seminara, Stephanie B.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA.
[Chan, Yee-Ming] Childrens Hosp, Div Endocrinol, Dept Med, Boston, MA 02115 USA.
[Lang-Muritano, Mariarosaria] Univ Childrens Hosp Zurich, Pediat Endocrine Unit, CH-8032 Zurich, Switzerland.
[Gaspert, Ariana] Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland.
[Lavoie, Helene B.] CHU Montreal, Div Endocrinol, Dept Med, Montreal, PQ H2X 3J4, Canada.
[Lavoie, Helene B.] PROCREA Clin, Montreal, PQ H4P 2R2, Canada.
[Amory, John K.] Univ Washington, Med Ctr, Div Gen Internal Med, Seattle, WA 98195 USA.
RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, 55 Fruit St,BHX 5, Boston, MA 02114 USA.
EM seminara.stephanie@mgh.harvard.edu
RI PITTELOUD, Nelly/K-2709-2014
FU National Institutes of Health/National Institute of Child Health and
Human Development [U54 HD028138, F32 HD056759]
FX We thank Martin Dym for assistance with interpretation of testicular
histology. This work was supported by National Institutes of
Health/National Institute of Child Health and Human Development Grant
U54 HD028138. Y.-M. C. received support from National Institutes of
Health/National Institute of Child Health and Human Development Grant
F32 HD056759.
NR 46
TC 86
Z9 88
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 14
PY 2009
VL 106
IS 28
BP 11703
EP 11708
DI 10.1073/pnas.0903449106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470KD
UT WOS:000267972700051
PM 19567835
ER
PT J
AU Ho, O
Larsen, K
Polacino, P
Li, Y
Anderson, D
Song, RJ
Ruprecht, RM
Hu, SL
AF Ho, On
Larsen, Kay
Polacino, Patricia
Li, Yun
Anderson, David
Song, Ruijiang
Ruprecht, Ruth M.
Hu, Shiu-Lok
TI Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C
simian-human immunodeficiency virus
SO RETROVIROLOGY
LA English
DT Article
ID CD4(+) T-CELLS; NEUTRALIZING ANTIBODY-RESPONSES; PIG-TAILED MACAQUES;
ACUTE SIV INFECTION; RHESUS MACAQUES; IN-VIVO; HIV-1 INFECTION;
GASTROINTESTINAL-TRACT; AIDS PATHOGENESIS; VIRAL REPLICATION
AB Background: Although pig-tailed macaques (Macaca nemestrina) have been used in AIDS research for years, less is known about the early immunopathogenic events in this species, as compared to rhesus macaques (Macaca mulatta). Similarly, the events in early infection are well-characterized for simian immunodeficiency viruses (SIV), but less so for chimeric simian-human immunodeficiency viruses (SHIV), although the latter have been widely used in HIV vaccine studies. Here, we report the consequences of intrarectal infection with a CCR5-tropic clade C SHIV-1157ipd3N4 in pig-tailed macaques.
Results: Plasma and cell-associated virus was detectable in peripheral blood and intestinal tissues of all four pig-tailed macaques following intrarectal inoculation with SHIV-1157ipd3N4. We also observed a rapid and irreversible loss of CD4(+) T cells at multiple mucosal sites, resulting in a marked decrease of CD4:CD8 T cell ratios 0.5-4 weeks after inoculation. This depletion targeted subsets of CD4(+) T cells expressing the CCR5 coreceptor and having a CD28-CD95(+) effector memory phenotype, consistent with the R5-tropism of SHIV-1157ipd3N4. All three animals that were studied beyond the acute phase seroconverted as early as week 4, with two developing cross-clade neutralizing antibody responses by week 24. These two animals also demonstrated persistent plasma viremia for > 48 weeks. One of these animals developed AIDS, as shown by peripheral blood CD4(+) T-cell depletion starting at 20 weeks post inoculation.
Conclusion: These findings indicate that SHIV-1157ipd3N4-induced pathogenesis in pig-tailed macaques followed a similar course as SIV-infected rhesus macaques. Thus, R5 SHIV-C-infection of pig-tailed macaques could provide a useful and relevant model for AIDS vaccine and pathogenesis research.
C1 [Ho, On; Li, Yun; Hu, Shiu-Lok] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.
[Larsen, Kay; Polacino, Patricia; Anderson, David; Hu, Shiu-Lok] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98121 USA.
[Song, Ruijiang; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Song, Ruijiang; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Song, Ruijiang] Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA.
RP Hu, SL (reprint author), Univ Washington, Dept Pharmaceut, Box 357610, Seattle, WA 98195 USA.
EM onh@bart.rprc.washington.edu; kayl@bart.rprc.washington.edu;
patf@bart.rprc.washington.edu; yunli@bart.rprc.washington.edu;
davea@bart.rprc.washington.edu; rsong@adarc.org;
ruth_ruprecht@dfci.harvard.edu; hus@bart.rprc.washington.edu
RI Hu, Shiu-Lok/A-3196-2008
OI Hu, Shiu-Lok/0000-0003-4336-7964
FU NIH [P51 RR0166, P01 AI24048]
FX We thank the veterinary and animal care staff at the WaNPRC for
excellent care of the macaques; Drs. Steve Kelley and Keith Vogel, and
Leon Flanary and Joel Ahrens for mucosal sample collections; Dr. Robert
Murnane for histopathological analyses; Heather Mack, Ryan Wallerstedt,
Valerie Teske, Xuebing Li, Taryn Urion, and Modou Mbowe for expert
technical assistance; and Drs. Don Sodora, Ron Veazey, Louis Picker, and
John Fanton, and Kiran Mir and Amanda Leone for helpful discussions.
This study is supported in part by NIH grants and contracts P51 RR0166 (
WaNPRC) and P01 AI24048 ( RMR and SLH).
NR 80
TC 13
Z9 14
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JUL 14
PY 2009
VL 6
AR 65
DI 10.1186/1742-4690-6-65
PG 16
WC Virology
SC Virology
GA 487TR
UT WOS:000269299800001
PM 19602283
ER
PT J
AU Kruse, GR
Chapula, BT
Ikeda, S
Nkhoma, M
Quiterio, N
Pankratz, D
Mataka, K
Chi, BH
Bond, V
Reid, SE
AF Kruse, Gina R.
Chapula, Bushimbwa Tambatamba
Ikeda, Scott
Nkhoma, Mavis
Quiterio, Nicole
Pankratz, Debra
Mataka, Kaluba
Chi, Benjamin H.
Bond, Virginia
Reid, Stewart E.
TI Burnout and use of HIV services among health care workers in Lusaka
District, Zambia: a cross-sectional study
SO HUMAN RESOURCES FOR HEALTH
LA English
DT Article
ID SOUTH-AFRICA; ANTIRETROVIRAL TREATMENT; SCALING-UP; HIV/AIDS; OUTCOMES;
THERAPY; JOB; PERCEPTIONS; MORTALITY; COUNTRIES
AB Background: Well-documented shortages of health care workers in sub-Saharan Africa are exacerbated by the increased human resource demands of rapidly expanding HIV care and treatment programmes. The successful continuation of existing programmes is threatened by health care worker burnout and HIV-related illness.
Methods: From March to June 2007, we studied occupational burnout and utilization of HIV services among health providers in the Lusaka public health sector. Providers from 13 public clinics were given a 36-item, self-administered questionnaire and invited for focus group discussions and key-informant interviews.
Results: Some 483 active clinical staff completed the questionnaire (84% response rate), 50 staff participated in six focus groups, and four individuals gave interviews. Focus group participants described burnout as feeling overworked, stressed and tired. In the survey, 51% reported occupational burnout. Risk factors were having another job (RR 1.4 95% CI 1.2-1.6) and knowing a co-worker who left in the last year (RR 1.6 95% CI 1.3-2.2). Reasons for co-worker attrition included: better pay (40%), feeling overworked or stressed (21%), moving away (16%), death (8%) and illness (5%). When asked about HIV testing, 370 of 456 (81%) reported having tested; 240 (50%) tested in the last year. In contrast, discussion groups perceived low testing rates. Both discussion groups and survey respondents identified confidentiality as the prime reason for not undergoing HIV testing.
Conclusion: In Lusaka primary care clinics, overwork, illness and death were common reasons for attrition. Programmes to improve access, acceptability and confidentiality of health care services for clinical providers and to reduce workplace stress could substantially affect workforce stability.
C1 [Kruse, Gina R.; Ikeda, Scott; Nkhoma, Mavis; Quiterio, Nicole; Pankratz, Debra; Mataka, Kaluba; Chi, Benjamin H.; Reid, Stewart E.] CIDRZ, Lusaka, Zambia.
[Kruse, Gina R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Chapula, Bushimbwa Tambatamba] Zambian Minist Hlth, Lusaka Dist Hlth Management Team, Lusaka, Zambia.
[Ikeda, Scott] Montefiore Med Ctr, Dept Family & Social Med, Bronx, NY 10467 USA.
[Quiterio, Nicole] Robert Wood Johnson Univ Hosp, Bristol Myers Squibb Childrens Hosp, Dept Pediat, New Brunswick, NJ USA.
[Chi, Benjamin H.] Univ Alabama, Dept Obstet & Gynecol, Sch Med, Birmingham, AL 35294 USA.
[Chi, Benjamin H.] Univ Alabama, Dept Obstet & Gynecol, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Bond, Virginia] ZAMBART Project, Lusaka, Zambia.
[Bond, Virginia] London Sch Hyg & Trop Med, Dept Publ Hlth & Policy, Hlth Policy Unit, London WC1, England.
[Reid, Stewart E.] Univ Alabama, Sch Med, Div Infect Dis, Birmingham, AL USA.
RP Reid, SE (reprint author), CIDRZ, Lusaka, Zambia.
EM gkruse@partners.org; bushitamba@doctors.org.uk; scott.ikeda@gmail.com;
mavis.nkhoma@cidrz.org; nicole.quiterio@gmail.com;
debra.pankratz@cidrz.org; kaluba.mataka@cidrz.org;
benjamin.chi@cidrz.org; gbond@zambart.org.zm; stewart.reid@cidrz.org
OI Reid, Stewart/0000-0001-7779-4820
FU FIC NIH HHS [K01 TW006670]
NR 30
TC 30
Z9 30
U1 1
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1478-4491
J9 HUM RESOUR HEALTH
JI Hum. Resour. Health
PD JUL 13
PY 2009
VL 7
AR 55
DI 10.1186/1478-4491-7-55
PG 10
WC Health Policy & Services; Industrial Relations & Labor
SC Health Care Sciences & Services; Business & Economics
GA 482LM
UT WOS:000268890400002
PM 19594917
ER
PT J
AU Holmans, P
Green, EK
Pahwa, JS
Ferreira, MAR
Purcell, SM
Sklar, P
Owen, MJ
O'Donovan, MC
Craddock, N
AF Holmans, Peter
Green, Elaine K.
Pahwa, Jaspreet Singh
Ferreira, Manuel A. R.
Purcell, Shaun M.
Sklar, Pamela
Owen, Michael J.
O'Donovan, Michael C.
Craddock, Nick
CA Wellcome Trust Case Control Consor
TI Gene Ontology Analysis of GWA Study Data Sets Provides Insights into the
Biology of Bipolar Disorder
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; COMMON DISEASES; MOOD
DISORDERS; LINKS; AXIS; PRIORITIZATION; SCHIZOPHRENIA; PATHOGENESIS;
VARIANTS
AB We present a method for testing overrepresentation of biological pathways, indexed by gene-ontology terms, in lists of significant SNPs from genome-wide association studies. This method corrects for linkage disequilibrium between SNPs, variable gene size, and multiple testing of nonindependent pathways. The method was applied to the Wellcome Trust Case-Control Consortium Crohn disease (CD) data set. At a general level, the biological basis of CD is relatively well known for a complex genetic trait, and it thus acted as a test of the method. The method, known as ALIGATOR (Association LIst Go AnnoTatOR), successfully detected biological pathways implicated in CD. The method was also applied to a meta-analysis of bipolar disorder, and it implicated the modulation of transcription and cellular activity, including that which occurs via hormonal action, as an important player in pathogenesis.
C1 [Holmans, Peter; Green, Elaine K.; Pahwa, Jaspreet Singh; Owen, Michael J.; O'Donovan, Michael C.; Craddock, Nick] Sch Med, Dept Psychol Med & Neurol, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF23 6BQ, S Glam, Wales.
[Ferreira, Manuel A. R.; Purcell, Shaun M.; Sklar, Pamela] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Ferreira, Manuel A. R.; Purcell, Shaun M.; Sklar, Pamela] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Ferreira, Manuel A. R.; Purcell, Shaun M.; Sklar, Pamela] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
[Ferreira, Manuel A. R.; Purcell, Shaun M.; Sklar, Pamela] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Ferreira, Manuel A. R.; Purcell, Shaun M.; Sklar, Pamela] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
[Ferreira, Manuel A. R.] Genet Epidemiol Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
RP Holmans, P (reprint author), Sch Med, Dept Psychol Med & Neurol, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF23 6BQ, S Glam, Wales.
EM holmanspa@cardiff.ac.uk
RI Ferreira, Manuel/D-3609-2013; Holmans, Peter/F-4518-2015;
OI Holmans, Peter/0000-0003-0870-9412; O'Donovan,
Michael/0000-0001-7073-2379
FU Medical Research Council; Wellcome Trust
NR 42
TC 244
Z9 250
U1 3
U2 22
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 10
PY 2009
VL 85
IS 1
BP 13
EP 24
DI 10.1016/j.ajhg.2009.05.011
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 470RO
UT WOS:000267997600004
PM 19539887
ER
PT J
AU Lee, JH
Ryu, H
Kowall, NW
AF Lee, Junghee
Ryu, Hoon
Kowall, Neil W.
TI Motor neuronal protection by L-arginine prolongs survival of mutant SOD1
(G93A) ALS mice
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Amyotrophic lateral sclerosis (ALS); L-Arginine; Motor neuron;
Polyamines; Superoxide dismutase 1 (SOD1)
ID AMYOTROPHIC-LATERAL-SCLEROSIS; HYPERCHOLESTEROLEMIC MICE;
SUPEROXIDE-DISMUTASE; INHIBITION; POLYAMINES; GLUTAMATE; ARGINASE;
GROWTH
AB Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. Despite the fact that many different therapeutic strategies have been applied to prevent disease progression, no cure or effective therapy is currently available for ALS. We found that L-arginine protects cultured motor neurons from excitotoxic injury. We also found that L-arginine supplementation both prior to and after the onset of motor neuron degeneration in mtSOD1 (G93A) transgenic ALS mice significantly slowed the progression of neuropathology in lumbar spinal cord, delayed onset of motor dysfunction, and prolonged life span. Moreover, L-arginine treatment was associated with preservation of arginase I activity and neuroprotective polyamines in spinal cord motor neurons. Our findings show that L-arginine has potent in vitro and in vivo neuroprotective properties and may be a candidate for therapeutic trials in ALS. Published by Elsevier Inc
C1 [Lee, Junghee; Ryu, Hoon; Kowall, Neil W.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Kowall, Neil W.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA.
[Lee, Junghee; Ryu, Hoon; Kowall, Neil W.] VA Boston Healthcare Syst, Neurol Serv, Boston, MA 02130 USA.
[Lee, Junghee; Ryu, Hoon; Kowall, Neil W.] VA Boston Healthcare Syst, Geriatr Res & Educ & Clin Ctr, Boston, MA 02130 USA.
RP Lee, JH (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
EM junghee@bu.edu; nkowall@bu.edu
RI Kowall, Neil/G-6364-2012
OI Kowall, Neil/0000-0002-6624-0213
FU NIA NIH HHS [P30 AG013846-09, P30 AG013846, P30 AG13846]; NINDS NIH HHS
[R01 NS052724-03, R01 NS052724, NS52724]
NR 23
TC 14
Z9 14
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 10
PY 2009
VL 384
IS 4
BP 524
EP 529
DI 10.1016/j.bbrc.2009.05.015
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 454NN
UT WOS:000266689300024
PM 19427829
ER
PT J
AU Svendsen, JM
Smogorzewska, A
Sowa, ME
O'Connell, BC
Gygi, SP
Elledge, SJ
Harper, JW
AF Svendsen, Jennifer M.
Smogorzewska, Agata
Sowa, Mathew E.
O'Connell, Brenda C.
Gygi, Steven P.
Elledge, Stephen J.
Harper, J. Wade
TI Mammalian BTBD12/SLX4 Assembles A Holliday Junction Resolvase and Is
Required for DNA Repair
SO CELL
LA English
DT Article
ID STRUCTURE-SPECIFIC ENDONUCLEASE; SACCHAROMYCES-CEREVISIAE; MEIOTIC
CROSSOVERS; MUS81-EME1; IDENTIFICATION; RESOLUTION; MECHANISM; PROTEINS;
DAMAGE; YEAST
AB Structure-specific endonucleases mediate cleavage of DNA structures formed during repair of collapsed replication forks and double-strand breaks (DSBs). Here, we identify BTBD12 as the human ortholog of the budding yeast DNA repair factor Slx4p and D. melanogaster MUS312. Human SLX4 forms a multiprotein complex with the ERCC4(XPF)-ERCC1, MUS81-EME1, and SLX1 endonucleases and also associates with MSH2/MSH3 mismatch repair complex, telomere binding complex TERF2(TRF2)-TERF2IP(RAP1), the protein kinase PLK1 and the uncharacterized protein C20orf94. Depletion of SLX4 causes sensitivity to mitomycin C and camptothecin and reduces the efficiency of DSB repair in vivo. SLX4 complexes cleave 3' flap, 5' flap, and replication fork structures; yet unlike other endonucleases associated with SLX4, the SLX1-SLX4 module promotes symmetrical cleavage of static and migrating Holliday junctions (HJs), identifying SLX1-SLX4 as a HJ resolvase. Thus, SLX4 assembles a modular toolkit for repair of specific types of DNA lesions and is critical for cellular responses to replication fork failure.
C1 [Svendsen, Jennifer M.; Sowa, Mathew E.; O'Connell, Brenda C.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Smogorzewska, Agata; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Smogorzewska, Agata; Elledge, Stephen J.] Brigham & Womens Hosp, Howard Hughes Med Inst, Dept Med, Div Genet, Boston, MA 02115 USA.
[Smogorzewska, Agata] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Harper, JW (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM wade_harper@hms.harvard.edu
RI Smogorzewska, Agata/B-8891-2011
FU National Institutes of Health; Centers for Medical Countermeasures
Against Radiation; Stewart Trust; Burroughs Wellcome Fund; American
Cancer Society; [T32CA09216]
FX We thank Clare McGowan, Richard Wood, Orlando Scharer, Joyce Reardon,
Laura Niedernhofer, Maria Jasin, Steve West, and Guang Hu for reagents,
John Rouse, Jim Haber, Jeff Sekelsky, Monica Colaiacovo, and Pierre-
Henri Gaillard for communicating results prior to publication, and
Alberto Ciccia and Maria Jasin for discussions. This work was supported
by grants from the National Institutes of Health to S.J.E., S.P.G., and
J.W.H., a Centers for Medical Countermeasures Against Radiation grant to
S.J.E., and by a grant from the Stewart Trust to J.W.H.A.S. is supported
by T32CA09216 to the Pathology Department at the Massachusetts General
Hospital and by an award from the Burroughs Wellcome Fund. B.C.O. is
supported by a postdoctoral fellowship from the American Cancer Society.
S.J.E. is an investigator of the Howard Hughes Medical Institute.
NR 34
TC 252
Z9 263
U1 1
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 10
PY 2009
VL 138
IS 1
BP 63
EP 77
DI 10.1016/j.cell.2009.06.030
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 468UN
UT WOS:000267848600015
PM 19596235
ER
PT J
AU Emery, B
Agalliu, D
Cahoy, JD
Watkins, TA
Dugas, JC
Mulinyawe, SB
Ibrahim, A
Ligon, KL
Rowitch, DH
Barres, BA
AF Emery, Ben
Agalliu, Dritan
Cahoy, John D.
Watkins, Trent A.
Dugas, Jason C.
Mulinyawe, Sara B.
Ibrahim, Adilijan
Ligon, Keith L.
Rowitch, David H.
Barres, Ben A.
TI Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator
Required for CNS Myelination
SO CELL
LA English
DT Article
ID OLIGODENDROCYTE DIFFERENTIATION; NERVOUS-SYSTEM; NKX2.2; BRAIN; SOX10;
OLIG1; EXPRESSION; LINEAGE; BINDING; PROTEIN
AB The transcriptional control of CNS myelin gene expression is poorly understood. Here we identify gene model 98, which we have named myelin gene regulatory factor (MRF), as a transcriptional regulator required for CNS myelination. Within the CNS, MRF is specifically expressed by postmitotic oligodendrocytes. MRF is a nuclear protein containing an evolutionarily conserved DNA binding domain homologous to a yeast transcription factor. Knockdown of MRF in oligodendrocytes by RNA interference prevents expression of most CNS myelin genes; conversely, overexpression of MRF within cultured oligodendrocyte progenitors or the chick spinal cord promotes expression of myelin genes. In mice lacking MRF within the oligodendrocyte lineage, premyelinating oligodendrocytes are generated but display severe deficits in myelin gene expression and fail to myelinate. These mice display severe neurological abnormalities and die because of seizures during the third postnatal week. These findings establish MRF as a critical transcriptional regulator essential for oligodendrocyte maturation and CNS myelination.
C1 [Emery, Ben; Agalliu, Dritan; Cahoy, John D.; Watkins, Trent A.; Dugas, Jason C.; Mulinyawe, Sara B.; Ibrahim, Adilijan; Barres, Ben A.] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
[Ligon, Keith L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Rowitch, David H.] Univ Calif San Francisco, Dept Pediat, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
[Rowitch, David H.] Univ Calif San Francisco, Inst Regenerat Med, San Francisco, CA 94143 USA.
RP Emery, B (reprint author), Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
EM bemery@stanford.edu
RI Emery, Ben/I-6223-2013;
OI Emery, Ben/0000-0002-9132-3045
FU National Eye Institute [RO1 EY10257]; Australian NHMRC CJ Martin
FX We thank Professor Klaus-Armin Nave for kindly providing the CNP-Cre
mouse line. We are indebted to Lydia-Marie Joubert for processing
samples for TEM and Elizabeth Zou for processing samples for Affymetrix
analysis. This work was funded by the National Eye Institute (RO1
EY10257, B. A. B.) and the Myelin Repair Foundation. B. E. is supported
by an Australian NHMRC CJ Martin award.
NR 27
TC 141
Z9 145
U1 3
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 10
PY 2009
VL 138
IS 1
BP 172
EP 185
DI 10.1016/j.cell.2009.04.031
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 468UN
UT WOS:000267848600023
PM 19596243
ER
PT J
AU Kleiner, S
Nguyen-Tran, V
Bare, O
Huang, XM
Spiegelman, B
Wu, ZD
AF Kleiner, Sandra
Nguyen-Tran, Van
Bare, Olivia
Huang, Xueming
Spiegelman, Bruce
Wu, Zhidan
TI PPAR delta Agonism Activates Fatty Acid Oxidation via PGC-1 alpha but
Does Not Increase Mitochondrial Gene Expression and Function
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SKELETAL-MUSCLE; COACTIVATOR PGC-1-ALPHA; TRANSCRIPTIONAL CONTROL;
METABOLIC SYNDROME; ENERGY-METABOLISM; RECEPTOR; CELLS; GAMMA; OBESITY;
ALPHA
AB PPAR delta (peroxisome proliferator-activated receptor delta) is a regulator of lipid metabolism and has been shown to induce fatty acid oxidation (FAO). PPAR delta transgenic and knock-out mice indicate an involvement of PPAR delta in regulating mitochondrial biogenesis and oxidative capacity; however, the precise mechanisms by which PPAR delta regulates these pathways in skeletal muscle remain unclear. In this study, we determined the effect of selective PPAR delta agonism with the synthetic ligand, GW501516, on FAO and mitochondrial gene expression in vitro and in vivo. Our results show that activation of PPAR delta by GW501516 led to a robust increase in mRNA levels of key lipid metabolism genes. Mitochondrial gene expression and function were not induced under the same conditions. Additionally, the activation of Pdk4 transcription by PPAR delta was coactivated by PGC-1 alpha. PGC-1 alpha, but not PGC-1 beta, was essential for full activation of Cpt-1b and Pdk4 gene expression via PPAR beta agonism. Furthermore, the induction of FAO by PPAR delta agonism was completely abolished in the absence of both PGC-1 alpha and PGC-1 beta Conversely, PGC-1 alpha-driven FAO was independent of PPAR delta. Neither GW501516 treatment nor knockdown of PPAR delta affects PGC-1 alpha-induced mitochondrial gene expression in primary myotubes. These results demonstrate that pharmacological activation of PPAR delta induces FAO via PGC-1 alpha. However, PPAR delta agonism does not induce mitochondrial gene expression and function. PGC-1 alpha-induced FAO and mitochondrial biogenesis appear to be independent of PPAR delta.
C1 [Nguyen-Tran, Van] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
[Kleiner, Sandra; Spiegelman, Bruce] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kleiner, Sandra; Spiegelman, Bruce] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kleiner, Sandra; Bare, Olivia; Huang, Xueming; Wu, Zhidan] Novartis Inst Biomed Res Inc, Cardiovasc & Metab Dis Area, Cambridge, MA 02139 USA.
RP Wu, ZD (reprint author), 100 Technol Sq, Cambridge, MA 02139 USA.
EM zhidan.wu@novartis.com
NR 25
TC 67
Z9 69
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 10
PY 2009
VL 284
IS 28
BP 18624
EP 18633
DI 10.1074/jbc.M109.008797
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467BP
UT WOS:000267711500011
PM 19435887
ER
PT J
AU Kwak, SY
Wiedemann-Bidlack, FB
Beniash, E
Yamakoshi, Y
Simmer, JP
Litman, A
Margolis, HC
AF Kwak, Seo-Young
Wiedemann-Bidlack, Felicitas B.
Beniash, Elia
Yamakoshi, Yasuo
Simmer, James P.
Litman, Amy
Margolis, Henry C.
TI Role of 20-kDa Amelogenin (P148) Phosphorylation in Calcium Phosphate
Formation in Vitro
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PORCINE-AMELOGENINS; MOUSE AMELOGENINS; ENAMEL; HYDROXYAPATITE; GROWTH;
CRYSTALS; NUCLEATION; PARTICLES; CARBONATE; PROTEINS
AB The potential role of amelogenin phosphorylation in enamel formation is elucidated through in vitro mineralization studies. Studies focused on the native 20-kDa porcine amelogenin proteolytic cleavage product P148 that is prominent in developing enamel. Experimental conditions supported spontaneous calcium phosphate precipitation with the initial formation of amorphous calcium phosphate (ACP). In the absence of protein, ACP was found to undergo relatively rapid transformation to randomly oriented plate-like apatitic crystals. In the presence of non-phosphorylated recombinant full-length amelogenin, rP172, a longer induction period was observed during which relatively small ACP nanoparticles were transiently stabilized. In the presence of rP172, these nanoparticles were found to align to form linear needle-like particles that subsequently transformed and organized into parallel arrays of apatitic needle-like crystals. In sharp contrast to these findings, P148, with a single phosphate group on serine 16, was found to inhibit calcium phosphate precipitation and stabilize ACP formation for more than 1 day. Additional studies using non- phosphorylated recombinant (rP147) and partially dephosphorylated forms of P148 (dephoso-P148) showed that the single phosphate group in P148 was responsible for the profound effect on mineral formation in vitro. The present study has provided, for the first time, evidence suggesting that the native proteolytic cleavage product P148 may have an important functional role in regulating mineralization during enamel formation by preventing unwanted mineral formation within the enamel matrix during the secretory stage of amelogenesis. Results obtained have also provided new insights into the functional role of the highly conserved hydrophilic C terminus found in full-length amelogenin. found in full-length amelogenin.
C1 [Kwak, Seo-Young; Wiedemann-Bidlack, Felicitas B.; Litman, Amy; Margolis, Henry C.] Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA.
[Beniash, Elia] Univ Pittsburgh, Dept Oral Biol, Pittsburgh, PA 15261 USA.
[Yamakoshi, Yasuo; Simmer, James P.] Univ Michigan, Dent Res Lab, Ann Arbor, MI 48109 USA.
RP Margolis, HC (reprint author), 140 Fenway, Boston, MA 02115 USA.
EM hmargolis@forsyth.org
FU National Institutes of Health [DE-016376, T32 DE-007327]
FX Supported in part by National Institutes of Health Grant T32 DE-007327.
NR 43
TC 49
Z9 52
U1 1
U2 13
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 10
PY 2009
VL 284
IS 28
BP 18972
EP 18979
DI 10.1074/jbc.M109.020370
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467BP
UT WOS:000267711500047
PM 19443653
ER
PT J
AU Goodwin, PJ
Ligibel, JA
Stambolic, V
AF Goodwin, Pamela J.
Ligibel, Jennifer A.
Stambolic, Vuk
TI Metformin in Breast Cancer: Time for Action
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID ACTIVATED PROTEIN-KINASE; INSULIN; TARGET; PATHWAY; RISK
C1 [Goodwin, Pamela J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Goodwin, Pamela J.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[Ligibel, Jennifer A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Stambolic, Vuk] Univ Hlth Network, Ontario Canc Inst, Div Signaling Biol, Toronto, ON, Canada.
RP Goodwin, PJ (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.
RI Goodwin, Pamela/K-1477-2013
NR 19
TC 120
Z9 128
U1 0
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2009
VL 27
IS 20
BP 3271
EP 3273
DI 10.1200/JCO.2009.22.1630
PG 3
WC Oncology
SC Oncology
GA 468LZ
UT WOS:000267821400003
PM 19487373
ER
PT J
AU Colman, RJ
Anderson, RM
Johnson, SC
Kastman, EK
Kosmatka, KJ
Beasley, TM
Allison, DB
Cruzen, C
Simmons, HA
Kemnitz, JW
Weindruch, R
AF Colman, Ricki J.
Anderson, Rozalyn M.
Johnson, Sterling C.
Kastman, Erik K.
Kosmatka, Kristopher J.
Beasley, T. Mark
Allison, David B.
Cruzen, Christina
Simmons, Heather A.
Kemnitz, Joseph W.
Weindruch, Richard
TI Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
SO SCIENCE
LA English
DT Article
ID DIETARY RESTRICTION; ADULT MALE; LIFE-SPAN; MACAQUES
AB Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species.
C1 [Colman, Ricki J.; Anderson, Rozalyn M.; Johnson, Sterling C.; Cruzen, Christina; Simmons, Heather A.; Kemnitz, Joseph W.; Weindruch, Richard] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
[Johnson, Sterling C.; Kastman, Erik K.; Kosmatka, Kristopher J.; Kemnitz, Joseph W.; Weindruch, Richard] Univ Wisconsin, Dept Med, Madison, WI 53706 USA.
[Johnson, Sterling C.; Kastman, Erik K.; Kosmatka, Kristopher J.; Weindruch, Richard] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA.
[Beasley, T. Mark; Allison, David B.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Kemnitz, Joseph W.] Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA.
RP Colman, RJ (reprint author), Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
EM rcolman@primate.wisc.edu; rhweindr@wisc.edu
RI Kastman, Erik/N-6645-2016;
OI Kastman, Erik/0000-0001-7221-9042; Allison, David/0000-0003-3566-9399
FU NIH [P01 AG-11915, P51 RR000167]; Research Facilities Improvement
Program [RR15459-01, RR020141-01]; William S. Middleton Memorial
Veterans Hospital
FX We acknowledge the excellent technical assistance provided by S. Baum,
J. Christensen, J. A. Adriansjach, C. E. Armstrong, D. G. McLaren, C.
Dizack, D. Shanmuganayagam, J. Root, and the Animal Care, Veterinary and
Pathology Staff of the WNPRC. R.W. is a cofounder and member of the
board of LifeGen Technologies, a company focused on nutritional
genomics, including the impact of dietary interventions on the aging
process. This work was supported by NIH grants P01 AG-11915 and P51
RR000167. This research was conducted in part at the WNPRC, which
received support from Research Facilities Improvement Program grant
numbers RR15459-01 and RR020141-01. This research was supported in part
by facilities and resources at the William S. Middleton Memorial
Veterans Hospital.
NR 19
TC 940
Z9 963
U1 22
U2 192
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 JUL 10
PY 2009
VL 325
IS 5937
BP 201
EP 204
DI 10.1126/science.1173635
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468FK
UT WOS:000267802000047
PM 19590001
ER
PT J
AU Brockman, MA
Kwon, DS
Tighe, DP
Pavlik, DF
Rosato, PC
Sela, J
Porichis, F
Le Gall, S
Waring, MT
Moss, K
Jessen, H
Pereyra, F
Kavanagh, DG
Walker, BD
Kaufmann, DE
AF Brockman, Mark A.
Kwon, Douglas S.
Tighe, Daniel P.
Pavlik, David F.
Rosato, Pamela C.
Sela, Jennifer
Porichis, Filippos
Le Gall, Sylvie
Waring, Michael T.
Moss, Kristin
Jessen, Heiko
Pereyra, Florencia
Kavanagh, Daniel G.
Walker, Bruce D.
Kaufmann, Daniel E.
TI IL-10 is up-regulated in multiple cell types during viremic HIV
infection and reversibly inhibits virus-specific T cells
SO BLOOD
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC VIRAL-INFECTION; ACTIVE
ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; INTERLEUKIN-10 PRODUCTION;
CYTOKINE PRODUCTION; IMMUNE DYSFUNCTION; PD-1 EXPRESSION; IFN-GAMMA;
TNF-ALPHA
AB Murine models indicate that interleukin-10 (IL-10) can suppress viral clearance, and interventional blockade of IL-10 activity has been proposed to enhance immunity in chronic viral infections. Increased IL-10 levels have been observed during HIV infection and IL-10 blockade has been shown to enhance T-cell function in some HIV-infected subjects. However, the categories of individuals in whom the IL-10 pathway is up-regulated are poorly defined, and the cellular sources of IL-10 in these subjects remain to be determined. Here we report that blockade of the IL-10 pathway augmented in vitro proliferative capacity of HIV-specific CD4 and CD8 T cells in individuals with ongoing viral replication. IL-10 blockade also increased cytokine secretion by HIV-specific CD4 T cells. Spontaneous IL-10 expression, measured as either plasma IL-10 protein or IL-10 mRNA in peripheral blood mononuclear cells (PBMCs), correlated positively with viral load and diminished after successful antiretroviral therapy. IL-10 mRNA levels were up-regulated in multiple PBMC subsets in HIV-infected subjects compared with HIV-negative controls, particularly in T, B, and natural killer (NK) cells, whereas monocytes were a major source of IL-10 mRNA in HIV-infected and -uninfected individuals. These data indicate that multiple cell types contribute to IL-10-mediated immune suppression in the presence of uncontrolled HIV viremia. (Blood. 2009; 114: 346-356)
C1 [Brockman, Mark A.; Kwon, Douglas S.; Tighe, Daniel P.; Pavlik, David F.; Rosato, Pamela C.; Sela, Jennifer; Porichis, Filippos; Le Gall, Sylvie; Waring, Michael T.; Moss, Kristin; Pereyra, Florencia; Kavanagh, Daniel G.; Walker, Bruce D.; Kaufmann, Daniel E.] Massachusetts Gen Hosp, MIT & Harvard, Ragon Inst, Charlestown, MA USA.
[Brockman, Mark A.; Kwon, Douglas S.; Porichis, Filippos; Le Gall, Sylvie; Pereyra, Florencia; Kavanagh, Daniel G.; Walker, Bruce D.; Kaufmann, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA.
[Kwon, Douglas S.; Waring, Michael T.; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Jessen, Heiko] Jessen Praxis, Berlin, Germany.
[Pereyra, Florencia] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Kaufmann, DE (reprint author), Massachusetts Gen Hosp E, Partners AIDS Res Ctr, Rm 6618B,149 13th St, Charlestown, MA 02129 USA.
EM dkaufmann@partners.org
OI Brockman, Mark/0000-0001-6432-1426
FU National Heart, Lung and Blood Institute of the National Institutes of
Health (Bethesda, MD) [R01-HL092565]; AIDS Research Foundation; Howard
Hughes Medical Institute; Bill and Melinda Gates Foundation
FX This study was supported by the National Heart, Lung and Blood Institute
of the National Institutes of Health (Bethesda, MD; R01-HL092565 [D. E.
K.]), the Concerned Parents for AIDS Research Foundation (D. E. K., B.
D. W.), the Howard Hughes Medical Institute (B. D. W.), the Bill and
Melinda Gates Foundation (Seattle, WA), and a gift from the Mark and
Lisa Schwartz Foundation.
NR 61
TC 128
Z9 131
U1 0
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 9
PY 2009
VL 114
IS 2
BP 346
EP 356
DI 10.1182/blood-2008-12-191296
PG 11
WC Hematology
SC Hematology
GA 471MK
UT WOS:000268061700020
PM 19365081
ER
PT J
AU Fulciniti, M
Tassone, P
Hideshima, T
Vallet, S
Nanjappa, P
Ettenberg, SA
Shen, ZX
Patel, N
Tai, YT
Chauhan, D
Mitsiades, C
Prabhala, R
Raje, N
Anderson, KC
Stover, DR
Munshi, NC
AF Fulciniti, Mariateresa
Tassone, Pierfrancesco
Hideshima, Teru
Vallet, Sonia
Nanjappa, Puru
Ettenberg, Seth A.
Shen, Zhenxin
Patel, Nipun
Tai, Yu-tzu
Chauhan, Dharminder
Mitsiades, Constantine
Prabhala, Rao
Raje, Noopur
Anderson, Kenneth C.
Stover, David R.
Munshi, Nikhil C.
TI Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple
myeloma
SO BLOOD
LA English
DT Article
ID CANCER BONE METASTASES; MARROW STROMAL CELLS; GROWTH IN-VIVO;
NF-KAPPA-B; WNT PATHWAY; OSTEOBLAST DIFFERENTIATION; SERUM
CONCENTRATIONS; TUMOR PROGRESSION; BETA-CATENIN; MURINE MODEL
AB Decreased activity of osteoblasts (OBs) contributes to osteolytic lesions in multiple myeloma (MM). The production of the soluble Wnt inhibitor Dickkopf-1 (DKK1) by MM cells inhibits OB activity, and its serum level correlates with focal bone lesions in MM. Therefore, we have evaluated bone anabolic effects of a DKK1 neutralizing antibody (BHQ880) in MM. In vitro BHQ880 increased OB differentiation, neutralized the negative effect of MM cells on osteoblastogenesis, and reduced IL-6 secretion. In a severe combined immunodeficiency (SCID)-hu murine model of human MM, BHQ880 treatment led to a significant increase in OB number, serum human osteocalcin level, and trabecular bone. Although BHQ880 had no direct effect on MM cell growth, it significantly inhibited growth of MM cells in the presence of bone marrow stromal cells (BMSCs) in vitro. This effect was associated with inhibition of BMSC/MM cell adhesion and production of IL-6. In addition, BHQ880 up-regulated beta-catenin level while down-regulating nuclear factor-kappa B (NF-kappa B) activity in BMSC. Interestingly, we also observed in vivo inhibition of MM cell growth by BHQ880 treatment in the SCID-hu murine model. These results confirm DKK1 as an important therapeutic target in myeloma and provide the rationale for clinical evaluation of BHQ880 to improve bone disease and to inhibit MM growth. (Blood. 2009; 114: 371-379)
C1 [Fulciniti, Mariateresa; Hideshima, Teru; Vallet, Sonia; Nanjappa, Puru; Tai, Yu-tzu; Chauhan, Dharminder; Mitsiades, Constantine; Raje, Noopur; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Fulciniti, Mariateresa; Prabhala, Rao; Munshi, Nikhil C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA.
[Fulciniti, Mariateresa; Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Catanzaro, Italy.
[Ettenberg, Seth A.; Stover, David R.] Novartis Inst Biomed Res, Cambridge, MA USA.
[Shen, Zhenxin; Patel, Nipun] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Munshi, NC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St,M1B28, Boston, MA 02115 USA.
EM Nikhil_Munshi@DFCI.Harvard.edu
FU Department of Veterans Affairs Merit Review Awards; National Institutes
of Health [RO1-124929, P50-100007, PO1-78378]; Associazione Italiana per
la Ricerca sul Cancro (AIRC)
FX This work was supported in part by grants from the Department of
Veterans Affairs Merit Review Awards, the National Institutes of Health
(grant nos. RO1-124929 [N.C.M.], P50-100007, and PO1-78378 [N.C.M. and
K. C. A.]), and Associazione Italiana per la Ricerca sul Cancro (AIRC).
NR 51
TC 184
Z9 202
U1 3
U2 11
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 JUL 9
PY 2009
VL 114
IS 2
BP 371
EP 379
DI 10.1182/blood-2008-11-191577
PG 9
WC Hematology
SC Hematology
GA 471MK
UT WOS:000268061700023
PM 19417213
ER
PT J
AU Shen, YP
Nunes, F
Stemmer-Rachamimov, A
James, M
Mohapatra, G
Plotkin, S
Betensky, RA
Engler, DA
Roy, J
Ramesh, V
Gusella, JF
AF Shen, Yiping
Nunes, Fabio
Stemmer-Rachamimov, Anat
James, Marianne
Mohapatra, Gayatry
Plotkin, Scott
Betensky, Rebecca A.
Engler, David A.
Roy, Jennifer
Ramesh, Vijaya
Gusella, James F.
TI Genomic profiling distinguishes familial multiple and sporadic multiple
meningiomas
SO BMC MEDICAL GENOMICS
LA English
DT Article
ID GENE-EXPRESSION; ANAPLASTIC MENINGIOMAS; OLIGONUCLEOTIDE MICROARRAYS;
INTRACRANIAL MENINGIOMAS; NEUROFIBROMATOSIS TYPE-2; DISTINCT PATTERNS;
TUMOR-SUPPRESSOR; NF2 GENE; HYBRIDIZATION; DNA
AB Background: Meningiomas may occur either as familial tumors in two distinct disorders, familial multiple meningioma and neurofibromatosis 2 (NF2), or sporadically, as either single or multiple tumors in individuals with no family history. Meningiomas in NF2 and approximately 60% of sporadic meningiomas involve inactivation of the NF2 locus, encoding the tumor suppressor merlin on chromosome 22q. This study was undertaken to establish whether genomic profiling could distinguish familial multiple meningiomas from sporadic solitary and sporadic multiple meningiomas.
Methods: We compared 73 meningiomas presenting as sporadic solitary (64), sporadic multiple (5) and familial multiple (4) tumors using genomic profiling by array comparative genomic hybridization (array CGH).
Results: Sporadic solitary meningiomas revealed genomic rearrangements consistent with at least two mechanisms of tumor initiation, as unsupervised cluster analysis readily distinguished tumors with chromosome 22 deletion (associated with loss of the NF2 tumor suppressor) from those without chromosome 22 deletion. Whereas sporadic meningiomas without chromosome 22 loss exhibited fewer chromosomal imbalance events overall, tumors with chromosome 22 deletion further clustered into two major groups that largely, though not perfectly, matched with their benign (WHO Grade I) or advanced (WHO Grades II and III) histological grade, with the latter exhibiting a significantly greater degree of genomic imbalance (P < 0.001). Sporadic multiple meningiomas showed a frequency of genomic imbalance events comparable to the atypical grade solitary tumors. By contrast, familial multiple meningiomas displayed no imbalances, supporting a distinct mechanism for the origin for these tumors.
Conclusion: Genomic profiling can provide an unbiased adjunct to traditional meningioma classification and provides a basis for exploring the different genetic underpinnings of tumor initiation and progression. Most importantly, the striking difference observed between sporadic and familial multiple meningiomas indicates that genomic profiling can provide valuable information for differential diagnosis of subjects with multiple meningiomas and for considering the risk for tumor occurrence in their family members.
C1 [Shen, Yiping; James, Marianne; Ramesh, Vijaya; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA.
[Nunes, Fabio] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Stemmer-Rachamimov, Anat; Mohapatra, Gayatry; Roy, Jennifer] Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA.
[Stemmer-Rachamimov, Anat; Mohapatra, Gayatry; Roy, Jennifer] Massachusetts Gen Hosp, Pathol Lab, Boston, MA 02114 USA.
[Stemmer-Rachamimov, Anat; Mohapatra, Gayatry; Roy, Jennifer] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Stemmer-Rachamimov, Anat; Mohapatra, Gayatry; Plotkin, Scott; Roy, Jennifer] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Plotkin, Scott] Massachusetts Gen Hosp, Pappas Ctr Neuro Oncol, NF Clin, Boston, MA 02114 USA.
[Betensky, Rebecca A.; Engler, David A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA.
EM yshen3@partners.org; fnunes@partners.org;
ASTEMMERRACHAMIMOV@PARTNERS.ORG; james@helix.mgh.harvard.edu;
gmohapatra@partners.org; splotkin@partners.org;
betensky@hsph.harvard.edu; engler@byu.edu; royj@helix.mgh.harvard.edu;
ramesh@helix.mgh.harvard.edu; gusella@helix.mgh.harvard.edu
FU S. Sydney De Young Foundation [DAMD17-02-1-0646]; National Institutes of
Health [NS24279]; Armenise Foundation, NF Inc.; Children's Tumor
Foundation [2005-01-004]
FX Support for this project was received from the S. Sydney De Young
Foundation, the Department of Defense Neurofibromatosis Research Program
(DAMD17-02-1-0646), the National Institutes of Health (NS24279), the
Armenise Foundation, NF Inc. NE, and by a Young Investigator Award
(2005-01-004) from the Children's Tumor Foundation (to YS).
NR 55
TC 16
Z9 16
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD JUL 9
PY 2009
VL 2
AR 42
DI 10.1186/1755-8794-2-42
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 533HA
UT WOS:000272813100002
PM 19589153
ER
PT J
AU Vlajkovic, SM
Housley, GD
Thorne, PR
Gupta, R
Enjyoji, K
Cowan, PJ
Liberman, MC
Robson, SC
AF Vlajkovic, Srdjan M.
Housley, Gary D.
Thorne, Peter R.
Gupta, Rita
Enjyoji, Keiichi
Cowan, Peter J.
Liberman, M. Charles
Robson, Simon C.
TI Preservation of cochlear function in Cd39 deficient mice
SO HEARING RESEARCH
LA English
DT Article
DE CD39; NTPDase1; Ectonucleotidase; Purinergic signalling; Knockout mice;
Hearing
ID NUCLEOSIDE TRIPHOSPHATE DIPHOSPHOHYDROLASE-1; RAT COCHLEA;
UP-REGULATION; CATALYTIC PROPERTIES; PROTECTION; ECTONUCLEOTIDASES;
RECEPTOR; INJURY; EXPRESSION; ADENOSINE
AB Signalling actions of extracellular nucleotides via P2 receptors influence cellular function in most tissues. In the inner ear, P2 receptor signaling is involved in many processes including the regulation of hearing sensitivity and the cochlea's response to noise stress. CD39 (NTPDase1/ENTPD1) is an ectonucleotidase (ecto-nucleoside triphosphate diphosphohydrolase) that can hydrolyse purine and pyrimidine nucleoside tri- and di-phosphates to generate monophosphate nucleosides. Mice null for Cd39 exhibit major alterations in haemostasis and profound alterations in inflammatory and thrombotic reactions. Studies in the cochlea have suggested the involvement of purinergic-type signals that could be modulated by CD39 in regulation of cochlear blood flow and also auditory neurotransmission. This study aimed to determine the auditory phenotype of adult Cd39 null mice on the C57BL6 background. Auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) were unaffected in Cd39-deficient mice across the range of test frequencies, suggesting normal neural and outer hair cell function. Mutant mice also showed little difference to wild type mice in vulnerability to acoustic trauma. Gene expression analysis of other membrane-bound NTPDases with comparable hydrolytic activity demonstrated an up-regulation of Entpd2 and Entpd8 in the cochleae of Cd39 deficient mice. These findings suggest that Cd39 deletion alone does not adversely affect cochlear function, possibly as compensatory up-regulation of other surface located NTPDases may offset predicted alterations in cochlear homeostasis. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Vlajkovic, Srdjan M.; Housley, Gary D.; Thorne, Peter R.; Gupta, Rita] Univ Auckland, Fac Med & Hlth Sci, Dept Physiol, Auckland 1142, New Zealand.
[Thorne, Peter R.] Univ Auckland, Fac Med & Hlth Sci, Discipline Audiol, Auckland 1142, New Zealand.
[Enjyoji, Keiichi; Robson, Simon C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Cowan, Peter J.] Univ Melbourne, St Vincents Hosp Melbourne, Immunol Res Ctr, Melbourne, Vic, Australia.
[Cowan, Peter J.] Univ Melbourne, Dept Med, Melbourne, Vic, Australia.
[Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
RP Vlajkovic, SM (reprint author), Univ Auckland, Fac Med & Hlth Sci, Dept Physiol, 85 Pk Rd,Private Bag 92019, Auckland 1142, New Zealand.
EM s.vlajkovic@auckland.ac.nz; g.housley@unsw.edu.au;
pr.thorne@auckland.ac.nz; r.gupta@aucklan-d.ac.nz;
kenjoji@caregroup.harvard.edu; Peter.COWAN@svh-m.org.au;
Charles_Liberman@meei.harvard.edu; srobson@bidmc.harvard.edu
OI Cowan, Peter/0000-0001-9016-4954; Housley, Gary/0000-0002-8413-588X;
Vlajkovic, Srdjan/0000-0001-8548-6844
FU Health Research Council (NZ); Deafness Research Foundation (NZ);
Auckland Medical Research Foundation; National Institute on Deafness and
other Communicative Disorders [DC RO1 00188]; RNID
FX This study was supported by the Health Research Council (NZ), Deafness
Research Foundation (NZ), Auckland Medical Research Foundation, the
National Institute on Deafness and other Communicative Disorders (DC RO1
00188 to MCQ, and RNID (UK).
NR 35
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD JUL 9
PY 2009
VL 253
IS 1-2
BP 77
EP 82
DI 10.1016/j.heares.2009.03.009
PG 6
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 471SR
UT WOS:000268079100009
PM 19327391
ER
PT J
AU Rosowski, JJ
Cheng, JT
Ravicz, ME
Hulli, N
Hernandez-Montes, M
Harrington, E
Furlong, C
AF Rosowski, John J.
Cheng, Jeffrey Tao
Ravicz, Michael E.
Hulli, Nesim
Hernandez-Montes, Maria
Harrington, Ellery
Furlong, Cosme
TI Computer-assisted time-averaged holograms of the motion of the surface
of the mammalian tympanic membrane with sound stimuli of 0.4-25 kHz
SO HEARING RESEARCH
LA English
DT Article
DE Tympanic membrane; Middle-ear sound transmission; Middle-ear models
ID HUMAN MIDDLE-EAR; FINITE-ELEMENT METHOD; VIBRATION MEASUREMENT; TEMPORAL
BONES; CAT EARDRUM; MODEL; TRANSMISSION; GERBIL; MECHANICS
AB Time-averaged holograms describing the sound-induced motion of the tympanic membrane (TM) in cadaveric preparations from three mammalian species and one live ear were measured using opto-electronic holography. This technique allows rapid measurements of the magnitude of motion of the tympanic membrane surface at frequencies as high as 25 kHz. The holograms measured in response to low and middle-frequency sound stimuli are similar to previously reported time-averaged holograms. However, at higher frequencies (f > 4 kHz), our holograms reveal unique TM surface displacement patterns that consist of highly-ordered arrangements of multiple local displacement magnitude maxima, each of which is surrounded by nodal areas of low displacement magnitude. These patterns are similar to modal patterns (two-dimensional standing waves) produced by either the interaction of surface waves traveling in multiple directions or the uniform stimulation of modes of motion that are determined by the structural properties and boundary conditions of the TM. From the ratio of the displacement magnitude peaks to nodal valleys in these apparent surface waves, we estimate a Standing Wave Ratio of at least 4 that is consistent with energy reflection coefficients at the TM boundaries of at least 0.35. It is also consistent with small losses within the uniformly stimulated modal surface waves. We also estimate possible TM surface wave speeds that vary with frequency and species from 20 to 65 m/s, consistent with other estimates in the literature. The presence of standing. wave or modal phenomena has previously been intuited from measurements of TM function, but is ignored in some models of tympanic membrane function. Whether these standing waves result either from the interactions of multiple surface waves that travel along the membrane, or by uniformly excited modal displacement patterns of the entire TM surface is still to be determined. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Rosowski, John J.; Cheng, Jeffrey Tao; Ravicz, Michael E.; Furlong, Cosme] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Hulli, Nesim; Hernandez-Montes, Maria; Harrington, Ellery; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA.
[Hulli, Nesim; Hernandez-Montes, Maria; Harrington, Ellery; Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA.
[Rosowski, John J.; Cheng, Jeffrey Tao; Ravicz, Michael E.; Furlong, Cosme] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA.
RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM john_rosowski@meei.harvard.edu
FU NIDCD; WPI; MEEI
FX This work was funded by the NIDCD, the WPI, the MEEI and a generous
donor.
NR 53
TC 57
Z9 58
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD JUL 9
PY 2009
VL 253
IS 1-2
BP 83
EP 96
DI 10.1016/j.heares.2009.03.010
PG 14
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 471SR
UT WOS:000268079100010
PM 19328841
ER
PT J
AU Wang, JH
Gostissa, M
Yan, CT
Goff, P
Hickernell, T
Hansen, E
Difilippantonio, S
Wesemann, DR
Zarrin, AA
Rajewsky, K
Nussenzweig, A
Alt, FW
AF Wang, Jing H.
Gostissa, Monica
Yan, Catherine T.
Goff, Peter
Hickernell, Thomas
Hansen, Erica
Difilippantonio, Simone
Wesemann, Duane R.
Zarrin, Ali A.
Rajewsky, Klaus
Nussenzweig, Andre
Alt, Frederick W.
TI Mechanisms promoting translocations in editing and switching peripheral
B cells
SO NATURE
LA English
DT Article
ID END-JOINING PATHWAY; CHROMOSOMAL TRANSLOCATIONS; V(D)J RECOMBINATION;
RECEPTOR REVISION; BONE-MARROW; DNA BREAKS; LYMPHOCYTE DEVELOPMENT;
GENE-REGULATION; AID; EXPRESSION
AB Variable, diversity and joining gene segment (V(D) J) recombination assembles immunoglobulin heavy or light chain (IgH or IgL) variable region exons in developing bone marrow B cells, whereas class switch recombination (CSR) exchanges IgH constant region exons in peripheral B cells. Both processes use directed DNA double-strand breaks (DSBs) repaired by non-homologous end-joining (NHEJ). Errors in either V(D) J recombination or CSR can initiate chromosomal translocations, including oncogenic IgH locus (Igh) to c-myc (also known as Myc) translocations of peripheral B cell lymphomas. Collaboration between these processes has also been proposed to initiate translocations. However, the occurrence of V(D) J recombination in peripheral B cells is controversial. Here we show that activated NHEJ-deficient splenic B cells accumulate V(D) J-recombination-associated breaks at the lambda IgL locus (Igl), as well as CSR-associated Igh breaks, often in the same cell. Moreover, Igl and Igh breaks are frequently joined to form translocations, a phenomenon associated with specific Igh-Igl co-localization. Igh and c-myc also co-localize in these cells; correspondingly, the introduction of frequent c-myc DSBs robustly promotes Igh-c-myc translocations. Our studies show peripheral B cells that attempt secondary V(D) J recombination, and determine a role for mechanistic factors in promoting recurrent translocations in tumours.
C1 [Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
[Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Rajewsky, Klaus; Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Difilippantonio, Simone; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Wesemann, Duane R.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
RI Wang, Jing/M-7813-2015
OI Wang, Jing/0000-0003-4343-2527
FU National Insitutes of Health (NIH) [5P01CA92625]; Leukemia and Lymphoma
Society of America (LLS) SCORE; NCI
FX We thank Alt laboratory members for discussions, and Y. L. Chen, J. M.
Bianco and M. Moghimi for technical assistance. This work was supported
by the National Insitutes of Health (NIH) grant 5P01CA92625 and a
Leukemia and Lymphoma Society of America (LLS) SCORE grant to F. W. A.
and K. R. M. G. is and J. H. W. was a Special Fellow of the LLS. J. H.
W. and D. R. W. are supported by an NIH training grant and C. T. Y. was
supported by an NCI training grant. A. N. is supported by the Intramural
Research program of the NIH, NCI, Center for Cancer Research. F. W. A.
is an Investigator of the Howard Hughes Medical Institute.
NR 50
TC 87
Z9 90
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 231
EP U94
DI 10.1038/nature08159
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000035
PM 19587764
ER
PT J
AU Naveiras, O
Nardi, V
Wenzel, PL
Hauschka, PV
Fahey, F
Daley, GQ
AF Naveiras, Olaia
Nardi, Valentina
Wenzel, Pamela L.
Hauschka, Peter V.
Fahey, Frederic
Daley, George Q.
TI Bone-marrow adipocytes as negative regulators of the haematopoietic
microenvironment
SO NATURE
LA English
DT Article
ID STEM-CELL NICHE; INSULIN-RESISTANCE; PROGENITOR CELLS; SELF-RENEWAL;
IN-VIVO; DIFFERENTIATION; GROWTH; IDENTIFICATION; ROSIGLITAZONE;
ADIPONECTIN
AB Osteoblasts and endothelium constitute functional niches that support haematopoietic stem cells in mammalian bone marrow(1-3). Adult bone marrow also contains adipocytes, the number of which correlates inversely with the haematopoietic activity of the marrow. Fatty infiltration of haematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia(4). To explore whether adipocytes influence haematopoiesis or simply fill marrow space, we compared the haematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. Here we show, by flow cytometry, colony-forming activity and competitive repopulation assay, that haematopoietic stem cells and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 'fatless' mice, which are genetically incapable of forming adipocytes(5), and in mice treated with the peroxisome proliferator-activated receptor-c inhibitor bisphenol A diglycidyl ether, which inhibits adipogenesis(6), marrow engraftment after irradiation is accelerated relative to wild-type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone-marrow microenvironment, and indicate that antagonizing marrow adipogenesis may enhance haematopoietic recovery in clinical bone-marrow transplantation.
C1 [Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA.
[Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Daley, George Q.] Manton Ctr Orphan Dis, Boston, MA 02115 USA.
[Hauschka, Peter V.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA.
[Hauschka, Peter V.] Harvard Univ, Sch Med, Dept Oral & Dev Biol, Boston, MA 02115 USA.
[Hauschka, Peter V.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Fahey, Frederic] Harvard Univ, Childrens Hosp, Sch Med, Dept Radiol,Div Nucl Med PET, Boston, MA 02115 USA.
RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
RI Wenzel, Pamela/A-2992-2010
FU Barrie de la Maza Foundation; National Institutes of Health (NIH)
[T32-HL-7623]; Burroughs Wellcome Fund; Leukemia and Lymphoma Society
FX We thank S. Lazo-Kallanian, J. Daley, G. Losyev and R. Mathieu for
assistance with flow cytometry; R. Bronson for assistance with
pathological analysis; P. Dunning, E. Snay and S. Carlton for assistance
with small animal imaging; S. Loewer for translation of historical
references; and S. McKinney-Freeman, A. Yabuuchi, K. Ng and R. Chapman
for mouse and technical assistance. O.N. was partially funded by the
Barrie de la Maza Foundation. P. L. W. was supported by a Hematology
Training Grant from the National Institutes of Health (NIH T32-HL-7623).
G. Q. D. was supported by grants from the NIH and the NIH Director's
Pioneer Award of the NIH Roadmap for Medical Research. G. Q. D. is the
recipient of the Clinical Scientist Award in Translational Research from
the Burroughs Wellcome Fund and the Leukemia and Lymphoma Society, and
is an Investigator of the Howard Hughes Medical Institute.
NR 33
TC 369
Z9 392
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 259
EP U124
DI 10.1038/nature08099
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000041
PM 19516257
ER
PT J
AU Ganem, NJ
Godinho, SA
Pellman, D
AF Ganem, Neil J.
Godinho, Susana A.
Pellman, David
TI A mechanism linking extra centrosomes to chromosomal instability
SO NATURE
LA English
DT Article
ID MEROTELIC KINETOCHORE ORIENTATION; MAMMALIAN TISSUE-CELLS; CANCER-CELLS;
CLONAL EVOLUTION; ANEUPLOIDY; AMPLIFICATION; MITOSIS; POPULATIONS;
ABERRATIONS; PROGRESSION
AB Chromosomal instability (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes(1-4). However, a direct mechanistic link between extra centrosomes and CIN has not been established. It has been proposed that extra centrosomes generate CIN by promoting multipolar anaphase, a highly abnormal division that produces three or more aneuploid daughter cells. Here we use long-term live-cell imaging to demonstrate that cells with multiple centrosomes rarely undergo multipolar cell divisions, and the progeny of these divisions are typically inviable. Thus, multipolar divisions cannot explain observed rates of CIN. In contrast, we observe that CIN cells with extra centrosomes routinely undergo bipolar cell divisions, but display a significantly increased frequency of lagging chromosomes during anaphase. To define the mechanism underlying this mitotic defect, we generated cells that differ only in their centrosome number. We demonstrate that extra centrosomes alone are sufficient to promote chromosome missegregation during bipolar cell division. These segregation errors are a consequence of cells passing through a transient 'multipolar spindle intermediate' in which merotelic kinetochore-microtubule attachment errors accumulate before centrosome clustering and anaphase. These findings provide a direct mechanistic link between extra centrosomes and CIN, two common characteristics of solid tumours. We propose that this mechanism may be a common underlying cause of CIN in human cancer.
C1 [Ganem, Neil J.; Godinho, Susana A.; Pellman, David] Harvard Univ, Sch Med,Dept Pediat Oncol, Dana Farber Canc Inst,Dept Cell Biol, Howard Hughes Med Inst,Childrens Hosp, Boston, MA 02115 USA.
RP Pellman, D (reprint author), Harvard Univ, Sch Med,Dept Pediat Oncol, Dana Farber Canc Inst,Dept Cell Biol, Howard Hughes Med Inst,Childrens Hosp, 44 Binney St, Boston, MA 02115 USA.
EM david_pellman@dfci.harvard.edu
FU Leukemia and Lymphoma Society; NIH [GM083299]
FX We would like to thank D. Compton, R. King, D. Livingston, A. Manning,
T. Rapoport, J. Shah, T. Stukenberg and members of the Pellman
laboratory for comments and discussion of the manuscript; L. Cameron for
setting up the confocal microscope; P. Schow for help with FACS; D.
Neuberg for help with statistical analysis; C. King for help with the
model figure; J. Iwasa for creating the animations; and L. Moreau and S.
Thompson for technical advice on chromosome spreads and FISH analysis.
Reagents were provided by D. Compton, S. Gollin, R. King, A. Khodjakov,
E. Nigg and G. Wahl. N.J.G. is a fellow of the Leukemia and Lymphoma
Society and D. P. is an HHMI Investigator. This work was supported by
NIH grant GM083299.
NR 30
TC 583
Z9 595
U1 16
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 278
EP U146
DI 10.1038/nature08136
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000045
PM 19506557
ER
PT J
AU Neilson, EG
Farris, AB
AF Neilson, Eric G.
Farris, Alton B.
TI A Woman with Abdominal Pain, Weight Loss, and Renal Failure Acute and
chronic tubulointerstitial nephritis associated with uveitis (TINU or
Dobrin's syndrome).
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID POLYARTERITIS-NODOSA; HELICOBACTER-PYLORI; INTERSTITIAL NEPHRITIS;
FANCONI-SYNDROME; AUTOANTIBODIES; VASCULITIS; DIAGNOSIS; CELLS
C1 [Neilson, Eric G.] Vanderbilt Univ Sch Med, Nashville, TN USA.
[Neilson, Eric G.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Farris, Alton B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Farris, Alton B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Neilson, EG (reprint author), Vanderbilt Univ Sch Med, Nashville, TN USA.
NR 30
TC 2
Z9 3
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 JUL 9
PY 2009
VL 361
IS 2
BP 179
EP 187
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467OS
UT WOS:000267748900013
PM 19587344
ER
PT J
AU Iglehart, JD
Silver, DP
AF Iglehart, J. Dirk
Silver, Daniel P.
TI Synthetic Lethality -- A New Direction in Cancer-Drug Development.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID HOMOLOGOUS RECOMBINATION; PARP INHIBITOR; SENSITIVITY; RESISTANCE;
REPAIR; MUTATIONS; THERAPY; SCREEN
C1 [Iglehart, J. Dirk] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Iglehart, J. Dirk] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Silver, Daniel P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA.
RP Iglehart, JD (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
NR 13
TC 88
Z9 91
U1 3
U2 12
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 JUL 9
PY 2009
VL 361
IS 2
BP 189
EP 191
DI 10.1056/NEJMe0903044
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467OS
UT WOS:000267748900014
PM 19553640
ER
PT J
AU Vavvas, D
Brodowska, K
AF Vavvas, Demetrios
Brodowska, Katarzyna
TI Traumatic Bleb.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Vavvas, Demetrios; Brodowska, Katarzyna] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Vavvas, D (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
EM dvavvas@partners.org
OI Vavvas, Demetrios/0000-0002-8622-6478
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 9
PY 2009
VL 361
IS 2
BP E2
EP E2
DI 10.1056/NEJMicm0802306
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467OS
UT WOS:000267748900012
PM 19587336
ER
PT J
AU Chauhan, VP
Lanning, RM
Diop-Frimpong, B
Mok, W
Brown, EB
Padera, TP
Boucher, Y
Jain, RK
AF Chauhan, Vikash P.
Lanning, Ryan M.
Diop-Frimpong, Benjamin
Mok, Wilson
Brown, Edward B.
Padera, Timothy P.
Boucher, Yves
Jain, Rakesh K.
TI Multiscale Measurements Distinguish Cellular and Interstitial Hindrances
to Diffusion In Vivo
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID FLUORESCENCE CORRELATION SPECTROSCOPY; SOLID TUMORS;
EXTRACELLULAR-SPACE; TRANSPORT; COLLAGEN; ENVIRONMENT; MICROSCOPY;
MUSCLE; BRAIN; PORE
AB Molecular cancer therapy relies on interstitial diffusion for drug distribution in solid tumors. A mechanistic understanding of how tumor components affect diffusion is necessary to advance cancer drug development. Yet, because of limitations in current techniques, it is unclear how individual tissue components hinder diffusion. We developed multiscale fluorescence recovery after photobleaching (MS-FRAP) to address this deficiency. Diffusion measurements facilitated by MS-FRAP distinguish the diffusive hindrance of the interstitial versus cellular constituents in living tissue. Using multiscale diffusion measurements in vivo, we resolved the contributions of these two major tissue components toward impeding diffusive transport in solid tumors and subcutaneous tissue in mice. We further used MS-FRAP in interstitial matrix-mimetic gels and in vivo to show the influence of physical interactions between collagen and hyaluronan on diffusive hindrance through the interstitium. Through these studies, we show that interstitial hyaluronan paradoxically improves diffusion and that reducing cellularity enhances diffusive macromolecular transport in solid tumors.
C1 [Chauhan, Vikash P.; Lanning, Ryan M.; Diop-Frimpong, Benjamin; Mok, Wilson; Padera, Timothy P.; Boucher, Yves; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
[Chauhan, Vikash P.; Lanning, Ryan M.; Diop-Frimpong, Benjamin; Mok, Wilson; Padera, Timothy P.; Boucher, Yves; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Chauhan, Vikash P.; Diop-Frimpong, Benjamin] Harvard Univ, Harvard Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Lanning, Ryan M.; Diop-Frimpong, Benjamin] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Brown, Edward B.] Univ Rochester, Med Ctr, Dept Biomed Engn, New York, NY 14642 USA.
RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
EM jain@steele.mgh.harvard.edu
RI Chauhan, Vikash/H-8172-2013;
OI Chauhan, Vikash/0000-0001-9126-2302; Padera, Timothy/0000-0002-3453-9384
FU National Institutes of Health [5P01CA080124-08, 2T32CA073479-11];
Department of Defense Breast Cancer Research Program [W81X-WH-06-1-0436]
FX This work was supported by the National Institutes of Health (grants
5P01CA080124-08 and 2T32CA073479-11 to R.K.J.) and Department of Defense
Breast Cancer Research Program (grant W81X-WH-06-1-0436 to R.M.L.).
NR 25
TC 30
Z9 30
U1 2
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUL 8
PY 2009
VL 97
IS 1
BP 330
EP 336
DI 10.1016/j.bpj.2009.03.064
PG 7
WC Biophysics
SC Biophysics
GA 469BV
UT WOS:000267871000033
PM 19580771
ER
PT J
AU Peterson, PN
Ambardekar, AV
Jones, PG
Krumholz, HM
Schelbert, E
Spertus, JA
Rumsfeld, JS
Masoudi, FA
AF Peterson, Pamela N.
Ambardekar, Amrut V.
Jones, Philip G.
Krumholz, Harlan M.
Schelbert, Erik
Spertus, John A.
Rumsfeld, John S.
Masoudi, Frederick A.
TI Increased Mortality among Survivors of Myocardial Infarction with Kidney
Dysfunction: the Contribution of Gaps in the use of Guideline-Based
Therapies
SO BMC CARDIOVASCULAR DISORDERS
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE;
HEART-FAILURE; INSUFFICIENCY; OUTCOMES; ASSOCIATION; INHIBITORS;
ASPIRIN; EVENTS
AB Background: We assessed the degree to which differences in guideline-based medical therapy for acute myocardial infarction (AMI) contribute to the higher mortality associated with kidney disease.
Methods: In the PREMIER registry, we evaluated patients from 19 US centers surviving AMI. Cox regression evaluated the association between estimated glomerular filtration rate (GFR) and time to death over two years, adjusting for demographic and clinical variables. The contribution of variation in guideline-based medical therapy to differences in mortality was then assessed by evaluating the incremental change in the hazard ratios after further adjustment for therapy.
Results: Of 2426 patients, 26% had GFR >= 90, 44% had GFR = 60- < 90, 22% had GFR = 30- < 60, and 8% had GFR < 30 ml/min/1.73 m(2). Greater degrees of renal dysfunction were associated with greater 2-year mortality and lower rates of guideline-based therapy among eligible patients. For patients with severely decreased GFR, adjustment for differences in guideline-based therapy did not significantly attenuate the relationship with mortality (HR 3.82, 95% CI 2.39-6.11 partially adjusted; HR = 3.90, 95% CI 2.42-6.28 after adjustment for treatment differences).
Conclusion: Higher mortality associated with reduced GFR after AMI is not accounted for by differences in treatment factors, underscoring the need for novel therapies specifically targeting the pathophysiological abnormalities associated with kidney dysfunction to improve survival.
C1 [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA.
[Peterson, Pamela N.; Ambardekar, Amrut V.; Rumsfeld, John S.; Masoudi, Frederick A.] Univ Colorado Denver, Aurora, CO USA.
[Jones, Philip G.; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Schelbert, Erik] Natl Inst Hlth, Bethesda, MD USA.
[Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA.
[Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
RP Peterson, PN (reprint author), Denver Hlth Med Ctr, Denver, CO USA.
EM pamela.peterson@uchsc.edu; Amrut.Ambardekar@uchsc.edu;
pgjones@saint-lukes.org; Harlan.Krumholz@yale.edu;
Schelberteb@nhlbi.nih.gov; spertusj@umkc.edu; John.Rumsfeld@uchsc.edu;
Fred.Masoudi@uchsc.edu
OI Schelbert, Erik/0000-0003-0356-4437
NR 26
TC 4
Z9 4
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2261
J9 BMC CARDIOVASC DISOR
JI BMC Cardiovasc. Disord.
PD JUL 8
PY 2009
VL 9
AR 29
DI 10.1186/1471-2261-9-29
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 477AN
UT WOS:000268488400001
PM 19586550
ER
PT J
AU Fjell, AM
Westlye, LT
Amlien, I
Espeseth, T
Reinvang, I
Raz, N
Agartz, I
Salat, DH
Greve, DN
Fischl, B
Dale, AM
Walhovd, KB
AF Fjell, Anders M.
Westlye, Lars T.
Amlien, Inge
Espeseth, Thomas
Reinvang, Ivar
Raz, Naftali
Agartz, Ingrid
Salat, David H.
Greve, Doug N.
Fischl, Bruce
Dale, Anders M.
Walhovd, Kristine B.
TI Minute Effects of Sex on the Aging Brain: A Multisample Magnetic
Resonance Imaging Study of Healthy Aging and Alzheimer's Disease
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; HUMAN
CEREBRAL-CORTEX; DEMENTIA RATING CDR; ADULT HUMAN BRAIN; IN-VIVO;
CORTICAL THICKNESS; GRAY-MATTER; WHITE-MATTER; YOUNG ADULTS
AB Age is associated with substantial macrostructural brain changes. While some recent magnetic resonance imaging studies have reported larger age effects in men than women, others find no sex differences. As brain morphometry is a potentially important tool in diagnosis and monitoring of age-related neurological diseases, e.g., Alzheimer's disease (AD), it is important to know whether sex influences brain aging. We analyzed cross-sectional magnetic resonance scans from 1143 healthy participants from seven subsamples provided by four independent research groups. In addition, 96 patients with mild AD were included. Estimates of cortical thickness continuously across the brain surface, as well as volume of 17 subcortical structures, were obtained by use of automated segmentation tools (FreeSurfer). In the healthy participants, no differences in aging slopes between women and men were found in any part of the cortex. Pallidum corrected for intracranial volume showed slightly higher age correlations for men. The analyses were repeated in each of the seven subsamples, and the lack of age x sex interactions was largely replicated. Analyses of the AD sample showed no interactions between sex and age for any brain region. We conclude that sex has negligible effects on the age slope of brain volumes both in healthy participants and in AD.
C1 [Fjell, Anders M.; Westlye, Lars T.; Amlien, Inge; Espeseth, Thomas; Reinvang, Ivar; Walhovd, Kristine B.] Univ Oslo, Dept Psychol, Ctr Study Human Cognit, N-0317 Oslo, Norway.
[Agartz, Ingrid] Univ Oslo, Dept Psychiat, N-0317 Oslo, Norway.
[Fjell, Anders M.; Walhovd, Kristine B.] Ullevaal Univ Hosp, Dept Neuropsychiat, N-0317 Oslo, Norway.
[Raz, Naftali] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA.
[Raz, Naftali] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA.
[Agartz, Ingrid] Diakonhjemmet Hosp, Dept Psychiat Res, N-0319 Oslo, Norway.
[Agartz, Ingrid] Karolinska Hosp & Inst, Psychiat Sect, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
[Salat, David H.; Greve, Doug N.; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr,Dept Radiol, Charlestown, MA 02129 USA.
[Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Dale, Anders M.] Univ Calif San Diego, Multimodal Imaging Lab, La Jolla, CA 92093 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 Fjell, AM (reprint author), Univ Oslo, Dept Psychol, Ctr Study Human Cognit, Pb 1094 Blindern, N-0317 Oslo, Norway.
EM andersmf@psykologi.uio.no
RI Dale, Anders/A-5180-2010;
OI Agartz, Ingrid/0000-0002-9839-5391; Westlye, Lars T./0000-0001-8644-956X
FU Howard Hughes Medical Institute; NCRR NIH HHS [P41 RR014075, P41
RR014075-075751, P41 RR014075-075752, P41 RR014075-075753, P41
RR014075-086765, P41 RR014075-086766, P41 RR014075-086767, P41
RR014075-098601, P41 RR014075-098602, P41 RR014075-098603, P41
RR014075-105995, P41 RR014075-105996, P41 RR014075-105997, P41-RR14075,
R01 RR016594, R01 RR016594-01A1, R01 RR016594-02, R01 RR016594-03, R01
RR016594-04, R01 RR16594-01A1, R01-RR13609, RR 16594, RR14075, U24
RR021382]; NIA NIH HHS [P01 AG003991, P01 AG003991-219005, P01
AG003991-229005, P01 AG003991-239005, P01 AG003991-249005, P01
AG003991-259005, P01 AG03991, P50 AG005681, P50 AG005681-170029, P50
AG005681-180029, P50 AG005681-18S10029, P50 AG005681-18S20029, P50
AG005681-18S30029, P50 AG005681-190029, P50 AG005681-19S10029, P50
AG005681-19S20029, P50 AG05681, R01 AG034556, R37 AG011230,
R37-AG11230]; NIBIB NIH HHS [R01EB006758, R01 EB001550, R01 EB006758,
R01 EB006758-01A1, R01 EB006758-02, R01 EB006758-03, R01 EB006758-03S1,
U54 EB005149]; NIMH NIH HHS [P20 MH071616, P50 MH071616]; NINDS NIH HHS
[R01 NS052585, R01 NS052585-01, R01 NS052585-01A1, R01 NS052585-02, R01
NS052585-02S1, R01 NS052585-03, R01 NS052585-04, R01-NS39581]
NR 76
TC 47
Z9 48
U1 2
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 8
PY 2009
VL 29
IS 27
BP 8774
EP 8783
DI 10.1523/JNEUROSCI.0115-09.2009
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 468KY
UT WOS:000267818400018
PM 19587284
ER
PT J
AU Hogberg, B
Liedl, T
Shih, WM
AF Hogberg, Bjorn
Liedl, Tim
Shih, William M.
TI Folding DNA Origami from a Double-Stranded Source of Scaffold
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID THERMODYNAMICS; FORMAMIDE; SHAPES
AB Combined heat and chemical denaturation of double-stranded DNA scaffold strands in the presence of staple strands, followed by a sudden temperature drop and then stepwise dialysis to remove the chemical denaturant, leads to self-assembly of two distinct DNA-origami structures.
C1 [Hogberg, Bjorn] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Hogberg, B (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM Bjorn_Hogberg@dfci.harvard.edu; Tim_Liedl@dfci.harvard.edu;
William_Shih@dfci.harvard.edu
RI Liedl, Tim/O-7539-2014;
OI Liedl, Tim/0000-0002-0040-0173; Hogberg, Bjorn/0000-0003-2715-7887
FU NIH HHS [1DP2OD004641-01, DP2 OD004641, DP2 OD004641-01]
NR 10
TC 54
Z9 55
U1 2
U2 36
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 JUL 8
PY 2009
VL 131
IS 26
BP 9154
EP +
DI 10.1021/ja902569x
PG 3
WC Chemistry, Multidisciplinary
SC Chemistry
GA 466AT
UT WOS:000267633300011
PM 19566089
ER
PT J
AU Ahmad, M
Zhang, YQ
Liu, H
Rose, ME
Graham, SH
AF Ahmad, Muzamil
Zhang, Yuquin
Liu, Hao
Rose, Marie E.
Graham, Steven H.
TI Prolonged opportunity for neuroprotection in experimental stroke with
selective blockade of cyclooxygenase-2 activity
SO BRAIN RESEARCH
LA English
DT Article
DE Cerebral ischemia; Therapeutic window; Clinical significance;
Valdecoxib; COX-2 inhibitor
ID FOCAL CEREBRAL-ISCHEMIA; BRAIN-DAMAGE; NEURONS; COX-2; INHIBITION;
RECEPTORS; RATS; NEUROTOXICITY; INFLAMMATION; CONTRIBUTES
AB The post-treatment effects of the selective cyclooxygenase (COX)-2 inhibitor, valdecoxib, were investigated in a rat model of temporary focal ischemia. Valdecoxib reduced basal brain prostaglandin E(2) concentrations at dosages that did not affect serum thromboxane B(2), consistent with a selective COX-2 effect. Temporary focal cerebral ischemia was produced in rats by middle cerebral artery occlusion for 90 min. There was increased expression of COX-2 protein detected by Western blot and immunocytochemistry within neurons in the ischemic cortex at 4 and 24 h after ischemia. Rats were treated with vehicle or valdecoxib IS min before or 1.5, 3 and 6 h after cerebral ischemia. Rats were sacrificed and brain infarction volume determined 24 h after ischemia. Valdecoxib treatment was associated with a decrease in infarction volume when administered 15 min before, and 1.5 or 3 h but not 6 h after cerebral ischemia, There were no differences in physiological parameters during the procedure. Valdecoxib administered at 1.5 h after ischemia significantly reduced the concentrations of prostaglandin E(2) in ischemic penumbral cortex as compared to the vehicle-treated group and contralateral non-ischemic cortex. These results suggest that COX-2 inhibition with valdecoxib is effective when initiated both before and after middle cerebral artery occlusion. Published by Elsevier B.V.
C1 VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
RP Graham, SH (reprint author), VA Pittsburgh Healthcare, Geriatr Res Educ & Clin Ctr 00GRH, Highland Dr, Pittsburgh, PA 15205 USA.
EM sgra@pitt.edu
FU NIH [R01 NS37459]
FX This work was supported by NIH R01 NS37459 (SHG).
NR 27
TC 19
Z9 21
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 JUL 7
PY 2009
VL 1279
BP 168
EP 173
DI 10.1016/j.brainres.2009.05.020
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 466PI
UT WOS:000267674100018
PM 19446533
ER
PT J
AU Grant, RW
Middleton, B
AF Grant, Richard W.
Middleton, Blackford
TI Improving primary care for patients with complex chronic diseases: Can
health information technology play a role?
SO CANADIAN MEDICAL ASSOCIATION JOURNAL
LA English
DT Editorial Material
ID DECISION-SUPPORT-SYSTEMS; QUALITY
C1 [Grant, Richard W.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Grant, Richard W.; Middleton, Blackford] Harvard Univ, Sch Med, Boston, MA USA.
[Middleton, Blackford] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Middleton, Blackford] Partners HealthCare Syst, Clin Informat Res & Dev, Wellesley, MA USA.
RP Grant, RW (reprint author), 50-9 Staniford St, Boston, MA 02114 USA.
