FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Kulke, MH
Blaszkowsky, L
Zhu, AX
Florio, S
Regan, E
Ryan, DP
Chan, JA
AF Kulke, Matthew H.
Blaszkowsky, Lawrence
Zhu, Andrew X.
Florio, Sarah
Regan, Eileen
Ryan, David P.
Chan, Jennifer A.
TI Phase I/II Study of Everolimus (RAD001) in Combination With Temozolomide
(TMZ) in Patients With Advanced Pancreatic Neuroendocrine Tumors (NET)
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Kulke, Matthew H.; Florio, Sarah; Regan, Eileen; Chan, Jennifer A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kulke, Matthew H.; Chan, Jennifer A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Blaszkowsky, Lawrence; Zhu, Andrew X.; Ryan, David P.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD MAR
PY 2011
VL 40
IS 2
BP 328
EP 328
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 719VN
UT WOS:000287239700045
ER
PT J
AU Oberg, K
Kulke, M
Pavel, M
Phan, A
Hoosen, S
St Peter, J
Cherfi, A
Yao, JC
AF Oberg, Kjell
Kulke, Matthew
Pavel, Marianne
Phan, Alexandria
Hoosen, Sakina
St Peter, Jessica
Cherfi, Azzeddine
Yao, James C.
TI Evaluation of Chromogranin A and Neuron-Specific Enolase as Predictors
of Response to Everolimus Therapy in Patients With Advanced Pancreatic
Neuroendocrine Tumors (pNET)
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Oberg, Kjell] Uppsala Univ, Uppsala, Sweden.
[Kulke, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pavel, Marianne] Charite, D-13353 Berlin, Germany.
[Phan, Alexandria; Yao, James C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Hoosen, Sakina; St Peter, Jessica] Novartis Pharmaceut, Novartis Oncol, E Hanover, NJ 07936 USA.
[Cherfi, Azzeddine] Novartis Pharma Serv AG, Basel, Switzerland.
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 0885-3177
J9 PANCREAS
JI Pancreas
PD MAR
PY 2011
VL 40
IS 2
BP 329
EP 330
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 719VN
UT WOS:000287239700051
ER
PT J
AU Ter-Minassian, M
Wang, ZX
Asomaning, K
Wu, MC
Liu, CY
Paulus, JK
Liu, G
Bradbury, PA
Zhai, RH
Su, L
Frauenhoffer, CS
Hooshmand, SM
DeVivo, I
Lin, XH
Christiani, DC
Kulke, MH
AF Ter-Minassian, Monica
Wang, Zhaoxi
Asomaning, Kofi
Wu, Michael C.
Liu, Chen-Yu
Paulus, Jessica K.
Liu, Geoffrey
Bradbury, Penelope A.
Zhai, Rihong
Su, Li
Frauenhoffer, Christine S.
Hooshmand, Susanne M.
DeVivo, Immaculata
Lin, Xihong
Christiani, David C.
Kulke, Matthew H.
TI Genetic Associations With Sporadic Neuroendocrine Tumor Risk
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Ter-Minassian, Monica; Wang, Zhaoxi; Asomaning, Kofi; Liu, Chen-Yu; Zhai, Rihong; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA.
[Paulus, Jessica K.; DeVivo, Immaculata; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wu, Michael C.; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Liu, Geoffrey; Bradbury, Penelope A.] Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada.
[Ter-Minassian, Monica; Frauenhoffer, Christine S.; Hooshmand, Susanne M.; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD MAR
PY 2011
VL 40
IS 2
BP 333
EP 334
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 719VN
UT WOS:000287239700066
ER
PT J
AU Ter-Minassian, M
Chan, JA
Frauenhoffer, CS
Hooshmand, SM
Asomaning, K
Lin, XH
Christiani, DC
Kulke, MH
AF Ter-Minassian, Monica
Chan, Jennifer A.
Frauenhoffer, Christine S.
Hooshmand, Susanne M.
Asomaning, Kofi
Lin, Xihong
Christiani, David C.
Kulke, Matthew H.
TI Prospective Analysis of Clinical Outcomes and Prognostic Factors in
Patients With Neuroendocrine Tumors (NETs)
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Ter-Minassian, Monica; Asomaning, Kofi; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol EOME Program, Boston, MA 02115 USA.
[Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Ter-Minassian, Monica; Chan, Jennifer A.; Frauenhoffer, Christine S.; Hooshmand, Susanne M.; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD MAR
PY 2011
VL 40
IS 2
BP 334
EP 334
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 719VN
UT WOS:000287239700067
ER
PT J
AU Snarr, BS
Rowley, CP
Phan, SV
Achanti, A
Hendrix, GH
AF Snarr, Brian S.
Rowley, Christopher P.
Phan, Stephanie V.
Achanti, Anand
Hendrix, Grady H.
TI Prolonged Sinus Pauses with Hydromorphone in the Absence of Cardiac
Conduction Disease
SO SOUTHERN MEDICAL JOURNAL
LA English
DT Article
DE bradycardia; hydromorphone; opioid receptor; sinus pause; vagal response
AB A 49-year-old male had open sigmoid colectomy with colorectal anastomosis for sigmoid diverticulitis. The patient was given patient-controlled analgesia (PCA) hydromorphone and subsequently developed bradycardia with prolonged sinus pauses up to 7.1 seconds. The pauses resolved shortly after the hydromorphone was discontinued. This is the first case report to our knowledge of reversible prolonged sinus pauses associated with the use of hydromorphone. Animal studies support a role for opioid signaling at the sinoatrial (SA) node. Hydromorphone is a potential cause of prolonged sinus pauses and should be taken into consideration when monitoring a patient on hydromorphone for pain control.
C1 [Snarr, Brian S.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Snarr, BS (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, 173 Ashley Ave,Room BSB 648,POB 250508, Charleston, SC 29425 USA.
EM snarr@musc.edu
NR 7
TC 1
Z9 2
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0038-4348
J9 SOUTH MED J
JI South.Med.J.
PD MAR
PY 2011
VL 104
IS 3
BP 239
EP 240
DI 10.1097/SMJ.0b013e318206f6d3
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 722ZE
UT WOS:000287473400017
PM 21297541
ER
PT J
AU Pihlajamaki, M
O'Keefe, K
O'Brien, J
Blacker, D
Sperling, RA
AF Pihlajamaki, Maija
O'Keefe, Kelly
O'Brien, Jackie
Blacker, Deborah
Sperling, Reisa A.
TI Failure of repetition suppression and memory encoding in aging and
Alzheimer's disease
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Aging; Alzheimer's disease; Functional magnetic resonance imaging;
Medial temporal lobe; Memory; Repetition suppression
ID MILD COGNITIVE IMPAIRMENT; MEDIAL TEMPORAL-LOBE; RECOGNITION MEMORY;
HIPPOCAMPAL-FORMATION; PERIRHINAL CORTEX; NEURAL MECHANISMS;
FAMILIARITY; FMRI; TEMPOROPOLAR; ACTIVATION
AB The suppression of neural activity in the medial temporal lobe (MTL) has been suggested as a marker of successful recognition of familiarity in healthy subjects, but to be impaired in patients with Alzheimer's disease (AD). In this study, we investigated whether the ability to suppress MTL activity during repeated exposure to face-name pairs was related to the ability to successfully encode novel associations in 90 individuals ranging from healthy young and older subjects to mildly impaired elderly and AD patients. Activity in the anterior MTL during Repeated stimuli was inversely related to performance in post-scan associative recognition for the Novel face-name pairs. In a subset (n = 60) of subjects undergoing more detailed neuropsychological testing, greater MTL Repeated activity was correlated with worse word-list delayed recall performance. Failure of response suppression to familiar information may be a sensitive marker of MTL dysfunction and memory impairment in aging and prodromal AD.
C1 [Pihlajamaki, Maija] Kuopio Univ Hosp, Dept Neurol, Kuopio 70211, Finland.
[Pihlajamaki, Maija] Univ Eastern Finland, Inst Clin Med, Neurol Unit, Kuopio 70211, Finland.
[Pihlajamaki, Maija; Sperling, Reisa A.] Harvard Univ, Sch Med, Memory Disorders Unit, Dept Neurol,Brigham & Womens Hosp, Boston, MA 02115 USA.
[O'Keefe, Kelly; O'Brien, Jackie; Blacker, Deborah; Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA.
[Sperling, Reisa A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA.
RP Pihlajamaki, M (reprint author), Kuopio Univ Hosp, Dept Neurol, POB 1777, Kuopio 70211, Finland.
EM Maija.Pihlajamaki@uef.fi
FU Academy of Finland [108188, 214050]; Kuopio University Hospital EVO;
National Institute of Aging [AG027435, AG04953, AG00513421]
FX This study was supported by Academy of Finland grants # 108188 and #
214050, Kuopio University Hospital EVO grants, as well as National
Institute of Aging grants AG027435, AG04953 and AG00513421. We thank the
staff of the Massachusetts General Hospital Gerontology Research Unit
and Brigham and Women's Hospital Memory Disorders Unit Clinical Research
for assistance with subject recruitment, evaluation, and data
management, as well as Mary Foley, Larry White, and the Athinoula A.
Martinos Center staff for assistance with MRI data collection. We
express special gratitude to the subjects who participated in this
study.
NR 37
TC 8
Z9 8
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1931-7557
J9 BRAIN IMAGING BEHAV
JI Brain Imaging Behav.
PD MAR
PY 2011
VL 5
IS 1
BP 36
EP 44
DI 10.1007/s11682-010-9110-3
PG 9
WC Neuroimaging
SC Neurosciences & Neurology
GA 709TQ
UT WOS:000286464700004
PM 21161449
ER
PT J
AU Roffman, JL
Brohawn, DG
Friedman, JS
Dyckman, KA
Thakkar, KN
Agam, Y
Vangel, MG
Goff, DC
Manoach, DS
AF Roffman, Joshua L.
Brohawn, David G.
Friedman, Jesse S.
Dyckman, Kara A.
Thakkar, Katharine N.
Agam, Yigal
Vangel, Mark G.
Goff, Donald C.
Manoach, Dara S.
TI MTHFR 677C > T effects on anterior cingulate structure and function
during response monitoring in schizophrenia: a preliminary study
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Schizophrenia; Functional MRI; Genetics; Executive function; Anterior
cingulate cortex; Diffusion tensor imaging
ID METHYLENETETRAHYDROFOLATE REDUCTASE DEFICIENCY; SURFACE-BASED ANALYSIS;
WHITE-MATTER; CORTICAL SURFACE; C677T POLYMORPHISM; EXECUTIVE FUNCTION;
COORDINATE SYSTEM; GENE POLYMORPHISM; CORTEX; BRAIN
AB Patients with schizophrenia exhibit deficient response monitoring as indexed by blunted activation of the dorsal anterior cingulate cortex (dACC) and functionally related regions during error commission. This pattern may reflect heritable alterations of dACC function. We examined whether the hypofunctional 677C > T variant in MTHFR, a candidate schizophrenia risk gene, contributed to our previous findings of blunted error-related dACC activation and reduced microstructural integrity of dACC white matter. Eighteen medicated outpatients with schizophrenia underwent diffusion tensor imaging and performed an antisaccade paradigm during functional magnetic resonance imaging (fMRI). T allele carriers exhibited significantly less error-related activation than C/C patients in bilateral dACC and substantia nigra, regions that are thought to mediate dopamine-dependent error-based reinforcement learning. T carrier patients also showed significantly lower fractional anisotropy in bilateral dACC. These findings suggest that the MTHFR 677T allele blunts response monitoring in schizophrenia, presumably via effects on dopamine signaling and dACC white matter microstructural integrity.
C1 [Roffman, Joshua L.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Roffman, Joshua L.; Brohawn, David G.; Friedman, Jesse S.; Dyckman, Kara A.; Thakkar, Katharine N.; Agam, Yigal; Goff, Donald C.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Roffman, Joshua L.; Brohawn, David G.; Friedman, Jesse S.; Dyckman, Kara A.; Thakkar, Katharine N.; Agam, Yigal; Vangel, Mark G.; Goff, Donald C.; Manoach, Dara S.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Vangel, Mark G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Vangel, Mark G.; Manoach, Dara S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Roffman, JL (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 2606, Charlestown, MA 02129 USA.
EM jroffman@partners.org
OI Thakkar, Katharine/0000-0002-0026-2030
FU National Institute for Mental Health [R01 MH67720]; NARSAD; Bank of
America, Co-Trustee; Bushrod H. Campbell and Adah F. Hall Charity Fund;
Howard Hughes Medical Institute Physician Scientist Early Career Award;
Mental Illness Neuroscience Discovery (MIND) Institute [DOE
DE-FG02-99ER62764]; National Center for Research Resources [P41RR14075];
Alden Trust; Charles A. King Trust
FX This work was supported by the National Institute for Mental Health (R01
MH67720) and NARSAD Independent Investigator Award (to DSM); the Charles
A. King Trust, Bank of America, Co-Trustee and the Bushrod H. Campbell
and Adah F. Hall Charity Fund, Alden Trust, and Howard Hughes Medical
Institute Physician Scientist Early Career Award (to JLR); the Mental
Illness Neuroscience Discovery (MIND) Institute (DOE DE-FG02-99ER62764);
and the National Center for Research Resources (P41RR14075). We thank
Doug Greve for helpful discussions regarding the manuscript. None of the
authors report any conflicts of interest. In memory of Jesse Friedman.
NR 66
TC 12
Z9 13
U1 3
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1931-7557
J9 BRAIN IMAGING BEHAV
JI Brain Imaging Behav.
PD MAR
PY 2011
VL 5
IS 1
BP 65
EP 75
DI 10.1007/s11682-010-9111-2
PG 11
WC Neuroimaging
SC Neurosciences & Neurology
GA 709TQ
UT WOS:000286464700007
PM 21190096
ER
PT J
AU Favis, R
Sun, Y
van de Velde, H
Broderick, E
Levey, L
Meyers, M
Mulligan, G
Harousseau, JL
Richardson, PG
Ricci, DS
AF Favis, Reyna
Sun, Yu
van de Velde, Helgi
Broderick, Erin
Levey, Laura
Meyers, Michael
Mulligan, George
Harousseau, Jean-Luc
Richardson, Paul G.
Ricci, Deborah S.
TI Genetic variation associated with bortezomib-induced peripheral
neuropathy
SO PHARMACOGENETICS AND GENOMICS
LA English
DT Article
DE bortezomib; candidate gene association study; genetic variation;
multiple myeloma; peripheral neuropathy
ID ADVANCED MULTIPLE-MYELOMA; OF-THE-LITERATURE; NF-KAPPA-B;
PROTEIN-INTERACTION; NEUROTOXICITY; REVERSIBILITY; COMPLEX; CANCER;
DYNEIN; CELLS
AB Objective To develop a predictive genetic signature for the development of bortezomib-induced peripheral neuropathy (PN).
Methods Two thousand and sixteen single-nucleotide polymorphisms (SNPs) were genotyped in 139 samples from myeloma patients treated with bortezomib-melphalan-prednisone in the VISTA phase 3 trial. Single-marker association analysis for PN onset and time/cumulative dose to PN onset using the Cox proportional hazards model and multiple covariates was performed under additive, dominant, and recessive genotypic models, followed by correction for multiplicity. Associations were also pursued in a cohort of 212 samples from patients treated with bortezomib-dexamethasone in the IFM 2005-01 phase 3 trial.
Results In the VISTA cohort, after Bonferroni correction, two SNPs significantly associated with time to onset of PN [CTLA4 rs4553808, false discovery rate (FDR)=0.002] and time to onset of grade of at least 2 PN (PSMB1 rs1474642, FDR=0.014). Using FDR less than 0.05 as the threshold, two additional SNPs significantly associated with time to onset of grade of at least 2 (CTSS rs12568757, FDR=0.027) or grade of at least 3 PN (GJE1 rs11974610, FDR=0.041). DYNC1I1 rs916758 significantly associated (FDR=0.012) with cumulative dose to onset of grade of at least 2 PN. These associations were generally not detected in the IFM 2005-01 cohort, although CTLA4 rs4553808 showed the same trend in association with time to onset (P=0.138). In addition, in the IFM 2005-01 cohort, TCF4 rs1261134 significantly associated with onset of any neurologic event (FDR=0.048).
Conclusion Genes associated with immune function (CTLA4, CTSS), reflexive coupling within Schwann cells (GJE1), drug binding (PSMB1), and neuron function (TCF4, DYNC1I1) associated with bortezomib-induced PN in this study. Pharmacogenetics and Genomics 21:121-129 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Favis, Reyna; Sun, Yu; Broderick, Erin; Levey, Laura; Meyers, Michael; Ricci, Deborah S.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ 08869 USA.
[Mulligan, George] Millennium Pharmaceut Inc, Cambridge, MA USA.
[Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[van de Velde, Helgi] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium.
[Harousseau, Jean-Luc] Ctr Rene Gauducheau, F-44035 Nantes, France.
RP Ricci, DS (reprint author), Johnson & Johnson Pharmaceut Res & Dev, 920 Route 202, Raritan, NJ 08869 USA.