EM rgrant@partners.org
RI Tao, Youyou/D-2367-2014;
OI Grant, Richard/0000-0002-6164-8025
NR 10
TC 5
Z9 5
U1 0
U2 0
PU CMA-CANADIAN MEDICAL ASSOC
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA
SN 0820-3946
J9 CAN MED ASSOC J
JI Can. Med. Assoc. J.
PD JUL 7
PY 2009
VL 181
IS 1-2
BP 17
EP 18
DI 10.1503/cmaj.091101
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 464XJ
UT WOS:000267542600003
PM 19581613
ER
PT J
AU Sgroi, DC
AF Sgroi, Dennis C.
TI Breast Cancer Src Activity: Bad to the Bone
SO CANCER CELL
LA English
DT Editorial Material
ID METASTASIS
C1 [Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Res Unit, Boston, MA 02129 USA.
[Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA.
[Sgroi, Dennis C.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA.
RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Res Unit, Boston, MA 02129 USA.
EM dsgroi@partners.org
NR 8
TC 6
Z9 6
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD JUL 7
PY 2009
VL 16
IS 1
BP 1
EP 2
DI 10.1016/j.ccr.2009.06.010
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 468AR
UT WOS:000267786100001
PM 19573804
ER
PT J
AU Vasudevan, KM
Barbie, DA
Davies, MA
Rabinovsky, R
McNear, CJ
Kim, JJ
Hennessy, BT
Tseng, H
Pochanard, P
Kim, SY
Dunn, IF
Schinzel, AC
Sandy, P
Hoersch, S
Sheng, Q
Gupta, PB
Boehm, JS
Reiling, JH
Silver, S
Lu, YL
Stemke-Hale, K
Dutta, B
Joy, C
Sahin, AA
Gonzalez-Angulo, AM
Lluch, A
Rameh, LE
Jacks, T
Root, DE
Lander, ES
Mills, GB
Hahn, WC
Sellers, WR
Garraway, LA
AF Vasudevan, Krishna M.
Barbie, David A.
Davies, Michael A.
Rabinovsky, Rosalia
McNear, Chontelle J.
Kim, Jessica J.
Hennessy, Bryan T.
Tseng, Hsiuyi
Pochanard, Panisa
Kim, So Young
Dunn, Ian F.
Schinzel, Anna C.
Sandy, Peter
Hoersch, Sebastian
Sheng, Qing
Gupta, Piyush B.
Boehm, Jesse S.
Reiling, Jan H.
Silver, Serena
Lu, Yiling
Stemke-Hale, Katherine
Dutta, Bhaskar
Joy, Corwin
Sahin, Aysegul A.
Gonzalez-Angulo, Ana Maria
Lluch, Ana
Rameh, Lucia E.
Jacks, Tyler
Root, David E.
Lander, Eric S.
Mills, Gordon B.
Hahn, William C.
Sellers, William R.
Garraway, Levi A.
TI AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in
Human Cancer
SO CANCER CELL
LA English
DT Article
ID 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1; MAMMARY EPITHELIAL-CELLS;
HYDROPHOBIC MOTIF PHOSPHORYLATION; BREAST-CANCER; PHOSPHATIDYLINOSITOL
3-KINASES; CAENORHABDITIS-ELEGANS; HOMOLOGY DOMAIN; HIGH-FREQUENCY; MTOR
COMPLEX; ACTIVATION
AB Dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer. PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis largely through activation of the AKT/PKB kinase. However, here we show through phosphoprotein profiling and functional genomic studies that many PIK3CA mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation and a diminished reliance on AKT for anchorage-independent growth. Instead, these cells retain robust PDK1 activation and membrane localization and exhibit dependency on the PDK1 substrate SGK3. SGK3 undergoes PI3K- and PDK1-dependent activation in PIK3CA mutant cancer cells. Thus, PI3K may promote cancer through both AKT-dependent and AKT-independent mechanisms. Knowledge of differential PI3K/PDK1 signaling could inform rational therapeutics in cancers harboring PIK3CA mutations.
C1 [Vasudevan, Krishna M.; Barbie, David A.; Rabinovsky, Rosalia; McNear, Chontelle J.; Kim, Jessica J.; Tseng, Hsiuyi; Pochanard, Panisa; Kim, So Young; Dunn, Ian F.; Schinzel, Anna C.; Sheng, Qing; Hahn, William C.; Sellers, William R.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Vasudevan, Krishna M.; Rabinovsky, Rosalia; McNear, Chontelle J.; Kim, Jessica J.; Kim, So Young; Dunn, Ian F.; Schinzel, Anna C.; Hahn, William C.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Vasudevan, Krishna M.; Rabinovsky, Rosalia; Dunn, Ian F.; Sheng, Qing; Hahn, William C.; Garraway, Levi A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Dunn, Ian F.; Sheng, Qing; Hahn, William C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Barbie, David A.; Kim, So Young; Dunn, Ian F.; Schinzel, Anna C.; Gupta, Piyush B.; Boehm, Jesse S.; Silver, Serena; Root, David E.; Lander, Eric S.; Hahn, William C.; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Sellers, William R.] Novartis Inst BioMed Res, Cambridge, MA 02139 USA.
[Davies, Michael A.; Hennessy, Bryan T.; Lu, Yiling; Stemke-Hale, Katherine; Dutta, Bhaskar; Joy, Corwin; Sahin, Aysegul A.; Gonzalez-Angulo, Ana Maria; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Sandy, Peter; Hoersch, Sebastian; Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Reiling, Jan H.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA.
[Lluch, Ana] Univ Valencia, Clin Hosp, Valencia 46010, Spain.
[Rameh, Lucia E.] Boston Biomed Res Inst, Watertown, MA 02472 USA.
[Barbie, David A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Garraway, LA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM levi_garraway@dfci.harvard.edu
RI Stemke-Hale, Katherine/K-9113-2013;
OI Stemke-Hale, Katherine/0000-0002-1231-4192; Boehm,
Jesse/0000-0002-6795-6336
FU Prostate Cancer Foundation; Burroughs-Wellcome Fund; Department of
Defense [PC073284]; American Society for Clinical Oncology; Human
Frontier Fellowship Organization; National Human Genome Research
Institute; Susan Madden Fund; Starr Cancer Consortium [1A-1 1]; National
Institutes of Health [T32CA09172-33, P50CA093459, R33CA128625,
P01CA050661, P50CA112967, P30CA14051, R01CA085912, DP20DO02750-01];
Novartis, Inc
FX We thank Erica Bauerlein for shRNA constructs; Len Pennacchio, Jan-Fang
Cheng, Mandy Madiredio, Stefan Frohling, Claudia Scholl, and Raymond
Wadlow for technical assistance; Tamas Balla for the PH-AKT GFP
construct; Pablo Tamayo for statistical help; and Payman Amin, Stephen
Basham, Amit Duft, Matthew Meyerson, David Livingston, DavidSabatini,
and members of the Garraway laboratory for helpful discussions. This
work was supported by the Prostate Cancer Foundation, the
Burroughs-Wellcome Fund (L.A.G.), the Department of Defense grant
PC073284(K.M.V.), the American Society for Clinical Oncology (M.A. D.);
the Human Frontier Fellowship Organization (J.H.R.); the National Human
Genome Research Institute (E.S.L.); the Susan Madden Fund (D.A.B.); the
Starr Cancer Consortium 1A-1 1 (W.C.H.); and the National Institutes of
Health grants T32CA09172-33 (D.A.B.), P50CA093459 (M.A.D.), R33CA128625,
P01CA050661 (W.C.H.), P50CA112967, P30CA14051 (T.J.), R01CA085912
("W.R.S. and L.A.G.), and DP20DO02750-01 (L.A.G.). G.B.M. is a
consultant for Amira Pharmaceuticals, Inc., Arcxis Biotech nologies,
Catena Pharmaceuticals, Genentech, Inc., GlaxoSmith Kline, Lpath
Therapeutics, PTV Sciences, QLT, Inc., Sernafore Pharmaceuticals, and
Signal Pharmaceuticals. W.R.S. is an employee for Novartis, Inc. W.C.H.
and L.A.G. are consultants for and received sponsored research support
from Novartis, Inc.
NR 56
TC 273
Z9 281
U1 2
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD JUL 7
PY 2009
VL 16
IS 1
BP 21
EP 32
DI 10.1016/j.ccr.2009.04.012
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 468AR
UT WOS:000267786100006
PM 19573809
ER
PT J
AU McGillicuddy, LT
Fromm, JA
Hollstein, PE
Kubek, S
Beroukhim, R
De Raedt, T
Johnson, BW
Williams, SMG
Nghiemphu, P
Liau, LM
Cloughesy, TF
Mischel, PS
Parret, A
Seiler, J
Moldenhauer, G
Scheffzek, K
Stemmer-Rachamimov, AO
Sawyers, CL
Brennan, C
Messiaen, L
Mellinghoff, IK
Cichowski, K
AF McGillicuddy, Lauren T.
Fromm, Jody A.
Hollstein, Pablo E.
Kubek, Sara
Beroukhim, Rameen
De Raedt, Thomas
Johnson, Bryan W.
Williams, Sybil M. G.
Nghiemphu, Phioanh
Liau, Linda M.
Cloughesy, Tim F.
Mischel, Paul S.
Parret, Annabel
Seiler, Jeanette
Moldenhauer, Gerd
Scheffzek, Klaus
Stemmer-Rachamimov, Anat O.
Sawyers, Charles L.
Brennan, Cameron
Messiaen, Ludwine
Mellinghoff, Ingo K.
Cichowski, Karen
TI Proteasomal and Genetic Inactivation of the NF1 Tumor Suppressor in
Gliomagenesis
SO CANCER CELL
LA English
DT Article
ID NEUROFIBROMATOSIS TYPE-1 GENE; PROTEIN-KINASE-C; HUMAN
GLIOBLASTOMA-MULTIFORME; SOMATIC MUTATIONS; UBIQUITIN LIGASE;
BRAIN-TUMORS; CELLS; SENESCENCE; ACTIVATION; PATHWAY
AB Loss-of-function mutations in the NF1 tumor suppressor result in deregulated Ras signaling and drive tumorigenesis in the familial cancer syndrome neurofibromatosis type I. However, the extent to which NF1 inactivation promotes sporadic tumorigenesis is unknown. Here we report that NF1 is inactivated in sporadic gliomas via two mechanisms: excessive proteasomal degradation and genetic loss. NF1 protein destabilization is triggered by the hyperactivation of protein kinase C (PKC) and confers sensitivity to PKC inhibitors. However, complete genetic loss, which only occurs when p53 is inactivated, mediates sensitivity to mTOR inhibitors. These studies reveal an expanding role for NF1 inactivation in sporadic gliomagenesis and illustrate how different mechanisms of inactivation are utilized in genetically distinct tumors, which consequently impacts therapeutic sensitivity.
C1 [McGillicuddy, Lauren T.; Fromm, Jody A.; Hollstein, Pablo E.; De Raedt, Thomas; Johnson, Bryan W.; Williams, Sybil M. G.; Cichowski, Karen] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[McGillicuddy, Lauren T.; Fromm, Jody A.; Hollstein, Pablo E.; Beroukhim, Rameen; De Raedt, Thomas; Johnson, Bryan W.; Williams, Sybil M. G.; Cichowski, Karen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[McGillicuddy, Lauren T.; Fromm, Jody A.; Hollstein, Pablo E.; Beroukhim, Rameen; De Raedt, Thomas; Johnson, Bryan W.; Williams, Sybil M. G.; Stemmer-Rachamimov, Anat O.; Cichowski, Karen] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Kubek, Sara; Mellinghoff, Ingo K.] Cornell Univ, Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10021 USA.
[Beroukhim, Rameen] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA.
[Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[De Raedt, Thomas; Johnson, Bryan W.; Cichowski, Karen] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA.
[Nghiemphu, Phioanh; Cloughesy, Tim F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Liau, Linda M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA.
[Mischel, Paul S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Parret, Annabel; Seiler, Jeanette; Scheffzek, Klaus] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany.
[Parret, Annabel; Seiler, Jeanette; Scheffzek, Klaus] European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany.
[Moldenhauer, Gerd] German Canc Res Ctr, Translat Immunol Unit, D-69120 Heidelberg, Germany.
[Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sawyers, Charles L.; Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Brennan, Cameron] Cornell Univ, Weill Cornell Med Coll, Dept Neurosurg, New York, NY 10021 USA.
[Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
[Messiaen, Ludwine] Univ Alabama, Dept Genet, Med Genom Lab, Birmingham, AL 35242 USA.
[Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA.
RP Cichowski, K (reprint author), Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM kcichowski@rics.bwh.harvard.edu
RI Sawyers, Charles/G-5327-2016;
OI Brennan, Cameron/0000-0003-4064-8891; Parret,
Annabel/0000-0003-0635-8890
FU Brain Tumor Funders' Collaborative; NCI [R01 CA111754-01]; DOD
[W81XWH-08-1-0136]; Children's Tumor Foundation; Landesstiftung
Baden-Wuerttemberg, Germany
FX We thank Wade Harper, Steve Elledge, Gerard Evan, and Bill Hahn for
helpful discussions and Maria Debiec-Rychter for samples. This work was
supported by grants from the Brain Tumor Funders' Collaborative (I.K.M.,
T.F.C., and P.S.M.), NCI (R01 CA111754-01) (K.C.), DOD
(W81XWH-08-1-0136) (K.C.), The Children's Tumor Foundation (L.T.M.,
S.M.G.W., and A.P.), and Landesstiftung Baden-Wuerttemberg, Germany
(K.S.).
NR 49
TC 69
Z9 71
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 JUL 7
PY 2009
VL 16
IS 1
BP 44
EP 54
DI 10.1016/j.ccr.2009.05.009
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 468AR
UT WOS:000267786100008
PM 19573811
ER
PT J
AU Reddy, VY
Neuzil, P
Themistoclakis, S
Danik, SB
Bonso, A
Rossillo, A
Raviele, A
Schweikert, R
Ernst, S
Kuck, KH
Natale, A
AF Reddy, Vivek Y.
Neuzil, Petr
Themistoclakis, Sakis
Danik, Stephan B.
Bonso, Aldo
Rossillo, Antonio
Raviele, Antonio
Schweikert, Robert
Ernst, Sabine
Kuck, Karl-Heinz
Natale, Andrea
TI Visually-Guided Balloon Catheter Ablation of Atrial Fibrillation
Experimental Feasibility and First-in-Human Multicenter Clinical Outcome
SO CIRCULATION
LA English
DT Article; Proceedings Paper
CT 81st Annual Scientific Session of the American-Heart-Association
CY NOV 08-12, 2008
CL New Orleans, LA
SP Amer Heart Assoc
DE ablation; atrial fibrillation; catheter ablation; lasers; pulmonary
veins
ID PULMONARY VEIN ISOLATION; CIRCUMFERENTIAL ULTRASOUND ABLATION;
CONDUCTION; OSTIUM; LESIONS; SYSTEM
AB Background-Electric isolation of the pulmonary veins (PVs) can successfully treat patients with paroxysmal atrial fibrillation. However, it remains technically challenging to identify the left atrial-PV junction and sequentially position the ablation catheter in a point-by-point contiguous fashion to isolate the PVs. In this study, a novel endoscopic ablation system was used to directly visualize and ablate tissue at the left atrial-PV junction with laser energy.
Methods and Results-This study consisted of 2 phases: a short-term (n = 9) and long-term (n = 11) canine experimental validation phase and a multicenter clinical feasibility phase (n = 30 paroxysmal atrial fibrillation patients). After transseptal puncture, the balloon-based endoscopic ablation system was advanced to each PV ostium, and arcs of laser energy (90 to 360) were projected onto the target left atrial-PV junction. Electric PV isolation was defined with a circular multielectrode catheter. In the short-term preclinical experimental phase, 15 of 17 targeted PVs (88%) were successfully isolated. Pathological examination revealed well-demarcated circumferential lesions with minimal endothelial disruption. In the long-term experiments, 9 of 10 targeted veins (90%) remained persistently isolated (at 4 to 8 weeks). In the clinical phase, 105 of 116 PVs (91%) were successfully isolated. After a single procedure, the 12-month drug-free rate of freedom from atrial fibrillation was 60% (18 of 30 patients). There were no significant PV stenoses, but adverse events included 1 episode of cardiac tamponade, 1 stroke without residual defect, and 1 asymptomatic phrenic nerve palsy.
Conclusion-This study establishes the feasibility of a novel paradigm for AF ablation: direct visualization to guide catheter ablation of the left atrial-PV junction. (Circulation. 2009; 120: 12-20.)
C1 [Reddy, Vivek Y.] Mt Sinai Sch Med, New York, NY USA.
[Reddy, Vivek Y.; Danik, Stephan B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Reddy, Vivek Y.; Danik, Stephan B.] Harvard Univ, Sch Med, Boston, MA USA.
[Reddy, Vivek Y.; Neuzil, Petr] Homolka Hosp, Prague, Czech Republic.
[Themistoclakis, Sakis; Bonso, Aldo; Rossillo, Antonio; Raviele, Antonio; Natale, Andrea] Umberto Hosp, Venice, Italy.
[Schweikert, Robert] Akron Gen Med Ctr, Akron, OH USA.
[Ernst, Sabine; Kuck, Karl-Heinz] St Georg Hosp, Hamburg, Germany.
[Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA.
RP Reddy, VY (reprint author), Univ Miami, Miller Sch Med, 1400 NW 12th Ave,Suite 4062, Miami, FL 33136 USA.
EM vreddy@med.miami.edu
NR 18
TC 49
Z9 49
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 7
PY 2009
VL 120
IS 1
BP 12
EP 20
DI 10.1161/CIRCULATIONAHA.108.840587
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 468BO
UT WOS:000267788500004
PM 19546385
ER
PT J
AU Wills, AM
Cronin, S
Slowik, A
Kasperaviciute, D
Van Es, MA
Morahan, JM
Valdmanis, PN
Meininger, V
Melki, J
Shaw, CE
Rouleau, GA
Fisher, EMC
Shaw, PJ
Morrison, KE
Pamphlett, R
Van den Berg, LH
Figlewicz, DA
Andersen, PM
Al-Chalabi, A
Hardiman, O
Purcell, S
Landers, JE
Brown, RH
AF Wills, A-M.
Cronin, S.
Slowik, A.
Kasperaviciute, D.
Van Es, M. A.
Morahan, J. M.
Valdmanis, P. N.
Meininger, V.
Melki, J.
Shaw, C. E.
Rouleau, G. A.
Fisher, E. M. C.
Shaw, P. J.
Morrison, K. E.
Pamphlett, R.
Van den Berg, L. H.
Figlewicz, D. A.
Andersen, P. M.
Al-Chalabi, A.
Hardiman, O.
Purcell, S.
Landers, J. E.
Brown, R. H., Jr.
TI A large-scale international meta-analysis of paraoxonase gene
polymorphisms in sporadic ALS
SO NEUROLOGY
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; GENOME-WIDE ASSOCIATION; CLUSTER
POLYMORPHISMS; DISEASE; SUSCEPTIBILITY; POPULATION; LINKAGE; DIAGNOSIS;
CRITERIA
AB Background: Six candidate gene studies report a genetic association of DNA variants within the paraoxonase locus with sporadic amyotrophic lateral sclerosis (ALS). However, several other large studies, including five genome-wide association studies, have not duplicated this finding.
Methods: We conducted a meta-analysis of 10 published studies and one unpublished study of the paraoxonase locus, encompassing 4,037 ALS cases and 4,609 controls, including genome-wide association data from 2,018 ALS cases and 2,425 controls.
Results: The combined fixed effects odds ratio (OR) for rs662(PON1Q192R) was 1.09(95% confidence interval [CI], 1.02-1.16, p = 0.01); the genotypic OR for RR homozygotes at Q192R was 1.25 (95% CI, 1.07-1.45, p = 0.0004); the combined OR for rs854560(PON1L55M) was 0.97(95% CI, 0.86-1.10, p = 0.62); the OR for rs10487132 (PON2) was 1.08 (95% CI, 0.92-1.27, p = 0.35). Although the rs662 polymorphism reached a nominal level of significance, no polymorphism was significant after multiple testing correction. In the subanalysis of samples with genome-wide data from which population outliers were removed, rs662 had an OR of 1.06 (95% CI, 0.97-1.16, p = 0.22).
Conclusions: In contrast to previous positive smaller studies, our genetic meta-analysis showed no significant association of amyotrophic lateral sclerosis (ALS) with the PON locus. This is the largest meta-analysis of a candidate gene in ALS to date and the first ALS meta-analysis to include data from whole genome association studies. The findings reinforce the need for much larger and more collaborative investigations of the genetic determinants of ALS. Neurology (R) 2009; 73: 16-24
C1 [Wills, A-M.; Landers, J. E.; Brown, R. H., Jr.] Massachusetts Gen Hosp, Neuromuscular Res Lab, Charlestown, MA USA.
[Cronin, S.; Hardiman, O.] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland.
[Slowik, A.] Jagiellonian Univ, Dept Neurol, Krakow, Poland.
[Kasperaviciute, D.; Fisher, E. M. C.] UCL Inst Neurol, Dept Neurodegenerat Dis, London, England.
[Van Es, M. A.; Van den Berg, L. H.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Neurol, Netherlands ALS Ctr, Utrecht, Netherlands.
[Morahan, J. M.; Pamphlett, R.] Univ Sydney, Dept Pathol, Stacey MND Lab, Sydney, NSW 2006, Australia.
[Morahan, J. M.] Royal Prince Alfred Hosp, Dept Mol & Clin Genet, Sydney, NSW, Australia.
[Valdmanis, P. N.; Rouleau, G. A.] Univ Montreal, CHUM Res Ctr, Ctr Excellence Neur, Montreal, PQ H3C 3J7, Canada.
[Valdmanis, P. N.; Rouleau, G. A.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Meininger, V.] Hop La Pitie Salpetriere, Ctr Referent SLA, Paris, France.
[Melki, J.] Hadassah Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel.
[Shaw, C. E.; Al-Chalabi, A.] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, MRC Ctr Neurodegenerat Res, London WC2R 2LS, England.
[Shaw, P. J.] Univ Sheffield, Sch Med, Acad Neurol Unit, Sheffield S10 2TN, S Yorkshire, England.
[Morrison, K. E.] Univ Birmingham, Sch Med, Inst Biomed Res, Dept Clin Neurosci, Birmingham B15 2TT, W Midlands, England.
[Figlewicz, D. A.] Univ Michigan, Ann Arbor, MI USA.
[Figlewicz, D. A.] ALS Soc Canada, Ann Arbor, MI USA.
[Andersen, P. M.] Umea Univ Hosp, Dept Neurol, Umea, Sweden.
[Hardiman, O.] Trinity Coll Dublin, Inst Neurosci, Dublin, Ireland.
[Purcell, S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Wills, AM (reprint author), CNY 114-3125,114 16th St, Charlestown, MA 02129 USA.
EM awills@partners.org
RI Kasperaviciute, Dalia/D-1493-2009; Shaw, Pamela/A-7620-2010; Al-Chalabi,
Ammar/E-5361-2010; Shaw, Pamela/E-6193-2010;
OI Al-Chalabi, Ammar/0000-0002-4924-7712; Hardiman,
Orla/0000-0003-2610-1291
FU Medical Research Council [G0500289, , G0600974, G0400149, G0900688];
NIEHS NIH HHS [R01 ES013482-01]; Wellcome Trust [, 089701]
NR 37
TC 35
Z9 35
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL 7
PY 2009
VL 73
IS 1
BP 16
EP 24
DI 10.1212/WNL.0b013e3181a18674
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 463VP
UT WOS:000267461000005
PM 19321847
ER
PT J
AU Zhu, XP
El Fakhri, G
AF Zhu, Xuping
El Fakhri, Georges
TI Monte Carlo modeling of cascade gamma rays in Y-86 PET imaging:
preliminary results
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID YTTRIUM-86; RADIATION; I-124; BR-76; 2D
AB Y-86 is a PET agent that could be used as an ideal surrogate to allow personalized dosimetry in Y-90 radionuclide therapy. However, Y-86 also emits cascade gamma rays. We have developed a Monte Carlo program based on SimSET (Simulation System for Emission Tomography) to model cascade gamma rays in PET imaging. The new simulation was validated with the GATE simulation package. Agreements within 15% were found in spatial resolution, apparent scatter fraction (ratio of coincidences outside peak regions in line source sinograms), single and coincidence statistics and detected photons energy distribution within the PET energy window. A discrepancy of 20% was observed in the absolute scatter fraction, likely caused by differences in the tracking of higher energy cascade gamma photons. On average, the new simulation is 6 times faster than GATE, and the computing time can be further improved by using variance reduction techniques currently available in SimSET. Comparison with phantom acquisitions showed agreements in spatial resolutions and the general shape of projection profiles; however, the standard scatter correction method on the scanner is not directly applicable to Y-86 PET as it leads to incorrect scatter fractions. The new simulation was used to characterize Y-86 PET. Compared with conventional F-18 PET, in which major contamination at low count rates comes from scattered events, cascade gamma-involved events are more important in Y-86 PET. The two types of contaminations have completely different distribution patterns, which should be considered for the corrections of their effects. Our approach will be further improved in the future in the modeling of random coincidences and tracking of high-energy photons, and simulation results will be used for the development of correction methods in Y-86 PET.
C1 [Zhu, Xuping] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Zhu, XP (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM xzhu4@Partners.org; elfakhri@pet.mgh.harvard.edu
FU NIH [R21-CA134812]; Society of Nuclear Medicine Pilot Research Grant
FX This work is supported by NIH grant R21-CA134812 and a Society of
Nuclear Medicine Pilot Research Grant.
NR 16
TC 4
Z9 4
U1 0
U2 0
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JUL 7
PY 2009
VL 54
IS 13
BP 4181
EP 4193
DI 10.1088/0031-9155/54/13/014
PG 13
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 459UW
UT WOS:000267137200014
PM 19521011
ER
PT J
AU Shackelford, DB
Vasquez, DS
Corbeil, J
Wu, SL
Leblanc, M
Wu, CL
Vera, DR
Shaw, RJ
AF Shackelford, David B.
Vasquez, Debbie S.
Corbeil, Jacqueline
Wu, Shulin
Leblanc, Mathias
Wu, Chin-Lee
Vera, David R.
Shaw, Reuben J.
TI mTOR and HIF-1 alpha-mediated tumor metabolism in an LKB1 mouse model of
Peutz-Jeghers syndrome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE AMPK; FDG-PET; glycolysis; hamartoma; polyposis
ID TUBEROUS SCLEROSIS COMPLEX; GROWTH-FACTOR EXPRESSION; CELL-GROWTH;
MAMMALIAN TARGET; STK11 DELETIONS; MESSENGER-RNA; CANCER-CELLS;
RAPAMYCIN; POLYPOSIS; KINASE
AB Peutz-Jeghers syndrome (PJS) is a familial cancer disorder due to inherited loss of function mutations in the LKB1/STK11 serine/threonine kinase. PJS patients develop gastrointestinal hamartomas with 100% penetrance often in the second decade of life, and demonstrate an increased predisposition toward the development of a number of additional malignancies. Among mitogenic signaling pathways, the mammalian-target of rapamycin complex 1 (mTORC1) pathway is hyperactivated in tissues and tumors derived from LKB1-deficient mice. Consistent with a central role for mTORC1 in these tumors, rapamycin as a single agent results in a dramatic suppression of preexisting GI polyps in LKB1+/- mice. However, the key targets of mTORC1 in LKB1-deficient tumors remain unknown. We demonstrate here that these polyps, and LKB1- and AMPK-deficient mouse embryonic fibroblasts, show dramatic up-regulation of the HIF-1 alpha transcription factor and its downstream transcriptional targets in an rapamycin-suppressible manner. The HIF-1 alpha targets hexokinase II and Glut1 are up-regulated in these polyps, and using FDG-PET, we demonstrate that LKB1+/- mice show increased glucose utilization in focal regions of their GI tract corresponding to these gastrointestinal hamartomas. Importantly, we demonstrate that polyps from human Peutz-Jeghers patients similarly exhibit up-regulated mTORC1 signaling, HIF-1 alpha, and GLUT1 levels. Furthermore, like HIF-1 alpha and its target genes, the FDG-PET signal in the GI tract of these mice is abolished by rapamycin treatment. These findings suggest a number of therapeutic modalities for the treatment and detection of hamartomas in PJS patients, and potential for the screening and treatment of the 30% of sporadic human lung cancers bearing LKB1 mutations.
C1 [Shackelford, David B.; Vasquez, Debbie S.; Leblanc, Mathias; Shaw, Reuben J.] Salk Inst Biol Studies, Dulbecco Ctr Canc Res, La Jolla, CA 92037 USA.
[Shackelford, David B.; Vasquez, Debbie S.; Shaw, Reuben J.] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
[Corbeil, Jacqueline; Vera, David R.] Univ Calif San Diego, Moores Canc Ctr, Mol Imaging Program, Dept Radiol, La Jolla, CA 92093 USA.
[Wu, Shulin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Wu, Shulin; Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Shaw, RJ (reprint author), Salk Inst Biol Studies, Dulbecco Ctr Canc Res, La Jolla, CA 92037 USA.
EM shaw@salk.edu
FU National Institutes of Health [P01 CA120964]; National Cancer Institute
[P50 CA128346]; American Cancer Society; V Foundation for Cancer
Research; [T32 CA009370]
FX We thank Lauri Aaltonen and Sini Marttinen (Biomedicum Helsinki,
Helsinki) for the Finnish Peutz-Jeghers patient samples, Keith Laderoute
(SRI International, Menlo Park, CA) and Benoit Viollet (Institut Cochin,
Paris) for their generous donation of the isogenic SV40-immortalized
wild-type and AMPKa1/a2 double deficient MEFs, and Dr. Carl Ho
(University of California San Diego, La Jolla, CA) for his assistance in
analyzing the FDG-PET data. We thank Katja Lamia for critical reading of
the manuscript. This work was supported in part from grants from the
National Institutes of Health (P01 CA120964 to R. J. S. and C.- L. W.),
National Cancer Institute (P50 CA128346 to D. R. V.), American Cancer
Society (R. J. S.), and V Foundation for Cancer Research (R. J. S). D.
B. S. was supported by training grant T32 CA009370 to the Salk Institute
Center for Cancer Research.
NR 59
TC 102
Z9 106
U1 4
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 JUL 7
PY 2009
VL 106
IS 27
BP 11137
EP 11142
DI 10.1073/pnas.0900465106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468DX
UT WOS:000267796100050
PM 19541609
ER
PT J
AU He, CW
Qu, XY
Cui, LB
Wang, JD
Kang, JX
AF He, Chengwei
Qu, Xiying
Cui, Libin
Wang, Jingdong
Kang, Jing X.
TI Improved spatial learning performance of fat-1 mice is associated with
enhanced neurogenesis and neuritogenesis by docosahexaenoic acid
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cognitive function; omega-3 fatty acids; transgenic fat-1 mice; neural
stem cells
ID POLYUNSATURATED FATTY-ACIDS; PROLIFERATOR-ACTIVATED RECEPTOR;
RETINOID-X-RECEPTOR; GENE-EXPRESSION; IN-VITRO; NEURONAL
DIFFERENTIATION; ADULT NEUROGENESIS; ARACHIDONIC-ACID; DENTATE GYRUS;
GRANULE CELLS
AB Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LC-PUFA), highly enriched in the central nervous system, is critical for brain development and function. It has been shown that DHA deficiency impairs cognitive performance whereas DHA supplementation improves the condition. However, the mechanisms underlying the role of DHA in brain development and function remain to be elucidated. By using transgenic fat-1 mice rich in endogenous n-3 PUFA, we show that increased brain DHA significantly enhances hippocampal neurogenesis shown by an increased number of proliferating neurons and neuritogenesis, evidenced by increased density of dendritic spines of CA1 pyramidal neurons in the hippocampus. Concurrently, fat-1 mice exhibit a better spatial learning performance in the Morris water maze compared with control WT littermates. In vitro experiments further demonstrate that DHA promotes differentiation and neurite outgrowth of neuronal cells derived from mouse ES cells and increases the proliferation of cells undergoing differentiation into neuronal lineages from the ES cells. These results together provide direct evidence for a promoting effect of DHA on neurogenesis and neuritogenesis and suggest that this effect may be a mechanism underlying its beneficial effect on behavioral performance.
C1 [He, Chengwei; Qu, Xiying; Wang, Jingdong; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA.
[Cui, Libin] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Cui, Libin] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, 149 13th St,Room 4433, Charlestown, MA 02129 USA.
EM kang.jing@mgh.harvard.edu
FU National Institutes of Health [CA113605]
FX We thank Dr. Alexander Leaf for critically reviewing the manuscript,
Anna Kreshock for histopathology services, Piet Habbel for assistance in
the analysis of neurite, and Zerong You and Jinsheng Yang for technical
assistance in Morris water maze test. This work was partially supported
by National Institutes of Health Grant CA113605.
NR 40
TC 98
Z9 108
U1 5
U2 14
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 JUL 7
PY 2009
VL 106
IS 27
BP 11370
EP 11375
DI 10.1073/pnas.0904835106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468DX
UT WOS:000267796100090
PM 19549874
ER
PT J
AU Park, SM
Kim, SY
Earle, CC
Jeong, SY
Yun, YH
AF Park, Sang Min
Kim, Sun-Young
Earle, Craig C.
Jeong, Seung-Yong
Yun, Young Ho
TI What is the most cost-effective strategy to screen for second primary
colorectal cancers in male cancer survivors in Korea?
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Cost-effectiveness; Second primary colorectal cancer; Screening; Cancer
survivor
ID CONTRAST BARIUM ENEMA; SURVEILLANCE GUIDELINES; ENDOSCOPIC PERFORATION;
RISK; COLONOSCOPY; POLYPS; COLON; POPULATION; SOCIETY; RECTUM
AB AIM: To identify a cost-effective strategy of second primary colorectal cancer (CRC) screening for cancer survivors in Korea using a decision-analytic model.
METHODS: A Markov model estimated the clinical and economic consequences of a simulated 50-year-old male cancer survivors' cohort, and we compared the results of eight screening strategies: no screening, fecal occult blood test (FOBT) annually, FOBT every 2 years, sigmoidoscopy every 5 years, double contrast barium enema every 5 years, and colonoscopy every 10 years (COL10), every 5 years (COL5), and every 3 years (COL3). We included only direct medical costs, and our main outcome measures were discounted lifetime costs, life expectancy, and incremental cost-effectiveness ratio (ICER).
RESULTS: In the base-case analysis, the non-dominated strategies in cancer survivors were COL5, and COL3. The ICER for COL3 in cancer survivors was $5593/life-year saved (LYS), and did not exceed $10000/LYS in one-way sensitivity analyses. If the risk of CRC in cancer survivors is at least two times higher than that in the general population, COL5 had an ICER of less than $10500/LYS among both good and poor prognosis of index cancer. If the age of cancer survivors starting CRC screening was decreased to 40 years, the ICER of COL5 was less than $7400/LYS regardless of screening compliance.
CONCLUSION: Our study suggests that more strict and frequent recommendations for colonoscopy such as COL5 and COL3 could be considered as economically reasonable second primary CRC screening strategies for Korean male cancer survivors. (C) 2009 The WIG Press and Baishideng. All rights reserved.
C1 [Yun, Young Ho] Natl Canc Ctr, Div Canc Control, Goyang 411769, Gyeonggi Do, South Korea.
[Park, Sang Min] Seoul Natl Univ, Coll Med, Dept Family Med, Seoul Natl Univ Hosp, Seoul 110799, South Korea.
[Park, Sang Min] Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02115 USA.
[Park, Sang Min] Natl Canc Ctr, Div Canc Control, Goyang, Gyeonggi, South Korea.
[Kim, Sun-Young] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA 02115 USA.
[Earle, Craig C.] Harvard Univ, Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol,Med Sch, Boston, MA 02108 USA.
[Jeong, Seung-Yong] Seoul Natl Univ, Coll Med, Dept Surg, Seoul Natl Univ Hosp, Seoul 110799, South Korea.
RP Yun, YH (reprint author), Natl Canc Ctr, Div Canc Control, 809 Madu Dong, Goyang Si 411769, Gyeonggi Do, South Korea.
EM lawyun08@ncc.re.kr
RI Yun, Young Ho/J-5560-2012; Park, Sang Min/J-5484-2012; Jeong,
Seung-Yong/J-5643-2012
FU Harvard School of Public Health; National Cancer Center [07104221]
FX Supported by Takemi Program in International Health at Harvard School of
Public Health and by National Cancer Center Grant, No. 07104221
NR 46
TC 4
Z9 6
U1 0
U2 3
PU W J G PRESS
PI BEIJING
PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345,
BEIJING 100023, PEOPLES R CHINA
SN 1007-9327
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD JUL 7
PY 2009
VL 15
IS 25
BP 3153
EP 3160
DI 10.3748/wjg.15.3153
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 468YT
UT WOS:000267861500011
PM 19575496
ER
PT J
AU Mao, YD
Sun, QM
Wang, XF
Ouyang, Q
Han, L
Jiang, L
Han, D
AF Mao, Youdong
Sun, Quanmei
Wang, Xiufeng
Ouyang, Qi
Han, Li
Jiang, Lei
Han, Dong
TI In vivo nanomechanical imaging of blood-vessel tissues directly in
living mammals using atomic force microscopy
SO APPLIED PHYSICS LETTERS
LA English
DT Article
ID CELLS; STRESS; STIFFNESS; MECHANICS; NETWORKS
AB Atomic force microscopy (AFM) is difficult to achieve in living mammals but is necessary for understanding mechanical properties of tissues in their native form in organisms. Here we report in vivo nanomechanical imaging of blood-vessel tissues directly in living mammalians by AFM combined with surgical operations. Nanomechanical heterogeneity of blood vessels is observed across the diverse microenvironments of the same tissues in vivo. This method is further used to measure the counteractive nanomechanical changes in real time during drug-induced vasodilation and vasoconstriction in vivo, demonstrating appealing potential in characterization of in vivo nanomechanical dynamics of native tissues. (C) 2009 American Institute of Physics. [DOI:10.1063/1.3167546]
C1 [Mao, Youdong; Sun, Quanmei; Han, Dong] Natl Ctr Nanosci & Technol, Beijing 100080, Peoples R China.
[Mao, Youdong] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Mao, Youdong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wang, Xiufeng] Tsinghua Univ, Dept Phys, Beijing 100084, Peoples R China.
[Ouyang, Qi] Peking Univ, Sch Phys, Beijing 100871, Peoples R China.
[Han, Li] Chinese Acad Sci, Inst Elect Engn, Beijing 100190, Peoples R China.
[Jiang, Lei] Chinese Acad Sci, Inst Chem, Beijing 100190, Peoples R China.
RP Han, D (reprint author), Natl Ctr Nanosci & Technol, Beijing 100080, Peoples R China.
EM jianglei@iccas.ac.cn; dhan@nanoctr.cn
RI jiang, lei/E-8437-2010; Jiang, Lei/B-1066-2011
FU National Science Foundation of China [90709054]; Ministry of Science and
Technology of China [2006CB705600, 2009CB930200]
FX We thank J.H. Wang, L. Chen, and P. Chen for their assistance during
experiment. This work was supported by the National Science Foundation
of China (Grant No. 90709054) and the project of 973 in Ministry of
Science and Technology of China (Grant Nos. 2006CB705600 and
2009CB930200).
NR 15
TC 22
Z9 27
U1 7
U2 31
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0003-6951
J9 APPL PHYS LETT
JI Appl. Phys. Lett.
PD JUL 6
PY 2009
VL 95
IS 1
AR 013704
DI 10.1063/1.3167546
PG 3
WC Physics, Applied
SC Physics
GA 470NV
UT WOS:000267983200102
ER
PT J
AU Bienvenu, OJ
Wang, Y
Shugart, YY
Welch, JM
Grados, MA
Fyer, AJ
Rauch, SL
McCracken, JT
Rasmussen, SA
Murphy, DL
Cullen, B
Valle, D
Hoehn-Saric, R
Greenberg, BD
Pinto, A
Knowles, JA
Piacentini, J
Pauls, DL
Liang, KY
Willour, VL
Riddle, M
Samuels, JF
Feng, G
Nestadt, G
AF Bienvenu, O. J.
Wang, Y.
Shugart, Y. Y.
Welch, J. M.
Grados, M. A.
Fyer, A. J.
Rauch, S. L.
McCracken, J. T.
Rasmussen, S. A.
Murphy, D. L.
Cullen, B.
Valle, D.
Hoehn-Saric, R.
Greenberg, B. D.
Pinto, A.
Knowles, J. A.
Piacentini, J.
Pauls, D. L.
Liang, K. Y.
Willour, V. L.
Riddle, M.
Samuels, J. F.
Feng, G.
Nestadt, G.
TI Sapap3 and Pathological Grooming in Humans: Results From the OCD
Collaborative Genetics Study
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE genes; Dlgap3; obsessive-compulsive disorder; nail biting;
trichotillomania
ID OBSESSIVE-COMPULSIVE DISORDER; SPECTRUM DISORDERS; PEDIATRIC PROBANDS;
ANXIETY DISORDERS; TRANSPORTER GENE; LINKAGE ANALYSIS; MESSENGER-RNA;
TRICHOTILLOMANIA; FAMILY; ASSOCIATION
AB SAP90/PSD95-associated protein (SAPAP) family proteins are post-synaptic density (PSD) components that interact with other proteins to form a key scaffolding complex at excitatory (glutamatergic) synapses. A recent study found that mice with a deletion of the Sapap3 gene groomed themselves excessively, exhibited increased anxiety-like behaviors, and had cortico-striatal synaptic defects, all of which were preventable with lentiviral-mediated expression of Sapap3 in the striatum; the behavioral abnormalities were also reversible with fluoxetine. In the current study, we sought to determine whether variation within the human Sapap3 gene was associated with grooming disorders (GDs: pathologic nail biting, pathologic skin picking, and/or trichotillomania) and/or obsessive-compulsive disorder (OCD) in 383 families thoroughly phenotyped for OCD genetic studies. We conducted family-based association analyses using the FBAT and GenAssoc statistical packages. Thirty-two percent of the 1,618 participants met criteria for a GD, and 65% met criteria for OCD. Four of six SNPs were nominally associated (P < 0.05) with at least one GD (genotypic relative risks: 1.6-3.3), and all three haplotypes were nominally associated with at least one GD (permuted P < 0.05). None of the SNPs or haplotypes were significantly associated with OCD itself. We conclude that Sapap3 is a promising functional candidate gene for human GDs, though further work is necessary to confirm this preliminary evidence of association. (C) 2008 Wiley-Liss, Inc.
C1 [Bienvenu, O. J.; Wang, Y.; Grados, M. A.; Cullen, B.; Hoehn-Saric, R.; Willour, V. L.; Riddle, M.; Samuels, J. F.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
[Shugart, Y. Y.] Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Welch, J. M.; Feng, G.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
[Fyer, A. J.; Knowles, J. A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Fyer, A. J.; Knowles, J. A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Rauch, S. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA.
[McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles Sch Med, Los Angeles, CA 90024 USA.
[Rasmussen, S. A.; Greenberg, B. D.; Pinto, A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
[Valle, D.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA.
[Pauls, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Liang, K. Y.] Johns Hopkins Univ, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
RP Bienvenu, OJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 115, Baltimore, MD 21287 USA.
EM jbienven@jhmi.edu
RI Piacentini, John/C-4645-2011; Citations, TLC SAB/C-4006-2011; Liang,
Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017;
OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905
FU NIH [MH50125, RR00052, NS42609, MH64543, MH66284]
FX NIH grants MH50125, RR00052, NS42609, MH64543, and MH66284 supported
this study. The authors thank the many families who have participated in
the OCD Collaborative Genetics Study (OCGS); the Obsessive-Compulsive
Foundation; Ann Pulver, PhD, Kathleen Merikangas, PhD, David Houseman,
MD, and Alec Wilson, PhD, for consultation; and clinicians and
coordinators at each OCGS site: Providence (Maria Mancebo, PhD, Richard
Marsland, RN, and Shirley Yen, PhD); New York (Renee Goodwin, PhD,
Joshua Lipsitz, PhD, and Jessica Page, PsyD); Baltimore (Laura Eisen,
BS, Karan Lamb, PsyD, Tracey Lichner, PhD, Yung-mei Leong, PhD, and
Krista Vermillion, BA); Boston (Dan Geller, MD, Anne Chosak, PhD,
Michelle Wedig, BS, Evelyn Stewart, MD, Michael Jenike, MD, Beth
Gershuny, PhD, and Sabine Wilhelm, PhD); Bethesda (Lucy Justement, Diane
Kazuba, V. Holland LaSalle-Ricci, and Theresa B. DeGuzman); and Los
Angeles (R. Lindsey Bergman, PhD, Susanna Chang, PhD, Audra Langley,
PhD, and Amanda Pearlman, BA).
NR 63
TC 70
Z9 75
U1 2
U2 12
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUL 5
PY 2009
VL 150B
IS 5
BP 710
EP 720
DI 10.1002/ajmg.b.30897
PG 11
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 464BZ
UT WOS:000267481100010
PM 19051237
ER
PT J
AU Doyle, AE
Ferreira, MAR
Sklar, PB
Lasky-Su, J
Petty, C
Fusillo, SJ
Seidman, LJ
Willcutt, EG
Smoller, JW
Purcel, S
Biederman, J
Faraone, SV
AF Doyle, Alysa E.
Ferreira, Manuel A. R.
Sklar, Pamela B.
Lasky-Su, Jessica
Petty, Carter
Fusillo, Steven J.
Seidman, Larry J.
Willcutt, Erik G.
Smoller, Jordan W.
Purcel, Shaun
Biederman, Joseph
Faraone, Stephen V.
TI Multivariate Genomewide Linkage Scan of Neurocognitive Traits and ADHD
Symptoms: Suggestive Linkage to 3q13 (vol 147B, pg 1399, 2008)
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Correction
C1 [Doyle, Alysa E.; Petty, Carter; Fusillo, Steven J.; Seidman, Larry J.; Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA.
[Doyle, Alysa E.; Ferreira, Manuel A. R.; Sklar, Pamela B.; Smoller, Jordan W.; Purcel, Shaun] Massachusetts Gen Hosp, Psychiat & Neurodevel Genet Unit, Boston, MA 02114 USA.
[Doyle, Alysa E.; Ferreira, Manuel A. R.; Sklar, Pamela B.; Seidman, Larry J.; Smoller, Jordan W.; Purcel, Shaun; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA.
[Ferreira, Manuel A. R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Lasky-Su, Jessica] Brigham & Womens Hosp, Channing Labs, Boston, MA 02115 USA.
[Seidman, Larry J.] Div Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr Publ Psychiat, Boston, MA USA.
[Willcutt, Erik G.] Univ Colorado, Boulder, CO 80309 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci & Physiol, Syracuse, NY USA.
RP Doyle, AE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUL 5
PY 2009
VL 150B
IS 5
BP 751
EP 751
DI 10.1002/ajmg.b.30997
PG 1
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 464BZ
UT WOS:000267481100015
ER
PT J
AU Mega, JL
Braunwald, E
Mohanavelu, S
Burton, P
Poulter, R
Misselwitz, F
Hricak, V
Barnathan, ES
Bordes, P
Witkowski, A
Markov, V
Oppenheimer, L
Gibson, CM
AF Mega, J. L.
Braunwald, E.
Mohanavelu, S.
Burton, P.
Poulter, R.
Misselwitz, F.
Hricak, V.
Barnathan, E. S.
Bordes, P.
Witkowski, A.
Markov, V.
Oppenheimer, L.
Gibson, C. M.
CA ATLAS ACS-TIMI 46 Study Grp
TI Rivaroxaban versus placebo in patients with acute coronary syndromes
(ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial
SO LANCET
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; TOTAL KNEE ARTHROPLASTY; ANTITHROMBOTIC
THERAPY; HIP-ARTHROPLASTY; UNSTABLE ANGINA; LONG-TERM; ASPIRIN;
WARFARIN; ENOXAPARIN; THROMBOPROPHYLAXIS
AB Background Rivaroxaban is an oral direct factor Xa inhibitor that has been effective in prevention of venous thromboembolism in patients undergoing elective orthopaedic surgery. However, its use after acute coronary syndromes has not been investigated. In this setting, we assessed the safety and efficacy of rivaroxaban and aimed to select the most favourable dose and dosing regimen.
Methods In this double-blind, dose-escalation, phase II study, undertaken at 297 sites in 27 countries, 3491 patients stabilised after an acute coronary syndrome were stratified on the basis of investigator decision to use aspirin only (stratum 1, n=761) or aspirin plus a thienopyridine (stratum 2, n=2730). Participants were randomised within each strata and dose tier with a block randomisation method at 1:1:1 to receive either placebo or rivaroxaban (at doses 5-20 mg) given once daily or the same total daily dose given twice daily. The primary safety endpoint was clinically significant bleeding (TIMI major, TIMI minor, or requiring medical attention); the primary efficacy endpoint was death, myocardial infarction, stroke, or severe recurrent ischaemia requiring revascularisation during 6 months. Safety analyses included all participants who received at least one dose of study drug; efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00402597.
Findings Three patients in stratum 1 and 26 in stratum 2 never received the study drug. The risk of clinically significant bleeding with rivaroxaban versus placebo increased in a dose-dependent manner (hazard ratios [HRs] 2.21 [95% Cl 1.25-3.91] for 5 mg, 3.35 [2.31-4.87] for 10 mg, 3.60 [2.32-5.58] for 15 mg, and 5.06 [3.45-7.42] for 20 mg doses; p<0.0001). Rates of the primary efficacy endpoint were 5.6% (126/2331) for rivaroxaban versus 7.0% (79/1160) for placebo (HR 0.79 [0.60-1.05], p=0.10). Rivaroxaban reduced the main secondary efficacy endpoint of death, myocardial infarction, or stroke compared with placebo (87/2331 [3.9%] vs 62/1160 [5.5%]; HR 0.69, [95% CI 0.50-0.96], p=0.0270). The most common adverse event in both groups was chest pain (248/2309 [10.7%] vs 118/1153 [10.2%]).
Interpretation The use of an oral factor Xa inhibitor in patients stabilised after an acute coronary syndrome increases bleeding in a dose-dependent manner and might reduce major ischaemic outcomes. On the basis of these observations, a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway.
C1 [Mega, J. L.; Braunwald, E.] Harvard Univ, Div Cardiovasc, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Mega, J. L.; Braunwald, E.; Mohanavelu, S.] TIMI Study Grp, Boston, MA USA.
[Burton, P.; Barnathan, E. S.; Oppenheimer, L.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA.
[Poulter, R.] Univ Queensland, Royal Brisbane Hosp, Herston, Qld, Australia.
[Misselwitz, F.] Bayer HealthCare, Wuppertal, Germany.
[Hricak, V.] Natl Heart Inst, Bratislava, Slovakia.
[Bordes, P.] Hosp Gen Univ Alicante, Alicante, Spain.
[Witkowski, A.] Inst Cardiol, Warsaw, Poland.
[Markov, V.] State Inst Res Cardiol Inst, Tomsk, Russia.
[Gibson, C. M.] Harvard Univ, Sch Med, Beth Israel Hosp, Div Cardiovasc, Boston, MA USA.
RP Mega, JL (reprint author), Harvard Univ, Div Cardiovasc, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA.
EM jmega@partners.org
RI Walters, Darren/A-7069-2011; Sinkiewicz, Wladyslaw/G-5169-2014;
Ponikowski, Piotr/O-6454-2015
OI Ponikowski, Piotr/0000-0002-3391-7064
FU Johnson & Johnson Pharmaceutical Research Development; Bayer Healthcare
AG
FX This study is supported by research grants from Johnson & Johnson
Pharmaceutical Research & Development and Bayer Healthcare AG.
NR 22
TC 219
Z9 228
U1 1
U2 29
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 JUL 4
PY 2009
VL 374
IS 9683
BP 29
EP 38
DI 10.1016/S0140-6736(09)60738-8
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467UO
UT WOS:000267768800031
ER
PT J
AU Adamovich, DA
Nakamura, F
Worth, A
Burns, S
Thrasher, AJ
Hartwig, JH
Snapper, SB
AF Adamovich, David A.
Nakamura, Fumihiko
Worth, Austen
Burns, Siobhan
Thrasher, Adrian J.
Hartwig, John H.
Snapper, Scott B.
TI Activating mutations of N-WASP alter Shigella pathogenesis
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE N-WASP; Shigella; Actin tails; Bacterial pathogenesis; Autophagy; Actin
polymerization
ID ACTIN-BASED MOTILITY; ALDRICH-SYNDROME PROTEIN; CONGENITAL NEUTROPENIA;
ARP2/3 COMPLEX; FLEXNERI; PHOSPHORYLATION; POLYMERIZATION;
AUTOINHIBITION; CELLS
AB The pathogenesis of Shigella requires binding to the host protein N-WASP. To examine the roles of structural conformation and phospho-regulation of N-WASP during Shigello pathogenesis, mutant N-WASP constructs predicted to result in a constitutively open conformation (L229P and L232P) or either a phospho-mimicking (Y253E) or phospho-disruptive (Y253F) Structure were constructed. Pyrene actin assays demonstrated that the N-WASP L229P and L232P constructs are Constitutively active. Despite the increase in actin polymerization seen in vitro, cell lines expressing N-WASP L229P and L232P Supported shorter actin tails when infected with Shigella. Shigella actin tails were unchanged in cells expressing N-WASP phospho-regulation mutant proteins. Shigella invasion, intracellular, and intercellular motility were not altered in cells expressing N-WASP L229P or L232P. However, plaque numbers were increased in cells expressing N-WASP L229P and L232P. These data demonstrate that N-WASP Structural conformation is an important regulator of Shigella pathogenesis in distinct segments of its lifecycle. (C) 2009 Elsevier Inc. All rights reserved
C1 [Adamovich, David A.; Snapper, Scott B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Nakamura, Fumihiko; Hartwig, John H.; Snapper, Scott B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Nakamura, Fumihiko; Hartwig, John H.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Worth, Austen; Burns, Siobhan; Thrasher, Adrian J.] UCL, Mol Immunol Unit, Inst Child Hlth, London WC1N 1EH, England.
[Adamovich, David A.] Harvard Univ, Sch Med, Biol & Biomed Sci Grad Program, Boston, MA 02115 USA.
RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
EM ssnapper@hms.harvard.edu
RI Nakamura, Fumihiko/N-5476-2016
FU NIH [5R01 AI052354, 5P01 HL59561]
FX This work was supported by NIH 5R01 AI052354 and 5P01 HL59561 to S.B.S.
NR 23
TC 6
Z9 6
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 3
PY 2009
VL 384
IS 3
BP 284
EP 289
DI 10.1016/j.bbrc.2009.04.050
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 453XY
UT WOS:000266647400003
PM 19379711
ER
PT J
AU Carnemolla, A
Fossale, E
Agostoni, E
Michelazzi, S
Calligaris, R
De Maso, L
Del Sal, G
MacDonald, ME
Persichetti, F
AF Carnemolla, Alisia
Fossale, Elisa
Agostoni, Elena
Michelazzi, Silvia
Calligaris, Raffaella
De Maso, Luca
Del Sal, Giannino
MacDonald, Marcy E.
Persichetti, Francesca
TI Rrs1 Is Involved in Endoplasmic Reticulum Stress Response in Huntington
Disease
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID KNOCK-IN MICE; PROTEIN L11-BINDING PROTEIN; CAG REPEAT INSTABILITY; 5S
RIBOSOMAL-RNA; SACCHAROMYCES-CEREVISIAE; CELL-DEATH; NEURODEGENERATIVE
DISEASE; NUCLEAR-ENVELOPE; GENE-EXPRESSION; ER STRESS
AB The induction of Rrs1 expression is one of the earliest events detected in a presymptomatic knock-in mouse model of Huntington disease (HD). Rrs1 up-regulation fulfills the HD criteria of dominance, striatal specificity, and polyglutamine dependence. Here we show that mammalian Rrs1 is localized both in the nucleolus as well as in the endoplasmic reticulum ( ER) of neurons. This dual localization is shared with its newly identified molecular partner 3D3/lyric. We then show that both genes are induced by ER stress in neurons. Interestingly, we demonstrate that ER stress is an early event in a presymptomatic HD mouse model that persists throughout the life span of the rodent. We further show that ER stress also occurs in postmortem brains of HD patients.
C1 [Carnemolla, Alisia; Agostoni, Elena; Michelazzi, Silvia; Calligaris, Raffaella; De Maso, Luca; Persichetti, Francesca] Scuola Int Super Studi Avanzati, Sector Neurobiol, I-34151 Trieste, Italy.
[Fossale, Elisa; MacDonald, Marcy E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Del Sal, Giannino] Area Sci Pk Padriciano, Lab Nazl CIB, I-34149 Trieste, Italy.
[Del Sal, Giannino] Univ Trieste, Dipartimento Sci Vita, I-34127 Trieste, Italy.
RP Persichetti, F (reprint author), Univ Piemonte Orientale, Dipartimento Sci Ambiente & Vita, Alessandria, Italy.
EM persiche@sissa.it
OI DEL SAL, GIANNINO/0000-0003-2185-6003
FU Telethon Foundation of Italy [GGP06264]; Italian Government; Comitato
Interministerale per la Programmazione Economica/Friuli Venezia Giulia,
Italy
FX This work was supported by Telethon Foundation of Italy Grant GGP06264,
by the Italian Government ( Brain Gain Program, Ministero
dell'Istruzione, dell'Universita e della Ricerca), and by Comitato
Interministerale per la Programmazione Economica/Friuli Venezia Giulia,
Italy Grant GRAND.
NR 32
TC 57
Z9 57
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 3
PY 2009
VL 284
IS 27
BP 18167
EP 18173
DI 10.1074/jbc.M109.018325
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467BW
UT WOS:000267712400028
PM 19433866
ER
PT J
AU Abdel-Wahab, O
Mullally, A
Hedvat, C
Garcia-Manero, G
Patel, J
Wadleigh, M
Malinge, S
Yao, JJ
Kilpivaara, O
Bhat, R
Huberman, K
Thomas, S
Dolgalev, I
Heguy, A
Paietta, E
Le Beau, MM
Beran, M
Tallman, MS
Ebert, BL
Kantarjian, HM
Stone, RM
Gilliland, DG
Crispino, JD
Levine, RL
AF Abdel-Wahab, Omar
Mullally, Ann
Hedvat, Cyrus
Garcia-Manero, Guillermo
Patel, Jay
Wadleigh, Martha
Malinge, Sebastien
Yao, JinJuan
Kilpivaara, Outi
Bhat, Rukhmi
Huberman, Kety
Thomas, Sabrena
Dolgalev, Igor
Heguy, Adriana
Paietta, Elisabeth
Le Beau, Michelle M.
Beran, Miloslav
Tallman, Martin S.
Ebert, Benjamin L.
Kantarjian, Hagop M.
Stone, Richard M.
Gilliland, D. Gary
Crispino, John D.
Levine, Ross L.
TI Genetic characterization of TET1, TET2, and TET3 alterations in myeloid
malignancies
SO BLOOD
LA English
DT Article
ID TYROSINE KINASE JAK2; ACTIVATING MUTATION; POLYCYTHEMIA-VERA;
MYELOPROLIFERATIVE DISORDERS; ESSENTIAL THROMBOCYTHEMIA;
HIGH-THROUGHPUT; LEUKEMIA; SEQUENCE; MYELOFIBROSIS; METAPLASIA
AB Disease alleles that activate signal transduction are common in myeloid malignancies; however, there are additional unidentified mutations that contribute to myeloid transformation. Based on the recent identification of TET2 mutations, we evaluated the mutational status of TET1, TET2, and TET3 in myeloproliferative neoplasms (MPNs), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). Sequencing of TET2 in 408 paired tumor/normal samples distinguished between 68 somatic mutations and 6 novel single nucleotide polymorphisms and identified TET2 mutations in MPN (27 of 354, 7.6%), CMML (29 of 69, 42%), AML (11 of 91, 12%), and M7 AML (1 of 28, 3.6%) samples. We did not identify somatic TET1 or TET3 mutations or TET2 promoter hypermethylation in MPNs. TET2 mutations did not cluster in genetically defined MPN, CMML, or AML subsets but were associated with decreased overall survival in AML (P = .029). These data indicate that TET2 mutations are observed in different myeloid malignancies and may be important in AML prognosis. (Blood. 2009; 114:144-147)
C1 [Abdel-Wahab, Omar; Patel, Jay; Kilpivaara, Outi; Huberman, Kety; Thomas, Sabrena; Dolgalev, Igor; Heguy, Adriana; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, Dept Med, New York, NY 10065 USA.
[Mullally, Ann; Wadleigh, Martha; Stone, Richard M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Mullally, Ann; Ebert, Benjamin L.; Gilliland, D. Gary] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA.
[Hedvat, Cyrus; Yao, JinJuan] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Garcia-Manero, Guillermo; Beran, Miloslav; Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Malinge, Sebastien; Bhat, Rukhmi; Tallman, Martin S.; Crispino, John D.] Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Paietta, Elisabeth] New York Med Coll, Montefiore Med Ctr, North Div, New York, NY USA.
[Le Beau, Michelle M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Ebert, Benjamin L.; Gilliland, D. Gary] Harvard Stem Cell Inst, Boston, MA USA.
[Ebert, Benjamin L.] Harvard & Massachusetts Inst Technol, Broad Inst, Boston, MA USA.
[Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10065 USA.
EM leviner@mskcc.org
OI HEDVAT, CYRUS/0000-0003-0045-3491; Dolgalev, Igor/0000-0003-4451-126X;
Yao, JinJuan/0000-0003-4692-9969; Abdel-Wahab, Omar/0000-0002-3907-6171;
Crispino, John/0000-0002-8182-8306
FU Howard Hughes Medical Institute; NCI NIH HHS [R01 CA101774-07,
CA10863101, R01 CA101774, U10 CA021115, U24 CA114737]; NHLBI NIH HHS
[HL082677, K08 HL082677]
NR 22
TC 322
Z9 332
U1 1
U2 26
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 JUL 2
PY 2009
VL 114
IS 1
BP 144
EP 147
DI 10.1182/blood-2009-03-210039
PG 4
WC Hematology
SC Hematology
GA 468CA
UT WOS:000267789800022
PM 19420352
ER
PT J
AU Desmedt, C
Giobbie-Hurder, A
Neven, P
Paridaens, R
Christiaens, MR
Smeets, A
Lallemand, F
Haibe-Kains, B
Viale, G
Gelber, RD
Piccart, M
Sotiriou, C
AF Desmedt, Christine
Giobbie-Hurder, Anita
Neven, Patrick
Paridaens, Robert
Christiaens, Marie-Rose
Smeets, Ann
Lallemand, Francoise
Haibe-Kains, Benjamin
Viale, Giuseppe
Gelber, Richard D.
Piccart, Martine
Sotiriou, Christos
TI The Gene expression Grade Index: a potential predictor of relapse for
endocrine-treated breast cancer patients in the BIG 1-98 trial
SO BMC MEDICAL GENOMICS
LA English
DT Article
ID POSTMENOPAUSAL WOMEN; ADJUVANT TAMOXIFEN; RANDOMIZED-TRIAL; LETROZOLE;
ANASTROZOLE
AB Background: We have previously shown that the Gene expression Grade Index (GGI) was able to identify two subtypes of estrogen receptor (ER)-positive tumors that were associated with statistically distinct clinical outcomes in both untreated and tamoxifen-treated patients. Here, we aim to investigate the ability of the GGI to predict relapses in postmenopausal women who were treated with tamoxifen (T) or letrozole (L) within the BIG 1-98 trial.
Methods: We generated gene expression profiles (Affymetrix) and computed the GGI for a matched, case-control sample of patients enrolled in the BIG 1-98 trial from the two hospitals where frozen samples were available. All relapses (cases) were identified from patients randomized to receive monotherapy or from the switching treatment arms for whom relapse occurred before the switch. Each case was randomly matched with four controls based upon nodal status and treatment (T or L). The prognostic value of GGI was assessed as a continuous predictor and divided at the median. Predictive accuracy of GGI was estimated using time-dependent area under the curve (AUC) of the ROC curves.
Results: Frozen samples were analyzable for 48 patients (10 cases and 38 controls). Seven of the 10 cases had been assigned to receive L. Cases and controls were comparable with respect to menopausal and nodal status, local and chemotherapy, and HER2 positivity. Cases were slightly older than controls and had a larger proportion of large, poorly differentiated ER+/PgR- tumors. The GGI was significantly and linearly related to risk of relapse: each 10-unit increase in GGI resulted in an increase of approximately 11% in the hazard rate (p = 0.02). Within the subgroups of patients with node-positive disease or who were treated with L, the hazard of relapse was significantly greater for patients with GGI at or above the median. AUC reached a maximum of 78% at 27 months.
Conclusion: This analysis supports the GGI as a good predictor of relapse for ER-positive patients, even among patients who receive L. Validation of these results, in a larger series from BIG 1-98, is planned using the simplified GGI represented by a smaller set of genes and tested by qRT-PCR on paraffin-embedded tissues.
C1 [Desmedt, Christine; Lallemand, Francoise; Haibe-Kains, Benjamin; Piccart, Martine; Sotiriou, Christos] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium.
[Neven, Patrick; Paridaens, Robert; Christiaens, Marie-Rose; Smeets, Ann] Katholieke Univ Leuven, UZ Gasthuisberg, Leuven, Belgium.
[Viale, Giuseppe] European Inst Oncol, Milan, Italy.
[Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Frontier Sci & Technol Res Fdn, IBCSG Stat Ctr,Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Sotiriou, C (reprint author), Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium.
EM christine.desmedt@bordet.be; agiohur@jimmy.harvard.edu;
patrick.neven@uz.kuleuven.ac.be; robert.paridaens@uz.kuleuven.ac.be;
marie-rose.christiaens@uz.kuleuven.ac.be; anne.smeets@uz.kuleuven.ac.be;
francoise.lallemand@bordet.be; bhaibeka@ulb.ac.be;
giuseppe.viale@ieo.it; gelber@jimmy.harvard.edu;
martine.piccart@bordet.be; christos.sotiriou@bordet.be
RI Haibe-Kains, Benjamin/D-3702-2011;
OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Desmedt,
Christine/0000-0002-5223-5579
FU Breast Cancer Research Foundation; Belgian Federation Against Cancer;
Belgian Foundation for Scientific Research FNRS; Novartis; National
Cancer Institute [CA-75362]
FX This work was supported, in part, by the Breast Cancer Research
Foundation, by the Belgian Federation Against Cancer, by the Belgian
Foundation for Scientific Research FNRS (C.D. and C.S.). The BIG 1-98
trial was sponsored by Novartis and coordinated by IBCSG. The IBCSG
Statistical Center is partially supported by National Cancer Institute
Grant CA-75362 (R.D.G. and A.G.-H.). We thank the BIG 1-98 Collaborative
Group and International Breast Cancer Study Group (IBCSG), Bern,
Switzerland, for their collaboration.
NR 16
TC 41
Z9 41
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD JUL 2
PY 2009
VL 2
AR 40
DI 10.1186/1755-8794-2-40
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 533GY
UT WOS:000272812900001
PM 19573224
ER
PT J
AU Geijsen, N
Hochedlinger, K
AF Geijsen, Niels
Hochedlinger, Konrad
TI gPS Navigates Germ Cells to Pluripotency
SO CELL STEM CELL
LA English
DT Editorial Material
ID STEM-CELLS; MOUSE TESTIS; GENERATION
AB The establishment of pluripotent stem cell lines from explanted testes has been hampered by a poor understanding of their cellular origin. In this issue of Cell Stem Cell, Ko et al. (2009) reproducibly generate pluripotent cell lines from murine testes and unequivocally demonstrate their origin from spermatogonial stem cells.
C1 [Geijsen, Niels; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Geijsen, Niels; Hochedlinger, Konrad] Harvard Stem Cell Inst, Ctr Canc, Boston, MA 02114 USA.
[Geijsen, Niels] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
[Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Geijsen, N (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.
EM ngeijsen@mgh.harvard.edu; khochedlinger@helix.mgh.harvard.edu
FU NICHD NIH HHS [R01 HD048769]
NR 11
TC 10
Z9 11
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD JUL 2
PY 2009
VL 5
IS 1
BP 3
EP 4
DI 10.1016/j.stem.2009.06.012
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 469ET
UT WOS:000267879200002
PM 19570505
ER
PT J
AU Schindler, JW
Van Buren, D
Foudi, A
Krejci, O
Qin, JZ
Orkin, SH
Hock, H
AF Schindler, Jeffrey W.
Van Buren, Denille
Foudi, Adlen
Krejci, Ondrej
Qin, Jinzhong
Orkin, Stuart H.
Hock, Hanno
TI TEL-AML1 Corrupts Hematopoietic Stem Cells to Persist in the Bone Marrow
and Initiate Leukemia
SO CELL STEM CELL
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T(12/21) TRANSLOCATION; ADULT
HEMATOPOIESIS; FUSION GENE; MICE; DIFFERENTIATION; TRANSFORMATION;
TEL/AML1; RUNX1; FETAL
AB The initial steps in the pathogenesis of acute leukemia remain incompletely understood. The TEL-AML1 gene fusion, the hallmark translocation in Childhood Acute Lymphoblastic Leukemia and the first hit, occurs years before the clinical disease, most often in utero. We have generated mice in which TEL-AML1 expression is driven from the endogenous promoter and can be targeted to specific populations. TEL-AML1 renders mice prone to malignancy after chemical mutagenesis when expressed in hematopoietic stem cells (HSCs), but not in early lymphoid progenitors. We reveal that TEL-AML1 markedly increases the number of HSCs and predominantly maintains them in the quiescent (Go) stage of the cell cycle. TEL-AML1(+) HSCs retain self-renewal properties and contribute to hematopoiesis, but fail to out-compete normal HSCs. Our work shows that stem cells are susceptible to subversion by weak oncogenes that can subtly alter their molecular program to provide a latent reservoir for the accumulation of further mutations.
C1 [Schindler, Jeffrey W.; Van Buren, Denille; Foudi, Adlen; Krejci, Ondrej; Qin, Jinzhong; Hock, Hanno] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Schindler, Jeffrey W.; Van Buren, Denille; Foudi, Adlen; Krejci, Ondrej; Qin, Jinzhong; Hock, Hanno] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Orkin, Stuart H.; Hock, Hanno] Harvard Stem Cell Inst, Boston, MA 02111 USA.
[Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02111 USA.
[Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02111 USA.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02111 USA.
RP Hock, H (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM hock.hanno@mgh.harvard.edu
FU NCI NIH HHS [P01 CA68486]
NR 43
TC 49
Z9 49
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD JUL 2
PY 2009
VL 5
IS 1
BP 43
EP 53
DI 10.1016/j.stem.2009.04.019
PG 11
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 469ET
UT WOS:000267879200009
PM 19570513
ER
PT J
AU Zou, JZ
Maeder, ML
Mali, P
Pruett-Miller, SM
Thibodeau-Beganny, S
Chou, BK
Chen, GB
Ye, ZH
Park, IH
Daley, GQ
Porteus, MH
Joung, JK
Cheng, L
AF Zou, Jizhong
Maeder, Morgan L.
Mali, Prashant
Pruett-Miller, Shondra M.
Thibodeau-Beganny, Stacey
Chou, Bin-Kuan
Chen, Guibin
Ye, Zhaohui
Park, In-Hyun
Daley, George Q.
Porteus, Matthew H.
Joung, J. Keith
Cheng, Linzhao
TI Gene Targeting of a Disease-Related Gene in Human Induced Pluripotent
Stem and Embryonic Stem Cells
SO CELL STEM CELL
LA English
DT Article
ID ZINC-FINGER NUCLEASES; HUMAN SOMATIC-CELLS; HUMAN BLASTOCYSTS;
MAMMALIAN-CELLS; DEFINED FACTORS; LINES; DIFFERENTIATION; FIBROBLASTS;
EXPRESSION; LOCUS
AB We report here homologous recombination (HR)-mediated gene targeting of two different genes in human PS cells (hiPSCs) and human ES cells (hESCs). HR-mediated correction of a chromosomally integrated mutant GFP reporter gene reaches efficiencies of 0.14%-0.24% in both cell types transfected by donor DNA with plasmids expressing zinc finger nucleases (ZFNs). Engineered ZFNs that induce a sequence-specific double-strand break in the GFP gene enhanced HR-mediated correction by > 1400-fold without detectable alterations in stem cell karyotypes or pluripotency. Efficient HR-mediated insertional mutagenesis was also achieved at the endogenous PIG-A locus, with a > 200-fold enhancement by ZFNs targeted to that gene. Clonal PIG-A null hESCs and iPSCs with normal karyotypes were readily obtained. The phenotypic and biological defects were rescued by PIG-A transgene expression. Our study provides the first demonstration of HR-mediated gene targeting in hiPSCs and shows the power of ZFNs for inducing specific genetic modifications in hiPSCs, as well as hESCs.
C1 [Pruett-Miller, Shondra M.; Porteus, Matthew H.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Pruett-Miller, Shondra M.; Porteus, Matthew H.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Zou, Jizhong; Mali, Prashant; Chou, Bin-Kuan; Chen, Guibin; Ye, Zhaohui; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA.
[Mali, Prashant] Johns Hopkins Univ, Sch Med, Grad Program Biomed Engn, Baltimore, MD 21205 USA.
[Chou, Bin-Kuan; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Grad Program Cellular & Mol Med, Baltimore, MD 21205 USA.
[Ye, Zhaohui; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Grad Program Immunol, Baltimore, MD 21205 USA.
[Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA.
[Maeder, Morgan L.; Thibodeau-Beganny, Stacey; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA 02129 USA.
[Maeder, Morgan L.; Thibodeau-Beganny, Stacey; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA.
[Park, In-Hyun; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Park, In-Hyun; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Park, In-Hyun; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Porteus, MH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
EM matthew.porteus@utsouthwestern.edu; jjoung@partners.org;
lcheng@welch.jhu.edu
RI Zou, Jizhong/B-4902-2011;
OI Ye, Zhaohui/0000-0001-5272-9168
FU Stem Cell Research Foundation [S2005-026]; Johns Hopkins Institute for
Cell Engineering; NIH [R01 HL073781, R01GM069906, R21RR024189,
R21HL091808, R01 HL079295]; Maryland Stem Cell Research Postdoctoral
Fellowship Grant; Cystic Fibrosis Foundation; Burroughs-Wellcome Fund
FX We thank Sarah Dowey and the Johns Hopkins Hospital Prenatal
Cytogenetics Laboratory for professional karyotyping. We also thank
three anonymous reviewers for suggestions that helped us in revision.
This work is funded in part by the Stem Cell Research Foundation
(S2005-026), Johns Hopkins Institute for Cell Engineering, and the NIH
grant R01 HL073781 to L.C. J.Z. is supported by a Maryland Stem Cell
Research Postdoctoral Fellowship Grant. J.K.J.'s group is supported by
the NIH (R01GM069906, R21RR024189, and R21HL091808), the Cystic Fibrosis
Foundation, and the MGH Pathology Service. M.H.P.'s lab is supported by
the state of Texas, NIH R01 HL079295, and by a Career Development Award
from the Burroughs-Wellcome Fund. G.Q.D. is an Investigator of Howard
Hughes Medical Institute.
NR 41
TC 311
Z9 323
U1 4
U2 27
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD JUL 2
PY 2009
VL 5
IS 1
BP 97
EP 110
DI 10.1016/j.stem.2009.05.023
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 469ET
UT WOS:000267879200014
PM 19540188
ER
PT J
AU Bu, L
Jiang, X
Martin-Puig, S
Caron, L
Zhu, SJ
Shao, Y
Roberts, DJ
Huang, PL
Domian, IJ
Chien, KR
AF Bu, Lei
Jiang, Xin
Martin-Puig, Silvia
Caron, Leslie
Zhu, Shenjun
Shao, Ying
Roberts, Drucilla J.
Huang, Paul L.
Domian, Ibrahim J.
Chien, Kenneth R.
TI Human ISL1 heart progenitors generate diverse multipotent cardiovascular
cell lineages
SO NATURE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; CARDIAC PROGENITORS; SMOOTH-MUSCLE; CARDIOMYOCYTE;
DIFFERENTIATION; CARDIOGENESIS; POPULATION; PRECURSORS; CONTRIBUTE;
ORIGINS
AB The generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential(1-4). Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart(5-8). In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1(+) cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that purified ISL1(+) primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine.
C1 [Bu, Lei; Jiang, Xin; Martin-Puig, Silvia; Caron, Leslie; Zhu, Shenjun; Shao, Ying; Huang, Paul L.; Domian, Ibrahim J.; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Bu, Lei; Jiang, Xin; Martin-Puig, Silvia; Caron, Leslie; Domian, Ibrahim J.; Chien, Kenneth R.] Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA.
[Roberts, Drucilla J.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs,Med Sch, Boston, MA 02114 USA.
RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charles River Plaza,CPZN 3208,185 Cambridge St, Boston, MA 02114 USA.
EM krchien@partners.org
OI Martin-Puig, Silvia/0000-0003-3048-6729
FU Foundation Alfonso Martin Escudero, Spain; Harvard Stem Cell Institute;
Leducq Foundation
FX We thank C. Cowan for advice on human ES cell culture and
electroporation; A. Nagy for providing the DsRed-MST plasmid; Y. Qyang
for discussion and comments; E. Hansson for a critical reading of this
manuscript; M. Lindsay and M. Ortega-Molina for help on human fetal
heart anatomy; L. B. Prickett-Rice and K. Folz-Donahue for flow
cytometry support; and Advanced Bioscience Resources for providing the
human fetal tissues. S. M. P. is funded by Foundation Alfonso Martin
Escudero, Spain. This study is supported by Harvard Stem Cell Institute
and the Leducq Foundation.
NR 25
TC 285
Z9 304
U1 2
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 113
EP U130
DI 10.1038/nature08191
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200040
PM 19571884
ER
PT J
AU Donohoe, ME
Silva, SS
Pinter, SF
Xu, N
Lee, JT
AF Donohoe, Mary E.
Silva, Susana S.
Pinter, Stefan F.
Xu, Na
Lee, Jeannie T.
TI The pluripotency factor Oct4 interacts with Ctcf and also controls
X-chromosome pairing and counting
SO NATURE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; DOSAGE COMPENSATION; INACTIVATION; TRANSCRIPTION;
CHOICE; TSIX; IDENTIFICATION; INITIATION; ACTIVATOR; PROTEIN
AB Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors(1,2). During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) in which one female X chromosome is silenced to achieve gene dosage parity between the sexes(3-5). Somatic XCI is regulated by homologous X-chromosome pairing(6,7) and counting(8-10), and by the random choice of future active and inactive X chromosomes. XCI and cell differentiation are tightly coupled(11), as blocking one process compromises the other(8,12) and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X chromosome reactivation(2). Recent evidence suggests coupling of Xist expression to pluripotency factors occurs(13), but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1)(14) lies at the top of the XCI hierarchy, and regulates XCI by triggering X-chromosome pairing and counting. Oct4 directly binds Tsix and Xite, two regulatory noncoding RNA genes of the X-inactivation centre(15,16), and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein-protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in the inactivation of both X chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-chromosome reprogramming.
C1 [Donohoe, Mary E.; Silva, Susana S.; Pinter, Stefan F.; Xu, Na; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Donohoe, Mary E.; Silva, Susana S.; Pinter, Stefan F.; Xu, Na; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Donohoe, Mary E.; Silva, Susana S.; Pinter, Stefan F.; Xu, Na; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM lee@molbio.mgh.harvard.edu
OI Pinter, Stefan/0000-0003-4750-1403
FU National Institutes of Health [GM58839]
FX We thank N. Stavropoulos and J. Lopilato for their contributions to the
early phase of this work. We also thank J. Zhao, J. A. Erwin and J. Ahn
for critical reading of the manuscript and all laboratory members for
stimulating discussion. This work was funded by a National Institutes of
Health grant to J. T. L. (GM58839). J. T. L. is an Investigator of the
Howard Hughes Medical Institute.
NR 30
TC 159
Z9 163
U1 2
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 128
EP U147
DI 10.1038/nature08098
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200043
PM 19536159
ER
PT J
AU Perkins, BA
Aiello, LP
Krolewski, AS
AF Perkins, Bruce A.
Aiello, Lloyd Paul
Krolewski, Andrzej S.
TI Diabetes Complications and the Renin-Angiotensin System.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CONTROLLED-TRIAL; RENAL-FUNCTION; PROGRESSION; NEPHROPATHY; CANDESARTAN;
RETINOPATHY; THERAPY; RISK
C1 [Perkins, Bruce A.] Univ Toronto, Dept Med, Div Endocrinol, Toronto, ON, Canada.
[Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Aiello, Lloyd Paul] Beetham Eye Inst, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Perkins, BA (reprint author), Univ Toronto, Dept Med, Div Endocrinol, Toronto, ON, Canada.
NR 13
TC 11
Z9 15
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 2
PY 2009
VL 361
IS 1
BP 83
EP 85
DI 10.1056/NEJMe0904293
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 464UK
UT WOS:000267533100015
PM 19571288
ER
PT J
AU Herring, A
Wilper, A
Himmelstein, DU
Woolhandler, S
Espinola, JA
Brown, DFM
Camargo, CA
AF Herring, Andrew
Wilper, Andrew
Himmelstein, David U.
Woolhandler, Steffie
Espinola, Janice A.
Brown, David F. M.
Camargo, Carlos A., Jr.
TI Increasing Length of Stay Among Adult Visits to US Emergency
Departments, 2001-2005
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Society-for-Academic-Emergency-Medicine (SAEM)
CY JUN 02, 2008
CL Washington, DC
SP Soc Acad Emergency Med
DE length of stay; crowding; emergency service; hospital/trends; emergency
service; hospital/utilization; healthcare disparities/trends
ID INTENSIVE-CARE-UNIT; AMBULANCE DIVERSION; CRITICALLY-ILL; IMPACT;
ASSOCIATION; MORTALITY; CAPACITY; ACCESS; LONGER; LEAVE
AB Background: Emergency departments (EDs) are traditionally designed to provide rapid evaluation and stabilization and are neither staffed nor equipped to provide prolonged care. Longer ED length of stay (LOS) may compromise quality of care and contribute to delays in the emergency evaluation of other patients.
Objectives: The objective was to determine whether ED LOS increased between 2001 and 2005 and whether trends varied by patient and hospital factors.
Methods: This was a retrospective analysis of a nationally representative sample of 138,569 adult ED visits from the National Hospital Ambulatory Medical Care Survey (NHAMCS), 2001 to 2005. ED LOS was measured from registration to discharge. Results: Median ED LOS increased 3.5% per year from 132 minutes in 2001 to 154 minutes in 2005 (p-value for trend < 0.001). There was a larger increase among critically ill patients for whom ED LOS increased 7.0% annually from 185 minutes in 2001 to 254 minutes in 2005 (p-value for trend < 0.01). ED LOS was persistently longer for black/African American, non-Hispanic patients (10.6% longer) and Hispanic patients (13.9% longer) than for non-Hispanic white patients, and these differences did not diminish over time. Among factors potentially associated with increasing ED LOS, a large increase was found (60.1%, p-value for trend < 0.001) in the use of advanced diagnostic imaging (computed tomography [CT], magnetic resonance imaging [MR], and ultrasound [US]) and in the proportion of ED visits at which five or more diagnostic or screening tests were ordered (17.6% increase, p-value for trend = 0.001). The proportion of uninsured patients was stable throughout the study period, and EDs with predominately privately insured patients experienced significant increases in ED LOS (4.0% per year from 2001 to 2005, p-value for trend < 0.01).
Conclusions: Emergency department LOS in the United States is increasing, especially for critically ill patients for whom time-sensitive interventions are most important. The disparity of longer ED LOS for African Americans and Hispanics is not improving. ACADEMIC EMERGENCY MEDICINE 2009; 16:609-616 (c) 2009 by the Society for Academic Emergency Medicine
C1 [Herring, Andrew] Highland Gen Hosp, Dept Emergency Med, Alameda Cty Med Ctr, Oakland, CA USA.
[Wilper, Andrew; Himmelstein, David U.; Woolhandler, Steffie; Brown, David F. M.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA.
[Wilper, Andrew; Himmelstein, David U.; Woolhandler, Steffie] Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA.
[Espinola, Janice A.; Brown, David F. M.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Herring, A (reprint author), Highland Gen Hosp, Dept Emergency Med, Alameda Cty Med Ctr, Oakland, CA USA.
EM andrew.a.herring@gmail.com
NR 37
TC 60
Z9 62
U1 2
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD JUL
PY 2009
VL 16
IS 7
BP 609
EP 616
DI 10.1111/j.1553-2712.2009.00428.x
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 466JD
UT WOS:000267656500007
PM 19538503
ER
PT J
AU Soremekun, OA
Noble, VE
Liteplo, AS
Brown, DFM
Zane, RD
AF Soremekun, Olanrewaju A.
Noble, Vicki E.
Liteplo, Andrew S.
Brown, David F. M.
Zane, Richard D.
TI Financial Impact of Emergency Department Ultrasound
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT Research Forum of the American-College-of-Emergency-Physicians
CY OCT 24-28, 2008
CL Chicago, IL
SP Amer Coll Emergency Phys
DE emergency department ultrasound; financial impact
ID CONTROLLED CLINICAL-TRIAL; POINT-OF-CARE; LIMITED ULTRASONOGRAPHY;
SONOGRAPHY; PROGRAM; TRAUMA
AB Objectives: There is limited information on the financial implications of an emergency department ultrasound (ED US) program. The authors sought to perform a fiscal analysis of an integrated ED US program.
Methods: A retrospective review of billing data was performed for fiscal year (FY) 2007 for an urban academic ED with an ED US program. The ED had an annual census of 80,000 visits and 1,101 ED trauma activations. The ED is a core teaching site for a 4-year emergency medicine (EM) residency, has 35 faculty members, and has 24-hour availability of all radiology services including formal US. ED US is utilized as part of evaluation of all trauma activations and for ED procedures. As actual billing charges and reimbursement rates are institution-specific and proprietary information, relative value units (RVUs) and reimbursement based on the Centers for Medicare & Medicaid Services (CMS) 2007 fee schedule (adjusted for fixed diagnosis-related group [DRG] payments and bad debt) was used to determine revenue generated from ED US. To estimate potential volume, assumptions were made on improvement in documentation rate for diagnostic scans (current documentation rates based on billed volume versus diagnostic studies in diagnostic image database), with no improvements assumed for procedural ED US. Expenses consist of three components-capital costs, training costs, and ongoing operational costs-and were determined by institutional experience. Training costs were considered sunken expenses by this institution and were thus not included in the original return on investment (ROI) calculation, although for this article a second ROI calculation was done with training cost estimates included. For the purposes of analysis, certain key assumptions were made. We utilized a collection rate of 45% and hospitalization rates (used to adjust for fixed DRG payments) of 33% for all diagnostic scans, 100% for vascular access, and 10% for needle placement. An optimal documentation rate of 95% was used to estimate potential revenue.
Results: In FY 2007, 486 limited echo exams of abdomen (current procedural terminology [CPT] 76705) and 480 limited echo cardiac exams were performed (CPT 93308) while there were 78 exams for US-guided vascular access (CPT 76937) and 36 US-guided needle placements when performing paracentesis, thoracentesis, or location of abscess for drainage (CPT 76492). Applying the 2007 CMS fee schedule and above assumptions, the revenue generated was 578 RVUs and $35,541 ($12,934 in professional physician fees and $22,607 in facility fees). Assuming optimal documentation rates for diagnostic ED US scans, ED US could have generated 1,487 RVUs and $94,593 ($33,953 in professional physician fees and $60,640 in facility fees). Program expenses include an initial capital expense (estimated at $120,000 for two US machines) and ongoing operational costs ($68,640 per year to cover image quality assurance review, continuing education, and program maintenance). Based on current revenue, there would be an annual operating loss, and thus an ROI cannot be calculated. However, if potential revenue is achieved, the annual operating income will be $22,846 per year with an ROI of 4.9 years to break even with initial investment.
Conclusions: Determining an ROI is a required procedure for any business plan for establishing an ED US program. Our analysis demonstrates that an ED US program that captures charges for trauma and procedural US and achieves the potential billing volume breaks even in less than 5 years, at which point it would generate a positive margin. ACADEMIC EMERGENCY MEDICINE 2009; 16:674-680 (c) 2009 by the Society for Academic Emergency Medicine
C1 [Soremekun, Olanrewaju A.] Brigham & Womens Hosp, Harvard Affiliated EM Residency Program, Boston, MA 02115 USA.
[Noble, Vicki E.; Liteplo, Andrew S.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA.
[Noble, Vicki E.; Liteplo, Andrew S.; Brown, David F. M.; Zane, Richard D.] Harvard Univ, Sch Med, Boston, MA USA.
[Zane, Richard D.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
RP Soremekun, OA (reprint author), Brigham & Womens Hosp, Harvard Affiliated EM Residency Program, 75 Francis St, Boston, MA 02115 USA.
EM osoremekun1@partners.org
RI Siry, Bonnie/D-7189-2017
NR 18
TC 3
Z9 3
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD JUL
PY 2009
VL 16
IS 7
BP 674
EP 680
DI 10.1111/j.1553-2712.2009.00447.x
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA 466JD
UT WOS:000267656500018
PM 19549014
ER
PT J
AU Lyss-Lerman, P
Teherani, A
Aagaard, E
Loeser, H
Cooke, M
Harper, GM
AF Lyss-Lerman, Pamela
Teherani, Arianne
Aagaard, Eva
Loeser, Helen
Cooke, Molly
Harper, G. Michael
TI What Training Is Needed in the Fourth Year of Medical School? Views of
Residency Program Directors
SO ACADEMIC MEDICINE
LA English
DT Article
ID 4TH-YEAR CURRICULUM; CLINICAL EDUCATION; FAMILY MEDICINE; STUDENTS;
SKILLS; SUBINTERNSHIP; PERCEPTIONS; OUTCOMES; PROJECT
AB Purpose
To identify common struggles of interns, determine residency program directors' (PDs') views of the competencies to be gained in the fourth year of medical school, and apply this information to formulate goals of curricular reform and student advising.
Method
In 2007, semistructured interviews were conducted with 30 PDs in the 10 most common specialty choices of students the University of California, San Francisco, School of Medicine to assess the PDs' priorities for knowledge, skills, and attitudes to be acquired in the fourth year. Interviews were coded to identify major themes.
Results
Common struggles of interns were lack of self-reflection and improvement, poor organizational skills, underdeveloped professionalism, and lack of medical knowledge. The Accreditation Council for Graduate Medical Education competencies of patient care, practice-based learning and improvement, interpersonal and communication skills, and professionalism were deemed fundamental to fourth-year students' development. Rotations recommended across specialties were a subinternship in a student's future field and in internal medicine (IM), rotations in an IM subspecialty, critical care, and emergency and ambulatory medicine. PDs encouraged minimizing additional time spent in the student's future field. Suggested coursework included an intensively coached transitional subinternship and courses to improve students' medical knowledge.
Conclusions
PDs deemed the fourth year to have a critical role in the curriculum. There was consensus about expected fourth-year competencies and the common clinical experiences that best prepare students for residency training. These findings support using the fourth year to transition students to graduate medical training and highlight areas for curricular innovation.
C1 [Harper, G. Michael] Univ Calif San Francisco, Sch Med, Dept Med, Div Geriatr, San Francisco, CA 94143 USA.
[Harper, G. Michael] San Francisco VA Med Ctr, San Francisco, CA USA.
[Aagaard, Eva] Univ Colorado, Dept Med, Denver Sch Med, Denver, CO USA.
[Teherani, Arianne] Univ Calif San Francisco, Sch Med, Off Med Educ, San Francisco, CA USA.
RP Harper, GM (reprint author), 4150 Clement St,Box 181G, San Francisco, CA 94121 USA.
EM Michael.harper3@med.va.gov
NR 33
TC 84
Z9 84
U1 2
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD JUL
PY 2009
VL 84
IS 7
BP 823
EP 829
PG 7
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 466IT
UT WOS:000267655500007
PM 19550170
ER
PT J
AU Hacker, KA
Williams, S
Myagmarjav, E
Cabral, H
Murphy, M
AF Hacker, Karen A.
Williams, Sandra
Myagmarjav, Enkhbolor
Cabral, Howard
Murphy, Michael
TI Persistence and Change in Pediatric Symptom Checklist Scores Over 10 to
18 Months
SO ACADEMIC PEDIATRICS
LA English
DT Article
DE mental health; parental concern; Pediatric Symptom Checklist; referral;
screening
ID MENTAL-HEALTH PROBLEMS; PSYCHIATRIC-DISORDERS; PSYCHOSOCIAL DYSFUNCTION;
CARE VISITS; CHILD; MANAGEMENT; SETTINGS; SCHOOL; IDENTIFICATION;
ADOLESCENTS
AB Objective.-There are many studies of the Pediatric Symptom Checklist (PSC), but none has followed a naturalistic sample longitudinally. We aimed to examine persistence and change in PSC scores over time in children seen in an ambulatory pediatric setting.
Methods.-The sample of 1033 patients was PSC screened at 2 consecutive preventive care visits (10 to 18 months apart) in 2 pediatric clinics. Longitudinal analyses were conducted to assess predictors of change in PSC category and score.
Results.-Approximately 30% of the initially screened population did not return for preventive pediatric care. Those who did not return were significantly more likely to have positive PSC scores than those who returned (8% compared with 4.3%, P < .01). PSC scores were highly stable at visit 2 for those who initially scored negative, but they fluctuated more for those who initially scored positive. After controlling for sociodemographic variables and counseling at either visit, referral at visit 1 (P < .0001) predicted changes in mean PSC scores at visit 2. On average, PSC score decreased 3.2 points among those referred at visit 1 but increased 1.6 points in nonreferred children.
Conclusions.-This is the first study to document the stability and change in PSC scores in a sample of ambulatory pediatric patients. The statistically significant association between pediatrician referral and improved PSC scores provides evidence for the value of referral in primary care, although the study did not examine the relationship between PSC screening and referral. The high rate of positive scores in children who did not return for follow-up suggests the need for alternative strategies for this population.
C1 [Hacker, Karen A.; Williams, Sandra] Cambridge Hlth Alliance, Inst Community Hlth, Cambridge, MA 02141 USA.
[Myagmarjav, Enkhbolor] Cambridge Hlth Alliance, Dept Qual Management, Cambridge, MA 02141 USA.
[Cabral, Howard] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Murphy, Michael] Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA.
RP Hacker, KA (reprint author), Cambridge Hlth Alliance, Inst Community Hlth, 163 Gore St, Cambridge, MA 02141 USA.
EM khacker@challiance.org
FU Healthy Tomorrows Partnership for Children Program; Maternal and Child
Health Bureau; Health Resources and Services Administration; American
Academy of Pediatrics [H57MC07372]
FX Supported in part by a grant through the Healthy Tomorrows Partnership
for Children Program, a public private partnership between the Maternal
and Child Health Bureau, the Health Resources and Services
Administration, and the American Academy of Pediatrics (grant
H57MC07372; PI, Karen A. Hacker, MD).; None of the authors has any
financial interests in the subject contained in this article. Dr Murphy
is one of the developers of the Pediatric Symptom Checklist, which is
free to users.; We thank the primary care providers, office staff, and
patients of Cambridge and Somerville Pediatrics for their efforts in
collecting study information and for their ongoing commitment to the
mental health needs of their population.
NR 33
TC 15
Z9 15
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1876-2859
J9 ACAD PEDIATR
JI Acad. Pediatr.
PD JUL-AUG
PY 2009
VL 9
IS 4
BP 270
EP 277
PG 8
WC Pediatrics
SC Pediatrics
GA 573KV
UT WOS:000275913200012
PM 19487170
ER
PT J
AU Nagata, K
Okawa, T
Honma, A
Endo, S
Kudo, S
Yoshida, H
AF Nagata, Koichi
Okawa, Tomohiko
Honma, Akihiro
Endo, Shungo
Kudo, Shin-ei
Yoshida, Hiroyuki
TI Full-laxative Versus Minimum-laxative Fecal-tagging CT Colonography
Using 64-detector Row CT: Prospective Blinded Comparison of Diagnostic
Performance, Tagging Quality, and Patient Acceptance
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Colorectal neoplasms; bowel preparation; fecal tagging; computed
tomography; colonography
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; BOWEL PREPARATION;
SODIUM-PHOSPHATE; CONVENTIONAL COLONOSCOPY; CATHARTIC PREPARATION;
VIRTUAL COLONOSCOPY; CONTRAST-MEDIUM; TRIAL; FEASIBILITY
AB Rationale and Objectives. To compare prospectively 64-detector-row computed tomographic colonography (CTC) after a full-laxative tagging-based preparation (full preparation) with a minimum-laxative tagging-based preparation (minimum preparation) with respect to diagnostic performance in the detection of polyps, tagging quality, and patient acceptance.
Materials and Methods. Consecutive 10 1 patients at high risk for developing colorectal cancer were alternately assigned to either a full preparation group (n = 51) or a minimum preparation group (n = 50) for fecal-tagging CTC. The full preparation consisted of administration of 2-L polyethylene glycol solution with 20 mL of sodium diatrizoate for fecal tagging. The minimum preparation consisted of ingestion of a total of 45 mL of sodium diatrizoate during the 3 days before and 1 0 mL of sodium picosulfate solution the night before CT. Colonoscopy was used as the reference standard. We assessed the accuracy of polyp detection and the tagging quality for each preparation. All patients were given questionnaires related to their acceptance.
Results. Per-patient sensitivity, specificity, and positive and negative predictive values for polyps >= 6 mm were as follows: full preparation group, 97%, 92%, 88%, and 98%, respectively; minimum preparation group, 88%, 68%, 56%, and 92%, respectively. Average visual subjective tagging scores for the full and minimum preparation groups were 94.6% and 76.1%, respectively (P < .0001). Minimum preparation was better tolerated than full preparation.
Conclusion. Although full-laxative and minimum-laxative fecal-tagging CTC yielded an equally high sensitivity in the detection of polyps >= 6 min, the full-laxative fecal-tagging CTC yielded a better specificity than did the minimum-laxative fecal-tagging CTC. Thus, it is desirable to offer patients an option of either full-laxative fecal-tagging CTC for highest diagnostic accuracy and ability to perforin a same-day therapeutic colonoscopy without additional bowel preparation, or minimum-laxative fecal-tagging CTC for those unwilling to undergo full preparation but willing to accept moderate decrease in specificity.
C1 [Nagata, Koichi; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Nagata, Koichi; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Okawa, Tomohiko; Honma, Akihiro] Tokyo W Tokushukai Hosp, Dept Radiol, Tokyo, Japan.
[Endo, Shungo; Kudo, Shin-ei] Showa Univ, No Yokohama Hosp, Ctr Digest Dis, Yokohama, Kanagawa, Japan.
RP Nagata, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA.
EM Nagata7@aol.com
NR 41
TC 17
Z9 17
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD JUL
PY 2009
VL 16
IS 7
BP 780
EP 789
DI 10.1016/j.acra.2008.12.027
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 462WN
UT WOS:000267388900002
PM 19375954
ER
PT J
AU Caravan, P
AF Caravan, Peter
TI Protein-Targeted Gadolinium-Based Magnetic Resonance Imaging (MRI)
Contrast Agents: Design and Mechanism of Action
SO ACCOUNTS OF CHEMICAL RESEARCH
LA English
DT Review
ID ELECTRON-SPIN RELAXATION; HUMAN SERUM-ALBUMIN; WATER EXCHANGE-RATE;
HYDRATION NUMBER; ENDOR SPECTROSCOPY; HIGH RELAXIVITY; GD3+ COMPLEXES;
MS-325; BINDING; ANGIOGRAPHY
AB Magnetic resonance imaging (MRI) is a powerful medical diagnostic technique: it can penetrate deep into tissue, provide excellent soft tissue contrast with sub-millimeter resolution, and does not employ ionizing radiation. Targeted contrast agents provide an additional layer of molecular specificity to the wealth of anatomical and functional information already attainable by MRI. However, the major challenge for molecular MR imaging is sensitivity: micromolar concentrations of Gd-III are required to cause a detectable signal change, which makes detecting proteins by MR[ a challenge.
Protein-targeted MRI contrast agents are bifunctional molecules comprising a protein-targeting moiety and typically one or more gadolinium chelates for detection by MRI. The ability of the contrast agent to enhance the MR image is termed relaxivity, and it depends upon many molecular factors, including protein binding itself. As in other imaging modalities, protein binding provides the pharmacokinetic effect of concentrating the agent at the region of interest. Unique to MRI, protein binding provides the pharmacodynamic effect of increasing the relaxivity of the contrast agent, thereby increasing the MR signal. In designing new agents, optimization of both the targeting function and the relaxivity is critical.
In this Account, we focus on optimization of the relaxivity of targeted agents. Relaxivity depends upon speciation, chemical structure, and dynamic processes, such as water exchange kinetics and rotational tumbling rates. We describe mechanistic studies that relate these factors to the observed relaxivities and use these findings as the basis of rational design of improved agents. In addition to traditional biochemical methods to characterize ligand-protein interactions, the presence of the metal ion enables more obscure biophysical techniques, such as relaxometry and electron nuclear double resonance, to be used to elucidate the mechanism of relaxivity differences.
As a case study, we explore the mechanism of action of the serum-albumin-targeted angiography agent MS-325 and closely related compounds and show how small changes in the metal chelate can impact relaxivity. We found that, while protein binding generally improves relaxivity by slowing the tumbling rate of the complex, in some cases, the protein itself can also negatively affect hydration of the metal complex and/or inner-sphere water exchange. Drawing on these findings, we designed next-generation agents targeting albumin, fibrin, or collagen and incorporating up to four gadolinium chelates. Through judicious molecular design, we show that high-relaxivity complexes with high target affinity can be realized.
C1 [Caravan, Peter] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Caravan, P (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM caravan@nmr.mgh.harvard.edu
NR 45
TC 218
Z9 221
U1 12
U2 108
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0001-4842
EI 1520-4898
J9 ACCOUNTS CHEM RES
JI Accounts Chem. Res.
PD JUL
PY 2009
VL 42
IS 7
BP 851
EP 862
DI 10.1021/ar800220p
PG 12
WC Chemistry, Multidisciplinary
SC Chemistry
GA 479NA
UT WOS:000268665100005
PM 19222207
ER
PT J
AU Moy, TI
Conery, AL
Larkins-Ford, J
Wu, G
Mazitschek, R
Casadei, G
Lewis, K
Carpenter, AE
Ausubel, FM
AF Moy, Terence I.
Conery, Annie L.
Larkins-Ford, Jonah
Wu, Gang
Mazitschek, Ralph
Casadei, Gabriele
Lewis, Kim
Carpenter, Anne E.
Ausubel, Frederick M.
TI High-Throughput Screen for Novel Antimicrobials using a Whole Animal
Infection Model
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID ANTIBACTERIAL DRUG DISCOVERY; CAENORHABDITIS-ELEGANS; C-ELEGANS;
INHIBITORS; BACTERIAL; ASSAY
AB The nematode Coenorhabditis elegons is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C elegons can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen. Here, we describe an automated, high-throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C elegans infected with E faecalis. Using a robot to dispense live, infected animals into 384-well plates and automated microscopy and image analysis, we identified 28 compounds and extracts not previously reported to have antimicrobial properties, including six structural classes that cure infected C elegons animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use.
C1 [Moy, Terence I.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Moy, Terence I.; Conery, Annie L.; Larkins-Ford, Jonah; Wu, Gang; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Moy, Terence I.; Conery, Annie L.; Larkins-Ford, Jonah; Wu, Gang; Ausubel, Frederick M.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Casadei, Gabriele; Lewis, Kim] Northeastern Univ, Dept Biol, Boston, MA 02115 USA.
[Carpenter, Anne E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM ausubel@molbio.mgh.harvard.edu
RI Carpenter, Anne/C-4982-2008; Mazitschek, Ralph/E-3741-2013
OI Carpenter, Anne/0000-0003-1555-8261; Mazitschek,
Ralph/0000-0002-1105-689X
FU NCI NIH HHS [N01-CO-12400, N01 CO012400, N01CO12400]; NIAID NIH HHS [R01
AI072508, R01 AI072508-01, R01 AI072508-02]; NIDDK NIH HHS [P30
DK040561, P30 DK040561-14]
NR 23
TC 104
Z9 113
U1 1
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD JUL
PY 2009
VL 4
IS 7
BP 527
EP 533
DI 10.1021/cb900084v
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 473TS
UT WOS:000268233000005
PM 19572548
ER
PT J
AU Raw, M
Regan, S
Rigotti, NA
McNeill, A
AF Raw, Martin
Regan, Susan
Rigotti, Nancy A.
McNeill, Ann
TI A survey of tobacco dependence treatment guidelines in 31 countries
SO ADDICTION
LA English
DT Article
DE Tobacco dependence treatment; national treatment guidelines; survey
ID TREATMENT SERVICES
AB The Framework Convention on Tobacco Control (FCTC) asks countries to develop and disseminate comprehensive evidence-based guidelines and promote adequate treatment for tobacco dependence, yet to date no summary of the content of existing guidelines exists. This paper describes the national tobacco dependence treatment guidelines of 31 countries.
A questionnaire on tobacco dependence treatment guidelines was sent by e-mail to a convenience sample of contacts working in tobacco control in 31 countries in 2007. Completed questionnaires were received from respondents in all 31 countries. During the course of these enquiries we also made contact with people in 14 countries that did not have treatment guidelines and sent them a short questionnaire asking about their plans to produce guidelines.
The survey instrument was a 17-item questionnaire asking the following key questions: do the guidelines recommend brief interventions, intensive behavioural support, medications; which medications; do the guidelines apply to the whole health-care system and all professionals; do they refer explicitly to the Cochrane database; are they based on another country's guidelines; are they national or more local; are they endorsed formally by government; did they undergo peer review; who funded them; where were they published; do they include evidence on cost effectiveness of treatment?
According to respondents, all their countries' guidelines recommended brief advice, intensive behavioural support and nicotine replacement therapy (NRT); 84% recommended bupropion; 19% recommended varenicline; and 35% recommended telephone quitlines. Nearly half (48%) included cost-effectiveness evidence. Seventy-one per cent were supported formally by their government and 65% were supported financially by the government. Most (84%) used the Cochrane reviews as a source of evidence, 84% underwent a peer review process and 55% were based on the guidelines of other countries, most often the United States and England.
Overall, the guidelines reviewed followed the evidence base closely, recommending brief interventions, intensive behavioural support and NRT, and most recommended bupropion. Varenicline was not on the market in most of the countries in this survey when their guidelines were written, illustrating the need for guidelines to be updated periodically. None recommended interventions not proven to be effective, and some recommended explicitly against specific interventions (for lack of evidence). Most were peer-reviewed, many through lengthy and rigorous procedures, and most were endorsed or supported formally by their governments. Some countries that did not have guidelines expressed a need for technical support, emphasizing the need for countries to share experience, something the FCTC process is well placed to support.
C1 [Raw, Martin; McNeill, Ann] Univ Nottingham, UK Ctr Tobacco Control Studies, Div Epidemiol & Publ Hlth, Nottingham NGS 1PB, England.
[Regan, Susan; Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA.
[Regan, Susan; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA.
RP Raw, M (reprint author), Univ Nottingham, UK Ctr Tobacco Control Studies, Div Epidemiol & Publ Hlth, City Hosp Nottingham, Clin Sci Bldg, Nottingham NGS 1PB, England.
EM martin@martinraw.com
OI Regan, Susan/0000-0003-0940-2017
FU Society for the Study of Addiction; Doreen McIntyre; Global Treatment
Partnership; Pfizer; International Non-Governmental Coalition Against
Tobacco (INGCAT)
FX We gratefully acknowledge the Society for the Study of Addiction for
financial support for the data analysis and writing-up of this report,
Doreen McIntyre and the Global Treatment Partnership for financial
support of the survey and Catherine Slevin for research assistance with
the survey. We thank the following for advice on various aspects of the
project, including development of the questionnaire: Mira Aghi, Peter
Anderson, Linda Bailey, Rick Botelho, David Graham, Joe Gitchell, Paul
Hooper, John Hughes, Natasha Jategaonkar, Luk Joossens, Hayden McRobbie,
Yumiko Mochizukiy, Hana Ross, Peter Selby, Karen Slama, Fran Stillman,
Ken Wassum, Robert West and Heather Wipfli. Finally, we thank sincerely
the many country contacts who completed the questionnaire and without
whom this survey could not have happened. The Society for the Study of
Addiction is a learned society based in Britain. The Global Treatment
Partnership was a project funded by Pfizer and other organizations,
hosted by the International Non-Governmental Coalition Against Tobacco
(INGCAT), whose director was, at the time of the project, Doreen
McIntyre.
NR 16
TC 17
Z9 17
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD JUL
PY 2009
VL 104
IS 7
BP 1243
EP 1250
DI 10.1111/j.1360-0443.2009.02584.x
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 454MK
UT WOS:000266686000025
PM 19563566
ER
PT J
AU Yaremchuk, MJ
Chen, YC
AF Yaremchuk, Michael J.
Chen, Yi-Chieh
TI Bridge of Bone Canthopexy
SO AESTHETIC SURGERY JOURNAL
LA English
DT Article
AB Bridge of bone canthopexy has utility when significant movements of canthal position are required. It is a technique whereby the lateral canthal structures are purchased with a figure-of-eight suture of titanium wire. Drill holes are placed in the lateral orbital rim using the zygomaticofrontal sutures as reference landmarks. A canthal fixation point (the inferior drill hole) creates a measured distance from a fixed anatomic point (the zygomaticofrontal suture) assuring accurate and symmetric canthus positioning. Wire suture fixation over the bridge of bone created by the two drill holes provides maximum stability to counter soft tissue deforming forces. Fine adjustments can be made to the canthal position by twisting or untwisting the wire ends. (Aesthetic Surg J 2009;29:323-329.)
C1 [Yaremchuk, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yaremchuk, Michael J.] Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA.
[Chen, Yi-Chieh] Chang Gung Mem Hosp, Taipei 10591, Taiwan.
RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA.
EM dr.y@dryaremchuk.com
NR 12
TC 4
Z9 4
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1090-820X
J9 AESTHET SURG J
JI Aesthet. Surg. J.
PD JUL
PY 2009
VL 29
IS 4
BP 323
EP 329
DI 10.1016/j.asj.2009.07.001
PG 7
WC Surgery
SC Surgery
GA V20KV
UT WOS:000208139800014
PM 19717067
ER
PT J
AU Ghebremichael, M
Paintsil, E
Ickovics, JR
Vlahov, D
Schuman, P
Boland, R
Schoenbaum, E
Moore, J
Zhang, HP
AF Ghebremichael, Musie
Paintsil, Elijah
Ickovics, Jeannette R.
Vlahov, David
Schuman, Paula
Boland, Robert
Schoenbaum, Ellie
Moore, Janet
Zhang, Heping
TI Longitudinal association of alcohol use with HIV disease progression and
psychological health of women with HIV
SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
LA English
DT Article
DE alcohol use; HIV/AIDS; multilevel longitudinal models; CD4+T-cells;
depression
ID NATIONAL COMORBIDITY SURVEY; IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE
ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; CD4 CELL COUNT; DEPRESSIVE
SYMPTOMS; COMMUNITY SAMPLE; PSYCHIATRIC-DISORDERS; EPIDEMIOLOGY
RESEARCH; MAJOR DEPRESSION
AB We evaluated the association of alcohol consumption and depression, and their effects on HIV disease progression among women with HIV. The study included 871 women with HIV who were recruited from 19931995 in four US cities. The participants had physical examination, medical record extraction, and venipuncture, CD4+ T-cell Counts determination, measurement of depression symptoms (using the self-report Center for Epidemiological Studies-Depression Scale), and alcohol use assessment at enrollment, and semiannually until March 2000. Multilevel random coefficient ordinal models as well as multilevel models with joint responses were used in the analysis. There was no significant association between level of alcohol use and CD4+ T-cell counts. When participants were stratified by antiretroviral therapy (ART) Use. the association between alcohol and CD4+ T-cell did not reach statistical significance. The association between alcohol consumption and depression was significant (p < 0.001). Depression had a significant negative effect on CD4+ T-cell counts over time regardless of ART use. Our findings Suggest that alcohol consumption has a direct association with depression, Moreover, depression is associated with HIV disease progression. Our findings have implications for the provision of alcohol use interventions and psychological resources to improve the health of women with HIV.
C1 [Ghebremichael, Musie] Harvard Univ, Dept Biostat, Boston, MA 02115 USA.
[Ghebremichael, Musie] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Paintsil, Elijah] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Paintsil, Elijah] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA.
[Ickovics, Jeannette R.; Zhang, Heping] Yale Univ, Sch Publ Hlth, Dept Epidemiol, New Haven, CT USA.
[Ickovics, Jeannette R.; Zhang, Heping] Yale Univ, Sch Publ Hlth, Dept Publ Hlth, New Haven, CT USA.
[Vlahov, David] New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA.
[Schuman, Paula] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA.
[Boland, Robert] Brown Univ, Dept Psychiat, Providence, RI 02912 USA.
[Schoenbaum, Ellie] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA.
[Moore, Janet] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Ghebremichael, M (reprint author), Harvard Univ, Dept Biostat, Boston, MA 02115 USA.
EM musie@jimmy.harvard.edu
FU CSP VA [U64/CU106795, U64/CU200714, U64/CU306802, U64/CU506831]; NIDA
NIH HHS [5 U01-DA017387-03S1, K02 DA017713, K02 DA017713-05,
K02-DA017713, R01-DA076750-02, U01 DA017387, U01 DA017387-03S1]; NIMH
NIH HHS [T32-MH014235, T32 MH014235, T32 MH014235-31]
NR 47
TC 18
Z9 20
U1 5
U2 9
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0954-0121
J9 AIDS CARE
JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv
PD JUL
PY 2009
VL 21
IS 7
BP 834
EP 841
DI 10.1080/09540120802537864
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychology, Multidisciplinary; Respiratory System; Social Sciences,
Biomedical
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychology; Respiratory System; Biomedical Social Sciences
GA 478DZ
UT WOS:000268569300004
PM 20024739
ER
PT J
AU Reisner, SL
Mimiaga, MJ
Skeer, M
Mayer, KH
AF Reisner, Sari L.
Mimiaga, Matthew J.
Skeer, Margie
Mayer, Kenneth H.
TI Beyond Anal Sex: Sexual Practices Associated with HIV Risk Reduction
among Men Who Have Sex with Men in Boston, Massachusetts
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID PSYCHOSOCIAL HEALTH-PROBLEMS; SUBSTANCE USE; ALCOHOL-USE; BEHAVIORS
AB Men who have sex with men (MSM) continue to bear a disproportionate HIV and sexually transmitted disease (STD) burden. The current study examined the frequency and associations of sexual risk reduction behaviors among a sample of MSM in the greater Boston, Massachusetts area. One hundred eighty-nine MSM completed a one-time behavioral and psychosocial assessment between March 2006 and May 2007. Logistic regression procedures examined the association of demographic, psychosocial, and behavioral factors with risk reduction practices. Twenty percent of the sample reported rimming, mutual masturbation, digital penetration, using sex toys, or 100% condom use as a means to reduce their risk of acquiring or transmitting HIV in the prior 12 months. In bivariate analyses, risk reducers were more likely to disclose their MSM status (i.e., be "out''; odds ratio [OR] = 3.64; p < 0.05), and report oral sex with a condom in the prior 12 months (OR = 4.85; p < 0.01). They were less likely to report: depression (Center for Epidemiologic Studies Depression Scale [CES-D] score 16+; OR = 0.48; p < 0.05), a history of one or more sexually transmitted diseases (STDs; OR = 0.40; p < 0.05), and meeting sexual partners at public cruising areas (OR = 0.32; p < 0.01). In a multivariable model, risk reducers were less likely to report: alcohol use during sex (adjusted odds ratio [AOR] = 0.33; p < 0.05), depression (CESD score 16+; AOR = 0.32; p < 0.05), or meeting sexual partners at public cruising areas (AOR = 0.30; p < 0.05), or via the Internet (AOR = 0.12; p < 0.05) in the previous 12 months. Identifying and understanding such factors associated with risk reduction behaviors may be important to consider in designing effective prevention interventions to promote sexual health for MSM.
C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Skeer, Margie; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA 02119 USA.
[Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Skeer, Margie] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA.
RP Mimiaga, MJ (reprint author), Fenway Community Hlth, Fenway Inst, Prudential Tower,4th Floor,800 Boylston St, Boston, MA 02119 USA.
EM mmimiaga@fenwayhealth.org
FU National Institutes of Health [P30 AI42853]
FX Funding for some investigator and staff time was from the Lifespan/
Tufts/ Brown University Center for AIDS Research grant (National
Institutes of Health # P30 AI42853).
NR 33
TC 19
Z9 19
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD JUL
PY 2009
VL 23
IS 7
BP 545
EP 550
DI 10.1089/apc.2008.0249
PG 6
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 472UD
UT WOS:000268156800008
PM 19534602
ER
PT J
AU Leo-Lieber, MA
AF Leo-Lieber, Maria Anna
TI Beyond Science: My Memories of Charles S. Lieber
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Biographical-Item
C1 [Leo-Lieber, Maria Anna] Mt Sinai Sch Med MALL, New York, NY USA.
[Leo-Lieber, Maria Anna] James J Peters VA Med Ctr, Sp Bronx, NY USA.
RP Leo-Lieber, MA (reprint author), Mt Sinai Sch Med MALL, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUL
PY 2009
VL 33
IS 7
BP 1123
EP 1124
DI 10.1111/j.1530-0277.2009.00999.x
PG 2
WC Substance Abuse
SC Substance Abuse
GA 461PR
UT WOS:000267281200004
ER
PT J
AU Barnes, DE
Yaffe, K
Belfor, N
Jagust, WJ
DeCarli, C
Reed, BR
Kramer, JH
AF Barnes, Deborah E.
Yaffe, Kristine
Belfor, Nataliya
Jagust, William J.
DeCarli, Charles
Reed, Bruce R.
Kramer, Joel H.
TI Computer-based Cognitive Training for Mild Cognitive Impairment Results
from a Pilot Randomized, Controlled Trial
SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS
LA English
DT Article; Proceedings Paper
CT 10th International Conference on Alzheimers Disease and Related
Disorders
CY JUL 16-18, 2006
CL Madrid, SPAIN
DE human; aged; cognition; cognitive rehabilitation; memory;
neuropsychologic tests; randomized controlled trial; mild cognitive
impairment
ID ALZHEIMERS-DISEASE PATIENTS; HEALTHY OLDER-ADULTS;
CHOLINESTERASE-INHIBITORS; MEMORY ENHANCEMENT; REHABILITATION; DEMENTIA;
STIMULATION; PROGRAM; PEOPLE; INTERVENTION
AB We performed a pilot randomized, controlled trial of intensive, computer-based cognitive training in 47 subjects with mild cognitive impairment. The intervention group performed exercises specifically designed to improve auditory processing speed and accuracy for 100 min/d, 5 d/wk for 6 weeks; the control group performed more passive computer activities (reading, listening, visuospatial game) for similar amounts of time. Subjects had a mean age of 74 years and 60% were men; 77% successfully completed training. On our primary outcome, Repeatable Battery for Assessment of Neuropsychological Status total scores improved 0.36 standard deviations (SD) in the intervention group (P = 0.097) compared with 0.03 SD in the control group (P = 0.88) for a nonsignificant difference between the groups of 0.33 SD (P = 0.26). On 12 secondary outcome measures, most differences between the groups were not statistically significant. However, we observed a pattern in which effect sizes for verbal learning and memory measures tended to favor the intervention group whereas effect sizes for language and visuospatial function measures tended to favor the control group, which raises the possibility that these training programs may have domain-specific effects. We conclude that intensive, computer-based mental activity is feasible in subjects with mild cognitive impairment and that larger trials are warranted.
C1 [Barnes, Deborah E.; Yaffe, Kristine; Belfor, Nataliya] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Kramer, Joel H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA.
[Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, Mental Hlth Res Serv, San Francisco, CA USA.
[DeCarli, Charles; Reed, Bruce R.] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA.
[Jagust, William J.] Univ Calif Berkeley, Dept Neurosci, Berkeley, CA 94720 USA.
[Jagust, William J.] Univ Calif Berkeley, Dept Publ Hlth, Berkeley, CA 94720 USA.
RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St 151R, San Francisco, CA 94121 USA.
EM Deborah.Barnes@ucsf.edu
FU NIA NIH HHS [P30 AG010129, K01 AG 024069, K01 AG024069, K01 AG024069-04,
P30 AG010129-17, P30 AG010129-18]
NR 37
TC 93
Z9 97
U1 5
U2 54
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0893-0341
J9 ALZ DIS ASSOC DIS
JI Alzheimer Dis. Assoc. Dis.
PD JUL-SEP
PY 2009
VL 23
IS 3
BP 205
EP 210
PG 6
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA 495QO
UT WOS:000269909300005
PM 19812460
ER
PT J
AU Chao, LL
Pa, J
Duarte, A
Schuff, N
Weiner, MW
Kramer, JH
Miller, BL
Freeman, KM
Johnson, JK
AF Chao, Linda L.
Pa, Judy
Duarte, Audrey
Schuff, Norbert
Weiner, Michael W.
Kramer, Joel H.
Miller, Bruce L.
Freeman, Katie M.
Johnson, Julene K.
TI Patterns of Cerebral Hypoperfusion in Amnestic and Dysexecutive MCI
SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS
LA English
DT Article
DE mild cognitive impairment (MCI); memory; executive function; perfusion;
MRI
ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; BRAIN; PRECUNEUS;
DEMENTIA; MATTER; MRI
AB Although early studies on mild cognitive impairment (MCI) focused on memory dysfunction; more recent Studies suggest that MCI is clinically heterogeneous. The objective of this study is to examine patterns of cerebral perfusion in anmestic (N = 12) and nonamnestic (N = 12) single-domain MCI patients from 4 a priori regions of interest: middle and superior frontal cortex, posterior cingulate, and precuneus, to compare them relative to healthy controls (N = 12), and to correlate perfusion with neuropsychologic measures. Relative to controls, all MCI patients had hypoperfusion in the posterior cingulate, bilaterally. MCI patients with executive dysfunctions also showed hypoperfusion in bilateral middle frontal cortex and the left precuneus relative to controls and in the left middle frontal cortex, left posterior cingulate, and left precuneus relative to amnestic MCI patients. Perfusion in the posterior cingulate correlated positively with memory performance whereas perfusion in all 4 a priori regions of interest, predominately on the left side, correlated with executive function performance. The finding that single-domain MCI patients with prominent deficits in different cognitive domains exhibited different patterns of hypoperfusion relative to controls supports the existence of distinct subgroups of MCI. These data further Suggest that cognitive impairment in MCI is related to cerebral hypoperfusion.
C1 [Chao, Linda L.; Duarte, Audrey; Schuff, Norbert; Weiner, Michael W.] Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Chao, Linda L.; Schuff, Norbert; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA.
[Pa, Judy; Kramer, Joel H.; Miller, Bruce L.; Freeman, Katie M.; Johnson, Julene K.] Univ Calif San Francisco, Memory & Aging Ctr, Dept Neurol, San Francisco, CA 94121 USA.
[Duarte, Audrey] Georgia Inst Technol, Dept Psychol, Atlanta, GA 30332 USA.
RP Chao, LL (reprint author), Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, 4150 Clement St,114M, San Francisco, CA 94121 USA.
EM linda.chao@ucsf.edu
FU NIH NIA [R01 AG022538, R01 AG010897, P50 AG0300601]
FX Supported by NIH NIA R01 AG022538, R01 AG010897, P50 AG0300601.
NR 41
TC 41
Z9 43
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0893-0341
J9 ALZ DIS ASSOC DIS
JI Alzheimer Dis. Assoc. Dis.
PD JUL-SEP
PY 2009
VL 23
IS 3
BP 245
EP 252
PG 8
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA 495QO
UT WOS:000269909300012
PM 19812467
ER
PT J
AU Appelbaum, E
Abraham, JM
Pride, YB
Harrigan, CJ
Peters, DC
Biller, LH
Manning, WJ
Gibson, CM
AF Appelbaum, Evan
Abraham, JoEllyn M.
Pride, Yuri B.
Harrigan, Caitlin J.
Peters, Dana C.
Biller, Leah H.
Manning, Warren J.
Gibson, C. Michael
TI Association of Thrombolysis in Myocardial Infarction Myocardial
Perfusion Grade with cardiovascular magnetic resonance measures of
infarct architecture after primary percutaneous coronary intervention
for ST-segment elevation myocardial infarction
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID MICROVASCULAR OBSTRUCTION; VENTRICULAR-TACHYCARDIA; HETEROGENEITY;
DYSFUNCTION; MORPHOLOGY; MORTALITY
AB Background Primary percutaneous coronary intervention (pPCI) routinely restores normal epicardial flow among patients with ST-segment elevation myocardial infarction (STEMI). However, impairment of myocardial perfusion frequently persists. The goal of this analysis was to determine whether impaired myocardial perfusion was associated with cardiovascular magnetic resonance-defined abnormalities in infarct architecture, including infarct size (IS), infarct surface area (ISA), infarct border zone (IBZ), and infarct complexity (IC).
Methods Thirty-one patients with STEMI treated with pPCI were included in the analysis. Cardiovascular magnetic resonance was performed within 7 days of presentation and repeated at 3 months. Infarct complexity was defined as the ratio of actual ISA to an idealized smooth ISA and normalized to IS.
Results Impaired Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) (<3) was associated with larger ISA at baseline (78.2 +/- 25.3 cm(2) vs 40.3 +/- 30.3 cm(2), P = .02) and follow-up (58.8 +/- 27.5 cm(2) vs 26.3 +/- 20.2 cm(2), P = .03) and larger IBZ at follow-up (7.8% +/- 2.7% vs 4.1% +/- 3.3%, P = .02). At follow-up, ISA, when normalized to 15, was significantly higher among patients with impaired myocardial perfusion (TMPG <3) (6.9 +/- 2.5 vs 5.9 +/- 2.4 cm(2)/%, P = .03). Thrombolysis in MI myocardial perfusion grade <3 was also associated with increased IC at follow-up (52% +/- 12% vs 33% +/- 16%, P = .01).
Conclusions Impaired TMPG is associated with larger ISA, IBZ, and increased IC. At 3 months, TMPG remained associated with ISA and IC after adjusting for IS, suggesting that impaired TMPG after pPCI is associated with infarct architecture after healing, independent of IS. (Am Heart J 2009; 158:84-91.)
C1 [Appelbaum, Evan; Manning, Warren J.; Gibson, C. Michael] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Cardiovasc Med, Boston, MA USA.
[Appelbaum, Evan; Harrigan, Caitlin J.; Biller, Leah H.; Manning, Warren J.; Gibson, C. Michael] PERFUSE Core Labs, Boston, MA USA.
[Appelbaum, Evan; Harrigan, Caitlin J.; Biller, Leah H.; Manning, Warren J.; Gibson, C. Michael] Data Coordinating Ctr, Boston, MA USA.
[Peters, Dana C.; Manning, Warren J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA.
RP Gibson, CM (reprint author), 350 Longwood Ave,1st Floor, Boston, MA 02115 USA.
EM mgibson@perfuse.org
FU American College of Cardiology Foundation; Merck Adult Cardiology
Research Fellowship Award; Harvard/Massachusetts Institute of
Technology/Pfizer; Merck Clinical Investigator Training Program
FX This study was supported in part by grants from the American College of
Cardiology Foundation, Merck Adult Cardiology Research Fellowship Award,
Harvard/Massachusetts Institute of Technology/Pfizer, Merck Clinical
Investigator Training Program.
NR 22
TC 13
Z9 14
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD JUL
PY 2009
VL 158
IS 1
BP 84
EP 91
DI 10.1016/j.ahj.2009.04.012
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 465ZU
UT WOS:000267630600013
PM 19540396
ER
PT J
AU Dumaine, RL
Montalescot, G
Steg, PG
Ohman, EM
Eagle, K
Bhatt, DL
AF Dumaine, Raphaelle L.
Montalescot, Gilles
Steg, Ph. Gabriel
Ohman, E. Magnus
Eagle, Kim
Bhatt, Deepak L.
CA REACH Registry Investigators
TI Renal function, atherothrombosis extent, and outcomes in high-risk
patients
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE CORONARY SYNDROME; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR EVENTS;
CREATININE CLEARANCE; CONTROLLED-TRIAL; HEMODIALYSIS; INSUFFICIENCY;
ATORVASTATIN; ASSOCIATION; PREVENTION
AB Background Although prior data showed an association between chronic kidney disease (CKD) and atherothrombotic events, little is known about the risk profile and specific outcomes of atherothrombotic outpatients with CKD.
Methods More than 69,000 outpatients at risk of atherothrombotic events were enrolled in the REACH Registry. Creatinine clearance (CrCl) was available for 51,208 patients divided into A groups: normal (CrCl >= 90 mL/min, n = 13,949), mild (60-89 mL/min, n = 19,474), moderate (30-59 mL/min, n = 15,883), and severe CKD (CrCl <30 mL/min, n = 1902). Baseline characteristics, number of arterial beds overtly affected, medications, overall mortality, cardiovascular death, myocardial infarction, stroke, congestive heart failure, peripheral arterial events, and bleeding events were assessed according to renal function.
Results The number of arterial beds affected increased with severity of CKD. However, patients with severe CKD were less likely to receive medications of proven benefit. Severe CKD was an independent correlate of all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, peripheral arterial revascularization, or amputation.
Conclusion One third of outpatients at risk for atherothrombotic events have moderate to severe CKD. They are less likely to receive beneficial therapies despite a higher atherothrombotic burden and worse outcomes. (Am Heart J 2009; 158:141-8.)
C1 [Dumaine, Raphaelle L.; Montalescot, Gilles] Pitie Salpetriere Univ Hosp, Paris, France.
[Steg, Ph. Gabriel] Bichat Claude Bernard Univ Hosp, Paris, France.
[Ohman, E. Magnus] Duke Univ, Durham, NC USA.
[Eagle, Kim] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA.
RP Montalescot, G (reprint author), CHU Pitie Salpetriere, Inst Cardiol, 47 Boul Hop, F-75013 Paris, France.
EM gilles.montalescot@psl.aphp.fr
NR 19
TC 19
Z9 19
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD JUL
PY 2009
VL 158
IS 1
BP 141
EP U11
DI 10.1016/j.ahj.2009.05.011
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 465ZU
UT WOS:000267630600021
PM 19540404
ER
PT J
AU Gibson, CM
Pride, YB
Buros, JL
Ciaglo, LN
Morrow, DA
Scirica, BM
Stone, PH
AF Gibson, C. Michael
Pride, Yuri B.
Buros, Jacqueline L.
Ciaglo, Lauren N.
Morrow, David A.
Scirica, Benjamin M.
Stone, Peter H.
CA TIMI Study Grp
TI Timing and Duration of Myocardial Ischemia on Holter Monitoring
Following Percutaneous Coronary Intervention and Their Association With
Clinical Outcomes (a PROTECT-TIMI 30 Substudy Analysis)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LONG-TERM PROGNOSIS; UNSTABLE ANGINA; SILENT ISCHEMIA; RISK SCORE;
INFARCTION; REPERFUSION; DEATH
AB In patients with unstable angina, evidence of myocardial ischemia on Holter monitoring is associated with an adverse prognosis. However, the association of duration and timing of ischemia on Holter monitoring with outcomes after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTEACSs) has not been systematically evaluated. PROTECT-TIMI 30 randomized 857 patients with NSTEACSs undergoing PCI to eptifibatide plus a heparin product or bivalirudin monotherapy. Patients underwent continuous Holter monitoring following PCI, and the association between ischemia and clinical outcomes was evaluated retrospectively. Forty-three patients (5.0%) had ischemia on Holter after PCI. Any ischemia was associated with a significant increase in the incidence of death or myocardial infarction (MI) within 48 hours (32.6% vs 6.1%, odds ratio 7.S, 95% confidence interval 3.70 to 15.10, p <0.001). In patients who developed ischemia, there was a 1.44-fold increase in the odds for death or MI for every 30 minutes of ischemia (95% confidence interval 1.12 to 1.84, p = 0.004). Duration of ischemic events was related to their timing, such that ischemic events that occurred within the first 4 hours after PCI (median duration 141 minutes, interquartile range 36 to 227.5) were significantly longer than events occurring 4 to 24 hours after PCI (median duration 32.8 minutes, interquartile range 17.5 to 118, p = 0.041). In conclusion, early ischemia after PCI for NSTEACS is of longer duration, and longer duration of ischemia recognized by Holter monitoring is associated with an increased incidence of death or MI. Holter monitoring may be a useful surrogate end point in clinical trials. (c) 2009 Elsevier Inc. (Am J Cardiol 2009;104:36-40)
C1 [Gibson, C. Michael; Buros, Jacqueline L.; Ciaglo, Lauren N.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, TIMI Study Grp,Div Cardiovasc Med, Boston, MA 02115 USA.
[Pride, Yuri B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA.
[Morrow, David A.; Scirica, Benjamin M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA.
[Stone, Peter H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA USA.
RP Gibson, CM (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, TIMI Study Grp,Div Cardiovasc Med, Boston, MA 02115 USA.
EM mgibson@timi.org
OI Buros, Jacqueline/0000-0001-9588-4889
FU Millennium Pharmaceuticals, Cambridge, Massachusetts; Schering-Plough
Research Institute, Kermilworth, New Jersey
FX This word was supported in part by grants from Millennium
Pharmaceuticals, Cambridge, Massachusetts, and Schering-Plough Research
Institute, Kermilworth, New Jersey.
NR 19
TC 2
Z9 2
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 1
PY 2009
VL 104
IS 1
BP 36
EP 40
DI 10.1016/j.amjcard.2009.02.044
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469JX
UT WOS:000267895100008
PM 19576318
ER
PT J
AU Friedewald, VE
Kornman, KS
Beck, JD
Genco, R
Goldfine, A
Libby, P
Offenbacher, S
Ridker, PM
Van Dyke, TE
Roberts, WC
AF Friedewald, Vincent E.
Kornman, Kenneth S.
Beck, James D.
Genco, Robert
Goldfine, Allison
Libby, Peter
Offenbacher, Steven
Ridker, Paul M.
Van Dyke, Thomas E.
Roberts, William C.
TI The American Journal of Cardiology and Journal of Periodontology
Editors' Consensus: Periodontitis and Atherosclerotic Cardiovascular
Disease
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Editorial Material
ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; ALVEOLAR BONE LOSS;
DENSITY-LIPOPROTEIN CHOLESTEROL; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INDUCED
GINGIVAL HYPERPLASIA; NUTRITION EXAMINATION SURVEY; PERIPHERAL
ARTERIAL-DISEASE; DEPENDENT DIABETES-MELLITUS; CALCIUM-CHANNEL BLOCKERS
C1 [Friedewald, Vincent E.] Univ Notre Dame, Notre Dame, IN 46556 USA.
[Friedewald, Vincent E.] Univ Texas Med Sch Houston, Dept Internal Med, Houston, TX USA.
[Kornman, Kenneth S.] Interleukin Genet, Waltham, MA USA.
[Beck, James D.] Univ N Carolina, Sch Dent, Chapel Hill, NC USA.
[Genco, Robert] SUNY Buffalo, Dept Oral Biol, Amherst, NY USA.
[Genco, Robert] SUNY Buffalo, Dept Microbiol, Amherst, NY USA.
[Goldfine, Allison; Libby, Peter] Harvard Univ, Sch Med, Boston, MA USA.
[Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Libby, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ridker, Paul M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA.
[Van Dyke, Thomas E.] Boston Univ, Clin Res Ctr, Goldman Sch Dent Med, Boston, MA 02215 USA.
[Roberts, William C.] Baylor Univ, Med Ctr Proceedings, Dallas, TX USA.
[Roberts, William C.] Baylor Univ, Med Ctr, Baylor Heart & Vasc Inst, Dallas, TX USA.
[Roberts, William C.] Baylor Hlth Care Syst, A Webb Roberts Ctr Continuing Med Educ, Dallas, TX USA.
RP Friedewald, VE (reprint author), Univ Notre Dame, Notre Dame, IN 46556 USA.
EM vfriedew@nd.edu
NR 122
TC 105
Z9 110
U1 0
U2 9
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 JUL 1
PY 2009
VL 104
IS 1
BP 59
EP 68
DI 10.1016/j.amjcard.2009.05.002
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469JX
UT WOS:000267895100012
PM 19576322
ER
PT J
AU Schnabel, RB
Larson, MG
Yamamoto, JF
Kathiresan, S
Rong, J
Levy, D
Keaney, JF
Wang, TJ
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate B.
Larson, Martin G.
Yamamoto, Jennifer F.
Kathiresan, Sekar
Rong, Jian
Levy, Daniel
Keaney, John F., Jr.
Wang, Thomas J.
Vasan, Ramachandran S.
Benjamin, Emelia J.
TI Relation of Multiple Inflammatory Biomarkers to Incident Atrial
Fibrillation
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID C-REACTIVE PROTEIN; OSTEOPROTEGERIN LEVELS; PLASMA OSTEOPROTEGERIN;
DIABETIC-PATIENTS; INTERLEUKIN-6; METAANALYSIS; HEART; RISK;
THROMBOGENESIS; POPULATION
AB Basic and clinical studies have suggested that inflammation predisposes to atrial fibrillation (AF). We assessed the association of 12 circulating inflammatory biomarkers (i.e., C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase A2 [mass and activity], monocyte chemoattractant protein-1, myelo-peroxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II) with incident AF in 2863 Framingham Offspring Study participants (mean age 60.7 years, SD = 9.4, 55% women). During follow-up (median 6 years), 148 participants (43% women) developed incident AF. In the multivariable proportional hazards models, the inflammatory biomarker panel was associated with incident AF (p = 0.03). With stepwise selection (p <0.01 for entry and retention), log-transformed osteoprotegerin was associated with incident AF (hazard ratio per SD 1.30, 95% confidence interval 1.08 to 1.56, p = 0.006). Adjusting for interim myocardial infarction or heart failure attenuated the association between osteoprotegerin and incident AF (hazard ratio 1.18, 95% confidence interval 0.98 to 1.43, p = 0.09). In conclusion, circulating osteoprotegerin concentration was significantly associated with incident AF in our community-based sample, possibly mediated by interim cardiovascular events. (c) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;104:92-96)
C1 [Schnabel, Renate B.; Larson, Martin G.; Yamamoto, Jennifer F.; Rong, Jian; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Natl Heart Lung Blood Inst, Framingham Study, Framingham, MA USA.
[Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany.
[Yamamoto, Jennifer F.] Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA USA.
[Yamamoto, Jennifer F.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Kathiresan, Sekar; Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA.
[Kathiresan, Sekar] Broad Inst Harvard, Cambridge, MA USA.
[Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Med Dept, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
RP Benjamin, EJ (reprint author), Natl Heart Lung Blood Inst, Framingham Study, Framingham, MA USA.
EM melia@bu.edu
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health/National Heart, Lung, Blood Institute
[N01-HC-25195, 6R01-NS 17950]; National Institutes of Health [HL064753,
HL076784, AG028321, R01HL71039]; National Institutes of Health Research
Career Award [K24 HL04334]; Deutsche Forschungsgemeinschaft (German
Research Foundation) Research Fellowship [SCHN 1149/1-1]; Doris Duke
Charitable Foundation Clinical Scientist Development Award
[1K231-11-083102]
FX This study was supported by National Institutes of Health/National
Heart, Lung, Blood Institute Grants N01-HC-25195 and 6R01-NS 17950, and
National Institutes of Health Grants HL064753. HL076784, and AG028321
(E. J. Benjamin), 1 R01HL71039 (R. S. Vasan), Bethesda, Maryland;
National Institutes of Health Research Career Award K24 HL04334 (R. S.
Vasan), Bethesda, Maryland Deutsche Forschungsgemeinschaft (German
Research Foundation) Research Fellowship SCHN 1149/1-1 (R. B. Schnabel),
Bonn, Germany; and Grant 1K231-11-083102, Doris Duke Charitable
Foundation Clinical Scientist Development Award (S. Kathiresan), New
York, New York.
NR 28
TC 68
Z9 71
U1 0
U2 6
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 JUL 1
PY 2009
VL 104
IS 1
BP 92
EP 96
DI 10.1016/j.amjcard.2009.02.053
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469JX
UT WOS:000267895100016
PM 19576326
ER
PT J
AU Baggish, AL
Weiner, RB
Yared, K
Wang, F
Kupperman, E
Hutter, AM
Picard, MH
Wood, MJ
AF Baggish, Aaron L.
Weiner, Rory B.
Yared, Kibar
Wang, Francis
Kupperman, Eli
Hutter, Adolph M., Jr.
Picard, Michael H.
Wood, Malissa J.
TI Impact of Family Hypertension History on Exercise-Induced Cardiac
Remodeling
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LEFT-VENTRICULAR STRUCTURE; CONVERTING ENZYME GENE; SYSTEMIC
HYPERTENSION; POLYMORPHISM; MASS; ASSOCIATION; COMMITTEE; YOUNG
AB Left ventricular (LV) hypertrophy is a well-established, but highly variable, finding among exercise-trained persons. The causes for the variability in LV remodeling in response to exercise training remain incompletely understood. The present study sought to determine whether a family history of hypertension is a determinant of the cardiac response to exercise training. The cardiac parameters in 60 collegiate rowers (30 men/30 women; age 19.8 +/- 1.1 years) with (family history positive [FH+], n = 22) and without (family history negative [FH-], n = 38) a FH of hypertension were studied with echocardiography before and after 90 days of rowing training. The LV mass increased significantly in both groups. However, the LV mass increased significantly more in FH- persons (Delta 17 +/- 5 g/m(2)) than in FH+ persons (Delta 9 +/- 6 g/m(2), p <0.001) with distinctly differently patterns of LV hypertrophy between the 2 groups. FH- athletes experienced eccentric LV hypertrophy (relative wall thickness index 0.39 +/- 0.4) characterized by LV dilation. In contrast, FH+ athletes developed concentric LV hypertrophy (relative wall thickness index 0.44 +/- 0.3; p <0.001) characterized by LV wall thickening. Furthermore, the eccentric LV remodeling in FH- athletes was associated with a more robust enhancement of LV diastolic function than the concentric LV remodeling that occurred in FH+ athletes. In conclusion, these findings suggest that patterns of exercise-induced LV remodeling are strongly associated with FH history status. (c) 2009 Elsevier Inc. (Am J Cardiol 2009;104:101-106)
C1 [Baggish, Aaron L.; Weiner, Rory B.; Yared, Kibar; Hutter, Adolph M., Jr.; Picard, Michael H.; Wood, Malissa J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Wang, Francis; Kupperman, Eli] Harvard Univ, Univ Hlth Serv, Cambridge, MA 02138 USA.
RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
EM abaggish@partners.org
OI Picard, Michael/0000-0002-9264-3243
NR 20
TC 10
Z9 12
U1 0
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 1
PY 2009
VL 104
IS 1
BP 101
EP 106
DI 10.1016/j.amjcard.2009.02.052
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469JX
UT WOS:000267895100018
PM 19576328
ER
PT J
AU Noseworthy, PA
Rosenberg, MA
Fifer, MA
Palacios, IF
Lowry, PA
Ruskin, JN
Sanborn, DM
Picard, MH
Vlahakes, GJ
Mela, T
Das, S
AF Noseworthy, Peter A.
Rosenberg, Michael A.
Fifer, Michael A.
Palacios, Igor F.
Lowry, Patricia A.
Ruskin, Jeremy N.
Sanborn, Danita M.
Picard, Michael H.
Vlahakes, Gus J.
Mela, Theofanie
Das, Saumya
TI Ventricular Arrhythmia Following Alcohol Septal Ablation for Obstructive
Hypertrophic Cardiomyopathy
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID OUTFLOW TRACT OBSTRUCTION; SUDDEN CARDIAC DEATH; TRANSCORONARY ABLATION;
TACHYCARDIA; RISK; PREVENTION; SURVIVAL
AB We sought to assess the risk of sudden cardiac death (SCD) and ventricular arrhythmia after alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy. ASA is a nonsurgical alternative to septal myectomy for treatment of symptomatic, drug-refractory, obstructive hypertrophic cardiomyopathy. The effect of ASA on ventricular arrhythmia risk is not well established. We examined the rates of SCD among 89 patients treated with ASA. The secondary end point was ventricular tachycardia/ventricular fibrillation (VT/VF), appropriate implantable cardioverter defibrillator (ICD) therapy, or cardiac arrest after ASA among those with implanted ICDs or permanent pacemakers (n = 42). Patients were classified as either high-risk or low-risk on the basis of established clinical indications for ICD implantation. No mortality was attributable to SCD at a mean follow-up of 5.0 +/- 2.3 years in the entire cohort. Among the 42 patients with an ICD or permanent pacemaker, 9 had documented VT/VF, cardiac arrest, or appropriate ICD therapy, resulting in an annual event rate of 4.9%/year. The annual event rate for VT/VF, cardiac arrest, or appropriate ICD therapy was 2.8%/year (4 of 29 patients) in low-risk patients and 13.4% in high-risk patients (5 of 13 patients). A 10-mm Hg increase in the immediate post-ASA gradient was associated with a hazard ratio of 2.66 for arrhythmic events (95% confidence interval 1.55 to 4.56, p <0.001). In conclusion, ASA was performed in patients with highly symptomatic, drug-refractory hypertrophic cardiomyopathy with no mortality attributable to SCD and an annual rate of VT/VF, cardiac arrest, or appropriate ICD therapy of 4.9%/year. (c) 2009 Elsevier Inc. (Am J Cardiol 2009;104:128-132)
C1 [Ruskin, Jeremy N.; Mela, Theofanie; Das, Saumya] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Noseworthy, Peter A.; Fifer, Michael A.; Palacios, Igor F.; Lowry, Patricia A.; Sanborn, Danita M.; Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Vlahakes, Gus J.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA.
[Rosenberg, Michael A.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA.
RP Das, S (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
EM sdas@partners.org
OI Picard, Michael/0000-0002-9264-3243
FU American College of Cardiology- Pfizer, Bethesda, Maryland; Merck,
Whitehouse Station
FX Dr. Das was funded by a career development grant from American College
of Cardiology- Pfizer, Bethesda, Maryland. Dr. Fifer has received a
research grant from Merck, Whitehouse Station, NJ (2 >=$10,000) and
private donations (2 >=$10,000) for research in hypertrophic
cardionlyopathy, as well as honoraria for speaking on hypertrophic
cardiomyopathy.
NR 16
TC 35
Z9 38
U1 0
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 1
PY 2009
VL 104
IS 1
BP 128
EP 132
DI 10.1016/j.amjcard.2009.02.056
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469JX
UT WOS:000267895100023
PM 19576333
ER
PT J
AU Imamura, F
Lichtenstein, AH
Dallal, GE
Meigs, JB
Jacques, PF
AF Imamura, Fumiaki
Lichtenstein, Alice H.
Dallal, Gerard E.
Meigs, James B.
Jacques, Paul F.
TI Confounding by Dietary Patterns of the Inverse Association Between
Alcohol Consumption and Type 2 Diabetes Risk
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE alcohol drinking; bias (epidemiology); confounding factors
(epidemiology); diabetes mellitus; type 2; diet; factor analysis;
statistical; least-squares analysis; proportional hazards models
ID FOOD-FREQUENCY QUESTIONNAIRE; PROPENSITY SCORE; NUTRITIONAL
EPIDEMIOLOGY; DRINKING PATTERNS; HEART-DISEASE; VALIDITY;
REPRODUCIBILITY; FRAMINGHAM; MELLITUS; BIAS
AB The ability to interpret epidemiologic observations is limited because of potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as standard risk factors and selected nutrients, the authors modeled the longitudinal association between alcohol consumption and 7-year risk of type 2 diabetes mellitus in 2,879 healthy adults enrolled in the Framingham Offspring Study (1991-2001) by Cox proportional hazard models. After adjustment for standard risk factors, consumers of >= 9.0 drinks/week had a significantly lower risk of type 2 diabetes mellitus compared with abstainers (hazard ratio = 0.47, 95% confidence interval (CI): 0.27, 0.81). Adjustment for selected nutrients had little effect on the hazard ratio, whereas adjustment for dietary pattern variables by factor analysis significantly shifted the hazard ratio away from null (hazard ratio = 0.33, 95% CI: 0.17, 0.64) by 40.0% (95% CI: 16.8, 57.0; P = 0.002). Dietary pattern variables by partial least squares showed similar results. Therefore, the observed inverse association, consistent with past studies, was confounded by dietary patterns, and this confounding was not captured by individual nutrient adjustment. The data suggest that alcohol intake, not dietary patterns associated with alcohol intake, is responsible for the observed inverse association with type 2 diabetes mellitus risk.
C1 [Imamura, Fumiaki; Lichtenstein, Alice H.; Dallal, Gerard E.; Jacques, Paul F.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Imamura, Fumiaki; Lichtenstein, Alice H.; Dallal, Gerard E.; Jacques, Paul F.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM paul.jacques@tufts.edu
OI Imamura, Fumiaki/0000-0002-6841-8396
FU NHLBI NIH HHS [N01HC25195, N01-HC-25195]; NIDDK NIH HHS [K24-DK090140]
NR 34
TC 26
Z9 26
U1 0
U2 3
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 JUL 1
PY 2009
VL 170
IS 1
BP 37
EP 45
DI 10.1093/aje/kwp096
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 463NZ
UT WOS:000267440200005
PM 19429876
ER
PT J
AU Cavusoglu, E
Chopra, V
Gupta, A
Choksi, PU
Ruwende, C
Yanamadala, S
Frishman, WH
Pinsky, DJ
Marmur, JD
AF Cavusoglu, Erdal
Chopra, Vineet
Gupta, Amit
Choksi, Palak U.
Ruwende, Cyril
Yanamadala, Sunitha
Frishman, William H.
Pinsky, David J.
Marmur, Jonathan D.
TI Relation of Baseline Serum Potassium Levels to Angiographic Findings in
Patients With Known or Suspected Coronary Artery Disease
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
ID SPONTANEOUSLY HYPERTENSIVE RATS; ACUTE MYOCARDIAL-INFARCTION; BLOOD-CELL
COUNT; CARDIAC MORTALITY; PREDICTOR
AB BACKGROUND
In experimental animal studies, potassium has been demonstrated to protect against the development of atherosclerosis through a variety of mechanisms. Data regarding the role of potassium in the development of human atherosclerosis are sparse. The objective of this study was to determine the association between plasma potassium levels and angiographically defined coronary artery disease (CAD).
METHODS
In a cohort of 389 male patients undergoing coronary angiography for a variety of clinical indications, the association between baseline serum potassium levels and the extent of angiographically defined atherosclerosis was analyzed. Adjustments were made for clinical and laboratory variables (including inflammatory markers) known to be associated with atherosclerosis.
RESULTS
By multivariate logistic regression analysis, baseline serum potassium levels were an independent predictor of the presence of multivessel disease (odds ratio (OR) 1.31, 95% confidence interval (CI) 1.01-1.69; P<0.05). In addition, in the non-myocardial infarction subpopulation of patients, serum potassium was also an independent predictor of the presence of multivessel disease by multivariate logistic regression analysis (OR 1.34, 95% Cl, 1.02-1.76; P<0.05). In the myocardial infarction (MI) subpopulation, serum potassium was not a predictor of multivessel disease, possibly due to the confounding effect of hypokalemia known-to be present during MI.
CONCLUSIONS
These data demonstrate that a simple baseline serum potassium level is independently associated with the presence of multivessel disease, even in the context of clinical CAD risk factors and other established inflammatory markers.
C1 [Cavusoglu, Erdal; Gupta, Amit; Marmur, Jonathan D.] Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA.
[Cavusoglu, Erdal; Chopra, Vineet; Choksi, Palak U.] Bronx Vet Affairs Med Ctr, Dept Med, Bronx, NY USA.
[Ruwende, Cyril; Yanamadala, Sunitha; Pinsky, David J.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Frishman, William H.] New York Med Coll, Dept Med, Westchester Med Ctr, Valhalla, NY 10595 USA.
RP Cavusoglu, E (reprint author), Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA.
EM ECavusoglu@aol.com
NR 12
TC 2
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 0895-7061
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD JUL
PY 2009
VL 22
IS 7
BP 754
EP 762
DI 10.1038/ajh.2009.65
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 462IX
UT WOS:000267346100012
PM 19373212
ER
PT J
AU Egan, BM
Basile, JN
Rehman, SU
Davis, PB
Grob, CH
Riehle, JF
Walters, CA
Lackland, DT
Merali, C
Sealey, JE
Laragh, JH
AF Egan, Brent M.
Basile, Jan N.
Rehman, Shakaib U.
Davis, Phillip B.
Grob, Curt H., III
Riehle, Jessica Flynn
Walters, Christine A.
Lackland, Daniel T.
Merali, Carmen
Sealey, Jean E.
Laragh, John H.
TI Plasma Renin Test-Guided Drug Treatment Algorithm for Correcting
Patients With Treated but Uncontrolled Hypertension: A Randomized
Controlled Trial
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
ID CONVERTING-ENZYME-INHIBITOR; BLOOD-PRESSURE RESPONSE; RESISTANT
HYPERTENSION; LARAGHS LESSONS; CLINICAL PEARLS; ANTIHYPERTENSIVE ACTION;
RENAL-FUNCTION; THERAPY; PATHOPHYSIOLOGY; DIAGNOSIS
AB BACKGROUND
Undefined pathophysiologic mechanisms likely contribute to unsuccessful anti hypertensive drug therapy. The renin test-guided therapeutic (RTGT) algorithm is based on the concept that, irrespective of current drug treatments, subnormal plasma renin activity (PRA) (<0.65 ng/ml/h) indicates sodium-volume excess "V" hypertension, whereas values >= 0.65 indicate renin-angiotensin vasoconstriction excess "R" hypertension.
METHODS
The RTGT algorithm was applied to treated, uncontrolled hypertensives and compared to clinical hypertension specialists' care (CHSC) without access to PRA. RTGT protocol: "V" patients received natriuretic anti-"V"drugs (diuretics, spironolactone, calcium antagonists, or alpha(1)-blockers) while withdrawing antirenin "R" drugs (converting enzyme inhibitors, angiotensin receptor antagonists, or beta-blockers). Converse strategies were applied to "R" patients. Eighty-four ambulatory hypertensives were randomized and 77 qualified for the intention-to-treat analysis including 38 in RTGT (63.9 +/- 1.8 years; baseline blood pressure (BP) 157.0 +/- 2.6/87.1 +/- 2.0 mm Hg; PRA 5.8 +/- 1.6; 3.1 +/- 0.3 antihypertensive drugs) and 39 in CHSC (58.0 +/- 2.0 years; BD 153.6 +/- 2.3/91.9 +/- 2.0; PRA 4.6 +/- 1.1; 2.7 +/- 0.2 drugs).
RESULTS
BP was controlled in 28/38 (74% (RTGT)) vs. 23/39 (59% (CHSC)), P=0.17, falling to 127.9 +/- 2.3/73.1 +/- 1.8 vs. 134.0 +/- 2.8/79.8 +/- 1.9 mm Hg, respectively. Systolic BP (SBP) fell more with RTGT (-29.1 +/- 3.2 vs. -19.2 +/- 3.2 mm Hg, P=0.03), whereas diastolic BP (DBP) declined similarly (P=0.32). Although final anti hypertensive drug numbers were similar (3.1 +/- 0.2 (RTGT) vs. 3.0 +/- 0.3 (CHSC), P=0.73) in "V" patients, 60% (RTGT) vs. 11% (CHSC) of "R" drugs were withdrawn and BP medications were reduced (-0.5 +/- 03 vs. +0.7 +/- 0.3, P=0.01).
CONCLUSIONS
In treated but uncontrolled hypertension, RTGT improves control and lowers BP equally well or better than CHSC, indicating that RTGT provides a reasonable strategy for correcting treated but uncontrolled hypertension.
C1 [Egan, Brent M.; Basile, Jan N.; Rehman, Shakaib U.; Davis, Phillip B.; Grob, Curt H., III; Lackland, Daniel T.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Basile, Jan N.; Rehman, Shakaib U.] Ralph H Johnson VA Med Ctr, Dept Med, Charleston, SC USA.
[Riehle, Jessica Flynn; Walters, Christine A.; Lackland, Daniel T.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA.
[Merali, Carmen; Laragh, John H.] Weill Cornell Med Coll, Dept Cardiothorac Surg, New York, NY USA.
[Sealey, Jean E.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
RP Egan, BM (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
EM eganbm@musc.edu
RI Sealey, Jean/A-9562-2009
FU New York Presbyterian Hospital; National Institutes of Health [HL04290];
Ralph H. Johnson Veterans Affairs Hospital
FX This research was supported by grants from the New York Presbyterian
Hospital, National Institutes of Health HL04290, and the Ralph H.
Johnson Veterans Affairs Hospital.
NR 49
TC 59
Z9 59
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0895-7061
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD JUL
PY 2009
VL 22
IS 7
BP 792
EP 801
DI 10.1038/ajh.2009.63
PG 10
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 462IX
UT WOS:000267346100017
PM 19373213
ER
PT J
AU Pfeffer, MA
Burdmann, EA
Chen, CY
Cooper, ME
de Zeeuw, D
Eckardt, KU
Ivanovich, P
Kewalramani, R
Levey, AS
Lewis, EF
McGill, J
McMurray, JJV
Parfrey, P
Parving, HH
Remuzzi, G
Singh, AK
Solomon, SD
Toto, R
Uno, H
AF Pfeffer, Marc A.
Burdmann, Emmanuel A.
Chen, Chao-Yin
Cooper, Mark E.
de Zeeuw, Dick
Eckardt, Kai-Uwe
Ivanovich, Peter
Kewalramani, Reshma
Levey, Andrew S.
Lewis, Eldrin F.
McGill, Janet
McMurray, John J. V.
Parfrey, Patrick
Parving, Hans-Henrik
Remuzzi, Giuseppe
Singh, Ajay K.
Solomon, Scott D.
Toto, Robert
Uno, Hajime
CA TREAT Investigators
TI Baseline Characteristics in the Trial to Reduce Cardiovascular Events
With Aranesp Therapy (TREAT)
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Erythropoiesis-stimulating agents; anemia; diabetes; chronic kidney
disease
ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE;
RECOMBINANT-HUMAN-ERYTHROPOIETIN; HEMODIALYSIS-PATIENTS;
RANDOMIZED-TRIALS; DIABETES-MELLITUS; ANEMIA CORRECTION; MORTALITY;
OUTCOMES; RISK
AB Background: Anemia augments the already high rates of fatal and major nonfatal cardiovascular and renal events in individuals with type 2 diabetes. In 2004, we initiated the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). This report presents the baseline characteristics and therapies of TREAT participants and subgroups defined by the presence or absence of overt proteinuria and history of cardiovascular disease. The design of TREAT and baseline characteristics also are compared with 2 recent trials of nondialysis patients with chronic kidney disease (CKD) in which treatment with another erythropoiesis-stimulating agent targeting greater hemoglobin levels had either a neutral or adverse effect on clinical outcomes.
Study Design: Randomized trial.
Setting & Participants: 4,044 participants with type 2 diabetes, CKD (defined as estimated glomerular filtration rate of 20 to 60 mL/min/1.73 m(2)), and anemia (hemoglobin <= 11 g/dL) from 24 countries.
Intervention: Darbepoetin alfa to attempt to increase hemoglobin levels to 13 g/dL compared with placebo.
Outcomes: TREAT is an event-driven design to continue until approximately 1,203 patients experience a primary event: the composite end point of death or cardiovascular morbidity (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia). The composite end point of death or need for long-term renal replacement therapy also is a primary end point.
Conclusions: With several-fold more patient-years and a placebo arm, TREAT will provide a robust estimate of the safety and efficacy of darbepoetin alfa and generate prospective data regarding the risks of major cardiovascular and renal events in a contemporarily managed cohort of patients with type 2 diabetes, CKD, and anemia. Am J Kidney Dis 54:59-69. (c) 2009 by the National Kidney Foundation, Inc.
C1 [Pfeffer, Marc A.; Lewis, Eldrin F.; Singh, Ajay K.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA.
[Pfeffer, Marc A.; Lewis, Eldrin F.; Singh, Ajay K.; Solomon, Scott D.] Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA.
[Pfeffer, Marc A.; Lewis, Eldrin F.; Singh, Ajay K.; Solomon, Scott D.] Harvard Univ, Sch Med, Boston, MA USA.
[Burdmann, Emmanuel A.] Fac Med Sao Jose Rio Pret, Sao Jose Do Rio Preto, Brazil.
[Chen, Chao-Yin; Kewalramani, Reshma] Amgen Inc, Global Biostat & Epidemiol, Thousand Oaks, CA USA.
[Chen, Chao-Yin; Kewalramani, Reshma] Amgen Inc, Global Clin Dev, Thousand Oaks, CA USA.
[Cooper, Mark E.] Baker Heart Res Inst, Melbourne, Vic, Australia.
[de Zeeuw, Dick] Univ Groningen, Univ Med Ctr Groningen, Div Clin Pharmacol, NL-9713 AV Groningen, Netherlands.
[Eckardt, Kai-Uwe] Univ Erlangen Nurnberg, Dept Hypertens & Nephrol, Erlangen, Germany.
[Ivanovich, Peter] NW Univ Feinberg, Div Nephrol, Dept Med, Chicago, IL USA.
[Levey, Andrew S.] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
[McGill, Janet] Washington Univ, Sch Med, Med Ctr, St Louis, MO USA.
[McMurray, John J. V.] Univ Glasgow, Dept Cardiol, Glasgow G12 8QQ, Lanark, Scotland.
[Parfrey, Patrick] Hlth Sci Ctr, Div Nephrol, St John, NF, Canada.
[Parving, Hans-Henrik] Univ Copenhagen, Dept Med Endocrinol, Rigshosp, DK-1168 Copenhagen, Denmark.
[Remuzzi, Giuseppe] Mario Negri Inst Pharmacol Res, I-24100 Bergamo, Italy.
[Toto, Robert] Univ Texas SW, Dept Med, Dallas, TX USA.
[Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Pfeffer, MA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM mpfeffer@rics.bwh.harvard.edu
RI Cooper, Mark/E-8680-2010; Burdmann, Emmanuel/B-7023-2009; Solomon,
Scott/I-5789-2013; de Zeeuw, Dick/E-9080-2014;
OI Cooper, Mark/0000-0002-5953-642X; Burdmann,
Emmanuel/0000-0002-7644-8579; de Zeeuw, Dick/0000-0003-3434-7777;
mcmurray, john/0000-0002-6317-3975
FU Amgen
FX Amgen. which markets darbepoetin alfa, funded this study. Dr Pfeffer has
received support (research grant to Brigham and Women's Hospital) for
the conduct of TREAT and has served as a consultant to Amgen. Dr de
Zeeuw is a member of the TREAT Steering Committee (financial
compensation to the University Medical Center Groningen). Dr Burdniann
has received Support (research grant to Hospital de Base, Sao Jose do
Rio Preto Medical School) and has served as a consultant to Amgen. Dr
Parving has received lecture and consultant fees from Amgen. Dr Eckardt
has received lecture and Consulting fees from companies producing ESAs,
including Amgen. Johnson & Johnson, Roche. Affymax. Stada. Sandoz, and
Hexal. Drs Cooper and Ivanovich have received financial support from
Amgen for work related to the Study. Dr Solomon has received research
Support from Amgen. Dr Levey is a member of the TREAT Steering Committee
(financial compensation to Tufts Medical Center). Dr Lewis has received
Support (research grant to Brigham and Women's Hospital) from Amgen and
has served as a consultant( to Amgen. Dr McGill has received consulting
fees from Amgen (for the Executive Committee). Dr McMurray is a member
of the TREAT Steering Committee (financial compensation to Glasgow
University). Dr Parfrey has received research support from Amgen and
Ortho Biotech to pefform RCT,; of anemia therapy. Dr Remuzzi has
received lecture support from Merckm Amgen, and AstraZeneca. Drs Chen
and Kewalrainani are employees of Amgen.