EM DRicci@its.jnj.com
FU Johnson and Johnson Pharmaceutical Research & Development, L.L.C.;
Millennium Pharmaceuticals, Inc.
FX The authors would like to acknowledge the contribution of Dr Jesus San
Miguel to the design and clinical data interpretation of the VISTA study
and Professor Herve Avet-Loiseau for providing samples from the IFM
2005-01 study for this analysis. They would like to thank Andrew Jadwin
and Eric Danzeisen for expert technical support during this study. This
study is supported by Johnson and Johnson Pharmaceutical Research &
Development, L.L.C. and Millennium Pharmaceuticals, Inc.
NR 34
TC 30
Z9 33
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1744-6872
J9 PHARMACOGENET GENOM
JI Pharmacogenet. Genomics
PD MAR
PY 2011
VL 21
IS 3
BP 121
EP 129
DI 10.1097/FPC.0b013e3283436b45
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
GA 716MB
UT WOS:000286971900003
PM 21228734
ER
PT J
AU Canavese, M
Altruda, F
Silengo, L
Castiglioni, V
Scanziani, E
Radaelli, E
AF Canavese, M.
Altruda, F.
Silengo, L.
Castiglioni, V.
Scanziani, E.
Radaelli, E.
TI Clinical, pathological and immunological features of psoriatic-like
lesions affecting keratin 14-vascular endothelial growth factor
transgenic mice
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Article
DE Angiogenesis; VEGF; Disease animal models; Psoriasis; Skin
ID T-CELLS; MAST-CELLS; SKIN; EXPRESSION; ANGIOGENESIS; PATHOGENESIS; VEGF;
IMMUNOPATHOGENESIS; INTERLEUKIN-17; INFLAMMATION
AB Up-regulation of vascular endothelial growth factor (VEGF) plays a primary role in the pathogenesis of psoriasis. Transgenic mice over-expressing VEGF under the Keratin 14 (K14) promoter develop an inflammatory skin condition with many of the pathobiological features of human psoriasis.
In this work, the development of spontaneous psoriatic-like dermatitis in K14-VEGF transgenic mice was monitored from week 6 to week 44 and skin lesions were characterized clinically (application of a clinical score system comparable to the human Psoriasis Area and Severity Index), microscopically (histopathology, leukocyte subset and neoangiogensis) and immunologically (evaluation of local and systemic cytokine/chemokine profiles).
Based on PASI score system, three progressive clinical phases were identified: mild acute (8-14 weeks of age), moderate subacute (15-21 weeks of age) and severe chronic-active (22-44 weeks of age) dermatitis. Microscopically, skin lesions consisted of progressive proliferative psoriatic-like dermatitis dominated by dermo-epidermal infiltrates of CD3-positive lymphocytes, an increased number of mast cells and neoangiogenesis. Both local and systemic up-regulation of pro-inflammatory (IL-12, TNF-alpha, IL-6, MCP-1 and IL-8) and regulatory (IL-10) cytokines/chemokines was observed, mainly during the later stages of disease development.
The results obtained in this study further confirm the central role of VEGF over-expression in the development of psoriatic-like dermatitis. Similarly to what is reported for human psoriasis, both the local and systemic immunologic profiles observed in K14-VEGF transgenic mice suggest that a combined Th1 and Th17 response may be implicated in lesion development. The identification of three progressive stages of disease, each with peculiar clinicopathological features, renders the K14-VEGF transgenic mouse a valuable model to study novel immunotherapies for psoriasis.
C1 [Canavese, M.; Altruda, F.; Silengo, L.] Univ Turin, Dept Genet Biol & Biochem, I-10124 Turin, Italy.
[Castiglioni, V.; Scanziani, E.; Radaelli, E.] Filarete Fdn, Mouse & Anim Pathol Lab, Milan, Italy.
[Castiglioni, V.; Scanziani, E.; Radaelli, E.] Univ Milan, Fac Vet Med, Dept Vet Pathol Hyg & Publ Hlth, I-20122 Milan, Italy.
RP Canavese, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 13th St Bldg 149, Charlestown, MA 01029 USA.
EM miriamcanavese@yahoo.com
FU MerckSerono International S.A.
FX This work was supported by MerckSerono International S. A. We would like
to thank Merck-Serono-RBM, Colleretto Giacosa, Torino, Italy as host
Institute. Dr. PF Zaratin as Head of Immuno-pharmacology Department, Dr.
CH Ladel, Dr. B. Greco and Dr. V. Ardissone for their scientific support
and guidance. We also thank Dr. Pamela Ferro for organizing technical
help in maintaining the line; Dr. Michele Ardizzone, Dr. Cristiano
Marozzin and Dr. Raffaella Capobianco for their help in determining
pathological diagnosis. We also thank Dr Giovanni Manarolla for the
insightful comments. This work was supported by a Research Grant from
MerckSerono International S. A. The funders supported study design, data
collection and analysis, but they had no role in the decision to publish
and preparation of the manuscript.
NR 43
TC 7
Z9 7
U1 0
U2 4
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
EI 1699-5848
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD MAR
PY 2011
VL 26
IS 3
BP 285
EP 296
PG 12
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 702UK
UT WOS:000285921200001
PM 21210341
ER
PT J
AU Crenshaw, K
Shewchuk, RM
Qu, HY
Staton, LJ
Bigby, JA
Houston, TK
Allison, J
Estrada, CA
AF Crenshaw, Katie
Shewchuk, Richard M.
Qu, Haiyan
Staton, Lisa J.
Bigby, Judy Ann
Houston, Thomas K.
Allison, Jeroan
Estrada, Carlos A.
TI What Should We Include in a Cultural Competence Curriculum? An Emerging
Formative Evaluation Process to Foster Curriculum Development
SO ACADEMIC MEDICINE
LA English
DT Article
ID NOMINAL GROUP TECHNIQUE; WARD-ATTENDING ROUNDS; MEDICAL-EDUCATION;
HEALTH-CARE; PERSPECTIVES; JUDGMENTS; TOOL; PERCEPTIONS; ATTRIBUTES;
FACULTY
AB Purpose
To identify, prioritize, and organize components of a cultural competence curriculum to address disparities in cardiovascular disease.
Method
In 2006, four separate nominal group technique sessions were conducted with medical students, residents, community physicians, and academic physicians to generate and prioritize a list of concepts (i.e., ideas) to include in a curriculum. Afterward, 45 educators and researchers organized and prioritized the concepts using a card-sorting exercise. Multidimensional scaling (MDS) and hierarchical cluster analysis produced homogeneous groupings of related concepts and generated a cognitive map. The main outcome measures were the number of cultural competence concepts, their relative ranks, and the cognitive map.
Results
Thirty participants generated 61 concepts; 29 were identified by at least two participants. The cognitive map organized concepts into four clusters, interpreted as (1) patient's cultural background (e.g., information on cultures, habits, values), (2) provider and health care (e.g., clinical skills, awareness of one's bias, patient centeredness, professionalism), communication skills (e.g., history, stereotype avoidance, health disparities epidemiology), (3) cross-culture (e.g., idiomatic expressions, examples of effective communication), and (4) resources to manage cultural diversity (e.g., translator guides, instructions, community resources). The MDS two-dimensional solution demonstrated a good fit (stress = 0.07; R(2) = 0.97).
Conclusions
A novel, combined approach allowed stakeholders' inputs to identify and cognitively organize critical domains used to guide development of a cultural competence curriculum. Educators may use this approach to develop and organize educational content for their target audiences, especially in ill-defined areas like cultural competence.
C1 [Estrada, Carlos A.] Univ Alabama, Div Gen Internal Med, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, REAP Ctr Surg Med Acute Care Res & Transit, Deep S Ctr Effectiveness, Birmingham, AL USA.
[Estrada, Carlos A.] Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA.
[Crenshaw, Katie] Univ Alabama, Div Continuing Med Educ, Birmingham, AL USA.
[Shewchuk, Richard M.; Qu, Haiyan] Univ Alabama, Sch Hlth Related Profess, Hlth Serv Adm, Birmingham, AL USA.
[Staton, Lisa J.] Univ Tennessee, Coll Med Chattanooga, Chattanooga, TN USA.
[Staton, Lisa J.] Dept Internal Med, Chattanooga, TN USA.
[Bigby, Judy Ann] Commonwealth Massachusetts, Execut Off Hlth & Human Serv, Hlth & Human Serv, Boston, MA USA.
[Houston, Thomas K.] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Houston, Thomas K.] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Worcester, MA USA.
[Allison, Jeroan] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
RP Estrada, CA (reprint author), Univ Alabama, Div Gen Internal Med, Birmingham Vet Affairs Med Ctr, 732 Fac Off Tower,510 20th St S, Birmingham, AL USA.
EM cestrada@uab.edu
RI liu, jing/D-9482-2012; Houston, Thomas/F-2469-2013;
OI Allison, Jeroan/0000-0003-4472-2112
FU National Heart, Lung, and Blood Institute as part of the National
Consortium for Multicultural Education for Health Professionals [K07
HL081373-01]
FX This study was funded by a National Heart, Lung, and Blood Institute
(K07 HL081373-01) grant to Dr. Estrada as part of the National
Consortium for Multicultural Education for Health Professionals. The
funding source did not make any restrictions on the scope or reporting
of the study.
NR 46
TC 24
Z9 24
U1 5
U2 21
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 MAR
PY 2011
VL 86
IS 3
BP 333
EP 341
DI 10.1097/ACM.0b013e3182087314
PG 9
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 726AZ
UT WOS:000287690700021
PM 21248602
ER
PT J
AU Huddle, TS
AF Huddle, Thomas S.
TI Perspective: Medical Professionalism and Medical Education Should Not
Involve Commitments to Political Advocacy
SO ACADEMIC MEDICINE
LA English
DT Article
ID US PHYSICIANS; SCHOLARSHIP; IGNORANCE
AB It is increasingly suggested that political advocacy is a core professional responsibility for physicians. The author argues that this is an error. Advocacy on behalf of societal goals, even those goals as unexceptionable as the betterment of human health, is inevitably political. Claims that political advocacy are a professional responsibility are mistaken, the author argues, because (1) civic virtues are outside the professional realm, (2) even if civic virtues were professionally obligatory, it is unclear that civic participation is necessary for such virtue, and (3) the profession of medicine ought not to require any particular political stance of its members. Claims that academic health centers should systematically foster advocacy are also deeply problematic. Although advocacy may coexist alongside the core university activities of research and education, insofar as it infects those activities, advocacy is likely to subvert them, as advocacy seeks change rather than knowledge. And official efforts on behalf of advocacy will undermine university aspirations to objectivity and neutrality. American society has conferred remarkable success and prosperity on its medical profession. Physicians are deserving of such success only insofar as they succeed in offering society excellence and dedication in professional work. Mandatory professional advocacy must displace such work but cannot substitute for it. The medical profession should steadfastly resist attempts to add advocacy to its essential professional commitments.
C1 [Huddle, Thomas S.] UAB Sch Med, Div Gen Internal Med, Dept Med, Birmingham, AL 35294 USA.
[Huddle, Thomas S.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA.
RP Huddle, TS (reprint author), UAB Sch Med, Div Gen Internal Med, Dept Med, 1530 3rd Ave S,FOT 720, Birmingham, AL 35294 USA.
EM thuddle@uab.edu
RI liu, jing/D-9482-2012
NR 22
TC 33
Z9 33
U1 1
U2 6
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 MAR
PY 2011
VL 86
IS 3
BP 378
EP 383
DI 10.1097/ACM.0b013e3182086efe
PG 6
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 726AZ
UT WOS:000287690700028
PM 21248605
ER
PT J
AU Cai, WL
Lee, EY
Vij, A
Mahmood, SA
Yoshida, H
AF Cai, Wenli
Lee, Edward Y.
Vij, Abhinav
Mahmood, Soran A.
Yoshida, Hiroyuki
TI MDCT for Computerized Volumetry of Pneumothoraces in Pediatric Patients
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Computerized volumetry method; multidetector computed tomography (MDCT);
pneumothorax; quantification of pneumothorax; pediatric patients
ID BLUNT CHEST TRAUMA; SEVERELY INJURED PATIENTS; TUBE THORACOSTOMY; OCCULT
PNEUMOTHORACES; TOMOGRAPHY; COMPLICATIONS; MANAGEMENT; CT; AGREEMENT;
SIZE
AB Rationale and Objectives: Our purpose in this study was to develop an automated computer-aided volumetry (CAV) scheme for quantifying pneumothorax in multidetector computed tomography (MDCT) images for pediatric patients and to investigate the imaging parameters that may affect its accuracy.
Materials and Methods: Fifty-eight consecutive pediatric patients (mean age 12 6 years) with pneumothorax who underwent MDCT for evaluation were collected retrospectively for this study. All cases were imaged by a 16-or 64-MDCT scanner with weight-based kilovoltage, low-dose tube current, 1.0-1.5 pitch, 0.6-5.0 mm slice thickness, and a B70f (sharp) or B31f (soft) reconstruction kernel. Sixty-three pneumothoraces >= 1 mL were visually identified in the left (n = 30) and right (n = 33) lungs. Each identified pneumothorax was contoured manually on an Amira workstation V4.1.1 (Mercury Computer Systems, Chelmsford, MA) by two radiologists in consensus. The computerized volumes of the pneumothoraces were determined by application of our CAV scheme. The accuracy of our automated CAV scheme was evaluated by comparison between computerized volumetry and manual volumetry, for the total volume of pneumothoraces in the left and right lungs.
Results: The mean difference between the computerized volumetry and the manual volumetry for all 63 pneumothoraces >= 1 mL was 8.2%. For pneumothoraces >= 10 mL, >= 50 mL, and >= 200 mL, the mean differences were 7.7% (n = 57), 7.3% (n = 33), and 6.4% (n = 13), respectively. The correlation coefficient was 0.99 between the computerized volume and the manual volume of pneumothoraces. Bland-Altman analysis showed that computerized volumetry has a mean difference of -5.1% compared to manual volumetry. For all pneumothoraces >= 10 mL, the mean differences for slice thickness <= 1.25 mm, = 1.5 mm, and = 5.0 mm were 6.1% (n = 28), 3.5% (n = 10), and 12.2% (n = 19), respectively. For the two reconstruction kernels, B70f and B31f, the mean differences were 6.3% (n = 42, B70f) and 11.7% (n = 15, B31f11, respectively.
Conclusion: Our automated CAV scheme provides an accurate measurement of pneumothorax volume in MDCT images of pediatric patients. For accurate volumetric quantification of pneumothorax in children in MDCT images by use of the automated CAV scheme, we recommended reconstruction parameters based on a slice thickness <= 1.5 mm and the reconstruction kernel B70f.
C1 [Cai, Wenli; Vij, Abhinav; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Cai, Wenli; Vij, Abhinav; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Lee, Edward Y.; Mahmood, Soran A.] Childrens Hosp Boston, Dept Radiol, Boston, MA 02115 USA.
[Lee, Edward Y.; Mahmood, Soran A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,400C, Boston, MA 02114 USA.
EM Cai.Wenli@mgh.harvard.edu
FU Harvard Clinical and Translational Science Center, from the National
Center for Research Resources [1 UL1 RR025758-01]
FX From the Department of Radiology, Massachusetts General Hospital and
Harvard Medical School, 25 New Chardon Street, 400C, Boston, MA 02114
(W.C., A.V., H.Y.); Department of Radiology, Children's Hospital Boston
and Harvard Medical School, 300 Longwood Ave, Boston, MA 02115 S.A.M).
Received August 10, 2010; accepted November 1, 201(). This research was
conducted with the support of Grant Number 1 UL1 RR025758-01, Harvard
Clinical and Translational Science Center, from the National Center for
Research Resources. Address correspondence to: W.C. e-mail:
Cai.Wenli@mgh.harvard.edu
NR 26
TC 6
Z9 7
U1 0
U2 1
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 MAR
PY 2011
VL 18
IS 3
BP 315
EP 323
DI 10.1016/j.acra.2010.11.008
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 725BR
UT WOS:000287620700008
PM 21216160
ER
PT J
AU Feuchtner, GM
Spoeck, A
Lessick, J
Dichtl, W
Plass, A
Leschka, S
Mueller, S
Klauser, A
Scheffel, H
Wolf, F
Jaschke, W
Alkadhi, H
AF Feuchtner, Gudrun M.
Spoeck, Alexander
Lessick, Jonathan
Dichtl, Wolfgang
Plass, Andre
Leschka, Sebastian
Mueller, Silvana
Klauser, Andrea
Scheffel, Hans
Wolf, Florian
Jaschke, Werner
Alkadhi, Hatem
TI Quantification of Aortic Regurgitant Fraction and Volume with
Multi-detector Computed Tomography: Comparison with Echocardiography
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Multislice computed tomography; aortic regurgitation; automated 3-D
volume segmentation; aortic regurgitant volume
ID CORONARY-ARTERY-DISEASE; LEFT-VENTRICULAR FUNCTION;
CARDIOVASCULAR-MAGNETIC-RESONANCE; DIAGNOSTIC PERFORMANCE;
VALVE-REPLACEMENT; GLOBAL LEFT; ANGIOGRAPHY; CT; CARDIOLOGY; COMMITTEE
AB Rationale and Objectives: Evaluate quantification of the aortic regurgitant fraction and volume with computed tomography (CT).