NR 36
TC 32
Z9 34
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 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUL
PY 2009
VL 54
IS 1
BP 59
EP 69
DI 10.1053/j.ajkd.2009.04.008
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 499JC
UT WOS:000270214400012
PM 19501439
ER
PT J
AU Flythe, JE
Rueda, JF
Riscoe, MK
Watnick, S
AF Flythe, Jennifer E.
Rueda, Jose F.
Riscoe, Michael K.
Watnick, Suzanne
TI Silicate Nephrolithiasis After Ingestion of Supplements Containing
Silica Dioxide
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Silicate; silica; nephrolithiasis; over-the-counter supplements
ID MAGNESIUM TRISILICATE; URINARY CALCULI; UROLITHIASIS
AB Silicate calculi are common in some mammals, such as dogs and sheep, but extremely rare in humans. We report a case of silicate calculi in a woman using oral over-the-counter Uncaria tomentosa, Digestive Advantage and FlexProtex supplements. All 3 contained the excipient silica dioxide. Stone analysis showed composition of 100% silicate. The nephrolithiasis promptly abated after discontinuation of the products containing silica, then returned when the patient restarted her supplements. This case emphasizes the importance of stone analysis when obvious causes of nephrolithiasis are unclear and highlights the concerns of using over-the-counter supplements without substantial oversight. Am J Kidney Dis 54:127-130. (c) 2009 by the National Kidney Foundation, Inc.
C1 [Watnick, Suzanne] Portland VA Med Ctr, P3NEPH, Div Hosp & Specialty Med, Portland, OR 97239 USA.
[Rueda, Jose F.; Watnick, Suzanne] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97201 USA.
[Riscoe, Michael K.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA.
RP Watnick, S (reprint author), Portland VA Med Ctr, P3NEPH, Div Hosp & Specialty Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM suzanne.watnick@va.gov
NR 27
TC 4
Z9 5
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUL
PY 2009
VL 54
IS 1
BP 127
EP 130
DI 10.1053/j.ajkd.2008.10.042
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 499JC
UT WOS:000270214400020
PM 19100669
ER
PT J
AU Patel, TV
Rennke, HG
Sloan, JM
DeAngelo, DJ
Charytan, DM
AF Patel, Tejas V.
Rennke, Helmut G.
Sloan, J. Mark
DeAngelo, Daniel J.
Charytan, David M.
TI A Forgotten Cause of Kidney Injury in Chronic Myelomonocytic Leukemia
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Leukemia; renal failure; lysozyme; proteinuria; cation
ID NEPHROTIC SYNDROME; LYSOZYME MURAMIDASE; PROGNOSTIC-FACTORS;
RENAL-FAILURE; PATIENT; SERUM; PROTEINURIA; DYSFUNCTION; DAUNOMYCIN;
AGENT
C1 [Charytan, David M.] Brigham & Womens Hosp, Div Renal, Ctr Clin Biometr, Boston, MA 02120 USA.
[Rennke, Helmut G.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02120 USA.
[Sloan, J. Mark; DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Charytan, DM (reprint author), Brigham & Womens Hosp, Div Renal, Ctr Clin Biometr, 1620 Tremont St, Boston, MA 02120 USA.
EM dcharytan@partners.org
OI Sloan, John/0000-0001-7069-4528
FU National Institutes of Health [T32-DK07527-23]
FX This, work was Supported by National Institutes of Health Grant
T32-DK07527-23 to Dr Patel.
NR 28
TC 9
Z9 9
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUL
PY 2009
VL 54
IS 1
BP 159
EP 164
DI 10.1053/j.ajkd.2008.11.013
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 499JC
UT WOS:000270214400024
PM 19185401
ER
PT J
AU Hendricks, AE
Latourelle, JC
Lunetta, KL
Cupples, LA
Wheeler, V
MacDonald, ME
Gusella, JF
Myers, RH
AF Hendricks, Audrey E.
Latourelle, Jeanne C.
Lunetta, Kathryn L.
Cupples, L. Adrienne
Wheeler, Vanessa
MacDonald, Marcy E.
Gusella, James F.
Myers, Richard H.
TI Estimating the Probability of de novo HD Cases From Transmissions of
Expanded Penetrant CAG Alleles in the Huntington Disease Gene From Male
Carriers of High Normal Alleles (27-35 CAG)
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Huntington disease; high normal alleles; intermediate alleles; mutable
normal alleles; genetic counseling; de novo
ID 29 TRINUCLEOTIDE REPEATS; INTERMEDIATE ALLELES; PARKINSONS-DISEASE;
INSTABILITY; ONSET; AGE; CHROMOSOMES; MECHANISMS; MUTATION; SIZE
AB Huntington disease (HD) is a dominantly transmitted neurodegenerative disorder that arises from expansion of a CAG trinucleotide repeat on chromosome4p16.3. CAG repeat allele lengths are defined as fully penetrant at >= 40, reduced penetrance at 36-39, high normal at 27-35, and normal at <= 26. Fathers, but not mothers, with high normal alleles are at risk of transmitting potentially penetrant HD alleles (>= 36) to offspring. We estimated the conditional probability of an offspring inheriting an expanded penetrant allele given a father with a high normal allele by applying probability definitions and rules to estimates of HD incidence, paternal birth rate, frequency of de novo HD, and frequency of high normal alleles in the general population. The estimated probability that a male high normal allele carrier will have an offspring with an expanded penetrant allele ranges from 1/6,241 to 1/951. These estimates may be useful in genetic counseling for male high normal allele carriers. (C) 2009 Wiley-Liss, Inc.
C1 [Hendricks, Audrey E.; Lunetta, Kathryn L.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Wheeler, Vanessa; MacDonald, Marcy E.; Gusella, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
RP Hendricks, AE (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.
EM baera@bu.edu
RI Hendricks, Audrey/I-4127-2016;
OI Hendricks, Audrey/0000-0002-7152-0287; Latourelle,
Jeanne/0000-0002-4218-9572; Lunetta, Kathryn/0000-0002-9268-810X;
Cupples, L. Adrienne/0000-0003-0273-7965; Myers,
Richard/0000-0002-8365-2674
FU Huntington's Disease Center Without walls [P50 NS 16367]; Jerry
MacDonald HD research fund; Huntington's Disease Society of America;
Massachusetts Huntington's Disease Society of America; HDSA; HDSA
[NS049206]; NIH NCRR [ISIORR163736-OIAI]
FX This study was supported by P50 NS 16367 "Huntington's Disease Center
Without walls," the Jerry MacDonald HD research fund, the Huntington's
Disease Society of America, the Massachusetts Huntington's Disease
Society of America, the HDSA Coalition for the Cure, and by NINDS
NS049206. This research was conducted using the Boston University Linux
Cluster for Genetic Analysis (LinGA) funded by the NIH NCRR (National
Center for Research Resources) Shared Instrurrientation grant
(ISIORR163736-OIAI).
NR 27
TC 20
Z9 20
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUL
PY 2009
VL 149A
IS 7
BP 1375
EP 1381
DI 10.1002/ajmg.a.32901
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 467VA
UT WOS:000267770000002
PM 19507258
ER
PT J
AU Wilhelm-Leen, ER
Hall, YN
Tamura, MK
Chertow, GM
AF Wilhelm-Leen, Emilee R.
Hall, Yoshio N.
Tamura, Manjula K.
Chertow, Glenn M.
TI Frailty and Chronic Kidney Disease: The Third National Health and
Nutrition Evaluation Survey
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Body composition; Chronic kidney disease; Frailty
ID GLOMERULAR-FILTRATION-RATE; FUNCTIONAL DECLINE; DIALYSIS PATIENTS; SERUM
CREATININE; OLDER-ADULTS; PREDICTION; WOMEN
AB BACKGROUND: Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease.
METHODS: We used data from the Third National Health and Nutrition Examination Survey to estimate the prevalence of frailty among persons with chronic kidney disease. We created a definition of frailty based on established validated criteria, modified to accommodate available data. We used logistic regression to determine whether and to what degree stages of chronic kidney disease were associated with frailty. We also examined factors that might mediate the association between frailty and chronic kidney disease.
RESULTS: The overall prevalence of frailty was 2.8%. However, among persons with moderate to severe chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m(2)), 20.9% were frail. The odds of frailty were significantly increased among all stages of chronic kidney disease, even after adjustment for the residual effects of age, sex, race, and prevalent chronic diseases. The odds of frailty associated with chronic kidney disease were only marginally attenuated with additional adjustment for sarcopenia, anemia, acidosis, inflammation, vitamin D deficiency, hypertension, and cardiovascular disease. Frailty and chronic kidney disease were independently associated with mortality.
CONCLUSION: Frailty is significantly associated with all stages of chronic kidney disease and particularly with moderate to severe chronic kidney disease. Potential mechanisms underlying the chronic kidney disease and frailty connection remain elusive. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 664-671
C1 [Wilhelm-Leen, Emilee R.; Tamura, Manjula K.; Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Dept Med, Palo Alto, CA 94304 USA.
[Hall, Yoshio N.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA.
[Hall, Yoshio N.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Wilhelm-Leen, ER (reprint author), Stanford Univ, Sch Med, Div Nephrol, Dept Med, 780 Welch Rd,Suite 106, Palo Alto, CA 94304 USA.
EM ewilhelm@stanford.edu
RI Kurella Tamura, Manjula/C-8284-2014
OI Kurella Tamura, Manjula/0000-0001-5227-2479
FU Stanford University School of Medicine Medical Scholars Program
FX This research was funded by a grant from the Stanford University School
of Medicine Medical Scholars Program.
NR 23
TC 104
Z9 107
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUL
PY 2009
VL 122
IS 7
BP 664
EP U86
DI 10.1016/j.amjmed.2009.01.026
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 462HF
UT WOS:000267341000014
PM 19559169
ER
PT J
AU Choi, AI
Rodriguez, RA
Bacchetti, P
Bertenthal, D
Hernandez, GT
O'Hare, AM
AF Choi, Andy I.
Rodriguez, Rudolph A.
Bacchetti, Peter
Bertenthal, Daniel
Hernandez, German T.
O'Hare, Ann M.
TI White/Black Racial Differences in Risk of End-stage Renal Disease and
Death
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Kidney disease; Mortality; Racial disparities
ID CHRONIC KIDNEY-DISEASE; OF-VETERANS-AFFAIRS; UNITED-STATES;
ETHNIC-DIFFERENCES; AFRICAN-AMERICAN; MORTALITY; PREVALENCE;
STRATIFICATION; BENEFICIARIES; ASCERTAINMENT
AB BACKGROUND: End-stage renal disease disproportionately affects black persons, but it is unknown when in the course of chronic kidney disease racial differences arise. Understanding the natural history of racial differences in kidney disease may help guide efforts to reduce disparities.
METHODS: We compared white/black differences in the risk of end-stage renal disease and death by level of estimated glomerular filtration rate (eGFR) at baseline in a national sample of 2,015,891 veterans between 2001 and 2005.
RESULTS: Rates of end-stage renal disease among black patients exceeded those among white patients at all levels of baseline eGFR. The adjusted hazard ratios for end-stage renal disease associated with black versus white race for patients with an eGFR >= 90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73m(2), respectively, were 2.14 (95% confidence interval [CI], 1.72-2.65), 2.30 (95% CI, 2.02-2.61), 3.08 (95% CI, 2.74-3.46), 2.47 (95% CI, 2.26-2.70), 1.86 (95% CI, 1.75-1.98), and 1.23 (95% CI, 1.12-1.34). We observed a similar pattern for mortality, with equal or higher rates of death among black persons at all levels of eGFR. The highest risk of mortality associated with black race also was observed among those with an eGFR 45-59 mL/min/1.73m(2) (hazard ratio 1.32, 95% CI, 1.27-1.36).
CONCLUSION: Racial differences in the risk of end-stage renal disease appear early in the course of kidney disease and are not explained by a survival advantage among blacks. Efforts to identify and slow progression of chronic kidney disease at earlier stages may be needed to reduce racial disparities. Published by Elsevier Inc. The American Journal of Medicine (2009) 122, 672-678
C1 [Choi, Andy I.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA.
[Rodriguez, Rudolph A.; O'Hare, Ann M.] Univ Washington, Seattle, WA 98195 USA.
[Rodriguez, Rudolph A.; O'Hare, Ann M.] VA Puget Sound Healthcare Syst, Dept Med, Seattle, WA USA.
[Choi, Andy I.; Bacchetti, Peter] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Bertenthal, Daniel] San Francisco VA Med Ctr, VA Res Enhancement Award Program, San Francisco, CA USA.
[Hernandez, German T.] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Med, El Paso, TX USA.
RP Choi, AI (reprint author), San Francisco VA Med Ctr, Dept Med, Box 111J,4150 Clement St, San Francisco, CA 94121 USA.
EM andy.choi@ucsf.edu
FU National Kidney Foundation; National Institutes of Health
[K23DK080645-01A1, K23AG028980-03, R01AI069952-03]; W. K. Kellogg
Scholars in Health Disparities Program; Paso del Norte Health
Foundation's Center for Border Health Research; San Francisco VA
Research Enhancement Award Program
FX This study was supported by a fellowship grant from the National Kidney
Foundation, grants from the National Institutes of Health
(K23DK080645-01A1, K23AG028980-03, R01AI069952-03), W. K. Kellogg
Scholars in Health Disparities Program, Paso del Norte Health
Foundation's Center for Border Health Research, and the San Francisco VA
Research Enhancement Award Program to Improve Care for Older Veterans.
These funding sources had no involvement in the design or execution of
this study.
NR 38
TC 52
Z9 52
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUL
PY 2009
VL 122
IS 7
BP 672
EP 678
DI 10.1016/j.amjmed.2008.11.021
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 462HF
UT WOS:000267341000015
PM 19559170
ER
PT J
AU Stefancyk, AL
AF Stefancyk, Amanda L.
TI Safe and Reliable Care
SO AMERICAN JOURNAL OF NURSING
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA.
RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA.
EM astefancyk@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-936X
J9 AM J NURS
JI Am. J. Nurs.
PD JUL
PY 2009
VL 109
IS 7
BP 70
EP 71
PG 2
WC Nursing
SC Nursing
GA 465SO
UT WOS:000267607700020
ER
PT J
AU Minkoff, H
Ecker, J
AF Minkoff, Howard
Ecker, Jeffrey
TI The California octuplets and the duties of reproductive endocrinologists
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
DE assisted reproductive technology; ethics; octuplets; reproductive
endocrinology
AB The recent birth of octuplets unleashed a firestorm of publicity, casting a harsh light on the mother and her presumed inadequacies as a parent. It also raised questions about the role of reproductive endocrinologists. Herein we consider 3 aspects of this question: should reproductive endocrinologists consider the economic interests of society, should they consider parenting abilities, and should the number of embryos transferred be limited? We conclude that the ethical obligation of reproductive endocrinologists does not extend to protection of society's economic interests; that reproductive endocrinologists, although poorly trained and situated to gauge an individual's ability to parent, can in extreme circumstances refuse to provide assisted reproductive technology; and that a firm limit on the number of transferred embryos is ethically and medically appropriate.
C1 [Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA.
[Minkoff, Howard] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Ecker, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA.
RP Minkoff, H (reprint author), Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA.
NR 6
TC 2
Z9 2
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUL
PY 2009
VL 201
IS 1
AR 15.e1
DI 10.1016/j.ajog.2009.04.053
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 465PM
UT WOS:000267599300006
PM 19576370
ER
PT J
AU Masoud, MI
Masoud, I
Kent, RL
Gowharji, N
Hassan, AH
Cohen, LE
AF Masoud, Mohamed I.
Masoud, Ibrahim
Kent, Ralph L., Jr.
Gowharji, Nour
Hassan, Ali H.
Cohen, Laurie E.
TI Relationship between blood-spot insulin-like growth factor 1 levels and
hand-wrist assessment of skeletal maturity
SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS
LA English
DT Article
ID FILTER-PAPER; FACTOR-I; IGF-I; HEALTHY-CHILDREN; FACIAL GROWTH; BODY
HEIGHT; BONE-GROWTH; HORMONE; SOMATOMEDIN; MATURATION
AB Introduction: Accurate prediction of the timing of the pubertal growth spurt and the amount of remaining growth are factors that affect treatment decisions in orthodontics, orthognathic surgery, and dental implantology. For many years, medical and dental professionals have considered hand-wrist radiographs the method of choice for the assessment of skeletal maturity. Insulin-like growth factor 1 (IGF-1) mirrors growth hormone levels and is used by endocrinologists to diagnose growth hormone disturbances. Methods: The objective of this study was to establish a relationship between IGF-1 levels collected from blood-spot samples and hand-wrist radiographs at various skeletal stages. Eighty-four subjects (45 female, 39 male) between the ages of 5 and 25 were included in the study. Each subject had personal information, a hand-wrist radiograph, and a blood-spot sample collected on the same day. Results: The IGF-1 levels were highest at the hand-wrist skeletal stages that were previously associated with the greatest amount of mandibular growth. These levels were significantly higher than at prepuburtal and postpubertal stages. In the postpubertal group, the IGF-1 levels were lower as the subjects' ages increased and they moved away from the onset of puberty. Conclusions: Longitudinal data are necessary to confirm the usefulness of this technique in predicting the timing, the intensity, and the end of the growth spurt. (Am J Orthod Dentofacial Orthop 2009; 136: 59-64)
C1 [Hassan, Ali H.] King Abdulaziz Univ, Div Orthodont, Jeddah 21413, Saudi Arabia.
[Masoud, Mohamed I.] Dent Specialty Clin, Jeddah, Saudi Arabia.
[Kent, Ralph L., Jr.] Forsyth Inst, Boston, MA USA.
[Masoud, Mohamed I.; Kent, Ralph L., Jr.] Harvard Univ, Sch Dent Med, Dept Oral Epidemiol & Hlth Policy, Boston, MA 02115 USA.
[Cohen, Laurie E.] Childrens Hosp, Neuroendocrinol Program, Boston, MA 02115 USA.
RP Masoud, MI (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Epidemiol & Hlth Policy, 188 Longwood Ave,REB 402, Boston, MA 02115 USA.
EM masoudortho@gmail.com
RI Hassan, Ali/A-3007-2013
OI Hassan, Ali/0000-0002-6132-862X
NR 45
TC 7
Z9 7
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0889-5406
EI 1097-6752
J9 AM J ORTHOD DENTOFAC
JI Am. J. Orthod. Dentofac. Orthop.
PD JUL
PY 2009
VL 136
IS 1
BP 59
EP 64
DI 10.1016/j.ajodo.2007.07.023
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 466WR
UT WOS:000267695500019
PM 19577149
ER
PT J
AU Au, P
Tam, J
Duda, DG
Lin, PC
Munn, LL
Fukumura, D
Jain, RK
AF Au, Patrick
Tam, Joshua
Duda, Dan G.
Lin, Pei-Chun
Munn, Lance L.
Fukumura, Dai
Jain, Rakesh K.
TI Paradoxical Effects of PDGF-BB Overexpression in Endothelial Cells on
Engineered Blood Vessels In Vivo
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID GROWTH-FACTOR; VASCULAR-PERMEABILITY; MOLECULAR REGULATION;
ANGIOGENESIS; VEGF; PERICYTES; DIFFERENTIATION; EXPRESSION; MATURATION;
MONOCYTES
AB Therapeutic revascularization with either exogenous angiogenic growth factors or vascular cells has yet to demonstrate efficacy in the clinic. Injection of angiogenic growth factors often produces unstable and abnormal blood vessels. Blood vascular networks derived from implanted endothelial cells persist only transiently due to the insufficient recruitment of perivascular cells. We hypothesize that a combination of the two approaches may act synergistically to yield a better result. To enhance the recruitment of perivascular cells, human umbilical vein endothelial cells were genetically modified to overexpress platelet-derived growth factor (PDGF)-BB. PDGF-BB overexpression promoted both proliferation and migration of perivascular precursor cells (10T1/2 cells) in vitro. When mock-infected endothelial cells were implanted alone in vivo, they formed transient blood vascular networks that regressed by day 30. PDGF-BB overexpression enhanced the survival of endothelial cells in vivo. However, the PDGF-BB-expressing vessel network failed to establish patent blood flow. Co-implantation of PDGF-BB-overexpressing endothelial cells with 10T1/2 cells paradoxically resulted in the rapid regression of the vascular networks in vivo. PDGF-BB stimulated the expression of both chemokine (C-C motif) ligand 2 (CCL2) and CCL7 in 10T1/2 cells and led to the increased accumulation of macrophages in vivo. These results suggest a potential negative interaction between angiogenic growth factors and vascular cells; their use in combination should be carefully tested in vivo for such opposing effects. (Am J Pathol 2009, 175:294-302; DOI: 10.2353/ajpath.2009.080887)
C1 [Au, Patrick; Tam, Joshua; Duda, Dan G.; Lin, Pei-Chun; Munn, Lance L.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA.
[Au, Patrick; Tam, Joshua] MIT, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA.
RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, 100 Blossom St,Cox 7, Boston, MA 02114 USA.
EM jain@steele.mgh.harvard.edu
RI Lin, Pei-Chun/A-3200-2013; Munn, Lance/L-3950-2016
OI Munn, Lance/0000-0003-0698-7232
FU American Heart Association Predoctoral Fellowship; National Institutes
of Health [P01-CA80124, R01-CA96915, R01-CA115767, R01-CA126642,
R01CA85140]; Federal Share/NCI Proton Beam Program Income Grants
FX Supported in part by American Heart Association Predoctoral Fellowship
(PA) and National Institutes of Health grants P01-CA80124 (RKJ, DF),
R01-CA96915 (DIF), R01-CA115767 (RKJ), R01-CA126642 (RKJ), R01CA85140
(RKJ), and Federal Share/NCI Proton Beam Program Income Grants (RKJ,
DGD).
NR 33
TC 21
Z9 23
U1 1
U2 3
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUL
PY 2009
VL 175
IS 1
BP 294
EP 302
DI 10.2353/ajpath.2009.080887
PG 9
WC Pathology
SC Pathology
GA 464MG
UT WOS:000267508600027
PM 19477947
ER
PT J
AU Dicianno, BE
Gaines, A
Collins, DM
Lee, S
AF Dicianno, Brad E.
Gaines, Anna
Collins, Diane M.
Lee, Shannon
TI Mobility, Assistive Technology Use, and Social Integration Among Adults
with Spina Bifida
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Depression; Rehabilitation; Socialization; Spinal Dysraphism; Self-Help
Devices; Walking; Wheelchairs
ID QUALITY-OF-LIFE; YOUNG-ADULTS; FUNCTIONAL INDEPENDENCE; CORD-INJURY;
ADOLESCENTS; MENINGOMYELOCELE; HYDROCEPHALUS; DETERMINANTS; CHILDREN;
MYELOMENINGOCELE
AB Objective: Many individuals with spina bifida have impairments that limit mobility and functional independence. Sedentary lifestyles and social isolation are very prevalent. This study evaluated the association between the use of mobility devices and degree of socialization.
Design: A retrospective chart review was performed on 208 adults with spina bifida attending a university-based clinic. Data collected included the Craig Handicap Assessment Reporting Technique-Short Form, Beck Depression Inventory, and data on wheelchair and other assistive technology use. We hypothesized that community and home mobility and social Integration, as measured by the Craig Handicap Assessment Reporting Technique-Short Form, would be lower for manual and power wheelchair users than for ambulators, regardless of depression scores or shunt history.
Results: We found that individuals with spina bifida who used both manual and power wheelchairs do have lower daily home and community activity levels compared with ambulators, but that most individuals with spina bifida have low social integration and economic self-sufficiency scores, regardless of whether they can ambulate or use wheelchairs. These findings were not explained by wheelchair quality because most were prescribed high-quality devices. A high prevalence of depression was also found.
Conclusions: Special considerations for wheelchair provision are discussed. Additional research is needed to identify other barriers to social integration.
C1 [Dicianno, Brad E.; Gaines, Anna; Collins, Diane M.; Lee, Shannon] Univ Pittsburgh, Human Engn Res Labs, Pittsburgh, PA 15260 USA.
[Dicianno, Brad E.; Collins, Diane M.] Univ Pittsburgh, Adult Spina Bifida Clin, Pittsburgh, PA 15260 USA.
[Dicianno, Brad E.; Collins, Diane M.; Lee, Shannon] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA.
[Dicianno, Brad E.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA.
[Dicianno, Brad E.; Gaines, Anna] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
[Dicianno, Brad E.; Collins, Diane M.] Ctr Excellence Wheelchairs & Associated Rehabil E, VA Pittsburgh HealthCare Syst, Pittsburgh, PA USA.
RP Dicianno, BE (reprint author), Suite 202 Kaufmann Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA.
OI Dicianno, Brad/0000-0003-0738-0192
NR 37
TC 20
Z9 20
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD JUL
PY 2009
VL 88
IS 7
BP 533
EP 541
DI 10.1097/PHM.0b013e3181aa41d4
PG 9
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 463CO
UT WOS:000267406400002
PM 19542778
ER
PT J
AU Larauche, M
Gourcerol, G
Wang, LX
Pambukchian, K
Brunnhuber, S
Adelson, DW
Rivier, J
Million, M
Tache, Y
AF Larauche, Muriel
Gourcerol, Guillaume
Wang, Lixin
Pambukchian, Karina
Brunnhuber, Stefan
Adelson, David W.
Rivier, Jean
Million, Mulugeta
Tache, Yvette
TI Cortagine, a CRF1 agonist, induces stresslike alterations of colonic
function and visceral hypersensitivity in rodents primarily through
peripheral pathways
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE CRF1 agonist; colonic motility; visceral pain; rat; mice; colonic
permeability; astressin; CP-154,526
ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; FACTOR
SIGNALING PATHWAYS; FACTOR-RELATED PEPTIDES; ENTERIC NERVOUS-SYSTEM;
COLORECTAL DISTENSION; RECEPTOR ANTAGONIST; MOTOR FUNCTION; MAST-CELLS;
RAT COLON
AB Larauche M, Gourcerol G, Wang L, Pambukchian K, Brunnhuber S, Adelson DW, Rivier J, Million M, Tache Y. Cortagine, a CRF1 agonist, induces stresslike alterations of colonic function and visceral hypersensitivity in rodents primarily through peripheral pathways. Am J Physiol Gastrointest Liver Physiol 297: G215-G227, 2009. First published April 30, 2009; doi:10.1152/ajpgi.00072.2009.-Corticotropin-releasing factor (CRF) 1 receptor (CRF1) activation in the brain is a core pathway orchestrating the stress response. Anatomical data also support the existence of CRF signaling components within the colon. We investigated the colonic response to intraperitoneal (ip) injection of cortagine, a newly developed selective CRF1 peptide agonist. Colonic motor function and visceral motor response (VMR) were monitored by using a modified miniaturized pressure transducer catheter in adult conscious male Sprague-Dawley rats and C57Bl/6 mice. Colonic permeability was monitored by the Evans blue method and myenteric neurons activation by Fos immunohistochemistry. Compared with vehicle, cortagine (10 mu g/kg ip) significantly decreased the distal colonic transit time by 45% without affecting gastric transit, increased distal and transverse colonic contractility by 35.6 and 66.2%, respectively, and induced a 7.1-fold increase in defecation and watery diarrhea in 50% of rats during the first hour postinjection whereas intracerebroventricular (icv) cortagine (3 mu g/rat) had lesser effects. Intraperitoneal (ip) cortagine also increased colonic permeability, activated proximal and distal colonic myenteric neurons, and induced visceral hypersensitivity to a second set of phasic colorectal distention (CRD). The CRF antagonist astressin (10 mu g/kg ip) abolished ip cortagine-induced hyperalgesia whereas injected icv it had no effect. In mice, cortagine (30 mu g/kg ip) stimulated defecation by 7.8-fold, induced 60% incidence of diarrhea, and increased VMR to CRD. Stresslike colonic alterations induced by ip cortagine in rats and mice through restricted activation of peripheral CRF1 receptors support a role for peripheral CRF1 signaling as the local arm of the colonic response to stress.
C1 [Larauche, Muriel; Gourcerol, Guillaume; Wang, Lixin; Pambukchian, Karina; Brunnhuber, Stefan; Adelson, David W.; Million, Mulugeta; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA USA.
[Larauche, Muriel; Gourcerol, Guillaume; Wang, Lixin; Pambukchian, Karina; Brunnhuber, Stefan; Adelson, David W.; Million, Mulugeta; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Neurobiol Stress,Dept Med, Los Angeles, CA 90095 USA.
[Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Rivier, Jean] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA USA.
RP Larauche, M (reprint author), W Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 111, Los Angeles, CA 90073 USA.
EM mlarauche@mednet.ucla.edu
OI Larauche, Muriel/0000-0003-3320-3675; Adelson, David/0000-0002-4623-6030
FU VA Career Scientist Award; National Institute of Diabetes and Digestive
and Kidney Diseases [R01 DK-57238, DK-33061, P50 DK-64539, DK AM 41301,
DK PO1-26741, DK-068155, T32 DK07180-3255]; French Society of
Gastroenterology (SNFGE)
FX The research was supported by a VA Career Scientist Award (Y. Tache),
National Institute of Diabetes and Digestive and Kidney Diseases Grants
R01 DK-57238 and DK-33061 (Y. Tache), P50 DK-64539 (Emeran Mayer), DK AM
41301 (Animal Model Core, Y. Tache), DK PO1-26741 (J. Rivier), DK-068155
(M. Million), T32 DK07180-32 (M. Larauche), and the French Society of
Gastroenterology (SNFGE; G. Gourcerol).
NR 67
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U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD JUL
PY 2009
VL 297
IS 1
BP G215
EP G227
DI 10.1152/ajpgi.00072.2009
PG 13
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 472RU
UT WOS:000268150500025
PM 19407218
ER
PT J
AU Nakano, T
Inoue, I
Alpers, DH
Akiba, Y
Katayama, S
Shinozaki, R
Kaunitz, JD
Ohshima, S
Akita, M
Takahashi, S
Koyama, I
Matsushita, M
Komoda, T
AF Nakano, Takanari
Inoue, Ikuo
Alpers, David H.
Akiba, Yasutada
Katayama, Shigehiro
Shinozaki, Rina
Kaunitz, Jonathan D.
Ohshima, Susumu
Akita, Masumi
Takahashi, Seiichiro
Koyama, Iwao
Matsushita, Makoto
Komoda, Tsugikazu
TI Role of lysophosphatidylcholine in brush-border intestinal alkaline
phosphatase release and restoration
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE Caco-2 cells; lipid absorption; small intestine; enzyme-labeled
fluorescence-97
ID SURFACTANT-LIKE PARTICLES; FAT; SECRETION; ABSORPTION; PROTEINS;
INHIBITION; PROTEASES; FISSION; SERUM; RATS
AB Nakano T, Inoue I, Alpers DH, Akiba Y, Katayama S, Shinozaki R, Kaunitz JD, Ohshima S, Akita M, Takahashi S, Koyama I, Matsushita M, Komoda T. Role of lysophosphatidylcholine in brush-border intestinal alkaline phosphatase release and restoration. Am J Physiol Gastrointest Liver Physiol 297: G207-G214, 2009. First published April 30, 2009; doi:10.1152/ajpgi.90590.2008.-Intestinal alkaline phosphatase (IAP) is a brush-border membrane ectoenzyme (BBM-IAP) that is released into the lumen (L-IAP) after a high-fat diet. We examined the effects of oil feeding and the addition of mixed-lipid micelles on the formation of L-IAP in oil-fed rat intestine, Caco-2 cell monolayers, and mouse intestinal loops. We localized IAP in the duodenum of rats fed corn oil using fluorescence microscopy with enzyme-labeled fluorescence-97 as substrate. Four hours after oil feeding, L-IAP increased similar to 10-fold accompanied by the loss of BBM-IAP, consistent with BBM-IAP release. Rat IAP isozyme mRNAs progressively increased 4-6 h after oil feeding, followed by the increase of IAP activity in the subapical location at 6 h, consistent with the restoration of IAP protein. Postprandial lipid-micelle components, sodium taurocholate with or without oleic acid, mono-oleylglycerol, cholesterol, or lysophosphatidylcholine (lysoPC) were applied singly or as mixed-lipid micelles to the apical surface of polarized Caco-2 cell monolayers. LysoPC increased L-IAP > 10-fold over basal release. LysoPC released IAP into the apical medium more than other intestinal brush-border enzymes, 5'-nucleotidase, sucrase, aminopeptidase N, and lactase, without comparable lactate dehydrogenase release or cell injury. LysoPC increased human IAP mRNA levels by 1.5-fold in Caco-2 cells. Luminally applied lysoPC also increased release of IAP preferentially in mouse intestinal loops. These data show that lysoPC accelerates the formation of L-IAP from BBM-IAP, followed by enhanced IAP synthesis, suggesting the role that lysoPC might play in the turnover of brush-border proteins.
C1 [Nakano, Takanari; Shinozaki, Rina; Takahashi, Seiichiro; Koyama, Iwao; Matsushita, Makoto; Komoda, Tsugikazu] Saitama Med Univ, Dept Biochem, Saitama, Japan.
[Inoue, Ikuo; Katayama, Shigehiro] Saitama Med Univ, Dept Endocrinol & Diabet, Saitama, Japan.
[Ohshima, Susumu; Akita, Masumi] Saitama Med Univ, Dept Morphol Sci, Biomed Res Ctr, Fac Med, Saitama, Japan.
[Alpers, David H.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Akiba, Yasutada; Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA.
[Nakano, Takanari; Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA.
[Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA USA.
RP Nakano, T (reprint author), W Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM nk.takanari@gmail.com
FU Japan Foundation of Applied Enzymology; NIH [DK56341, R01 DK54221];
Department of Veterans Affairs Merit Review Award
FX This work was supported in part by a grant from the Japan Foundation of
Applied Enzymology for T. Nakano, the CNRU grant from NIH, DK56341, for
partial support for D. H. Alpers, and a Department of Veterans Affairs
Merit Review Award and NIH-NIDDK R01 DK54221 for J. D. Kaunitz.
NR 34
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U1 1
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD JUL
PY 2009
VL 297
IS 1
BP G207
EP G214
DI 10.1152/ajpgi.90590.2008
PG 8
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 472RU
UT WOS:000268150500024
PM 19407215
ER
PT J
AU Mu, H
Wang, XW
Wang, H
Lin, P
Yao, QH
Chen, CY
AF Mu, Hong
Wang, Xinwen
Wang, Hao
Lin, Peter
Yao, Qizhi
Chen, Changyi
TI Lactosylceramide promotes cell migration and proliferation through
activation of ERK1/2 in human aortic smooth muscle cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE vascular smooth muscle cell; cell proliferation; oxidative stress;
extracellular signal-regulated kinase 1/2; antioxidant; vascular disease
ID ENDOTHELIAL-CELLS; PROTEIN-KINASES; ATHEROSCLEROSIS; GROWTH;
GLYCOSPHINGOLIPIDS; EXPRESSION; SELENIUM; DISEASE; ACCUMULATION;
ADHESION
AB Mu H, Wang X, Wang H, Lin P, Yao Q, Chen C. Lactosylceramide promotes cell migration and proliferation through activation of ERK1/2 in human aortic smooth muscle cells. Am J Physiol Heart Circ Physiol 297: H400-H408, 2009. First published May 22, 2009; doi: 10.1152/ajpheart.01254.2008.-Increased plasma levels of lactosylceramide (LacCer) have been associated with cardiovascular disease. However, it is largely unknown whether LacCer directly contributes to dysfunction of smooth muscle cells (SMCs), a key event in vascular lesion formation. In the present study, we determined the effects and potential mechanisms of LacCer on cell migration and proliferation in human aortic SMCs (AoSMCs). Cell migration and proliferation were determined by a modified Boyden chamber assay and nonradioactive colorimetric (MTS) assay, respectively. We found that LacCer significantly induced AoSMC migration and proliferation in a concentration- and time-dependent manner. In addition, LacCer significantly upregulated the expression of PDGFR-B, integrins (alpha(v) and beta(3)), and matrix metalloproteinases (matrix metalloproteinase-1 and -2) at both mRNA and protein levels, as determined by real-time PCR and Western blot analyses, respectively. Furthermore, LacCer increased superoxide anion production and the transient phosphorylation of ERK1/2 in AoSMCs, as determined by dihydroethidium staining and immunoassay, respectively. Accordingly, LacCer-induced cell migration and proliferation were effectively blocked by antioxidants (seleno-L-methionine and Mn tetrakis porphyrin) and by a specific ERK1/2 inhibitor. Thus, LacCer promotes cell migration and proliferation through oxidative stress and activation of ERK1/2 in AoSMCs. These findings demonstrate the functional role of LacCer in the vascular disease pathogenesis.
C1 [Mu, Hong; Wang, Xinwen; Wang, Hao; Lin, Peter; Yao, Qizhi; Chen, Changyi] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Mol Surg Res Ctr, Houston, TX 77030 USA.
[Lin, Peter; Yao, Qizhi; Chen, Changyi] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
RP Chen, CY (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg MARB413, 1 Baylor Plaza,Mail Stop BCM390, Houston, TX 77030 USA.
EM jchen@bcm.tmc.edu
FU Baylor College of Medicine and Michael E. DeBakey Veterans Affairs
Medical Center
FX This work was partially supported by the Baylor College of Medicine and
Michael E. DeBakey Veterans Affairs Medical Center (Houston, TX).
NR 34
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U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUL
PY 2009
VL 297
IS 1
BP H400
EP H408
DI 10.1152/ajpheart.01254.2008
PG 9
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 464GI
UT WOS:000267492900047
PM 19465542
ER
PT J
AU Kolliputi, N
Waxman, AB
AF Kolliputi, Narasaiah
Waxman, Aaron B.
TI IL-6 cytoprotection in hyperoxic acute lung injury occurs via
PI3K/Akt-mediated Bax phosphorylation
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE apoptosis; mitochondria; endothelial cells; JNK; cytokine; Bcl-2
ID DRUG-INDUCED APOPTOSIS; TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELLS;
MITOCHONDRIAL TRANSLOCATION; SIGNAL-TRANSDUCTION; INDUCED ACTIVATION;
MULTIPLE-MYELOMA; INTERLEUKIN-6; DEATH; PROTECTS
AB Kolliputi N, Waxman AB. IL-6 cytoprotection in hyperoxic acute lung injury occurs via PI3K/Akt-mediated Bax phosphorylation. Am J Physiol Lung Cell Mol Physiol 297: L6-L16, 2009. First published April 17, 2009; doi: 10.1152/ajplung. 90381.2008.-IL-6 overexpression protects mice from hyperoxic acute lung injury in vivo, and treatment with IL-6 protects cells from oxidant-mediated death in vitro. The mechanisms of protection, however, are not clear. We characterized the expression, localization, and regulation of Bax, a proapoptotic member of the Bcl-2 family, in wild-type (WT) and IL-6 lung-specific transgenic (Tg(+)) mice exposed to 100% O(2) and in human umbilical vein endothelial cells (HUVEC) treated with H(2)O(2) and IL-6. In control HUVEC treated with H(2)O(2) or in WT mice exposed to 100% O(2), a marked induction of Bax translocation and dimerization was associated with increased JNK and p38 kinase activity. In contrast, specific JNK or p38 kinase inhibitors or treatment with IL-6 inhibited Bax mitochondrial translocation and apoptosis of HUVEC. IL-6 Tg(+) mice exposed to 100% O(2) exhibited enhanced phosphatidylinositol 3-kinase (PI3K)/Akt kinase and increased serine phosphorylation of Bax at Ser184 compared with WT mice. The PI3K-specific inhibitor LY-2940002 blocked this IL-6-induced Bax phosphorylation and promoted cell death. Furthermore, IL-6 potently blocked hyperoxia-or oxidant-induced Bax insertion into mitochondrial membranes. Thus IL-6 functions in a cytoprotective manner, in part, by suppressing Bax translocation and dimerization through PI3K/Akt-mediated Bax phosphorylation.
C1 [Kolliputi, Narasaiah; Waxman, Aaron B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA.
RP Waxman, AB (reprint author), 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA.
EM ABWaxman@Partners.org
RI Kolliputi, Narasaiah/I-6050-2012
OI Kolliputi, Narasaiah/0000-0002-2654-1900
FU National Heart, Lung, and Blood Institute [RO1 HL-074859]
FX This work was supported by National Heart, Lung, and Blood Institute
Grant RO1 HL-074859 (to A. B. Waxman).
NR 44
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U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD JUL
PY 2009
VL 297
IS 1
BP L6
EP L16
DI 10.1152/ajplung.90381.2008
PG 11
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 474ID
UT WOS:000268276100002
PM 19376889
ER
PT J
AU Bhargava, P
AF Bhargava, Pankaj
TI VEGF kinase inhibitors: how do they cause hypertension?
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE neoangiogenesis; side effects; cancer
ID ENDOTHELIAL GROWTH-FACTOR; ADVANCED SOLID TUMORS; RENAL-CELL CARCINOMA;
PHASE-I; BLOOD-PRESSURE; ANGIOGENESIS INHIBITION; CAPILLARY RAREFACTION;
TYROSINE KINASE; FACTOR RECEPTOR; NITRIC-OXIDE
AB Bhargava P. VEGF kinase inhibitors: how do they cause hypertension?. Am J Physiol Regul Integr Comp Physiol 297: R1-R5, 2009. First published May 13, 2009; doi:10.1152/ajpregu.90502.2008.-Neoangiogenesis is a critical phenomenon enabling the growth and metastasis of tumors, and inhibitors of neoangiogenesis have been recently added to the armamentarium of anticancer therapies available for clinical use. Dysregulated signaling through the vascular endothelial growth factor ( VEGF) pathway has been implicated as a key mediator of neoangiogenesis in tumors. Agents that block signaling through the VEGF pathway demonstrated tumor shrinkage in preclinical models and were therefore developed as anticancer therapies for use in humans. VEGF kinase inhibitors are being used in the treatment of a wide variety of cancers, and recent studies have shown that patients will likely require long-term treatment with these agents. Hypertension has emerged as a frequent side effect associated with agents that block signaling through the VEGF pathway. A thorough understanding of the mechanisms underlying hypertension is crucial to developing appropriate therapeutic strategies for treating hypertension associated with VEGF kinase inhibitors. Several recent studies have advanced our understanding of the pathophysiology of hypertension associated with VEGF kinase inhibitors and will be the subject of this review.
C1 [Bhargava, Pankaj] AVEO Pharmaceut, Clin Res, Cambridge, MA 02139 USA.
[Bhargava, Pankaj] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA.
RP Bhargava, P (reprint author), AVEO Pharmaceut, Clin Res, 75 Sidney St,4th Fl, Cambridge, MA 02139 USA.
EM pbhargava@aveopharma.com
NR 52
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U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
EI 1522-1490
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD JUL
PY 2009
VL 297
IS 1
BP R1
EP R5
DI 10.1152/ajpregu.90502.2008
PG 5
WC Physiology
SC Physiology
GA 467CO
UT WOS:000267714300001
PM 19439616
ER
PT J
AU Ehrenkranz, PD
Pagan, JA
Begier, EM
Linas, BP
Madison, K
Armstrong, K
AF Ehrenkranz, Peter D.
Pagan, Jose A.
Begier, Elizabeth M.
Linas, Benjamin P.
Madison, Kristin
Armstrong, Katrina
TI Written Informed-Consent Statutes and HIV Testing
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID HEALTH-CARE SETTINGS; UNITED-STATES; PUBLIC-HEALTH; COST-EFFECTIVENESS;
EPIDEMIC; RISK; EXCEPTIONALISM; PHYSICIANS; EMERGENCY; END
AB Background: Almost 1 million Americans are infected with HIV, yet it is estimated that as many as 250,000 of them do not know their serostatus. This study examined whether people residing in states with statutes requiring written informed consent prior to HIV testing were less likely to report a recent HIV test.
Methods: The study is based on survey data from the 2004 Behavioral Risk Factor Surveillance System. Logistic regression was used to assess the association between residence in a state with a pre-test written informed-consent requirement and individual self-report of recent HIV testing. The regression analyses controlled for potential state- and individual-level confounders.
Results: Almost 17% of respondents reported that they had been tested for HIV in the prior 12 months. Ten states had statutes requiring written informed consent prior to routine HIV testing; nine of those were analyzed in this study. After adjusting for other state- and individual-level factors, people who resided in these nine states were less likely to report a recent history of HIV testing (OR=0.85; 95% CI=0.80, 0.90). The average marginal effect was -0.02 (p<0.001, 95% CI=-0.03, -0.01); thus, written informed-consent statutes are associated with a 12% reduction in HIV testing from the baseline testing level of 17%. The association between a consent requirement and lack of testing was greatest among respondents who denied HIV risk factors, were non-Hispanic whites, or who had higher levels of education.
Conclusions: This study's findings suggest that the removal of written informed-consent requirements might promote the non-risk-based routine-testing approach that the Centers for Disease Control and Prevention (CDC) advocates in its new testing guidelines. (Am J Prev Med 2009;37(1):57-63) (C) 2009 American journal of Preventive Medicine
C1 [Pagan, Jose A.] Univ Texas Pan Amer, Dept Econ & Finance, Edinburg, TX 78539 USA.
[Ehrenkranz, Peter D.; Armstrong, Katrina] Univ Penn, Dept Gen Med, Philadelphia, PA 19104 USA.
[Ehrenkranz, Peter D.; Pagan, Jose A.; Madison, Kristin; Armstrong, Katrina] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Madison, Kristin] Univ Penn, Sch Law, Philadelphia, PA 19104 USA.
[Begier, Elizabeth M.] New York City Dept Hlth & Mental Hyg, New York, NY USA.
[Linas, Benjamin P.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA.
RP Pagan, JA (reprint author), Univ Texas Pan Amer, Dept Econ & Finance, 1201 W Univ Dr, Edinburg, TX 78539 USA.
EM jpagan@utpa.edu
OI Linas, Benjamin/0000-0001-9574-7075
FU Robert Wood Johnson Foundation; National Institute of Allergy and
Infectious Diseases [K01A1073193]
FX The principal investigator, Peter Ehrenkranz, MD, MPH, had full access
to all the data in the study and takes responsibility for its integrity
and the accuracy of the data analysis. None of the authors has financial
interests, relationships, or affiliations relevant to the subject of the
manuscript. The work was funded by the Robert Wood Johnson Foundation
and its support of the Clinical Scholars Program. Dr. Linas acknowledges
tile financial support of the National Institute of Allergy and
Infectious Diseases (grant number K01A1073193).
NR 40
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2009
VL 37
IS 1
BP 57
EP 63
DI 10.1016/j.amepre.2009.03.011
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 462IE
UT WOS:000267343800009
PM 19423271
ER
PT J
AU Tuerk, PW
Grubaugh, AL
Hamner, MB
Foa, EB
AF Tuerk, Peter W.
Grubaugh, Anouk L.
Hamner, Mark B.
Foa, Edna B.
TI Diagnosis and Treatment of PTSD-Related Compulsive Checking Behaviors in
Veterans of the Iraq War: The Influence of Military Context on the
Expression of PTSD Symptoms
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID EXPOSURE; DISORDER
AB This case study presents an overview of the conceptualization and treatment of two veterans of the Iraq War who presented for combat-related treatment at a Veterans Administration Medical Center. In addition to posttraumatic stress disorder (PTSD) symptoms of reexperiencing, arousal, and avoidance, the veterans exhibited compulsive checking behaviors that appear to be influenced by theater-specific combat duties and traumatic events. These cases represent what the authors believe to be an increasingly common expression of PTSD in veterans of the Iraq and Afghanistan wars. Both veterans were treated with prolonged exposure therapy, which includes imaginal and in vivo exposure to anxiety-provoking stimuli, processing of traumatic events, and self-assessment of anxiety. Treatment also included in vivo exposure with response prevention techniques borrowed from the literature on obsessive-compulsive disorder to address compulsive checking behaviors within the ecological context of each patient's symptom presentation. Measures related to PTSD and depression were obtained before, during, and after treatment. Treatment was associated with significant declines in symptom severity and improved functioning for both veterans. The unique nature of the conflict in the Middle East represents role challenges for soldiers that affect symptom presentation. Variations in symptom presentation can in turn complicate efforts to identify and appropriately address PTSD-related health concerns in this population. Thus, clinicians and researchers must remain cognizant of how theater-specific duties influence the manifestation and treatment of PTSD in order to provide optimal care to a new generation of veterans.
C1 Ralph H Johnson Vet Affairs Med Ctr, Post Traumat Stress Clin Team, Charleston, SC USA.
Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
Univ Penn, Dept Psychiat, Ctr Treatment & Study Anxiety, Philadelphia, PA 19104 USA.
RP Tuerk, PW (reprint author), Charleston VAMC, Mental Hlth 116,109 Bee St, Charleston, SC 29401 USA.
EM Tuerk@musc.edu
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U1 1
U2 6
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2009
VL 166
IS 7
BP 762
EP 767
DI 10.1176/appi.ajp.2009.08091315
PG 6
WC Psychiatry
SC Psychiatry
GA 465RF
UT WOS:000267603800007
PM 19570938
ER
PT J
AU Torriani, M
Souto, SCL
Thomas, BJ
Ouellette, H
Bredella, MA
AF Torriani, Martin
Souto, Silvio C. L.
Thomas, Bijoy J.
Ouellette, Hugue
Bredella, Miriam A.
TI Ischiofemoral Impingement Syndrome: An Entity With Hip Pain and
Abnormalities of the Quadratus Femoris Muscle
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE femur; impingement; ischium; lesser trochanter; quadratus femoris muscle
ID LESSER TROCHANTER; TEAR
AB OBJECTIVE. The purpose of this study was to describe the MRI findings of an entity in which patients present with hip pain, abnormal MR signal intensity of the quadratus femoris muscle, and narrowing of the ischiofemoral space.
MATERIALS AND METHODS. We reviewed MR images of 12 hips in nine patients with hip pain and abnormal MR signal intensity of the quadratus femoris muscle. Using axial MR images, two musculoskeletal radiologists measured the ischiofemoral and quadratus femoris spaces. We also examined changes to muscles and tendons for the presence of edema and tears. Data were compared with 11 hips in 10 control subjects. Statistical analyses determined interobserver variability and differences between groups.
RESULTS. Subjects with an abnormal quadratus femoris muscle were all women 30-71 years old ( mean age, 53 years) and had significantly narrower ischiofemoral spaces when compared with control subjects (13 +/- 5 vs 23 +/- 8 mm, respectively; p = 0.002). The quadratus femoris space was significantly narrower in affected subjects (7 +/- 3 vs 12 +/- 4 mm; p = 0.002). Abnormalities of the quadratus femoris muscle included edema (100%), partial tear (33%), and fatty infiltration (8%). The hamstring tendons of affected subjects showed evidence of edema (50%) and partial tears (25%).
CONCLUSION. Ischiofemoral impingement may represent a cause of hip pain and should be considered in cases with MR signal abnormality of quadratus femoris muscle.
C1 [Torriani, Martin; Thomas, Bijoy J.; Ouellette, Hugue; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA.
[Torriani, Martin; Thomas, Bijoy J.; Ouellette, Hugue; Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Souto, Silvio C. L.] Tesla Med Diagnost, Pelotas, Rio Grande Sul, Brazil.
RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA.
EM mtorriani@hms.harvard.edu
NR 7
TC 71
Z9 77
U1 1
U2 5
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUL
PY 2009
VL 193
IS 1
BP 186
EP 190
DI 10.2214/AJR.08.2090
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 460XS
UT WOS:000267226600025
PM 19542413
ER
PT J
AU Hariri, S
Savidge, ET
Reinold, MM
Zachazewski, J
Gill, TJ
AF Hariri, Sanaz
Savidge, Edgar T.
Reinold, Michael M.
Zachazewski, James
Gill, Thomas J.
TI Treatment of Recalcitrant Iliotibial Band Friction Syndrome With Open
Iliotibial Band Bursectomy Indications, Technique, and Clinical Outcomes
SO AMERICAN JOURNAL OF SPORTS MEDICINE
LA English
DT Article
DE iliotibial band friction syndrome; iliotibial band bursectomy;
arthroscopy; lateral knee pain
ID MR-IMAGING FINDINGS; SURGICAL-TREATMENT; RUNNERS; KNEE; MANAGEMENT
AB Background: Iliotibial band friction syndrome (ITBFS) is an overuse injury causing lateral knee pain. There is evidence that the pathological lesion is in fact an inflamed bursa underlying the iliotibial band (ITB) rather than an inflamed ITB itself.
Hypothesis: Resection of the bursa underlying the ITB in ITBFS patients will relieve their pain and allow them to return to their preinjury activity level.
Study Design: Case series; Level of evidence, 4. Methods: We describe the technique of ITB bursectomy and report a minimal 20-month follow-up of patients who had ITB bursectomies performed by a single surgeon. The patients completed a survey detailing their preoperative and postoperative symptoms and activities.
Results: The senior author performed 12 consecutive cases of ITB bursectomies (12 patients). One was excluded from the study (previous microfracture). The average age at surgery was 32 years (standard deviation, 5; range, 24-41). There were 7 men and 4 women. Postoperatively, patients were able to return to their preinjury Tegner activity levels, and the visual analog pain scores decreased by an average of 6 points (P < .001). Six patients were completely satisfied with the surgical outcome, 3 were mostly satisfied, 2 were somewhat satisfied, and none were dissatisfied. Nine of 11 patients said that knowing what they know now, they would have the surgery performed again for the same problem.
Conclusion: Iliotibial band bursectomy successfully reduces knee pain in patients with ITBFS and allows them to return to their preinjury level of activity. The great majority of patients were satisfied with the results of the procedure.
C1 [Hariri, Sanaz] Massachusetts Gen Hosp, Dept Orthopaed Surg, Div Sports Med, YCOC, Boston, MA 02114 USA.
[Savidge, Edgar T.] MGH Sports Phys Therapy, Boston, MA USA.
[Zachazewski, James] Mass Gen Rehab Serv Foxborough, Dept Phys & Occupat Therapy, Foxboro, MA USA.
RP Hariri, S (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Div Sports Med, YCOC, 55 Fruit St,Suite 3700, Boston, MA 02114 USA.
EM sanaz@post.harvard.edu
NR 28
TC 5
Z9 6
U1 0
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0363-5465
J9 AM J SPORT MED
JI Am. J. Sports Med.
PD JUL
PY 2009
VL 37
IS 7
BP 1417
EP 1424
DI 10.1177/0363546509332039
PG 8
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 464OI
UT WOS:000267514400020
PM 19286912
ER
PT J
AU Wilks, JA
Liebig, C
Tasleem, SH
Haderxhanaj, K
Lee, L
Farrow, B
Awad, S
Berger, D
Albo, D
AF Wilks, Jonathan A.
Liebig, Catherine
Tasleem, Syed H.
Haderxhanaj, Kujtim
Lee, Liz
Farrow, Buckminster
Awad, Samir
Berger, David
Albo, Daniel
TI Rectal cancer patients benefit from implementation of a dedicated
colorectal cancer center in a Veterans affairs medical center
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Cancer center; Colorectal cancer; Clinical outcomes; Rectal cancer;
Veterans
ID RANDOMIZED-TRIAL; VOLUME; OUTCOMES; SURGERY; SPECIALIZATION;
RADIOTHERAPY; QUALITY; THERAPY
AB BACKGROUND: A dedicated colorectal cancer (CRC) center was created in a Veterans Affairs Medical Center with the intent of improving quality of patient care and multidisciplinary cooperation.
METHODS: Retrospective and prospective databases before and after creation of the CRC center, respectively, were created. Patients entered in each database included those requiring surgical intervention for CRC treatment. Statistical analyses included Fisher's exact, chi-square, and unpaired Student t tests as well as analysis of variance.
RESULTS: The overall quality of care of CRC patients has improved as evidenced by a larger percentage of complete, margin-negative resections (P <.05) as well as an increase in the number of lymph nodes excised at surgery (P <.0001). Furthermore, a multidisciplinary approach is clearly beneficial as evidenced by the increased number of CRC patients receiving appropriate multidisciplinary therapy (P <.0001).
CONCLUSIONS: A dedicated CRC center has significantly improved quality of care for CRC patients. (C) 2009 Published by Elsevier Inc.
C1 [Wilks, Jonathan A.; Liebig, Catherine; Tasleem, Syed H.; Haderxhanaj, Kujtim; Lee, Liz; Farrow, Buckminster; Awad, Samir; Berger, David; Albo, Daniel] Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Houston, TX 77030 USA.
[Wilks, Jonathan A.; Liebig, Catherine; Lee, Liz; Farrow, Buckminster; Awad, Samir; Berger, David; Albo, Daniel] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA.
RP Albo, D (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Houston, TX 77030 USA.
EM dalbo@bcm.edu
NR 15
TC 9
Z9 10
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD JUL
PY 2009
VL 198
IS 1
BP 100
EP 104
DI 10.1016/j.amjsurg.2008.09.020
PG 5
WC Surgery
SC Surgery
GA 467WK
UT WOS:000267773600017
PM 19268899
ER
PT J
AU Sano, Y
Hermsen, JL
Kang, W
Gomez, FE
Lan, J
Maeshima, Y
Kudsk, KA
AF Sano, Yoshifumi
Hermsen, Joshua L.
Kang, Woodae
Gomez, F. Enrique
Lan, Jinggang
Maeshima, Yoshinori
Kudsk, Kenneth A.
TI Parenteral nutrition maintains pulmonary IgA antibody transport
capacity, but not active transport, following injury
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Mucosal immunology; Injury; Enteral nutrition; Parenteral nutrition;
Polymeric immunoglobulin receptor
ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; MAJOR ABDOMINAL-TRAUMA; SECRETORY
COMPONENT; SEPTIC MORBIDITY; MUCOSAL IMMUNITY; ROUTE; EXPRESSION;
RESPONSES; BINDING; INTESTINE
AB BACKGROUND: Parenteral nutrition (PN) increases post-trauma pneumonia versus enteral feeding. PN impairs murine immunoglobulin A (IgA) airway defenses and abrogates a normal IgA increase following injury. This work investigates the effect of type/route of nutrition on lung IgA and its transport protein, polymeric immunoglobulin receptor (pIgR), after injury.
METHODS: Catheterized mice were randomized to Chow or PN for 5 days and sacrificed without injury (Chow: n = 12; PN n = 11), or 8 hours after laparotomy + neck incisions (Chow-injury: n = 11, PN-injury: n = 13). Bronchoalveolar lavage (BAL) and lung IgA levels were analyzed by enzyme-linked immunosorbent assay (ELISA) and lung pIgR by Western blot.
RESULTS: BAL IgA levels increased in Chow-injury versus PN-injury (P <.01) with no differences in pIgR. PN-injury tissue IgA levels decreased versus Chow (P <.01), Chow-injury (P <.01), and PN (P <.05).
CONCLUSIONS: PN impairs the airway IgA response to injury but not due to impaired IgA transport capacity/pIgR level. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Sano, Yoshifumi; Hermsen, Joshua L.; Kang, Woodae; Gomez, F. Enrique; Lan, Jinggang; Maeshima, Yoshinori; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Coll Med, Madison, WI 53706 USA.
[Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA.
RP Kudsk, KA (reprint author), Univ Wisconsin, Dept Surg, Coll Med, Madison, WI 53706 USA.
EM kudsk@surgery.wisc.edu
RI Lan, Jinggang/F-1776-2011
FU National Institutes of Health [R01 GM53439]; Office of Research and
Development, Biomedical Laboratory R&D Service, Department of Veterans
Affairs
FX Supported by Grant No. R01 GM53439 from the National Institutes of
Health and based on work supported in part by the Office of Research and
Development, Biomedical Laboratory R&D Service, Department of Veterans
Affairs.
NR 32
TC 13
Z9 13
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 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD JUL
PY 2009
VL 198
IS 1
BP 105
EP 109
DI 10.1016/j.amjsurg.2008.08.018
PG 5
WC Surgery
SC Surgery
GA 467WK
UT WOS:000267773600018
PM 19249732
ER
PT J
AU Collins, LC
Martyniak, A
Kandel, MJ
Stadler, ZK
Masciari, S
Miron, A
Richardson, AL
Schnitt, SJ
Garber, JE
AF Collins, Laura C.
Martyniak, Anthony
Kandel, Michaela J.
Stadler, Zsofia K.
Masciari, Serena
Miron, Alexander
Richardson, Andrea L.
Schnitt, Stuart J.
Garber, Judy E.
TI Basal Cytokeratin and Epidermal Growth Factor Receptor Expression Are
Not Predictive of BRCA1 Mutation Status in Women With Triple-negative
Breast Cancers
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE breast cancer; basal; BRCA1 mutation; basal cytokeratins
ID IMMUNOHISTOCHEMICAL MARKERS; EPITHELIAL PHENOTYPE; ESTROGEN-RECEPTOR;
TUMORS; CARCINOMA
AB Background: Over 80% of breast cancers in women with germline BRCA1 mutations are estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-negative ("triple negative") and most of these have a basal-like phenotype by expression profiling and immunophenotypic analysis. However, whether or not expression of biomarkers characteristic of basal-like breast cancers helps to define a subset of women with triple-negative breast cancers who are likely to harbor BRCA1 mutations is an Unresolved issue.
Methods: We randomly identified 165 women from the Dana-Farber/Harvard Cancer Center SPORE annotated specimen bank with primary invasive, triple-negative breast cancers. Tissue microarrays were constructed by obtaining triplicate 0.6 mm cores from available paraffin blocks from 130 cases: only unstained slides were available for immunostaining from 35 cases. Slides cut from the tissue microarrays and the unstained slides were immunostained for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (to confirm triple-negative status) and for several markers that have been reported to be useful in defining the basal-like phenotype, including basal cytokeratins CK5/6, CK14, and CK17 and epidermal growth factor receptor (EGFR). Full sequencing analysis for BRCA1 germline mutations was performed on blood specimens from all cases. The final Study population consisted of 144 cases in which (1) triple-negative status was confirmed; (2) there was sufficient material for analysis of basal cytokeratins and EGFR; and (3) germline BRCA1 mutation status was known.
Results: Among these triple-negative breast cancer cases, 97 (67%) expressed one or more basal cytokeratins and 102 (71%) showed EGFR expression. Basal cytokeratin expression was detected in 65% of the tumor from the 20 BRCA1 mutation carriers and in 68% of the cancers from women without mutations (P = NS). EGFR expression was identified in a similar proportion of tumors from women with and without BRCA1 Mutations (75% vs. 72%, P = NS).
Conclusions: Basal cytokeratin and EGFR expression are both highly prevalent among triple-negative breast cancers. The frequency of expression of basal cytokeratins and EGFR was similar in women with and without BRCA1 mutations. Therefore, although the expression of basal cytokeratins and/or EGFR can be used to identify triple-negative breast cancers that have a basal-like phenotype, expression of these markers alone is not sufficient to distinguish which women with triple-negative breast cancers are likely to harbor BRCA1 germline mutations.
C1 [Collins, Laura C.; Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Martyniak, Anthony; Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Martyniak, Anthony; Richardson, Andrea L.] Harvard Univ, Sch Med, Boston, MA USA.
[Masciari, Serena; Miron, Alexander; Garber, Judy E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Masciari, Serena; Miron, Alexander; Garber, Judy E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Kandel, Michaela J.] Dr Horst Schmidt Klin, Klin Gynakol & Gynakol Onkol, Wiesbaden, Germany.
[Stadler, Zsofia K.] Mem Sloan Kettering Canc Ctr, Div Med Oncol, New York, NY 10021 USA.
RP Collins, LC (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
EM lcollins@bidmc.harvard.edu
FU Breast Cancer Research Foundation; Dana-Farber/Harvard Cancer Center
Specialized Program in Research Excellence in Breast Cancer
FX Supported by a grant from the Breast Cancer Research Foundation and the
Dana-Farber/Harvard Cancer Center Specialized Program in Research
Excellence in Breast Cancer.
NR 17
TC 40
Z9 41
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD JUL
PY 2009
VL 33
IS 7
BP 1093
EP 1097
PG 5
WC Pathology; Surgery
SC Pathology; Surgery
GA 471GG
UT WOS:000268043400016
PM 19390427
ER
PT J
AU Samah, B
Porcheray, F
Horellou, P
Mabondzo, A
Clayette, P
Gras, G
AF Samah, Boubekeur
Porcheray, Fabrice
Horellou, Philippe
Mabondzo, Aloise
Clayette, Pascal
Gras, Gabriel
TI Neurotrophins differently regulate glutamate transport in macrophages
and astrocytes
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Samah, Boubekeur; Gras, Gabriel] CEA, Div Immunovirol, UMR E01, Fontenay Aux Roses, France.
[Samah, Boubekeur; Gras, Gabriel] Univ Paris Sud, DSV, iMETI, SIV, Fontenay Aux Roses, France.
[Porcheray, Fabrice] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA.
[Horellou, Philippe] Univ Paris Sud, INSERM, U802, Le Kremlin Bicetre, France.
[Mabondzo, Aloise] CEA, Div Pharmacol & Immunoanal, DSV IBITEC S SPI, Saclay, France.
[Clayette, Pascal] CEA, SPI BIO, Fontenay Aux Roses, France.
RI porcheray, fabrice/B-9505-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 20
EP 20
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800063
ER
PT J
AU Rathmell, JP
AF Rathmell, James P.
TI Toward Improving the Safety of Transforaminal Injection
SO ANESTHESIA AND ANALGESIA
LA English
DT Editorial Material
ID EPIDURAL STEROID INJECTIONS; INTRAVASCULAR PENETRATION; VERTEBRAL ARTERY
C1 [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care & Pain Med, Div Pain Med, Boston, MA 02114 USA.
[Rathmell, James P.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA.
RP Rathmell, JP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,GRB 444, Boston, MA 02114 USA.
EM jrathmell@partners.org
NR 13
TC 11
Z9 11
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD JUL
PY 2009
VL 109
IS 1
BP 8
EP 10
DI 10.1213/ane.0b013e3181a81ee1
PG 3
WC Anesthesiology
SC Anesthesiology
GA 461NT
UT WOS:000267275100004
PM 19535690
ER
PT J
AU Binshtok, AM
Gerner, P
Oh, SB
Puopolo, M
Suzuki, S
Roberson, DP
Herbert, T
Wang, CF
Kim, D
Chung, G
Mitani, AA
Wang, GK
Bean, BP
Woolf, CJ
AF Binshtok, Alexander M.
Gerner, Peter
Oh, Seog Bae
Puopolo, Michelino
Suzuki, Suzuko
Roberson, David P.
Herbert, Teri
Wang, Chi-Fei
Kim, Donghoon
Chung, Gehoon
Mitani, Aya A.
Wang, Ging Kuo
Bean, Bruce P.
Woolf, Clifford J.
TI Coapplication of Lidocaine and the Permanently Charged Sodium Channel
Blocker QX-314 Produces a Long-lasting Nociceptive Blockade in Rodents
SO ANESTHESIOLOGY
LA English
DT Article
ID VANILLOID RECEPTOR TRPV1; IN-VIVO; CAPSAICIN RECEPTOR;
LOCAL-ANESTHETICS; SENSORY NEURONS; PAIN; RAT; HYPERALGESIA; NERVE; SITE
AB Background: Nociceptive-selective local anesthesia is produced by entry of the permanently charged lidocaine-derivative QX-314 into nociceptors when coadministered with capsaicin, a transient receptor potential vanilloid 1 (TRPV1) channel agonist. However, the pain evoked by capsaicin before establishment of the QX-314-mediated block would limit clinical utility. Because TRPV1 channels are also activated by lidocaine, the authors tested whether lidocaine can substitute for capsaicin to introduce QX-314 into nociceptors through TRPV1 channels and produce selective analgesia.
Methods: Lidocaine (0.5% [17.5 mM], 1% [35 mM], and 2% [70 mM]) alone, QX-314 (0.2% [5-8 mM]) alone, and a combination of the two were injected subcutaneously and adjacent to the sciatic nerve in rats and mice. Mechanical and thermal responsiveness were measured, as was motor block.
Results: Coapplication of 0.2% QX-314 with lidocaine prolonged the nociceptive block relative to lidocaine alone, an effect attenuated in TRPV1 knockout mice. The 0.2% QX-314 alone had no effect when injected intraplantary or perineurally, and it produced only weak short-lasting inhibition of the cutaneous trunci muscle reflex. Perisciatic nerve injection of lidocaine with QX-314 produced a differential nociceptive block much longer than the transient motor block, lasting 2 h (for 1% lidocaine) to 9 h (2% lidocaine). Triple application of lidocaine, QX-314, and capsaicin further increased the duration of the differential block.
Conclusions: Coapplication of lidocaine and its quaternary derivative QX-314 produces a long-lasting, predominantly nociceptor-selective block, likely by facilitating QX-314 entry through TRPV1 channels. Delivery of QX-314 into nociceptors by using lidocaine instead of capsaicin produces sustained regional analgesia without nocifensive behavior.
C1 Brigham & Womens Hosp, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA.
EM cwoolf@partners.org
RI Chung, Gehoon/C-5714-2008
OI Chung, Gehoon/0000-0002-8036-0879
FU Harvard Medical School, Boston, Massachusetts; Ministry of Science and
Technology, Seoul, Republic of Korea [M103KV010015-08K2201-01510]
FX Received from the Department of Anesthesia and Critical Care,
Massachusetts General Hospital, the Department of Anesthesiology,
Perioperative, Pain Medicine, Brigham and Women's Hospital and Harvard
Medical School, Boston, Massachusetts. Submitted for publication August
24, 2008. Accepted for publication March 7, 2009. This research was
supported by Alice and Joseph Brooks Fund from Harvard Medical School,
Boston, Massachusetts, (to Dr. Oh) and by grant
M103KV010015-08K2201-01510 front Brain Research Center of the 21st
Century Frontier Research Program funded by the Ministry of Science and
Technology, Seoul, Republic of Korea (to Dr. Oh). Endo Pharmaceuticals
(Chadds Ford, Pennsylvania) has obtained a license to develop this
strategy with Harvard Medical School and the Massachusetts General
Hospital. This agreement was concluded after completion of this body of
work. Drs. Binshtok and Gerner authors contributed equally to this work.
NR 36
TC 49
Z9 50
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUL
PY 2009
VL 111
IS 1
BP 127
EP 137
PG 11
WC Anesthesiology
SC Anesthesiology
GA 462IY
UT WOS:000267346200022
PM 19512868
ER
PT J
AU Smith, AK
Fisher, J
Schonberg, MA
Pallin, DJ
Block, SD
Forrow, L
Phillips, RS
McCarthy, EP
AF Smith, Alexander K.
Fisher, Jonathan
Schonberg, Mara A.
Pallin, Daniel J.
Block, Susan D.
Forrow, Lachlan
Phillips, Russell S.
McCarthy, Ellen P.
TI Am I Doing the Right Thing? Provider Perspectives on Improving
Palliative Care in the Emergency Department
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID ILLNESS; TRENDS; LIFE; END
AB Study objective: Although the focus of emergency care is on the diagnosis and treatment of acute illnesses and injuries or the stabilization of patients for ongoing treatment, some patients may benefit from a palliative approach. Little is known about delivering palliative care in the emergency department (ED). We explore the attitudes, experiences, and beliefs of emergency providers about palliative care in the ED, using structured qualitative methods.
Methods: We studied 3 focus groups with 26 providers, including 14 physicians (10 residents, 4 attending physicians), 6 nurses, 2 social workers, and 4 technicians, working in 2 academic EDs in Boston. We used a grounded theory approach to code responses, resolving discrepancies by consensus.
Results: Six distinct themes emerged: (1) participants equated palliative care with end-of-life care; (2) participants disagreed about the feasibility and desirability of providing palliative care in the ED; (3) patients for whom a palliative approach has been established often visit the ED because family members are distressed by end-of-life symptoms; (4) lack of communication between outpatient and ED providers leads to undesirable outcomes leg, resuscitation of patients with a do-not-resuscitate order); (5) conflict around withholding life-prolonging treatment is common leg, between patient's family and written advance directives); and (6) training in pain management is inadequate.
Conclusion: Providers ranked improved communication and documentation from outpatient providers as their highest priority for improvement. Attitudinal and structural barriers may need to be overcome to improve palliative care in the ED. Despite targeted recruitment, attending physician participation was low. [Ann Emerg Med. 2009;54:86-93.]
C1 [Smith, Alexander K.; Schonberg, Mara A.; Forrow, Lachlan; Phillips, Russell S.; McCarthy, Ellen P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Fisher, Jonathan] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA.
[Smith, Alexander K.; Block, Susan D.] Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Pallin, Daniel J.] Childrens Hosp Boston, Div Emergency Med, Boston, MA USA.
RP Smith, AK (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St 181G, San Francisco, CA 94121 USA.
EM aksmith@ucsf.edu
RI Pallin, Daniel/H-6382-2013
OI Pallin, Daniel/0000-0002-8517-9702
FU The Julie Henry Fund at Beth Israel Deaconess Hospital; National
Research Service Award [5 T32 HP11001-19]
FX By Annals policy, all authors are required to disclose any and all
commercial, financial, and other relationships in any way related to the
subject of this article, that might create any potential conflict of
interest. See the Manuscript Submission Agreement in this issue for
examples of specific conflicts covered by this statement. This study was
performed in its entirety while Dr. Smith was a general medicine fellow
at Beth Israel Deaconess Medical Center. This research was supported by
The Julie Henry Fund at Beth Israel Deaconess Hospital. Dr. Smith was
supported by an institutional National Research Service Award, #5 T32
HP11001-19.
NR 17
TC 74
Z9 75
U1 2
U2 14
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD JUL
PY 2009
VL 54
IS 1
BP 86
EP 93
DI 10.1016/j.annemergmed.2008.08.022
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 468VX
UT WOS:000267853500018
ER
PT J
AU Moriyama, B
Henning, SA
Neuhauser, MM
Danner, RL
Walsh, TJ
AF Moriyama, Brad
Henning, Stacey A.
Neuhauser, Melinda M.
Danner, Robert L.
Walsh, Thomas J.
TI Continuous-infusion beta-Lactam Antibiotics During Continuous Venovenous
Hemofiltration for the Treatment of Resistant Gram-Negative Bacteria
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE Acinetobacter baumannii; beta-lactam; continuous infusion; continuous
venovenous hemofiltration; Pseudomonas aeruginosa
ID RENAL REPLACEMENT THERAPY; CRITICALLY-ILL PATIENTS;
PSEUDOMONAS-AERUGINOSA INFECTION; SINGLE-DOSE PHARMACOKINETICS; RABBIT
ENDOCARDITIS MODEL; IN-VITRO; CYSTIC-FIBROSIS; CLAVULANIC ACID;
INTERMITTENT INFUSION; ANTIMICROBIAL AGENTS
AB OBJECTIVE: To describe the rationale, principles, and dosage calculations for continuous-infusion beta-lactam antibiotics to treat multidrug-resistant bacteria in patients undergoing continuous venovenous hemofiltration (CVVH).
DATA SOURCES: A MEDLINE search (1968-November 2008) of the English-language literature was performed using the terms continuous infusion and Pseudomonas or Acinetobacter, hemofiltration or CVVH or hemodiafiltration or CVVHDF or continuous renal replacement therapy or pharmacokinetics; and terms describing different beta-lactam antibiotics.
STUDY SELECTION AND DATA EXTRACTION: In vitro, in vivo, and human studies were evaluated that used continuous-infusion beta-lactam antibiotics to treat Pseudomonas aeruginosa and Acinetobacter baumannii infections. Studies were reviewed that described the pharmacokinetics of beta-lactam antibiotics during CVVH as well as other modalities of continuous renal replacement therapy.
DATA SYNTHESIS: Continuous infusion of beta-lactam antibiotics, maintaining drug concentrations 4-5 times higher than the minimum inhibitory concentration, is a promising approach for managing infections caused by P. aeruginosa and A. baumannii. Safe yet effective continuous infusion therapy is made difficult by the occurrence of acute renal failure and the need for renal replacement therapy. Case series and pharmacokinetic properties indicate that several beta-lactam antimicrobials that have been studied for continuous infusion, such as cefepime, ceftazidime, piperacillin, ticarcillin, clavulanic acid, and tazobactam, are significantly cleared by hemofiltration. Methodology and formulas are provided that allow practitioners to calculate dosage regimens and reach target drug concentrations for continuous beta-lactam antibiotic infusions during CVVH based on a literature review, pharmacokinetic principles, and our experience at the National Institutes of Health Clinical Center.
CONCLUSIONS: Continuous infusion of beta-lactam antibiotics may be a useful treatment strategy for multidrug-resistant gram-negative infections in the intensive care unit. Well-established pharmacokinetic and pharmacodynamic principles can be used to safely reach and maintain steady-state target concentrations of beta-lactam antibiotics in critical illness complicated by acute renal failure requiring CVVH.
C1 [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Moriyama, Brad; Henning, Stacey A.] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
[Neuhauser, Melinda M.] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA.
[Danner, Robert L.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Walsh, TJ (reprint author), CRC 1-5750,10 Ctr Dr, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
FU National Institutes of Health
FX This work was supported in part by the intramural research program of
the National Institutes of Health.
NR 87
TC 9
Z9 10
U1 0
U2 1
PU HARVEY WHITNEY BOOKS CO
PI CINCINNATI
PA PO BOX 42696, CINCINNATI, OH 45242 USA
SN 1060-0280
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD JUL-AUG
PY 2009
VL 43
IS 7-8
BP 1324
EP 1337
DI 10.1345/aph.1L638
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 477IM
UT WOS:000268512700020
PM 19584386
ER
PT J
AU Colwell, AS
Driscoll, D
Breuing, KH
AF Colwell, Amy S.
Driscoll, Daniel
Breuing, Karl H.
TI Mastopexy Techniques After Massive Weight Loss An Algorithmic Approach
and Review of the Literature
SO ANNALS OF PLASTIC SURGERY
LA English
DT Article
DE massive weight loss; mastopexy; autoaugmentation; breast lift; breast
reduction; AlloDerm; spiral flap; ICAP; breast
ID ARTERY PERFORATOR FLAP; REDUCTION MAMMAPLASTY; VERTICAL MAMMAPLASTY;
AUGMENTATION; BREAST; SUSPENSION; SURGERY; UPDATE; BEWARE; SHAPE
AB Mastopexy after massive weight loss (MWL) poses unique challenges that may not be successfully addressed with traditional mastopexy procedures. Several novel techniques have been proposed to improve esthetic outcomes; however, little data exists to guide the plastic surgeon on choice of technique for individual patients. A literature review revealed 10 articles with specific emphasis on mastopexy techniques in MWL patients. These articles focused on ways to improve shape, projection, and long-term results, using autologous tissue alone or combined with breast implants. Key concepts include increasing volume of the breast by utilizing excess axillary tissue (lateral thoracic/spiral/intercostal artery perforator flap), modification of existing superomedial pedicle techniques to maximize breast volume, and increasing breast parenchymal support with suture fixation and dermal suspension. This article offers an algorithmic approach to treat breast ptosis in the MWL patient based on breast volume, axillary tissue, desired scar location, and preferred surgical technique.
C1 [Colwell, Amy S.; Driscoll, Daniel] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Div Plast Surg, Boston, MA 02115 USA.
[Breuing, Karl H.] Harvard Univ, Brigham & Womens Hosp, Div Plast Surg, Sch Med,Dept Surg, Boston, MA 02115 USA.
RP Colwell, AS (reprint author), Mass Gen Hosp, Div Plast Surg, 15 Parkman St Wang 435, Boston, MA 02114 USA.
EM acolwell@partners.org
NR 31
TC 13
Z9 16
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-7043
J9 ANN PLAS SURG
JI Ann. Plast. Surg.
PD JUL
PY 2009
VL 63
IS 1
BP 28
EP 33
DI 10.1097/SAP.0b013e318188b976
PG 6
WC Surgery
SC Surgery
GA 462GD
UT WOS:000267338100009
PM 19546668
ER
PT J
AU Kay, J
Westhovens, R
AF Kay, Jonathan
Westhovens, Rene
TI Methotrexate: the gold standard without standardisation
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Editorial Material
ID EARLY RHEUMATOID-ARTHRITIS; CONTROLLED-TRIAL; COMBINATION
C1 [Westhovens, Rene] Katholieke Univ Leuven, UZ Gasthuisberg, Dept Musculoskeletal, Div Rheumatol, B-3000 Louvain, Belgium.
[Kay, Jonathan] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
[Kay, Jonathan] Harvard Univ, Sch Med, Boston, MA USA.
RP Westhovens, R (reprint author), Katholieke Univ Leuven, UZ Gasthuisberg, Dept Musculoskeletal, Div Rheumatol, B-3000 Louvain, Belgium.
EM rene.westhovens@uz.kuleuven.ac.be
OI Kay, Jonathan/0000-0002-8970-4260
NR 14
TC 13
Z9 17
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD JUL
PY 2009
VL 68
IS 7
BP 1081
EP 1082
DI 10.1136/ard.2008.102822
PG 2
WC Rheumatology
SC Rheumatology
GA 457TP
UT WOS:000266956800001
PM 19525405
ER
PT J
AU Bakaeen, FG
Huh, J
LeMaire, SA
Coselli, JS
Sansgiry, S
Atluri, PV
Chu, DN
AF Bakaeen, Faisal G.