Materials and Methods: Fifty-three patients with aortic regurgitation (AR) and 29 controls were examined with 64-multi-detector CT coronary angiography and transthoracic echocardiography CITE). A dedicated software algorithm employing three-dimensional segmentation of left ventricle (LV) and right ventricle (RV) volumes and LV mass was applied. AR volume and fraction was calculated based on RV and LV stroke volumes (SV) and compared with echocardiography. The aortic regurgitant orifice area (ROA) was measured by CT.
Results: A good correlation of the AR fraction and AR volume determined by CT compared to echocardiography was found for mild, moderate, and severe AR with 14.2% +/- 9, 28.8% +/- 8, and 57.9% +/- 9 (r = 0.95, P < .001) for AR fraction, and 15.7 mL +/- 11.33 mL +/- 14, and 98.9 mL +/- 36 for AR volume (r = 0.92, P < .0001), respectively. CT correctly classified severity of AR in 93% of patients based of AR-fraction, and in 89% based on AR volume. The sensitivity and specificity of CT were 98% and specificity 90.3%. The specificity improved to 97%, if the ROA by CT was added as diagnostic criterion.
Conclusion: Aortic regurgitation fraction and volume can be accurately quantified from CT coronary angiography datasets. These parameters can assist clinical management, e.g. in case of pending cardiac surgery decision.
C1 [Feuchtner, Gudrun M.; Spoeck, Alexander; Klauser, Andrea] Innsbruck Med Univ, Dept Radiol 2, A-6020 Innsbruck, Austria.
[Dichtl, Wolfgang; Mueller, Silvana; Jaschke, Werner] Innsbruck Med Univ, Dept Cardiol, A-6020 Innsbruck, Austria.
[Feuchtner, Gudrun M.; Leschka, Sebastian; Scheffel, Hans; Alkadhi, Hatem] Univ Zurich Hosp, Inst Diagnost Radiol, Zurich, Switzerland.
[Lessick, Jonathan] Rambam Med Ctr, Dept Cardiol, Haifa, Israel.
[Plass, Andre] Univ Zurich Hosp, Cardiovasc Surg Clin, Zurich, Switzerland.
[Wolf, Florian] Vienna Med Univ, Dept Radiol, Vienna, Austria.
[Jaschke, Werner; Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR CT PET Program, Boston, MA 02114 USA.
RP Feuchtner, GM (reprint author), Innsbruck Med Univ, Dept Radiol 2, Anichstr 35, A-6020 Innsbruck, Austria.
EM Gudrun.Feuchtner@i-med.ac.at
OI Dichtl, Wolfgang/0000-0002-0421-2110; Lessick,
Jonathan/0000-0003-4430-712X
FU Philips Medical Systems
FX From the Departments of Radiology II (G.M.F., A.S., AK.) and Cardiology
(W.D., S.M., W.J), Innsbruck Medical University, Anichstrasse 35, A-6020
Innsbruck, Austria; Institute of Diagnostic Radiology, University
Hospital Zurich, Switzerland (G.M.F., S.L., H.S., HA.); Rambam Medical
Center, Department of Cardiology, Haifa, Israel (J.L.); Clinic for
Cardiovascular Surgery, University Hospital Zurich, Switzerland (A.P.);
Department of Radiology, Vienna Medical University, Vienna, Austria
(F.W.); Cardiac MR/CT/PET Program, Massachusetts General Hospital,
Boston, MA (H.A., W.J). Received September 20, 2010; accepted November
3, 2010. J. Lessick receives salary support from Philips Medical
Systems. Address correspondence to: G.M.F. e-mail:
Gudrun.Feuchtner@i-med.ac.at
NR 37
TC 7
Z9 7
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD MAR
PY 2011
VL 18
IS 3
BP 334
EP 342
DI 10.1016/j.acra.2010.11.006
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 725BR
UT WOS:000287620700010
PM 21295735
ER
PT J
AU Deng, XM
Yang, QK
Kwiatkowski, N
Sim, T
McDermott, U
Settleman, JE
Lee, JD
Gray, NS
AF Deng, Xianming
Yang, Qingkai
Kwiatkowski, Nicholas
Sim, Taebo
McDermott, Ultan
Settleman, Jeffrey E.
Lee, Jiing-Dwan
Gray, Nathanael S.
TI Discovery of a benzo[e]pyrimido-[5,4-b][1,4]diazepin-6(11H)-one as a
Potent and Selective Inhibitor of Big MAP Kinase 1
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE MAPK; BMK1; ERK5
ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION; IN-VIVO; PATHWAY;
EXPRESSION; CANCER; POLO-LIKE-KINASE-1; IDENTIFICATION; BI-2536; CELLS
AB Kinome-wide selectivity profiling of a collection of 2-amino-pyrido[2,3-d]pyrimidines followed by cellular structure activity relationship-guided optimization resulted in the identification of moderately potent and selective inhibitors of BMK1/ERK5 exemplified by 11, 18, and 21. For example, 11 possesses a dissociation constant (K(d)) for BMK1 of 19 nM, a cellular IC(50) for inhibiting epidermal growth factor induced BMK1 autophosphorylation of 0.19 +/- 0.04 mu M, and an Ambit KINOMEscan selectivity score (Ss) of 0.035. Inhibitors 18 and I 21 are also potent BMK1 inhibitors and possess favorable pharmacokinetic properties which enable their use as pharmacological probes of BMK1-dependent phenomena as well as starting points for further optimization efforts.
C1 [Deng, Xianming; Kwiatkowski, Nicholas; Sim, Taebo; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Yang, Qingkai; Lee, Jiing-Dwan] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Deng, Xianming; Kwiatkowski, Nicholas; Sim, Taebo; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[McDermott, Ultan; Settleman, Jeffrey E.] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA.
[McDermott, Ultan; Settleman, Jeffrey E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA.
EM jdlee@scripps.edu; Nathanael_Gray@dfci.harvard.edu
OI Yang, Qingkai/0000-0001-6628-5393; McDermott, Ultan/0000-0001-9032-4700
FU NIH [P41 GM079575-03, CA079871, CA114059]; University of California
[19XT-0084]; Sanger Research Centre
FX This work was supported by NIH Grant P41 GM079575-03 (N.S.G.), NIH
Grants CA079871 and CA114059 (J.-D.L.), funds from the Tobacco-Related
Disease, Research Program of the University of California, 19XT-0084
(J.-D.L.), and the Sanger Research Centre (U.M.).
NR 21
TC 22
Z9 22
U1 1
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD MAR
PY 2011
VL 2
IS 3
BP 195
EP 200
DI 10.1021/ml100304b
PG 6
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 735GN
UT WOS:000288401500002
ER
PT J
AU Medina, JL
Vujanovic, AA
Smits, JAJ
Irons, JG
Zvolensky, MJ
Bonn-Miller, MO
AF Medina, Johnna L.
Vujanovic, Anka A.
Smits, Jasper A. J.
Irons, Jessica G.
Zvolensky, Michael J.
Bonn-Miller, Marcel O.
TI Exercise and coping-oriented alcohol use among a trauma-exposed sample
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Trauma; Exercise; Alcohol; Coping; Anxiety
ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ASSAULT SURVIVORS; ANXIETY
SENSITIVITY; PHYSICAL-ACTIVITY; AEROBIC EXERCISE; USE MOTIVES; DRINKING;
ABUSE; PTSD; INTERVENTIONS
AB The present investigation examined the relation between exercise intensity and alcohol use coping motives among trauma-exposed adults. Participants were 114 adults (58 women; M(age) = 22.31 years, SD = 8.89) who reported exposure to at least one traumatic event (American Psychiatric Association, 2000) and alcohol use in the past 30 days. Partially consistent with expectation, engagement in vigorous-intensity activities (>= 6 resting metabolic rate [MET] score) demonstrated a significant, incremental (negative) association with alcohol use coping motives. This incremental association was observed after accounting for current alcohol consumption, non-criterion alcohol use motives, anxiety sensitivity, posttraumatic stress symptom severity, as well as engagement in light- and moderate-intensity activities (<6 resting MET score). Results are discussed in terms of better understanding the association between vigorous-intensity aerobic exercise and coping-oriented alcohol use among trauma-exposed individuals. Published by Elsevier Ltd.
C1 [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk Div 152, Menlo Pk, CA 94025 USA.
[Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA.
[Vujanovic, Anka A.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA.
[Vujanovic, Anka A.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Smits, Jasper A. J.] So Methodist Univ, Dept Psychol, Dallas, TX 75275 USA.
[Irons, Jessica G.] James Madison Univ, Dept Psychol, Harrisonburg, VA USA.
[Zvolensky, Michael J.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA.
RP Bonn-Miller, MO (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk Div 152, 795 Willow Rd, Menlo Pk, CA 94025 USA.
EM Marcel.Bonn-Miller@va.gov
RI Smits, Jasper/A-4350-2008;
OI Smits, Jasper/0000-0001-7128-9807; Smits, Jasper/0000-0003-1633-9693
FU Veterans Affairs (VA) Clinical Science Research and Development (CSRD);
National Institute on Drug Abuse (NIDA) [1 R01 DA027533, 1 R03
DA016566-01A2]
FX This work was supported, in part, by a Veterans Affairs (VA) Clinical
Science Research and Development (CSR&D) Career Development Award - 2,
granted to Dr. Bonn-Miller. This work was also supported by the National
Institute on Drug Abuse (NIDA) research grants (1 R01 DA027533 and 1 R03
DA016566-01A2) awarded to Dr. Zvolensky and by the NIDA research grant
R01DA027533 awarded to Dr. Smits. Neither VA nor NIDA had a role in the
study design, collection, analysis or interpretation of the data,
writing the manuscript, or the decision to submit the paper for
publication. The views expressed here are those of the authors and do
not necessarily represent those of the Department of Veterans Affairs.
NR 38
TC 8
Z9 8
U1 0
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD MAR
PY 2011
VL 36
IS 3
BP 274
EP 277
DI 10.1016/j.addbeh.2010.11.008
PG 4
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 722GD
UT WOS:000287419200020
PM 21111538
ER
PT J
AU Bergwitz, C
Juppner, H
AF Bergwitz, Clemens
Jueppner, Harald
TI Phosphate Sensing
SO ADVANCES IN CHRONIC KIDNEY DISEASE
LA English
DT Article
DE Human phosphate homeostasis; Bacterial phosphate sensor; Yeast phosphate
sensor; Metazoan phosphate sensor
ID PARATHYROID-HORMONE SECRETION; CHRONIC KIDNEY-DISEASE; FAMILIAL TUMORAL
CALCINOSIS; MESSENGER-RIBONUCLEIC-ACID; FRIZZLED-RELATED PROTEIN-4;
FIBROBLAST-GROWTH-FACTOR; CELL-LINE ST2; SACCHAROMYCES-CEREVISIAE;
INORGANIC-PHOSPHATE; VITAMIN-D
AB Human phosphate homeostasis is regulated at the level of intestinal absorption of phosphate from the diet, release of phosphate through bone resorption, and renal phosphate excretion, and involves the actions of parathyroid hormone, 1,25-dihydroxy-vitamin D, and fibroblast growth factor 23 to maintain circulating phosphate levels within a narrow normal range, which is essential for numerous cellular functions, for the growth of tissues and for bone mineralization. Prokaryotic and single cellular eukaryotic organisms such as bacteria and yeast "sense" ambient phosphate with a multi-protein complex located in their plasma membrane, which modulates the expression of genes important for phosphate uptake and metabolism (pho pathway). Database searches based on amino acid sequence conservation alone have been unable to identify metazoan orthologs of the bacterial and yeast phosphate sensors. Thus, little is known about how human and other metazoan cells sense inorganic phosphate to regulate the effects of phosphate on cell metabolism ("metabolic" sensing) or to regulate the levels of extracellular phosphate through feedback system(s) ("endocrine" sensing). Whether the "metabolic" and the "endocrine" sensor use the same or different signal transduction cascades is unknown. This article will review the bacterial and yeast phosphate sensors, and then discuss what is currently known about the metabolic and endocrine effects of phosphate in multicellular organisms and human beings. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved.
C1 [Bergwitz, Clemens] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA.
RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA.
EM cbergwitz@partners.org
FU NIDDK NIH HHS [K08 DK078361, K08 DK078361-04, R03 DK089127]
NR 166
TC 33
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U1 0
U2 25
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1548-5595
J9 ADV CHRONIC KIDNEY D
JI Adv. Chronic Kidney Dis.
PD MAR
PY 2011
VL 18
IS 2
BP 132
EP 144
DI 10.1053/j.ackd.2011.01.004
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA 741BW
UT WOS:000288839100012
PM 21406298
ER
PT J
AU Hanlon, JT
Sloane, RJ
Pieper, CF
Schmader, KE
AF Hanlon, Joseph T.
Sloane, Richard J.
Pieper, Carl F.
Schmader, Kenneth E.
TI Association of adverse drug reactions with drug-drug and drug-disease
interactions in frail older outpatients
SO AGE AND AGEING
LA English
DT Article
ID MEDICATION; APPROPRIATENESS; MANAGEMENT; EVENTS; ADULTS
C1 [Hanlon, Joseph T.] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Sloane, Richard J.; Pieper, Carl F.; Schmader, Kenneth E.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC USA.
[Pieper, Carl F.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA.
[Schmader, Kenneth E.] Duke Univ, Med Ctr, Dept Geriatr Med, Durham, NC USA.
[Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA.
RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Kaufman Med Bldg Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM jth14@pitt.edu
FU National Institutes of Health [R01-AG-15432]; Veterans Affairs
Cooperative Study Program 006; National Institute of Aging [P30AG024827,
T32 AG021885, 3U01 AG012553 K07AG033174, R01AG034056, 2R56AG027017];
National Institute of Mental Health [R34 MH082682]; National Institute
of Nursing Research [R01 NR010135]; Agency for Healthcare Research and
Quality [R01 HS017695, R01HS018721]; VA Health Services Research
[IIR-06-062]
FX This study was not funded by outside sources. The original GEM Drug
Study [8] was supported by the National Institutes of Health
[R01-AG-15432] and the Veterans Affairs Cooperative Study Program 006.
J.T.H. was supported by the following: National Institute of Aging
grants (P30AG024827, T32 AG021885, 3U01 AG012553 K07AG033174,
R01AG034056, 2R56AG027017), a National Institute of Mental Health grant
(R34 MH082682), a National Institute of Nursing Research grant (R01
NR010135), an Agency for Healthcare Research and Quality grants (R01
HS017695 and R01HS018721) and a VA Health Services Research grant
(IIR-06-062).
NR 16
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U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
J9 AGE AGEING
JI Age Ageing
PD MAR
PY 2011
VL 40
IS 2
BP 274
EP 277
DI 10.1093/ageing/afq158
PG 4
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 723DA
UT WOS:000287485200025
PM 21177281
ER
PT J
AU Hardy, H
Kumar, V
Doros, G
Farmer, E
Drainoni, ML
Rybin, D
Myung, D
Jackson, J
Backman, E
Stanic, A
Skolnik, PR
AF Hardy, Helene
Kumar, Vikram
Doros, Gheorghe
Farmer, Eric
Drainoni, Mari-Lynn
Rybin, Denis
Myung, Dan
Jackson, Jonathan
Backman, Elke
Stanic, Anela
Skolnik, Paul R.
TI Randomized Controlled Trial of a Personalized Cellular Phone Reminder
System to Enhance Adherence to Antiretroviral Therapy
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID IMPROVE ADHERENCE; MESSAGING SYSTEM; OUTCOMES; INTERVENTION; INFECTION;
FAILURE; SUPPORT; PATIENT; HEALTH; ADULTS
AB Adherence to antiretroviral therapy (ART) represents one of the strongest predictors of progression to AIDS, yet it is difficult for most patients to sustain high levels of adherence. This study compares the efficacy of a personalized cell phone reminder system (ARemind) in enhancing adherence to ART versus a beeper. Twenty-three HIV-infected subjects on ART with self-reported adherence less than 85% were randomized to a cellular phone (CP) or beeper (BP). CP subjects received personalized text messages daily; in contrast, BP subjects received a reminder beep at the time of dosing. Interviews were scheduled at weeks 3 and 6. Adherence to ART was measured by self-report (SR, 7-day recall), pill count (PC, past 30 days at baseline, then past 3 weeks), Medication Event Monitoring System (MEMS; cumulatively at 3 and 6 weeks), and via a composite adherence score constructed by combining MEMS, pill count, and self report. A mixed effects model adjusting for baseline adherence was used to compare adherence rates between the intervention groups at 3 and 6 weeks. Nineteen subjects completed all visits, 10 men and 9 females. The mean age was 42.7 +/- 6.5 years, 37% of subjects were Caucasian and 89% acquired HIV heterosexually. The average adherence to ART was 79% by SR and 65% by PC at baseline in both arms; over 6 weeks adherence increased and remained significantly higher in the ARemind group using multiple measures of adherence. A larger and longer prospective study is needed to confirm these findings and to better understand optimal reminder messages and user fatigue.