Huh, Joseph
LeMaire, Scott A.
Coselli, Joseph S.
Sansgiry, Shubhada
Atluri, Prasad V.
Chu, Danny
TI The July Effect: Impact of the Beginning of the Academic Cycle on
Cardiac Surgical Outcomes in a Cohort of 70,616 Patients
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID ARTERY-BYPASS SURGERY; TEACHING HOSPITALS; RESIDENT; IMPROVEMENT;
EXPERIENCE; MORTALITY; PROGRAM; SAFETY; LEVEL; RISK
AB Background. Because surgical residents' level of experience may be at its nadir early in the academic year, academic seasonality-or the "July effect"-could affect cardiac surgical outcomes.
Methods. Prospectively collected data from the Department of Veterans Affairs Continuous Improvement in Cardiac Surgery Program were used to identify 70,616 consecutive cardiac surgical procedures performed between October 1997 and October 2007. Morbidity and mortality rates were compared between early (July 1 to August 31, n = 11,975) and late (September 1 to June 30, n = 58,641) periods in the academic year. A prediction model was constructed by using stepwise logistic regression modeling.
Results. The two patient groups had similar demographic and risk variables. Isolated coronary artery bypass grafting accounted for 76.7% of early-period procedures and 75.8% of later-period procedures (p = 0.03). Morbidity rates did not differ significantly between the early (14.0%) and later periods (14.2%; odds ratio [OR], 1.01; 95% confidence interval [CI], 0.96 to 1.07; p = 0.67) and operative mortality was similar, 3.7% vs 3.9% (OR, 0.99; 95% CI, 0.89 to 1.11; p = 0.90). The early portion of the year was associated with longer cardiac ischemia times (84 +/- 40 vs 83 +/- 42 minutes), cardiopulmonary bypass times (126 +/- 52 vs 124 +/- 56 minutes), and total surgical times (295 +/- 90 vs 288 +/- 90 minutes; p < 0.05 for all).
Conclusions. The early part of the academic year was associated with slightly longer operative times; however, risk-adjusted outcomes were similar in both periods. This finding should lessen concerns about the quality of cardiac surgical care at the beginning of the academic year. (Ann Thorac Surg 2009;88:70-5) (C) 2009 by The Society of Thoracic Surgeons
C1 Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA.
RP Bakaeen, FG (reprint author), Michael E DeBakey VAMC, Dept Cardiothorac Surg, OCL 112,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM fbakaeen@bcm.edu
FU Offices of Research and Development; Northport and Eastern Colorado
Health Care System Denver Veterans Affairs Medical Centers
FX Stephen N. Palmer, PhD, ELS, contributed to the editing of this
manuscript. The CICSP-X study was initially funded by VA Health Services
Research and Development Grant #IHY 99214-1 (Dr Shroyer, Principal
Investigator), with ongoing support from the Office of Patient Care
Services, VA Central Office, Washington, DC. This project was supported
in part by the Offices of Research and Development at the Northport and
Eastern Colorado Health Care System Denver Veterans Affairs Medical
Centers. Special acknowledgment is given to Randy Johnson, Lisa Schade,
and Missy Bell, the team members responsible for the CICSP-X access to
care report sections, working under the leadership of Dr Gerald McDonald
(VA Central Office).
NR 19
TC 35
Z9 35
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUL
PY 2009
VL 88
IS 1
BP 70
EP 75
DI 10.1016/j.athoracsur.2009.04.022
PG 6
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 464ZV
UT WOS:000267550600011
PM 19559195
ER
PT J
AU O'Brien, SM
Shahian, DM
Filardo, G
Ferraris, VA
Haan, CK
Rich, JB
Normand, SLT
DeLong, ER
Shewan, CM
Dokholyan, RS
Peterson, ED
Edwards, FH
Anderson, RP
AF O'Brien, Sean M.
Shahian, David M.
Filardo, Giovanni
Ferraris, Victor A.
Haan, Constance K.
Rich, Jeffrey B.
Normand, Sharon-Lise T.
DeLong, Elizabeth R.
Shewan, Cynthia M.
Dokholyan, Rachel S.
Peterson, Eric D.
Edwards, Fred H.
Anderson, Richard P.
TI The Society of Thoracic Surgeons 2008 Cardiac Surgery Risk Models: Part
2-Isolated Valve Surgery
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID IN-HOSPITAL MORTALITY; REPLACEMENT; PREDICTION
AB Background. Adjustment for case-mix is essential when using observational data to compare surgical techniques or providers. That is most often accomplished through the use of risk models that account for preoperative patient factors that may impact outcomes. The Society of Thoracic Surgeons (STS) uses such risk models to create risk-adjusted performance reports for participants in the STS National Adult Cardiac Surgery Database (NCD). Although risk models were initially developed for coronary artery bypass surgery, similar models have now been developed for use with heart valve surgery, particularly as the proportion of such procedures has increased. The last published STS model for isolated valve surgery was based on data from 1994 to 1997 and did not include patients undergoing mitral valve repair. STS has developed new valve surgery models using contemporary data that include both valve repair as well as replacement. Expanding upon existing valve models, the new STS models include several nonfatal complications in addition to mortality.
Methods. Using STS data from 2002 to 2006, isolated valve surgery risk models were developed for operative mortality, permanent stroke, renal failure, prolonged ventilation (> 24 hours), deep sternal wound infection, reoperation for any reason, a major morbidity or mortality composite endpoint, prolonged postoperative length of stay, and short postoperative length of stay. The study population consisted of adult patients who underwent one of three types of valve surgery: isolated aortic valve replacement (n = 67,292), isolated mitral valve replacement (n = 21,229), or isolated mitral valve repair (n = 21,238). The population was divided into a 60% development sample and a 40% validation sample. After an initial empirical investigation, the three surgery groups were combined into a single logistic regression model with numerous interactions to allow the covariate effects to differ across these groups. Variables were selected based on a combination of automated stepwise selection and expert panel review.
Results. Unadjusted operative mortality (in-hospital regardless of timing, and 30-day regardless of venue) for all isolated valve procedures was 3.4%, and unadjusted in-hospital morbidity rates ranged from 0.3% for deep sternal wound infection to 11.8% for prolonged ventilation. The number of predictors in each model ranged from 10 covariates in the sternal infection model to 24 covariates in the composite mortality plus morbidity model. Discrimination as measured by the c-index ranged from 0.639 for reoperation to 0.799 for mortality. When patients in the validation sample were grouped into 10 categories based on deciles of predicted risk, the average absolute difference between observed versus predicted events within these groups ranged from 0.06% for deep sternal wound infection to 1.06% for prolonged postoperative stay.
Conclusions. The new STS risk models for valve surgery include mitral valve repair as well as multiple endpoints other than mortality. Model coefficients are provided and an online risk calculator is publicly available from The Society of Thoracic Surgeons website.
C1 [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[O'Brien, Sean M.; DeLong, Elizabeth R.; Dokholyan, Rachel S.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA.
[Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA.
[Ferraris, Victor A.] Univ Kentucky, Albert B Chandler Med Ctr, Div Cardiovasc & Thorac Surg, Lexington, KY 40536 USA.
[Haan, Constance K.; Edwards, Fred H.] Univ Florida, Div Cardiothorac Surg, Jacksonville, FL USA.
[Rich, Jeffrey B.] Sentara Cardiovasc Res Inst, Norfolk, VA USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA.
[Anderson, Richard P.] Soc Thorac Surg, Seattle, WA USA.
RP Shahian, DM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM dshahian@partners.org
RI O'Brien, Sean/H-6268-2013
NR 10
TC 388
Z9 404
U1 1
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUL
PY 2009
VL 88
IS 1
BP S23
EP S42
DI 10.1016/j.athoracsur.2009.05.056
PG 20
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 463YC
UT WOS:000267469100003
PM 19559823
ER
PT J
AU Shahian, DM
O'Brien, SM
Filardo, G
Ferraris, VA
Haan, CK
Rich, JB
Normand, SLT
DeLong, ER
Shewan, CM
Dokholyan, RS
Peterson, ED
Edwards, FH
Anderson, RP
AF Shahian, David M.
O'Brien, Sean M.
Filardo, Giovanni
Ferraris, Victor A.
Haan, Constance K.
Rich, Jeffrey B.
Normand, Sharon-Lise T.
DeLong, Elizabeth R.
Shewan, Cynthia M.
Dokholyan, Rachel S.
Peterson, Eric D.
Edwards, Fred H.
Anderson, Richard P.
TI The Society of Thoracic Surgeons 2008 Cardiac Surgery Risk Models: Part
1-Coronary Artery Bypass Grafting Surgery
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID NATIONAL DATABASE; MORTALITY-RATES; OUTCOMES; PREDICTION; PROGRAM; CURVE
AB Background. The first version of The Society of Thoracic Surgeons National Adult Cardiac Surgery Database (STS NCD) was developed nearly 2 decades ago. Since its inception, the number of participants has grown dramatically, patient acuity has increased, and overall outcomes have consistently improved. To adjust for these and other changes, all STS risk models have undergone periodic revisions. This report provides a detailed description of the 2008 STS risk model for coronary artery bypass grafting surgery (CABG).
Methods. The study population consisted of 774,881 isolated CABG procedures performed on adult patients aged 20 to 100 years between January 1, 2002, and December 31, 2006, at 819 STS NCD participating centers. This cohort was randomly divided into a 60% training (development) sample and a 40% test (validation) sample. The development sample was used to identify predictor variables and estimate model coefficients. The validation sample was used to assess model calibration and discrimination. Model outcomes included operative mortality, renal failure, stroke, reoperation for any cause, prolonged ventilation, deep sternal wound infection, composite major morbidity or mortality, prolonged length of stay (> 14 days), and short length of stay (< 6 days and alive). Candidate predictor variables were selected based on their availability in versions 2.35, 2.41, and 2.52.1 of the STS NCD and their presence in (or ability to be mapped to) version 2.61. Potential predictor variables were screened for overall prevalence in the study population, missing data frequency, coding concerns, bivariate relationships with outcomes, and their presence in previous STS or other CABG risk models. Supervised backwards selection was then performed with input from an expert panel of cardiac surgeons and biostatisticians. After successfully validating the fit of the models, the development and validation samples were subsequently combined, and the final regression coefficients were estimated using the overall combined (development plus validation) sample.
Results. The c-index for the mortality model was 0.812, and the c-indices for other endpoints ranged from 0.653 for reoperation to 0.793 for renal failure in the validation sample. Plots of observed versus predicted event rates revealed acceptable calibration in the overall population and in numerous subgroups. When patients were grouped into categories of predicted risk, the absolute difference between the observed and expected event rates was less than 1.5% for each endpoint. The final model intercept and coefficients are provided.
Conclusions. New STS risk models have been developed for CABG mortality and eight other endpoints. Detailed descriptions of model development and testing are provided, together with the final algorithm. Overall model performance is excellent. (Ann Thorac Surg 2009;88:S2-22) (C) 2009 by The Society of Thoracic Surgeons
C1 [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[O'Brien, Sean M.; DeLong, Elizabeth R.; Dokholyan, Rachel S.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA.
[Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA.
[Ferraris, Victor A.] Univ Kentucky, Albert B Chandler Med Ctr, Div Cardiovasc & Thorac Surg, Lexington, KY 40536 USA.
[Haan, Constance K.; Edwards, Fred H.] Univ Florida, Div Cardiothorac Surg, Jacksonville, FL USA.
[Rich, Jeffrey B.] Sentara Cardiovasc Res Inst, Norfolk, VA USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA.
[Anderson, Richard P.] Soc Thorac Surg, Seattle, WA USA.
RP Shahian, DM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM dshahian@partners.org
RI O'Brien, Sean/H-6268-2013
NR 35
TC 343
Z9 352
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUL
PY 2009
VL 88
IS 1
SU 1
BP S2
EP S22
DI 10.1016/j.athoracsur.2009.05.053
PG 21
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 463YC
UT WOS:000267469100002
PM 19559822
ER
PT J
AU Shahian, DM
O'Brien, SM
Filardo, G
Ferraris, VA
Haan, CK
Rich, JB
Normand, SLT
DeLong, ER
Shewan, CM
Dokholyan, RS
Peterson, ED
Edwards, FH
Anderson, RP
AF Shahian, David M.
O'Brien, Sean M.
Filardo, Giovanni
Ferraris, Victor A.
Haan, Constance K.
Rich, Jeffrey B.
Normand, Sharon-Lise T.
DeLong, Elizabeth R.
Shewan, Cynthia M.
Dokholyan, Rachel S.
Peterson, Eric D.
Edwards, Fred H.
Anderson, Richard P.
TI The Society of Thoracic Surgeons 2008 Cardiac Surgery Risk Models: Part
3-Valve Plus Coronary Artery Bypass Grafting Surgery
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID HEART-VALVE SURGERY; IN-HOSPITAL MORTALITY; NEW-YORK-STATE; OPERATIVE
MORTALITY; PREDICTION; STRATIFICATION; REPLACEMENT; EUROSCORE; DATABASE
AB Background. Since 1999, The Society of Thoracic Surgeons (STS) has published two risk models that can be used to adjust the results of valve surgery combined with coronary artery bypass graft surgery (CABG). The most recent was developed from data for patients who had surgery between 1994 and 1997 using operative mortality as the only endpoint. Furthermore, this model did not specifically consider mitral valve repair plus CABG, an increasingly common procedure. Consistent with STS policy of periodically updating and improving its risk models, new models for valve surgery combined with CABG have been developed. These models specifically address both perioperative morbidity and mitral valve repair, and they are based on contemporary data.
Methods. The final study population consisted of 101,661 procedures, including aortic valve replacement (AVR) plus CABG, mitral valve replacement (MVR) plus CABG, or mitral valve repair (MVRepair) plus CABG between January 1, 2002, and December 31, 2006. Model outcomes included operative mortality, stroke, deep sternal wound infection, reoperation, prolonged ventilation, renal failure, composite major morbidity or mortality, prolonged postoperative length of stay, and short postoperative length of stay. Candidate variables were screened for frequency of missing data, and imputation techniques were used where appropriate. Stepwise variable selection was employed, supplemented by advice from an expert panel of cardiac surgeons and biostatisticians. Several variables were forced into models to insure face validity (eg, atrial fibrillation for the permanent stroke model, sex for all models). Based on preliminary analyses of the data, a single model was employed for valve plus CABG, with indicator variables for the specific type of procedure. Interaction terms were included to allow for differential impact of predictor variables depending on procedure type. After validating the model in the 40% validation sample, the development and validation samples were then combined, and the final model coefficients were estimated using the overall 100% combined sample. The final logistic regression model was estimated using generalized estimating equations to account for clustering of patients within institutions.
Results. The c-index for mortality prediction for the overall valve plus CABG population was 0.75. Morbidity model c-indices for specific complications (permanent stroke, renal failure, prolonged ventilation > 24 hours, deep sternal wound infection, reoperation for any reason, major morbidity or mortality composite, and prolonged postoperative length of stay) for the overall group of valve plus CABG procedures ranged from 0.622 to 0.724, and calibration was excellent.
Conclusions. New STS risk models have been developed for heart valve surgery combined with CABG. These are the first valve plus CABG models that also include risk prediction for individual major morbidities, composite major morbidity or mortality, and short and prolonged length of stay. (Ann Thorac Surg 2009;88:S43-62) (C) 2009 by The Society of Thoracic Surgeons
C1 [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[O'Brien, Sean M.; DeLong, Elizabeth R.; Dokholyan, Rachel S.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA.
[Filardo, Giovanni] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX USA.
[Ferraris, Victor A.] Univ Kentucky, Albert B Chandler Med Ctr, Div Cardiovasc & Thorac Surg, Lexington, KY 40536 USA.
[Haan, Constance K.; Edwards, Fred H.] Univ Florida, Div Cardiothorac Surg, Jacksonville, FL USA.
[Rich, Jeffrey B.] Sentara Cardiovasc Res Inst, Norfolk, VA USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA.
[Anderson, Richard P.] Soc Thorac Surg, Seattle, WA USA.
RP Shahian, DM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM dshahian@partners.org
RI O'Brien, Sean/H-6268-2013
NR 23
TC 164
Z9 176
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUL
PY 2009
VL 88
IS 1
BP S43
EP S62
DI 10.1016/j.athoracsur.2009.05.055
PG 20
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 463YC
UT WOS:000267469100004
PM 19559824
ER
PT J
AU Shahian, DM
Edwards, FH
AF Shahian, David M.
Edwards, Fred H.
TI The Society of Thoracic Surgeons 2008 Cardiac Surgery Risk Models:
Introduction
SO ANNALS OF THORACIC SURGERY
LA English
DT Editorial Material
C1 [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Edwards, Fred H.] Univ Florida, Div Cardiothorac Surg, Jacksonville, FL USA.
RP Shahian, DM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM dshahian@partners.org
NR 0
TC 60
Z9 62
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUL
PY 2009
VL 88
IS 1
BP S1
EP S1
DI 10.1016/j.athoracsur.2009.05.054
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 463YC
UT WOS:000267469100001
PM 19559821
ER
PT J
AU Yang, QH
Hornick, JL
Granter, SR
Wang, LC
AF Yang, Qinghong
Hornick, Jason L.
Granter, Scott R.
Wang, Linda C.
TI Merkel Cell Carcinoma Lack of KIT Positivity and Implications for the
Use of Imatinib Mesylate
SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
LA English
DT Article
DE Merkel cell carcinoma; KIT; immunohistochemistry; imatinib mesylate
ID GASTROINTESTINAL STROMAL TUMORS; KINASE INHIBITOR STI571; C-KIT;
TYROSINE KINASE; LUNG-CANCER; THERAPEUTIC IMPLICATIONS;
DIFFERENTIAL-DIAGNOSIS; CD117 EXPRESSION; GENE-MUTATIONS; WILD-TYPE
AB The large variability (7% to 100%) in previously reported rates of receptor tyrosine kinase KIT expression in Merkel cell carcinoma (MCC) may be owing to the use of heat-induced epitope retrieval. High frequency of reported KIT reactivity by immunohistochemistry (IHC) in part prompted the initiation of a phase 2 clinical trial of imatinib mesylate (Gleevec, Novartis Pharmaceuticals, East Hanover, NJ) for the treatment of advanced MCC. Our experience has been that a small number of MCCs (12.5%) are positive for KIT by IHC. We also found a higher rate of apparently KIT-positive MCCs (75%) using heat-induced epitope retrieval. Our anecdotal experience with the use of imatinib mesylate has been disappointing. As IHC detection of KIT expression does not correlate with the presence of KIT-activating mutations, protein expression as tested by IHC should not be used to determine if patients would respond to imatinib mesylate. Indeed, our review of the literature and the apparent lack of efficacy of imatinib mesylate for MCC in a recent phase 2 trial suggest a minor role for KIT signaling in MCC tumorigenesis.
C1 [Wang, Linda C.] Harvard Univ, Dana Farber Brigham & Womens Canc Ctr, Dept Dermatol, Sch Med, Boston, MA 02115 USA.
[Yang, Qinghong; Hornick, Jason L.; Granter, Scott R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Wang, LC (reprint author), Harvard Univ, Dana Farber Brigham & Womens Canc Ctr, Dept Dermatol, Sch Med, 44 Binney St,SW 550, Boston, MA 02115 USA.
EM lcwang@partners.org
NR 40
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-3345
J9 APPL IMMUNOHISTO M M
JI Appl. Immunohistochem.
PD JUL
PY 2009
VL 17
IS 4
BP 276
EP 281
PG 6
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA 464AR
UT WOS:000267477100002
PM 19276970
ER
PT J
AU Laubach, HJ
Anderson, RR
Luger, T
Manstein, D
AF Laubach, Hans-Joachim
Anderson, Richard Rox
Luger, Thomas
Manstein, Dieter
TI Fractional Photothermolysis for Involuted Infantile Hemangioma
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID VASCULAR MALFORMATIONS; FACIAL HEMANGIOMA; CIRCULAR EXCISION;
LIPOSUCTION; MANAGEMENT; SCARS; LASER
C1 [Laubach, Hans-Joachim; Anderson, Richard Rox; Manstein, Dieter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Laubach, Hans-Joachim; Luger, Thomas] Univ Munster, Klin & Poliklin Haut & Geschlechtskrankheiten, Munster, Germany.
RP Laubach, HJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 305,50 Blossom St, Boston, MA 02114 USA.
EM hlaubach@partners.org
FU Reliant Technologies Inc.
FX Financial Disclosure: Dr Laubach has received travel expenses and
research funding from Reliant Technologies Inc; Dr Manstein has received
honoraria, research funding, and royalties from Reliant Technologies
Inc; Dr Luger has received research funding form Reliant Technologies
Inc; Dr Anderson has received honoraria, research funding, and royalties
from Reliant Technologies Inc.; Funding/Support: Reliant Technologies
Inc provided a consumable part of their laser device free of cost for
this study.
NR 27
TC 5
Z9 5
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD JUL
PY 2009
VL 145
IS 7
BP 748
EP 750
PG 3
WC Dermatology
SC Dermatology
GA 472MU
UT WOS:000268136900002
PM 19620554
ER
PT J
AU Healy, BC
Ali, EN
Guttmann, CRG
Chitnis, T
Glanz, BI
Buckle, G
Houtchens, M
Stazzone, L
Moodie, J
Berger, AM
Duan, Y
Bakshi, R
Khoury, S
Weiner, H
Ascherio, A
AF Healy, Brian C.
Ali, Eman N.
Guttmann, Charles R. G.
Chitnis, Tanuja
Glanz, Bonnie I.
Buckle, Guy
Houtchens, Maria
Stazzone, Lynn
Moodie, Jennifer
Berger, Annika M.
Duan, Yang
Bakshi, Rohit
Khoury, Samia
Weiner, Howard
Ascherio, Alberto
TI Smoking and Disease Progression in Multiple Sclerosis
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID CIGARETTE-SMOKING; DIAGNOSTIC-CRITERIA; OPTIC NEUROPATHY; RISK-FACTORS;
NICOTINE; EPIDEMIOLOGY; INFECTIONS; CHILDREN
AB Background: Although cigarette smokers are at increased risk of developing multiple sclerosis (MS), the effect of smoking on the progression of MS remains uncertain.
Objective: To establish the relationship between cigarette smoking and progression of MS using clinical and magnetic resonance imaging outcomes
Design: Cross-sectional survey and longitudinal follow-up for a mean of 3.29 years, ending January 15, 2008.
Setting: Partners MS Center (Boston, Massachusetts), a referral center for patients with MS.
Patients: Study participants included 1465 patients with clinically definite MS (25.1% men), with mean (range) age at baseline of 42.0 (16-75) years and disease duration of 9.4 (0-50.4) years. Seven hundred eighty patients (53.2%) were never-smokers, 428 (29.2%) were ex-smokers, and 257 (17.5%) were current smokers.
Main Outcome Measures: Smoking groups were compared for baseline clinical and magnetic resonance imaging characteristics as well as progression and sustained progression on the Expanded Disability Status Scale at 2 and 5 years and time to disease conversion to secondary progressive MS. In addition, the rate of on-study change in the brain parenchymal fraction and T2 hyperintense lesion volume were compared. Results: Current smokers had significantly worse disease at baseline than never-smokers in terms of Expanded Disability Status Scale score (adjusted P < .001), Multiple Sclerosis Severity Score (adjusted P < .001.), and brain parenchymal fraction (adjusted P = .004). In addition, current smokers were significantly more likely to have primary progressive MS (adjusted odds ratio, 2.41; 95% confidence interval, 1.09-5.34). At longitudinal analyses, MS in smokers progressed from relapsing-remitting to secondary progressive disease faster than in never-smokers (hazard ratio for current smokers vs never-smokers, 2.50; 95% confidence interval, 1.42-4.41). In addition, in smokers, the T2-weighted lesion volume increased faster (P = .02), and brain parenchymal fraction decreased faster (P = .02).
Conclusion: Our data suggest that cigarette smoke has an adverse influence on the progression of MS and accelerates conversion from a relapsing-remitting to a progressive course.
C1 [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA.
[Healy, Brian C.; Ali, Eman N.; Guttmann, Charles R. G.; Chitnis, Tanuja; Glanz, Bonnie I.; Buckle, Guy; Houtchens, Maria; Stazzone, Lynn; Moodie, Jennifer; Bakshi, Rohit; Khoury, Samia; Weiner, Howard] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Partners MS Ctr, Boston, MA 02115 USA.
[Guttmann, Charles R. G.; Berger, Annika M.; Duan, Yang; Bakshi, Rohit] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Imaging,Dept Radiol, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA.
[Healy, Brian C.] Massachusetts Gen Hosp, Dept Neurol, Ctr Biostat, Boston, MA 02114 USA.
RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 655 Huntington Ave,Bldg 2,3rd Floor, Boston, MA 02215 USA.
EM aascheri@hsph.harvard.edu
OI khoury, samia/0000-0003-3198-6063
FU Partners Multiple Sclerosis Center; National Institute of Neurological
Disorders and Stroke [R01 NS047467]; National Institutes of Health
Molecular Epidemiology
FX This study was supported by the Partners Multiple Sclerosis Center and
by grant R01 NS047467 from the National Institute of Neurological
Disorders and Stroke, National Institutes of Health Molecular
Epidemiology of Epstein-Barr Virus and Multiple Sclerosis (Dr Ascherio).
NR 36
TC 68
Z9 70
U1 2
U2 13
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD JUL
PY 2009
VL 66
IS 7
BP 858
EP 864
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 473EQ
UT WOS:000268189200007
PM 19597087
ER
PT J
AU Costello, DJ
Chiappa, KH
Siao, P
AF Costello, Daniel J.
Chiappa, Keith H.
Siao, Peter
TI Progressive Myoclonus Epilepsy With Demyelinating Peripheral Neuropathy
and Preserved Intellect
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID CEREBELLAR PATHOLOGY
AB Background: The progressive myoclonic epilepsies (PMEs) are a disparate group of syndromes whose common features include disabling myoclonus, progressive cognitive decline, and seizures, typically with a relentless deterioration over time.
Objective: To report a novel PME syndrome.
Design: Case report.
Setting: Epilepsy service in a tertiary care urban medical center.
Patient: A 24-year-old man with progressive myoclonus, seizures, and unique features of preserved intellect and demyelinating peripheral neuropathy.
Main Outcome Measure: Detailed clinical assessment, electrophysiologic studies, and survey of the literature.
Results: We characterize an unusual PME phenotype with unique features of preserved intellect and electrophysiologic evidence of a generalized demyelinating peripheral neuropathic condition. An extensive diagnostic evaluation did not reveal an underlying cause, and a literature survey did not identify other, similar clinical reports.
Conclusion: We describe a novel PME syndrome with preserved intellect and demyelinating peripheral neuropathy.
C1 [Costello, Daniel J.; Chiappa, Keith H.] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA.
[Siao, Peter] Massachusetts Gen Hosp, Dept Neurol, Neuromuscular & Electrophysiol Serv, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Costello, DJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, ACC 835,55 Fruit St, Boston, MA 02114 USA.
EM djcostello@partners.org
NR 6
TC 4
Z9 4
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD JUL
PY 2009
VL 66
IS 7
BP 898
EP 901
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 473EQ
UT WOS:000268189200014
PM 19597094
ER
PT J
AU Goyal, S
Chauhan, SK
Zhang, Q
Dana, R
AF Goyal, Sunali
Chauhan, Sunil K.
Zhang, Qiang
Dana, Reza
TI Amelioration of Murine Dry Eye Disease by Topical Antagonist to
Chemokine Receptor 2
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID HUMAN CORNEAL ENDOTHELIUM; GENE-EXPRESSION PROFILES; SJOGRENS-SYNDROME;
CHEMOTACTIC CYTOKINES; OCULAR SURFACE; TEAR FLUID; INFLAMMATION; CCR2;
KERATOCONJUNCTIVITIS; INTERLEUKIN-8
AB Objective: To determine the effect of a topical antagonist to the chemokine receptor 2 (CCR2) in a murine model of dry eye disease.
Methods: The effects of a topical CCR2 antagonist and a vehicle control treatment were studied in murine dry eyes. A controlled environment chamber induced dry eye by exposing mice to high-flow desiccated air. Corneal fluorescein staining and enumeration of corneal CD11b(+) and conjunctival CD3(+) T cells were performed in the different groups. Real-time polymerase chain reaction was performed to quantify expression of different inflammatory cytokine transcripts in the cornea and conjunctiva.
Results: Eyes receiving the formulation containing CCR2 antagonist showed a significant decrease in corneal fluorescein staining and decreased infiltration of corneal CD11b(+) cells and conjunctival T cells compared with the vehicle-treated and untreated dry eye groups. The CCR2 antagonist also significantly decreased messenger RNA expression levels of interleukins 1 alpha and 1 beta in the cornea, and tumor necrosis factor alpha and interleukin 1 beta in the conjunctiva.
Conclusion: Topical application of CCR2 antagonist is associated with significant improvement in dry eye disease and is reflected by a decrease in inflammation at the clinical, molecular, and cellular levels.
C1 [Goyal, Sunali; Chauhan, Sunil K.; Zhang, Qiang; Dana, Reza] Schepens Eye Res Inst, Boston, MA 02114 USA.
[Goyal, Sunali; Chauhan, Sunil K.; Zhang, Qiang; Dana, Reza] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Dana, Reza] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Dana, R (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM reza.dana@schepens.harvard.edu
FU Johnson & Johnson Vision Care, Inc.
FX This study was supported by Johnson & Johnson Vision Care, Inc.
NR 34
TC 33
Z9 34
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JUL
PY 2009
VL 127
IS 7
BP 882
EP 887
PG 6
WC Ophthalmology
SC Ophthalmology
GA 470CK
UT WOS:000267950500007
PM 19597109
ER
PT J
AU Talbert, ML
Ashwood, ER
Brownlee, NA
Clark, JR
Horowitz, RE
Lepoff, RB
Neumann, A
Otis, CN
Powell, SZE
Sodeman, TM
AF Talbert, Michael L.
Ashwood, Edward R.
Brownlee, Noel A.
Clark, Jimmy R.
Horowitz, Richard E.
Lepoff, Ronald B.
Neumann, Ann
Otis, Christopher N.
Powell, Suzanne Zein-Eldin
Sodeman, Thomas M.
TI Resident Preparation for Practice A White Paper From the College of
American Pathologists and Association of Pathology Chairs
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Editorial Material
ID SURGICAL-PATHOLOGY; ANATOMIC PATHOLOGY; CURRICULUM CONTENT; COMPETENCE;
PROPOSAL; FUTURE
C1 [Talbert, Michael L.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA.
[Ashwood, Edward R.] Univ Utah, Dept Pathol, Salt Lake City, UT USA.
[Ashwood, Edward R.] ARUP Labs Inc, Salt Lake City, UT USA.
[Brownlee, Noel A.] Greenville Hosp Syst & Pathol Associates & Consul, Dept Pathol, Greenville, SC USA.
[Clark, Jimmy R.] ACL Labs, SC, W Allis, WI USA.
[Horowitz, Richard E.] USC Sch Med, Dept Pathol, Los Angeles, CA USA.
[Horowitz, Richard E.] Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA.
[Lepoff, Ronald B.] Univ Colorado Hosp, Dept Pathol, Aurora, CO USA.
[Neumann, Ann] Coll Amer Pathologists, Northfield, IL USA.
[Otis, Christopher N.] Bayside Med Ctr, Dept Pathol, Springfield, MA USA.
[Powell, Suzanne Zein-Eldin] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA.
RP Talbert, ML (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, 940 Stanton L Young,BMSB 451, Oklahoma City, OK 73104 USA.
EM michael-talbert@ouhsc.edu
NR 18
TC 22
Z9 22
U1 0
U2 0
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD JUL
PY 2009
VL 133
IS 7
BP 1139
EP 1147
PG 9
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 464DI
UT WOS:000267484900015
PM 19642741
ER
PT J
AU Cowan, RE
Nash, MS
Collinger, JL
Koontz, AM
Boninger, ML
AF Cowan, Rachel E.
Nash, Mark S.
Collinger, Jennifer L.
Koontz, Alicia M.
Boninger, Michael L.
TI Impact of Surface Type, Wheelchair Weight, and Axle Position on
Wheelchair Propulsion by Novice Older Adults
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Aged; Biomechanics; Rehabilitation; Wheelchairs
ID KINETIC-ANALYSIS; SEAT POSITION; ENERGY-COST; SYSTEM TILT; BIOMECHANICS;
SHOULDER; STANDARD; ANGLES
AB Impact of surface type, wheelchair weight, and axle position on wheelchair propulsion by novice older adults.
Objective: To examine the impact of surface type, wheelchair weight, and rear axle position on older adult propulsion biomechanics.
Design: Crossover trial.
Setting: Biomechanics laboratory.
Participants: Convenience sample of 53 ambulatory older adults with minimal wheelchair experience (65-87y); men, n=20; women, n=33.
Intervention: Participants propelled 4 different wheelchair configurations over 4 surfaces: tile, low carpet, high carpet, and an 8% grade ramp (surface, chair order randomized). Chair configurations included (1) unweighted chair with an ante axle position, (2) 9.05kg weighted chair with an anterior axle position, (3) unweighted chair with a posterior axle position (Delta 0.08m), and (4) 9.05kg weighted chair with a posterior axle position (Delta 0.08m). Weight was added to a titanium folding chair, simulating the weight difference between very light and depot wheelchairs. Instrumented wheels measured propulsion kinetics.
Main Outcome Measures: Average self-selected velocity, push frequency, stroke length, peak resultant and tangential force.
Results: Velocity decreased as surface rolling resistance or chair weight increased. Peak resultant and tangential forces increased as chair weight increased, as surface resistance increased, and with a posterior axle position. The effect of a posterior axle position was greater on high carpet and the ramp. The effect of weight was constant, but was more easily observed on high carpet and ramp. The effects of axle position and weight were independent of one another.
Conclusion: Increased surface resistance decreases selfselected velocity and increases peak forces. Increased weight decreases self-selected velocity and increases forces. Anterior axle positions decrease forces, more so on high carpet. The effects of weight and axle position are independent. The greatest reductions in peak forces occur in lighter chairs with anterior axle positions.
C1 [Cowan, Rachel E.; Collinger, Jennifer L.; Koontz, Alicia M.; Boninger, Michael L.] Ctr Excellence Wheelchairs & Related Technol, VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA.
[Collinger, Jennifer L.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA.
[Boninger, Michael L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Cowan, Rachel E.; Koontz, Alicia M.; Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA.
[Collinger, Jennifer L.; Koontz, Alicia M.] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA.
[Collinger, Jennifer L.; Koontz, Alicia M.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA.
[Nash, Mark S.] Univ Miami, Miller Sch Med, Dept Neurol Surg, Miami, FL 33136 USA.
[Cowan, Rachel E.; Nash, Mark S.] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA.
RP Boninger, ML (reprint author), Ctr Excellence Wheelchairs & Related Technol, VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, 5180 Highland Dr 151R-1, Pittsburgh, PA 15206 USA.
EM boninger@pitt.edu
OI Boninger, Michael/0000-0001-6966-919X
FU National Institutes of Health [1 F31 HD053986-01, P30 AG024827,
AG023641]; National Science Foundation [DGE0333420]; Department of
Veterans Affairs Rehabilitation Research and Development [B3142C]
FX Supported by the National Institutes of Health (grant nos. 1 F31
HD053986-01, P30 AG024827, AG023641), the National Science Foundation
(DGE0333420, Graduate Research Fellowship), and the Department of
Veterans Affairs Rehabilitation Research and Development (grant no.
B3142C).
NR 21
TC 33
Z9 33
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD JUL
PY 2009
VL 90
IS 7
BP 1076
EP 1083
DI 10.1016/j.apmr.2008.10.034
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 470SA
UT WOS:000267999000002
PM 19577019
ER
PT J
AU Jaffer, FA
Libby, P
Weissleder, R
AF Jaffer, Farouc A.
Libby, Peter
Weissleder, Ralph
TI Optical and Multimodality Molecular Imaging Insights Into
Atherosclerosis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Review
DE atherosclerosis; molecular imaging; optical; fluorescence;
multimodality; nanoparticle
ID ULTRASMALL SUPERPARAMAGNETIC PARTICLES; EARLY-STAGE ATHEROSCLEROSIS;
CATHEPSIN-K ACTIVITY; MACROPHAGES IN-VIVO; OXIDE-ENHANCED MRI;
IRON-OXIDE; CARDIOVASCULAR-DISEASE; MAGNETIC NANOPARTICLES; INTRAPLAQUE
HEMORRHAGE; NONINVASIVE DETECTION
AB Imaging approaches that visualize molecular targets rather than anatomic structures aim to illuminate vital molecular and cellular aspects of atherosclerosis biology in vivo. Several such molecular imaging strategies stand ready for rapid clinical application. This review describes the growing role of in vivo optical molecular imaging in atherosclerosis and highlights its ability to visualize atheroma inflammation, calcification, and angiogenesis. In addition, we discuss advances in multimodality probes, both in the context of multimodal imaging as well as multifunctional, or "theranostic," nanoparticles. This review highlights particular molecular imaging strategies that possess strong potential for clinical translation. (Arterioscler Thromb Vasc Biol. 2009; 29: 1017-1024.)
C1 [Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Jaffer, Farouc A.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA.
[Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Libby, Peter] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Jaffer, Farouc A.; Libby, Peter; Weissleder, Ralph] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Cambridge, MA 02138 USA.
RP Jaffer, FA (reprint author), Simches Res Bldg,Room 3206,185 Cambridge St, Boston, MA 02114 USA.
EM fjaffer@mgh.harvard.edu
OI Jaffer, Farouc/0000-0001-7980-384X
FU Howard Hughes Medical Institute; NCI NIH HHS [R24 CA092782-05, R24
CA092782, R24-CA92782]; NHLBI NIH HHS [R01 HL078641, R01 HL078641-04,
R01-HL078641, U01 HL080731, U01 HL080731-04, UO1-HL080731]
NR 80
TC 100
Z9 104
U1 4
U2 29
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP 1017
EP U98
DI 10.1161/ATVBAHA.108.165530
PG 20
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500006
PM 19359659
ER
PT J
AU Butler, J
Kalogeropoulos, A
Georgiopoulou, V
de Rekeneire, N
Rodondi, N
Smith, AL
Hoffmann, U
Kanaya, A
Newman, AB
Kritchevsky, SB
Vasan, RS
Wilson, PWF
Harris, TB
AF Butler, Javed
Kalogeropoulos, Andreas
Georgiopoulou, Vasiliki
de Rekeneire, Nathalie
Rodondi, Nicolas
Smith, Andrew L.
Hoffmann, Udo
Kanaya, Alka
Newman, Anne B.
Kritchevsky, Stephen B.
Vasan, Ramachandran S.
Wilson, Peter W. F.
Harris, Tamara B.
CA Hlth ABC Study
TI Serum Resistin Concentrations and Risk of New Onset Heart Failure in
Older Persons The Health, Aging, and Body Composition (Health ABC) Study
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE heart failure; elderly; resistin
ID INSULIN-RESISTANCE; PLASMA RESISTIN; CARDIOVASCULAR EVENTS;
MYOCARDIAL-INFARCTION; INFLAMMATORY MARKERS; MULTIPLE IMPUTATION;
ISCHEMIC-STROKE; ADIPOSE-TISSUE; OBESITY; ATHEROSCLEROSIS
AB Objective-Resistin is associated with inflammation and insulin resistance and exerts direct effects on myocardial cells including hypertrophy and altered contraction. We investigated the association of serum resistin concentrations with risk for incident heart failure (HF) in humans.
Methods and Results-We studied 2902 older persons without prevalent HF (age, 73.6 +/- 2.9 years; 48.1% men; 58.8% white) enrolled in the Health, Aging, and Body Composition (Health ABC) Study. Correlation between baseline serum resistin concentrations (20.3 +/- 10.0 ng/mL) and clinical variables, biochemistry panel, markers of inflammation and insulin resistance, adipocytokines, and measures of adiposity was weak (all rho <0.25). During a median follow-up of 9.4 years, 341 participants (11.8%) developed HF. Resistin was strongly associated with risk for incident HF in Cox proportional hazards models controlling for clinical variables, biomarkers, and measures of adiposity (HR, 1.15 per 10.0 ng/mL in adjusted model; 95% CI, 1.05 to 1.27; P = 0.003). Results were comparable across sex, race, diabetes mellitus, and prevalent and incident coronary heart disease subgroups. In participants with available left ventricular ejection fraction at HF diagnosis (265 of 341; 77.7%), association of resistin with HF risk was comparable for cases with reduced versus preserved ejection fraction.
Conclusions-Serum resistin concentrations are independently associated with risk for incident HF in older persons. (Arterioscler Thromb Vasc Biol. 2009; 29: 1144-1149.)
C1 [Butler, Javed; Kalogeropoulos, Andreas; Georgiopoulou, Vasiliki; Smith, Andrew L.; Wilson, Peter W. F.] Emory Univ, Atlanta, GA 30322 USA.
[de Rekeneire, Nathalie] Epictr, Paris, France.
[Rodondi, Nicolas] Univ Lausanne, CH-1015 Lausanne, Switzerland.
[Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Kalogeropoulos, Andreas] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Harris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Butler, J (reprint author), Emory Univ Hosp, Div Cardiol, 1364 Clifton Rd NE,Suite AT 430, Atlanta, GA 30322 USA.
EM javed.butler@emory.edu
RI Kalogeropoulos, Andreas/A-9494-2009; Newman, Anne/C-6408-2013;
OI Kalogeropoulos, Andreas/0000-0002-1284-429X; Kritchevsky,
Stephen/0000-0003-3336-6781; Newman, Anne/0000-0002-0106-1150;
Ramachandran, Vasan/0000-0001-7357-5970
FU National Institute of Aging, National Institutes of Health, Bethesda Md;
[N01-AG-6-2101]; [N01-AG-62103]; [N01-AG-6-2106]; [2K24 HL04334]
FX This research was supported in part by the Intramural Research Program
of the National Institute of Aging, National Institutes of Health,
Bethesda Md, and by grants N01-AG-6-2101, N01-AG-62103, and
N01-AG-6-2106. Dr Vasan was supported by a research career award 2K24
HL04334.
NR 31
TC 41
Z9 42
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP 1144
EP U236
DI 10.1161/ATVBAHA.109.186783
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500025
PM 19372460
ER
PT J
AU Arany, ZP
Foo, SY
Chinsomboon, J
Girnun, G
Cooper, M
Ruas, J
Bommi-Reddy, A
Rangwala, S
Baek, KH
Rosenzweig, A
Spiegelman, B
AF Arany, Zolt P.
Foo, Shi-Yin
Chinsomboon, Jessica
Girnun, Geoff
Cooper, Marcus
Ruas, Jorge
Bommi-Reddy, Archana
Rangwala, Shamina
Baek, Kwan Hyuck
Rosenzweig, Anthony
Spiegelman, Bruce
TI HIF-Independent Regulation of Angiogenesis in Ischemia and Exercise
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Arany, Zolt P.; Foo, Shi-Yin; Chinsomboon, Jessica; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Girnun, Geoff; Cooper, Marcus; Ruas, Jorge; Bommi-Reddy, Archana; Rangwala, Shamina; Baek, Kwan Hyuck; Spiegelman, Bruce] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E16
EP E17
PG 2
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500062
ER
PT J
AU Higashimori, M
Tatro, JB
Moore, KJ
Galper, JB
Mendelsohn, ME
Beasley, D
AF Higashimori, Mie
Tatro, Jeffrey B.
Moore, Kathryn J.
Galper, Jonas B.
Mendelsohn, Michael E.
Beasley, Debbie
TI Role of Toll-like Receptors 2 and 4 in Early Arterial Inflammation and
Lipid Accumulation in Apolipoprotein E-Deficient Mice
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Higashimori, Mie; Tatro, Jeffrey B.; Galper, Jonas B.; Mendelsohn, Michael E.; Beasley, Debbie] Tufts Med Cntr, Boston, MA USA.
[Moore, Kathryn J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E113
EP E114
PG 2
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500545
ER
PT J
AU Martin, MC
Korepta, L
Dasilva, C
Andersen, ND
Monahan, TS
Ferran, C
LoGerfo, FW
AF Martin, Michelle C.
Korepta, Lindsey
Dasilva, Cleide
Andersen, Nicholas D.
Monahan, Thomas S.
Ferran, Christiane
LoGerfo, Frank W.
TI MARCKS Silencing Upregulates p27(kip1) Expression in Vascular Smooth
Muscle Cells in Vitro
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc, Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Martin, Michelle C.; Korepta, Lindsey; Dasilva, Cleide; Andersen, Nicholas D.; Monahan, Thomas S.; Ferran, Christiane; LoGerfo, Frank W.] BIDMC, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E120
EP E120
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500577
ER
PT J
AU van Gils, JM
Fernandes, LR
Derby, MC
Balcells, M
Alvarez-Leite, JI
Moore, KJ
AF van Gils, Janine M.
Fernandes, Luciana R.
Derby, Merran C.
Balcells, Mercedes
Alvarez-Leite, Jaqueline I.
Moore, Kathryn J.
TI Axonal Guidance Cues Mediate Monocyte Chemotaxis, and Their Expression
on Endothelial Cells Is Regulated by Atherosclerotic Stimuli
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [van Gils, Janine M.; Fernandes, Luciana R.; Derby, Merran C.; Moore, Kathryn J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Balcells, Mercedes] MIT, Cambridge, MA 02139 USA.
[Alvarez-Leite, Jaqueline I.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E61
EP E61
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500279
ER
PT J
AU Wong, MC
Hu, LH
Van Diepen, JA
Romijn, JA
Voshol, PJ
Havekes, LM
Shoelson, SE
Tamsma, JT
Rensen, PC
Hiemstra, PS
Berbee, JF
AF Wong, Man-Chi
Hu, Lihui
Van Diepen, Janna A.
Romijn, Johannes A.
Voshol, Peter J.
Havekes, Louis M.
Shoelson, Steven E.
Tamsma, Jouke T.
Rensen, Patrick C.
Hiemstra, Pieter S.
Berbee, Jimmy F.
TI Chronic Hepatic Inflammation Severely Aggravates Atherosclerosis
Development
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Wong, Man-Chi; Hu, Lihui; Van Diepen, Janna A.; Romijn, Johannes A.; Voshol, Peter J.; Tamsma, Jouke T.; Rensen, Patrick C.; Hiemstra, Pieter S.; Berbee, Jimmy F.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Havekes, Louis M.] TNO Biosci, Leiden, Netherlands.
[Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E98
EP E98
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500463
ER
PT J
AU Jones, KL
McHugh, GA
Glickstein, LJ
Steere, AC
AF Jones, Kathryn L.
McHugh, Gail A.
Glickstein, Lisa J.
Steere, Allen C.
TI Analysis of Borrelia burgdorferi Genotypes in Patients With Lyme
Arthritis High Frequency of Ribosomal RNA Intergenic Spacer Type 1
Strains in Antibiotic-Refractory Arthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID SENSU-STRICTO; HEMATOGENOUS DISSEMINATION; GENETIC DIVERSITY; JOINT
FLUID; NORTH-AMERICA; DISEASE; OSPC; MICE; ASSOCIATION; TURICATAE
AB Objective. Most of the Borrelia burgdorferi genotypes have been isolated from erythema migrans (EM) skin lesions in patients with Lyme disease. OspC type K strains, which are 16S-23S ribosomal RNA intergenic spacer type 2 (RST2) strains, are most commonly recovered, but a higher percentage of OspC type A strains (RST1), the next most commonly recovered type, is detectable in blood. The goal of this study was to determine the B burgdorferi genotypes in the joints of patients with Lyme arthritis.
Methods. Joint fluid samples from 124 patients seen over a 30-year period were analyzed for OspC types by semi-nested polymerase chain reaction (PCR) and sequencing, and for RSTs by nested PCR and restriction fragment length polymorphism analysis. These results were correlated with clinical outcome.
Results. OspC and RST genotypes were identified in 49 of the 124 joint fluid samples (40%). In these 49 samples, OspC type K strains (RST2) were identified in 21 samples (43%), OspC type A strains (RST1) were identified in 11 samples (22%), and 8 other OspC types and all 3 RSTs were identified among the remaining 17 samples (35%). However, among the 17 patients who had been treated with antibiotics according to current guidelines, all 7 patients who were infected with RST1 strains had antibiotic-refractory arthritis, compared with 4 of 6 patients infected with RST2 strains and only I of 4 infected with RST3 strains (P = 0.03).
Conclusion. Most of the B burgdorferi genotypes, particularly OspC type K (RST2), were identified in the joint fluid of patients with Lyme arthritis, and the genotype frequencies found in joints reflected those in EM skin lesions. However, RST1 strains were most frequent in patients with antibiotic-refractory arthritis. Our results help to further the understanding of the differential pathogenicity of strains of B burgdorferi.
C1 [Steere, Allen C.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Steere, AC (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 55 Fruit St,CNY 149-8301, Boston, MA 02114 USA.
EM asteere@partners.org
OI Jones, Kathryn/0000-0003-3815-5713
FU NIAMS NIH HHS [AR-20358, AR-007258, R01 AR020358, R01 AR020358-34, T32
AR007258, T32 AR007258-32]
NR 41
TC 27
Z9 27
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM
JI Arthritis Rheum.
PD JUL
PY 2009
VL 60
IS 7
BP 2174
EP 2182
DI 10.1002/art.24812
PG 9
WC Rheumatology
SC Rheumatology
GA 470HN
UT WOS:000267965900035
PM 19565522
ER
PT J
AU Zhou, Y
Xiao, XQ
Chen, LF
Yang, R
Shi, JD
Du, XL
Klocker, H
Park, I
Lee, C
Zhang, J
AF Zhou, Ying
Xiao, Xiang-Qian
Chen, Lin-Feng
Yang, Rui
Shi, Jian-Dang
Du, Xiao-Ling
Klocker, Helmut
Park, Irwin
Lee, Chung
Zhang, Ju
TI Proliferation and phenotypic changes of stromal cells in response to
varying estrogen/androgen levels in castrated rats
SO ASIAN JOURNAL OF ANDROLOGY
LA English
DT Article
DE androgens; castration; estrogen; prostatic hyperplasia; rat; stromal
cells
ID SMOOTH-MUSCLE-CELLS; BENIGN PROSTATIC HYPERPLASIA; MYOSIN ISOFORM
EXPRESSION; GENE-EXPRESSION; F344 RATS; ANDROGEN; ESTROGEN; ESTRADIOL;
DIFFERENTIATION; PATHOGENESIS
AB It is known that human benign prostatic hyperplasia might arise from an estrogen/androgen (E/T) imbalance. We studied the response of castrated rat prostate to different ratios of circulating E/T. The castrated male Wistar rats were randomly injected with E/T at different ratios for 4 weeks. The prostates of E/T (1:100) group showed a distinct prostatic hyperplasia response by prostatic index, hematoxylin and eosin staining, and quantitative immunohistochemical analysis of alpha-smooth muscle actin (SMA). In this group, cells positive for Vimentin, nonmuscle myosin heavy chain (NMMHC) and proliferating cell nuclear antigen (PCNA) increased in the stroma and epithelium. Furthermore, the mRNA levels of smooth muscle myosin heavy chain (SMMHC) and NMMHC increased. So E/T at a ratio of 1:100 can induce a stromal hyperplastic response in the prostate of castrated rats. The main change observed was an increase of smooth muscle cells, whereas some epithelial changes were also seen in the rat prostates.
C1 [Zhou, Ying; Xiao, Xiang-Qian; Yang, Rui; Shi, Jian-Dang; Du, Xiao-Ling; Zhang, Ju] Nankai Univ, Dept Biochem & Mol Biol, Coll Life Sci, Bioact Mat Key Lab,Minist Educ, Tianjin 300071, Peoples R China.
[Chen, Lin-Feng] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Klocker, Helmut] Innsbruck Med Univ, Dept Urol, A-6020 Innsbruck, Austria.
[Park, Irwin; Lee, Chung] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA.
RP Zhang, J (reprint author), Nankai Univ, Dept Biochem & Mol Biol, Coll Life Sci, Bioact Mat Key Lab,Minist Educ, Tianjin 300071, Peoples R China.
EM Shijd@nankai.edu.cn; zhangju@nankai.edu.cn
RI Lee, Chung-Chieh/B-7238-2009
FU National Basic Research Program [2009CB918900]; National Natural Science
Foundation of China [30672101, 30872592]; Specialized Research Fund for
the Doctoral Program of Higher Education [20070055023]; Tianjin
Municipal Science and Technology Commission [06YFSYSF02000,
07jczdjc08300]
FX This research was funded by the following grants: the National Basic
Research Program (973 Program, No. 2009CB918900), the National Natural
Science Foundation of China (grant No. 30672101, 30872592), the
Specialized Research Fund for the Doctoral Program of Higher Education
(No. 20070055023) and the key research project of Tianjin Municipal
Science and Technology Commission (grant No. 06YFSYSF02000,
07jczdjc08300). The authors declare that there is no conflict of
interest that would prejudice the impartiality of this scientific work.
NR 38
TC 12
Z9 13
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1008-682X
J9 ASIAN J ANDROL
JI Asian J. Androl.
PD JUL
PY 2009
VL 11
IS 4
BP 451
EP 459
DI 10.1038/aja.2009.28
PG 9
WC Andrology; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 465QB
UT WOS:000267600800007
PM 19483715
ER
PT J
AU Stephenson, LM
Miller, BC
Ng, A
Eisenberg, J
Zhao, ZJ
Cadwell, K
Graham, DB
Mizushima, NN
Xavier, R
Virgin, HW
Swat, W
AF Stephenson, Linda M.
Miller, Brian C.
Ng, Aylwin
Eisenberg, Jason
Zhao, Zijiang
Cadwell, Ken
Graham, Daniel B.
Mizushima, Noboru N.
Xavier, Ramnik
Virgin, Herbert W.
Swat, Wojciech
TI Identification of Atg5-dependent transcriptional changes and increases
in mitochondrial mass in Atg5-deficient T lymphocytes
SO AUTOPHAGY
LA English
DT Article
DE T cells; cell differentiation and development; transgenic/knockout mice;
ATG5; mitochondria
ID HOMEOSTATIC PROLIFERATION; CELL-DEATH; RAT HEPATOCYTES; AUTOPHAGY;
DISEASE; IMMUNITY; ATG5; MICE; DEGRADATION; TOLERANCE
AB Autophagy is implicated in many functions of mammalian cells such as organelle recycling, survival and differentiation, and is essential for the maintenance of T and B lymphocytes. Here, we demonstrate that autophagy is a constitutive process during T cell development. Deletion of the essential autophagy genes Atg5 or Atg7 in T cells resulted in decreased thymocyte and peripheral T cell numbers, and Atg5-deficient T cells had a decrease in cell survival. We employed functional-genetic and integrative computational analyses to elucidate specific functions of the autophagic process in developing T-lineage lymphocytes. Our whole-genome transcriptional profiling identified a set of 699 genes differentially expressed in Atg5-deficient and Atg5-sufficient thymocytes (Atg5-dependent gene set). Strikingly, the Atg5-dependent gene set was dramatically enriched in genes encoding proteins associated with the mitochondrion. In support of a role for autophagy in mitochondrial maintenance in T lineage cells, the deletion of Atg5 led to increased mitochondrial mass in peripheral T cells. We also observed a correlation between mitochondrial mass and Annexin-V staining in peripheral T cells. We propose that autophagy is critical for mitochondrial maintenance and T cell survival. We speculate that, similar to its role in yeast or mammalian liver cells, autophagy is required in T cells for the removal of damaged or aging mitochondria and that this contributes to the cell death of autophagy-deficient T cells.
C1 [Stephenson, Linda M.; Miller, Brian C.; Zhao, Zijiang; Cadwell, Ken; Graham, Daniel B.; Virgin, Herbert W.; Swat, Wojciech] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA.
[Virgin, Herbert W.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Ng, Aylwin; Eisenberg, Jason; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA.
[Mizushima, Noboru N.] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Tokyo, Japan.
[Mizushima, Noboru N.] Japan Sci & Technol Agcy, Kawaguchi, Saitama, Japan.
RP Swat, W (reprint author), Washington Univ, Dept Pathol & Immunol, Sch Med, 660 S Euclid Ave,Box 8118, St Louis, MO 63110 USA.
EM swat@wustl.edu
RI Mizushima, Noboru/C-3635-2009
OI Cadwell, Ken/0000-0002-5860-0661; Mizushima, Noboru/0000-0002-6258-6444
FU NIH [P30-AR048335, R01-A1061077, CA74730, U54A1057160, R01-A1062773,
R01-DK83756, 5-T32-A107163-27]; Ministry of Education, Culture, Sports,
Science and Technology, Japan; Toray Science Foundation; Crohn's and
Colitis Foundation of America; Damon Runyon Cancer Research Foundation
[DRG-1972-08]
FX Financial support for this work was provided by NIH grants P30-AR048335
and R01-A1061077 MS.), CA74730 and U54A1057160 (H.WV), R01-A1062773 and
R01-DK83756 (RX), 5-T32-A107163-27 (L.M.S.), Grants-in-Aid for
Scientific Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan, and the Toray Science Foundation (N.M).
A. N. is a recipient of a fellowship award from the Crohn's and Colitis
Foundation of America. K.C. is the Lallage Feazel Wall Fellow of the
Damon Runyon Cancer Research Foundation, DRG-1972-08.
NR 46
TC 94
Z9 96
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD JUL 1
PY 2009
VL 5
IS 5
BP 625
EP 635
PG 11
WC Cell Biology
SC Cell Biology
GA 473KQ
UT WOS:000268205300006
PM 19276668
ER
PT J
AU Sharpe, AL
Phillips, TJ
AF Sharpe, Amanda L.
Phillips, Tamara J.
TI Central urocortin 3 administration decreases limited-access ethanol
intake in nondependent mice
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE alcohol drinking; corticotrophin-releasing factor(2); ingestion;
microinjections; mouse; urocortin 3
ID CORTICOTROPIN-RELEASING-FACTOR; MESSENGER-RNA EXPRESSION; IMPAIRED
STRESS-RESPONSE; ANXIETY-LIKE BEHAVIOR; FACTOR-RECEPTOR; DEPENDENT RATS;
CENTRAL NUCLEUS; CRF RECEPTORS; FOOD-INTAKE; BRAIN
AB Stress and alcohol abuse are co-related. Acute alcohol is anxiolytic and stress is cited as a factor in relapse to alcohol use. A primary mediator of the stress response is the neuropeptide corticotropin-releasing factor (CRF). The CRF family of endogenous ligands includes urocortin 3 (Ucn 3), which binds selectively to the CRF type 2 receptor and has been implicated in ethanol consumption in dependent and withdrawing rats. The objective of this study was to examine the effect of Ucn 3, delivered centrally to nondependent mice, on limited-access ethanol consumption. Adult MUM mice were trained to self-administer 10% ethanol during daily, 2-h limited-access sessions, using lickometers to assess drinking patterns for both ethanol and water. Sterile saline or 0.3, 1, or 3 nmol of Ucn 3 was microinjected into the lateral ventricle immediately before the limited-access session in a within-subjects design. There was a significant decrease in ethanol (both ml and g/kg), but not water, intake following Ucn 3 treatment, explained by a change in size of the largest lick run. Food intake at both 2 h and 24 h after injection was statistically unaffected by Ucn 3 administration. These results establish a role for CRF type 2 receptors in a nondependent mouse model of ethanol self-ad ministration. Behavioural Pharmacology 20:346-351 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Sharpe, Amanda L.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Dept Behav Neurosci, Portland, OR 97201 USA.
[Phillips, Tamara J.] Portland VA Med Ctr, Res Serv, Portland, OR USA.
RP Sharpe, AL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol MC7756, 7703 Floyd Curl, San Antonio, TX 78229 USA.
EM sharpea@uthscsa.edu
FU National Institute on Alcohol Abuse and Alcoholism [AA014747, AA013331,
AA010760]; Department of Veterans Affairs
FX This study was supported by NIH grants from the National Institute on
Alcohol Abuse and Alcoholism AA014747 to A.L.S., AA013331 to TJ.P., and
AA010760 to TJ.P, and by the Department of Veterans Affairs.
NR 34
TC 16
Z9 16
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD JUL
PY 2009
VL 20
IS 4
BP 346
EP 351
DI 10.1097/FBP.0b013e32832f01ba
PG 6
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 477QW
UT WOS:000268534600007
PM 19581799
ER
PT J
AU Coaxum, SD
Garnovskaya, MN
Gooz, M
Baldys, A
Raymond, JR
AF Coaxum, Sonya D.
Garnovskaya, Maria N.
Gooz, Monika
Baldys, Aleksander
Raymond, John R.
TI Epidermal growth factor activates Na+/H+ exchanger in podocytes through
a mechanism that involves Janus kinase and calmodulin
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Cytosensor microphysiometer; ECAR; Phosphorylation; AG1478
ID RECEPTOR TYROSINE KINASE; NEPHROTIC SYNDROME; EGF-RECEPTOR;
INTRACELLULAR PH; 5-HT1A RECEPTOR; CELL BIOLOGY; PHOSPHORYLATION;
INJURY; INHIBITION; PROTEINS
AB Sodium-proton exchanger type 1 (NHE-1) is ubiquitously expressed, is activated by numerous growth factors, and plays significant roles in regulating intracellular pH and cellular volume, proliferation and cytoskeleton. Despite its importance, little is known about its regulation in renal glomerular podocytes. In the current work, we studied the regulation of NHE-1 activity by the epidermal growth factor receptor (EGFR) in cultured podocytes. RT-PCR demonstrated mRNAs for NHE-1 and NHE-2 in differentiated podocytes, as well as for EGFR subunits EGFR/ErbB1, Erb3, and ErbB4. EGF induced concentration-dependent increases in proton efflux in renal podocytes as assessed using a Cytosensor microphysiometer, were diminished in the presence of 5-(N-methyl-N-isobutyl) amiloride or in a sodium-free solution. Furthermore, pharmacological inhibitors of Janus kinase (Jak2) and calmodulin (CaM) attenuated EGF-induced NHE-1 activity. Co-immunoprecipitation studies determined that EGF induced formation of complexes between Jak2 and CaM, as well as between CaM and NHE-1. In addition, EGF increased levels of tyrosine phosphorylation of Jak2 and CaM. The EGFR kinase inhibitor, AG1478, blocked activation of NHE-1, but did not block EGF-induced phosphorylation of Jak2 or CaM. These results suggest that EGF induces NHE-1 activity in podocytes through two pathways: (1) EGF -> EGFR -> Jak2 activation (independent of EGFR tyrosine kinase activity) -> tyrosine phosphorylation of CaM -> CaM binding to NHE-1 -> conformational change of NHE-1 -> activation of NHE-1; and (2) EGF -> EGFR -> EGFR kinase activation -> association of CaM with NHE-1 (independent of Jak2) -> conformational change of NHE-1 -> activation of NHE-1. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Raymond, John R.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
Ralph H Johnson VA Med Ctr, Med & Res Serv, Charleston, SC USA.
RP Raymond, JR (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Colcock Hall,Off Provost,179 Ashley Ave, Charleston, SC 29425 USA.
EM raymondj@musc.edu
FU National Institutes of Health [DK52448, GM63909, DK52448-S2]; American
Heart Association [0655445U]
FX The authors want to thank Dr. Peter Mundel for his advice and
assistance, and donation of podocytes. We also would like to thank the
Hollings Cancer Center Molecular Imaging Facility at MUSC. This work was
supported by grants from the Department of Veterans Affairs (Merits
Awards and a REAP award to JRR and MNG), the National Institutes of
Health (DK52448 and GM63909 to JRR, and DK52448-S2 to SDC), the American
Heart Association (GIA 0655445U to MNG), and a laboratory endowment
jointly supported by the M.U.S.C. Division of Nephrology and Dialysis
Clinics, Inc. (JRR). The work also was supported by VA shared equipment
grants (confocal microscope and micro physiometer).
NR 50
TC 28
Z9 28
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JUL
PY 2009
VL 1793
IS 7
BP 1174
EP 1181
DI 10.1016/j.bbamcr.2009.03.006
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 467VY
UT WOS:000267772400006
PM 19341767
ER
PT J
AU Martin, PJ
Bachier, CR
Klingemann, HG
McCarthy, PL
Szabolcs, P
Uberti, JP
Schuster, MW
Weisdorf, D
Chao, NJ
Kebriaei, P
Shpall, EJ
MacMillan, ML
Soiffer, RJ
AF Martin, Paul J.
Bachier, Carlos R.
Klingemann, Hans-Georg
McCarthy, Philip L.
Szabolcs, Paul
Uberti, Joseph P.
Schuster, Michael W.
Weisdorf, Daniel
Chao, Nelson J.
Kebriaei, Partow
Shpall, Elizabeth J.
MacMillan, Margaret L.
Soiffer, Robert J.
TI Endpoints for Clinical Trials Testing Treatment of Acute
Graft-versus-Host Disease: A Joint Statement
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Review
DE Acute graft-versus-host disease; Clinical trials; Endpoints; Guidelines
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; HEMATOPOIETIC-CELL
TRANSPLANTATION; ALLOGENEIC MARROW TRANSPLANTATION; RANDOMIZED-TRIAL;
CROHNS-DISEASE; MULTIPLE-MYELOMA; RESPONSE CRITERIA; GRADING SYSTEMS;
INITIAL THERAPY
AB Currently, no agents are approved by the United States Food and Drug Administration (FDA) for either prevention or treatment of acute graft-versus-host disease (aGVHD). Formal precedents establishing a comparative basis for assessing the efficacy and safety of new investigational agents are still lacking. As a step toward addressing this problem, a panel of experts met on 2 occasions to reach consensus on recommendations for terminology describing a clinically meaningful primary endpoint in studies assessing treatment for aGVHD. The panel recommended terminology for "very good partial response" (VGPR) that includes both diagnostic and functional criteria. The central hypothesis leading to this proposal is that the potential harm of giving more treatment than needed to produce or maintain complete response exceeds the harm of slight under-treatment that may be associated with less than complete response. VGPR clearly cannot be used as the sole outcome measure in GVHD treatment trials, and must be considered in the context of survival and safety. The proposed use of VGPR as the primary endpoint in GVHD treatment trials will remain provisional until its use has been validated through experience.
C1 [Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Bachier, Carlos R.] Texas Transplant Inst, San Antonio, TX USA.
[Klingemann, Hans-Georg] Tufts Med Ctr, Boston, MA USA.
[McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Szabolcs, Paul; Chao, Nelson J.] Duke Univ, Med Ctr, Durham, NC USA.
[Uberti, Joseph P.] Barbara Ann Karmanos Canc Inst, Detroit, MI USA.
[Schuster, Michael W.] New York Presbyterian Hosp, New York, NY USA.
[Weisdorf, Daniel; MacMillan, Margaret L.] Univ Minnesota, Minneapolis, MN USA.
[Kebriaei, Partow; Shpall, Elizabeth J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Martin, PJ (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,1100 Fairview Ave N,D2-100, Seattle, WA 98109 USA.
EM pmartin@fherc.org
FU National Institutes of Health, Department of Health and Human Services
[CA18029]
FX The consensus meetings were held on September 11, 2007, and on May, 23,
2008, and were sponsored by Osiris Therapeutics, Inc., Columbia, MD.
Osiris provided honoraria to the participants (except P.J.M..), but did
not contribute to the meeting Output or to the content of this
manuscript. Effort by P.J.M. was supported by grant CA18029 from the
National Institutes of Health, Department of Health and Human Services.
NR 47
TC 26
Z9 26
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2009
VL 15
IS 7
BP 777
EP 784
DI 10.1016/j.bbmt.2009.03.012
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 465MD
UT WOS:000267588300002
PM 19539208
ER
PT J
AU Stiff, PJ
Bensinger, W
Abidi, MH
Gingrich, R
Artz, AS
Nademanee, A
Hansen, KS
Sobczak, C
Cutler, C
Bolwell, B
Shore, TB
Lazarus, HM
Yeager, AM
Lovelace, W
Guo, M
Dreiling, L
AF Stiff, Patrick J.
Bensinger, William
Abidi, Muneer H.
Gingrich, Roger
Artz, Andrew S.
Nademanee, Auayporn
Hansen, Keith S.
Sobczak, Christopher
Cutler, Corey
Bolwell, Brian
Shore, Tsiporah B.
Lazarus, Hillard M.
Yeager, Andrew M.
Lovelace, Wade
Guo, Matthew
Dreiling, Lyndah
TI Clinical and Ultrasonic Evaluation of Spleen Size during Peripheral
Blood Progenitor Cell Mobilization by Filgrastim: Results of an
Open-Label Trial in Normal Donors
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Stem cell; Mobilization; Spenomegaly; Spleen size
ID COLONY-STIMULATING FACTOR; SPONTANEOUS SPLENIC RUPTURE; HEMATOPOIETIC
STEM-CELLS; G-CSF; MULTIPLE-MYELOMA; HEALTHY DONORS; PATIENT;
TRANSPLANTATION; PEGFILGRASTIM; CANCER
AB Rare reports of splenic rupture have been associated with filgrastim treatment during peripheral blood progenitor cell (PBPC) mobilization in allogeneic donors. We performed a prospective study of spleen volume change in 309 normal donors who received filgrastim according to local institutional practices. Splenic assessments consisted of ultrasonography and clinical examination at baseline and on the first day of leukapheresis in 304 donors. Of these, 90 donors were also examined 2 and 4 days after the first leukapheresis and 7 days after the last leukapheresis. Median spleen volume increased 1.47-fold (range: 0.63 to 2.60) on the first leukapheresis day and declined to near pretreatment levels at 7 days after last leukapheresis. Nine percent of donors had >= 2-fold increase in splenic volume. Spleen palpability did not correlate with change in spleen volume. No donors experienced a splenic rupture. There was no correlation between change in spleen volume and filgrastim dosage, number of doses/day, peak absolute neutrophil count (ANC), CD34(+) yield, or donor baseline weight. Most donors experienced >= 1 adverse event, with 6 donors reporting serious adverse events. We conclude that the increase in splenic volume during PBPC mobilization in donors was transient, and that filgrastim was well tolerated in this study. This trial was registered at www.ClinicalTrials.gov as NCT00115128.
C1 [Stiff, Patrick J.] Loyola Univ, Med Ctr, Div Hematol Oncol, Maywood, IL 60153 USA.
[Bensinger, William] Fred Hutchinson Canc Res Ctr, Div Oncol, Seattle, WA 98104 USA.
[Abidi, Muneer H.] Wayne State Univ, Bone Marrow Transplant Program, Detroit, MI USA.
[Gingrich, Roger] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
[Artz, Andrew S.] Univ Chicago, Med Ctr, Div Hematol Oncol, Chicago, IL 60637 USA.
[Nademanee, Auayporn] City Hope Natl Med Ctr, Dept Hematol & Bone Marrow Transplant, Duarte, CA USA.
[Hansen, Keith S.] NW Marrow Transplant Program, Autologous Stem Cell Transplant Program, Portland, OR USA.
[Sobczak, Christopher] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Sobczak, Christopher] Med Coll Wisconsin, Dept Internal Med, Milwaukee, WI 53226 USA.
[Cutler, Corey] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Bolwell, Brian] Cleveland Clin, Taussig Canc Ctr, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44106 USA.
[Shore, Tsiporah B.] New York Presbyterian Hosp Cornell, Div Hematol Oncol, New York, NY USA.
[Lazarus, Hillard M.] Univ Hosp, Case Med Ctr, Dept Med, Cleveland, OH USA.
[Yeager, Andrew M.] Arizona Canc Ctr, Blood & Marrow Transplantat Program, Tucson, AZ USA.
[Lovelace, Wade; Guo, Matthew; Dreiling, Lyndah] Amgen Inc, Thousand Oaks, CA 91320 USA.
RP Stiff, PJ (reprint author), Loyola Univ Hlth Syst, 2160 S 1st Ave, Maywood, IL 60153 USA.
EM pstiff@lumc.edu
OI Abidi, Muneer/0000-0002-9936-6031
FU Amgen Inc.
FX This study was supported by research funding from Amgen Inc. Joan
O'Byrne, a paid consultant to Amgen Inc., and Loretta Spotila, a paid
consultant to RPS, Inc., assisted with the preparation of this
manuscript.
NR 27
TC 9
Z9 9
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2009
VL 15
IS 7
BP 827
EP 834
DI 10.1016/j.bbmt.2009.03.015
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 465MD
UT WOS:000267588300008
PM 19539214
ER
PT J
AU Ho, VT
Aldridge, J
Kim, HT
Cutler, C
Koreth, J
Armand, P
Antin, JH
Soiffer, RJ
Alyea, EP
AF Ho, Vincent T.
Aldridge, Julie
Kim, Haesook T.
Cutler, Corey
Koreth, John
Armand, Philippe
Antin, Joseph H.
Soiffer, Robert J.
Alyea, Edwin P.
TI Comparison of Tacrolimus and Sirolimus (Tac/Sir) versus Tacrolimus,
Sirolimus, and Mini-Methotrexate (Tac/Sir/MTX) as Acute
Graft-versus-Host Disease Prophylaxis after Reduced-Intensity
Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Graft-versus-host disease; Sirolimus; Rapamycin; Tacrolimus;
Methotrexate; Transplantation
ID LOW-DOSE METHOTREXATE; REGULATORY T-CELLS; HEMATOLOGIC MALIGNANCIES;
MYCOPHENOLATE-MOFETIL; COMPETING RISK; DONOR; RAPAMYCIN;
IMMUNOSUPPRESSION; INHIBITORS; LEUKEMIA
AB Previous studies have shown that adding sirolimus to a tacrolimus/mini-methotrexate regimen (Tac/Sir/MTX) as graft-versus-host disease (GVHD) prophylaxis produces low rates of acute GVHD (aGVHD) after reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). To assess whether posttransplantation methotrexate MTX can be safely eliminated altogether, we conducted a prospective clinical trial testing the combination of T and Sir alone (tac/sir) as GVHD prophylaxis after RIC SCT from matched related donors. We compared the results with patients who received (Tac/Sir/MTX) as GVHD prophylaxis after RIC SCT from matched related donors in a previous prospective study. Patients in both groups received i.v. fludarabine (Flu) 30 mg/m(2)/day and i.v. busulfan (Bu) 0.8 mg/kg/day on days -5 to -2 as conditioning, followed by transplantation of unmanipulated filgrastim-mobilized peripheral blood stem cells (PBSCS). After transplantation, patients in both groups received Tac and Sir orally starting on day -3, with doses adjusted to achieve trough serum levels of 5 to 10 ng/mL and 3 to 12 ng/mL, respectively. The patients in the Tac/Sir/MTX group also received mini-MTX therapy (S mg/m(2) i.v.) on days + 1, + 3, and + 6. Filgrastim 5 mu g/kg/day s.c. was started on day + I and continued until neutrophil engraftment. Twenty-nine patients received the Tac/Sir regimen, and 46 patients received the Tac/Sir/MTX regimen. The 2 groups were balanced in terms of age, sex, and disease characteristics. Engraftment was brisk and donor chimerism after transplantation robust in both groups. The cumulative incidence of grade II-IV aGVHD was similar in the 2 groups (17% for Tac/Sir versus 11% for Tac/Sir/MTX; P = .46). There also were no differences between the 2 groups in cumulative incidence of extensive chronic GVHD (cGVHD), treatment-related mortality (TRM), disease relapse, or survival. The Tac/Sir combination for GVHD prophylaxis is well tolerated and associated with a low incidence of aGVHD in matched related donor RIC SCT The omission of mini-MTX from the Tac/Sir GVHD prophylaxis regimen appears to have no adverse effect on the development of aGVHD.
C1 [Ho, Vincent T.; Cutler, Corey; Koreth, John; Armand, Philippe; Antin, Joseph H.; Soiffer, Robert J.; Alyea, Edwin P.] Harvard Univ, Sch Med, Ctr Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Aldridge, Julie; Kim, Haesook T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Ho, VT (reprint author), Harvard Univ, Sch Med, Ctr Hematol Oncol, Dana Farber Canc Inst, 44 Binney St,D1B06, Boston, MA 02115 USA.
EM Vincent_Ho@DFCI.Harvard.edu
RI ieong, bee/C-5840-2012
FU Ted and Eileen Pasquarello Research Fund; National Institutes of Health
[P01 HL070149-02]
FX Supported in part by the Ted and Eileen Pasquarello Research Fund and by
National Institutes of Health Grant P01 HL070149-02.
NR 23
TC 36
Z9 37
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2009
VL 15
IS 7
BP 844
EP 850
DI 10.1016/j.bbmt.2009.03.017
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 465MD
UT WOS:000267588300010
PM 19539216
ER
PT J
AU Browne, ML
Rasmussen, SA
Hoyt, AT
Waller, DK
Druschel, CM
Caton, AR
Canfield, MA
Lin, AE
Carmichael, SL
Romitti, PA
AF Browne, Marilyn L.
Rasmussen, Sonja A.
Hoyt, Adrienne T.
Waller, D. Kim
Druschel, Charlotte M.
Caton, Alissa R.
Canfield, Mark A.
Lin, Angela E.
Carmichael, Suzan L.
Romitti, Paul A.
CA Natl Birth Defects Prevention
TI Maternal Thyroid Disease, Thyroid Medication Use, and Selected Birth
Defects in the National Birth Defects Prevention Study
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Article
DE thyroid hormones; thyroxine; thyroid disease; congenital abnormalities;
birth defects
ID RISK-FACTORS; WOMEN; CRANIOSYNOSTOSIS; MALFORMATIONS
AB BACKGROUND: Although thyroid disorders are present in approximately 3%, of pregnant women, little is known about the association between maternal thyroid disease and birth defects. METHODS: We assessed the association between maternal thyroid disease, thyroid medication use, and 38 types of birth defects among 14,067 cases and 5875 controls in the National Birth Defects Prevention Study, a multisite, population-based, case-control study. Infants in this study were born between October 1997 and December 2004. Information on exposures including maternal diseases and use of medications was collected by telephone interview. RESULTS: We found statistically significant associations between maternal thyroid disease and left ventricular outflow tract obstruction heart defects (1.5; 95%, CI, 1.0-2.3), hydrocephaly (2.9; 951, CI, 1.6-5.2), hypospadias (1.6; 95%, CI, 1.0-2.5), and isolated anorectal atresia (2.4; 95%, CI, 1.2-4.6). Estimates for the association between periconceptional use of thyroxine and specific types of birth defects were similar to estimates for any thyroid disease. Given that antithyroid medication use was rare, we could not adequately assess risks for their use for most case groups. CONCLUSIONS: Our results are consistent with the positive associations between maternal thyroid disease or thyroid medication use and both hydrocephaly and hypospadias observed in some previous studies. New associations with left ventricular outflow tract obstruction heart defects and anorectal atresia may be chance findings. Birth Defects Research (Part A) 55:621-628, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Browne, Marilyn L.; Hoyt, Adrienne T.; Druschel, Charlotte M.; Caton, Alissa R.] New York State Dept Hlth, Congenital Malformat Registry, Troy, NY USA.
[Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA.
[Waller, D. Kim] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Canfield, Mark A.] Texas Dept State Hlth Serv, Austin, TX USA.
[Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA.
[Carmichael, Suzan L.] Calif Res Div, Oakland, CA USA.
[Romitti, Paul A.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
RP Browne, ML (reprint author), 547 River St,Room 200, Troy, NY 12180 USA.
EM mlb10@health.state.ny.us
RI Publications, NBDPS/B-7692-2013
FU Centers for Disease Control and Prevention [U50/CCU223184]
FX Supported by a cooperative agreement from the Centers for Disease
Control and Prevention (U50/CCU223184). Coding of drug information in
the NBDPS used the Stone Epidemiology Center Drug Dictionary, under
license from the Slone Epidemiology Center at Boston University.
NR 24
TC 16
Z9 17
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD JUL
PY 2009
VL 85
IS 7
BP 621
EP 628
DI 10.1002/bdra.20573
PG 8
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 476GE
UT WOS:000268426000005
PM 19215015
ER
PT J
AU Wo, JY
Shipley, WU
Dahl, DM
Coen, JJ
Heney, NM
Kaufman, DS
Zietman, AL
AF Wo, Jennifer Y.
Shipley, William U.
Dahl, Douglas M.
Coen, John J.
Heney, Niall M.
Kaufman, Donald S.
Zietman, Anthony L.
TI The results of concurrent chemo-radiotherapy for recurrence after
treatment with bacillus Calmette-Guerin for non-muscle-invasive bladder
cancer: is immediate cystectomy always necessary?
SO BJU INTERNATIONAL
LA English
DT Article
DE BCG; failure; selective bladder-preserving chemo-radiotherapy;
non-muscle invasive bladder cancer
ID TRANSITIONAL-CELL CARCINOMA; INTRAVESICAL THERAPY; TRANSURETHRAL
RESECTION; RADICAL CYSTECTOMY; MANAGEMENT; TRIAL; RISK; PRESERVATION
AB OBJECTIVES
To report our original experience in patients in whom bacille Calmette-Guerin (BCG) therapy has failed for T1 bladder cancer with subsequent progression to T2 disease treated with chemo-radiotherapy, as the management of recurrent high-grade T1 bladder cancer after failed BCG therapy is challenging, and radical cystectomy is the standard treatment because there are no well established second-line bladder-preserving therapies.
PATIENTS AND METHODS
From 1988 to 2002, 18 patients with T2 recurrence after failure of BCG therapy for T1 bladder cancer were treated with chemo-radiotherapy at the authors' institution. Patients received a visibly complete transurethral resection of the bladder tumour (TURBT) and concurrent chemo-radiotherapy with a mid-treatment evaluation after 40 Gy. Patients with less than a complete response had a prompt cystectomy; the others completed radiotherapy to 64-65 Gy. The primary treatment outcome was freedom from cystectomy due to recurrence not treatable by conservative measures; secondary outcomes included disease-specific (DSS) and overall survival (OS).