C1 [Hardy, Helene; Backman, Elke; Stanic, Anela; Skolnik, Paul R.] Boston Univ, Med Ctr, Ctr HIV AIDS Care & Res, Boston, MA USA.
[Kumar, Vikram; Myung, Dan; Jackson, Jonathan] Dimagi, Cambridge, MA USA.
[Doros, Gheorghe; Rybin, Denis] Boston Univ, Biostat Consulting Grp, Boston, MA 02215 USA.
[Farmer, Eric] Dept Pharm, LifeCare Program Clarian Hlth, Indianapolis, IN USA.
[Drainoni, Mari-Lynn] Boston Univ, Sch Publ Hlth, Ctr Hlth Qual Outcomes & Econ Res, Dept Hlth Policy & Management, Boston, MA USA.
[Backman, Elke] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA.
RP Hardy, H (reprint author), Bristol Myers Squibb Co, US Pharmaceut Med Affairs Virol Res & Dev, 777 Scudders Mill Rd, Plainsboro, NJ 08536 USA.
EM hhardy34@gmail.com
RI Emchi, Karma/Q-1952-2016;
OI Rybin, Denis/0000-0002-3657-4829
FU National Institute of Mental Health [1R43MH080655-01A1]
FX The authors want to thank the patients who participated to this research
project, Verizon Wireless for generously providing the cellular phones
utilized by the patients during this study, the National Institute of
Mental Health who provided the funding for the SBIR (1R43MH080655-01A1)
NR 26
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U1 0
U2 8
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 MAR
PY 2011
VL 25
IS 3
BP 153
EP 161
DI 10.1089/apc.2010.0006
PG 9
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 730VI
UT WOS:000288062800004
PM 21323532
ER
PT J
AU Kelly, JF
Stout, RL
Magill, M
Tonigan, JS
Pagano, ME
AF Kelly, John F.
Stout, Robert L.
Magill, Molly
Tonigan, J. Scott
Pagano, Maria E.
TI Spirituality in Recovery: A Lagged Mediational Analysis of Alcoholics
Anonymous' Principal Theoretical Mechanism of Behavior Change
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcoholics Anonymous; Spirituality; Self-Help Groups; Alcoholism;
Alcohol Dependence
ID SELF-HELP GROUPS; SUBSTANCE-ABUSE PATIENTS; PROJECT MATCH; 12-STEP
INVOLVEMENT; ADDICTION TREATMENT; DRINKING OUTCOMES; SOCIAL NETWORKS;
REDUCE DEMAND; HEALTH; PROGRAMS
AB Background: Evidence indicates Alcoholics Anonymous (AA) can play a valuable role in recovery from alcohol use disorder. While AA itself purports it aids recovery through "spiritual" practices and beliefs, this claim remains contentious and has been only rarely formally investigated. Using a lagged, mediational analysis, with a large, clinical sample of adults with alcohol use disorder, this study examined the relationships among AA, spirituality/religiousness, and alcohol use, and tested whether the observed relation between AA and better alcohol outcomes can be explained by spiritual changes.
Method: Adults (N = 1,726) participating in a randomized controlled trial of psychosocial treatments for alcohol use disorder (Project MATCH) were assessed at treatment intake, and 3, 6, 9, 12, and 15 months on their AA attendance, spiritual/religious practices, and alcohol use outcomes using validated measures. General linear modeling (GLM) and controlled lagged mediational analyses were utilized to test for mediational effects.
Results: Controlling for a variety of confounding variables, attending AA was associated with increases in spiritual practices, especially for those initially low on this measure at treatment intake. Results revealed AA was also consistently associated with better subsequent alcohol outcomes, which was partially mediated by increases in spirituality. This mediational effect was demonstrated across both outpatient and aftercare samples and both alcohol outcomes (proportion of abstinent days; drinks per drinking day).
Conclusions: Findings suggest that AA leads to better alcohol use outcomes, in part, by enhancing individuals' spiritual practices and provides support for AA's own emphasis on increasing spiritual practices to facilitate recovery from alcohol use disorder.
C1 [Kelly, John F.] Massachusetts Gen Hosp, Ctr Addict Med, Dept Psychiat, Boston, MA 02114 USA.
[Kelly, John F.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Stout, Robert L.] Decis Sci Inst PIRE, Providence, RI USA.
[Magill, Molly] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[Tonigan, J. Scott] Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM USA.
[Pagano, Maria E.] Case Western Reserve Univ, Sch Med, Dept Psychiat, WO Walker Ctr,Div Child Psychiat, Cleveland, OH 44106 USA.
RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, Dept Psychiat, 60 Staniford St,Suite 120, Boston, MA 02114 USA.
EM jkelly11@partners.org
FU US National Institute on Alcohol Abuse and Alcoholism [R21 AA016762]
FX This research was supported by a grant from the US National Institute on
Alcohol Abuse and Alcoholism (R21 AA016762; Mechanisms and Moderators of
Behavior Change in Alcoholics Anonymous).
NR 77
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U1 5
U2 26
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD MAR
PY 2011
VL 35
IS 3
BP 454
EP 463
DI 10.1111/j.1530-0277.2010.01362.x
PG 10
WC Substance Abuse
SC Substance Abuse
GA 731XF
UT WOS:000288143100009
PM 21158876
ER
PT J
AU Harrington, MB
Kraft, M
Grande, LJ
Rudolph, JL
AF Harrington, Mary Beth
Kraft, Malissa
Grande, Laura J.
Rudolph, James L.
TI INDEPENDENT ASSOCIATION BETWEEN PREOPERATIVE COGNITIVE STATUS AND
DISCHARGE LOCATION AFTER CARDIAC SURGERY
SO AMERICAN JOURNAL OF CRITICAL CARE
LA English
DT Article
ID CORONARY-ARTERY-BYPASS; CLOCK DRAWING TEST; GRAFT-SURGERY;
ALZHEIMERS-DISEASE; EXECUTIVE FUNCTION; RANDOMIZED TRIAL; IMPAIRMENT;
DELIRIUM; OUTCOMES; INTERVENTION
AB Background Among cardiac surgery patients, those with impaired cognitive status before surgery may have longer postoperative stays than do patients with normal status and may require additional care upon discharge.
Objectives To determine if preoperative scores on a screening measure for cognitive status (the Clock-in-the-Box), were associated with postoperative length of stay and discharge to a location other than home in patients who had cardiac surgery.
Methods A total of 181 consecutive patients scheduled for cardiac surgery at a single site were administered the Clock-in-the-Box as part of the preoperative evaluation. Scores on the Clock-in-the-Box tool, demographic and operative information, postoperative length of stay, and discharge location were collected retrospectively from medical records.
Results The mean age of the patients was 68.1 years (SD, 0.7), and 99% were men. Mean postoperative length of stay was 10.5 days (SD, 8.2), and 35 patients (19%) were discharged to a facility. Scores on the Clock-in-the-Box assessment were not associated with postoperative length of stay. Increasing age, living alone before surgery, and duration of cardiopulmonary bypass were associated with discharge to a facility and were used as covariates in adjusted analyses. After adjustment, better preoperative cognitive status reduced the risk of being discharged to a facility (adjusted relative risk, 0.93; 95% confidence interval, 0.89-0.98) after cardiac surgery.
Conclusions Cognitive screening before cardiac surgery can identify patients with impaired cognitive status who are less likely than patients with normal cognitive status to return home after cardiac surgery. (American Journal of Critical Care. 2011;20:129-137)
C1 [Harrington, Mary Beth; Rudolph, James L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Kraft, Malissa; Grande, Laura J.] VA Boston Healthcare Syst, Dept Psychol, Boston, MA USA.
[Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Rudolph, JL (reprint author), VABHS GRECC, JP-182,150 S Huntington Ave, Boston, MA 02130 USA.
EM jrudolph@partners.org
FU VA Rehabilitation Research career development award; National Institutes
of Health [AG023480, AG08812, AG029861]
FX Dr Rudolph was funded by a VA Rehabilitation Research career development
award. Additional support was provided by grants AG023480, AG08812, and
AG029861 from the National Institutes of Health.
NR 52
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U1 2
U2 5
PU AMER ASSOC CRITICAL CARE NURSES
PI ALISO VIEJO
PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA
SN 1062-3264
EI 1937-710X
J9 AM J CRIT CARE
JI Am. J. Crit. Care
PD MAR 1
PY 2011
VL 20
IS 2
BP 129
EP 137
DI 10.4037/ajcc2011275
PG 9
WC Critical Care Medicine; Nursing
SC General & Internal Medicine; Nursing
GA 728AO
UT WOS:000287846100006
PM 21362717
ER
PT J
AU Lin, JC
Karno, MP
Grella, CE
Warda, U
Liao, DH
Hu, PF
Moore, AA
AF Lin, James C.
Karno, Mitchell P.
Grella, Christine E.
Warda, Umme
Liao, Diana H.
Hu, Peifung
Moore, Alison A.
TI Alcohol, Tobacco, and Nonmedical Drug Use Disorders in US Adults Aged 65
Years and Older: Data From the 2001-2002 National Epidemiologic Survey
of Alcohol and Related Conditions
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Substance use disorder; alcohol; tobacco; nonmedical drug use
ID AT-RISK DRINKERS; DSM-IV ALCOHOL; UNITED-STATES; SUBSTANCE USE; NICOTINE
DEPENDENCE; COOCCURRING ALCOHOL; PREVALENCE; COMORBIDITY; ABUSE;
DISABILITY
AB Objectives: To examine the prevalence, sociodemographic, and health-related correlates of substance use disorders, including alcohol, tobacco, and nonmedical drug use among adults aged 65 years and older. Design: The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a cross-sectional survey of a population-based sample. Setting: The United States. Participants: Eight thousand two hundred five adults aged 65 years and older. Measurements: Prevalence of lifetime and past 12-month Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, determined alcohol, tobacco, and nonmedical drug use disorders. Results: Prevalence of any substance use disorder was 21.1% during the lifetime and 5.4% in the past 12 months. Lifetime and past 12-month alcohol use disorders were 16.1% and 1.5%; tobacco use disorders were 8.7% and 4.0%; and nonmedical drug use disorders were 0.6% and 0.2%, respectively. Younger age was associated with greater odds of any lifetime or past 12-month substance use disorders. Men and those who were divorced or separated had greater odds of both lifetime alcohol and tobacco use disorders. Very good or excellent self-rated health was associated with lower odds of lifetime and past 12-month tobacco use disorders. Younger age and being divorced or separated were associated with greater odds of lifetime nonmedical drug use disorder. Conclusions: More than one in five older adults ever had a substance use disorder, and more than 1 in 20 had a disorder in the past 12 months, primarily involving alcohol or tobacco. Older adults have increased comorbidities and use of medications, which can increase risks associated with substance use. (Am J Geriatr Psychiatry 2011; 19:292-299)
C1 [Lin, James C.] VA Greater Los Angeles Healthcare Syst, Dept Geriatr Med, Special Fellowship Adv Geriatr, Los Angeles, CA USA.
[Lin, James C.; Liao, Diana H.; Hu, Peifung; Moore, Alison A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Lin, James C.] Cheng Ching Hosp, Dept Med, Taichung, Taiwan.
[Karno, Mitchell P.; Grella, Christine E.; Warda, Umme; Moore, Alison A.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Integrated Subst Abuse Programs, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
RP Lin, JC (reprint author), 11301 Wilshire Ave,Bldg 220, Los Angeles, CA 90073 USA.
EM jlin1207@ucla.edu
FU National Institute on Drug Abuse [R01DA020944]; National Institute on
Alcoholism and Alcohol Abuse [K24AA15957]; National Institute on Aging
[P30AG028748]; VA
FX This work was supported by National Institute on Drug Abuse
(R01DA020944), the National Institute on Alcoholism and Alcohol Abuse
(K24AA15957), the National Institute on Aging (P30AG028748), and VA
Special Fellowship in Advanced Geriatrics.
NR 48
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U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2011
VL 19
IS 3
BP 292
EP 299
DI 10.1097/JGP.0b013e3181e898b4
PG 8
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 725QE
UT WOS:000287659900013
PM 20808122
ER
PT J
AU Perry, TW
Pugh, MJV
Waterer, GW
Nakashima, B
Orihuela, CJ
Copeland, LA
Restrepo, MI
Anzueto, A
Mortensen, EM
AF Perry, Theodore W.
Pugh, Mary Jo V.
Waterer, Grant W.
Nakashima, Brandy
Orihuela, Carlos J.
Copeland, Laurel A.
Restrepo, Marcos I.
Anzueto, Antonio
Mortensen, Eric M.
TI Incidence of Cardiovascular Events After Hospital Admission for
Pneumonia
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Cardiac arrhythmia; Cardiovascular disease; Congestive heart failure;
Myocardial infarction; Pneumonia
ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE MYOCARDIAL-INFARCTION; RECENT
RESPIRATORY-INFECTION; DISEASE; RISK; ASSOCIATION; INFLUENZA; OUTCOMES;
COMPLICATION; EXPRESSION
AB OBJECTIVE: Several studies have suggested an increased risk of cardiovascular events, primarily acute myocardial infarction, around the time of hospital admission for pneumonia. Therefore, we examined cardiovascular events, including myocardial infarction, congestive heart failure, unstable angina, stroke, and serious cardiac arrhythmias, within 90 days after hospitalization for pneumonia.
METHODS: By using data from the administrative databases of the Department of Veterans Affairs, we examined a cohort of subjects hospitalized with pneumonia between October 2001 and September 2007. Subjects were at least 65 years of age. We examined the incidence of myocardial infarction, congestive heart failure, cardiac arrhythmias, unstable angina, and stroke by International Classification of Diseases, Ninth Revision codes, excluding those with a diagnosis before the admission for pneumonia.
RESULTS: The cohort comprised 50,119 subjects with a mean age of 77.5 years (standard deviation 6.7 years), 98% of whom were male. The 90-day incidence of cardiovascular events was 1.5% for myocardial infarction, 10.2% for congestive heart failure, 9.5% for arrhythmia, 0.8% for unstable angina, and 0.2% for stroke. The majority of events occurred during the hospitalization for pneumonia.
CONCLUSION: A clinically important number of subjects in this cohort had a cardiovascular event within 90 days of hospital admission, suggesting that such events may have an important role in post-pneumonia mortality. Additional research is needed to determine whether interventions may reduce the number of cardiovascular events after pneumonia. Published by Elsevier Inc. . The American Journal of Medicine (2011) 124, 244-251
C1 [Perry, Theodore W.; Nakashima, Brandy; Copeland, Laurel A.; Restrepo, Marcos I.; Anzueto, Antonio; Mortensen, Eric M.] VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Div Gen Internal Med, Dept Med, San Antonio, TX 78229 USA.
[Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA.
[Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Copeland, Laurel A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Orihuela, Carlos J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA.
[Waterer, Grant W.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Waterer, Grant W.] Northwestern Univ, Evanston, IL USA.
RP Mortensen, EM (reprint author), VERDICT Res Program 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA.
EM mortensene@uthscsa.edu
RI Restrepo, Marcos/H-4442-2014;
OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563;
Copeland, Laurel/0000-0002-9478-0209
FU National Institute of Nursing Research [R01NR010828]; Department of
Veteran Affairs Veterans Integrated Service Network [17]; National
Health Institutes [KL2 RR025766]
FX The project described was supported by Grant R01NR010828 from the
National Institute of Nursing Research. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of Nursing Research or the
National Institutes of Health. This material is the result of work
supported with resources and the use of facilities at the South Texas
Veterans Health Care System. Dr Restrepo is supported by a Department of
Veteran Affairs Veterans Integrated Service Network 17 new faculty grant
and National Health Institutes Grant KL2 RR025766. The funding agencies
had no role in conducting the study or in the preparation, review, or
approval of the manuscript. 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 37
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U1 0
U2 4
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 MAR
PY 2011
VL 124
IS 3
BP 244
EP 251
DI 10.1016/j.amjmed.2010.11.014
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 732QM
UT WOS:000288203700020
PM 21396508
ER
PT J
AU Kayama, M
Nakazawa, T
Thanos, A
Morizane, Y
Murakami, Y
Theodoropoulou, S
Abe, T
Vavvas, D
Miller, JW
AF Kayama, Maki
Nakazawa, Toru
Thanos, Aristomenis
Morizane, Yuki
Murakami, Yusuke
Theodoropoulou, Sofia
Abe, Toshiaki
Vavvas, Demetrios
Miller, Joan W.