RESULTS
With a median follow-up of 7.0 years, only one patient had persistent tumour at re-staging TURBT and had an immediate cystectomy. Of the remaining 17 patients, 10 (59%) were free of any bladder recurrence. The actuarial 7-year DSS and OS were 70% and 58%, respectively. At 7 years, 54% of patients were alive with intact bladders and free of invasive recurrence.
CONCLUSIONS
In this study we specifically evaluated patients with apparently small muscle-invasive recurrences after BCG treatment for T1 bladder cancer. Selective bladder preservation with chemo-radiotherapy is possible, with low morbidity and a high chance of long-term bladder control. If successful in treating T2 recurrences after BCG therapy, it now seems timely to critically evaluate chemo-radiotherapy as an alternative to immediate cystectomy in the management of patients with T1 recurrences after BCG.
C1 [Shipley, William U.; Coen, John J.; Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
[Dahl, Douglas M.; Heney, Niall M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA.
[Kaufman, Donald S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA 02114 USA.
[Wo, Jennifer Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02114 USA.
RP Shipley, WU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St Cox 3, Boston, MA 02114 USA.
EM wshipley@partners.org
NR 16
TC 10
Z9 10
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD JUL
PY 2009
VL 104
IS 2
BP 179
EP 183
DI 10.1111/j.1464-410X.2008.08299.x
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 463IP
UT WOS:000267425900007
PM 19154448
ER
PT J
AU Stifani, S
Ma, QF
AF Stifani, Stefano
Ma, Qiufu
TI 'Runxs and regulations' of sensory and motor neuron subtype
differentiation: Implications for hematopoietic development
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Acute myeloid leukemia; Differentiation; Dorsal root ganglion; Motor
neurons; Nervous system; Proliferation; Runx; Sensory neurons; Spinal
cord
ID MULTIPLE CHROMOSOMAL TRANSLOCATIONS; ROOT GANGLION NEURONS; CORE-BINDING
FACTORS; T-CELL DEVELOPMENT; TRANSCRIPTION FACTOR; OSTEOBLAST
DIFFERENTIATION; NERVOUS-SYSTEM; DEPENDENT PHOSPHORYLATION;
GENE-EXPRESSION; CD4 REPRESSION
AB Runt-related ( RUNX) transcription factors are evolutionarily conserved regulators of a number of developmental mechanisms. RUNX proteins often control the balance between proliferation and differentiation and alterations of their functions are associated with different types of cancer and other human pathologies. Moreover, RUNX factors control important steps during the developmental acquisition of mature phenotypes. A number of investigations are beginning to shed light on the involvement of RUNX family members in the development of the nervous system. This review summarizes recent progress in the study of the roles of mammalian RUNX proteins during the differentiation of sensory and motor neurons in the peripheral and central nervous system, respectively. The implications of those findings for RUNX-mediated regulation of hematopoietic development will also be discussed. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Stifani, Stefano] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada.
[Ma, Qiufu] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
RP Stifani, S (reprint author), McGill Univ, Montreal Neurol Inst, 3801 Univ St, Montreal, PQ H3A 2B4, Canada.
EM stefano.stifani@mcgill.ca; qiufu_ma@dfci.harvard.edu
OI Stifani, Stefano/0000-0002-2376-7701
FU The Leukemia and Lymphoma Society in Provincetown, Massachusetts;
Canadian Institutes of Health Research [MOP-84577, MOP-42479];
NIH-National Institute of Dental and Craniofacial [1R01DE018025];
NIH-National Institute of Neurological Disorders and Stroke
[5P01NS047572]
FX This paper is based on presentations at the 15th International RUNX
Workshop sponsored by The Leukemia and Lymphoma Society in Provincetown,
Massachusetts from September 14-17, 2008. S. S. is a Chercheur National
of the Fonds de la Recherche en Sante du Quebec and research in his
laboratory is funded in part by the Canadian Institutes of Health
Research grants MOP-84577 and MOP-42479. Q. M. is a Claudia Adams Barr
Scholar, and research done in his lab is supported by NIH-National
Institute of Dental and Craniofacial Research Grant 1R01DE018025 and
NIH-National Institute of Neurological Disorders and Stroke Grant
5P01NS047572.
NR 66
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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 1079-9796
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD JUL-AUG
PY 2009
VL 43
IS 1
BP 20
EP 26
DI 10.1016/j.bcmd.2009.03.001
PG 7
WC Hematology
SC Hematology
GA 510GQ
UT WOS:000271076500004
PM 19349198
ER
PT J
AU Russell, M
Stark, J
Nayak, S
Miller, KK
Herzog, DB
Klibanski, A
Misra, M
AF Russell, Melissa
Stark, Jenna
Nayak, Shriddha
Miller, Karen K.
Herzog, David B.
Klibanski, Anne
Misra, Madhusmita
TI Peptide YY in adolescent athletes with amenorrhea, eumenorrheic athletes
and non-athletic controls
SO BONE
LA English
DT Article
DE Athletes; Adolescents; Peptide YY; Bone density; Bone turnover
ID GONADOTROPIN-RELEASING-HORMONE; MAPK SIGNALING PATHWAY; BONE-MINERAL
DENSITY; ANOREXIA-NERVOSA; HYPOTHALAMIC AMENORRHEA; LUTEINIZING-HORMONE;
ENERGY DEFICIENCY; HUMAN OSTEOBLASTS; EXERCISING WOMEN; GROWTH-HORMONE
AB Background: Bone mineral density (BMD) is lower in amenorrheic athletes (AA) compared with eumenorrheic athletes (EA). Decreased energy availability and altered levels of appetite regulating hormones (ghrelin and leptin) in AA contribute to hypogonadism, an important Cause of low BMD. The role of other nutritionally regulated hormones such as peptide YY (PYY) and adiponectin in mediating gonadal status and bone metabolism remains to be determined.
Objectives: Our objective was to determine whether PYY and adiponectin are higher in AA Compared with EA and contribute to hypogonadism and impaired bone metabolism in AA.
Methods: We determined PYY and adiponectin in 16 AA, 15 EA and 16 non-athletic controls 12-18 years old, and other nutritionally dependent hormones including ghrelin, leptin and IGF-1. We also measured testosterone, estradiol, PINP and NTX (markers of bone formation and resorption) and BMD.
Results: PYY was higher in AA than EA (111 +/- 52 vs. 61 +/- 29 pg/ml, p<0.05), whereas adiponectin did not differ between groups. Although activity scores did not differ, BMI was lower in AA than EA and a larger proportion (62.5% vs. 6.7%) reported disordered eating, indicating lower energy availability. PYY and adiponectin were independent predictors of testosterone in a regression model (p = 0.01 and 0.04), but did not predict estradiol. PYY, but not adiponectin, was an independent and negative predictor of PINP (p = 0.002) and lumbar bone mineral apparent density Z-scores (p = 0.045) in this model.
Conclusion: High PYY levels (but not adiponectin) differentiate AA from EA, and may be an important factor contributing to low bone density in athletes. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Russell, Melissa; Stark, Jenna; Nayak, Shriddha; Miller, Karen K.; Klibanski, Anne; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Russell, Melissa; Stark, Jenna; Nayak, Shriddha; Miller, Karen K.; Herzog, David B.; Klibanski, Anne; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA USA.
[Russell, Melissa; Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA.
[Herzog, David B.] Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA.
RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
EM mmisra@partners.org
FU NCRR NIH HHS [M01 RR001066, K23 RR018851-05, M01-RR-01066, K23
RR018851]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-14, P30DK040561,
R01 DK 062249, R01 DK062249]
NR 48
TC 35
Z9 35
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD JUL
PY 2009
VL 45
IS 1
BP 104
EP 109
DI 10.1016/j.bone.2009.03.668
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 458PT
UT WOS:000267036700012
PM 19344792
ER
PT J
AU Stewart, AJ
Devlin, PM
Mutyala, S
AF Stewart, Alexandra J.
Devlin, Phillip M.
Mutyala, Subhakar
TI Counterpoint: The dose rate argument-Does size matter after all?
SO BRACHYTHERAPY
LA English
DT Editorial Material
ID RATE INTRACAVITARY BRACHYTHERAPY; CERVIX CANCER BRACHYTHERAPY; UTERINE
CERVIX; INTERSTITIAL BRACHYTHERAPY; ENDOMETRIAL CANCER;
RANDOMIZED-TRIAL; RATE TANDEM; CARCINOMA; RADIATION; RECOMMENDATIONS
C1 [Devlin, Phillip M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Stewart, Alexandra J.] Royal Surrey Cty Hosp, Dept Radiotherapy, Surrey, England.
[Mutyala, Subhakar] Montefiore Med Ctr, Dept Radiat Oncol, Bronx, NY 10467 USA.
RP Devlin, PM (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA.
EM pdevlin@lroc.harvard.edu
NR 39
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1538-4721
J9 BRACHYTHERAPY
JI Brachytherapy
PD JUL-SEP
PY 2009
VL 8
IS 3
BP 273
EP 275
DI 10.1016/j.brachy.2009.06.003
PG 3
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 482YG
UT WOS:000268926000002
PM 19643374
ER
PT J
AU Mutyala, S
Devlin, PM
Stewart, AJ
AF Mutyala, Subhakar
Devlin, Phillip M.
Stewart, Alexandra J.
TI Rebuttal to Drs. Davidson, Hendry, and West: Once burned, twice shy?
SO BRACHYTHERAPY
LA English
DT Editorial Material
ID DOSE-RATE BRACHYTHERAPY; TRIAL; CARCINOMA; RATES
C1 [Mutyala, Subhakar] Montefiore Med Ctr, Dept Radiat Oncol, Bronx, NY 10467 USA.
[Devlin, Phillip M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Stewart, Alexandra J.] Royal Surrey Cty Hosp, Dept Radiotherapy, Surrey, England.
RP Mutyala, S (reprint author), Montefiore Med Ctr, Dept Radiat Oncol, 111 E 210th St, Bronx, NY 10467 USA.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1538-4721
J9 BRACHYTHERAPY
JI Brachytherapy
PD JUL-SEP
PY 2009
VL 8
IS 3
BP 277
EP 277
DI 10.1016/j.brachy.2009.06.002
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 482YG
UT WOS:000268926000004
PM 19643376
ER
PT J
AU Gow, DW
Keller, CJ
Eskandar, E
Meng, N
Cash, SS
AF Gow, David W., Jr.
Keller, Corey J.
Eskandar, Emad
Meng, Nate
Cash, Sydney S.
TI Parallel versus serial processing dependencies in the perisylvian speech
network: A Granger analysis of intracranial EEG data
SO BRAIN AND LANGUAGE
LA English
DT Article
DE Speech perception; iEEG; Granger causality; Dual pathway model; Spoken
word recognition; Functional connectivity; Speech perception;
Intracranial recording; Electrophysiology
ID FUNCTIONAL NEUROANATOMY; CAUSALITY ANALYSIS; HUMAN BRAIN; PERCEPTION;
FMRI; IDENTIFICATION; CONNECTIVITY; POTENTIALS; STREAMS; HUMANS
AB In this work, we apply Granger causality analysis to high spatiotemporal resolution intracranial EEG (iEEG) data to examine how different components of the left perisylvian language network interact during spoken language perception. The specific focus is on the characterization of serial versus parallel processing dependencies in the dominant hemisphere dorsal and ventral speech processing streams. Analysis of iEEG data from a large, 64-electrode grid implanted over the left perisylvian region in a single right-handed patient showed a consistent pattern of direct posterior superior temporal gyros influence over sites distributed over the entire ventral pathway for words, non-words, and phonetically ambiguous items that could be interpreted either as words or non-words. For the phonetically ambiguous items, this pattern was overlayed by additional dependencies involving the inferior frontal gyrus, which influenced activation measured at electrodes located in both ventral and dorsal stream speech structures. Implications of these results for understanding the functional architecture of spoken language processing and interpreting the role of the posterior superior temporal gyros in speech perception are discussed. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Gow, David W., Jr.] Massachusetts Gen Hosp, Cognit Behav Neurol Grp, Dept Neurol, Boston, MA 02114 USA.
[Gow, David W., Jr.; Keller, Corey J.; Meng, Nate] Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02114 USA.
[Gow, David W., Jr.] Salem State Coll, Dept Psychol, Salem, MA USA.
[Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Gow, DW (reprint author), Massachusetts Gen Hosp, Cognit Behav Neurol Grp, Dept Neurol, 175 Cambridge St,Suite S340, Boston, MA 02114 USA.
EM gow@helix.mgh.harvard.edu
OI Keller, Corey/0000-0003-0529-3490
FU NIDCD [R013108]
FX This work was supported by NIDCD grant R013108. We thank Eric Halgren
for early helpful discussions on the work, Christina Congleton and
Jennifer Segawa for their assistance in stimulus generation, and Andrew
Dykstra for providing some of the code used to analyze the data.
NR 43
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U1 3
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0093-934X
J9 BRAIN LANG
JI Brain Lang.
PD JUL
PY 2009
VL 110
IS 1
BP 43
EP 48
DI 10.1016/j.bandl.2009.02.004
PG 6
WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences;
Psychology, Experimental
SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences &
Neurology; Psychology
GA 459JR
UT WOS:000267098500006
PM 19356793
ER
PT J
AU George, MS
AF George, Mark S.
TI From the Editor-in-Chief's desk
SO BRAIN STIMULATION
LA English
DT Editorial Material
C1 [George, Mark S.] Univ S Carolina, Brain Stimulat Basic Translat & Clin Res Neuromod, Charleston, SC USA.
[George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP George, MS (reprint author), Univ S Carolina, Brain Stimulat Basic Translat & Clin Res Neuromod, Charleston, SC USA.
EM georgem@musc.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1935-861X
J9 BRAIN STIMUL
JI Brain Stimul.
PD JUL
PY 2009
VL 2
IS 3
BP 121
EP 122
DI 10.1016/j.brs.2009.06.002
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 478UQ
UT WOS:000268614300001
PM 20633410
ER
PT J
AU Castellon, S
Ganz, PA
AF Castellon, Steven
Ganz, Patricia A.
TI Neuropsychological studies in breast cancer: in search of chemobrain
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Editorial Material
ID COGNITIVE DYSFUNCTION; CHEMOTHERAPY; WOMEN; WORKSHOP; ESTROGEN; THERAPY
C1 [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA.
[Castellon, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA.
[Castellon, Steven] W Los Angeles Vet Affairs Med Ctr, Dept Mental Hlth & Psychiat, Los Angeles, CA 90073 USA.
RP Ganz, PA (reprint author), Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, 650 Charles Young Dr S,Room A2-125 CHS, Los Angeles, CA 90095 USA.
EM pganz@mednet.ucla.edu
NR 18
TC 15
Z9 15
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2009
VL 116
IS 1
BP 125
EP 127
DI 10.1007/s10549-008-0211-2
PG 3
WC Oncology
SC Oncology
GA 457QH
UT WOS:000266946700011
PM 18923899
ER
PT J
AU Colleoni, M
Bagnardi, V
Rotmensz, N
Gelber, RD
Viale, G
Pruneri, G
Veronesi, P
Torrisi, R
Cardillo, A
Montagna, E
Campagnoli, E
Luini, A
Intra, M
Galimberti, V
Scarano, E
Peruzzotti, G
Goldhirsch, A
AF Colleoni, Marco
Bagnardi, Vincenzo
Rotmensz, Nicole
Gelber, Richard D.
Viale, Giuseppe
Pruneri, Giancarlo
Veronesi, Paolo
Torrisi, Rosalba
Cardillo, Anna
Montagna, Emilia
Campagnoli, Elisabetta
Luini, Alberto
Intra, Mattia
Galimberti, Viviana
Scarano, Eloise
Peruzzotti, Giulia
Goldhirsch, Aron
TI Increasing steroid hormone receptors expression defines breast cancer
subtypes non responsive to preoperative chemotherapy
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Predictive factors; Primary therapy; Breast cancer
ID INTERNATIONAL EXPERT PANEL; SURGICAL ADJUVANT BREAST; NEOADJUVANT
CHEMOTHERAPY; SYSTEMIC TREATMENT; LOBULAR CARCINOMA; PREDICTIVE-VALUE;
PRIMARY TUMOR; RECOMMENDATIONS; ESTROGEN; ASSOCIATION
AB The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy (PCT) is unclear. We reviewed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT. The incidence of pathological complete remission (pCR) and outcome were assessed with respect to the degree of estrogen (ER) and progesterone receptor (PgR) expression (ER and PgR absent, vs. ER or PgR 0-49%, vs. ER and PgR a parts per thousand yen50% of the cells positive). A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors (17.7%) versus patients with tumors expressing high ER and PgR (0%) (OR 14.4 P < 0.001). Despite the higher incidence of pCR, a statistically significant worse disease-free survival (DFS), and overall survival (OS) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR (HR 6.4, 95% CI 3.5-11.6, for DFS; HR 3.6 95% CI 2.4-5.6 for OS). Response and outcome after PCT are correlated with the degree of expression of steroid hormone receptors. Studies on tailored preoperative therapies are needed.
C1 [Colleoni, Marco; Torrisi, Rosalba; Cardillo, Anna; Montagna, Emilia; Campagnoli, Elisabetta; Scarano, Eloise] European Inst Oncol, Dept Med, Res Unit Med Senol, I-20141 Milan, Italy.
[Bagnardi, Vincenzo; Rotmensz, Nicole] European Inst Oncol, Div Epidemiol & Biostat, I-20141 Milan, Italy.
[Bagnardi, Vincenzo] Univ Milano Bicocca, Dept Stat, Milan, Italy.
[Bagnardi, Vincenzo] Frontier Sci & Technol Res Fdn Inc, Milan, Italy.
[Gelber, Richard D.] Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA.
[Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA.
[Viale, Giuseppe; Pruneri, Giancarlo] European Inst Oncol, Div Pathol, I-20141 Milan, Italy.
[Viale, Giuseppe; Pruneri, Giancarlo; Veronesi, Paolo] Univ Milan, Sch Med, Milan, Italy.
[Veronesi, Paolo; Luini, Alberto; Intra, Mattia; Galimberti, Viviana] European Inst Oncol, Div Senol, I-20141 Milan, Italy.
RP Colleoni, M (reprint author), European Inst Oncol, Dept Med, Res Unit Med Senol, Via Ripamonti 435, I-20141 Milan, Italy.
EM marco.colleoni@ieo.it
FU European Institute of Oncology
FX We thank the patients, nurses and physicians at the European Institute
of Oncology.
NR 38
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U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2009
VL 116
IS 2
BP 359
EP 369
DI 10.1007/s10549-008-0223-y
PG 11
WC Oncology
SC Oncology
GA 458BR
UT WOS:000266988000016
PM 18941889
ER
PT J
AU Neuhausen, SL
Ozcelik, H
Southey, MC
John, EM
Godwin, AK
Chung, W
Iriondo-Perez, J
Miron, A
Santella, RM
Whittemore, A
Andrulis, IL
Buys, SS
Daly, MB
Hopper, JL
Seminara, D
Senie, RT
Terry, MB
AF Neuhausen, Susan L.
Ozcelik, Hilmi
Southey, Melissa C.
John, Esther M.
Godwin, Andrew K.
Chung, Wendy
Iriondo-Perez, Jeniffer
Miron, Alexander
Santella, Regina M.
Whittemore, Alice
Andrulis, Irene L.
Buys, Saundra S.
Daly, Mary B.
Hopper, John L.
Seminara, Daniela
Senie, Ruby T.
Terry, Mary Beth
CA Breast Canc Family Registry
TI BRCA1 and BRCA2 mutation carriers in the Breast Cancer Family Registry:
an open resource for collaborative research
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Biospecimen repository; Breast cancer; BRCA1; BRCA2
ID SENSITIVE GEL-ELECTROPHORESIS; UNKNOWN CLINICAL-SIGNIFICANCE; SEQUENCE
VARIANTS; TRUNCATING BRCA1; RISK; WOMEN; PREVALENCE
AB The Breast Cancer Family Registry is a resource for interdisciplinary and translational studies of the genetic epidemiology of breast cancer. This resource is available to researchers worldwide for collaborative studies. Herein, we report the results of testing for germline mutations in BRCA1 and BRCA2. We have tested 4,531 probands for mutations in BRCA1 and 4,084 in BRCA2. Deleterious mutations in BRCA1 and BRCA2 were identified for 9.8% of probands tested [233/4,531 (5.1%) for BRCA1 and 193/4,084 (4.7%) for BRCA2]. Of 1,385 Ashkenazi Jewish women tested for only the three founder mutations, 17.4% carried a deleterious mutation. In total, from the proband and subsequent family testing, 1,360 female mutation carriers (788 in BRCA1, 566 in BRCA2, 6 in both BRCA1 and BRCA2) have been identified. The value of the resource has been greatly enhanced by determining the germline BRCA1 and BRCA2 mutation statuses of nearly 6,000 probands.
C1 [Neuhausen, Susan L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA.
[Ozcelik, Hilmi] Mt Sinai Hosp, Div Epidemiol & Biostat, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
[John, Esther M.] No Calif Canc Ctr, Fremont, CA USA.
[Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Chung, Wendy] Columbia Univ, Dept Pediat & Med, New York, NY USA.
[Iriondo-Perez, Jeniffer] Res Triangle Inst, Raleigh, NC USA.
[Miron, Alexander] Dana Farber Canc Ctr, Dept Canc Biol, Boston, MA USA.
[Santella, Regina M.; Senie, Ruby T.; Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Whittemore, Alice] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Andrulis, Irene L.] Mt Sinai Hosp, Ontario Canc Genet Network, Fred A Litwin Ctr Canc Genet, Canc Care Ontario,Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Hopper, John L.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia.
[Seminara, Daniela] NCI, Epidemiol & Genet Res Program, Clin & Genet Epidemiol Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Seminara, Daniela] Breast Canc Family Registry, Bethesda, MD USA.
RP Neuhausen, SL (reprint author), Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA.
EM sneuhaus@uci.edu
RI Andrulis, Irene/E-7267-2013
FU National Cancer Institute; National Institutes of Health [CA-95-011];
Breast Cancer Family Registry and Principal Investigators [U01 CA69467];
Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01
CA69631]; Huntsman Cancer Institute [U01 CA69446]; Northern California
Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638];
Research Triangle Institute Informatics Support Center [RFP
N02PC45022-46]; National Health and Medical Research Council (NHMRC);
Victorian Breast Cancer Research Consortium (VBCRC); Ovarian Cancer
SPORE [P50 CA83638]
FX This work was supported by the National Cancer Institute, National
Institutes of Health under RFA # CA-95-011 and through cooperative
agreements with members of the Breast Cancer Family Registry and
Principal Investigators, including Cancer Care Ontario (U01 CA69467),
Columbia University (U01 CA69398), Fox Chase Cancer Center (U01
CA69631), Huntsman Cancer Institute (U01 CA69446), Huntsman Cancer
Institute (U01 CA69446), Northern California Cancer Center (U01
CA69417), University of Melbourne (U01 CA69638), and Research Triangle
Institute Informatics Support Center (RFP No. N02PC45022-46). Mutation
testing in Australia was supported by grants from the National Health
and Medical Research Council (NHMRC) and the Victorian Breast Cancer
Research Consortium (VBCRC). Mutation testing at Fox Chase Cancer Center
was in part supported by an Ovarian Cancer SPORE grant (P50 CA83638).
Mutation testing in Ontario was supported in part by Cancer Care
Ontario. We wish to thank members of the Ontario Cancer Genetics Network
for their contributions to the study. MCS is a Senior Research Fellow of
the NHMRC and JLH is an Australia Fellow and a VBCRC Group Leader. The
content of this manuscript does not necessarily reflect the views or
policies of the National Cancer Institute or any of the collaborating
centers in the Breast CFR, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government or the
Breast CFR.
NR 24
TC 30
Z9 30
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2009
VL 116
IS 2
BP 379
EP 386
DI 10.1007/s10549-008-0153-8
PG 8
WC Oncology
SC Oncology
GA 458BR
UT WOS:000266988000018
PM 18704680
ER
PT J
AU Souglakos, J
Philips, J
Wang, R
Marwah, S
Silver, M
Tzardi, M
Silver, J
Ogino, S
Hooshmand, S
Kwak, E
Freed, E
Meyerhardt, JA
Saridaki, Z
Georgoulias, V
Finkelstein, D
Fuchs, CS
Kulke, MH
Shivdasani, RA
AF Souglakos, J.
Philips, J.
Wang, R.
Marwah, S.
Silver, M.
Tzardi, M.
Silver, J.
Ogino, S.
Hooshmand, S.
Kwak, E.
Freed, E.
Meyerhardt, J. A.
Saridaki, Z.
Georgoulias, V.
Finkelstein, D.
Fuchs, C. S.
Kulke, M. H.
Shivdasani, R. A.
TI Prognostic and predictive value of common mutations for treatment
response and survival in patients with metastatic colorectal cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE KRAS; PIK3CA; BRAF; mutation; prediction; metastatic CRC
ID MISMATCH-REPAIR; PLUS IRINOTECAN; KRAS MUTATIONS; POOR SURVIVAL; BRAF
V600E; CETUXIMAB; FLUOROURACIL; LEUCOVORIN; GENE; EGFR
AB BACKGROUND: We address the prognostic and predictive value of KRAS, PIK3CA and BRAF mutations for clinical outcomes in response to active agents in the treatment of metastatic colorectal cancer (mCRC).
METHODS: We determined KRAS, BRAF and PIK3CA mutations in tumours from 168 patients treated for mCRC at two institutions. All patients received 5-FU-based first-line chemotherapy and treatment outcome was analysed retrospectively.
RESULTS: KRAS, BRAF and PIK3CA mutations were present in 62 (37%), 13 (8%) and 26 (15%) cases, respectively. Multivariate analysis uncovered BRAF mutation as an independent prognostic factor for decreased survival (hazard ratio (HR) 4.0, 95% confidence interval (CI) 2.1-7.6). In addition, patients with BRAF-mutant tumours had significantly lower progression-free survival (PFS: HR 4.0, 95% CI 2.2-7.4) than those whose tumors that carried wild-type BRAF. Among 92 patients treated using chemotherapy and cetuximab as salvage therapy, KRAS mutation was associated with lack of response (P = 0.002) and shorter PFS (P = 0.09). BRAF (P = 0.0005) and PIK3CA (P = 0.01) mutations also predicted reduced PFS in response to cetuximab salvage therapy.
CONCLUSIONS: These results underscore the potential of mutational profiling to identify CRCs with different natural histories or treatment responses. The adverse significance of BRAF mutation should inform patient selection and stratification in clinical trials. British Journal of Cancer (2009) 101, 465-472. doi:10.1038/sj.bjc.6605164 www.bjcancer.com Published online 14 July 2009 (C) 2009 Cancer Research UK
C1 [Souglakos, J.; Georgoulias, V.] Univ Hosp, Dept Med Oncol, Iraklion, Crete, Greece.
[Souglakos, J.; Saridaki, Z.; Georgoulias, V.] Univ Crete, Lab Tumor Biol, Iraklion, Crete, Greece.
[Philips, J.; Marwah, S.; Silver, J.; Ogino, S.; Hooshmand, S.; Freed, E.; Meyerhardt, J. A.; Fuchs, C. S.; Kulke, M. H.; Shivdasani, R. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wang, R.; Silver, M.; Finkelstein, D.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
[Tzardi, M.] Univ Hosp, Dept Pathol, Pathol Lab, Iraklion, Crete, Greece.
[Ogino, S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Kwak, E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kwak, E.; Meyerhardt, J. A.; Fuchs, C. S.; Kulke, M. H.; Shivdasani, R. A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Souglakos, J (reprint author), Univ Hosp Heraklion Voutes & Stavrakia, Dept Med Oncol, POB 1352, Iraklion 71110, Crete, Greece.
EM georgsec@med.uoc.gr; ramesh_shivdasani@dfci.harvard.edu
FU Dana-Farber Cancer Institute-Novartis Drug Discovery Program; National
Institutes of Health [P50CA127003]; Hellenic Society of Medical Oncology
FX We thank Laura MacConnaill and Levi Garraway for assistance with tumour
genotyping and Dr Robert Mayer for critical reading of the paper. The
study was supported by the Dana-Farber Cancer Institute-Novartis Drug
Discovery Program (RAS), SPORE grant P50CA127003 from the National
Institutes of Health and a research fellowship from the Hellenic Society
of Medical Oncology (JS).
NR 26
TC 157
Z9 167
U1 0
U2 4
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 JUL
PY 2009
VL 101
IS 3
BP 465
EP 472
DI 10.1038/sj.bjc.6605164
PG 8
WC Oncology
SC Oncology
GA 476KP
UT WOS:000268439500014
PM 19603024
ER
PT J
AU Chen, C
Reece, DE
Siegel, D
Niesvizky, R
Boccia, RV
Stadtmauer, EA
Abonour, R
Richardson, P
Matous, J
Kumar, S
Bahlis, NJ
Alsina, M
Vescio, R
Coutre, SE
Pietronigro, D
Knight, RD
Zeldis, JB
Rajkumar, V
AF Chen, Christine
Reece, Donna E.
Siegel, David
Niesvizky, Ruben
Boccia, Ralph V.
Stadtmauer, Edward A.
Abonour, Rafat
Richardson, Paul
Matous, Jeffrey
Kumar, Shaji
Bahlis, Nizar J.
Alsina, Melissa
Vescio, Robert
Coutre, Steven E.
Pietronigro, Dennis
Knight, Robert D.
Zeldis, Jerome B.
Rajkumar, Vincent
TI Expanded safety experience with lenalidomide plus dexamethasone in
relapsed or refractory multiple myeloma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article; Proceedings Paper
CT 48th Annual Meeting of the American-Society-of-Hematology
CY DEC 09-12, 2006
CL Orlando, FL
SP Amer Soc Hematol
DE multiple myeloma; relapsed; refractory; lenalidomide plus dexamethasone;
combination therapy
ID NEWLY-DIAGNOSED MYELOMA; THROMBOTIC COMPLICATIONS; COMBINATION THERAPY;
DRUG-RESISTANCE; THALIDOMIDE; PHASE-2; BORTEZOMIB; ASPIRIN; ANALOGS
AB P>Lenalidomide gained Food and Drug Administration (FDA) approval for treatment of patients with relapsed or refractory multiple myeloma (MM) in combination with dexamethasone in June 2006. In April 2005, the FDA and patient advocacy groups requested an expanded access programme to both provide lenalidomide to patients likely to benefit and obtain additional safety information. Relapsed/refractory MM patients received lenalidomide 25 mg/d (days 1-21) and dexamethasone 40 mg/d (days 1-4, 9-12, and 17-20 of cycles 1-4; days 1-4 only from cycle 5 onwards), in 4-week cycles until disease progression, study drug discontinuation, or lenalidomide approval. Of the 1438 patients enrolled, similar to 60% were male, median age was 64 years, and 61 center dot 7% had Durie-Salmon stage III disease. Median time on study was 15 center dot 4 weeks (range: 0 center dot 1-49 center dot 1) and median dose was 25 mg. The most common adverse events (AEs) were haematological (49%), gastrointestinal (59%), and fatigue (55%). The most common grade >= 3 AEs were haematological (45%), fatigue (10%), and pneumonia (7%). The most common serious AEs were pneumonia (8%), pyrexia (4%), and deep-vein thrombosis (3%). Primary cause of death was disease progression (10%). Safety data confirmed known AEs of lenalidomide plus dexamethasone therapy in patients with relapsed/refractory MM.
C1 [Rajkumar, Vincent] Mayo Clin, Div Hematol, Rochester, MN 55905 USA.
[Chen, Christine; Reece, Donna E.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Siegel, David] Hackensack Univ Med Ctr, Ctr Canc, Hackensack, NJ USA.
[Niesvizky, Ruben] Weill Cornell Med Coll, New York, NY USA.
[Boccia, Ralph V.] Ctr Canc & Blood Disorders, Bethesda, MD USA.
[Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Abonour, Rafat] Indiana Univ, Simon Canc Ctr, Indianapolis, IN USA.
[Richardson, Paul] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA.
[Bahlis, Nizar J.] Univ Calgary, Calgary, AB, Canada.
[Alsina, Melissa] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Vescio, Robert] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Vescio, Robert] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA.
[Coutre, Steven E.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Pietronigro, Dennis; Knight, Robert D.; Zeldis, Jerome B.] Celgene Corp, Summit, NJ USA.
RP Rajkumar, V (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA.
EM rajkumar.vincent@mayo.edu
RI Kumar, Shaji/A-9853-2008;
OI Kumar, Shaji/0000-0001-5392-9284; Rajkumar, S.
Vincent/0000-0002-5862-1833
NR 24
TC 42
Z9 42
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUL
PY 2009
VL 146
IS 2
BP 164
EP 170
DI 10.1111/j.1365-2141.2009.07728.x
PG 7
WC Hematology
SC Hematology
GA 466JL
UT WOS:000267657300005
PM 19545290
ER
PT J
AU Johri, AM
Kovacs, KA
Kafka, H
AF Johri, Amer M.
Kovacs, Katherine A.
Kafka, Henryk
TI An unusual case of infective endocarditis: Extension of a tricuspid
valve vegetation into the left atrium through a patent foramen ovale
SO CANADIAN JOURNAL OF CARDIOLOGY
LA English
DT Editorial Material
DE Echocardiography; Infective endocarditis; Patent foramen ovale
ID COMPLICATION
AB Tricuspid valve endocarditis frequently occurs in the setting of intravenous drug use. A case of tricuspid valve endocarditis in a 37-year-old woman with a history of intravenous cocaine use is described. Transthoracic echocardiography showed extension of the tricuspid valve mass through a patent foramen ovale and into the left atrium. One week after intravenous antibiotic treatment, the mass no longer traversed the patent foramen ovale, and only two smaller tricuspid valve vegetations remained. The present case demonstrates the value of performing a complete and thorough transthoracic echocardiography to visualize and evaluate both the right- and left-sided consequences of infective endocarditis in intravenous drug users. It also serves its it useful reminder to physicians caring for such patients that right-sided endocarditis can have important left-sided complications.
C1 [Johri, Amer M.; Kafka, Henryk] Queens Univ, Dept Med, Div Cardiol, Kingston, ON K7L 3N6, Canada.
[Kovacs, Katherine A.] Queens Univ, Dept Med, Div Gen Internal Med, Kingston, ON K7L 3N6, Canada.
RP Johri, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM amerjohri@gmail.com
NR 4
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0828-282X
J9 CAN J CARDIOL
JI Can. J. Cardiol.
PD JUL
PY 2009
VL 25
IS 7
BP 429
EP 431
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 471LO
UT WOS:000268059400008
PM 19584975
ER
PT J
AU Ebrahimi, F
Shafaroodi, H
Asadi, S
Nezami, BG
Ghasemi, M
Rahimpour, S
Hashemi, M
Doostar, Y
Dehpour, AR
AF Ebrahimi, Farzad
Shafaroodi, Hamed
Asadi, Shahrzad
Nezami, Behtash Ghazi
Ghasemi, Mehdi
Rahimpour, Sina
Hashemi, Mehrdad
Doostar, Yousef
Dehpour, Ahmad Reza
TI Sildenafil decreased cardiac cell apoptosis in diabetic mice: reduction
of oxidative stress as a possible mechanism
SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
LA English
DT Article
DE antioxidant; apoptosis; diabetes; heart; mice; reactive oxygen species;
sildenafil
ID CYTOCHROME-C RELEASE; MUSCLE-CELLS; CASPASE-3 ACTIVATION; SUPEROXIDE
FORMATION; ENDOTHELIAL-CELLS; HEART-FAILURE; DEATH; RATS;
CARDIOMYOPATHY; HYPERGLYCEMIA
AB Oxidative stress plays a dominant role in the pathogenesis of cardiac cell apoptosis in diabetic patients. Sildenafil has been demonstrated to have antioxidant effects. In this study, the effects of sildenafil on diabetes-induced cardiac cell apoptosis and the antioxidant status of diabetic mouse hearts were investigated. Diabetic mice showed lower body weight gains and heart weights compared with control mice, and sildenafil treatment did not increase these parameters in diabetic mice. Although apoptotic rates, caspase-3 enzyme activity, and malondialdehyde levels were significantly higher in diabetic mouse hearts than in controls, they were reduced in diabetic mice after sildenafil treatment. At the end of the first week, we observed no significant differences in antioxidant enzyme activities (CAT, GSH-Px, and SOD) in diabetic and control groups, whereas at the end of the second week of sildenafil treatment, antioxidant enzyme activities were higher in the diabetic group. In conclusion, our study indicated that sildenafil was beneficial to hearts of diabetic mice by reducing cardiac cell apoptosis, partially because of its antioxidant effects in the heart.
C1 [Ebrahimi, Farzad; Asadi, Shahrzad; Nezami, Behtash Ghazi; Ghasemi, Mehdi; Rahimpour, Sina; Dehpour, Ahmad Reza] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran.
[Ebrahimi, Farzad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Shafaroodi, Hamed] Islamic Azad Univ, Tehran Med Branch, Dept Pharmacol, Tehran, Iran.
[Hashemi, Mehrdad] Islamic Azad Univ, Tehran Med Branch, Dept Genet, Tehran, Iran.
[Doostar, Yousef] Islamic Azad Univ, Tabriz Branch, Dept Pathol, Tehran, Iran.
RP Dehpour, AR (reprint author), Univ Tehran Med Sci, Sch Med, Dept Pharmacol, POB 13145-784, Tehran, Iran.
EM dehpour@yahoo.com
OI dehpour, ahmad reza/0000-0002-8001-5565
NR 57
TC 17
Z9 17
U1 0
U2 3
PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
PI OTTAWA
PA 1200 MONTREAL ROAD, BUILDING M-55, OTTAWA, ON K1A 0R6, CANADA
SN 0008-4212
J9 CAN J PHYSIOL PHARM
JI Can. J. Physiol. Pharmacol.
PD JUL
PY 2009
VL 87
IS 7
BP 556
EP 564
DI 10.1139/Y09-036
PG 9
WC Pharmacology & Pharmacy; Physiology
SC Pharmacology & Pharmacy; Physiology
GA 486SH
UT WOS:000269217500007
PM 19767879
ER
PT J
AU Kufe, DW
AF Kufe, Donald W.
TI Functional targeting of the MUC1 oncogene in human cancers
SO CANCER BIOLOGY & THERAPY
LA English
DT Review
DE mucin; MUC1; transformation; dominant-negative mutants; gene signatures;
prognosis; druggable target
ID CARCINOMA-ASSOCIATED ANTIGEN; GROWTH-FACTOR RECEPTOR; BETA-CATENIN;
BREAST-CARCINOMA; MONOCLONAL-ANTIBODY; C-SRC; APOPTOTIC RESPONSE;
GENE-TRANSCRIPTION; CYTOPLASMIC TAIL; EPISIALIN MUC1
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Kufe, DW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM Donald_Kufe@dfci.harvard.edu
FU National Cancer Institute [CA97098, CA42802, CA100707]
FX This work was supported by Grants CA97098, CA42802 and CA100707 awarded
by the National Cancer Institute. Dr. Kufe has an ownership interest in
Genus Oncology and is a consultant to the company.
NR 64
TC 41
Z9 45
U1 0
U2 8
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD JUL 1
PY 2009
VL 8
IS 13
BP 1197
EP 1203
DI 10.4161/cbt.8.13.8844
PG 7
WC Oncology
SC Oncology
GA 486TC
UT WOS:000269220000003
PM 19556858
ER
PT J
AU Yang, C
Hornicek, FJ
Wood, KB
Schwab, JH
Mankin, H
Duan, ZF
AF Yang, Cao
Hornicek, Francis J.
Wood, Kirkham B.
Schwab, Joseph H.
Mankin, Henry
Duan, Zhenfeng
TI RAIDD expression is impaired in multidrug resistant osteosarcoma cell
lines
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE RAIDD; Multidrug resistance; Osteosarcoma; Apoptosis
ID DRUG-RESISTANCE; CANCER-CHEMOTHERAPY; OSTEOGENIC-SARCOMA;
CRYSTAL-STRUCTURE; ADAPTER MOLECULE; APOPTOSIS; CASPASE-2; PROTEIN;
PIDDOSOME; MECHANISM
AB To identify the apoptosis genes involved in the multidrug resistant phenotype of osteosarcoma.
Multidrug resistant human osteosarcoma cell line (U-2 OS MR) and a drug sensitive parental cell line (U-2 OS) were both treated with paclitaxel and analyzed by the gene array containing 96 apoptosis associated genes. The different expression of the special apoptosis associated genes were further analyzed by Western blot in the multidrug resistant osteosarcoma cell lines (U-2 OS MR, KH OS R2) and the drug sensitive parental cell lines (U-2 OS, KH OS). One of the disregulated gene, RAIDD, was transfected into the multidrug resistant osteosarcoma cells for functional studies.
RAIDD showed signs of significant expression in the U-2 OS cells after being treated with paclitaxel (P < 0.01). However, the induction of RAIDD did not occur in U-2 OS MR cells (P = 0.2). Subsequent analysis by Western blot confirmed the deficiency of the expression of RAIDD protein in U-2 OS MR. On the contrary, the expression of RAIDD could be significantly induced by paclitaxel and doxorubicin in U-2 OS cells as both time and dosage were deciding factors. It also demonstrated the cleavage of PARP associated with RAIDD expression in U-2 OS cells, but not however in U-2 OS MR cells after being treated with paclitaxel or doxorubicin. Similar results were found in osteosarcoma multidrug resistant cell line KH OS R2 and the drug sensitive parental cell line KH OS. Furthermore, over-expression of RAIDD in multidrug resistant cell lines could possibly reverse drug resistant phenotypes.
This study indicate that impaired expression of RAIDD in drug induced apoptosis may play a role in the multidrug resistance of osteosarcoma cells.
C1 [Yang, Cao; Hornicek, Francis J.; Wood, Kirkham B.; Schwab, Joseph H.; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Yang, Cao; Hornicek, Francis J.; Schwab, Joseph H.; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA.
[Yang, Cao] Huazhong Univ Sci & Technol, Dept Orthopaed Surg, Union Hosp, Tongji Med Coll, Wuhan 430022, Peoples R China.
RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
EM zduan@partners.org
OI Duan, Zhenfeng/0000-0002-8543-083X
FU Chinese Council of Scholarship; National Cancer Institute, NIH
(Nanotechnology Platform Partnership) [R01-CA119617]
FX Dr. C. Yang is supported through a grant from the Chinese Council of
Scholarship. Dr. Z. Duan is supported, in part, through a grant from the
National Cancer Institute, NIH ( Nanotechnology Platform Partnership),
R01-CA119617. Support has also been provided by the Gaetagno and
Wechsler funds.
NR 28
TC 12
Z9 13
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD JUL
PY 2009
VL 64
IS 3
BP 607
EP 614
DI 10.1007/s00280-008-0912-6
PG 8
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 458QP
UT WOS:000267038900019
PM 19125251
ER
PT J
AU Passer, BJ
Castelo-Branco, P
Buhrman, JS
Varghese, S
Rabkin, SD
Martuza, RL
AF Passer, B. J.
Castelo-Branco, P.
Buhrman, J. S.
Varghese, S.
Rabkin, S. D.
Martuza, R. L.
TI Oncolytic herpes simplex virus vectors and taxanes synergize to promote
killing of prostate cancer cells
SO CANCER GENE THERAPY
LA English
DT Article
DE prostate cancer; oncolytic HSV's; taxanes
ID SPINDLE ASSEMBLY CHECKPOINT; PROTEIN-SYNTHESIS; REPLICATION; DRUGS;
GENE; FLAVOPIRIDOL; COMBINATION; PACLITAXEL; APOPTOSIS; THERAPY
AB Genetically engineered oncolytic herpes simplex virus-1 (HSV-1) vectors selectively replicate in tumor cells causing direct killing whereas sparing normal cells. One clinical limitation of using oncolytic HSV vectors is their attenuated growth. We hypothesized that the appropriately chosen chemotherapeutic agent combined with an oncolytic HSV could be an effective means to promote augmented prostate cancer cell killing both in vitro and in vivo. Here we have identified that G47 Delta synergizes with the microtubule-stabilizing taxane agents docetaxel and paclitaxel to enhance the in vitro killing of prostate cancer cells. In vivo efficacy studies show that when combined with docetaxel, G47 Delta could be reduced at least 10-fold. Immunoblot analysis revealed that docetaxel-induced accumulation of the phospho-specific mitotic markers op18/stathmin or histone-H3 was markedly reduced by G47 Delta, which correlated with enhanced apoptosis and required active viral replication. Furthermore, cell-cycle analysis demonstrated that in the presence of G47 Delta, the majority of 4N cells arrested in mitosis were MPM-2-negative, indicative of cells exiting mitosis prematurely. These findings suggest that G47 Delta may act in part, on mitotically blocked cells to enhance cell death, which may account for the enhanced antitumor efficacy observed in vivo. Cancer Gene Therapy (2009) 16, 551-560; doi:10.1038/cgt.2009.10; published online 6 February 2009
C1 [Passer, B. J.] Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Passer, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Simches Res Bldg CRPZN 3800,185 Cambridge St, Boston, MA 02114 USA.
EM bpasser@partners.org
RI rabkin, samuel/C-2443-2012
OI rabkin, samuel/0000-0003-2344-2795
FU RLM [RO1 CA102139]
FX This study was in part supported by a grant to RLM (RO1 CA102139).
NR 31
TC 20
Z9 21
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0929-1903
J9 CANCER GENE THER
JI Cancer Gene Ther.
PD JUL
PY 2009
VL 16
IS 7
BP 551
EP 560
DI 10.1038/cgt.2009.10
PG 10
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Research & Experimental Medicine
GA 458QQ
UT WOS:000267039000002
PM 19197321
ER
PT J
AU Zhu, AX
Duda, DG
Sahani, DV
Jain, RK
AF Zhu, Andrew X.
Duda, Dan G.
Sahani, Dushyant V.
Jain, Rakesh K.
TI Development of Sunitinib in Hepatocellular Carcinoma: Rationale, Early
Clinical Experience, and Correlative Studies
SO CANCER JOURNAL
LA English
DT Article
DE sunitinib; hepatocellular carcinoma; angiogenesis; multitargeted
receptor tyrosine kinase inhibitor; clinical trials
ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR;
FACTOR-RECEPTOR-ALPHA; IN-VIVO; MICROVESSEL DENSITY; ANTITUMOR-ACTIVITY;
SU11248; CANCER; EXPRESSION; SORAFENIB
AB The approval of a multitargeted receptor tyrosine kinase inhibitor, sorafenib, with activity against vascular endothelial growth factor receptor-2 and -3, Raf-1 and B-Raf, platelet-derived growth factor receptor-alpha and -beta, and other kinases, has ushered in the era of molecular targeted agents in advanced hepatocellular carcinoma (HCC). Sunitinib malate is an oral, multitargeted inhibitor of vascular endothelial growth factor receptor-1, -2, and -3, platelet-derived growth factor receptor-alpha and -beta, and other kinases implicated in tumor growth, angiogenesis, and metastasis. Sunitinib has been approved in metastatic renal cell carcinoma and gastrointestinal stromal tumor and is undergoing active clinical development in HCC. Early evidence of antitumor activity and a promising safety profile for this agent have emerged from single arm phase 11 trials in United States, European, and Asian patients with advanced HCC. Correlative studies of imaging and circulating biomarkers have provided insights into the potential mechanism of action of sunitinib. Additional phase II studies using either single agent or in combination with chemotherapeutic agents are ongoing, and a phase III trial comparing sunitinib and sorafenib in advanced HCC is actively accruing patients. Here, we review the current progress and future directions for the development of sunitinib in advanced HCC.
C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tucker Gosnell Ctr Gastrointestinal Canc,Canc Ctr, Boston, MA 02163 USA.
RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tucker Gosnell Ctr Gastrointestinal Canc,Canc Ctr, Boston, MA 02163 USA.
EM azhu@partners.org
FU NCI NIH HHS [P01 CA080124]
NR 46
TC 21
Z9 23
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2009
VL 15
IS 4
BP 263
EP 268
PG 6
WC Oncology
SC Oncology
GA 482WN
UT WOS:000268921000001
PM 19672141
ER
PT J
AU Flanz, J
Smith, A
AF Flanz, Jacob
Smith, Alfred
TI Technology for Proton Therapy
SO CANCER JOURNAL
LA English
DT Review
DE proton therapy; proton therapy technology; proton accelerators; proton
treatment delivery techniques
ID BEAMS
AB The technology that is used for the production and delivery of therapeutic proton beams is reviewed. Increased interest in this treatment modality has inspired a new generation of technology development and research into methods that will make proton treatment facilities more widely available (less expensive) and more efficient. Proton beam therapy has been in use for more than 40 years; it remains a treatment modality of interest because it provides a highly conformal dose distribution to a wide variety of disease sites and the potential for improving clinical outcomes. Recent advances in beam scanning technology may represent the ultimate in external beam radiotherapy dose conformality and treatment delivery efficiency. We describe how this new technology can be integrated into a proton therapy facility.
C1 [Flanz, Jacob] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis F Burr Proton Therapy Ctr, Boston, MA 02114 USA.
[Smith, Alfred] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Ctr Global Oncol, Houston, TX 77030 USA.
RP Flanz, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis F Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA.
EM jflanz@partners.org
NR 11
TC 5
Z9 5
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2009
VL 15
IS 4
BP 292
EP 297
PG 6
WC Oncology
SC Oncology
GA 482WN
UT WOS:000268921000005
PM 19672145
ER
PT J
AU Efstathiou, JA
Trofimov, AV
Zietman, AL
AF Efstathiou, Jason A.
Trofimov, Alexei V.
Zietman, Anthony L.
TI Life, Liberty, and the Pursuit of Protons: An Evidence-Based Review of
the Role of Particle Therapy in the Treatment of Prostate Cancer
SO CANCER JOURNAL
LA English
DT Review
DE Proton beam therapy; prostate cancer; dose escalation; toxicity;
intensity modulated radiation therapy
ID RANDOMIZED CONTROLLED-TRIAL; RADIATION-THERAPY; DOSE-ESCALATION; 2ND
CANCERS; SKULL BASE; RADIOTHERAPY; BEAM; IRRADIATION; NEUTRON; TUMORS
AB Proton beam therapy (PBT) has been in use for a number of decades, though interest in PBT for localized prostate cancer has grown substantially in recent years. Protons offer the theoretical potential of achieving dose escalation and decreasing toxicity by capitalizing on unique physical dose deposition characteristics to avoid normal tissue. Although it has proven effective in a number of malignancies including as a means for dose escalation in prostate cancer, there is little published clinical data to support its comparative superiority over alternative forms of conformal radiation for prostate cancer. This review article explores the current evidence and clinical experience supporting PBT for prostate cancer, the uncertainties and controversies associated with this innovative technology, its potential economic implications, and future promise.
C1 [Efstathiou, Jason A.; Trofimov, Alexei V.; Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Efstathiou, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA.
EM jefstathiou@partners.org
NR 53
TC 18
Z9 18
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2009
VL 15
IS 4
BP 312
EP 318
PG 7
WC Oncology
SC Oncology
GA 482WN
UT WOS:000268921000008
PM 19672148
ER
PT J
AU Sorensen, AG
Batchelor, TT
Zhang, WT
Chen, PJ
Yeo, P
Wang, MY
Jennings, D
Wen, PY
Lahdenranta, J
Ancukiewicz, M
di Tomaso, E
Duda, DG
Jain, RK
AF Sorensen, A. Gregory
Batchelor, Tracy T.
Zhang, Wei-Ting
Chen, Poe-Jou
Yeo, Priscilla
Wang, Meiyun
Jennings, Dominique
Wen, Patrick Y.
Lahdenranta, Johanna
Ancukiewicz, Marek
di Tomaso, Emmanuelle
Duda, Dan G.
Jain, Rakesh K.
TI A "Vascular Normalization Index" as Potential Mechanistic Biomarker to
Predict Survival after a Single Dose of Cediranib in Recurrent
Glioblastoma Patients
SO CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; ANTIANGIOGENIC THERAPY; PROGNOSTIC-FACTORS;
TUMOR VASCULATURE; KINASE INHIBITOR; GLIOMA; GRADE; ANGIOGENESIS;
BEVACIZUMAB; METASTASES
AB Early imaging or blood biomarkers of tumor response are desperately needed to customize antiangiogenic therapy for cancer patients. Anti-vascular endothelial growth factor (VEGF) therapy can "normalize" brain tumor vasculature by decreasing vessel diameter and permeability, and thinning the abnormally thick basement membrane. We hypothesized that the extent of vascular normalization will be predictive of outcome of anti-VEGF therapy in glioblastoma. We use advanced magnetic resonance imaging methods to monitor vascular parameters and treatment response in 31 recurrent glioblastoma patients enrolled in a phase II trial of cediranib, an oral pan-VEGF receptor tyrosine kinase inhibitor. We evaluated the correlation between clinical outcome and magnetic resonance imaging-measured changes in vascular permeability/flow (i.e., K(trans)) and in microvessel volume, and the change of circulating collagen W levels, all after a single dose of cediranib. Here, we show that evaluation of biomarkers as early as after one day of anti-VEGF therapy with cediranib is predictive of response in patients with recurrent glioblastoma. Changes in K(trans) microvessel volume, and circulating collagen IV correlated with duration of overall survival and/or progression-free survival (P < 0.05). When we combined these three parameters into a "vascular normalization index," we found that it closely associated with overall survival (rho = 0.54; P = 0.004) and progression-free survival (rho = 0.6; P = 0.001). The vascular normalization index described here should be validated in randomized clinical trials. [Cancer Res 2009;69(13):5296-300]
C1 [Sorensen, A. Gregory; Zhang, Wei-Ting; Chen, Poe-Jou; Yeo, Priscilla; Wang, Meiyun; Jennings, Dominique] Massachusetts Gen Hosp, EL Steele Lab, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Lahdenranta, Johanna; Ancukiewicz, Marek; di Tomaso, Emmanuelle; Duda, Dan G.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Wen, Patrick Y.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, EL Steele Lab, AA Martinos Ctr Biomed Imaging, 100 Blossom St,Cox 734, Boston, MA 02114 USA.
EM sorensen@nmr.mgh.harvard.edu; jain@steele.mgh.harvard.edu
FU NIH [P01-CA80124, R01-CA115767, R21-CA117079, K24-CA125440,
R01-CA129371, P41-RR014075, M01-RR-01066]; Federal Share/National Cancer
Institute; Harvard Clinical and Translational Science Center; Montesi
Family Research Fund; Damon Runyon Foundation
FX We thank G. Gorospe, C. Koppel, T. Benner, M. Foley, O. Wu, and S.
Roberge for outstanding technical assistance.
NR 20
TC 194
Z9 200
U1 0
U2 13
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 JUL 1
PY 2009
VL 69
IS 13
BP 5296
EP 5300
DI 10.1158/0008-5472.CAN-09-0814
PG 5
WC Oncology
SC Oncology
GA 466VP
UT WOS:000267691800005
PM 19549889
ER
PT J
AU Goel, HL
Moro, L
Murphy-Ullrich, JE
Hsieh, CC
Wu, CL
Jiang, Z
Languino, LR
AF Goel, Hira Lal
Moro, Loredana
Murphy-Ullrich, Joanne E.
Hsieh, Chung-Cheng
Wu, Chin-Lee
Jiang, Zhong
Languino, Lucia R.
TI beta(1) Integrin Cytoplasmic Variants Differentially Regulate Expression
of the Antiangiogenic Extracellular Matrix Protein Thrombospondin 1
SO CANCER RESEARCH
LA English
DT Article
ID BENIGN PROSTATIC HYPERPLASIA; ENDOTHELIAL GROWTH-FACTOR;
CELL-PROLIFERATION; MONOCLONAL-ANTIBODIES; NEOPLASTIC PROSTATE; CANCER
PROGRESSION; TUMOR ANGIOGENESIS; MESSENGER-RNA; C-JUN; ADHESION
AB beta(1) integrins play an important role in regulating cell proliferation and survival. Using small interfering RNA or an inhibitory antibody to beta(1), we show here that, in vivo, beta(1) integrins are essential for prostate cancer growth. Among the five known beta(1) integrin cytoplasmic variants, two have been shown to differentially affect prostate cell functions. The beta(1A) variant promotes normal and cancer cell proliferation, whereas the beta(1C) variant, which is down-regulated in prostate cancer, inhibits tumor growth and appears to have a dominant effect On beta(1A). To investigate the mechanism by which beta(1C) inhibits the tumorigenic potential of beta(1A), we analyzed changes in gene expression in cells transfected with either beta(1C) or beta(1A). The results show that beta(1C) expression increases the levels of an extracellular matrix protein, thrombospondin 1 (TSP1), an angiogenesis inhibitor. TSPI protein levels are increased upon beta(1C) expression in prostate cancer cells as well as in beta(1)-null GD25 cells. We show that TSPI does not affect proliferation, apoptosis, or anchorage-independent growth of prostate cancer cells. In contrast, the newly synthesized TSPI, secreted by prostate cancer cells expressing beta(1C), prevents proliferation of endothelial cells. In conclusion, our novel findings indicate that expression of the beta(1C) integrin variant in prostate glands prevents cancer progression by up-regulation of TSP1 levels and inhibition of angiogenesis. [Cancer Res 2009;69(13):5374-82]
C1 [Goel, Hira Lal; Moro, Loredana; Hsieh, Chung-Cheng; Languino, Lucia R.] Univ Massachusetts, Dept Canc Biol, Prostate Canc Discovery & Dev Program, Sch Med, Worcester, MA 01605 USA.
[Jiang, Zhong] Univ Massachusetts, Dept Pathol, Sch Med, Worcester, MA 01605 USA.
[Murphy-Ullrich, Joanne E.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
[Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Wu, Chin-Lee] Harvard Univ, Sch Med, Boston, MA USA.
RP Languino, LR (reprint author), Univ Massachusetts, Dept Canc Biol, Prostate Canc Discovery & Dev Program, Sch Med, 364 Plantat St, Worcester, MA 01605 USA.
EM lucia.languino@umassmed.edu
OI Languino, Lucia/0000-0001-9011-7031
FU NIH [CA109874, CA89720, HIL79644, DK78038]; Department of Defense [PCRP
DAMD PC040221]; American Cancer Society [93-033]; Diabetes Endocrinology
Research Center [DK32520]
FX NIH grants CA109874 and CA89720 and Department of Defense grant PCRP
DAMD PC040221 (L.R. Languino), American Cancer Society institutional
research grant 93-033 (H.L. Goel), and NIH grants HIL79644 and DK78038
(J.E. Murphy-Ullrich).; The costs of publication of this article were
defrayed in part by the payment of page charges. This article must
therefore be hereby marked advertisement in accordance with 18 U.S.C.
Section 1734 solely to indicate this fact.; We thank I-leather Ehlers
for help during the preparation of this article and Drs. E. Sahai and G.
Taraboletti for reagents. Core resources supported by the Diabetes
Endocrinology Research Center (grant DK32520) were also used.
NR 55
TC 8
Z9 8
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 JUL 1
PY 2009
VL 69
IS 13
BP 5374
EP 5382
DI 10.1158/0008-5472.CAN-09-0186
PG 9
WC Oncology
SC Oncology
GA 466VP
UT WOS:000267691800015
PM 19549894
ER
PT J
AU Pomerantz, MM
Beckwith, CA
Regan, MM
Wyman, SK
Petrovics, G
Chen, YM
Hawksworth, DJ
Schumacher, FR
Mucci, L
Penney, KL
Stampfer, MJ
Chan, JA
Ardlie, KG
Fritz, BR
Parkin, RK
Lin, DW
Dyke, M
Herman, P
Lee, S
Oh, WK
Kantoff, PW
Tewari, M
McLeod, DG
Srivastava, S
Freedman, ML
AF Pomerantz, Mark M.
Beckwith, Christine A.
Regan, Meredith M.
Wyman, Stacia K.
Petrovics, Gyorgy
Chen, Yongmei
Hawksworth, Dorota J.
Schumacher, Fredrick R.
Mucci, Lorelei
Penney, Kathryn L.
Stampfer, Meir J.
Chan, Jennifer A.
Ardlie, Kristin G.
Fritz, Brian R.
Parkin, Rachael K.
Lin, Daniel W.
Dyke, Michelle
Herman, Paula
Lee, Steve
Oh, William K.
Kantoff, Philip W.
Tewari, Muneesh
McLeod, David G.
Srivastava, Shiv
Freedman, Matthew L.
TI Evaluation of the 8q24 Prostate Cancer Risk Locus and MYC Expression
SO CANCER RESEARCH
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CHROMOSOME 8Q24; C-MYC; BREAST-CANCER; RADICAL
PROSTATECTOMY; SUSCEPTIBILITY LOCI; VARIANT; CELLS; GENE; OVEREXPRESSION
AB Polymorphisms at 8q24 are robustly associated with prostate cancer risk. The risk variants are located in nonprotein coding regions and their mechanism has not been fully elucidated. To further dissect the function of this locus, we tested two hypotheses: (a) unannotated microRNAs (miRNA) are transcribed in the region, and (b) this region is a cis-acting enhancer. Using next generation sequencing, 8q24 risk regions were interrogated for known and novel miRNAs in histologically normal radical prostatectomy tissue. We also evaluated the association between the risk variants and transcript levels of multiple genes, focusing on the proto-oncogene, MYC. RNA expression was measured in histologically normal and tumor tissue from 280 prostatectomy specimens (from 234 European American and 46 African American patients), and paired germline DNA from each individual was genotyped for six 8q24 risk single nucleotide polymorphisms. No evidence was found for significant miRNA transcription within 8q24 prostate cancer risk loci. Likewise, no convincing association between RNA expression and risk allele status was detected in either histologically normal or tumor tissue. To our knowledge, this is one of the first and largest studies to directly assess miRNA in this region and to systematically measure MYC expression levels in prostate tissue in relation to inherited risk variants. These data will help to direct the future study of this risk locus. [Cancer Res 2009;69(13):5568-74]
C1 [Pomerantz, Mark M.; Beckwith, Christine A.; Dyke, Michelle; Herman, Paula; Lee, Steve; Oh, William K.; Kantoff, Philip W.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Schumacher, Fredrick R.; Mucci, Lorelei; Penney, Kathryn L.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wyman, Stacia K.; Fritz, Brian R.; Parkin, Rachael K.; Tewari, Muneesh] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA USA.
[Lin, Daniel W.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA.
[Schumacher, Fredrick R.; Mucci, Lorelei; Tewari, Muneesh] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA USA.
[Lin, Daniel W.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
[Lin, Daniel W.] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Petrovics, Gyorgy; Chen, Yongmei; Hawksworth, Dorota J.; McLeod, David G.; Srivastava, Shiv] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Rockville, MD USA.
[Stampfer, Meir J.; Chan, Jennifer A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada.
[Stampfer, Meir J.; Chan, Jennifer A.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada.
[Stampfer, Meir J.; Chan, Jennifer A.] Univ Calgary, Dept Oncol, Calgary, AB, Canada.
[Ardlie, Kristin G.] Broad Inst Harvard & MIT, Cambridge, MA USA.
RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana Bldg,Rm 710A,44 Binney St, Boston, MA 02115 USA.
EM matthew_freedman@dfci.harvard.edu
RI Oh, William/B-9163-2012
OI Oh, William/0000-0001-5113-8147
FU NIH [R01 CA129435]; Mayer Foundation; H. L. Snyder Medical Foundation;
National Cancer Institute [5P50CA90381]; American Society of Clinical
Oncology; Prostate Cancer Foundation; Fred Hutchinson Cancer Research
Center New Development funds; Canary Foundation; Pacific Northwest
Prostate Cancer Specialized Program of Research Excellence [P50
CA97186]; Chromosome Metabolism Training Grant [5 T32 CA09657-16]
FX NIH R01 CA129435 (M.L. Freedman), the Mayer Foundation (M.L. Freedman),
the H. L. Snyder Medical Foundation (M,L. Freedman), the
Dana-Farber/Harvard Cancer Center Prostate Cancer Specialized Programs
of Research Excellence (National Cancer Institute Grant no.
5P50CA90381), the American Society of Clinical Oncology (M.L. Freedman),
the Prostate Cancer Foundation (M.M. Pomerantz), the Fred Hutchinson
Cancer Research Center New Development funds, including support. from
the Canary Foundation (M. Tewari), Pilot Grant from the Pacific
Northwest Prostate Cancer Specialized Program of Research Excellence
Grant P50 CA97186 (M.Tewari), and Chromosome Metabolism Training Grant 5
T32 CA09657-16 (S.K. Wyman).
NR 36
TC 70
Z9 71
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2009
VL 69
IS 13
BP 5568
EP 5574
DI 10.1158/0008-5472.CAN-09-0387
PG 7
WC Oncology
SC Oncology
GA 466VP
UT WOS:000267691800039
PM 19549893
ER
PT J
AU Di Vizio, D
Kim, J
Hager, MH
Morello, M
Yang, W
Lafargue, CJ
True, LD
Rubin, MA
Adam, RM
Beroukhim, R
Demichelis, F
Freeman, MR
AF Di Vizio, Dolores
Kim, Jayoung
Hager, Martin H.
Morello, Matteo
Yang, Wei
Lafargue, Christopher J.
True, Lawrence D.
Rubin, Mark A.
Adam, Rosalyn M.
Beroukhim, Rameen
Demichelis, Francesca
Freeman, Michael R.
TI Oncosome Formation in Prostate Cancer: Association with a Region of
Frequent Chromosomal Deletion in Metastatic Disease
SO CANCER RESEARCH
LA English
DT Article
ID NUCLEAR RIBONUCLEOPROTEIN-K; PLASMA-MEMBRANE; SECRETED CAVEOLIN-1;
CELL-MIGRATION; TUMOR-GROWTH; PROTEIN; INVASION; EXPRESSION; MODES;
ACTIN
AB Oncosomes have recently been described as membrane-derived microvesicles secreted by cancer cells, which transfer oncogenic signals and protein complexes across cell boundaries. Here, we show the rapid formation and secretion of oncosomes from DU145 and LNCaP human prostate cancer cells. Oncosome formation was stimulated by epidermal growth factor receptor activation and also by overexpression of membrane-targeted Akt1. Microvesicles shed from prostate cancer cells contained numerous signal transduction proteins and were capable of activating rapid phospho-tyrosine and Akt pathway signaling, and stimulating proliferation and migration, in recipient tumor cells. They also induced a stromal reaction in recipient normal cells. Knockdown of the actin nucleating protein Diaphanous Related Formin 3 (DRF3/Dia2) by RNA interference enhanced rates of oncosome formation, indicating that these structures resemble, and may be identical to, nonapoptotic membrane blebs, a feature of the amoeboid form of cell motility. Analysis of primary and metastatic human prostate tumors using 100K single nucleotide polymorphism arrays revealed a significantly higher frequency of deletion of the locus encoding DRF3 (DIAPH3) in metastatic tumors (P = 0.001) in comparison with organ-confined tumors. Fluorescence in situ hybridization confirmed increased chromosomal loss of DIAPH3 in metastatic tumors in a different cohort of patients (P = 0.006). These data suggest that microvesicles shed from prostate cancer cells can alter the tumor microenvironment in a manner that may promote disease progression. They also show that DRF3 is a physiologically relevant protein that seems to regulate this process. [Cancer Res 2009;69(13):5601-9]
C1 [Freeman, Michael R.] Childrens Hosp, Enders Res Labs, Urol Dis Res Ctr, Boston, MA 02115 USA.
[Di Vizio, Dolores; Kim, Jayoung; Hager, Martin H.; Morello, Matteo; Yang, Wei; Adam, Rosalyn M.; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA.
[Freeman, Michael R.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Cambridge, MA 02138 USA.
[Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol & Canc Biol, Boston, MA USA.
[Beroukhim, Rameen] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Cambridge, MA 02138 USA.
[True, Lawrence D.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
[Lafargue, Christopher J.; Rubin, Mark A.; Demichelis, Francesca] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA.
[Demichelis, Francesca] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA.
[Beroukhim, Rameen] Broad Inst MIT & Harvard, Cambridge, MA USA.
RP Freeman, MR (reprint author), Childrens Hosp, Enders Res Labs, Urol Dis Res Ctr, Rm 1161,300 Longwood Ave, Boston, MA 02115 USA.
EM michael.freeman@childrens.harvard.edu
RI Yang, Wei/C-3047-2008;
OI Yang, Wei/0000-0003-2575-3570; Rubin, Mark/0000-0002-8321-9950;
Demichelis, Francesca/0000-0002-8266-8631
FU National Institutes of Diabetes, Digestive and Kidney Diseases
[R3747556]; National Cancer Institute (NCI) [P50 DK65298, R01 CA112303,
DAMD17-03-2-0033, K99 CA131472]; DOD PCRP [W81MVH-07-1-0148,
W81XWH-08-1-0139]; AUA Foundation/GlaxoSmithKline; Pacific Northwest
Prostate Cancer Specialized Programs of Research Excellence [CA97186,
NCI P01CA085859, K08CA122833, R01CA116337-01A1]
FX National Institutes of Diabetes, Digestive and Kidney Diseases R3747556.
P50 DK65298, National Cancer Institute (NCI) R01 CA112303 and
DAMD17-03-2-0033 (M.R. Freeman), NCI K99 CA131472 (D. Di Vizio), DOD
PCRP W81MVH-07-1-0148 (M.H. Hager), W81XWH-08-1-0139 (W Yang), the AUA
Foundation/GlaxoSmithKline (M.H. Hager), the Pacific Northwest Prostate
Cancer Specialized Programs of Research Excellence CA97186, NCI
P01CA085859 (L. True), K08CA122833 (R. Beroukhim), and R01CA116337-01A1
(M.A. Rubin and F. Demichelis). J. Kim is a Fislibein/ICA Scholar and a
New York Academy of Medicine Edwin Beer Scholar.
NR 45
TC 115
Z9 115
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2009
VL 69
IS 13
BP 5601
EP 5609
DI 10.1158/0008-5472.CAN-08-3860
PG 9
WC Oncology
SC Oncology
GA 466VP
UT WOS:000267691800043
PM 19549916
ER
PT J
AU Collins, AB
Smith, RN
Stone, JR
AF Collins, A. Bernard
Smith, R. Neal
Stone, James R.
TI Classification of amyloid deposits in diagnostic cardiac specimens by
immunofluorescence
SO CARDIOVASCULAR PATHOLOGY
LA English
DT Article
DE Amyloid; Amyloidosis; AH Amyloid; AL Amyloid; AA Amyloid;
Immunofluorescence; Misdiagnosis; Cardiac; Heart
ID CHAIN-ASSOCIATED AMYLOIDOSIS; PRIMARY SYSTEMIC AMYLOIDOSIS;
ATRIAL-NATRIURETIC-PEPTIDE; IMMUNOGLOBULIN HEAVY-CHAIN; STEM-CELL
TRANSPLANTATION; EMBEDDED BIOPSY SPECIMENS; LAMBDA-LIGHT-CHAIN;
IMMUNOHISTOCHEMICAL CLASSIFICATION; AL-AMYLOIDOSIS; ENDOMYOCARDIAL
BIOPSY
AB Background: At least 12 distinct forms of amyloidosis are known to involve the heart or great vessels. Patient treatment regimens require proper subtyping of amyloid deposits in small diagnostic cardiac specimens. A growing lack of confidence in immunohistochemical staining for subtyping amyloid has arisen primarily as a result of studies utilizing immunoperoxidase staining of formalin-fixed paraffin-embedded tissue. Immunofluorescence staining on fresh frozen tissue is generally considered superior to immunoperoxidase staining for subtyping amyloid; however, this technique has not previously been reported in a series of cardiac specimens. Methods: Amyloid deposits were subtyped in 17 cardiac specimens and 23 renal specimens using an immunofluorescence panel. Results: Amyloid deposits were successfully subtyped as AL, AH, or AA amyloid by immunofluorescence in 82% of cardiac specimens and 87% of renal specimens. In all cases, the amyloid classification was in good agreement with available clinical and laboratory assessments. A cross-study analysis of 163 cases of AL amyloidosis reveals probable systemic misdiagnosis of cardiac AL amyloidosis by the immunoperoxidase technique, but not by the immunofluorescence technique. Conclusions: Amyloid deposits can be reliably subtyped in small diagnostic cardiac specimens using immunofluorescence. The practical aspects of implementing an immunofluorescence
C1 [Collins, A. Bernard; Smith, R. Neal; Stone, James R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
RP Stone, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM jrstone@partners.org
FU Department of Pathology, Massachusetts General Hospital
FX This work was supported by the Department of Pathology, Massachusetts
General Hospital.
NR 80
TC 20
Z9 20
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-8807
J9 CARDIOVASC PATHOL
JI Cardiovasc. Pathol.
PD JUL-AUG
PY 2009
VL 18
IS 4
BP 205
EP 216
DI 10.1016/j.carpath.2008.05.004
PG 12
WC Cardiac & Cardiovascular Systems; Pathology
SC Cardiovascular System & Cardiology; Pathology
GA 474MK
UT WOS:000268287900003
PM 18619857
ER
PT J
AU Garcia, JA
Casserly, IP
AF Garcia, Joel A.
Casserly, Ivan P.
TI Use of the Boomerang Catalyst (TM) Advantage Closure Device to
Facilitate Complex Multistaged Percutaneous Revascularization Procedures
for the Treatment of Critical Limb Ischemia
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE Boomerang catalyst system; peripheral arterial disease; critical limb
ischemia; complex percutaneous revascularization
ID TRANSLUMINAL ANGIOPLASTY; EXPERIENCE
AB An increasing spectrum of complex peripheral arterial disease may be successfully treated using percutaneous revascularization techniques. A pair of challenging peripheral revascularization procedures in patients with critical limb ischemia is presented, where an array of interventional tools and techniques were required, and the off-label use of the Boomerang catalyst system closure device was important in managing a variety of complex arterial access issues and ultimately allowing procedural success. (C) 2009 Wiley-Liss, Inc.
C1 [Garcia, Joel A.; Casserly, Ivan P.] Univ Colorado Denver, Aurora, CO 80045 USA.
[Garcia, Joel A.] Denver Hlth Med Ctr, Denver, CO USA.
[Casserly, Ivan P.] Denver VA Med Ctr, Denver, CO USA.
RP Casserly, IP (reprint author), Univ Colorado Denver, Anschutz Med Campus,Leprino Off Bldg,12401 E 17th, Aurora, CO 80045 USA.
EM ivan.casserly@ucdenver.edu
NR 10
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1522-1946
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD JUL 1
PY 2009
VL 74
IS 1
BP 27
EP 36
DI 10.1002/ccd.21962
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469VG
UT WOS:000267928200007
PM 19530181
ER
PT J
AU Jaff, MR
AF Jaff, Michael R.
TI Chronically Anticoagulated Patients Who Need Surgery: Can
Low-Molecular-Weight Heparins Really Be Used to "Bridge" Patients
Instead of Intravenous Unfractionated Heparin?
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article; Proceedings Paper
CT Meeting on Vascular Interventional Advances
CY SEP 26-29, 2006
CL Las Vegas, NV
DE anticoagulants; bridging therapy; venous thromboembolism
ID MECHANICAL HEART-VALVE; ANTITHROMBOTIC THERAPY; CLINICAL-OUTCOMES;
MANAGEMENT; INTERRUPTION; THROMBOSIS; EMBOLISM; WARFARIN; DISEASE
AB Patients at high risk of arterial or venous thromboembolic events often receive chronic treatment with long-term oral anticoagulants such as warfarin. However, if these patients require an invasive procedure, they may require a temporary interruption of their warfarin therapy to minimize their bleeding risk during the procedure. As warfarin has a long half-life and an unpredictable pharmacokinetic profile, short-acting parenteral anticoagulants, such as unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH), may be of benefit in protecting the patient from thromboemboli while their warfarin dose is withheld. Such "bridging therapy" has traditionally been provided in-hospital with intravenous UFH; however, recent data have suggested that LMWH may be an effective alternative, with potential cost-savings due to the ability to provide bridging therapy in the outpatient setting. (C) 2009 Wiley-Liss, Inc.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, Boston, MA 02114 USA.
RP Jaff, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vasc Ctr, 55 Fruit St,GB 832, Boston, MA 02114 USA.
EM mjaff@partners.org
NR 19
TC 3
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1522-1946
EI 1522-726X
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD JUL 1
PY 2009
VL 74
IS 1
SU S
BP S17
EP S21
DI 10.1002/ccd.22000
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469VI
UT WOS:000267928400004
PM 19213061
ER
PT J
AU Benson, EK
Zhao, B
Sassoon, DA
Lee, SW
Aaronson, SA
AF Benson, Erica K.
Zhao, Bo
Sassoon, David A.
Lee, Sam W.
Aaronson, Stuart A.
TI Effects of p21 deletion in mouse models of premature aging
SO CELL CYCLE
LA English
DT Article
DE p21; premature aging; cellular senescence; tumorigenesis; Ku80; ATM;
TERC
ID ATM-DEFICIENT MICE; CELLULAR SENESCENCE; LIFE-SPAN; REPLICATIVE
SENESCENCE; ATAXIA-TELANGIECTASIA; HUMAN-CELLS; TELOMERE DYSFUNCTION;
HUMAN FIBROBLASTS; GENOME STABILITY; DNA-REPAIR
AB An approach to investigate the role of cellular senescence in organismal aging has been to abrogate signaling pathways known to induce cellular senescence and to assess the effects in mouse models of premature aging. Recently, we reported the effect of loss of function of p21, a gene implicated in p53-induced cellular senescence, in the background of the Ku80(-/-) premature aging mouse (Zhao et al., EMBO Rep 2009). Here, we provide an overview of the effects of p21 deletion in different models of premature aging.
C1 [Benson, Erica K.; Zhao, Bo; Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA.
[Sassoon, David A.] Univ Paris 06, INSERM, UMR S 787, Myol Grp, Paris, France.
[Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
RP Aaronson, SA (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl,POB 1130, New York, NY 10029 USA.
EM stuart.aaronson@mssm.edu
FU National Cancer Institute [PO1CA80058]
FX This work was supported by grant number PO1CA80058 from the National
Cancer Institute.
NR 59
TC 3
Z9 3
U1 1
U2 5
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUL 1
PY 2009
VL 8
IS 13
BP 2002
EP 2004
DI 10.4161/cc.8.13.8997
PG 3
WC Cell Biology
SC Cell Biology
GA 465RG
UT WOS:000267603900015
PM 19535900
ER
PT J
AU Nihal, M
Ahsan, H
Siddiqui, IA
Mukhtar, H
Ahmad, N
Wood, GS
AF Nihal, Minakshi
Ahsan, Haseeb
Siddiqui, Imtiaz A.
Mukhtar, Hasan
Ahmad, Nihal
Wood, Gary S.
TI (-)-Epigallocatechin-3-gallate (EGCG) sensitizes melanoma cells to
interferon induced growth inhibition in a mouse model of human melanoma
SO CELL CYCLE
LA English
DT Article
DE melanoma; chemoprevention; green tea; apoptosis; cell cycle; interferon
ID FACTOR-KAPPA-B; GREEN TEA; MALIGNANT-MELANOMA; SIGNALING PATHWAYS;
APOPTOSIS; CANCER; CHEMOPREVENTION; FAS; THERAPY; PROLIFERATION
AB Melanoma incidence has increased over the last few decades and metastatic melanoma is one of the hardest malignancies to treat. Thus, novel approaches are needed for an effective management of melanoma. Interferon-alpha 2b (IFN), an immunomodulatory cytokine commonly used in melanoma treatment, has shown marginal efficacy and often results in discontinuation of therapy due to toxicity. We earlier demonstrated that epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, caused cell cycle arrest and apoptosis of human melanoma cells via modulation in cki-cyclin-cdk machinery and Bcl-2 family proteins. This study was undertaken to determine if EGCG could enhance the anti-proliferative effects of IFN. In this study, we demonstrated that EGCG and/or IFN treatments to melanoma cells resulted in a marked (1) decrease in cell proliferation and colony formation ability, and (2) induction of apoptosis. Interestingly, the combination was found to be more effective than either of the agents alone. Further, the anti-proliferative effects of EGCG and/or IFN were accompanied with an increase in Fas protein levels and a decrease in nuclear factor NF kappa B/p65 in the nucleus as well as NF kappa B promoter activity. EGCG and/or IFN also resulted in an increase in Fas-L mediated apoptosis. Further, EGCG and/or IFN treatments resulted in a decrease in melanoma tumor growth and protein levels of proliferation marker PCNA, in athymic nude mice implanted with melanoma tumors. The combination of the two modalities demonstrated a better response than either of them alone. Our data suggest that EGCG could impart therapeutic advantage if used in conjunction with IFN.
C1 [Wood, Gary S.] Univ Wisconsin, Sch Med, Dept Dermatol, Madison, WI 53706 USA.
William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA.
RP Wood, GS (reprint author), Univ Wisconsin, Sch Med, Dept Dermatol, 1300 Univ Ave,Room B25, Madison, WI 53706 USA.
EM gwood@dermatol-ogy.wisc.edu
RI Ahsan, Haseeb/H-3085-2015
OI Ahsan, Haseeb/0000-0002-5313-5959
FU Department of Veterans Affairs; Dermatology Foundation; NIH [R21
CA116163]
FX This work was supported by Merit Review funding from the Department of
Veterans Affairs (to G. S. W.), a research grant from Dermatology
Foundation (to M.N.) and R21 CA116163 grant from the NIH (to M.N.). We
also thank Caleb Creswell for his help in this project.