TI Heat Shock Protein 70 (HSP70) Is Critical for the Photoreceptor Stress
Response after Retinal Detachment via Modulating Anti-Apoptotic Akt
Kinase
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID HEAT-SHOCK PROTEINS; EXPERIMENTAL GLAUCOMA; EXPERIMENTAL-MODEL;
SIGNALING PATHWAY; CELL-SURVIVAL; UP-REGULATION; IN-VIVO; ACTIVATION;
RAT; GERANYLGERANYLACETONE
AB Photoreceptor apoptosis is a major cause of vision loss in many ocular diseases. Significant progress has been made to elucidate the molecular pathways involved in this process, yet little is known about proteins counteracting these apoptotic pathways. It is established that heat shock proteins (HSPs) function as molecular helper proteins (chaperones) by preventing protein aggregation and facilitating refolding of dysfunctional proteins, critical to the survival of all organisms. Here, we investigated the role of HSP70 on photoreceptor survival after experimental retinal detachment (RD) in mice and rats. We found that HSP70 was up-regulated after RD and associated with phosphorylated Akt, thereby preventing its dephosphorylation and further activation of cell death pathways. Administration of quercetin, which inhibits HSP70 and suppresses Akt phosphorylation significantly increased photoreceptor apoptosis. Similarly, RD-induced photoreceptor apoptosis was augmented in mice carrying hypomorphic mutations of the genes encoding HSP70. On the other hand, administration of geranylgeranylacetone, which induces an increase in HSP70 significantly decreased photoreceptor apoptosis after RD through prolonged activation of Ala pathway. Thus, HSP70 may be a favorable potential target to increase photoreceptor cell survival after RD. (Am J Pathol 2011, 178:1080-1091; DOI: 10.1016/j.ajpath.2010.11.072)
C1 [Kayama, Maki; Nakazawa, Toru; Thanos, Aristomenis; Morizane, Yuki; Murakami, Yusuke; Theodoropoulou, Sofia; Vavvas, Demetrios; Miller, Joan W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
[Nakazawa, Toru] Tohoku Grad Univ, Sch Med, Dept Ophthalmol, Sendai, Miyagi, Japan.
[Abe, Toshiaki] Tohoku Univ, Grad Sch Med, Div Clin Cell Therapy, Sendai, Miyagi 980, Japan.
RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab, 243 Charles St, Boston, MA 02114 USA.
EM ntoru@oph.med.tohoku.ac.jp; joan_miller@meei.harvard.edu
OI Vavvas, Demetrios/0000-0002-8622-6478
FU Ministry of Education, Science, and Technology of Japan [21659395,
22689045]; Uehara Memorial Research Foundation; Takeda Research
Foundation; Imai Glaucoma Research Foundation; Bausch & Lomb
Vitreoretinal Fellowship; National Eye Institute [EY014104]
FX Supported by Grants-in-Aid from the Ministry of Education, Science, and
Technology of Japan (21659395 and 22689045 to T.N.), Uehara Memorial
Research Foundation, Takeda Research Foundation and Imai Glaucoma
Research Foundation (T.N.), a Bausch & Lomb Vitreoretinal Fellowship
(M.K. and Y.M.), and National Eye Institute grant EY014104 (MEEI Core
Grant).
NR 45
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U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2011
VL 178
IS 3
BP 1080
EP 1091
DI 10.1016/j.ajpath.2010.11.072
PG 12
WC Pathology
SC Pathology
GA 732LD
UT WOS:000288185600016
PM 21356360
ER
PT J
AU Bunni, MA
Kramarenko, II
Walker, L
Raymond, JR
Garnovskaya, MN
AF Bunni, Marlene A.
Kramarenko, Inga I.
Walker, Linda
Raymond, John R.
Garnovskaya, Maria N.
TI Role of integrins in angiotensin II-induced proliferation of vascular
smooth muscle cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE G protein-coupled receptors; signal transduction; extracellular
signal-regulated protein kinase 1 and 2
ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION; RECEPTOR ANTAGONIST;
ADHESION RECEPTORS; FOCAL ADHESIONS; BALLOON INJURY; EGF RECEPTOR;
ALPHA(V)BETA(3); HYPERTROPHY; EXPRESSION
AB Bunni MA, Kramarenko II, Walker L, Raymond JR, Garnovskaya MN. Role of integrins in angiotensin II-induced proliferation of vascular smooth muscle cells. Am J Physiol Cell Physiol 300: C647-C656, 2011. First published December 9, 2010; doi: 10.1152/ajpcell.00179.2010.-Angiotensin II (AII) binds to G protein-coupled receptor AT(1) and stimulates extracellular signal-regulated kinase (ERK), leading to vascular smooth muscle cells (VSMC) proliferation. Proliferation of mammalian cells is tightly regulated by adhesion to the extracellular matrix, which occurs via integrins. To study cross-talk between G protein-coupled receptor-and integrin-induced signaling, we hypothesized that integrins are involved in AII-induced proliferation of VSMC. Using Oligo GEArray and quantitative RT-PCR, we established that messages for alpha(1)-, alpha(5)-, alpha(V)-, and beta(1)-integrins are predominant in VSMC. VSMC were cultured on plastic dishes or on plates coated with either extracellular matrix or poly-D-lysine (which promotes electrostatic cell attachment independent of integrins). AII significantly induced proliferation in VSMC grown on collagen I or fibronectin, and this effect was blocked by the ERK inhibitor PD-98059, suggesting that AII-induced proliferation requires ERK activity. VSMC grown on collagen I or on fibronectin demonstrated approximately three-and approximately sixfold increases in ERK phosphorylation after stimulation with 100 nM AII, respectively, whereas VSMC grown on poly-D-lysine demonstrated no significant ERK activation, supporting the importance of integrin-mediated adhesion. AII-induced ERK activation was reduced by > 65% by synthetic peptides containing an RGD (arginine-glycine-aspartic acid) sequence that inhibit alpha(5)beta(1)-integrin, and by similar to 60% by the KTS (lysine-threonine-serine)-containing peptides specific for integrin-alpha(1)beta(1). Furthermore, neutralizing antibody against beta(1)-integrin and silencing of alpha(1), alpha(5), and beta(1) expression by transfecting VSMC with short interfering RNAs resulted in decreased AII-induced ERK activation. This work demonstrates roles for specific integrins (most likely alpha(5)beta(1) and alpha(1)beta(1)) in AII-induced proliferation of VSMC.
C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA.
Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA.
RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Dept Med Nephrol, 96 Jonathan Lucas St,MSC 629, Charleston, SC 29425 USA.
EM garnovsk@musc.edu
FU Department of Veterans Affairs Basic Laboratory RD Service; American
Heart Association [GIA 0655445U]; National Institutes of Health
[DK52448, GM63909]; Medical University of South Carolina Division of
Nephrology; Dialysis Clinics, Inc.
FX This work was supported by grants from the Department of Veterans
Affairs Basic Laboratory R&D Service (Merit Awards and a Research
Enhancement Award Program Award to M. N. Garnovskaya and J. R. Raymond),
American Heart Association (GIA 0655445U to M. N. Garnovskaya), the
National Institutes of Health (DK52448 and GM63909 to J. R. Raymond),
and a laboratory endowment jointly supported by the Medical University
of South Carolina Division of Nephrology and Dialysis Clinics, Inc. (J.
R. Raymond).
NR 41
TC 8
Z9 8
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD MAR
PY 2011
VL 300
IS 3
BP C647
EP C656
DI 10.1152/ajpcell.00179.2010
PG 10
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 727MI
UT WOS:000287803800027
PM 21148411
ER
PT J
AU Lu, L
Li, TT
Williams, G
Petit, E
Borowsky, M
Walker, WA
AF Lu, Lei
Li, Tiantian
Williams, Graham
Petit, Elizabeth
Borowsky, Mark
Walker, W. Allan
TI Hydrocortisone induces changes in gene expression and differentiation in
immature human enterocytes
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE microarray; immature enterocyte development; hydrocortisone;
polarity-associated genes; tight junction-associated genes
ID NEONATAL NECROTIZING ENTEROCOLITIS; SMALL-INTESTINE; IN-VITRO;
CHOLERA-TOXIN; EPITHELIAL POLARITY; FETAL ENTEROCYTES; MODULATION;
CELLS; GLUCOCORTICOIDS; RESPONSIVENESS
AB Lu L, Li T, Williams G, Petit E, Borowsky M, Walker WA. Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes. Am J Physiol Gastrointest Liver Physiol 300: G425-G432, 2011. First published December 9, 2010; doi:10.1152/ajpgi.00011.2010.-It is known that functional maturation of the small intestine occurring during the weaning period is facilitated by glucocorticoids (such as hydrocortisone, HC), including an increased expression of digestive hydrolases. However, the molecular mechanisms are not well understood, particularly in the human gut. Here we report a microarray analysis of HC-induced changes in gene expression in H4 cells (a well-characterized human fetal small intestinal epithelial cell line). This study identified a large number of HC-regulated genes, some involved in metabolism, cell cycle regulation, cell-cell or cell-extracellular matrix communication. HC also regulates the expression of genes important for cell maturation such as development of cell polarity, tight junction formation, and interactions with extracellular matrices. Using human small intestinal xenografts, we also show that HC can regulate the expression of genes important for intestinal epithelial cell maturation. Our dataset may serve as a useful resource for understanding and dissecting the molecular mechanisms of intestinal epithelial cell maturation.
C1 [Lu, Lei; Li, Tiantian; Petit, Elizabeth; Walker, W. Allan] Massachusetts Gen Hosp Children, Dev Gastroenterol Lab, Boston, MA USA.
[Borowsky, Mark] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Borowsky, Mark] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Williams, Graham] Depauw Univ, Greencastle, IN 46135 USA.
RP Lu, L (reprint author), Harvard Univ, Sch Med, Dev Gastroenterol Lab, Massachusetts Gen Hosp, 114 16th St 114-3503, Charlestown, MA 02129 USA.
EM lul@helix.mgh.harvard.edu
FU National Institutes of Health [R01-HD-12437,, R01-DK-70260,
P01-DK-33506, P30-DK-40561]
FX This work was supported by National Institutes of Health Grants
R01-HD-12437, R01-DK-70260, P01-DK-33506, and P30-DK-40561 (W. A.
Walker).
NR 37
TC 7
Z9 7
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 MAR
PY 2011
VL 300
IS 3
BP G425
EP G432
DI 10.1152/ajpgi.00011.2010
PG 8
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 728CA
UT WOS:000287850400007
PM 21148402
ER
PT J
AU David, V
Martin, A
Hedge, AM
Drezner, MK
Rowe, PSN
AF David, Valentin
Martin, Aline
Hedge, Anne-Marie
Drezner, Marc K.
Rowe, Peter S. N.
TI ASARM peptides: PHEX-dependent and -independent regulation of serum
phosphate
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE matrix extracellular phosphoglycoprotein; dentin matrix protein-1;
mineralization; osteomalacia; SIBLING proteins; fibroblast growth factor
23; X-linked hypophosphatemic rickets; 1,25 dihydroxy vitamin D3
ID MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; LINKED GLYCOPROTEINS SIBLINGS;
HUMAN OSTEOBLAST CELLS; BRUSH-BORDER; PHOSPHORYLATED OSTEOPONTIN;
PHOSPHONOCARBOXYLIC ACIDS; HYPOPHOSPHATEMIC RICKETS; PHOSPHONOFORMIC
ACID; BONE SIALOPROTEIN; KNOCKOUT MICE
AB David V, Martin A, Hedge A-M, Drezner MK, Rowe PS. ASARM peptides: PHEX-dependent and -independent regulation of serum phosphate. Am J Physiol Renal Physiol 300: F783-F791, 2011. First published December 22, 2010; doi:10.1152/ajprenal.00304.2010.-Increased acidic serine aspartate-rich MEPE-associated motif (ASARM) peptides cause mineralization defects in X-linked hypophosphatemic rickets mice (HYP) and "directly" inhibit renal phosphate uptake in vitro. However, ASARM peptides also bind to phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and are a physiological substrate for this bone-expressed, phosphate-regulating enzyme. We therefore tested the hypothesis that circulating ASARM peptides also "indirectly" contribute to a bone-renal PHEX-dependent hypophosphatemia in normal mice. Male mice (n = 5; 12 wk) were fed for 8 wk with a normal phosphorus and vitamin D(3) diet (1% P(i) diet) or a reduced phosphorus and vitamin D(3) diet (0.1% P(i) diet). For the final 4 wk, transplantation of mini-osmotic pumps supplied a continuous infusion of either ASARM peptide (5 mg.day(-1).kg(-1)) or vehicle. HYP, autosomal recessive hypophosphatemic rickets (ARHR), and normal mice (no pumps or ASARM infusion; 0.4% P(i) diet) were used in a separate experiment designed to measure and compare circulating ASARM peptides in disease and health. ASARM treatment decreased serum phosphate concentration and renal phosphate cotransporter (NPT2A) mRNA with the 1% P(i) diet. This was accompanied by a twofold increase in serum ASARM and 1,25-dihydroxy vitamin D(3) [1,25 (OH)(2)D(3)] levels without changes in parathyroid hormone. For both diets, ASARM-treated mice showed significant increases in serum fibroblast growth factor 23 (FGF23; +50%) and reduced serum osteocalcin (-30%) and osteopontin (-25%). Circulating ASARM peptides showed a significant inverse correlation with serum P(i) and a significant positive correlation with fractional excretion of phosphate. We conclude that constitutive overexpression of ASARM peptides plays a "component" PHEX-independent part in the HYP and ARHR hypophosphatemia. In contrast, with wild-type mice, ASARM peptides likely play a bone PHEX-dependent role in renal phosphate regulation and FGF23 expression. They may also coordinate FGF23 expression by competitively modulating PHEX/DMP1 interactions and thus bone-renal mineral regulation.
C1 [Rowe, Peter S. N.] Univ Kansas, Dept Internal Med, Div Nephrol & Hypertens, Kidney Inst,Med Ctr, Kansas City, KS 66160 USA.
[David, Valentin; Martin, Aline] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Drezner, Marc K.] Univ Wisconsin, Dept Med, Madison, WI USA.
[Drezner, Marc K.] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA.
RP Rowe, PSN (reprint author), Univ Kansas, Dept Internal Med, Div Nephrol & Hypertens, Kidney Inst,Med Ctr, MS 3018,3901 Rainbow Blvd, Kansas City, KS 66160 USA.
EM prowe@kumc.edu
FU National Institutes of Health (National Institute of Arthritis and
Musculoskeletal and Skin Diseases) [RO-1-AR51598-01, R01-AR-27032-26,
1K12-RR-017614, R01-SK-65830-1, M01-RR-03186-21]
FX We thank the National Institutes of Health (National Institute of
Arthritis and Musculoskeletal and Skin Diseases) for grant support to P.
S. N. Rowe (Grant RO-1-AR51598-01) and M. K. Drezner (Grants
R01-AR-27032-26, 1K12-RR-017614, R01-SK-65830-1, and M01-RR-03186-21).
NR 65
TC 30
Z9 30
U1 0
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD MAR
PY 2011
VL 300
IS 3
BP F783
EP F791
DI 10.1152/ajprenal.00304.2010
PG 9
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 730ZS
UT WOS:000288076700024
PM 21177780
ER
PT J
AU Japuntich, SJ
Leventhal, AM
Piper, ME
Bolt, DM
Roberts, LJ
Fiore, MC
Baker, TB
AF Japuntich, Sandra J.
Leventhal, Adam M.
Piper, Megan E.
Bolt, Daniel M.
Roberts, Linda J.
Fiore, Michael C.
Baker, Timothy B.
TI Smoker Characteristics and Smoking-Cessation Milestones
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID SOCIAL SUPPORT; QUITTING SMOKING; CLINICAL-TRIAL; TOBACCO USE; RELAPSE;
STRESS; MODELS; INTERVENTION; PREDICTORS; INTENSITY
AB Background: Contextual variables often predict long-term abstinence, but little is known about how these variables exert their effects. These variables could influence abstinence by affecting the ability to quit at all, or by altering risk of lapsing, or progressing from a lapse to relapse.
Purpose: To examine the effect of common predictors of smoking-cessation failure on smoking-cessation processes.
Methods: The current study (N = 1504, 58% female, 84% Caucasian; recruited from January 2005 to June 2007; data analyzed in 2009) uses the approach advocated by Shiffman et al. (2006), which measures cessation outcomes on three different cessation milestones (achieving initial abstinence, lapse risk, and the lapse-relapse transition) to examine relationships of smoker characteristics (dependence, contextual and demographic factors) with smoking-cessation process.
Results: High nicotine dependence strongly predicted all milestones: not achieving initial abstinence, and a higher risk of both lapse and transitioning from lapse to complete relapse. Numerous contextual and demographic variables were associated with higher initial cessation rates and/or decreased lapse risk at 6 months post-quit (e. g., ethnicity, gender, marital status, education, smoking in the workplace, number of smokers in the social network, and number of supportive others). However, aside from nicotine dependence, only gender significantly predicted the risk of transition from lapse to relapse.
Conclusions: These findings demonstrate that (1) higher nicotine dependence predicted worse outcomes across every cessation milestone; (2) demographic and contextual variables are generally associated with initial abstinence rates and lapse risk and not the lapse-relapse transition. These results identify groups who are at risk for failure at specific stages of the smoking-cessation process, and this may have implications for treatment. (Am J Prev Med 2011;40(3):286-294) (C) 2011 American Journal of Preventive Medicine
C1 [Japuntich, Sandra J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Japuntich, Sandra J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Leventhal, Adam M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Japuntich, Sandra J.; Piper, Megan E.; Fiore, Michael C.; Baker, Timothy B.] Univ Wisconsin, Dept Med, Ctr Tobacco Res & Intervent, Sch Med & Publ Hlth, Madison, WI USA.
[Bolt, Daniel M.] Univ Wisconsin, Dept Educ Psychol, Madison, WI 53706 USA.
[Roberts, Linda J.] Univ Wisconsin, Dept Human Dev & Family Studies, Madison, WI 53706 USA.
RP Japuntich, SJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM sjapuntich@partners.org
FU NIH/NIDA [P50 DA019706]; National Center for Research Resources, NIH
[M01 RR03186]; Institutional Clinical and Translational Science Award
(UW-Madison) [1KL2RR025012-01]; NIH [1K05CA139871, K08DA025041]; Pfizer;
Glaxo Wellcome; Sanofi; Nabi; GlaxoSmithKline; Nabi Biopharmaceuticals
FX This research was conducted at the University of Wisconsin-Madison and
was supported by Grant P50 DA019706 from NIH/NIDA; by Grant M01 RR03186
from the General Clinical Research Centers Program of the National
Center for Research Resources, NIH; by an Institutional Clinical and
Translational Science Award (UW-Madison; KL2 Grant 1KL2RR025012-01); and
by Grants 1K05CA139871 and K08DA025041 from the NIH. Medication was
provided to participants at no cost under a research agreement with
GlaxoSmithKline (GSK); no part of this manuscript was written or edited
by anyone employed by GSK. The authors are solely responsible for the
analyses, content, and writing of this article. The authors have full
control of all primary data, and they agree to allow the journal to
review the data if requested.; TBB has served as an investigator on
research projects sponsored by pharmaceutical companies including
Pfizer, Glaxo Wellcome, Sanofi, and Nabi. Over the past 3 years, MCF has
served as an investigator in research studies at the University of
Wisconsin that were funded by Pfizer, GlaxoSmithKline and Nabi
Biopharmaceuticals.
NR 63
TC 50
Z9 50
U1 3
U2 12
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 MAR
PY 2011
VL 40
IS 3
BP 286
EP 294
DI 10.1016/j.amepre.2010.11.016
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 722PB
UT WOS:000287445700006
PM 21335259
ER
PT J
AU Levinson, DF
Duan, JB
Oh, S
Wang, K
Sanders, AR
Shi, JX
Zhang, N
Mowry, BJ
Olincy, A
Amin, F
Cloninger, CR
Silverman, JM
Buccola, NG
Byerley, WF
Black, DW
Kendler, KS
Freedman, R
Dudbridge, F
Pe'er, I
Hakonarson, H
Bergen, SE
Fanous, AH
Holmans, PA
Gejman, PV
AF Levinson, Douglas F.
Duan, Jubao
Oh, Sang
Wang, Kai
Sanders, Alan R.
Shi, Jianxin
Zhang, Nancy
Mowry, Bryan J.
Olincy, Ann
Amin, Farooq
Cloninger, C. Robert
Silverman, Jeremy M.
Buccola, Nancy G.
Byerley, William F.
Black, Donald W.
Kendler, Kenneth S.
Freedman, Robert
Dudbridge, Frank
Pe'er, Itsik
Hakonarson, Hakon
Bergen, Sarah E.
Fanous, Ayman H.
Holmans, Peter A.
Gejman, Pablo V.
TI Copy Number Variants in Schizophrenia: Confirmation of Five Previous
Findings and New Evidence for 3q29 Microdeletions and VIPR2 Duplications
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 60th Annual Meeting of the American-Society-of-Human-Genetics
CY NOV 02-06, 2010
CL Washington, DC
SP Amer Soc Human Genet
ID 22Q11.2 DELETION SYNDROME; COMMON VARIANTS; GENOME; RISK; GENE;
ASSOCIATION; POPULATION; DISORDER; DISEASE; 16P11.2
AB Objective: To evaluate previously reported associations of copy number variants (CNVs) with schizophrenia and to identify additional associations, the authors analyzed CNVs in the Molecular Genetics of Schizophrenia study (MGS) and additional available data.
Method: After quality control, MGS data for 3,945 subjects with schizophrenia or schizoaffective disorder and 3,611 screened comparison subjects were available for analysis of rare CNVs (< 1% frequency). CNV detection thresholds were chosen that maximized concordance in 151 duplicate assays. Pointwise and genewise analyses were carried out, as well as analyses of previously reported regions. Selected regions were visually inspected and confirmed with quantitative polymerase chain reaction.
Results: In analyses of MGS data combined with other available data sets, odds ratios of 7.5 or greater were observed for previously reported deletions in chromosomes 1q21.1, 15q13.3, and 22q11.21, duplications in 16p11.2, and exon-disrupting deletions in NRXN1. The most consistently supported candidate associations across data sets included a 1.6-Mb deletion in chromosome 3q29 (21 genes, TFRC to BDH1) that was previously described in a mild-moderate mental retardation syndrome, exonic duplications in the gene for vasoactive intestinal peptide receptor 2 (VIPR2), and exonic duplications in C16orf72. The case subjects had a modestly higher genome-wide number of gene-containing deletions (> 100 kb and > 1 Mb) but not duplications.
Conclusions: The data strongly confirm the association of schizophrenia with 1q21.1, 15q13.3, and 22q11.21 deletions, 16p11.2 duplications, and exonic NRXN1 deletions. These CNVs, as well as 3q29 deletions, are also associated with mental retardation, autism spectrum disorders, and epilepsy. Additional candidate genes and regions, including VIPR2, were identified. Study of the mechanisms underlying these associations should shed light on the pathophysiology of schizophrenia. (Am J Psychiatry 2011; 168:302-316)
C1 [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
NorthShore Univ, HealthSyst Res Inst, Evanston, IL USA.
Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
Univ Penn, Philadelphia, PA 19104 USA.
NCI, Bethesda, MD 20892 USA.
Queensland Ctr Mental Hlth Res, Brisbane, Qld, Australia.
Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
Univ Colorado Denver, Dept Psychiat, Aurora, CO USA.
Atlanta VA Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA USA.
Emory Univ, Atlanta, GA 30322 USA.
Washington Univ, Dept Psychiat, St Louis, MO 63130 USA.
Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA.
Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA.
Univ Iowa, Mental Hlth Clin Res Ctr, Iowa City, IA USA.
Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA.
Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23284 USA.
London Sch Hyg & Trop Med, Dept Stat Genet & Epidemiol, London, England.
Columbia Univ, Dept Comp Sci, New York, NY 10027 USA.
Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
MIT, Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA 02139 USA.
Harvard Univ, Cambridge, MA 02138 USA.
Washington VA Med Ctr, Dept Psychiat, Washington, DC USA.
Georgetown Univ, Sch Med, Washington, DC USA.
Cardiff Univ, Biostat & Bioinformat Unit, Cardiff, S Glam, Wales.
RP Levinson, DF (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Suite A-3325,701 Welch Rd, Palo Alto, CA 94304 USA.
EM dflev@stanford.edu
RI Cloninger, Claude/F-5357-2012; Bergen, Sarah/I-8313-2012; Holmans,
Peter/F-4518-2015
OI Cloninger, Claude/0000-0003-3096-4807; Bergen,
Sarah/0000-0002-5888-0034; Buccola, Nancy/0000-0003-1378-4636; Holmans,
Peter/0000-0003-0870-9412
FU Medical Research Council [G1000718]; NCRR NIH HHS [U54 RR-020278, U54
RR020278]; NIMH NIH HHS [R01 MH059565, R01 MH-59565, R01 MH-59566, R01
MH-59571, R01 MH-59586, R01 MH-59587, R01 MH-59588, R01 MH-60870, R01
MH-60879, R01 MH-61675, R01 MH-67257, R01 MH-81800, R01 MH059566, R01
MH059571, R01 MH059586, R01 MH059587, R01 MH059588, R01 MH060870, R01
MH060879, R01 MH061675, R01 MH067257, R01 MH081800, U01 MH-46276, U01
MH-46289, U01 MH-46318, U01 MH-79469, U01 MH-79470, U01 MH046276, U01
MH046276-08, U01 MH046289, U01 MH046289-08, U01 MH046318, U01
MH046318-08, U01 MH079469, U01 MH079470]
NR 42
TC 226
Z9 229
U1 3
U2 30
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 MAR
PY 2011
VL 168
IS 3
BP 302
EP 316
DI 10.1176/appi.ajp.2010.10060876
PG 15
WC Psychiatry
SC Psychiatry
GA 729AG
UT WOS:000287916900014
PM 21285140
ER
PT J
AU Cromwell, MA
Carville, A
Mansfield, K
Klumpp, S
Westmoreland, SV
Lackner, AA
Johnson, RP
AF Cromwell, Mandy A.
Carville, Angela
Mansfield, Keith
Klumpp, Sherry
Westmoreland, Susan V.
Lackner, Andrew A.
Johnson, R. Paul
TI SIV-Specific CD8+T Cells are Enriched in Female Genital Mucosa of Rhesus
Macaques and Express Receptors for Inflammatory Chemokines
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE CD8+T cell responses; chemokines; CXCL9; CXCR3; mucosal immunity; SIV
ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; DENDRITIC CELLS;
INFECTION; KINETICS; MACROPHAGES; MIGRATION; RESPONSES; CERVIX
AB Problem
Mucosal T lymphocyte responses in the female reproductive tract, the primary site of HIV transmission in women, may be critical for initial control of virus infection. In addition, characterization of genital immune responses to HIV will be important for the development of a vaccine capable of preventing infection by this route.
Method of study
We analyzed lymphocytes isolated from vagina and cervix of chronically SIV-infected macaques for the frequency of SIV Gag tetramer-binding cells and expression of chemokine receptors.
Results
We found that the frequency of SIV-specific CD8+ T cell responses was 3- to 30-fold higher in genital tissues than in peripheral blood. SIV-specific CD8+ T cells in genital tissues expressed high levels of CXCR3 and CCR5, chemokine receptors normally expressed on memory T cells that home to inflamed tissues. Cells expressing CXCR3 colocalized with its chemokine ligand CXCL9 [monokine induced by interferon gamma, MIG] in the vaginal lamina propria.
Conclusion
These results indicate that the frequency of SIV-specific CD8+ T cells in the female genital mucosa is enriched compared with peripheral blood and provide initial information regarding the signals that direct recruitment of T cells to the female reproductive tract.
C1 [Cromwell, Mandy A.; Johnson, R. Paul] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA.
[Carville, Angela; Mansfield, Keith] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Primate Med, Southborough, MA 01772 USA.
[Klumpp, Sherry; Westmoreland, Susan V.; Lackner, Andrew A.] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Comparat Pathol, Southborough, MA 01772 USA.
[Johnson, R. Paul] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Boston, MA USA.
[Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough Campus,Pine Hill Dr,POB 9102, Southborough, MA 01772 USA.
EM paul_johnson@hms.harvard.edu
FU NIH [AI062412, AI071306, RR00168]
FX The authors thank John Altman (Emory University) for providing the Mamu
A*01 Gag tetramers and Andrew Luster (Massachusetts General Hospital)
for helpful discussions. This work was supported through NIH grants
AI062412, AI071306, and RR00168.
NR 16
TC 2
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD MAR
PY 2011
VL 65
IS 3
BP 242
EP 247
DI 10.1111/j.1600-0897.2010.00966.x
PG 6
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 717IP
UT WOS:000287037200010
PM 21223428
ER
PT J
AU Xiang, M
Yin, LH
Li, YH
Xiao, GZ
Vodovotz, Y
Billiar, TR
Wilson, MA
Fan, J
AF Xiang, Meng
Yin, Lianhua
Li, Yuehua
Xiao, Guozhi
Vodovotz, Yoram
Billiar, Timothy R.
Wilson, Mark A.
Fan, Jie
TI Hemorrhagic Shock Activates Lung Endothelial Reduced Nicotinamide
Adenine Dinucleotide Phosphate (NADPH) Oxidase Via Neutrophil NADPH
Oxidase
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE High mobility group box 1 (HMGB1); inflammation; lung; oxidants;
Toll-like receptor
ID OXYGEN SPECIES PRODUCTION; GLYCATION END-PRODUCTS;
TUMOR-NECROSIS-FACTOR; TLR2 UP-REGULATION; NAD(P)H OXIDASE;
CONFORMATIONAL-CHANGES; ALVEOLAR MACROPHAGES; LIVER ISCHEMIA;
ANGIOTENSIN-II; CUTTING EDGE
AB The vascular endothelium plays an important role in the regulation of inflammatory responses after trauma and hemorrhage. Interactions of neutrophils with endothelial cells (ECs) contribute to the activation of specific EC responses involved in innate immunity. We have previously reported that oxidants derived from the neutrophil reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a critical regulator to EC activation. Our objective was to test the role of neutrophil NADPH oxidase-derived oxidants in mediating and enhancing hemorrhagic shock (HS)-induced activation of lung endothelial NADPH oxidase. Mice were subjected to HS and neutrophil depletion. The mice were also replenished with the neutrophil from NADPH oxidase-deficient mice. The resultant activation of lung NADPH oxidase was analyzed. The in vivo studies were also recapitulated with in vitro neutrophil-EC coculture system. HS induces NADPH oxidase activation in neutrophils and lung through high-mobility group box 1/Toll-like receptor 4-dependent signaling. In neutropenic mice, shock-induced NADPH oxidase activation in the lung was reduced significantly, but was restored upon repletion with neutrophils obtained from wild-type mice subjected to shock, but not with neutrophils from shock mice lacking the gp91(phox) subunit of NADPH oxidase. The findings were recapitulated in mouse lung vascular ECs cocultured with neutrophils. The data further demonstrate that neutrophil-derived oxidants are key factors mediating augmented High mobility group box 1 (HMGB1)-induced endothelial NADPH oxidase activation through a Rac1-dependent, but p38 mitogen-activated protein kinase-independent, pathway. Oxidant signaling by neutrophil NADPH oxidase is an important determinant of activation of endothelial NADPH oxidase after HS.
C1 [Wilson, Mark A.; Fan, Jie] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Xiang, Meng; Li, Yuehua; Vodovotz, Yoram; Billiar, Timothy R.; Wilson, Mark A.; Fan, Jie] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA.
[Xiang, Meng; Yin, Lianhua] Fudan Univ, Dept Pathophysiol, Shanghai 200433, Peoples R China.
[Xiao, Guozhi] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
RP Fan, J (reprint author), VAPHS, Bldg 1,Room 2W109,Univ Dr, Pittsburgh, PA 15240 USA.
EM fanj2@upmc.edu
FU National Institutes of Health [R01-HL-079669]; National Institutes of
Health Center [P50-GM-53789]; U.S. Department of Veterans Affairs;
National Heart, Lung, and Blood Institute (NHLBI); National Institute of
General Medical Sciences; Department of Veterans Affairs; National
Institutes of Health (NIH)/NHLBI [R33-HL-089082]; NIH/National Institute
of Allergy and Infectious Diseases [R01-AI080799]; NIH/National
Institute of General Medical Sciences [P50-GM-53789]; NIH/National
Institute on Disability and Rehabilitation Research [H133E070024];
NIH/National Institute of Diabetes and Digestive and Kidney Diseases
[UO1 DK072146]
FX This work was supported by the National Institutes of Health grant
R01-HL-079669 (J.F. and M.A.W.), National Institutes of Health Center
grant P50-GM-53789 (T.R.B., Y.V. and J.F.), and a U.S. Department of
Veterans Affairs merit award (J.F.).; J.F. has received sponsored grants
from the National Heart, Lung, and Blood Institute (NHLBI) (more than
$100,000), National Institute of General Medical Sciences (more than
$100,000), and Department of Veterans Affairs (more than $100,000); Y.V.
owns stock in Immunetrics, Inc. (more than $100,000), and has served as
a principal investigator (PI) for the National Institutes of Health
(NIH)/NHLBI (PI of grant R33-HL-089082, more than $100,000),
NIH/National Institute of Allergy and Infectious Diseases (co-PI of
grant R01-AI080799, more than $100,000), NIH/National Institute of
General Medical Sciences (Project V PI on grant P50-GM-53789, more than
$100,000), NIH/National Institute on Disability and Rehabilitation
Research (Project 1 PI on grant H133E070024, more than $100,000), and
NIH/National Institute of Diabetes and Digestive and Kidney Diseases
(Supplement PI on grant UO1 DK072146, $50,001-100,000); none of the
other authors has a financial relationship with a commercial entity that
has an interest in the subject of this manuscript.
NR 48
TC 11
Z9 12
U1 0
U2 3
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD MAR
PY 2011
VL 44
IS 3
BP 333
EP 340
DI 10.1165/rcmb.2009-0408OC
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 753KN
UT WOS:000289772400012
PM 20418360
ER
PT J
AU Palanisamy, A
Baxter, MG
Keel, PK
Xie, ZC
Crosby, G
Culley, DJ
AF Palanisamy, Arvind
Baxter, Mark G.
Keel, Pamela K.
Xie, Zhongcong
Crosby, Gregory
Culley, Deborah J.
TI Rats Exposed to Isoflurane In Utero during Early Gestation Are
Behaviorally Abnormal as Adults
SO ANESTHESIOLOGY
LA English
DT Article
ID PRENATAL ETHANOL EXPOSURE; GABA-A RECEPTOR; GUINEA-PIG;
LEARNING-DISABILITIES; COGNITIVE DYSFUNCTION; FETAL EXPOSURE; BIRTH
COHORT; BRAIN; ANESTHESIA; HIPPOCAMPAL
AB Background: Preclinical evidence suggests that commonly used anesthetic agents induce long-lasting neurobehavioral changes when administered early in life, but there has been virtually no attention to the neurodevelopmental consequences for the fetus of maternal anesthesia. This study tested the hypothesis that fetal rats exposed to isoflurane during maternal anesthesia on gestational day 14, which corresponds to the second trimester in humans, would be behaviorally abnormal as adults.