NR 31
TC 19
Z9 20
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUL 1
PY 2009
VL 8
IS 13
BP 2057
EP 2063
DI 10.4161/cc.8.13.8862
PG 7
WC Cell Biology
SC Cell Biology
GA 465RG
UT WOS:000267603900023
PM 19502799
ER
PT J
AU Maynard, CJ
Cappai, R
Volitakis, I
Laughton, KM
Masters, CL
Bush, AI
Li, QX
AF Maynard, Christa J.
Cappai, Roberto
Volitakis, Irene
Laughton, Katrina M.
Masters, Colin L.
Bush, Ashley I.
Li, Qiao-Xin
TI Chronic Exposure to High Levels of Zinc or Copper has Little Effect on
Brain Metal Homeostasis or A beta Accumulation in Transgenic APP-C100
Mice
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Alzheimer's disease; Amyloid-beta peptide; Copper; Zinc; APP-C100
ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; MOUSE
MODEL; PLAQUE-FORMATION; IMMUNE-RESPONSE; EXCESS COPPER; UP-REGULATION;
BINDING-SITE; DIETARY ZINC
AB Aberrant metal homeostasis may enhance the formation of reactive oxygen species and A beta oligomerization and may therefore be a contributing factor in Alzheimer's disease. This study investigated the effect of chronic high intake of dietary Zn or Cu on brain metal levels and the accumulation and solubility of A beta in vivo, using a transgenic mouse model that over expresses the C-terminal containing A beta fragment of human amyloid precursor protein but does not develop amyloid deposits. Exposure to chronic high Zn or Cu in the drinking water resulted in only slight elevations of the respective metals in the brain. Total A beta levels were unchanged although soluble A beta levels were slightly decreased, without visible plaque formation, enhanced gliosis, antioxidant upregulation or neuronal loss. This study indicates that brain metal levels are only marginally altered by long term oral exposure to extremely high Cu or Zn levels, and that this does not induce A beta-amyloid formation in human A beta expressing, amyloid-free mice, although this is sufficient to modulate A beta solubility in vivo.
C1 [Maynard, Christa J.; Cappai, Roberto; Laughton, Katrina M.; Masters, Colin L.; Bush, Ashley I.; Li, Qiao-Xin] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
[Maynard, Christa J.; Cappai, Roberto; Volitakis, Irene; Laughton, Katrina M.; Masters, Colin L.; Bush, Ashley I.; Li, Qiao-Xin] Mental Hlth Res Inst Victoria, Oxidat Disorders Lab, Parkville, Vic 3052, Australia.
[Maynard, Christa J.; Cappai, Roberto; Volitakis, Irene; Laughton, Katrina M.; Masters, Colin L.; Bush, Ashley I.; Li, Qiao-Xin] Mental Hlth Res Inst Victoria, Alzheimers Dis Div, Parkville, Vic 3052, Australia.
[Bush, Ashley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol,Genet & Aging Res Unit, Charlestown, MA 02129 USA.
[Bush, Ashley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA.
RP Li, QX (reprint author), Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
EM q.li@unimelb.edu.au
RI Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007;
OI Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069;
Volitakis, Irene/0000-0003-0766-817X
FU National Health and Medical Research Council of Australia
FX We thank Ms. Tina Cardamone for assisting with immunohistochemistry.
This work was supported in part by grants from the National Health and
Medical Research Council of Australia.
NR 52
TC 11
Z9 12
U1 2
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD JUL
PY 2009
VL 29
IS 5
BP 757
EP 767
DI 10.1007/s10571-009-9401-7
PG 11
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 458AQ
UT WOS:000266983100016
PM 19381799
ER
PT J
AU Azim, E
Shnider, SJ
Cederquist, GY
Sohur, US
Macklis, JD
AF Azim, Eiman
Shnider, Sara J.
Cederquist, Gustav Y.
Sohur, U. Shivraj
Macklis, Jeffrey D.
TI Lmo4 and Clim1 Progressively Delineate Cortical Projection Neuron
Subtypes during Development
SO CEREBRAL CORTEX
LA English
DT Article
DE callosal; corticospinal; cortical development; Lmo4; Clim1; Ldb2;
subcerebral; subtype identity
ID DEVELOPING CEREBRAL-CORTEX; LIM-HOMEODOMAIN ACTIVITY; ACTIVITY IN-VIVO;
DEVELOPING NEOCORTEX; PYRAMIDAL NEURONS; HOMEOBOX GENES; MOTOR-NEURON;
SPECIFICATION; CELL; DIFFERENTIATION
AB Molecular controls over the development of the exceptional neuronal subtype diversity of the cerebral cortex are now beginning to be identified. The initial subtype fate decision early in the life of a neuron, and the malleability of this fate when the balance of key postmitotic signals is modified, reveals not only that a neuron is deterministically set on a general developmental path at its birth, but also that this program must he precisely executed during postmitotic differentiation. Here, we show that callosal projection neurons (CPN) and subcerebral projection neurons (subcerebral PN) in layer V of the neocortex share aspects of molecular identity after their birth that are progressively resolved during differentiation. The LIM-homeodomain-related genes Lmo4 and Clim1 are initially expressed by both CPN and subcerebral PN in layer V, and only during mid to late differentiation does expression of Lmo4 and Clim1 become largely segregated into distinct neuronal subtypes. This progressive postmitotic resolution of molecular identity reveals similarities and possibly shared evolutionary origin between layer V CPN and subcerebral PN, and provides insight into how and when these neuronal subtypes achieve their distinct identities during cortical development.
C1 [Azim, Eiman; Shnider, Sara J.; Cederquist, Gustav Y.; Sohur, U. Shivraj; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg,Program Neurosci, Boston, MA 02114 USA.
[Azim, Eiman; Shnider, Sara J.; Cederquist, Gustav Y.; Sohur, U. Shivraj; Macklis, Jeffrey D.] Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurol,Program Neurosci, Boston, MA 02114 USA.
[Azim, Eiman; Shnider, Sara J.; Cederquist, Gustav Y.; Sohur, U. Shivraj; Macklis, Jeffrey D.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs, Boston, MA 02114 USA.
[Azim, Eiman; Shnider, Sara J.; Cederquist, Gustav Y.; Sohur, U. Shivraj; Macklis, Jeffrey D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Azim, Eiman; Shnider, Sara J.; Cederquist, Gustav Y.; Sohur, U. Shivraj; Macklis, Jeffrey D.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Shnider, Sara J.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
RP Macklis, JD (reprint author), Harvard Univ, Sch Med, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg,Program Neurosci, Boston, MA 02114 USA.
EM jeffrey_macklis@hms.harvard.edu
OI Cederquist, Gustav/0000-0003-4749-6093; Azim, Eiman/0000-0002-1015-1772
FU National Institutes of Health [NS49553, NS45523, NS41590]; Harvard Stem
Cell Institute; Spastic Paraplegia Foundation; Travis Roy Foundation;
Massachusetts Spinal Cord Injury Research Fund; Jane and Lee Seidman
Fund; Emily and Robert Pearlstein Fund for Nervous System Repair;
National Institutes Of Health predoctoral NRSA [F31 NS060421]; NRSA [F31
NS063516]
FX National Institutes of Health (NS49553 and NS45523; additional
infrastructurc Supported by NS41590); Harvard Stem Cell Institute;
Spastic Paraplegia Foundation; Travis Roy Foundation; Massachusetts
Spinal Cord Injury Research Fund; Jane and Lee Seidman Fund for CNS
Research; Emily and Robert Pearlstein Fund for Nervous System Repair
to.J.D.M.; National Institutes Of Health predoctoral NRSA (F31 NS060421)
parrially supported E.A.; National Institutes of Health predoctoral NRSA
(F31 NS063516) partially supported SJ.S.; Harvard Stem Cell Institute
Internship Program partially Supported G.C.; and Cerebral Palsy Research
Fund and fellowship from the Lefler Center for the Study of
Neurodegenerative Disorders partially Supported U.S.S.
NR 42
TC 21
Z9 22
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD JUL
PY 2009
VL 19
BP I62
EP I69
DI 10.1093/cercor/bhp030
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 473JO
UT WOS:000268202500008
PM 19366868
ER
PT J
AU Zier, LS
Burack, JH
Micco, G
Chipman, AK
Frank, JA
White, DB
AF Zier, Lucas S.
Burack, Jeffrey H.
Micco, Guy
Chipman, Anne K.
Frank, James A.
White, Douglas B.
TI Surrogate Decision Makers' Responses to Physicians' Predictions of
Medical Futility
SO CHEST
LA English
DT Article
ID CARE; LIFE; RISKS; TEXAS; END
AB Background: Although physicians sometimes use the futility rationale to limit the use of life-sustaining treatments, little is known about how surrogate decision makers view this rationale. We sought to determine the attitudes of surrogates of patients who are critically ill toward whether physicians can predict futility and whether these attitudes predict surrogates' willingness to discontinue life support when faced with predictions of futility.
Methods: This multicenter, mixed qualitative and quantitative study took place at three hospitals in California from 2006 to 2007. We conducted semistructured interviews with surrogate decision makers for 50 patients who were critically ill and incapacitated that addressed their beliefs about medical futility and inductively developed an organizing framework to describe these beliefs. We used a hypothetical scenario with a modified time-trade-off design to examine the relationship between a patient's prognosis and a surrogate's willingness to withdraw life support. We used a mixed-effects regression model to examine the association between surrogates' attitudes about futility and their willingness to limit life support in the face of a very poor prognosis. Validation methods included the use and integration of multiple data sources, multidisciplinary analysis, and member checking.
Results: Sixty-four percent of surrogates (n = 32; 95% confidence interval [CI], 49 to 77%) expressed doubt about the accuracy of physicians' futility predictions, 32% of surrogates (n = 16; 95% CI, 20 to 47%) elected to continue life support with a < 1% survival estimate, and 18% of surrogates (n = 9; 95% CI, 9 to 31%) elected to continue treatment when the physician believed that the patient had no chance of survival. Surrogates with religious objections to the futility rationale (n = 18) were more likely to request continued life support (odds ratio, 4; 95% CI, 1.2 to 14.0; p = 0.03) than those with secular or experiential objections (n = 15; odds ratio, 0.95; 95% CI, 0.3 to 3.4; p = 0.90).
Conclusions: Doubt about physicians' ability to predict medical futility is common among surrogate decision makers. The nature of the doubt may have implications for responding to conflicts about futility in clinical practice. (CHEST 2009,136.-110-117)
C1 [White, Douglas B.] Univ Calif San Francisco, Program Med Eth, Dept Med, San Francisco, CA 94143 USA.
[Frank, James A.; White, Douglas B.] Univ Calif San Francisco, Div Pulm & Crit Care Med, Sch Med, San Francisco, CA 94143 USA.
[Zier, Lucas S.; Burack, Jeffrey H.; Micco, Guy; Chipman, Anne K.] Univ Calif Berkeley, San Francisco Joint Med Program, Berkeley, CA 94720 USA.
[Burack, Jeffrey H.; Micco, Guy] Univ Calif Berkeley, Sch Publ Hlth, Div Community Hlth & Human Dev, Berkeley, CA 94720 USA.
[Burack, Jeffrey H.] Alta Bates Summit Med Ctr, E Bay AIDS Res Inst, Oakland, CA USA.
[Frank, James A.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP White, DB (reprint author), Univ Calif San Francisco, Program Med Eth, Dept Med, 521 Parnassus Ave,Suite C-126,Box 0903, San Francisco, CA 94143 USA.
EM dwhite@medicine.ucsf.edu
FU University of California; Berkeley-Universitv of California, San
Francisco; National Center for Research Resources [KL2 RR0241301];
National Institutes of Health; Greenwall Foundation
FX This project was supported by it grant from the University of
California, Berkeley-Universitv of California, San Francisco joint
Medical Program (Mr. Zier grant from the University of California, San
Francisco Dealt s Office Medical St-tident Besearch Program (1kir.
Zier), and a grant front the National Center for Research Resources [KL2
RR0241301, a component of the National Institute of Health and the
National Institutes of Health Roadmap for Medical Research (Dr. White).
Dr. White is also supported by it grant from the Greenwall Foundation
Facility Scholars Program.
NR 25
TC 32
Z9 32
U1 1
U2 6
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUL
PY 2009
VL 136
IS 1
BP 110
EP 117
DI 10.1378/chest.08-2753
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 467YG
UT WOS:000267779000017
PM 19318665
ER
PT J
AU Fihn, SD
AF Fihn, Stephan D.
TI Improving Quality Lessons From the Department of Veterans Affairs
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Editorial Material
DE Editorials; hypertension
ID HEALTH-CARE-SYSTEM; TRANSFORMATION
C1 [Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, NW Hlth Serv, Res & Dev Ctr Excellence, Seattle, WA 98101 USA.
[Fihn, Stephan D.] Univ Washington, Dept Med & Hlth Serv, Div Gen Internal Med, Seattle, WA 98195 USA.
RP Fihn, SD (reprint author), VA Puget Sound Hlth Care Syst, NW Hlth Serv, Res & Dev Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM stephan.fihn@va.gov
NR 13
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2009
VL 2
IS 4
BP 294
EP 296
DI 10.1161/CIRCOUTCOMES.109.884353
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 575NP
UT WOS:000276074200003
PM 20031853
ER
PT J
AU Singer, DE
Chang, YC
Fang, MC
Borowsky, LH
Pomernacki, NK
Udaltsova, N
Go, AS
AF Singer, Daniel E.
Chang, Yuchiao
Fang, Margaret C.
Borowsky, Leila H.
Pomernacki, Niela K.
Udaltsova, Natalia
Go, Alan S.
TI Should Patient Characteristics Influence Target Anticoagulation
Intensity for Stroke Prevention in Nonvalvular Atrial Fibrillation? The
ATRIA Study
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE atrial fibrillation; anticoagulation; prevention and control; stroke
ID CLINICAL CLASSIFICATION SCHEMES; RANDOMIZED CONTROLLED-TRIAL; ORAL
ANTICOAGULANT; RISK-FACTORS; ANTITHROMBOTIC THERAPY; BLEEDING
COMPLICATIONS; INTRACRANIAL HEMORRHAGE; CEREBRAL-ISCHEMIA; NATIONAL
REGISTRY; PLUS ASPIRIN
AB Background-Randomized trials and observational studies support using an international normalized ratio (INR) target of 2.0 to 3.0 for preventing ischemic stroke in atrial fibrillation. We assessed whether the INR target should be adjusted based on selected patient characteristics.
Methods and Results-We conducted a case-control study nested within the ATRIA cohort's 9217 atrial fibrillation patients taking warfarin to define the relationship between INR level and the odds of thromboembolism (TE; mainly stroke) and of intracranial hemorrhage (ICH) relative to INR 2.0 to 2.5. We identified 396 TE cases and 164 ICH cases during follow-up. Each case was compared with 4 randomly selected controls matched on calendar date and stroke risk factors using matched univariable analyses and conditional logistic regression. We explored modification of the INR-outcome relationships by the following stroke risk factors: prior stroke, age, and CHADS(2) risk score. Overall, the odds of TE were low and stable above INR 1.8. Compared with INR 2.0 to 2.5, the relative odds of TE increased strikingly at INR <1.8 (eg, odds ratio, 3.72; 95% CI, 2.67 to 5.19, at INR 1.4 to 1.7). The odds of ICH increased markedly at INR values >3.5 (eg, odds ratio, 3.56; 95% CI: 1.70 to 7.46, at INR 3.6 to 4.5). The relative odds of ICH were consistently low at INR <3.6. There was no evidence of lower ICH risk at INR levels <2.0. These patterns of risk did not differ substantially by history of stroke, age, or CHADS2 risk score.
Conclusions-Our results confirm that the current standard of INR 2.0 to 3.0 for atrial fibrillation falls in the optimal INR range. Our findings do not support adjustment of INR targets according to previously defined stroke risk factors. (Circ Cardiovasc Qual Outcomes. 2009;2:297-304.)
C1 [Singer, Daniel E.; Chang, Yuchiao; Borowsky, Leila H.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA.
[Fang, Margaret C.; Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Pomernacki, Niela K.; Udaltsova, Natalia; Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
RP Singer, DE (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM dsinger@partners.org
FU National Institute on Aging [R01 AG15478, K23 AG28978]; National Heart,
Lung, and Blood Institute [U19 HL91179]; Massachusetts General Hospital;
Johnson Johnson
FX Funding for the study was provided by the National Institute on Aging
(R01 AG15478 and K23 AG28978), the National Heart, Lung, and Blood
Institute (U19 HL91179), and the Eliot B. and Edith C. Shoolman fund of
Massachusetts General Hospital. The funding sources had no role in study
design, data collection, data analysis, data interpretation, or writing
of this manuscript.; Dr Singer has consulted for Medtronic, Bayer
Healthcare, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson,
Bristol-Myers Squibb, Pfizer, and Sanofi Aventis and has received
research support from Daiichi Sankyo. Dr Go has received research
support from Johnson & Johnson. Drs Chang, Fang, and Udaltsova and Ms
Borowsky and Ms Pomernacki declare no conflicts of interest.
NR 42
TC 57
Z9 58
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2009
VL 2
IS 4
BP 297
EP U30
DI 10.1161/CIRCOUTCOMES.108.830232
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 575NP
UT WOS:000276074200004
PM 20031854
ER
PT J
AU Mancini, GBJ
Bates, ER
Maron, DJ
Hartigan, P
Dada, M
Gosselin, G
Kostuk, W
Sedlis, SP
Shaw, LJ
Berman, DS
Berger, PB
Spertus, J
Mavromatis, K
Knudtson, M
Chaitman, BR
O'Rourke, RA
Weintraub, WS
Teo, K
Boden, WE
AF Mancini, G. B. John
Bates, Eric R.
Maron, David J.
Hartigan, Pamela
Dada, Marcin
Gosselin, Gilbert
Kostuk, William
Sedlis, Steven P.
Shaw, Leslee J.
Berman, Daniel S.
Berger, Peter B.
Spertus, John
Mavromatis, Kreton
Knudtson, Merril
Chaitman, Bernard R.
O'Rourke, Robert A.
Weintraub, William S.
Teo, Koon
Boden, William E.
CA COURAGE Trial Investigators Coordi
TI Quantitative Results of Baseline Angiography and Percutaneous Coronary
Intervention in the COURAGE Trial
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE coronary angiography; ventricular ejection fraction; gender identity;
delivery of health care; revascularization; stent
ID CONTROLLED CLINICAL-TRIAL; 3 THERAPEUTIC STRATEGIES; ARTERY-DISEASE;
MASS-II; SURGERY; ANGIOPLASTY; MEDICINE; ANGINA; VIVO
AB Background-COURAGE compared outcomes in stable coronary patients randomized to optimal medical therapy plus percutaneous coronary intervention (PCI) versus optimal medical therapy alone.
Methods and Results-Angiographic data were analyzed by treatment arm, health care system (Veterans Administration, US non-Veterans Administration, Canada), and gender. Veterans Administration patients had higher prevalence of coronary artery bypass graft surgery and left ventricular ejection fraction <= 50%. Men had worse diameter stenosis of the most severe lesion, higher prevalence of prior coronary artery bypass graft surgery, lower left ventricular ejection fraction, and more 3-vessel disease that included a proximal left anterior descending lesion (P<0.0001 for all comparisons versus women). Failure to cross rate (3%) and visual angiographic success of stent procedures (97%) were similar to contemporary practice in the National Cardiovascular Data Registry. Quantitative angiographic PCI success was 93% (residual lesion <50% in-segment) and 82% (<20% in-stent), with only minor nonsignificant differences among health care systems and genders. Event rates were higher in patients with higher jeopardy scores and more severe vessel disease, but rates were similar irrespective of treatment strategy. Within the PCI plus optimal medical therapy arm, complete revascularization was associated with a trend toward lower rate of death or nonfatal myocardial infarction. Complete revascularization was similar between genders and among health care systems.
Conclusions-PCI success and completeness of revascularization did not differ significantly by health care system or gender and were similar to contemporary practice. Angiographic burden of disease affected overall event rates but not response to an initial strategy of PCI plus optimal medical therapy or optimal medical therapy alone. (Circ Cardiovasc Qual Outcomes. 2009;2:320-327.)
C1 [Mancini, G. B. John] Univ British Columbia, Vancouver Hosp, Cardiovasc Imaging Res Core Lab, Vancouver, BC V5Z 1M9, Canada.
[Bates, Eric R.] Univ Michigan, Med Ctr, Ann Arbor, MI USA.
[Maron, David J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Hartigan, Pamela] Connecticut VA Healthcare Syst, Vet Affairs Cooperat Studies Program Coordinating, West Haven, CT USA.
[Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA.
[Gosselin, Gilbert] Univ Montreal, Montreal Heart Inst, Montreal, PQ H3C 3J7, Canada.
[Kostuk, William] Univ Western Ontario, London Hlth Sci Ctr, London, ON, Canada.
[Sedlis, Steven P.] NYU, Sch Med, VA New York Harbor Hlth Care Syst New York Campus, New York, NY 10003 USA.
[Shaw, Leslee J.; Mavromatis, Kreton] Emory Univ, Sch Med, Atlanta, GA USA.
[Berman, Daniel S.] Univ Calif Los Angeles, Cedars Sinai Heart Inst, Los Angeles, CA USA.
[Berger, Peter B.] Geisinger Med Ctr, Danville, PA 17822 USA.
[Spertus, John] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA.
[Knudtson, Merril] Univ Calgary, Calgary, AB T2N 1N4, Canada.
[Chaitman, Bernard R.] St Louis Univ Hosp, St Louis, MO USA.
[O'Rourke, Robert A.] S Texas Vet Healthcare Syst, San Antonio, TX USA.
[O'Rourke, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA.
[Teo, Koon] McMaster Univ, Med Ctr, Hamilton, ON, Canada.
[Boden, William E.] SUNY, Sch Med & Biomed Sci, Buffalo Gen Hosp, Kaleida Hlth, New York, NY USA.
RP Mancini, GBJ (reprint author), Univ British Columbia, Vancouver Hosp, Cardiovasc Imaging Res Core Lab, 10209-2775 Laurel St, Vancouver, BC V5Z 1M9, Canada.
EM mancini@interchange.ubc.ca
OI Sedlis, Steven/0000-0002-8194-8017
FU Merck Co; Pfizer Pharmaceuticals; Bristol-Myers-Squibb Medical Imaging;
Fujisawa; Kos Pharmaceuticals; Data Scope; AstraZeneca; Key
Pharmaceutical Co Ltd; Sanofi Aventis Inc; First Horizon; Nycomed
Amersham; Department of Veterans Administration; Astellas Healthcare;
Medtronic; GE; Siemens; Molecular Insight Pharma; Sicor; CIHR; Canadian
Cardiovascular Society; Merck
FX This work was supported by the Cooperative Studies Program of the
Department of Veterans Affairs Office of Research and Development, in
collaboration with the Canadian Institute of Health Research;
unrestricted research grants have been obtained from Merck & Co, Pfizer
Pharmaceuticals, Bristol-Myers-Squibb Medical Imaging, Fujisawa, Kos
Pharmaceuticals, Data Scope, AstraZeneca, Key Pharmaceutical Co Ltd,
Sanofi Aventis Inc, First Horizon, and Nycomed Amersham. All industrial
funding in support of the trial has been directed through the Department
of Veterans Administration.; Dr Mancini has received honoraria from
GlaxoSmthKline, Merck, Pfizer, and sanofi-aventis. Dr Berman has
received research grants and honoraria from Astellas Healthcare,
Medtronic, GE, Siemens, and Molecular Insight Pharma; has ownership
interest in Spectrum Dynamics; serves as a consultant for Astellas,
Fluoro Pharma, and Magellan; and has received software royalties from
CSMC. Dr Berger has ownership interest in Lumen and has served on the
consultancy/ad board for PlaCor, Accumetrics, The Medicines Company, and
Eli Lilly/Daiichi-Sankyo. Dr Spertus has received research grants from
Sicor; other research Support from Roche Diagnostics; has ownership
interest in SAQ, KCCQ, and PTQ; and has served as a consultant for
United Healthcare. Dr Knudtson has received research grants from CIHR;
honoraria from the Canadian Cardiovascular Society; and has served as an
expert witness for a defendant in medical civil action suit. Dr Chaitman
has received research grants from Merck; served on the speakers' bureau
for CV Therapeutics; and serves on the consultancy/ad boards for Sanofi
Aventis and Merck. Dr O'Rourke has received research grants from BARI-2D
and has served as a consultant for the PACE-MI Study. Dr Weintraub has
received research grants from Sanofi Aventis, AstraZeneca, Otsuka, and
Bristol Myers Squibb; served as an expert witness for Pfizer nad
AstraZeneca; and served as a consultant for GlaxoSmithKline, Indigo
Pharmaceuticals, Sanofi Aventis, and CV Therapeutics. Dr Teo has
received research grants from CIHR; other research support from
Boehringer-Ingelheim; honoraria from Boehringer-Ingelheim; and has
served as a consultant for Boehringer-Ingelheim.
NR 19
TC 18
Z9 18
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2009
VL 2
IS 4
BP 320
EP U97
DI 10.1161/CIRCOUTCOMES.108.830091
PG 48
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 575NP
UT WOS:000276074200007
PM 20031857
ER
PT J
AU Arnold, SV
Morrow, DA
Lei, Y
Cohen, DJ
Mahoney, EM
Braunwald, E
Chan, PS
AF Arnold, Suzanne V.
Morrow, David A.
Lei, Yang
Cohen, David J.
Mahoney, Elizabeth M.
Braunwald, Eugene
Chan, Paul S.
TI Economic Impact of Angina After an Acute Coronary Syndrome Insights From
the MERLIN-TIMI 36 Trial
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE angina; cost and cost analysis; health status
ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; TRANSMYOCARDIAL LASER
REVASCULARIZATION; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; HEALTH-STATUS;
CLINICAL-OUTCOMES; REFRACTORY ANGINA; INTERVENTION; RANOLAZINE
AB Background-Angina in patients with coronary artery disease is associated with worse quality of life; however, the relationship between angina frequency and resource utilization is unknown.
Methods and Results-Using data from the MERLIN-TIMI 36 trial, we assessed the association between the extent of angina after an acute coronary syndrome (ACS) and subsequent cardiovascular resource utilization among 5460 stable outpatients who completed the Seattle Angina Questionnaire at 4 months after an ACS and who were then followed for an additional 8 months. Angina frequency was categorized as none (score, 100; 2739 patients), monthly (score, 61 to 99; 1608 patients), weekly (score, 31 to 60; 854 patients), and daily (score, 0 to 30; 259 patients). Multivariable regression models evaluated the association between angina frequency and overall costs attributable to cardiovascular hospitalizations, outpatient visits and procedures, and medications. As compared with no angina, overall costs increased in a graded fashion with higher angina frequency-no angina, $2928 (reference); monthly angina, $3909 (adjusted relative cost ratio, 1.29; 95% CI, 1.21 to 1.39); weekly angina, $4558 (adjusted relative cost ratio, 1.52; 95% CI, 1.48 to 1.67); and daily angina, $6949 (adjusted relative cost ratio, 2.32; 95% CI, 2.01 to 2.69; P for trend <0.001). Differences in costs were attributable primarily to higher rates of ACS hospitalization and coronary revascularization among patients with more severe angina.
Conclusion-Among stable outpatients after ACS, a direct graded relationship was found between higher angina frequency and healthcare costs. As compared with patients without angina, patients with daily angina had a >2-fold increase in resource utilization and incremental costs of $4000 after 8 months of follow-up. (Circ Cardiovasc Qual Outcomes. 2009;2:344-353.)
C1 [Arnold, Suzanne V.; Lei, Yang; Cohen, David J.; Mahoney, Elizabeth M.; Chan, Paul S.] St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Morrow, David A.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
RP Chan, PS (reprint author), St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA.
EM pchan@cc-pc.com
FU CV Therapeutics
FX The MERLIN-TIMI 36 Trial was funded by a grant from CV Therapeutics.
NR 36
TC 46
Z9 46
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2009
VL 2
IS 4
BP 344
EP U130
DI 10.1161/CIRCOUTCOMES.108.829523
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 575NP
UT WOS:000276074200010
PM 20031860
ER
PT J
AU Rose, AJ
Berlowitz, DR
Manze, M
Orner, MB
Kressin, NR
AF Rose, Adam J.
Berlowitz, Dan R.
Manze, Meredith
Orner, Michelle B.
Kressin, Nancy R.
TI Comparing Methods of Measuring Treatment Intensification in Hypertension
Care
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE hypertension; chronic disease; research; quality of health care;
ambulatory care
ID BLOOD-PRESSURE CONTROL; CLINICAL INERTIA; MEDICATION ADHERENCE; DIABETES
CARE; HEALTH-CARE; MANAGEMENT; QUALITY; THERAPY; COHORT
AB Background-Greater treatment intensification (TI) improves hypertension control. However, we do not know the ideal way to measure TI for research and quality improvement efforts. We compared the ability of different TI measures to predict blood pressure (BP) control.
Methods and Results-We enrolled 819 hypertensive outpatients from an urban academic hospital. Each patient was assigned 3 scores to characterize TI. The any/none score divides patients into those who had any therapy increases during the study versus none. The norm-based method models the chance of a medication increase at each visit, then scores each patient based on whether they received more or fewer medication increases than predicted. The standard-based method is similar to the norm-based method but expects a medication increase whenever the blood pressure is uncontrolled. We compared the ability of these scores to predict the final systolic blood pressure (SBP). The any/none score showed a paradoxical result: any therapy increase was associated with SBP 4.6 mm Hg higher than no increase (P < 0.001). The norm-based method score did not predict SBP in a linear fashion (P = 0.18); further investigation revealed a U-shaped relationship between the norm-based method score and SBP. However, the standard-based method score was a strong linear predictor of SBP (2.1 mm Hg lower for each additional therapy increase per 10 visits, P < 0.001). Similarly, the standard-based method predicted dichotomized blood pressure control, as measured by SBP <140 mm Hg (odds ratio, 1.30; P < 0.001).
Conclusions-Our results suggest that standard-based method is the preferred measure of treatment intensity for hypertension care. (Circ Cardiovasc Qual Outcomes. 2009;2:385-391.)
C1 [Rose, Adam J.; Berlowitz, Dan R.; Orner, Michelle B.; Kressin, Nancy R.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA.
[Rose, Adam J.; Berlowitz, Dan R.; Manze, Meredith; Kressin, Nancy R.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Berlowitz, Dan R.; Manze, Meredith] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA.
RP Rose, AJ (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70, Bedford, MA 01730 USA.
EM adamrose@bu.edu
OI Kressin, Nancy/0000-0003-2767-4286
FU National Institutes of Health [HL072814]; Department of Veterans
Affairs, Health Services Research and Development Service [RCS 02-066-1]
FX This research was supported by a grant from the National Institutes of
Health (HL072814, N. R. Kressin, Principal Investigator). Dr Rose is
supported by a career development award from the Department of Veterans
Affairs, Health Services Research and Development Service. Dr Kressin is
supported by a Research Career Scientist award from the Department of
Veterans Affairs, Health Services Research and Development Service (RCS
02-066-1). The views expressed in this article are those of the authors
and do not necessarily represent the views of the Department of Veterans
Affairs.
NR 26
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2009
VL 2
IS 4
BP 385
EP U178
DI 10.1161/CIRCOUTCOMES.108.838649
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 575NP
UT WOS:000276074200015
PM 20031865
ER
PT J
AU Shah, RV
Chen-Tournoux, AA
Picard, MH
van Kimmenade, RRJ
Januzzi, JL
AF Shah, Ravi V.
Chen-Tournoux, Annabel A.
Picard, Michael H.
van Kimmenade, Roland R. J.
Januzzi, James L.
TI Serum Levels of the Interleukin-1 Receptor Family Member ST2, Cardiac
Structure and Function, and Long-Term Mortality in Patients With Acute
Dyspnea
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE echocardiography; heart failure; biomarker; prognosis
ID DECOMPENSATED HEART-FAILURE; EMERGENCY-DEPARTMENT PRIDE; NATRIURETIC
PEPTIDE LEVELS; MYOCARDIAL-INFARCTION; ADMISSION; BIOMARKER; OUTCOMES;
SYSTEM
AB Background-ST2, a biomarker of cardiomyocyte stretch, powerfully predicts poor outcomes in patients with acute dyspnea, but nothing is known about associations between soluble ST2 (sST2) and cardiac structure and function, or whether sST2 retains prognostic meaning in the context of such measures.
Methods and Results-One hundred thirty-four dyspneic patients with and without decompensated heart failure had echocardiography during index admission and vital status was ascertained at 4 years. Echocardiographic and clinical correlates of sST2 as well as independent predictors of death at 4 years were identified. sST2 correlated with left ventricular end-systolic dimensions/volumes and left ventricular ejection fraction. sST2 was inversely associated with right ventricular fractional area change (rho=-0.18; P=0.046), higher right ventricular systolic pressure (rho=0.26; P=0.005), and right ventricular hypokinesis (P<0.001) and was correlated with tissue Doppler Ea wave peak velocity, but not to other indices of diastolic function. In multivariate regression, independent predictors of sST2 included right ventricular systolic pressure (t=2.29; P=0.002), left ventricular ejection fraction (t=-2.15; P=0.05) and dimensions (end systolic, t=2.57; end diastolic, t=2.98; both P<0.05), amino-terminal pro-B-type natriuretic peptide (t=3.31; P=0.009), heart rate (t=2.59; P=0.01), and presence of jugular venous distension (t=2.00; P=0.05). In a Cox proportional hazards model that included echocardiographic results and other biomarkers, sST2 independently predicted death at 4 years (hazard ratio=2.70; P=0.003).
Conclusions-Among dyspneic patients with and without acute heart failure, sST2 concentrations are associated with prevalent cardiac abnormalities on echocardiography, a more decompensated hemodynamic profile and are associated with long-term mortality, independent of echocardiographic, clinical, or other biochemical markers of risk. (Circ Heart Fail. 2009;2:311-319.)
C1 [Shah, Ravi V.; Chen-Tournoux, Annabel A.; Picard, Michael H.; Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
[Shah, Ravi V.; Picard, Michael H.; Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
[van Kimmenade, Roland R. J.] Univ Hosp Maastricht, Dept Cardiol, Az Maastricht, Netherlands.
RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA.
EM jjanuzzi@partners.org
RI Kimmenade, R.R.J./L-4432-2015;
OI Picard, Michael/0000-0002-9264-3243
FU National Heart, Lung, and Blood Institute Heart Failure Research
Network, Boston, Mass; Balson Scholar Fund, Boston, Mass;
Interuniversity Cardiology Institute of the Netherlands (ICIN)
FX This study was supported by grant from the National Heart, Lung, and
Blood Institute Heart Failure Research Network, Boston, Mass (to
R.V.S.); in part by the Balson Scholar Fund, Boston, Mass (to J.L.J.);
and by a research fellowship of the Interuniversity Cardiology Institute
of the Netherlands (ICIN) (to R.R.J.v.K.).
NR 19
TC 78
Z9 81
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD JUL
PY 2009
VL 2
IS 4
BP 311
EP 319
DI 10.1161/CIRCHEARTFAILURE.108.833707
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 477PF
UT WOS:000268530300006
PM 19808354
ER
PT J
AU Spinale, FG
Escobar, GP
Mukherjee, R
Zavadzkas, JA
Saunders, SM
Jeffords, LB
Leone, AM
Beck, C
Bouges, S
Stroud, RE
AF Spinale, Francis G.
Escobar, G. Patricia
Mukherjee, Rupak
Zavadzkas, Juozas A.
Saunders, Stuart M.
Jeffords, Laura B.
Leone, Allyson M.
Beck, Christy
Bouges, Shenikqua
Stroud, Robert E.
TI Cardiac-Restricted Overexpression of Membrane Type-1 Matrix
Metalloproteinase in Mice Effects on Myocardial Remodeling With Aging
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE matrix; myocardial remodeling; ventricular function; aging
ID TGF-BETA SIGNALS; 1-MATRIX METALLOPROTEINASE; EXTRACELLULAR-MATRIX;
VENTRICULAR-FUNCTION; BINDING-PROTEINS; ACTIVATION; MT1-MMP; CELLS;
CARDIOMYOPATHY; TRAFFICKING
AB Background-The direct consequences of a persistently increased myocardial expression of the unique matrix metallo-proteinase (MMP) membrane type-1 (MT1-MMP) on myocardial remodeling remained unexplored.
Methods and Results-Cardiac-restricted MT1-MMPexp was constructed in mice using the full-length human MT1-MMP gene ligated to the myosin heavy chain promoter, which yielded approximately a 200% increase in MT1-MMP when compared with age/strain-matched wild-type (WT) mice. Left ventricular (LV) function and geometry was assessed by echocardiography in 3-month ("young") WT (n=32) and MT1-MMPexp (n=20) mice and compared with 14-month ("middle-aged") WT (n=58) and MT1-MMPexp (n=35) mice. LV end-diastolic volume was similar between the WT and MT1-MMPexp young groups, as was LV ejection fraction. In the middle-aged WT mice, LV end-diastolic volume and ejection fraction was similar to young WT mice. However, in the MT1-MMPexp middle-aged mice, LV end-diastolic volume was approximate to 43% higher and LV ejection fraction 40% lower (both P<0.05). Moreover, in the middle-aged MT1-MMPexp mice, myocardial fibrillar collagen increased by nearly 2-fold and was associated with approximate to 3-fold increase in the processing of the profibrotic molecule, latency-associated transforming growth factor binding protein. In a second study, 14-day survival after myocardial infarction was significantly lower in middle-aged MT1-MMPexp mice.
Conclusions-Persistently increased myocardial MT1-MMP expression, in and of itself, caused LV remodeling, myocardial fibrosis, dysfunction, and reduced survival after myocardial injury. These findings suggest that MT1-MMP plays a mechanistic role in adverse remodeling within the myocardium. (Circ Heart Fail. 2009;2:351-360.)
C1 [Spinale, Francis G.; Escobar, G. Patricia; Mukherjee, Rupak; Zavadzkas, Juozas A.; Saunders, Stuart M.; Jeffords, Laura B.; Leone, Allyson M.; Beck, Christy; Bouges, Shenikqua; Stroud, Robert E.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA.
[Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Div Cardiothorac Surg, Charleston, SC USA.
RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Room 625,114 Doughty St, Charleston, SC 29425 USA.
EM wilburnm@musc.edu
FU National Institutes of Health [HL059165, PO I HL048788, HL078650];
Veterans' Affairs Health Administration
FX This study was supported by National Institutes of Health grants
HL059165, PO I HL048788, and HL078650 and a Merit Award from the
Veterans' Affairs Health Administration.
NR 30
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Z9 27
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD JUL
PY 2009
VL 2
IS 4
BP 351
EP 360
DI 10.1161/CIRCHEARTFAILURE.108.844845
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 477PF
UT WOS:000268530300011
PM 19808359
ER
PT J
AU Potash, J
Anderson, KC
AF Potash, Jesse
Anderson, Kenneth C.
TI What's Your Line?
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
C1 [Potash, Jesse; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM kenneth_anderson@dfci.harvard.edu
NR 0
TC 5
Z9 5
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 1
PY 2009
VL 15
IS 13
BP 4251
EP 4251
DI 10.1158/1078-0432.CCR-09-1364
PG 1
WC Oncology
SC Oncology
GA 482SF
UT WOS:000268908300001
PM 19549765
ER
PT J
AU Carpenter, EL
Mick, R
Rech, AJ
Beatty, GL
Colligon, TA
Rosenfeld, MR
Kaplan, DE
Chang, KM
Domchek, SM
Kanetsky, PA
Fecher, LA
Flaherty, KT
Schuchter, LM
Vonderheide, RH
AF Carpenter, Erica L.
Mick, Rosemarie
Rech, Andrew J.
Beatty, Gregory L.
Colligon, Theresa A.
Rosenfeld, Myrna R.
Kaplan, David E.
Chang, Kyong-Mi
Domchek, Susan M.
Kanetsky, Peter A.
Fecher, Leslie A.
Flaherty, Keith T.
Schuchter, Lynn M.
Vonderheide, Robert H.
TI Collapse of the CD27+B-Cell Compartment Associated with Systemic
Plasmacytosis in Patients with Advanced Melanoma and Other Cancers
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MEMORY B-CELLS; ANTIGEN-PRESENTING CELLS; LUPUS-ERYTHEMATOSUS; T-CELLS;
IMMUNE-RESPONSES; HIV-1 INFECTION; SERUM-LEVELS; LYMPHOCYTES;
POPULATION; EXPRESSION
AB Purpose: Disturbed peripheral blood B-cell homeostasis complicates certain infections and autoimmune diseases, such as HIV and systemic lupus erythematosus, but has not been reported in cancer. This study aimed to investigate whether B-cell physiology was altered in the presence of melanoma and other cancers.
Experimental Design: Flow cytometry was used to identify phenotypic differences in B cells from patients with melanoma and normal donors. In vitro stimulated 8 cells were assessed for responsiveness and also used as stimulators of allogeneic T cells in mixed lymphocyte reactions.
Results: We show B-cell dysregulation in patients with advanced melanoma (n = 26) and other solid tumors (n = 13), marked by a relative and absolute loss of CD27+ (memory) B cells and associated with an aberrant systemic plasmacytosis. Functionally, B cells from patients with melanoma inefficiently up-regulated immunoregulatory molecules and weakly secreted cytokines in response to CD40 and toll-like receptor 9 agonists. Stimulated B cells from patients induced proliferation of alloreactive CD4+ T cells, but these T cells poorly secreted IFN gamma and interleukin-2. These effects were recapitulated by using purified normal donor CD27(neg) B cells in these same assays, linking the predominance of CD27(neg) B cells in patients with the observed functional hyporesponsiveness. Indeed, B-cell dysfunction in patients strongly correlated with the extent of loss of CD27+ B cells in peripheral blood.
Conclusions: Disturbed B-cell homeostasis is a previously unrecognized feature of patients with advanced melanoma and other cancers and may represent an unanticipated mechanism of immune incompetence in cancer.
C1 [Carpenter, Erica L.; Rech, Andrew J.; Beatty, Gregory L.; Colligon, Theresa A.; Vonderheide, Robert H.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Mick, Rosemarie; Rosenfeld, Myrna R.; Chang, Kyong-Mi; Domchek, Susan M.; Kanetsky, Peter A.; Fecher, Leslie A.; Flaherty, Keith T.; Schuchter, Lynn M.; Vonderheide, Robert H.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Kaplan, David E.; Chang, Kyong-Mi] Univ Penn, Sch Med, Gastroenterol Sect, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Beatty, Gregory L.; Domchek, Susan M.; Fecher, Leslie A.; Flaherty, Keith T.; Schuchter, Lynn M.; Vonderheide, Robert H.] Univ Penn, Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Kaplan, David E.; Chang, Kyong-Mi] Univ Penn, Sch Med, Div Gastroenterol, Dept Med, Philadelphia, PA 19104 USA.
[Rosenfeld, Myrna R.] Univ Penn, Sch Med, Div Neurooncol, Dept Neurol, Philadelphia, PA 19104 USA.
[Mick, Rosemarie; Kanetsky, Peter A.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Vonderheide, RH (reprint author), Univ Penn, Sch Med, Abramson Family Canc Res Inst, 551 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA.
EM rhv@exchange.upenn.edu
OI Kaplan, David E./0000-0002-3839-336X; Rosenfeld,
Myrna/0000-0001-5095-2534
FU NIH [CA093372, CA09140, CA16520, AI47519, RR017625]; Breast Cancer
Research Foundation; VA Career Development Award
FX NIH grants CA093372 (R.H.Vonderheide), CA09140 (E.L. Carpenter), CA16520
(R.H.Vonderheide), AI47519 (K-M. Chang), and RR017625 (D.E. Kaplan);
Breast Cancer Research Foundation (R.H. Vonderheide); VA Career
Development Award (D.E. Kaplan); and a gift from Mark and Paula Solomon
(R.H. Vonderheide).
NR 49
TC 23
Z9 24
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 1
PY 2009
VL 15
IS 13
BP 4277
EP 4287
DI 10.1158/1078-0432.CCR-09-0537
PG 11
WC Oncology
SC Oncology
GA 482SF
UT WOS:000268908300007
PM 19549767
ER
PT J
AU Ogino, S
Nosho, K
Irahara, N
Kure, S
Shima, K
Baba, Y
Toyoda, S
Chen, L
Giovannucci, EL
Meyerhardt, JA
Fuchs, CS
AF Ogino, Shuji
Nosho, Katsuhiko
Irahara, Natsumi
Kure, Shoko
Shima, Kaori
Baba, Yoshifumi
Toyoda, Saori
Chen, Li
Giovannucci, Edward L.
Meyerhardt, Jeffrey A.
Fuchs, Charles S.
TI A Cohort Study of Cyclin D1 Expression and Prognosis in 602 Colon Cancer
Cases
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; TUMOR-INFILTRATING LYMPHOCYTES;
COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; BETA-CATENIN; LINE-1
HYPOMETHYLATION; MISMATCH REPAIR; POOR-PROGNOSIS; BRAF MUTATION;
CARCINOMA
AB Purpose: Cyclin D1 and cyclin-dependent kinases (CDK) are commonly activated in colorectal cancer. The activity of cyclin D1 can be blocked by CDK inhibitors, including p27 (CDKN1B) and p21 (CDKN1A, which is induced by p53). However, prognostic significance of tumoral cyclin D1 remains uncertain, and no previous study has considered potential confounding effect of p53, p21, p27, and related molecular events [microsatellite instability (MSI), CpG island methylator phenotype, and LINE-1 hypomethylation].
Experimental Design: Among 602 colon cancer patients (stage I-IV) in two prospective cohort studies, cyclin D1 overexpression was detected in 330 (55%) tumors by immunohistochemistry. Cox proportional hazard models computed hazard ratios (HR) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and tumoral molecular features, including p53, p21, p27, cyclooxygenase-2, fatty acid synthase, LINE-1 methylation, CpG island methylator phenotype, MSI, BMI, KRAS, and BRAF.
Results: Cyclin D1 overexpression was associated with a low cancer-specific mortality in Kaplan-Meier analysis (P = 0.006), and in both univariate Cox regression [unadjusted HR, 0.64; 95% confidence interval (CI), 0.47-0.88; P = 0.0063] and multivariate analyses (adjusted HR, 0.57; 95% Cl, 0.39-0.84; P = 0.0048). Similar findings were observed for an overall mortality (adjusted HR, 0.74; 95% Cl, 0.57-0.98; P = 0.036). Notably, the effect of cyclin D1 on survival might differ by MSI status (P(interaction) = 0.008). Compared with tumors that were both cyclin D1 - negative and MSI-low/microsatellite stable, the presence of either cyclin D1 or MSI-high or both seemed to confer better clinical outcome (adjusted HR point estimates, 0.10-0.65).
Conclusions: Cyclin D1 overexpression is associated with longer survival in colon cancer.
C1 [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Med Sch,Dept Med Oncol, Boston, MA 02115 USA.
[Ogino, Shuji; Chen, Li] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol,Med Sch,Dept Med Oncol, 44 Binney St,Room JF 215C, Boston, MA 02115 USA.
EM shuji.ogino@dfci.harvard.edu
FU U.S. NIH [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA97992, K07
CA122826]; Bennett Family Fund; Entertainment Industry Foundation
National Colorectal Cancer Research Alliance; Japan Society for
Promotion of Science
FX U.S. NIH P01 CA87969 (S. Hankinson), P01 CA55075 (W. Willett), P50
CA127003 (C.S. Fuchs), K07 CA97992 (J.A. Meyerhardt), and K07 CA122826
(S. Ogino); the Bennett Family Fund; and the Entertainment Industry
Foundation National Colorectal Cancer Research Alliance. K. Nosho was
supported by a fellowship grant from the Japan Society for Promotion of
Science. The content is solely the responsibility of the authors and
does not necessarily represent the official views of National Cancer
Institute or NIH. Funding agencies did not have any role in the design
of the study; the collection, analysis, or interpretation of the data;
the decision to submit the manuscript for publication; or the writing of
the manuscript.
NR 51
TC 34
Z9 35
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 1
PY 2009
VL 15
IS 13
BP 4431
EP 4438
DI 10.1158/1078-0432.CCR-08-3330
PG 8
WC Oncology
SC Oncology
GA 482SF
UT WOS:000268908300023
PM 19549773
ER
PT J
AU Tan, G
Thornby, J
Hammond, DC
Strehl, U
Canady, B
Arnemann, K
Kaiser, DA
AF Tan, Gabriel
Thornby, John
Hammond, D. Corydon
Strehl, Ute
Canady, Brittany
Arnemann, Kelly
Kaiser, David A.
TI Meta-Analysis of EEG Biofeedback in Treating Epilepsy
SO CLINICAL EEG AND NEUROSCIENCE
LA English
DT Article
DE EEG Biofeedback; Epilepsy; Meta-Analysis; Neurofeedback; Neurotherapy;
Seizure
ID SENSORIMOTOR RHYTHM; SEIZURE PREDICTION; SLEEP EEG; CAT
AB About one third of patients with epilepsy do not benefit from medical treatment. For these patients electroencephalographic (EEG) biofeedback is a viable alternative. EEG biofeedback, or neurofeedback, normalizes or enhances EEG activity by means of operant conditioning. While dozens of scientific reports have been published on neurofeedback for seizure disorder, most have been case series with too few subjects to establish efficacy, The purpose of this paper is to meta-analyze existing research on neurofeedback and epilepsy.
We analyzed every EEG biofeedback study indexed in MedLine, PsychInfo, and PsychLit databases between 1970 and 2005 on epilepsy that provided seizure frequency change in response to feedback. Sixty-three studies have been published, 10 of which provided enough outcome information to be included in a meta-analysis. All studies consisted of patients whose seizures were not controlled by medical therapies, which is a very important factor to keep in mind when interpreting the results. Nine of 10 studies reinforced sensorimotor rhythms (SMR) while 1 study trained slow cortical potentials (SCP). All studies reported an overall mean decreased seizure incidence following treatment and 64 out of 87 patients (74%) reported fewer weekly seizures in response to EEG biofeedback. Treatment effect was mean log (post/pre) where pre and post represent number of seizures per week prior to treatment and at final evaluation, respectively. Due to prevalence of small groups, Hedges's g was computed for effect size, As sample heterogeneity was possible (Q test, p=.18), random effects were assumed and the effect of intervention was -0.233, SE=0.057, z=-4.11, P<.001.
Based on this meta-analysis, EEG operant conditioning was found to produce a significant reduction on seizure frequency. This finding is especially noteworthy given the patient group, individuals who had been unable to control their seizures with medical treatment.
C1 [Tan, Gabriel; Thornby, John] Michael E DeBakey Vet Affairs Hosp, Houston, TX USA.
[Tan, Gabriel; Thornby, John] Baylor Coll Med, Houston, TX 77030 USA.
[Hammond, D. Corydon] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Strehl, Ute] Univ Tubingen, Tubingen, Germany.
[Canady, Brittany] Geisinger Med Ctr, Danville, PA 17822 USA.
[Arnemann, Kelly] Audie L Murphy Vet Affairs Hosp, San Antonio, TX USA.
[Kaiser, David A.] Wavestate Inc, Marina Del Rey, CA USA.
RP Tan, G (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 145, Houston, TX 77030 USA.
EM tan.gabriel@va.gov
NR 40
TC 63
Z9 64
U1 3
U2 14
PU EEG & CLINICAL NEUROSCIENCE SOC (E C N S)
PI WHEATON
PA 805 W LIBERTY DR, PO BOX 725, WHEATON, IL 60187 USA
SN 1550-0594
J9 CLIN EEG NEUROSCI
JI Clin. EEG Neurosci.
PD JUL
PY 2009
VL 40
IS 3
BP 173
EP 179
PG 7
WC Clinical Neurology; Neurosciences; Neuroimaging; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 477NV
UT WOS:000268526700006
PM 19715180
ER
PT J
AU Kanwal, F
Gralnek, IM
Hays, RD
Zeringue, A
Durazo, F
Han, SB
Saab, S
Bolus, R
Spiegel, BMR
AF Kanwal, Fasiha
Gralnek, Ian M.
Hays, Ron D.
Zeringue, Angelique
Durazo, Francisco
Han, Steven B.
Saab, Sammy
Bolus, Roger
Spiegel, Brennan M. R.
TI Health-Related Quality of Life Predicts Mortality in Patients With
Advanced Chronic Liver Disease
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
ID SERUM SODIUM; HEART-FAILURE; UNITED-STATES; SURVIVAL; TRANSPLANTATION;
MELD; CIRRHOSIS; CANCER; MODEL; POPULATION
AB BACKGROUND & AIMS: It is well-established that cirrhosis negatively impacts health-related quality of life (HRQOL). However, it is less clear how to use this information in everyday clinical practice. If HRQOL predicted survival in cirrhosis, then measuring HRQOL would have important clinical implications. We sought to measure the association between HRQOL and survival in patients with cirrhosis and investigated whether the relationship between HRQOL and Survival is independent of Model for End-Stage Liver Disease (MELD). METHODS: We measured HRQOL in 156 patients with cirrhosis awaiting liver transplantation by using the Short Form Liver Disease Quality of Life instrument. We followed patients prospectively and used Cox proportional hazard models to measure the independent effect of baseline HRQOL on survival, adjusting for MELD and other covariates. RESULTS: During a mean 9-month follow-up, 26 (17%) patients died, and 30 (20%) received liver transplants. In unadjusted analysis, higher baseline HRQOL predicted lower mortality (hazard ratio, 0.96; 95% confidence interval, 0.94-0.99). Specifically, for each 1-point increase in HRQOL, there was a 4% decrease in mortality. These results did not change after adjusting for MELD scores, patient demographics, or psychosocial characteristics; the MELD score accounted for 1% of the variation in HRQOL scores (P=.18). Survival was most strongly predicted by activities of daily living, health distress, sleep disturbance, and perceived disease stigma. CONCLUSIONS: Higher HRQOL predicts lower mortality in patients with cirrhosis. This relationship is independent of MELD; MELD does not capture liver-specific HRQOL. Beyond its use as a secondary outcome in clinical trials, HRQOL could be used to predict survival of patients with advanced liver disease.
C1 [Kanwal, Fasiha; Zeringue, Angelique] John Cochran VA Med Ctr, St Louis, MO USA.
[Kanwal, Fasiha] St Louis Univ, Div Gastroenterol, St Louis, MO 63103 USA.
[Kanwal, Fasiha; Bolus, Roger; Spiegel, Brennan M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA.
[Gralnek, Ian M.] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel.
[Hays, Ron D.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA.
[Hays, Ron D.] RAND Corp, Santa Monica, CA USA.
[Durazo, Francisco; Han, Steven B.; Saab, Sammy; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA.
[Han, Steven B.; Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol & Hepatol, Los Angeles, CA USA.
RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA.
EM bspiegel@mednet.ucla.edu
RI Zeringue, Angelique/I-1755-2012; Hays, Ronald/D-5629-2013
FU NIA NIH HHS [P30AG021684-07]; NIDDK NIH HHS [2P30 DK 041301-17]
NR 33
TC 47
Z9 47
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD JUL
PY 2009
VL 7
IS 7
BP 793
EP 799
DI 10.1016/j.cgh.2009.03.013
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476HP
UT WOS:000268430500017
PM 19306949
ER
PT J
AU Ross, RW
Zietman, AL
Xie, WL
Coen, JJ
Dahl, DM
Shipley, WU
Kaufman, DS
Islam, T
Guimaraes, AR
Weissleder, R
Harisinghani, M
AF Ross, Robert W.
Zietman, Anthony L.
Xie, Wanling
Coen, John J.
Dahl, Douglas M.
Shipley, William U.
Kaufman, Donald S.
Islam, Tina
Guimaraes, Alexander R.
Weissleder, Ralph
Harisinghani, Mukesh
TI Lymphotropic nanoparticle-enhanced magnetic resonance imaging (LNMRI)
identifies occult lymph node metastases in prostate cancer patients
prior to salvage radiation therapy
SO CLINICAL IMAGING
LA English
DT Article
DE Nanoparticle MR imaging; Ferumoxtran-10; Lymph nodes; Metastases;
Salvage radiation therapy
ID RADICAL RETROPUBIC PROSTATECTOMY; SUPERPARAMAGNETIC IRON-OXIDE; PSA
FAILURE; RADIOTHERAPY; ANTIGEN
AB Twenty-six patients with prostate cancer status post-radical prostatectomy who were candidates for salvage radiation therapy (SRT) underwent lymphotropic nanoparticle enhanced MRI (LNMRI) using superparamagnetic nanoparticle ferumoxtran-10. LNMRI was well tolerated, with only two adverse events, both Grade 2. Six (23%) of the 26 patients, previously believed to be node negative, tested lymph node positive by LNMRI. A total of nine positive lymph nodes were identified in these six patients, none of which were enlarged based on size criteria. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Islam, Tina] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA.
[Zietman, Anthony L.; Coen, John J.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Dahl, Douglas M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Kaufman, Donald S.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA.
[Ross, Robert W.; Xie, Wanling] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Zietman, Anthony L.; Coen, John J.; Dahl, Douglas M.; Shipley, William U.; Kaufman, Donald S.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Islam, T (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, 55 Fruit St, Boston, MA 02114 USA.
EM islam.tina@mgh.harvard.edu
FU Bertucci Foundation and an American Society of Clinical Oncology Career
Development Award; AMAG Pharmaceuticals, Inc. (Cambridge, MA, USA)
FX Support provided by the Bertucci Foundation and an American Society of
Clinical Oncology Career Development Award ( to RWR). Imaging agent
provided by AMAG Pharmaceuticals, Inc. (Cambridge, MA, USA). No
conflicts of interest are reported.
NR 17
TC 53
Z9 54
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0899-7071
J9 CLIN IMAG
JI Clin. Imaging
PD JUL-AUG
PY 2009
VL 33
IS 4
BP 301
EP 305
DI 10.1016/j.clinimag.2009.01.013
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 533GL
UT WOS:000272811600008
PM 19559353
ER
PT J
AU Jones, KL
Seward, RJ
Ben-Menachem, G
Glickstein, LJ
Costello, CE
Steere, AC
AF Jones, Kathryn L.
Seward, Robert J.
Ben-Menachem, Gil
Glickstein, Lisa J.
Costello, Catherine E.
Steere, Allen C.
TI Strong IgG antibody responses to Borrelia burgdorferi glycolipids in
patients with Lyme arthritis, a late manifestation of the infection
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Lyme disease; Bacterial infection; Borrelia burgdorferi; Antibodies;
Glycolipid antigens
ID T-CELLS; CHOLESTERYL GALACTOSIDE; DISEASE; RECOMBINANT; ANTIGENS;
PEPTIDE; VACCINE
AB In this study, the membrane lipids of B. burgdorferi were separated into 16 fractions; the components in each fraction were identified, and the immunogenicity of each fraction was determined by ELISA using sera from Lyme disease patients. Only the 2 glycolipids, acylated cholesteryl galactoside (ACG, BbGL-I) and monogalactosyl diacylglycerol (MgaID, BbGL-II), were immunogenic. Early in the infection, 24 of 84 patients (29%) who were convalescent from erythema migrans and 19 of the 35 patients (54%) with neuroborreliosis had weak IgG responses to purified MgaID, and a smaller percentage of patients had early responses to synthetic ACG. However, almost all of 75 patients with Lyme arthritis, a late disease manifestation, had strong IgG reactivity with both glycolipids. Thus, almost all patients with Lyme arthritis have strong IgG antibody responses to B. burgdorferi glycolipid antigens. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Jones, Kathryn L.; Seward, Robert J.; Glickstein, Lisa J.; Steere, Allen C.] Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Med Sch, Boston, MA 02114 USA.
[Ben-Menachem, Gil] NICHHD, NIH, Bethesda, MD 20892 USA.
[Seward, Robert J.; Costello, Catherine E.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
RP Steere, AC (reprint author), Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Med Sch, 55 Fruit St,Charlestown Navy Yard 149-8301, Boston, MA 02114 USA.
EM asteere@partners.org
OI Costello, Catherine/0000-0003-1594-5122; Jones,
Kathryn/0000-0003-3815-5713
FU National Institutes of Health [RO1 AR-20358, P41 RR10888, S10 RR 15942,
AR-007258]; English, Bonter, Mitchell Foundation; Eshe Fund;
Lyme/Arthritis Research Fund at Massachusetts General Hospital; Walter
J. and Lille A. Berbecker Foundation
FX We thank Dr. Nitin Damle in Wakefield, Rhode Island, and Dr. Vijay
Sikand in East Lyme, Connecticut, for obtaining serum samples from
patients with erythema migrans, Mr. Vincent Poszgay for making the
synthetic preparation of ACG (BbGL-I), Dr. Rachel Schneerson for
providing the preparation for our study, Ms. Gail McHugh for help in the
processing and storage of serum samples, Ms. Colleen Squires for
assistance with the preparation of this manuscript, and Dr. Shiv Pillai
for helpful discussions. This work was supported by funding from the
National Institutes of Health (RO1 AR-20358 to ACS and P41 RR10888 and
S10 RR 15942 to CEC), the English, Bonter, Mitchell Foundation, the Eshe
Fund, and the Lyme/Arthritis Research Fund at Massachusetts General
Hospital. K.L.J. received support from a scholarship from the Walter J.
and Lille A. Berbecker Foundation for the study of Lyme disease, and
from the National Institutes of Health training grant AR-007258.
NR 29
TC 11
Z9 12
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD JUL
PY 2009
VL 132
IS 1
BP 93
EP 102
DI 10.1016/j.clim.2009.03.510
PG 10
WC Immunology
SC Immunology
GA 457SY
UT WOS:000266954900010
PM 19342303
ER
PT J
AU Palevsky, PM
AF Palevsky, Paul M.
TI Defining Contrast-Induced Nephropathy
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID RADIOCONTRAST-INDUCED NEPHROPATHY; ACUTE-RENAL-FAILURE; RANDOMIZED
CONTROLLED-TRIAL; HIGH-RISK PATIENTS; SODIUM-BICARBONATE;
CORONARY-ANGIOGRAPHY; PREVENTION; MEDIA; METAANALYSIS; NEPHROTOXICITY
C1 [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Sect, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA.
[Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15240 USA.
RP Palevsky, PM (reprint author), Univ Pittsburgh, Sch Med, Renal Sect, VA Pittsburgh Healthcare Syst, Room 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA.
EM palevsky@pitt.edu
OI Palevsky, Paul/0000-0002-7334-5400
NR 29
TC 7
Z9 7
U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD JUL
PY 2009
VL 4
IS 7
BP 1151
EP 1153
DI 10.2215/CJN.03410509
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 466WC
UT WOS:000267693400001
PM 19541810
ER
PT J
AU Hinson, VK
Goetz, CG
Leurgans, S
Fan, W
Nguyen, T
Hsu, A
AF Hinson, Vanessa K.
Goetz, Christopher G.
Leurgans, Sue
Fan, Wenqing
Nguyen, Tiffany
Hsu, Ann
TI Reducing Dosing Frequency of Carbidopa/Levodopa: Double-Blind Crossover
Study Comparing Twice-Daily Bilayer Formulation of Carbidopa/Levodopa
(IPX054) Versus 4 Daily Doses of Standard Carbidopa/Levodopa in Stable
Parkinson Disease Patients
SO CLINICAL NEUROPHARMACOLOGY
LA English
DT Review
DE Parkinson disease; levodopa; randomized clinical trials
ID CAPTURE
AB Objective: We compared IPX054, a bilayer tablet of immediate- and extended-release carbidop-/levodopa (CD/LD) given twice daily to standard CD/LD given 4 times daily in patients with stable Parkinson disease (PD).
Methods: Twelve PD patients with no or mild fluctuations oil CD/LD 25/100 mg 4 times daily were randomized to a double-blind crossover comparison with IPX054 (50/200 mg) twice daily. At the end of each 2-week treatment, patients were video recorded while performing a modified Unified Parkinson's Disease Rating Scale motor examination and Rush Dyskinesia Rating Scale at 30-minute intervals over 8.5 hours. The primary Outcome measure was the number of videotape epochs rated as "ON" without troublesome dyskinesia by a blinded observer (Wilcoxon signed rank tests).
Results: The 9 men and 3 women had a mean age of 69 years and mean PD duration of 6 years. IPX054 and CD/LD showed no significant differences in the primary outcome measure (mean number of video epochs rated as ON without troublesome dyskinesia; P = 0.14). The mean time to ON was improved with IPX054 (P = 0.014), and the mean modified Unified Parkinson's Disease Rating Scale scores slightly favored IPX054 (14.4 vs 16.9; P = 0.052.). Mean Rush Dyskinesia Rating Scale scores were not significantly different between IPX054 and CD/LD (0.45 vs 0.69; P = 0.25). No patient developed troublesome dyskinesias.
Conclusions: in stable PD patients, no difference was detected between twice-daily treatment with IPX054 and CD/LD given 4 times daily In this group, substitution with IPX054 reduced closing frequency while maintaining CD/LD efficacy. In clinical practice, this case of administration may offer improved treatment compliance.
C1 [Hinson, Vanessa K.] Med Univ S Carolina, Movement Disorders Program, Dept Neurosci, Charleston, SC 29425 USA.
[Hinson, Vanessa K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Goetz, Christopher G.; Leurgans, Sue; Fan, Wenqing] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Nguyen, Tiffany; Hsu, Ann] IMPAX Labs Inc, Hayward, CA USA.
RP Hinson, VK (reprint author), Med Univ S Carolina, Movement Disorders Program, Dept Neurosci, 326 Calhoun St,Suite 308, Charleston, SC 29425 USA.
EM hinsonvk@musc.edu
NR 14
TC 3
Z9 5
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-5664
J9 CLIN NEUROPHARMACOL
JI Clin. Neuropharmacol.
PD JUL-AUG
PY 2009
VL 32
IS 4
BP 189
EP 192
DI 10.1097/WNF.0b013e3181a27fae
PG 4
WC Clinical Neurology; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 481VX
UT WOS:000268841600003
PM 19620848
ER
PT J
AU Huddleston, JI
Scarborough, DM
Goldvasser, D
Freiberg, AA
Malchau, H
AF Huddleston, James I.
Scarborough, Donna Moxley
Goldvasser, Dov
Freiberg, Andrew A.
Malchau, Henrik
TI How Often Do Patients with High-Flex Total Knee Arthroplasty Use High
Flexion?
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID IN-VIVO DETERMINATION; FOLLOW-UP; FUNCTIONAL-ACTIVITIES; FLUOROSCOPIC
ANALYSIS; ENERGY-EXPENDITURE; OPTIMIZING FLEXION; CRUCIATE LIGAMENT;
PHYSICAL-ACTIVITY; TOTAL CONDYLAR; DEEP FLEXION
AB Although high-flexion TKA designs aim to safely accommodate deep flexion, it is unknown how often patients use deep flexion outside the laboratory. We used a validated smart-activity monitor to document the prevalence of knee flexion greater than 90 degrees in 20 consecutive patients (21 knees) who had high-flexion TKAs, at a minimum of 2 years' followup. Patients wore the device continuously for a mean of 35.7 +/- 0.5 hours. The 21 knees flexed more than 90 for an average of 10 +/- 3.8 minutes (0.5%). Activities performed with flexion greater than 90 degrees were, on average, 70% in single-limb stance, 12% moving from sitting to standing, 8% walking, 7% moving from standing to reclining, 2% stepping, 0.9% moving from lying to standing, and 0.1% running. Eight knees flexed greater than 120 for an average of 2.2 minutes (range, 0.2-15 minutes), or 0.1% of the testing time. Activities performed with flexion greater than 120 degrees were, on average, 90% in single-limb stance, 6% moving from sitting to standing, 3% walking, 0.6% moving from standing to reclining, 0.3% stepping, and 0.1% moving from lying to standing. Peak flexion used at any time during testing was, on average, 84% +/- 11% of maximum postoperative flexion (125 degrees +/- 12 degrees). These patients rarely used deep flexion.
C1 [Huddleston, James I.] Stanford Univ, Med Ctr, Dept Orthopaed Surg, Stanford, CA 94305 USA.
[Scarborough, Donna Moxley; Goldvasser, Dov; Freiberg, Andrew A.; Malchau, Henrik] Harvard Med Sch, Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA USA.
RP Huddleston, JI (reprint author), Stanford Univ, Med Ctr, Dept Orthopaed Surg, 300 Pasteur Dr,R 149, Stanford, CA 94305 USA.
EM jhuddleston@stanford.edu
FU Harris Orthopaedic Biomechanics and Biomaterials Laboratory; Stanford
University Medical Center
FX This work was performed at the Harris Orthopaedic Biomechanics and
Biomaterials Laboratory and Stanford University Medical Center.
NR 65
TC 15
Z9 20
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD JUL
PY 2009
VL 467
IS 7
BP 1898
EP 1906
DI 10.1007/s11999-009-0874-y
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 453ZS
UT WOS:000266652000041
PM 19421828
ER
PT J
AU Lin, HW
O'Neill, A
Cunningham, MJ
AF Lin, Harrison W.
O'Neill, Allison
Cunningham, Michael J.
TI Ludwig's Angina in the Pediatric Population
SO CLINICAL PEDIATRICS
LA English
DT Editorial Material
DE Ludwig's angina; abscess; submental; submandibular; pediatric
ID COMPLICATION; NECK
AB As many as 1 in 3 of cases of Ludwig's angina Occur in children and adolescents, and pediatricians are therefore ideally Situated to detect these individuals at an early stage of their potentially life-threatening disease. The early identification and referral of children afflicted with Ludwig's angina to tertiary care centers allows for the rapid initiation of medical therapy and the consultation of those emergency services critical to providing such patients with optimal diagnostic and therapeutic interventions. This review provides an overview of the anatomical and pathophysiological considerations in Ludwig's angina and describes practical management principles to assist pediatricians in the diagnosis and treatment of this disease. Included in this review is an evidence-based algorithm for airway management.
C1 [Lin, Harrison W.; Cunningham, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
[Lin, Harrison W.; Cunningham, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[O'Neill, Allison] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM harrison_lin@meei.harvard.edu
NR 22
TC 4
Z9 4
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD JUL
PY 2009
VL 48
IS 6
BP 583
EP 587
DI 10.1177/0009922809333095
PG 5
WC Pediatrics
SC Pediatrics
GA 456MP
UT WOS:000266851100001
PM 19286617
ER
PT J
AU Oreskovic, NM
Sawicki, GS
Kinane, TB
Winickoff, JP
Perrin, JM
AF Oreskovic, Nicolas M.
Sawicki, Gregory S.
Kinane, T. Bernard
Winickoff, Jonathan P.
Perrin, James M.
TI Travel Patterns to School Among Children With Asthma
SO CLINICAL PEDIATRICS
LA English
DT Article
DE asthma; active commuting; physical activity; school; environment
ID PHYSICAL-ACTIVITY; POLLUTANT EXPOSURE; CHILDHOOD; IMPACT; PREVALENCE;
EXERCISE; WALKING; HEALTH
AB Background. Active commuting to school provides regular exercise, which can improve asthma symptoms. Little is known about how children with asthma travel to school. Objective. To identify travel patterns and parental perceptions surrounding mode of travel to school among children with asthma. Methods. Cross-sectional study of 176 children with asthma aged 5 to 15 years. Parents completed questionnaires assessing mode of travel to school, physical activity, asthma control, physician counseling, and factors influencing parental decisions. Data analysis included descriptive and bivariate statistics. Results. Few (16%) children with asthma actively commute to school. Active travelers lived closer to school, and "distance" was the most frequently reported factor influencing a parent's decision regarding travel mode to school. Parents reported few concerns about pollution and little physician counseling on active travel. Conclusion. Few children with asthma actively travel to school. Asthma-specific concerns do not appear to guide parental decisions on travel mode to school.
C1 [Oreskovic, Nicolas M.; Kinane, T. Bernard; Winickoff, Jonathan P.; Perrin, James M.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Pediat, Boston, MA 02114 USA.
[Sawicki, Gregory S.] Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Dept Pediat, 50 Staniford St,Suite 901, Boston, MA 02114 USA.
EM noreskovic@partners.org
OI Oreskovic, Nicolas/0000-0001-8702-8636
FU Deborah Munroe Noonan Memorial Fund
FX The authors wish to thank Gabriel Malseptic and Nathan Demars for their
excellent research assistance. This study was funded by the Deborah
Munroe Noonan Memorial Fund. The Deborah Munroe Noonan Memorial Fund
played no role in acquiring or analyzing the data, or in preparing the
manuscript. Dr. Oreskcovic had full access to the data in the study and
takes responsibility for the integrity of the data and the accuracy of
the data analysis.
NR 25
TC 5
Z9 5
U1 2
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD JUL
PY 2009
VL 48
IS 6
BP 632
EP 640
DI 10.1177/0009922809335323
PG 9
WC Pediatrics
SC Pediatrics
GA 456MP
UT WOS:000266851100008
PM 19420183
ER
PT J
AU Sawaya, HHB
de Souza, RBC
Carrasco, S
Goldenstein-Schainberg, C
AF Braga Sawaya, Heloisa Helena
Christmann de Souza, Romy Beatriz
Carrasco, Solange
Goldenstein-Schainberg, Claudia
TI Altered adhesion molecules expression on peripheral blood mononuclear
cells from patients with systemic sclerosis and clinical correlations
SO CLINICAL RHEUMATOLOGY
LA English
DT Article
DE Adhesion molecules; ICAM-1; ICAM-3; Pathogenesis; Scleroderma; Systemic
sclerosis
ID L-SELECTIN; LOCALIZED SCLERODERMA; INVOLVEMENT; LYMPHOCYTES; RECEPTOR;
SERA; SKIN
AB The aim of the study was to evaluate the expressions of adhesion molecules (AM) on peripheral blood mononuclear cells (PBMNC) from systemic sclerosis (SSc) patients. Thirty-one SSc patients (ACR) and 20 normal subjects were selected for the study. PBMNC were analyzed for LFA-1 alpha, LFA-1 beta, ICAM-3, ICAM-1, and l-selectin expressions. ICAM-3 expression was decreased while ICAM-1 was increased on SSc PBMNC, compared to controls (p = 0.04 and 0.003, respectively). A positive association was found between LFA-1 alpha (r = 0.37, p = 0.03), LFA-1 beta (r = 0.38, p = 0.002), ICAM-3 (r = 0.42, p = 0.01), and l-selectin (r = 0.38, p = 0.03) expressions and greater number of immunosuppressive drugs taken by SSc patients. Also, anti-centromeric positive SSc patients had lower expressions of LFA-1 alpha, LFA-1 beta, ICAM-3, and l-selectin. Lower expression of ICAM-3 and higher expression of ICAM-1 suggest that AMs may be involved in the pathogenesis of scleroderma.
C1 [Christmann de Souza, Romy Beatriz; Goldenstein-Schainberg, Claudia] Univ Sao Paulo, Div Rheumatol, BR-01246000 Sao Paulo, Brazil.
[Braga Sawaya, Heloisa Helena] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
RP de Souza, RBC (reprint author), Univ Sao Paulo, Div Rheumatol, Av Dr Arnaldo,455-3 Andar Reumatol,Sala 3107, BR-01246000 Sao Paulo, Brazil.
EM romy.souza@gmail.com
RI Carrasco, Solange/G-5144-2012
NR 26
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0770-3198
J9 CLIN RHEUMATOL
JI Clin. Rheumatol.
PD JUL
PY 2009
VL 28
IS 7
BP 847
EP 851
DI 10.1007/s10067-009-1124-0
PG 5
WC Rheumatology
SC Rheumatology
GA 451CI
UT WOS:000266447900013
PM 19225705
ER
PT J
AU Nierenberg, AA
AF Nierenberg, Andrew A.
TI Distress: To Treat or Not to Treat?
SO CNS SPECTRUMS
LA English
DT Editorial Material
ID BORDERLINE PERSONALITY-DISORDER; THERAPY; MODEL
C1 [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Boston, MA 02163 USA.
[Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA.
[Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA.
[Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA.
NR 12
TC 1
Z9 1
U1 0
U2 0
PU M B L COMMUNICATIONS, INC
PI NEW YORK
PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA
SN 1092-8529
J9 CNS SPECTRUMS
JI CNS Spectr.
PD JUL
PY 2009
VL 14
IS 7
BP 344
EP 345
PG 2
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 483JB
UT WOS:000268959100001
PM 19773708
ER
PT J
AU Stedman, MR
Gagnon, DR
Lew, RA
Solomon, DH
Losina, E
Brookhart, MA
AF Stedman, Margaret R.
Gagnon, David R.
Lew, Robert A.
Solomon, Daniel H.
Losina, Elena
Brookhart, M. Alan
TI A SAS macro for a clustered permutation test
SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
LA English
DT Article
DE Permutation test; Cluster randomized trial; Clustered permutation test;
SAS macro
ID COMMUNITY INTERVENTION TRIALS; DESIGN
AB The clustered per-mutation test is a nonparametric method of significance testing for correlated data. It is often used in cluster randomized trials where groups of patients rather than individuals are randomized to either a treatment or control intervention. We describe a flexible and efficient SAS macro that implements the 2-sample clustered permutation test. We discuss the theory and applications behind this test as well as details of the SAS code. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Stedman, Margaret R.; Solomon, Daniel H.; Brookhart, M. Alan] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA.
[Stedman, Margaret R.; Gagnon, David R.; Lew, Robert A.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Gagnon, David R.; Lew, Robert A.] Boston VA Healthcare Syst, VA Cooperat Studies, MAVERIC, Boston, MA USA.
[Solomon, Daniel H.; Brookhart, M. Alan] Harvard Univ, Sch Med, Boston, MA USA.
[Solomon, Daniel H.; Losina, Elena] Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA.
RP Stedman, MR (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
EM mstedman2@partners.org
OI Gagnon, David/0000-0002-6367-3179; Stedman, Margaret/0000-0001-9271-8332
FU National Institutes of Health [AG-027400]
FX This work was supported by a grant from the National Institutes of
Health (AG-027400) awarded to M. Alan Brookhart.
NR 11
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-2607
J9 COMPUT METH PROG BIO
JI Comput. Meth. Programs Biomed.
PD JUL
PY 2009
VL 95
IS 1
BP 89
EP 94
DI 10.1016/j.cmpb.2009.02.005
PG 6
WC Computer Science, Interdisciplinary Applications; Computer Science,
Theory & Methods; Engineering, Biomedical; Medical Informatics
SC Computer Science; Engineering; Medical Informatics
GA 447JR
UT WOS:000266187900008
PM 19321221
ER
PT J
AU Jurkunas, U
Behlau, I
Colby, K
AF Jurkunas, Ula
Behlau, Irmgard
Colby, Kathryn
TI Fungal Keratitis: Changing Pathogens and Risk Factors
SO CORNEA
LA English
DT Article; Proceedings Paper
CT 110th Annual Meeting of the American-Academy-of-Ophthalmology
CY NOV 11-14, 2006
CL Las Vegas, NV
SP Amer Acad Ophthalmol
DE fungal keratitis; filamentous fungi; contact lens wear; voriconazole;
corneal transplantation; keratoprosthesis; therapeutic keratoplasty;
Fusarium; Candida
ID CONTACT-LENS WEAR; FUSARIUM KERATITIS; TRIAZOLE ANTIFUNGAL;
VORICONAZOLE; OUTBREAK; SPECTRUM
AB Purpose: To describe changes in demographics and pathogens for fungal keratitis cases diagnosed at the Massachusetts Eye and Ear Infirmary.
Methods: Patient demographics, clinical and laboratory findings, treatment and outcomes of 46 cases of culture-proven fungal keratitis diagnosed from January 2004 through November 2007 were compared with 23 cases of fungal keratitis previously collected over a similar period from January 1999 through November 2002.
Results: During 2004-2007, the rate of fungal keratitis was 1.0 cases per month, an increase from the baseline rate of 0.5 cases per month during 1999-2002. The proportion of cases caused by filamentous fungi increased from 30% (1999-2002) to 65% (2004-2007) (P=0.01). Soft contact lens wear accounted for 41% of fungal keratitis cases in 2004-2007, as compared with 17% in 1999-2002. The majority of patients (70%) received oral antifungal treatment in addition to topical amphotericin B and natamycin. Seventeen patients (40%) required therapeutic keratoplasty. Patients with a history of conical transplant had the highest rate of therapeutic keratoplasties (67%) and had the poorest visual outcome (40% counting fingers or less). In the contact lens group, 94% of patients maintained vision of at least 20/40 and only 12% required surgery to control the infection.
Conclusions: There has been an increase in fungal keratitis in the Boston area and a change in the causative pathogens and risk factors for infection. Filamentous fungi now account for the majority of fungal keratitis cases, whereas yeasts were the predominant pathogen in the past. Soft contact lens wear is currently the most common risk factor for development of fungal keratitis.
C1 [Jurkunas, Ula; Behlau, Irmgard; Colby, Kathryn] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Jurkunas, Ula; Behlau, Irmgard; Colby, Kathryn] Schepens Eye Res Inst, Boston, MA USA.
[Jurkunas, Ula; Colby, Kathryn] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Behlau, Irmgard] Harvard Univ, Sch Med, Dept Internal Med, Boston, MA USA.
[Behlau, Irmgard] Mt Auburn Hosp, Div Infect Dis, Cambridge, MA USA.
RP Colby, K (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,Suite 727, Boston, MA 02114 USA.
EM kacolby@meei.harvard.edu
NR 19
TC 41
Z9 46
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0277-3740
EI 1536-4798
J9 CORNEA
JI Cornea
PD JUL
PY 2009
VL 28
IS 6
BP 638
EP 643
PG 6
WC Ophthalmology
SC Ophthalmology
GA 463EP
UT WOS:000267412500005
PM 19512908
ER
PT J
AU Kahn, JM
Asch, RJ
Iwashyna, TJ
Haynes, K
Rubenfeld, GD
Angus, DC
Asch, DA
AF Kahn, Jeremy M.
Asch, Rebecca J.
Iwashyna, Theodore J.