Methods: Timed, pregnant rats were randomly assigned on gestational day 14 to receive 1.4% isoflurane in 100% oxygen (n = 3) or 100% oxygen (n = 2) for 4 h. Beginning at 8 weeks of age, male offspring (N = 12-14 in control and anesthesia groups, respectively) were evaluated for spontaneous locomotor activity, hippocampal-dependent learning and memory (i.e., spontaneous alternations, novel object recognition, and radial arm maze), and anxiety (elevated plus maze).
Results: Isoflurane anesthesia was physiologically well tolerated by the dams. Adult rats exposed prenatally to isoflurane were not different than controls on spontaneous locomotor activity, spontaneous alternations, or object recognition memory, but made more open arm entries on the elevated plus maze and took longer and made more errors of omission on the radial arm maze.
Conclusions: Rats exposed to isoflurane in utero at a time that corresponds to the second trimester in humans have impaired spatial memory acquisition and reduced anxiety, compared with controls. This suggests the fetal brain may be adversely affected by maternal anesthesia, and raises the possibility that vulnerability to deleterious neurodevelopmental effects of isoflurane begins much earlier in life than previously recognized.
C1 [Palanisamy, Arvind; Crosby, Gregory; Culley, Deborah J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesia, Cambridge, MA 02138 USA.
[Xie, Zhongcong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA USA.
[Keel, Pamela K.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA.
[Baxter, Mark G.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA.
RP Culley, DJ (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA.
EM dculley@zeus.bwh.harvard.edu
FU National Institutes of Health (Bethesda, Maryland) [R01 AG20253, R01
GM088817, K08NS048140, R21AG029856, R01 GM088801, KO8 GM077057];
Department of Anesthesiology, Perioperative, and Pain Medicine of the
Brigham & Women's Hospital
FX This study was supported by National Institutes of Health (Bethesda,
Maryland) Grants R01 AG20253 and R01 GM088817 (Gregory Crosby);
K08NS048140, R21AG029856 and R01 GM088801 (Zhongcong Xie); KO8 GM077057
(Deborah J. Culley) and by an intramural fellowship awarded by the
Department of Anesthesiology, Perioperative, and Pain Medicine of the
Brigham & Women's Hospital (Arvind Palanisamy). Presented in part as a
poster presentation at the Association of University Anesthesiologists
57th Annual Meeting, Denver, Colorado, April 7-9, 2010 and as an oral
presentation at the Society for Obstetric Anesthesia and Perinatology
42nd Annual Meeting, San Antonio, Texas, May 12-16, 2010.
NR 51
TC 43
Z9 48
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD MAR
PY 2011
VL 114
IS 3
BP 521
EP 528
DI 10.1097/ALN.0b013e318209aa71
PG 8
WC Anesthesiology
SC Anesthesiology
GA 725QH
UT WOS:000287660300011
PM 21307768
ER
PT J
AU Wang, E
Feng, Y
Zhang, M
Zou, L
Li, Y
Buys, ES
Huang, PG
Brouckaert, P
Chao, W
AF Wang, E.
Feng, Yan
Zhang, Ming
Zou, Lin
Li, Yan
Buys, Emmanuel S.
Huang, Peigen
Brouckaert, Peter
Chao, Wei
TI Toll-like Receptor 4 Signaling Confers Cardiac Protection against
Ischemic Injury via Inducible Nitric Oxide Synthase- and Soluble
Guanylate Cyclase-dependent Mechanisms
SO ANESTHESIOLOGY
LA English
DT Article
ID MYOCARDIAL-ISCHEMIA; ISCHEMIA/REPERFUSION INJURY; DELAYED PROTECTION;
REPERFUSION INJURY; INNATE IMMUNITY; KNOCKOUT MICE; TNF-ALPHA; IN-VIVO;
MYD88; ENDOTOXIN
AB Background: Prior administration of a small dose of lipopolysaccharide confers a cardiac protection against ischemia-reperfusion injury. However, the signaling mechanisms that control the protection are incompletely understood. We tested the hypothesis that Toll-like receptor 4 (TLR4) mediates the ability of lipopolysaccharide to protect against cardiac ischemia-reperfusion injury through distinct intracellular pathways involving myeloid differentiation factor 88 (MyD88), TIR-domain-containing adaptor protein-inducing interferon-beta-mediated transcription factor (Trif), inducible nitric oxide synthase (iNOS), and soluble guanylate cyclase (sGC).
Methods: Wild-type mice and genetically modified mice, that is TLR4-deficient (TLR4(-def)), TLR2 knockout (TLR2(-/-)), MyD88(-/-), Trif(-/-), iNOS(-/-), and sGC alpha 1(-/-), were treated with normal saline or 0.1 mg/kg lipopolysaccharide intraperitoneally. Twenty-four hours later, isolated hearts were perfused in a Langendorff apparatus and subsequently subjected to 30 min global ischemia and reperfusion for as long as 60 min. Left ventricular function and myocardial infarction sizes were examined.
Results: Compared with saline-treated mice, lipopolysaccharide-treated mice had markedly improved left ventricular developed pressure and dP/dt(max) (P < 0.01) and reduced myocardial infarction sizes (37.2 +/- 3.4% vs. 19.8 +/- 4.9%, P < 0.01) after ischemia-reperfusion. The cardiac protectiveeffect of lipopolysaccharide was abolished in the TLR4(-def) and MyD88(-/-) mice but remained intact in TLR2(-/-) or Trif(-/-) mice. iNOS(-/-) mice or wild-type mice treated with the iNOS inhibitor 1400W failed to respond to the TLR4-induced nitric oxide production and were not protected by the lipopolysaccharide preconditioning. Although sGC alpha(-/-)(1) mice had robust nitric oxide production in response to lipopolysaccharide, they were not protected by the TLR4-elicited cardiac protection.
Conclusions: TLR4 activation confers a potent cardiac protection against ischemia-reperfusion injury via a MyD88-dependent, but Trif-independent, mechanism. iNOS/sGC are essential for the TLR4-induced cardiac protection.
C1 [Wang, E.; Feng, Yan; Zhang, Ming; Zou, Lin; Li, Yan; Chao, Wei] Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med,Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
[Wang, E.] Cent S Univ, Xiangya Hosp, Dept Anesthesiol, Changsha, Peoples R China.
[Huang, Peigen] Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Brouckaert, Peter] Univ Ghent, Dept Mol Biomed Res, Flanders Inst Biotechnol, B-9000 Ghent, Belgium.
[Brouckaert, Peter] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium.
RP Chao, W (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med,Anesthesia Ctr Crit Care Res, GRJ 4-444,55 Fruit St, Boston, MA 02114 USA.
EM wchao@partners.org
RI Feng, Yan/H-5808-2012
FU National Institutes of Health (Bethesda, Maryland) [GM-080906]; American
Heart Association (Dallas, Texas) [0755890T]
FX This work was supported by the National Institutes of Health grant
GM-080906 (Bethesda, Maryland) and American Heart Association grant
0755890T (Dallas, Texas).
NR 51
TC 22
Z9 27
U1 2
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD MAR
PY 2011
VL 114
IS 3
BP 603
EP 613
DI 10.1097/ALN.0b013e31820a4d5b
PG 11
WC Anesthesiology
SC Anesthesiology
GA 725QH
UT WOS:000287660300021
PM 21270629
ER
PT J
AU Anderson, CD
Biffi, A
Rahman, R
Ross, OA
Jagiella, JM
Kissela, B
Cole, JW
Cortellini, L
Rost, NS
Cheng, YC
Greenberg, SM
de Bakker, PIW
Brown, RD
Brott, TG
Mitchell, BD
Broderick, JP
Worrall, BB
Furie, KL
Kittner, SJ
Woo, D
Slowik, A
Meschia, JF
Saxena, R
Rosand, J
AF Anderson, Christopher D.
Biffi, Alessandro
Rahman, Rosanna
Ross, Owen A.
Jagiella, Jeremiasz M.
Kissela, Brett
Cole, John W.
Cortellini, Lynelle
Rost, Natalia S.
Cheng, Yu-Ching
Greenberg, Steven M.
de Bakker, Paul I. W.
Brown, Robert D., Jr.
Brott, Thomas G.
Mitchell, Braxton D.
Broderick, Joseph P.
Worrall, Bradford B.
Furie, Karen L.
Kittner, Steven J.
Woo, Daniel
Slowik, Agnieszka
Meschia, James F.
Saxena, Richa
Rosand, Jonathan
CA Int Stroke Genetics Consortium
TI Common Mitochondrial Sequence Variants in Ischemic Stroke
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID WHITE-MATTER LESIONS; CEREBRAL AMYLOID ANGIOPATHY; GENOME-WIDE
ASSOCIATION; DISEASE; POWER; POLYMORPHISMS; EPIDEMIOLOGY; DYSFUNCTION;
RISK
AB Objective: Rare mitochondrial mutations cause neurologic disease, including ischemic stroke and MRI white matter changes. We investigated whether common mitochondrial genetic variants influence risk of sporadic ischemic stroke and, in patients with stroke, the volume of white matter hyperintensity (WMHV).
Methods: In this multicenter, mitochondrial genome-wide association study (GWAS), 2284 ischemic stroke cases and 1728 controls from the International Stroke Genetics Consortium were genotyped for 64 mitochondrial single nucleotide polymorphisms (SNPs). Imputation resulted in 144 SNPs, which were tested in each cohort and in meta-analysis for ischemic stroke association. A genetic score of all mitochondrial variants was also tested in association with ischemic stroke.
Results: No individual SNP reached adjusted significance in meta-analysis. A genetic score comprised of the summation of contributions from individual variants across the mitochondrial genome showed association with ischemic stroke in meta-analysis (odds ratio [OR] 1.13, p < 0.0001) with minimal heterogeneity (I(2) = 0.00). This ischemic stroke score was robust to permutation, and was also associated with WMHV in 792 nested case individuals with ischemic stroke (p = 0.037).
Interpretation: In this mitochondrial GWAS of ischemic stroke, a genetic score comprised of the sum of all common variants in the mitochondrial genome showed association with ischemic stroke. In an independent analysis of a related trait, this same score correlated with WMHV in stroke cases. Despite this aggregate association, no individual variant reached significance. Substantially larger studies will be required to identify precise sequence variants influencing cerebrovascular disease. ANN NEUROL 2011;69:471-480
C1 [Anderson, Christopher D.; Biffi, Alessandro; Rahman, Rosanna; Cortellini, Lynelle; Rost, Natalia S.; Furie, Karen L.; Saxena, Richa; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Anderson, Christopher D.; Biffi, Alessandro; Rahman, Rosanna; Cortellini, Lynelle; Rost, Natalia S.; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Anderson, Christopher D.; Biffi, Alessandro; Rahman, Rosanna; Cortellini, Lynelle; Rost, Natalia S.; de Bakker, Paul I. W.; Saxena, Richa; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Ross, Owen A.; Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Jagiella, Jeremiasz M.; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland.
[Kissela, Brett; Broderick, Joseph P.; Woo, Daniel] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA.
[Cole, John W.; Cheng, Yu-Ching; Mitchell, Braxton D.; Kittner, Steven J.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA.
[de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA.
[Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA.
RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA.
EM jrosand@partners.org
RI Ross, Owen/D-7573-2013; de Bakker, Paul/B-8730-2009;
OI de Bakker, Paul/0000-0001-7735-7858; Anderson,
Christopher/0000-0002-0053-2002; Mitchell, Braxton/0000-0003-4920-4744;
Kissela, Brett/0000-0002-9773-4013
FU GENEVA Consortium; CIDR Genotyping and Data Coordinating Center at the
University of Washington, Seattle, WA; American Heart Association/Bugher
Foundation Centers for Stroke Prevention Research [0775010N]; Deane
Institute for Integrative Study of Atrial Fibrillation and Stroke
FX We acknowledge the many study coordinators and technologists at all
sites who assisted in the collection and analysis of samples for the
current study. We also acknowledge the GENEVA Consortium, including the
CIDR Genotyping and Data Coordinating Center at the University of
Washington, Seattle, WA, for their support of the University of Maryland
GEOS Study.; This research was supported by a grant from the American
Heart Association/Bugher Foundation Centers for Stroke Prevention
Research (0775010N (C. D. A., A. B., J.R., K. L. F.)); Deane Institute
for Integrative Study of Atrial Fibrillation and Stroke (J.R., K. L.
F.); Marriott Disease Risk and Regenerative Medicine Initiative Award in
Individualized Medicine (O.A.R.); Marriott Mitochondrial Fund (O.A.R.);
Marriott Disease Risk and Regenerative Medicine Initiative Award in
Individualized Medicine (O.A.R.); National Institute for Neurologic
Disorders and Stroke (R01NS059727 (J.R.), R01NS42733 (J.F.M),
P50NS051343-04 (K. L. F., J.R.), K23NS064052 (N.S.R.), K24NS056207 (S.
M. G.), R01NS042147 (S. M. G.), R01NS039987 (J.F.M.), R01NS36695 (D. W.,
J.P.B., B. K.), R01NS30678 (D. W., J.P.B., B. K.)); Greater Cincinnati
Foundation Grant (D. W., J.P.B., B. K.); Myron and Jane Hanley Award in
Stroke Research (D. W.); Fulbright Foundation (R. R.); American
Association of University Women (R. R.); and the State Committee for
Scientific Research (Poland) (2 PO5 CO1226 (A. S., J.M.J.)).
NR 33
TC 16
Z9 16
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD MAR
PY 2011
VL 69
IS 3
BP 471
EP 480
DI 10.1002/ana.22108
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 744FW
UT WOS:000289081300010
PM 20839239
ER
PT J
AU Shi, M
Bradner, J
Hancock, AM
Chung, KA
Quinn, JF
Peskind, ER
Galasko, D
Jankovic, J
Zabetian, CP
Kim, HM
Leverenz, JB
Montine, TJ
Ginghina, C
Kang, UJ
Cain, KC
Wang, Y
Aasly, J
Goldstein, D
Zhang, J
AF Shi, Min
Bradner, Joshua
Hancock, Aneeka M.
Chung, Kathryn A.
Quinn, Joseph F.
Peskind, Elaine R.
Galasko, Douglas
Jankovic, Joseph
Zabetian, Cyrus P.
Kim, Hojoong M.
Leverenz, James B.
Montine, Thomas J.
Ginghina, Carmen
Kang, Un Jung
Cain, Kevin C.
Wang, Yu
Aasly, Jan
Goldstein, David
Zhang, Jing
TI Cerebrospinal Fluid Biomarkers for Parkinson Disease Diagnosis and
Progression
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID MULTIPLE SYSTEM ATROPHY; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN;
TAU-PROTEIN; FRACTALKINE-RECEPTOR; LEWY BODIES; CSF; DEMENTIA;
INFLAMMATION; MICROGLIA
AB Objective: There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of Parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or alpha-synuclein in the cerebrospinal fluid (CSF) is a potential index for Parkinson disease diagnosis, but not for PD severity.
Methods: Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (A beta(1-42)), Flt3 ligand, and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these 5 markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and alpha-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally.
Results: The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease (AD) and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/A beta(1-42) that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples.
Interpretation: We have demonstrated that this panel of 7 CSF proteins could aid in Parkinson disease diagnosis, differential diagnosis, and correlation with disease severity and progression. ANN NEUROL 2011;69:570-580
C1 [Shi, Min; Bradner, Joshua; Hancock, Aneeka M.; Montine, Thomas J.; Ginghina, Carmen; Wang, Yu; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA.
[Peskind, Elaine R.; Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA.
[Zabetian, Cyrus P.; Kim, Hojoong M.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA.
[Cain, Kevin C.] Univ Washington, Sch Med, Dept Biostat, Seattle, WA 98104 USA.
[Chung, Kathryn A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Peskind, Elaine R.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Zabetian, Cyrus P.; Kim, Hojoong M.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA.
[Galasko, Douglas] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Jankovic, Joseph] Baylor Coll Med, Parkinsons Dis Ctr, Houston, TX 77030 USA.
[Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA.
[Kang, Un Jung] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA.
[Wang, Yu] Huazhong Univ Sci & Technol, Dept Neurosurg, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China.
[Aasly, Jan] St Olavs Hosp, Dept Neurol, Trondheim, Norway.
[Goldstein, David] NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA.
RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA.