Haynes, Kevin
Rubenfeld, Gordon D.
Angus, Derek C.
Asch, David A.
TI Physician attitudes toward regionalization of adult critical care: A
national survey
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE patient transfer; triage; intensive care; mechanical ventilation;
healthcare systems
ID LUNG-PROTECTIVE VENTILATION; PEDIATRIC INTENSIVE-CARE; UNITED-STATES;
HOSPITAL MORTALITY; FAMILY-MEMBERS; RESPONSE RATES; VOLUME; BARRIERS;
ORGANIZATION; OUTCOMES
AB Objective: Regionalization has been proposed as a method to improve outcomes for patients with critical illness. We sought to determine intensivist physician attitudes and potential barriers to the regionalization of adult critical care.
Design: Mail survey.
Setting. United States.
Subjects: Actively practicing physicians specializing in adult critical care, emergency medicine, or internal medicine listed in the 2008 American Medical Association Physician Masterfile (n = 1200).
Interventions: None.
Measurements and Main Results: There were 569 eligible respondents (effective response rate = 53.0%). Respondents were similar to nonrespondents. Fifty-nine percent of respondents thought their hospital would mainly receive patients under a regionalized system, and 30% thought their hospital would mainly send patients. Opinions were split about whether regionalization would improve overall patient survival (52% agreed) and healthcare efficiency (66% agreed). Specialists in anesthesiology and surgery-critical care, academic physicians, and physicians who perceived that they would mainly receive patients were more likely to believe that regionalization would improve outcomes and efficiency (p < 0.001). The most commonly endorsed barriers to regionalization were personal strain on patient's families (66% agreed), current lack of a strong central authority (64% agreed), and the potential to overwhelm capacity at large hospitals (55% agreed). Commonly endorsed strategies to implement regionalization included using objective criteria to determine eligibility for transfer (87% agreed), developing common information technology platforms across hospitals (86% agreed), and demonstrating in a clinical trial that regionalization is beneficial (81% agreed).
Conclusions: Intensivist physicians have mixed opinions about regionalization, with little consensus about whether regionalization will improve outcomes. Most felt that regionalization will improve patient outcomes, but many expressed concerns about unintended adverse consequences. Respondents identified several barriers and potential implementation strategies that can help policymakers design a regionalized system of critical care in the United States. (Crit Care Med 2009; 37:2149-2154)
C1 [Kahn, Jeremy M.; Asch, Rebecca J.] Univ Penn, Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA.
[Kahn, Jeremy M.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Kahn, Jeremy M.; Haynes, Kevin] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Iwashyna, Theodore J.] Univ Michigan, Div Pulm & Crit Care, Ann Arbor, MI 48109 USA.
[Rubenfeld, Gordon D.] Sunnybrook Hlth Sci Ctr, Program Trauma Crit Care & Emergency Med, Toronto, ON M4N 3M5, Canada.
[Angus, Derek C.] Univ Penn, Lab Clin Res Invest & Syst Modeling Acute Illness, Dept Crit Care Med, Philadelphia, PA 19104 USA.
[Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ & Res & Promot, Philadelphia, PA USA.
RP Kahn, JM (reprint author), Univ Penn, Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA.
EM jmkahn@mail.med.upenn.edu
RI Angus, Derek/E-9671-2012;
OI Asch, David/0000-0002-7970-286X; Iwashyna, Theodore/0000-0002-4226-9310
FU Society of Critical Care Medicine; National Institutes of Health
[K23HL082650]
FX This work was funded by a research grant from the Society of Critical
Care Medicine. Dr. Kahn is supported by a career development award from
the National Institutes of Health (K23HL082650).
NR 32
TC 33
Z9 34
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUL
PY 2009
VL 37
IS 7
BP 2149
EP 2154
DI 10.1097/CCM.0b013e3181a009d0
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA 461DQ
UT WOS:000267245200001
PM 19455025
ER
PT J
AU Bellani, G
Messa, C
Guerra, L
Spagnolli, E
Foti, G
Patroniti, N
Fumagalli, R
Musch, G
Fazio, F
Pesenti, A
AF Bellani, Giacomo
Messa, Cristina
Guerra, Luca
Spagnolli, Ester
Foti, Giuseppe
Patroniti, Nicolo
Fumagalli, Roberto
Musch, Guido
Fazio, Ferruccio
Pesenti, Antonio
TI Lungs of patients with acute respiratory distress syndrome show diffuse
inflammation in normally aerated regions: A
[18F]-fluoro-2-deoxy-D-glucose PET/CT study
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE artificial respiration; adult respiratory distress syndrome;
positron-emission tomography; mechanical ventilators; x-ray computed
tomography
ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; METABOLIC-ACTIVITY;
GLUCOSE-UPTAKE; NEUTROPHIL SEQUESTRATION; VASCULAR-PERMEABILITY;
SKELETAL-MUSCLE; FDG-PET; INJURY; VENTILATION
AB Objective: Neutrophilic inflammation plays a key role in the pathogenesis of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Positron emission tomography (PET) with [(18)F]-fluoro-2-deoxy-D-glucose ((18)FDG) can be used to image cellular metabolism that, during lung inflammatory processes, likely reflects neutrophils activity. The aim of this study was to assess the magnitude and regional distribution of inflammatory metabolic activity in the lungs of patients with ALI/ARDS by PET with (18)FDG.
Design: Prospective clinical investigation.
Patients. Ten patients with ALI/ARDS; four spontaneously breathing and two mechanically ventilated subjects, without known lung disease, served as controls.
Interventions. In each individual we performed an (18)FDG PET/computed tomography of the thorax.
Measurements and Main Results. (18)FDG cellular influx rate constant (K(i)) was computed for the imaged lung field and for regions of interest, grouping voxels with similar density. In all patients with ALI/ARDS, K(i) was higher than in controls, also after accounting for the increased lung density. K(i) values differed greatly among patients, but in all patients K(i) of the normally aerated regions was much higher (2- to 24-fold) than in controls. Whereas in some patients the highest K(i) values corresponded to regions with the lowest aeration, in others these regions had lower K(i) than normally and mildly hypoaerated regions.
Conclusion: In patents with ALI/ARDS, undergoing mechanical ventilation since days, the metabolic activity of the lungs is markedly increased across the entire lung density spectrum. The intensity of this activation and its regional distribution, however, vary widely within and between patents. (Crit Care Med 2009; 37:2216-2222)
C1 [Bellani, Giacomo; Spagnolli, Ester; Fumagalli, Roberto; Pesenti, Antonio] Univ Milano Bicocca, Dept Expt Med, Monza, MI, Italy.
[Messa, Cristina; Fazio, Ferruccio] Univ Milano Bicocca, Ctr Bioimmagini Mol, Monza, MI, Italy.
[Bellani, Giacomo; Spagnolli, Ester; Foti, Giuseppe; Patroniti, Nicolo; Fumagalli, Roberto; Pesenti, Antonio] San Gerardo Hosp, Dept Perioperat Med & Intens Care, Monza, MI, Italy.
[Guerra, Luca] San Gerardo Hosp, Nucl Med Unit, Monza, MI, Italy.
[Messa, Cristina; Fazio, Ferruccio] CNR, Inst Mol Bioimaging & Physiol, Milan, Italy.
[Musch, Guido] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA USA.
RP Messa, C (reprint author), Univ Milano Bicocca, Dept Expt Med, Monza, MI, Italy.
EM antonio.pesenti@unimib.it
RI Bellani, Giacomo/D-2379-2010; Pesenti, Antonio/H-7483-2012; Foti,
Giuseppe/K-8627-2016; Patroniti, Nicolo/K-6347-2016;
OI Bellani, Giacomo/0000-0002-3089-205X; Patroniti,
Nicolo/0000-0003-3600-193X; foti, giuseppe/0000-0002-8698-2046
FU European Society of Intensive Care Medicine; Italian Ministry of
Education, University and Research
FX Supported, in part, by a grant from the European Society of Intensive
Care Medicine (ECCRN Young Investigator Award 2006) and by a national
grant of the Italian Ministry of Education, University and Research
(FIRB 2001 and Fondo di Internazionalizzazione 2005).
NR 49
TC 63
Z9 64
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUL
PY 2009
VL 37
IS 7
BP 2216
EP 2222
DI 10.1097/CCM.0b013e3181aab31f
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA 461DQ
UT WOS:000267245200012
PM 19487931
ER
PT J
AU Fukudome, EY
Alam, HB
AF Fukudome, Eugene Y.
Alam, Hasan B.
TI Hypothermia in multisystem trauma
SO CRITICAL CARE MEDICINE
LA English
DT Review
DE trauma; hemorrhagic shock; lethal injury; exsanguination; cardiac
arrest; resuscitation; therapeutic hypothermia; emergency preservation
for resuscitation; suspended animation
ID UNCONTROLLED HEMORRHAGIC-SHOCK; EXSANGUINATION CARDIAC-ARREST;
EMERGENCY-DEPARTMENT THORACOTOMY; SPINAL-CORD-INJURY; MILD PERIOPERATIVE
HYPOTHERMIA; CONVENTIONAL RINGERS SOLUTION; SECONDARY BRAIN-INJURY;
PROLONGS SURVIVAL-TIME; PROFOUND HYPOTHERMIA; SWINE MODEL
AB Exsanguinating hemorrhage is a common clinical feature of multisystem trauma that results in death or severe disability. Cardiovascular collapse resulting from hemorrhage is unresponsive to conventional methods of cardiopulmonary resuscitation. Even when bleeding is controlled rapidly, adequate circulation cannot be restored in time to avoid neurologic consequences that appear after only 5 mins of cerebral ischemia and hypoperfusion. Reperfusion adds further insult to injury. A novel solution to this problem would be to institute a therapy that makes cells and organs more resistant to ischemic injury, thereby extending the time they can tolerate such an insult. Hypothermia can attenuate some effects of ischemia and reperfusion. Accumulating preclinical data demonstrate that hypothermia can be induced safely and rapidly to achieve emergency preservation for resuscitation during lethal hemorrhage. Hypothermia may be an effective therapeutic approach for otherwise lethal traumatic hemorrhage, and a clinical trial to determine its utility is warranted. (Crit Care Med 2009; 37[Suppl.]:S265-S272)
C1 [Alam, Hasan B.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Alam, HB (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
EM hbalam@partners.org
NR 123
TC 20
Z9 24
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUL
PY 2009
VL 37
IS 7
BP S265
EP S272
DI 10.1097/CCM.0b013e3181aa60ac
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA 461DT
UT WOS:000267245500012
PM 19535957
ER
PT J
AU Rosendorff, C
Black, HR
AF Rosendorff, Clive
Black, Henry R.
TI Evidence for a lower target blood pressure for people with heart disease
SO CURRENT OPINION IN CARDIOLOGY
LA English
DT Review
DE blood pressure; cardiovascular risk; coronary artery disease;
hypertension
ID ISOLATED SYSTOLIC HYPERTENSION; RANDOMIZED CONTROLLED-TRIAL;
CARDIOVASCULAR OUTCOMES; ACTIVE TREATMENT; PREVENTION; ATHEROSCLEROSIS;
METAANALYSIS; HYPERTROPHY; MANAGEMENT; MORTALITY
AB Purpose of review
The review assesses the evidence for the benefit of lower blood pressure (BP) targets in hypertension management.
Recent findings
The current consensus target for the treatment of hypertension is a BP of below 140/90 mmHg for all patients, and a BP of below 130/80 mmHg for those with diabetes or chronic kidney disease. Recently added to the list of conditions warranting the lower BP target are coronary artery disease and coronary artery disease equivalents (stroke, carotid disease, aortic aneurysm, and peripheral vascular disease), as well as those individuals with a Framingham Risk Score of at least 10%. One theoretical issue with lower BP targets may be the existence of a J-shaped curve of BP versus cardiovascular event rate, implying a greater risk, especially of myocardial ischemia, of lowering diastolic BP, which is also the filling pressure of the coronary arteries, below the lower limit of coronary autoregulation. The evidence that this is not a compelling concern is provided by animal studies, clinical trials with both surrogate and hard endpoints, and epidemiologic data.
Summary
There is at present no proof that more aggressive treatment is harmful and much indirect evidence that it may be beneficial, although the clinical trials that specifically address this question are still in progress.
C1 [Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY 10468 USA.
[Rosendorff, Clive] Mt Sinai Sch Med, New York, NY USA.
[Black, Henry R.] NYU, Sch Med, New York, NY USA.
RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Med 111,130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM clive.rosendorff@va.gov
NR 24
TC 8
Z9 11
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0268-4705
J9 CURR OPIN CARDIOL
JI Curr. Opin. Cardiol.
PD JUL
PY 2009
VL 24
IS 4
BP 318
EP 324
DI 10.1097/HCO.0b013e32832bfb48
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 461PE
UT WOS:000267279500008
PM 19395951
ER
PT J
AU Comper, WD
Russo, LM
AF Comper, Wayne D.
Russo, Leileata M.
TI The glomerular filter: an imperfect barrier is required for perfect
renal function
SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
LA English
DT Review
DE albumin retrieval pathway; albuminuria; glomerular charge; proximal
tubular cell
ID DIABETIC-NEPHROPATHY; FILTRATION-RATE; FRACTIONAL CLEARANCE; ALBUMIN
ABSORPTION; BASEMENT-MEMBRANE; MOLECULAR-SIZE; KIDNEY; PROTEINURIA; RAT;
MECHANISMS
AB Purpose of review
There is currently a major debate on the mechanisms of albuminuria, and this review appraises recent studies in this area.
Recent findings
The traditional view of albuminuria is that it is the result of damage to an essentially impermeable glomerular barrier. However, over the years, critical evidence for this traditional model has been shown to be flawed. An alternative explanation has evolved in which the glomerular filter governs albumin permeability by size selectivity alone. This means that the filter offers a significant barrier to albumin, but it is imperfect - the barrier leaks albumin. The virtue of this leakage is that it endows the filter an in-built anticlogging mechanism. The filtered albumin, if not rescued, would be excreted at nephrotic levels in the urine. There is evidence that proximal tubular cells participate in retrieving most of this filtered albumin to return it back to the blood supply intact. A small amount of the filtered albumin is not retrieved but directed toward lysosomal degradation, and the peptide products are exocytosed into the tubular lumen and excreted.
Summary
In acquired and chemically induced kidney disease, albuminuria is the result of dysfunction in proximal tubular cell processing of albumin rather than alterations in glomerular permeability.
C1 [Comper, Wayne D.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
[Comper, Wayne D.] Exosome Diagnost Inc, New York, NY USA.
[Russo, Leileata M.] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
[Russo, Leileata M.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Russo, Leileata M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Comper, WD (reprint author), Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
EM wcomper@hotmail.com
NR 57
TC 29
Z9 30
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-4821
J9 CURR OPIN NEPHROL HY
JI Curr. Opin. Nephrol. Hypertens.
PD JUL
PY 2009
VL 18
IS 4
BP 336
EP 342
DI 10.1097/MNH.0b013e32832cb96a
PG 7
WC Urology & Nephrology; Peripheral Vascular Disease
SC Urology & Nephrology; Cardiovascular System & Cardiology
GA 464JL
UT WOS:000267501100012
PM 19474730
ER
PT J
AU Fuller, BE
Loftis, JM
Rodriguez, VL
McQuesten, MJ
Hauser, P
AF Fuller, Bret E.
Loftis, Jennifer M.
Rodriguez, Veronica L.
McQuesten, Matthew J.
Hauser, Peter
TI Psychiatric and substance use disorders comorbidities in veterans with
hepatitis C virus and HIV coinfection
SO CURRENT OPINION IN PSYCHIATRY
LA English
DT Article
DE coinfection; hepatitis C virus; HIV
ID UNITED-STATES VETERANS; SEVERE MENTAL-ILLNESS; INFECTION; CARE;
PREVALENCE; METHAMPHETAMINE; PERFORMANCE; DEPRESSION; DIAGNOSIS; THERAPY
AB Purpose of review
A growing number of veterans in the Veterans Health Administration are coinfected with HIV and hepatitis C virus. This review covers timely research relative to comorbid conditions that are common in this population including psychiatric diagnoses, substance use disorders and neurocognitive problems.
Recent findings
Current literature on the psychiatric, substance use disorders and cognitive problems of the coinfected population show that not only are rates of morbidity higher in the coinfected population but that this affects antiviral treatments as well. There is new evidence that brain injuries and infiltration of the virus into the central nervous system may be responsible for cognitive dysfunction. Cotesting, particularly in hepatitis C infected individuals, is not done routinely despite shared risk factors.
Summary
With this understanding of the comorbidities of the coinfected population, integrated healthcare models involving mental health, internal medicine, substance abuse treatment and internal medicine are crucial to work with these medically and psychologically complex patients.
C1 [Fuller, Bret E.; Hauser, Peter] Portland VA Med Ctr, Div Mental Hlth, Portland, OR 97210 USA.
[Fuller, Bret E.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
[Loftis, Jennifer M.] VA Med Ctr, Res Serv, Portland, OR USA.
[Loftis, Jennifer M.; Hauser, Peter] JENS Lab, Portland, OR USA.
[Hauser, Peter] Oregon Hlth & Sci Univ, Dept Internal Med, Dept Psychiat, Portland, OR 97201 USA.
RP Fuller, BE (reprint author), Portland VA Med Ctr, Div Mental Hlth, 3170 SW US Vet Pk Rd,Mailcode P3MHDC, Portland, OR 97210 USA.
EM bret.fuller@va.gov
NR 46
TC 9
Z9 9
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7367
J9 CURR OPIN PSYCHIATR
JI Curr. Opin. Psychiatr.
PD JUL
PY 2009
VL 22
IS 4
BP 401
EP 408
DI 10.1097/YCO.0b013e32832cadb9
PG 8
WC Psychiatry
SC Psychiatry
GA 460LT
UT WOS:000267189900012
PM 19436202
ER
PT J
AU Friedman, ES
Wisniewski, SR
Gilmer, W
Nierenberg, AA
Rush, AJ
Fava, M
Zisook, S
Balasubramani, GK
Trivedi, MH
AF Friedman, Edward S.
Wisniewski, Stephen R.
Gilmer, William
Nierenberg, Andrew A.
Rush, A. John
Fava, Maurizio
Zisook, Sidney
Balasubramani, G. K.
Trivedi, Madhukar H.
TI SOCIODEMOGRAPHIC, CLINICAL, AND TREATMENT CHARACTERISTICS ASSOCIATED
WITH WORSENED DEPRESSION DURING TREATMENT WITH CITALOPRAM: RESULTS OF
THE NIMH STAR*D TRIAL
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE citalopram; SSRI; antidepressant treatment; worsened depression;
intolerance
ID SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE;
POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; ILLNESS
RATING-SCALE; REPORT QIDS-SR; RELIEVE DEPRESSION; MAJOR DEPRESSION;
PSYCHOMETRIC EVALUATION; SERTRALINE TREATMENT
AB Context: Outcomes of antidepressant medication treatment for major depressive disorder include remission, response, and nonresponse. But nonresponse can include depression that worsened over the course of treatment, an outcome that has received scant attention. Objective: To describe baseline sociodemographic, clinical, and treatment characteristics associated with worsened depression during a trial of citalopram. Design, participants, and settings: Open-label clinical trial of 2,876 adult outpatients seen in 18 primary and 23 psychiatric-care settings. Intervention: Citalopram was delivered using measurement-based care and flexible dosing with the aim of achieving symptom remission. Symptom and side effect ratings were obtained at each treatment visit. Main outcome measures: Worsened depression was defined as an exit score ! 3 points above the pretreatment (baseline) score on the 16-item QIDS-SR. Baseline sociodemographic, clinical, and treatment characteristics were examined for association with worsened depression. Results: Of 2,864 outpatients who returned for >= 2 post baseline visits, 150 (5.2%) had worsened depression at study exit. Baseline characteristics independently associated with increased worsened depression included African-American race (OR = 2.02), having less than a college education (OR = 2.36), posttraumatic stress disorder (OR = 1.78), drug abuse (OR = 1.97), hypochondriasis (OR = 2.74). Participants with worsened depression spent less time in treatment; had fewer treatment visits; exited the study sooner; bad more frequent, intense, and burdensome adverse effects; and were more intolerant of medication. Conclusions: The presence of certain baseline characteristics indicated a greater likelibood of worsened depression during antidepressant treatment. Patients with these characteristics should be monitored closely during treatment and may be candidates for more aggressive treatment. Depression and Anxiety 26:612-621, 2009. Published 2009 Wiley-Liss, Inc.
C1 [Friedman, Edward S.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15213 USA.
[Gilmer, William] Northwestern Univ, Dept Psychiat, Chicago, IL 60611 USA.
[Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA.
[Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
[Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Zisook, Sidney] Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA.
[Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Div Mood Disorders, Dallas, TX 75390 USA.
RP Friedman, ES (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM friedmane@upmc.edu
OI Wisniewski, Stephen/0000-0002-3877-9860; Rush,
Augustus/0000-0003-2004-2382; Goundappa K,
Balasubramani/0000-0001-7221-1825
FU National Institute of Mental Health; National Institutes of Health
[N01MH90003]; NIMH [1UO1MH61562-01A2 MHT, R01MH064062-01A2 MHT]
FX Contract grant sponsors: National Institute of Mental Health; National
Institutes of Health; Contract grant number: N01MH90003; Contract grant
sponsors: NIMH; Contract grant number: 1UO1MH61562-01A2 MHT;
R01MH064062-01A2 MHT;
NR 44
TC 16
Z9 17
U1 1
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JUL
PY 2009
VL 26
IS 7
BP 612
EP 621
DI 10.1002/da.20568
PG 10
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 467KQ
UT WOS:000267738000004
PM 19382183
ER
PT J
AU Warden, D
Rush, AJ
Wisniewski, SR
Lesser, IM
Thase, ME
Balasubramani, GK
Shores-Wilson, K
Nierenberg, AA
Trivedi, MH
AF Warden, Diane
Rush, A. John
Wisniewski, Stephen R.
Lesser, Ira M.
Thase, Michael E.
Balasubramani, G. K.
Shores-Wilson, Kathy
Nierenberg, Andrew A.
Trivedi, Madhukar H.
TI INCOME AND ATTRITION IN THE TREATMENT OF DEPRESSION: A STAR*D REPORT
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE attrition; adherence; depression; antidepressant; predictors
ID SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE;
ILLNESS RATING-SCALE; REPORT QIDS-SR; SOCIOECONOMIC-STATUS; QUICK
INVENTORY; SOCIODEMOGRAPHIC PREDICTORS; ANTIDEPRESSANT TREATMENT;
PSYCHOMETRIC EVALUATION; MAJOR DEPRESSION
AB Background: Attrition, or dropping out of treatment, remains a major issue in the care of depressed outpatients. Whether different factors are associated with attrition for different socioeconomic groups is not known. This report assessed whether attrition rates and predictors of attrition differed among depressed outpatients with different income levels. Methods: Outpatients with non-psychotic major depressive disorder treated for up to 14 weeks with citalopram in the first step of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study were divided by household incomes of <$20,000, $20,000-<$40,000, and >=$40,000. Attrition rates and sociodemographic and clinical correlates of attrition were identified for each group. Results: Regardless of income level, remission rates were lower for participants who dropped out of treatment. Attrition rates increased as income decreased. For all income levels, younger age was independently associated with attrition. For the lowest income level, less education, better mental health functioning, being oil public insurance, and having more concurrent Axis I conditions were associated with a greater likelihood of attrition. For the middle income group, less education, better mental health functioning, being Black or of another non-White race, and treatment in a psychiatric versus primary-care setting predicted greater attrition. For the highest income group, being Hispanic, having a family history of drug abuse, and melancholic features predicted attrition. Atypical symptom features (middle income group) and recurrent depression (highest income group) were associated with retention. Conclusions: Efforts to retain patients in antidepressant treatment should focus especially on less educated patients with lower household incomes and younger patients. Depression and Anxiety 26:622-633, 2009. Publisbed 2009 Wiley-Liss, Inc.
C1 [Warden, Diane; Rush, A. John; Shores-Wilson, Kathy; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
[Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore.
[Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA.
[Lesser, Ira M.] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Dept Psychiat, Torrance, CA 90509 USA.
[Thase, Michael E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Nierenberg, Andrew A.] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA.
RP Warden, D (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
EM Diane.Warden@UTSouthwestern.edu
OI Wisniewski, Stephen/0000-0002-3877-9860; Rush,
Augustus/0000-0003-2004-2382; Goundappa K,
Balasubramani/0000-0001-7221-1825
FU National Institute of Mental Health, National Institutes of Health
[N01MH90003]; National Alliance for Research on Schizophrenia and
Depression
FX Contract/grant sponsor: National Institute of Mental Health, National
Institutes of Health, contract grant number: N01MH90003; National
Alliance for Research on Schizophrenia and Depression.
NR 58
TC 24
Z9 25
U1 3
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JUL
PY 2009
VL 26
IS 7
BP 622
EP 633
DI 10.1002/da.20541
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 467KQ
UT WOS:000267738000005
PM 19582825
ER
PT J
AU Asgari, MM
Bertenthal, D
Sen, S
Sahay, A
Chren, MM
AF Asgari, Maryam M.
Bertenthal, Daniel
Sen, Saunak
Sahay, Anju
Chren, Mary-Margaret
TI Patient Satisfaction After Treatment of Nonmelanoma Skin Cancer
SO DERMATOLOGIC SURGERY
LA English
DT Article
ID MOHS MICROGRAPHIC SURGERY; SQUAMOUS-CELL CARCINOMA; CARE; BASAL;
MORBIDITY; VETERANS
AB BACKGROUND Patient satisfaction is an important aspect of patient-centered care but has not been systematically studied after treatment of nonmelanoma skin cancer (NMSC), the most prevalent cancer.
OBJECTIVE To compare patient satisfaction after treatment for NMSC and to determine factors associated with better satisfaction.
METHODS We prospectively measured patient, tumor, and care characteristics in 834 consecutive patients at two centers before and after destruction, excision, and Mohs surgery. We evaluated factors associated with short-term and long-term satisfaction.
RESULTS In all treatment groups, patients were more satisfied with the interpersonal manners of the staff, communication, and financial aspects of their care than with the technical quality, time with the clinician, and accessibility of their care (p<.05). Short-term satisfaction did not differ across treatment groups. In multivariable regression models adjusting for patient, tumor, and care characteristics, higher long-term satisfaction was independently associated with younger age, better pretreatment mental health and skin-related quality of life, and treatment with Mohs surgery (p<.05).
CONCLUSIONS Long-term patient satisfaction after treatment of NMSC is related to pretreatment patient characteristics (mental health, skin-related quality of life) and treatment type (Mohs) but not tumor characteristics. These results can guide informed decision-making for treatment of NMSC.
C1 [Chren, Mary-Margaret] Univ Calif San Francisco, San Francisco VAMC, Dept Dermatol, San Francisco, CA 94121 USA.
[Asgari, Maryam M.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Bertenthal, Daniel; Sen, Saunak; Sahay, Anju; Chren, Mary-Margaret] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA.
[Sen, Saunak] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA.
RP Chren, MM (reprint author), Univ Calif San Francisco, San Francisco VAMC, Dept Dermatol, 4150 Clement St,151 R, San Francisco, CA 94121 USA.
EM chrenm@derm.ucsf.edu
RI Asgari, Maryam/O-4947-2016
FU NIAMS NIH HHS [K24 AR052667, K24 AR052667-01, K23 AR051037-03, K23
AR051037]
NR 27
TC 24
Z9 24
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1076-0512
J9 DERMATOL SURG
JI Dermatol. Surg.
PD JUL
PY 2009
VL 35
IS 7
BP 1041
EP 1049
DI 10.1111/j.1524-4725.2009.01181.x
PG 9
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 466JT
UT WOS:000267658700004
PM 19438672
ER
PT J
AU Seale, P
Lazar, MA
AF Seale, Patrick
Lazar, Mitchell A.
TI Brown Fat in Humans: Turning up the Heat on Obesity
SO DIABETES
LA English
DT Editorial Material
ID ADIPOSE-TISSUE; TRANSCRIPTIONAL CONTROL; ADULT HUMANS; THERMOGENESIS;
PRDM16; MUSCLE; MICE; MEN
C1 [Seale, Patrick] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Seale, Patrick] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Lazar, Mitchell A.] Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Lazar, Mitchell A.] Inst Diabet Obes & Metab, Philadelphia, PA USA.
RP Seale, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM patrick_seale@dfci.harvard.edu; lazar@mail.med.upenn.edu
FU NIDDK NIH HHS [DK-49210, DK-081605, DK-49780, K99 DK081605, P01
DK049210, R00 DK081605, R01 DK049780]
NR 17
TC 54
Z9 56
U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUL
PY 2009
VL 58
IS 7
BP 1482
EP 1484
DI 10.2337/db09-0622
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 466VF
UT WOS:000267690700004
PM 19564460
ER
PT J
AU Estall, JL
Kahn, M
Cooper, MP
Fisher, FM
Wu, MK
Laznik, D
Qu, LS
Cohen, DE
Shulman, GI
Spiegelman, BM
AF Estall, Jennifer L.
Kahn, Mario
Cooper, Marcus P.
Fisher, Ffolliott Martin
Wu, Michele K.
Laznik, Dina
Qu, Lishu
Cohen, David E.
Shulman, Gerald I.
Spiegelman, Bruce M.
TI Sensitivity of Lipid Metabolism and Insulin Signaling to Genetic
Alterations in Hepatic Peroxisome Proliferator-Activated Receptor-gamma
Coactivator-1 alpha Expression
SO DIABETES
LA English
DT Article
ID COA DEHYDROGENASE-DEFICIENCY; FATTY-ACID OXIDATION; ENERGY-METABOLISM;
NUCLEAR RECEPTORS; SKELETAL-MUSCLE; KNOCKOUT MICE; LIVER-DISEASE;
RESISTANCE; PGC-1-ALPHA; PGC-1
AB OBJECTIVE-The peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1 family of transcriptional coactivators controls hepatic function by modulating the expression of key metabolic enzymes. Hepatic gain of function and complete genetic ablation of PGC-1 alpha show that this coactivator is important for activating the programs of gluconeogenesis, fatty acid oxidation, oxidative phosphorylation, and lipid secretion during times of nutrient deprivation. However, how moderate changes in PGC-1 alpha activity affect metabolism and energy homeostasis has yet to be determined.
RESEARCH DESIGN AND METHODS-To identify key metabolic pathways that may be physiologically relevant in the context of reduced hepatic PGC-1 alpha levels, we used the Cre/Lox system to create mice heterozygous for PGC-1 alpha specifically within the liver (LH mice).
RESULTS-These mice showed fasting hepatic steatosis and diminished ketogenesis associated with decreased expression of genes involved in mitochondrial beta-oxidation. LH mice also exhibited high circulating levels of triglyceride that correlated with increased expression of genes involved in triglyceride-rich lipoprotein assembly. Concomitant with defects in lipid metabolism, hepatic insulin resistance was observed both in LH mice fed a high-fat diet as well as in primary hepatocytes.
CONCLUSIONS-These data highlight both the dose-dependent and long-term effects of reducing hepatic PGC-1 alpha levels, underlining the importance of tightly regulated PGC-1 alpha expression in the maintenance of lipid homeostasis and glucose metabolism. Diabetes 58:1499-1508, 2009
C1 [Estall, Jennifer L.; Cooper, Marcus P.; Laznik, Dina; Qu, Lishu; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Estall, Jennifer L.; Cooper, Marcus P.; Laznik, Dina; Qu, Lishu; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kahn, Mario; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA.
[Kahn, Mario; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Kahn, Mario; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA.
[Fisher, Ffolliott Martin] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, Boston, MA 02115 USA.
[Wu, Michele K.; Cohen, David E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol,Dept Med, Boston, MA 02115 USA.
RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu
FU National Research Council of Canada; National Institutes of Health
[DK061562]
FX J.L.E. is supported by a postdoctoral fellowship from the Canadian
Institutes of Health Research and the H.L. Holmes Award for Postdoctoral
Studies from the National Research Council of Canada. National
Institutes of Health Grant DK061562 (to B.M.S.) supported the work
described in this report.
NR 41
TC 62
Z9 62
U1 1
U2 8
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD JUL
PY 2009
VL 58
IS 7
BP 1499
EP 1508
DI 10.2337/db08-1571
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 466VF
UT WOS:000267690700007
PM 19366863
ER
PT J
AU Prokopenko, I
Zeggini, E
Hanson, RL
Mitchell, BD
Rayner, NW
Akan, P
Baier, L
Das, SK
Elliott, KS
Fu, M
Frayling, TM
Groves, CJ
Gwilliam, R
Scott, LJ
Voight, BF
Hattersley, AT
Hu, C
Morris, AD
Ng, M
Palmer, CNA
Tello-Ruiz, M
Vaxillaire, M
Wang, CR
Stein, L
Chan, J
Jia, WP
Froguel, P
Elbein, SC
Deloukas, P
Bogardus, C
Shuldiner, AR
McCarthy, MI
AF Prokopenko, Inga
Zeggini, Eleftheria
Hanson, Robert L.
Mitchell, Braxton D.
Rayner, N. William
Akan, Pelin
Baier, Leslie
Das, Swapan K.
Elliott, Katherine S.
Fu, Mao
Frayling, Timothy M.
Groves, Christopher J.
Gwilliam, Rhian
Scott, Laura J.
Voight, Benjamin F.
Hattersley, Andrew T.
Hu, Cheng
Morris, Andrew D.
Ng, Maggie
Palmer, Colin N. A.
Tello-Ruiz, Marcela
Vaxillaire, Martine
Wang, Cong-rong
Stein, Lincoln
Chan, Juliana
Jia, Weiping
Froguel, Philippe
Elbein, Steven C.
Deloukas, Panos
Bogardus, Clifton
Shuldiner, Alan R.
McCarthy, Mark I.
CA Int Type 2 Diabet 1q Consortium
TI Linkage Disequilibrium Mapping of the Replicated Type 2 Diabetes Linkage
Signal on Chromosome 1q
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; NUCLEAR FACTOR-4-ALPHA GENE; GK RAT;
SUSCEPTIBILITY; LOCI; VARIANTS; RISK; POPULATION; DISEASES; SAMPLES
AB OBJECTIVE-Linkage of the chromosome 1q21-25 region to type 2 diabetes has been demonstrated in multiple ethnic groups. We performed common variant fine-mapping across a 23-Mb interval in a multiethnic sample to search for variants responsible for this linkage signal.
RESEARCH DESIGN AND METHODS-In all, 5,290 single nucleotide polymorphisms (SNPs) were successfully genotyped in 3,179 type 2 diabetes case and control subjects from eight populations with evidence of 1q linkage. Samples were ascertained using strategies designed to enhance power to detect variants causal for 1q linkage. After imputation, we estimate similar to 80% coverage of common variation across the region (r(2) > 0.8, Europeans). Association signals of interest were evaluated through in silico replication and de novo genotyping in similar to 8,500 case subjects and 12,400 control subjects.
RESULTS-Association mapping of the 23-Mb region identified two strong signals, both of which were restricted to the subset of European-descent samples. The first mapped to the NOS1AP (CAPON) gene region (lead SNP: rs7538490, odds ratio 1.38 [95% CI 1.21-1.571, P = 1.4 x 10(-6), in 999 case subjects and 1,190 control subjects); the second mapped within an extensive region of linkage disequilibrium that includes the ASH1L and PKLR genes (lead SNP: rs11264371, odds ratio 1.48 [1.18-1.761, P = 1.0 x 10(-5), under a dominant model). However, there was no evidence for association at either signal on replication, and, across all data (>24,000 subjects), there was no indication that these variants were causally related to type 2 diabetes status.
CONCLUSIONS-Detailed fine-mapping of the 23-Mb region of replicated linkage has failed to identify common variant signals contributing to the observed signal. Future studies should focus on identification of causal alleles of lower frequency and higher penetrance. Diabetes 58:1704-1709, 2009
C1 [Prokopenko, Inga; Zeggini, Eleftheria; Rayner, N. William; Elliott, Katherine S.; Groves, Christopher J.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Prokopenko, Inga; Rayner, N. William; Groves, Christopher J.; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Zeggini, Eleftheria; Akan, Pelin; Gwilliam, Rhian; Deloukas, Panos] Wellcome Trust Sanger Inst, Cambridge, England.
[Hanson, Robert L.; Baier, Leslie; Bogardus, Clifton] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
[Mitchell, Braxton D.; Fu, Mao; Shuldiner, Alan R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Das, Swapan K.; Elbein, Steven C.] Cent Arkansas Vet Healthcare Syst, Endocrinol Sect, Med Serv, Little Rock, AR USA.
[Das, Swapan K.] Univ Arkansas Med Sci, Div Endocrinol & Metab, Dept Internal Med, Coll Med, Little Rock, AR 72205 USA.
[Frayling, Timothy M.; Hattersley, Andrew T.] Peninsula Med Sch, Inst Clin & Biomed Sci, Exeter, Devon, England.
[Scott, Laura J.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Scott, Laura J.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Voight, Benjamin F.] Broad Inst Harvard, Cambridge, MA USA.
[Voight, Benjamin F.] MIT, Cambridge, MA 02139 USA.
[Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Voight, Benjamin F.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Voight, Benjamin F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Hu, Cheng; Wang, Cong-rong; Jia, Weiping] Shanghai Jiao Tong Univ, Shanghai Diabet Inst, Dept Endocrinol & Metab, Peoples Hosp 6, Shanghai 200030, Peoples R China.
[Morris, Andrew D.] Univ Dundee, Diabet Res Grp, Biomed Res Inst, Dundee, Scotland.
[Ng, Maggie; Chan, Juliana] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China.
[Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Inst, Dundee DD1 9SY, Scotland.
[Tello-Ruiz, Marcela; Stein, Lincoln] Cold Spring Harbor Lab, New York, NY USA.
[Vaxillaire, Martine; Froguel, Philippe] Univ Lille 2, CNRS, Inst Biol, UMR 8090, Lille, France.
[Vaxillaire, Martine; Froguel, Philippe] Univ Lille 2, Inst Pasteur, Lille, France.
[Stein, Lincoln] Ontario Inst Canc Res, Toronto, ON, Canada.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England.
[McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7LJ, England.
RP McCarthy, MI (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM mark.mccarthy@drl.ox.ac.uk
RI Study, GoDARTS/K-9448-2016; Hu, Cheng/C-3346-2008; Palmer,
Colin/C-7053-2008; Morris, Andrew/C-2837-2009; Voight,
Benjamin/F-1775-2011; Hossain, Sarah /C-7332-2009; Jia,
Weiping/B-7483-2012; Deloukas, Panos/B-2922-2013; Hanson,
Robert/O-3238-2015; Prokopenko, Inga/H-3241-2014; Chan, Juliana
/B-7918-2016;
OI Palmer, Colin/0000-0002-6415-6560; Hossain, Sarah /0000-0003-1355-0979;
Deloukas, Panos/0000-0001-9251-070X; Hanson, Robert/0000-0002-4252-7068;
Prokopenko, Inga/0000-0003-1624-7457; Chan, Juliana
/0000-0003-1325-1194; Zeggini, Eleftheria/0000-0003-4238-659X; Mitchell,
Braxton/0000-0003-4920-4744
FU Intramural NIH HHS; Medical Research Council [G0601201(79675), G0600331,
G0601201, G0601261]; NCI NIH HHS [K07-CA67960]; NCRR NIH HHS [M01
RR014288, M01 RR14288]; NIA NIH HHS [T32 AG000219, T32-AG00219]; NIDDK
NIH HHS [K24-DK02673, P30 DK079637, R01 DK039311, R01 DK054261, R01
DK073490, R01-DK073490, R01-DK39311, R01-DK54261, U01 DK058026,
U01-DK58026]; Wellcome Trust [072960, 077011, 079557, 088885, GR072960]
NR 24
TC 18
Z9 20
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUL
PY 2009
VL 58
IS 7
BP 1704
EP 1709
DI 10.2337/db09-0081
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 466VF
UT WOS:000267690700032
PM 19389826
ER
PT J
AU Meigs, JB
AF Meigs, James B.
TI Multiple Biomarker Prediction of Type 2 Diabetes
SO DIABETES CARE
LA English
DT Editorial Material
ID METABOLIC SYNDROME; GLUCOSE-TOLERANCE; ENDOTHELIAL DYSFUNCTION;
CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; MELLITUS; MARKERS;
METAANALYSIS; ADIPONECTIN; COMMUNITIES
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02115 USA.
RP Meigs, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02115 USA.
EM jmeigs@partners.org
FU NIDDK NIH HHS [K24 DK080140]
NR 25
TC 14
Z9 14
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2009
VL 32
IS 7
BP 1346
EP 1348
DI 10.2337/dc09-0754
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 469EK
UT WOS:000267878300044
PM 19564478
ER
PT J
AU Zrebiec, J
AF Zrebiec, John
TI A National Study of the Diabetes Educator Report on a Practice Analysis
Conducted by the National Certification Board for Diabetes Educators
SO DIABETES EDUCATOR
LA English
DT Article
AB Purpose
The practice analysis described in this report was conducted by the National Certification Board for Diabetes Educators (NCBDE) to (1) provide a basis for documenting the continuing validity of the Certification Examination for Diabetes Educators, (2) define new areas that should be assessed in future certification examinations, and (3) ensure that the content of certification examinations is related to practice.
Methods
The study involved developing a diabetes educator job task list and survey, distributing 4103 surveys, and analyzing survey responses from a multidisciplinary and geographically representative sample of certified diabetes educators.
Results
Eight hundred thirty-six surveys were suitable for analysis, with relevant demographic subgroups adequately represented. Based on survey data, an examination matrix and detailed content outline was constructed that will be used by NCBDE to assemble future test forms.
Conclusions
Certification examination specifications were developed directly related to the important activities that diabetes educators perform. Future forms of the certification examination will continue to be matched to job-related, criterion-referenced test specifications and will have strong evidence of content validity. Future forms of the exam will contain 200 items at specified cognitive levels with a representative sampling of tasks within 3 core areas from the detailed content outline.
C1 [Zrebiec, John] Natl Certificat Board Diabet Educators, Arlington Hts, IL USA.
RP Zrebiec, J (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM zrebiec@joslin.harvard.edu
FU National Certification Board for Diabetes Educators
FX NCBDE appreciated the psychometric expertise of Steven Nettles, EdD, and
Christopher Traynor, MS, from Applied Measurement Professionals, Inc.,
and the managerial skill of Joyce Bohren, retired CEO of NCBDE. In
particular, NCBDE is grateful to the members of the Practice Analysis
Advisory Committee for contributing their time and sharing their
professional experience while guiding this complex project. The
committee included Stephen Ponder, MD, CDE, Co-Chairperson; Joni Beck,
PharmD, BC-ADM, CDE; Karen Bolderman, RD, LDN, CDE; Renea Bradley, RN,
CDE; Ned Crockett, MD, CDE; Marjorie Cypress, PhD, C-ANP, CDE; Wendy
Kushion, MSN, APRN-BC, CDE; Sandy Muchnick, MEd, CDE; Claudia
Shwide-Slavin, MS, RD, BC-ADM, CDE; Phyllis Secraw, RN, CDE; Carrie
Swift, MS, RD, BC-ADM, CDE. Funding was provided by the National
Certification Board for Diabetes Educators.
NR 3
TC 1
Z9 1
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0145-7217
J9 DIABETES EDUCATOR
JI Diabetes Educ.
PD JUL
PY 2009
VL 35
IS 4
BP 657
EP 663
DI 10.1177/0145721709336300
PG 7
WC Endocrinology & Metabolism; Public, Environmental & Occupational Health
SC Endocrinology & Metabolism; Public, Environmental & Occupational Health
GA 474TK
UT WOS:000268306800011
PM 19448043
ER
PT J
AU Cadena, J
Thompson, GR
Ho, TT
Medina, E
Hughes, DW
Patterson, TF
AF Cadena, Jose
Thompson, George R., III
Ho, Tony T.
Medina, Edward
Hughes, Darrel W.
Patterson, Thomas F.
TI Immune reconstitution inflammatory syndrome after cessation of the tumor
necrosis factor alpha blocker adalimumab in cryptococcal pneumonia
SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
LA English
DT Article
DE Cryptococcus; TNF-alpha inhibitors; Adalimumab; Immune reconstitution
ID PARADOXICAL RESPONSE; THERAPY; TUBERCULOSIS
AB Tumor necrosis factor a antagonists have proven efficacious for a variety of autoimmune-mediated diseases. However, recent data have highlighted the risk of invasive fungal infections with their use. These agents are typically discontinued when infectious complications occur during therapy; however, the immune reconstitution inflammatory syndrome (IRIS) tray be seen after drug cessation. We describe the 1st case of IRIS secondary to cryptococcal pneumonia after cessation of adalimumab. Published by Elsevier Inc.
C1 [Cadena, Jose; Thompson, George R., III; Ho, Tony T.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA.
[Medina, Edward] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Cadena, Jose; Thompson, George R., III; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Hughes, Darrel W.] Univ Hlth Syst, Dept Pharm, San Antonio, TX 78229 USA.
RP Thompson, GR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA.
EM thompsong2@uthscsa.edu
NR 11
TC 12
Z9 12
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0732-8893
J9 DIAGN MICR INFEC DIS
JI Diagn. Microbiol. Infect. Dis.
PD JUL
PY 2009
VL 64
IS 3
BP 327
EP 330
DI 10.1016/j.diagmicrobio.2009.03.019
PG 4
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 461OL
UT WOS:000267277300014
PM 19501793
ER
PT J
AU Vincent, RK
Odorico, JS
AF Vincent, Robert K.
Odorico, Jon S.
TI Reduced serum concentration is permissive for increased in vitro
endocrine differentiation from murine embryonic stem cells
SO DIFFERENTIATION
LA English
DT Article
DE Embryonic stem cells; Endocrine differentiation; Fetal calf serum; Serum
replacement; Pancreatic duodenal homeobox 1; Neurogenin 3;
Tetracycline-inducible
ID INSULIN-PRODUCING CELLS; PANCREATIC BETA-CELLS; DIRECTED
DIFFERENTIATION; ISLET DIFFERENTIATION; TARGETED EXPRESSION;
GENE-TRANSCRIPTION; EXOCRINE PANCREAS; PROGENITORS; MAFA; PDX-1
AB Embryonic stem cells (ESCs) have been shown to be capable of differentiating into pancreatic progenitors and insulin-producing cells in vitro. However, before ESC derivatives can be used in clinical settings, efficient selective differentiation needs to be achieved. Essential to improving ESC differentiation to islet endocrine cells is an understanding of the influences of extrinsic signals and transcription factors on cell specification. Herein, we investigate the influence of serum-supplemented growth conditions on the differentiation of murine ESCs to endocrine lineages in the context of over-expression of two pancreatic transcription factors, Pdx1 and Ngn3.
To study the effect of different serum formulations and concentrations on the ability of murine ESCs to differentiate into endocrine cells in vitro, cells were grown into embryoid bodies and then differentiated in various serum replacement (SR), fetal calf serum (FCS) and serum-free conditions. Using immunohistochemistry and quantitative real-time RT-PCR (QPCR), we found that, of the conditions tested, 1% SR differentiation medium resulted in the highest levels of insulin-1 mRNA and significantly increased the total number of insulin-expressing cells. Applying this knowledge to cell lines in which Pdx1 or Ngn3 transgene expression could be induced by exposure to doxycycline we differentiated TetPDX1 and TetNgn3 ESCs under conditions of either 10% FCS or 1% SR medium. In the presence of 10% serum, induced expression of either Pdx1 or Ngn3 in differentiating ESCs resulted in modest increases in hormone transcripts and cell counts. However, changing the serum formulation from 10% FCS to 1% SR significantly enhanced the number of insulin+/C-peptide+ cells in parallel with increased insulin-1 transcript levels in both inducible cell lines. In summary, these data demonstrate that induced expression of key pancreatic transcription factors in combination with low serum/SR concentrations increases endocrine cell differentiation from murine ESCs. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.
C1 [Vincent, Robert K.; Odorico, Jon S.] Univ Wisconsin, Sch Med & Publ Hlth, Div Transplantat, Dept Surg, Madison, WI 53792 USA.
[Vincent, Robert K.; Odorico, Jon S.] WiCell Res Inst, Madison, WI 53792 USA.
[Vincent, Robert K.; Odorico, Jon S.] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA.
RP Odorico, JS (reprint author), Univ Wisconsin Hosp, Dept Surg, Div Transplantat, H4-756 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA.
EM jon@surgery.wisc.edu
NR 59
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Z9 2
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
J9 DIFFERENTIATION
JI Differentiation
PD JUL
PY 2009
VL 78
IS 1
BP 24
EP 34
DI 10.1016/j.diff.2009.03.006
PG 11
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 555RP
UT WOS:000274532000003
PM 19446949
ER
PT J
AU Yermilov, I
Jain, S
Sekeris, E
Bentrem, DJ
Hines, OJ
Reber, HA
Ko, CY
Tomlinson, JS
AF Yermilov, Irina
Jain, Sushma
Sekeris, Evan
Bentrem, David J.
Hines, Oscar J.
Reber, Howard A.
Ko, Clifford Y.
Tomlinson, James S.
TI Utilization of Parenteral Nutrition Following Pancreaticoduodenectomy:
Is Routine Jejunostomy Tube Placement Warranted?
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Pancreaticoduodenectomy; Parenteral nutrition; Enterostomy tube;
Postoperative nutrition
ID SINGLE-INSTITUTION EXPERIENCE; PANCREATIC-CANCER; MORBIDITY; MORTALITY;
RESECTION; LENGTH; TRIAL; COSTS
AB Introduction Complications following pancreaticoduodenectomy (PD) often necessitate nutritional support. This study analyzes the utilization of parenteral nutrition (TPN) during the surgical admission as evidence for or against routine jejunostomy placement. Methods The California Cancer Registry (1994-2003) was linked to the California Inpatient File; PD for adenocarcinoma was performed in 1,873 patients. TPN use and enterostomy tube placement were determined and preoperative characteristics predictive of TPN use during the surgical admission were identified. Results Fourteen percent of patients received TPN, 23% underwent enterostomy tube placement, and 63% received no supplemental nutritional support. TPN was associated with longer hospital stay (18 vs. 13 days, P < 0.0001). The Charlson Comorbidity Index (CCI) a parts per thousand yen 3 had nearly two-fold greater odds of receiving TPN (odds ratio [OR] = 1.85, P < 0.005). Conclusion Approximately 1 in 6 patients undergoing PD received TPN, which was associated with prolonged hospital stay. CCI a parts per thousand yen 3 was associated with increased odds of TPN utilization. Selected jejunostomy placement in patients with high CCI is worthy of consideration.
C1 [Yermilov, Irina; Ko, Clifford Y.; Tomlinson, James S.] VA Greater Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90073 USA.
[Yermilov, Irina; Jain, Sushma; Sekeris, Evan; Hines, Oscar J.; Reber, Howard A.; Ko, Clifford Y.; Tomlinson, James S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA.
[Bentrem, David J.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA.
[Hines, Oscar J.; Reber, Howard A.; Tomlinson, James S.] Univ Calif Los Angeles, Ctr Pancreat Dis, Los Angeles, CA USA.
RP Tomlinson, JS (reprint author), VA Greater Angeles Healthcare Syst, Dept Surg, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM James.Tomlinson@va.gov
NR 24
TC 13
Z9 16
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD JUL
PY 2009
VL 54
IS 7
BP 1582
EP 1588
DI 10.1007/s10620-008-0526-1
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 454AV
UT WOS:000266654900030
PM 18958617
ER
PT J
AU Iezzoni, LI
AF Iezzoni, Lisa I.
TI Public Health Goals for Persons With Disabilities: Looking Ahead to 2020
SO DISABILITY AND HEALTH JOURNAL
LA English
DT Editorial Material
DE disability; public health; Healthy People
ID DISPARITIES
AB Much of this article first appeared as testimony of Dr. Iezzoni before the U.S. Senate Health, Education, Labor, and Pensions Committee, Washington, DC, January 27, 2009. Dr. Iezzoni serves on the Secretary's Advisory Committee on National Health Promotion and Disease Prevention Objectives for 2020. This article represents her personal views and not the views of the committee. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Iezzoni, Lisa I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
EM liezzoni@partners.org
NR 16
TC 16
Z9 16
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-6574
J9 DISABIL HEALTH J
JI Disabil. Health J.
PD JUL
PY 2009
VL 2
IS 3
BP 111
EP 115
DI 10.1016/j.dhjo.2009.03.002
PG 5
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health; Rehabilitation
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Rehabilitation
GA 668QM
UT WOS:000283284700001
PM 21122749
ER
PT J
AU Kahn, R
Biswas, K
Childress, AR
Shoptaw, S
Fudala, PJ
Gorgon, L
Montoya, I
Collins, J
McSherry, F
Li, SH
Chiang, N
Alathari, H
Watson, D
Liberto, J
Beresford, T
Stock, C
Wallace, C
Gruber, V
Elkashef, A
AF Kahn, Roberta
Biswas, Kousick
Childress, Anna-Rose
Shoptaw, Steve
Fudala, Paul J.
Gorgon, Liza
Montoya, Ivan
Collins, Joseph
McSherry, Frances
Li, Shou-Hua
Chiang, Nora
Alathari, Husam
Watson, Donnie
Liberto, Joseph
Beresford, Thomas
Stock, Christopher
Wallace, Christopher
Gruber, Valerie
Elkashef, Ahmed
TI Multi-center trial of baclofen for abstinence initiation in severe
cocaine-dependent individuals
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Cocaine; Dependence; Baclofen
ID RECEPTOR AGONISTS BACLOFEN; LONGITUDINAL DATA-ANALYSIS; HIGH-DOSE
BACLOFEN; GABA(B) RECEPTOR; ALCOHOL-DEPENDENCE; SEEKING BEHAVIOR; RATS;
SYMPTOMS; NICOTINE; REINSTATEMENT
AB Background: Cocaine dependence is a major public health problem for which there is no FDA-approved pharmacological treatment. Baclofen is a GABA(B) receptor agonist that in preclinical and early pilot clinical trials has shown promise for the treatment of cocaine dependence. The purpose of this multi-site, double-blind study, was to compare the safety and efficacy of baclofen (60 mg/day) vs placebo in an 8-week treatment of individuals with severe cocaine dependence. The primary Outcome measure was subjects' self-reported cocaine use substantiated by urine benzoylecgonine (BE). Analysis of the data did not show a significant difference between the groups treated with baclofen and placebo. The current results do not support a role for 60 mg baclofen in treating cocaine dependence in the population studied. The contrast of this result to earlier, preclinical and human pilot data with baclofen may reflect the trial's focus on severe cocaine-dependent users, and/or the need for a higher baclofen dose. Baclofen's potential as a relapse prevention agent was not tested by the current design, but may be a useful target for future studies. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Kahn, Roberta; Gorgon, Liza; Montoya, Ivan; Li, Shou-Hua; Chiang, Nora; Elkashef, Ahmed] NIDA, DPMCDA, Bethesda, MD 20892 USA.
[Biswas, Kousick; Collins, Joseph; McSherry, Frances] Cooperat Studies Program Coordinating Ctr 151E, DVA, Perry Point, MD 21902 USA.
[Fudala, Paul J.] Reckitt Benckiser Pharmaceut Inc, Richmond, VA 23235 USA.
[Shoptaw, Steve; Watson, Donnie] Friends Res Inst Inc, Los Angeles, CA USA.
[Childress, Anna-Rose] Univ Penn, Sch Med, Dept Psychiat, Addict Treatment Res Ctr, Philadelphia, PA 19104 USA.
[Alathari, Husam] Inova Ctr Addict Treatment Serv, Falls Church, VA 22042 USA.
[Watson, Donnie] Univ Calif Los Angeles, Integrated Substance Abuse Program, Torrance, CA 90502 USA.
[Liberto, Joseph] VA Maryland Hlth Care Syst MH 116, Baltimore, MD 21201 USA.
[Beresford, Thomas] Eastern Colorado Vet Affairs Healthcare Syst, Psychiat Serv 116, Denver, CO 80220 USA.
[Stock, Christopher] Vet Affairs Salt Lake City Healthcare Syst, Salt Lake City, UT 84148 USA.
[Wallace, Christopher] S Texas Vet Healthcare Syst, Vet Affairs Med Ctr Psychiat Serv 116A, San Antonio, TX 78229 USA.
[Gruber, Valerie] San Francisco Gen Hosp, San Francisco, CA 94110 USA.
RP Kahn, R (reprint author), NIDA, DPMCDA, 6001 Execut Blvd,Rm 4123,MSC 9551, Bethesda, MD 20892 USA.
EM rkan@nida.nih.gov
FU National Institute on Drug Abuse [Y1-DA4006]
FX This study was Supported by the National Institute on Drug Abuse through
the Department of Veterans Affairs Cooperative Studies Program
(Interagency Agreement No. Y1-DA4006).
NR 35
TC 42
Z9 42
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD JUL 1
PY 2009
VL 103
IS 1-2
BP 59
EP 64
DI 10.1016/j.drugalcdep.2009.03.011
PG 6
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 455LG
UT WOS:000266760700009
PM 19414226
ER
PT J
AU Russom, A
Irimia, D
Toner, M
AF Russom, Aman
Irimia, Daniel
Toner, Mehmet
TI Chemical gradient-mediated melting curve analysis for genotyping of SNPs
SO ELECTROPHORESIS
LA English
DT Article
DE Chemical gradient; Formamide; Melting curve analysis; SNP; Urea
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ALLELE-SPECIFIC HYBRIDIZATION;
FLOW-THROUGH DEVICE; MONOLAYERED BEADS; DNA HYBRIDIZATION;
LOW-TEMPERATURE; REAL-TIME; ARRAYS; UREA; FORMAMIDE
AB This report describes a microfluidic solid-phase chemical gradient-mediated melting curve analysis method for SNP analysis. The method is based on allele-specific denaturation to discriminate mismatched (MM) from perfectly matched (PM) DNA duplexes upon exposure to linear chemical gradient. PM and MM DNA duplexes conjugated on beads are captured in a microfluidic gradient generator device designed with dams, keeping the beads trapped perpendicular to a gradient generating channel. Two denaturants, formamide and urea, were tested for their ability to destabilize the DNA duplex by competing with Watson-Crick pairing. Upon exposure to the chemical gradient, rapid denaturing profile was monitored in real time using fluorescence microscopy. The results show that the two duplexes exhibit different kinetics of denaturation profiles, enabling discrimination of MM from PM DNA duplexes to score SNP.
C1 [Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA.
Shriners Hosp Children, Boston, MA USA.
RP Toner, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA.
EM mtoner@hms.harvard.edu
RI Russom, Aman/B-1675-2012;
OI Irimia, Daniel/0000-0001-7347-2082; Russom, Aman/0000-0002-0242-358X
FU National Institute of Health BioMEMS Resource Center [P41 grant, P41
EB-002503]
FX This work was supported by the National Institute of Health BioMEMS
Resource Center (P41 grant, P41 EB-002503). The authors thank Octavio
Hurtado and White Will for assistance.
NR 38
TC 4
Z9 4
U1 0
U2 8
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 0173-0835
J9 ELECTROPHORESIS
JI Electrophoresis
PD JUL
PY 2009
VL 30
IS 14
BP 2536
EP 2543
DI 10.1002/elps.200800729
PG 8
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 484JV
UT WOS:000269041500017
PM 19593749
ER
PT J
AU Miller, SJ
Jessen, WJ
Mehta, T
Hardiman, A
Sites, E
Kaiser, S
Jegga, AG
Li, H
Upadhyaya, M
Giovannini, M
Muir, D
Wallace, MR
Lopez, E
Serra, E
Nielsen, GP
Lazaro, C
Stemmer-Rachamimov, A
Page, G
Aronow, BJ
Ratner, N
AF Miller, Shyra J.
Jessen, Walter J.
Mehta, Tapan
Hardiman, Atira
Sites, Emily
Kaiser, Sergio
Jegga, Anil G.
Li, Hua
Upadhyaya, Meena
Giovannini, Marco
Muir, David
Wallace, Margaret R.
Lopez, Eva
Serra, Eduard
Nielsen, G. Petur
Lazaro, Conxi
Stemmer-Rachamimov, Anat
Page, Grier
Aronow, Bruce J.
Ratner, Nancy
TI Integrative genomic analyses of neurofibromatosis tumours identify SOX9
as a biomarker and survival gene
SO EMBO MOLECULAR MEDICINE
LA English
DT Article
DE MPNST; neurofibroma; NF1; Schwann cell; Sox9
ID NERVE SHEATH TUMORS; TRANSCRIPTION FACTOR SOX10; CREST STEM-CELLS;
SCHWANN-CELLS; DERMAL NEUROFIBROMAS; NF1 MUTATION; GLIAL-CELLS;
EXPRESSION; PROTEIN; IDENTIFICATION
AB Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n - 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n = 22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n = 13), benign neurofibromas (NF) (n = 26) and MPNST (n = 6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumours - caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1.
C1 [Miller, Shyra J.; Hardiman, Atira; Sites, Emily; Ratner, Nancy] Univ Cincinnati, Coll Med, Div Expt Hematol, Cincinnati, OH 45221 USA.
[Miller, Shyra J.; Hardiman, Atira; Sites, Emily; Ratner, Nancy] Univ Cincinnati, Coll Med, Div Canc Biol, Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Jessen, Walter J.; Kaiser, Sergio; Jegga, Anil G.; Aronow, Bruce J.] Univ Cincinnati, Coll Med, Div Biomed Informat, Cincinnati Childrens Hosp,Res Fdn, Cincinnati, OH USA.
[Mehta, Tapan; Page, Grier] Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA.
[Li, Hua; Wallace, Margaret R.] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA.
[Upadhyaya, Meena] Univ Wales Coll Cardiff, Coll Med, Inst Med Genet, Cardiff CF1 3NS, S Glam, Wales.
[Giovannini, Marco] Fdn Jean Dausset CEPH, INSERM, U434, Paris, France.
[Muir, David] Univ Florida, Dept Pediat, Gainesville, FL USA.
[Muir, David] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA.
[Lopez, Eva; Serra, Eduard] Inst Catala Oncol, Ctr Genet Med & Mol, Barcelona, Spain.
[Lopez, Eva; Serra, Eduard; Lazaro, Conxi] IDIBELL, Barcelona, Spain.
[Lazaro, Conxi] Inst Catala Oncol, Lab Recerca Translac, Barcelona, Spain.
[Nielsen, G. Petur; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Nielsen, G. Petur; Stemmer-Rachamimov, Anat] Harvard Univ, Sch Med, Boston, MA USA.
RP Ratner, N (reprint author), Univ Cincinnati, Coll Med, Div Expt Hematol, Cincinnati, OH 45221 USA.
EM nancy.ratner@cchmc.org
RI Serra, Eduard/K-1332-2013;
OI Serra, Eduard/0000-0003-2895-9857; Jegga, Anil/0000-0002-4881-7752;
Jessen, Walter/0000-0003-3840-4337
FU DAMD [DOD W81XWH-04-1-0273]; Hayward Foundation; NINDS [K01-NS049191];
[T32 CA 59268]
FX We gratefully acknowledge Dr Patrick Wood of the Miami Project to Cure
Paralysis for providing human Schwann cells obtained from the cauda
equina of organ donors. The cauda equine were provided by the University
of Miami Life Alliance Organ Procurement Agency (Dr David Levi,
Director). Cincinnati Children's Hospital Affymetrix GeneChip Core (Dr
Steve Potter, Sean Smith and Hung-Chi Liang) performed microarray
hybridization. We thank Drs Larry Gelbert (Eli Lilly) and Chris Roberts
(Rosetta) for extensive input into the development and progress of the
NF1 microarray consortium. This study was supported by the DAMD (DOD
W81XWH-04-1-0273). MRW was supported by the Hayward Foundation. SM was
the recipient of NINDS Translational Neuroscience Award K01-NS049191 and
ES was supported by T32 CA 59268.
NR 52
TC 52
Z9 52
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1757-4676
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD JUL
PY 2009
VL 1
IS 4
BP 236
EP 248
DI 10.1002/emmm.200900027
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 543GY
UT WOS:000273563200007
PM 20049725
ER
PT J
AU Loyola, A
Tagami, H
Bonaldi, T
Roche, D
Quivy, JP
Imhof, A
Nakatani, Y
Dent, SYR
Almouzni, G
AF Loyola, Alejandra
Tagami, Hideaki
Bonaldi, Tiziana
Roche, Daniele
Quivy, Jean Pierre
Imhof, Axel
Nakatani, Yoshihiro
Dent, Sharon Y. R.
Almouzni, Genevieve
TI The HP1 alpha-CAF1-SetDB1-containing complex provides H3K9me1 for
Suv39-mediated K9me3 in pericentric heterochromatin
SO EMBO REPORTS
LA English
DT Article
DE CAF1; H3K9 methylation; HP1 alpha; pericentric heterochromatin; SetDB1
ID ZINC-FINGER PROTEINS; HISTONE H3; DROSOPHILA SU(VAR)3-9;
DNA-REPLICATION; HP1; METHYLTRANSFERASE; METHYLATION; LYSINE-9;
PROGRESSION; REPRESSION
AB Trimethylation of lysine 9 in histone H3 (H3K9me3) enrichment is a characteristic of pericentric heterochromatin. The hypothesis of a stepwise mechanism to establish and maintain this mark during DNA replication suggests that newly synthesized histone H3 goes through an intermediate methylation state to become a substrate for the histone methyltransferase Suppressor of variegation 39 (Suv39H1/H2). How this intermediate methylation state is achieved and how it is targeted to the correct place at the right time is not yet known. Here, we show that the histone H3K9 methyltransferase SetDB1 associates with the specific heterochromatin protein 1 alpha (HP1 alpha)-chromatin assembly factor 1 (CAF1) chaperone complex. This complex monomethylates K9 on non-nucleosomal histone H3. Therefore, the heterochromatic HP1 alpha-CAF1-SetDB1 complex probably provides H3K9me1 for subsequent trimethylation by Suv39H1/H2 in pericentric regions. The connection of CAF1 with DNA replication, HP1 alpha with heterochromatin formation and SetDB1 for H3K9me1 suggests a highly coordinated mechanism to ensure the propagation of H3K9me3 in pericentric heterochromatin during DNA replication.
C1 [Loyola, Alejandra; Roche, Daniele; Quivy, Jean Pierre; Almouzni, Genevieve] Inst Curie, UPMC, CNRS, UMR218, F-75248 Paris 05, France.
[Loyola, Alejandra] Fdn Ciencia Vida, Santiago, Chile.
[Loyola, Alejandra] Univ San Sebastian, Santiago, Chile.
[Loyola, Alejandra; Dent, Sharon Y. R.] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Unit 1000, Houston, TX 77030 USA.
[Tagami, Hideaki; Nakatani, Yoshihiro] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Tagami, Hideaki; Nakatani, Yoshihiro] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Bonaldi, Tiziana] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy.
[Imhof, Axel] Histone Modificat Grp, D-80336 Munich, Germany.
[Imhof, Axel] Munich Ctr Integrated Prot Sci, D-80336 Munich, Germany.
RP Almouzni, G (reprint author), Inst Curie, UPMC, CNRS, UMR218, 26 Rue Ulm, F-75248 Paris 05, France.
EM genevieve.almouzni@curie.fr
RI Bonaldi, Tiziana/K-5075-2016
OI Bonaldi, Tiziana/0000-0003-3556-1265
FU Odyssey Scholarship; CONICYT [CCTE-PFB16]
FX A. L. is supported by an Odyssey Scholarship and CONICYT Program
CCTE-PFB16.
NR 22
TC 95
Z9 97
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD JUL
PY 2009
VL 10
IS 7
BP 769
EP 775
DI 10.1038/embor.2009.90
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 465PQ
UT WOS:000267599700021
PM 19498464
ER
PT J
AU Khan, AA
Bilezikian, JP
Potts, JT
AF Khan, Aliya A.
Bilezikian, John P.
Potts, John T., Jr.
TI ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM: A COMMENTARY ON THE REVISED
GUIDELINES
SO ENDOCRINE PRACTICE
LA English
DT Editorial Material
ID 3RD INTERNATIONAL WORKSHOP; MILD PRIMARY HYPERPARATHYROIDISM;
CLINICAL-TRIAL; SURGERY; MANAGEMENT; DIAGNOSIS
C1 [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
[Khan, Aliya A.] McMaster Univ, Div Endocrinol, Hamilton, ON, Canada.
[Khan, Aliya A.] McMaster Univ, Div Geriatr, Hamilton, ON, Canada.
[Potts, John T., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Bilezikian, JP (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, 630 W 168th St,Ph 8 W 864, New York, NY 10032 USA.
EM jpb2@columbia.edu
FU NIDDK NIH HHS [R01 DK032333-26, R01 DK032333, R01 DK032333-27]
NR 22
TC 4
Z9 4
U1 0
U2 1
PU AMER ASSOC CLIN ENDOCRINOL
PI JACKSONVILLE
PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA
SN 1530-891X
J9 ENDOCR PRACT
JI Endocr. Pract.
PD JUL-AUG
PY 2009
VL 15
IS 5
BP 494
EP 498
DI 10.4158/EP09162.CO
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 482XJ
UT WOS:000268923600014
PM 19546049
ER
PT J
AU Barnwell, LFS
Lugo, JN
Lee, WL
Willis, SE
Gertz, SJ
Hrachovy, RA
Anderson, AE
AF Barnwell, L. Forbes S.
Lugo, Joaquin N.
Lee, Wai L.
Willis, Sarah E.
Gertz, Shira J.
Hrachovy, Richard A.
Anderson, Anne E.
TI Kv4.2 knockout mice demonstrate increased susceptibility to convulsant
stimulation
SO EPILEPSIA
LA English
DT Article
DE A-type K channel; Channelopathies; Seizures; Status epilepticus; Mouse
ID CA1 PYRAMIDAL NEURONS; POTASSIUM CHANNEL GENE; RAT HIPPOCAMPAL SLICE;
EPILEPTIFORM ACTIVITY; DOWN-REGULATION; HUMAN EPILEPSY; K+ CURRENT;
CURRENTS; SEIZURE; REPOLARIZATION
AB P>Purpose:
Kv4.2 subunits contribute to the pore-forming region of channels that express a transient, A-type K(+) current (A-current) in hippocampal CA1 pyramidal cell dendrites. Here, the A-current plays an important role in signal processing and synaptic integration. Kv4.2 knockout mice show a near elimination of the A-current in area CA1 dendrites, producing increased excitability in this region. In these studies, we evaluated young adult Kv4.2 knockout mice for spontaneous seizures and the response to convulsant stimulation in the whole animal in vivo and in hippocampal slices in vitro.
Methods:
Electroencephalogram electrode-implanted Kv4.2 knockout and wild-type mice were observed for spontaneous behavioral and electrographic seizures. The latency to seizure and status epilepticus onset in Kv4.2 knockout and wild-type mice was assessed following intraperitoneal injection of kainate. Extracellular field potential recordings were performed in hippocampal slices from Kv4.2 knockout and wild-type mice following the bath application of bicuculline.
Results:
No spontaneous behavioral or electrographic seizures were observed in Kv4.2 knockout mice. Following kainate, Kv4.2 knockout mice demonstrated a decreased seizure and status epilepticus latency as well as increased mortality compared to wild-type littermates. The background strain modified the seizure susceptibility phenotype in Kv4.2 knockout mice. In response to bicuculline, slices from Kv4.2 knockout mice exhibited an increase in epileptiform bursting in area CA1 as compared to wild-type littermates.
Discussion:
These studies show that loss of Kv4.2 channels is associated with enhanced susceptibility to convulsant stimulation, supporting the concept that Kv4.2 deficiency may contribute to aberrant network excitability and regulate seizure threshold.
C1 [Anderson, Anne E.] Baylor Coll Med, Feigin Ctr 955, Dept Neurol, Houston, TX 77030 USA.
[Lugo, Joaquin N.; Lee, Wai L.; Anderson, Anne E.] Baylor Coll Med, Dept Pediat, Neurol Sect, Cain Fdn Labs, Houston, TX 77030 USA.
[Gertz, Shira J.] Baylor Coll Med, Dept Pediat, Sect Pediat Crit Care Med, Houston, TX 77030 USA.
[Anderson, Anne E.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
[Hrachovy, Richard A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
RP Anderson, AE (reprint author), Baylor Coll Med, Feigin Ctr 955, Dept Neurol, 1102 Bates St,MC 3-6365, Houston, TX 77030 USA.
EM annea@bcm.tmc.edu
FU NIH/NINDS [NS049427, NS039943, K01-NS046328, F32NS056664]; Epilepsy
Foundation Postdoctoral Fellowship; Partnership for Pediatric Research
in Epilepsy/Epilepsy Foundation; Citizens United for Research in
Epilepsy
FX Disclosures: None of the authors has any conflict of interest to
disclose.
NR 42
TC 28
Z9 29
U1 0
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUL
PY 2009
VL 50
IS 7
BP 1741
EP 1751
DI 10.1111/j.1528-1167.2009.02086.x
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 466KJ
UT WOS:000267660800008
PM 19453702
ER
PT J
AU Evans, CH
Liu, FJ
Glatt, V
Hoyland, JA
Kirker-Head, C
Walsh, A
Betz, O
Wells, JW
Betz, V
Porter, RM
Saad, FA
Gerstenfeld, LC
Einhorn, TA
Harris, MB
Vrahas, MS
AF Evans, C. H.
Liu, F. -J.
Glatt, V.
Hoyland, J. A.
Kirker-Head, C.
Walsh, A.
Betz, O.
Wells, J. W.
Betz, V.
Porter, R. M.
Saad, F. A.
Gerstenfeld, L. C.
Einhorn, T. A.
Harris, M. B.
Vrahas, M. S.
TI USE OF GENETICALLY MODIFIED MUSCLE AND FAT GRAFTS TO REPAIR DEFECTS IN
BONE AND CARTILAGE
SO EUROPEAN CELLS & MATERIALS
LA English
DT Article
DE Adenovirus; bone morphogenetic protein; large segmental defects;
cartilage repair; bone healing; gene therapy; animal models; facilitated
endogenous repair; tissue engineering; fibrodysplasia ossificans
progressiva
AB We report a novel technology for the rapid healing of large osseous and chondral defects, based upon the genetic modification of autologous skeletal muscle and fat grafts. These tissues were selected because they not only possess mesenchymal progenitor cells and scaffolding properties, but also can be biopsied, genetically modified and returned to the patient in a single operative session. First generation adenovirus vector carrying cDNA encoding human bone morphogenetic protein-2 (Ad. BMP-2) was used for gene transfer to biopsies of muscle and fat. To assess bone healing, the genetically modified ("gene activated") tissues were implanted into 5mm-long critical size, mid-diaphyseal, stabilized defects in the femora of Fischer rats. Unlike control defects, those receiving gene-activated muscle underwent rapid healing, with evidence of radiologic bridging as early as 10 days after implantation and restoration of full mechanical strength by 8 weeks. Histologic analysis suggests that the grafts rapidly differentiated into cartilage, followed by efficient endochondral ossification. Fluorescence in situ hybridization detection of Y-chromosomes following the transfer of male donor muscle into female rats demonstrated that at least some of the osteoblasts of the healed bone were derived from donor muscle. Gene activated fat also healed critical sized defects, but less quickly than muscle and with more variability. Anti-adenovirus antibodies were not detected. Pilot studies in a rabbit osteochondral defect model demonstrated the promise of this technology for healing cartilage defects. Further development of these methods should provide ways to heal bone and cartilage more expeditiously, and at lower cost, than is presently possible.
C1 [Evans, C. H.; Liu, F. -J.; Glatt, V.; Wells, J. W.; Porter, R. M.] Harvard Univ, Ctr Adv Orthopaed Studies, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Evans, C. H.; Liu, F. -J.; Betz, O.; Wells, J. W.; Betz, V.; Porter, R. M.] Harvard Univ, Brigham & Womens Hosp, Ctr Mol Orthopaed, Sch Med, Boston, MA 02115 USA.
[Hoyland, J. A.] Univ Manchester, Tissue Injury & Repair Res Grp, Manchester, Lancs, England.
[Kirker-Head, C.; Walsh, A.] Tufts Cummings Sch Vet Med, Orthopaed Res Lab, Grafton, MA USA.
[Betz, V.; Vrahas, M. S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Saad, F. A.] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
[Gerstenfeld, L. C.; Einhorn, T. A.] Boston Univ, Med Ctr, Dept Orthoped Surg, Boston, MA USA.
[Harris, M. B.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
RP Evans, CH (reprint author), Harvard Univ, Ctr Adv Orthopaed Studies, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave,RN-115, Boston, MA 02215 USA.
EM cevans@bidmc.harvard.edu
RI Liu, Fangjun/B-1012-2012; Hoyland, Judith/P-5168-2014; Wells,
James/C-7480-2011;
OI Hoyland, Judith/0000-0003-4876-5208; Wells, James/0000-0002-9618-6940;
/0000-0002-0477-1211
FU NIAMS, NIH [R01 AR 050243]; AO Foundation
FX This research was funded by NIH grant R01 AR 050243 from NIAMS (to CHE)
and the AO Foundation (to MSV and CHE). The authors thank Thomas J. Gill
III, MD, Department of Orthopaedic Surgery, Massachusetts General
Hospital, for his advice to use Fischer rats.
NR 40
TC 50
Z9 50
U1 0
U2 3
PU AO RESEARCH INSTITUTE DAVOS-ARI
PI DAVOS
PA CLAVADELERSTRASSE 8, DAVOS, CH 7270, SWITZERLAND
SN 1473-2262
J9 EUR CELLS MATER
JI Eur. Cells Mater.
PD JUL-DEC
PY 2009
VL 18
BP 96
EP 111
PG 16
WC Cell & Tissue Engineering; Engineering, Biomedical; Materials Science,
Biomaterials
SC Cell Biology; Engineering; Materials Science
GA V20CC
UT WOS:000208117100009
PM 20073015
ER
PT J
AU Muehlschlegel, JD
Perry, TE
Liu, KY
Nascimben, L
Fox, AA
Collard, CD
Avery, EG
Aranki, SF
D'Ambra, MN
Shernan, SK
Body, SC
AF Muehlschlegel, Jochen D.
Perry, Tjoervi E.
Liu, Kuang-Yu
Nascimben, Luigino
Fox, Amanda A.
Collard, Charles D.
Avery, Edwin G.
Aranki, Sary F.
D'Ambra, Michael N.
Shernan, Stanton K.
Body, Simon C.
CA CABG Genomics Investigators
TI Troponin is superior to electrocardiogram and creatinine kinase MB for
predicting clinically significant myocardial injury after coronary
artery bypass grafting
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Cardiopulmonary bypass; Electrocardiography; Surgery; Mortality;
Enzymes; Troponin
ID UNIVERSAL DEFINITION; CARDIAC-SURGERY; HEART-SURGERY; Q-WAVES;
INFARCTION; ASSAY; MULTICENTER; PERFORMANCE; MORTALITY; SURVIVAL
AB Cardiac biomarkers are routinely elevated after uncomplicated cardiac surgery to levels considered diagnostic of myocardial infarction in ambulatory populations. We investigated the diagnostic power of electrocardiogram (ECG) and cardiac biomarker criteria to predict clinically relevant myocardial injury using benchmarks of mortality and increased hospital length of stay (HLOS) in patients undergoing coronary artery bypass graft (CABG) surgery.
Perioperative ECGs, creatinine kinase MB fraction, and cardiac troponin I (cTnI) were assessed in 545 primary CABG patients. None of the ECG criteria for myocardial injury predicted mortality or HLOS. However, post-operative day (POD) 1 cTnI levels independently predicted 5-year mortality (hazard ratio = 1.42; 95% CI 1.14-1.76 for each 10 mu g/L increase; P = 0.009), while adjusting for baseline demographic characteristics and perioperative risk factors. Moreover, cTnI was the only biomarker that significantly improved the prediction of 5-year mortality estimated by the logistic Euroscore (P = 0.02). Furthermore, the predictive value of cTnI for 5-year mortality was replicated in a separately collected cohort of 1031 CABG patients using cardiac troponin T.
Electrocardiogram diagnosis of post-operative myocardial injury after CABG does not independently predict an increased risk of 5-year mortality or HLOS. Conversely, cTnI is independently associated with an increased risk of mortality and prolonged HLOS.
C1 [Muehlschlegel, Jochen D.; Perry, Tjoervi E.; Liu, Kuang-Yu; Nascimben, Luigino; Fox, Amanda A.; D'Ambra, Michael N.; Shernan, Stanton K.; Body, Simon C.] Harvard Univ, Brigham & Womens Hosp, Dept Anaesthesiol Perioperat & Pain Med, Sch Med, Boston, MA 02115 USA.
[Collard, Charles D.] St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anaesthesia, Houston, TX USA.
[Avery, Edwin G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anaesthesia & Crit Care, Div Cardiac Anaesthesia,Heart Ctr, Boston, MA USA.
[Aranki, Sary F.] Harvard Univ, Brigham & Womens Hosp, Div Cardiac Surg, Sch Med, Boston, MA 02115 USA.
RP Muehlschlegel, JD (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Anaesthesiol Perioperat & Pain Med, Sch Med, CWN L1,75 Francis St, Boston, MA 02115 USA.
EM jmuehlschlegel@partners.org
FU Bayerw Fellowship in Blood Conservation, Biosite Inc., San Diego, CA,
USA; NIH [HL-068774]; NCRR [M01 02558]; Society of Cardiovascular
Anaesthesiologists Research Starter Grant; Siemens Medical Solutions
Diagnostics, Tarrytown, NY
FX This work was supported by the Bayerw Fellowship in Blood Conservation,
Biosite Inc., San Diego, CA, USA (J.D.M.); NIH (HL-068774 to S. C. B.,
NCRR M01 02558 to C. D. C. and A. A. F.); Society of Cardiovas