EM zhangj@uw.edu
RI Shi, Min/G-6165-2012;
OI Shi, Min/0000-0002-6901-2558; Zabetian, Cyrus/0000-0002-7739-4306
FU NIH [NIEHS] [ES004696]; NIH [NINDS] [NS057567, NS060252, NS062684]; NIH
[NIA] [AG025327, AG033398, AG005136, AG008017]; NIH [NCRR]
[UL1RR025014]; Dana Foundation; Parkinson's Disease Foundation; Michael
J. Fox Foundation; Friends of Alzheimer's Research; Alzheimer's
Association of Western and Central Washington; Department of Veterans
Affairs; NIH; Oregon Health and Science Univeristy; American Parkinson
Disease Association; Alzheimer's center, NIH; Center of Excellence of
the National Parkinson Foundation; Michael J Fox Foundation
FX This research was supported by the NIH [ES004696 (J.Z.) from NIEHS,
NS057567 (J.Z.), NS060252 (J.Z.), NS062684 (T.J.M., C.P.Z., J.B.L. and
J.Z.) from NINDS, AG025327 (J.Z.), AG033398 (J.Z.), AG005136 (E. R. P
and T.J.M.), AG008017 (K. A. C. and J.F.Q.) from NIA and UL1RR025014 (K.
C. C) from NCRR]; Dana Foundation (J.F.Q.); Parkinson's Disease
Foundation (C.P.Z.); Michael J. Fox Foundation (C.P.Z. and J.Z.);
Friends of Alzheimer's Research (E. R. P.); Alzheimer's Association of
Western and Central Washington (E. R. P.); Department of Veterans
Affairs (C.P.Z. and E. R. P.).; K. C. C. and J.Z. received grant(s) from
the NIH. A. M. H., C. G., J. B. and M. S. were supported by the NIH
grants. K. A. C. received grant(s) from the Oregon Health and Science
Univeristy; C.P.Z. received grants from The American Parkinson Disease
Association, Department of Veterans Affairs, Michael J. Fox Foundation,
NIH, and The Parkinson's Disease Foundation. J. F. Q. received an
Alzheimer's center grant from the NIH. J. J. has grant(s) pending from
the Center of Excellence of the National Parkinson Foundation. T. J. M.
received grant funding and has grant(s) pending from the NIH. U. J. K.
has been a consultant for CVS/caremark and has grants pending from the
Michael J Fox Foundation and the NIH. All other authors had nothing to
report.
NR 54
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U1 4
U2 22
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD MAR
PY 2011
VL 69
IS 3
BP 570
EP 580
DI 10.1002/ana.22311
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 744FW
UT WOS:000289081300020
PM 21400565
ER
PT J
AU Okereke, OI
Copeland, M
Hyman, BT
Wanggaard, T
Albert, MS
Blacker, D
AF Okereke, Olivia I.
Copeland, Maura
Hyman, Bradley T.
Wanggaard, Taylor
Albert, Marilyn S.
Blacker, Deborah
TI The Structured Interview & Scoring Tool-Massachusetts Alzheimer's
Disease Research Center (SIST-M) Development, Reliability, and
Cross-Sectional Validation of a Brief Structured Clinical Dementia
Rating Interview
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; MINI-MENTAL-STATE; INFORMANT INTERVIEW;
WEIGHTED KAPPA; QUESTIONNAIRE; MULTICENTER; PREDICTION; AGREEMENT;
VALIDITY; DECLINE
AB Background: The Clinical Dementia Rating (CDR) and CDR Sum-of-Boxes can be used to grade mild but clinically important cognitive symptoms of Alzheimer disease. However, sensitive clinical interview formats are lengthy.
Objectives: To develop a brief instrument for obtaining CDR scores and to assess its reliability and cross-sectional validity.
Methods: Using legacy data from expanded interviews conducted among 347 community-dwelling older adults in a longitudinal study, we identified 60 questions (from a possible 131) about cognitive functioning in daily life using clinical judgment, inter-item correlations, and principal components analysis. Items were selected in 1 cohort (n=147), and a computer algorithm for generating CDR scores was developed in this same cohort and rerun in a replication cohort (n =200) to evaluate how well the 60 items retained information from the original 131 items. Short interviews based on the 60 items were then administered to 50 consecutively recruited older individuals, with no symptoms or mild cognitive symptoms, at an Alzheimer's Disease Research Center. Clinical Dementia Rating scores based on short interviews were compared with those from independent long interviews.
Results: In the replication cohort, agreement between short and long CDR interviews ranged from kappa=0.65 to 0.79, with kappa=0.76 for Memory, kappa=0.77 for global CDR, and intraclass correlation coefficient for CDRSum-of-Boxes=0.89. In the cross-sectional validation, short interview scores were slightly lower than those from long interviews, but good agreement was observed for global CDR and Memory (kappa >= 0.70) as well as for CDR Sum-of-Boxes (intraclass correlation coefficient = 0.73).
Conclusion: The Structured Interview & Scoring Tool Massachusetts Alzheimer's Disease Research Center is a brief, reliable, and sensitive instrument for obtaining CDR scores in persons with symptoms along the spectrum of mild cognitive change.
C1 [Okereke, Olivia I.; Copeland, Maura; Wanggaard, Taylor; Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Hyman, Bradley T.; Blacker, Deborah] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Albert, Marilyn S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Okereke, OI (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Ste 2691, Charlestown, MA 02129 USA.
EM ookereke@partners.org
RI Okereke, Olivia/R-9934-2016
FU Harvard NeuroDiscovery Center; National Institutes of Health
[P01-AG004953, P50-AG005134]
FX This study was supported by the Harvard NeuroDiscovery Center and grants
P01-AG004953 and P50-AG005134 (the Massachusetts Alzheimer's Disease
Research Center) from the National Institutes of Health.
NR 35
TC 3
Z9 3
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD MAR
PY 2011
VL 68
IS 3
BP 343
EP 350
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 735JE
UT WOS:000288409400011
PM 21403019
ER
PT J
AU Wylie-Sears, J
Aikawa, E
Levine, RA
Yang, JH
Bischoff, J
AF Wylie-Sears, Jill
Aikawa, Elena
Levine, Robert A.
Yang, Jeong-Hee
Bischoff, Joyce
TI Mitral Valve Endothelial Cells With Osteogenic Differentiation Potential
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE endothelium; heart valves; vascular biology; EMT; endothelial cells;
mitral valve; osteogenic differentiation
ID MESENCHYMAL STEM-CELLS; MUSCLE-LIKE CELLS; PROGENITOR CELLS;
HEART-VALVE; INTERSTITIAL-CELLS; IN-VITRO; AORTIC VALVES; CALCIFICATION;
VIVO; ADAPTATION
AB Objective-Cardiac valvular endothelium is unique in its ability to undergo endothelial-to-mesenchymal transformation, a differentiation process that is essential for valve development and has been proposed as mechanism for replenishing the interstitial cells of mature valves. We hypothesized that the valvular endothelium contains endothelial cells that are direct precursors to osteoblastic valvular interstitial cells (VICs).
Methods and Results-Clonal cell populations from ovine mitral valve leaflets were isolated by single cell plating. Mitral valvular endothelial and mesenchymal clones were tested for osteogenic, adipogenic, and chondrogenic differentiation, determined by the expression of lineage-specific markers. Mitral valvular endothelial clones showed a propensity for osteogenic, as well as chondrogenic differentiation that was comparable to a mitral valvular VIC clone and to bone marrow-derived mesenchymal stem cells. Osteogenic differentiation was not detected in nonvalvular endothelial cells. Regions of osteocalcin expression, a marker of osteoblastic differentiation, were detected along the endothelium of mitral valves that had been subjected in vivo to mechanical stretch.
Conclusion-Mitral valve leaflets contain endothelial cells with multilineage mesenchymal differentiation potential, including osteogenic differentiation. This unique feature suggests that postnatal mitral valvular endothelium harbors a reserve of progenitor cells that can contribute to osteogenic and chondrogenic VICs. (Arterioscler Thromb Vasc Biol. 2011;31:598-607.)
C1 [Wylie-Sears, Jill; Yang, Jeong-Hee; Bischoff, Joyce] Harvard Univ, Sch Med, Vasc Biol Program, Childrens Hosp Boston, Boston, MA 02115 USA.
[Wylie-Sears, Jill; Yang, Jeong-Hee; Bischoff, Joyce] Harvard Univ, Sch Med, Dept Surg, Childrens Hosp Boston, Boston, MA 02115 USA.
[Aikawa, Elena] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
RP Bischoff, J (reprint author), Harvard Univ, Sch Med, Vasc Biol Program, Childrens Hosp Boston, Boston, MA 02115 USA.
EM joyce.bischoff@childrens.harvard.edu
OI Bischoff, Joyce/0000-0002-6367-1974
FU NIH [HL060490]; Leducq Fondation Mitral Network [07CVD04]
FX This work was supported initially by NIH grant HL060490 and then by
Leducq Fondation Mitral Network grant 07CVD04.
NR 39
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U1 0
U2 7
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 MAR
PY 2011
VL 31
IS 3
BP 598
EP 607
DI 10.1161/ATVBAHA.110.216184
PG 10
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 722CZ
UT WOS:000287409900020
PM 21164078
ER
PT J
AU Makimura, H
Stanley, TL
Sun, NL
Connelly, JM
Hemphill, LC
Hrovat, MI
Systrom, DM
Grinspoon, SK
AF Makimura, Hideo
Stanley, Takara L.
Sun, Noelle
Connelly, Jean M.
Hemphill, Linda C.
Hrovat, Mirko I.
Systrom, David M.
Grinspoon, Steven K.
TI Increased skeletal muscle phosphocreatine recovery after sub-maximal
exercise is associated with increased carotid intima-media thickness
SO ATHEROSCLEROSIS
LA English
DT Article
DE MRS; Spectroscopy; Mitochondria; Cardiovascular risk
ID MAGNETIC-RESONANCE-SPECTROSCOPY; MITOCHONDRIAL-FUNCTION; ADULTS
AB Background: The association between skeletal muscle mitochondrial function and CVD risk in healthy subjects is unknown.
Methods: Forty subjects were evaluated for CVD risk with lipid profile, oral glucose tolerance test and measurement of carotid intima-media thickness (cIMT). Skeletal muscle mitochondrial function was determined by phosphocreatine recovery after sub-maximal exercise with (31)Phosphorous-MRS and represented as tau PCr.
Results: tau PCr was positively associated with age (r = +0.41; P = 0.009) and cIMT (r = +0.50; P = 0.001) on univariate analyses. In multivariate regression analysis controlling for age, the association between tau PCr and cIMT remained significant (beta = 0.003; P = 0.03). This association remained significant after controlling for traditional risk factors for CVD including age, gender, tobacco use, BMI, blood pressure, cholesterol and fasting glucose in a combined model (beta = 0.003; P = 0.04; R(2) = 0.53; P = 0.008 for overall model).
Conclusions: These data suggest a novel association between skeletal muscle tau PCr and increased cIMT, independent of age or traditional CVD risk factors. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Makimura, Hideo; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
[Makimura, Hideo; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Makimura, Hideo; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Stanley, Takara L.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA.
[Connelly, Jean M.; Hemphill, Linda C.] Massachusetts Gen Hosp, Boston Heart Fdn, Boston, MA 02114 USA.
[Hrovat, Mirko I.; Systrom, David M.] Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA.
[Hrovat, Mirko I.; Systrom, David M.] Mirtech Inc, Brockton, MA 02301 USA.
RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 211, Boston, MA 02114 USA.
EM hmakimura@partners.org
OI Systrom, David/0000-0002-9610-6330
FU National Center for Research Resources [1UL1RR025758-01]; Center for
Functional Neuroimaging Technologies [P41RR14075]; National Institutes
of Health [1R01HL085268-01A1, K24DK064545-06]
FX Studies were conducted at the Clinical Research Center of the
Massachusetts Institute of Technology and the Massachusetts General
Hospital funded by grant number 1UL1RR025758-01, Harvard Clinical and
Translational Science Center, from the National Center for Research
Resources. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National Center
For Research Resources or the National Institutes of Health.
31P-MRS imaging studies were conducted at the Athinoula A.
Martinos Center for Biomedical Imaging which receives funding from the
Center for Functional Neuroimaging Technologies P41RR14075. This work
was supported in part by the National Institutes of Health grant
1R01HL085268-01A1 (to SG) and K24DK064545-06 (to SG). Sponsors did not
play any role in the study design; in the collection, analysis and
interpretation of the data; in the writing of the report; and in the
decision to submit the paper for publication.
NR 14
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Z9 1
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD MAR
PY 2011
VL 215
IS 1
BP 214
EP 217
DI 10.1016/j.atherosclerosis.2010.11.037
PG 4
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 730CN
UT WOS:000288008700033
PM 21185022
ER
PT J
AU Waltz, P
Carchman, EH
Young, AC
Rao, J
Rosengart, MR
Kaczorowski, D
Zuckerbraun, BS
AF Waltz, Paul
Carchman, Evie H.
Young, Atalie C.
Rao, Jayashree
Rosengart, Matthew R.
Kaczorowski, David
Zuckerbraun, Brian S.
TI Lipopolysaccaride induces autophagic signaling in macrophages via a
TLR4, heme oxygenase-1 dependent pathway
SO AUTOPHAGY
LA English
DT Article
DE sepsis; tumor necrosis factoralpha; RAW 264.7; peritoneal macrophages
ID CARBON-MONOXIDE; MYCOBACTERIUM-TUBERCULOSIS; INNATE IMMUNITY;
GENE-TRANSFER; CELLS; LIVER; EXPRESSION; PROTECTION; IL-1-BETA; PROTEINS
AB Toll-like receptor (TLR) signaling is an important part of the innate immune response. One of the downstream responses to TLR4 signaling upon lipopolysaccharide (LPS) stimulation is the induction of autophagy, which is a key response to multiple stressors. An additional adaptive signaling molecule that is involved in the response to stress is heme oxygenase-1 (HO-1). HO-1 signaling is essential to limit inflammation and restore homeostasis. We found that LPS induced autophagic signaling in macrophages via a TLR4, HO-1 dependent pathway in macrophages. These data add to the developing contribution of autophagic signaling as part of the inflammatory response.
C1 [Zuckerbraun, Brian S.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA.
[Waltz, Paul; Carchman, Evie H.; Young, Atalie C.; Rao, Jayashree; Rosengart, Matthew R.; Kaczorowski, David; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA.
RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA.
EM zuckerbraunbs@upmc.edu
FU NIGMS NIH HHS [R01 GM082830]
NR 41
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U1 1
U2 12
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD MAR
PY 2011
VL 7
IS 3
BP 315
EP 320
DI 10.4161/auto.7.3.14044
PG 6
WC Cell Biology
SC Cell Biology
GA 728BU
UT WOS:000287849800009
PM 21307647
ER
PT J
AU Groblewski, PA
Franken, FH
Cunningham, CL
AF Groblewski, Peter A.
Franken, Frederick H.
Cunningham, Christopher L.
TI Inhibition of extracellular signal-regulated kinase (ERK) activity with
SL327 does not prevent acquisition, expression, and extinction of
ethanol-seeking behavior in mice
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Extinction; ERK; SL327; Conditioned place preference; Ethanol; DBA/2J
ID CONDITIONED PLACE PREFERENCE; FEAR-POTENTIATED STARTLE; ACTIVATED
PROTEIN-KINASE; D-CYCLOSERINE; NUCLEUS-ACCUMBENS; INDUCED SENSITIZATION;
AMYGDALA DOPAMINE; PATHWAY; RECEPTORS; AVERSION
AB Although extracellular signal-regulated kinase (ERK) activity is essential for the acquisition of a variety of associative learning tasks, its involvement in the acquisition and extinction of ethanol (EtOH)-induced conditioned place preference (CPP) remains unknown. Therefore, in these experiments we examined the effects of the ERK-kinase (MEK)-inhibitor SL327 on acquisition and expression of EtOH-CPP as well as the dose- and time-dependent effects of SL327 on CPP extinction. The parametric findings of Experiment 1 showed that three 30-min (but not 15- or 5-min) non-reinforced trials were required to completely extinguish EtOH-CPP in male, DBA/2J mice. In Experiments 2 and 3, SL327 (30 and 50 mg/kg), administered 30 or 90 min prior to extinction trials, was unable to impair EtOH-CPP extinction. Experiment 4 showed that SL327 (50 mg/kg) had no effect on acquisition of EtOH-CPP or the development of EtOH-induced sensitization during conditioning. When administered prior to testing in Experiments 5 and 6, SL327 did not alter expression of EtOH-CPP but did reduce test activity. Importantly, SL327 significantly reduced pERK protein levels when assessed in the dorsal striatum and motor cortex (Experiment 7). Together, these data suggest that EtOH-related learning and EtOH reward in mice, as assessed with CPP, are not impaired by the systemically administered MEK-inhibitor SL327. Published by Elsevier B.V.
C1 [Groblewski, Peter A.; Franken, Frederick H.; Cunningham, Christopher L.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
[Groblewski, Peter A.; Cunningham, Christopher L.] Portland Alcohol Res Ctr, Portland, OR 97239 USA.
[Franken, Frederick H.] Portland VA Med Ctr, Portland, OR USA.
RP Groblewski, PA (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, L470,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM groblews@ohsu.edu
FU National Institutes of Health [AA018052, AA007702, DA07262]; American
Psychological Association; N.L. Tartar Research Fund
FX This research was supported by grants from the National Institutes of
Health (AA018052, AA007702, DA07262), the American Psychological
Association, and the N.L. Tartar Research Fund. We would like to thank
Courtney Zerizef for her contributions to Experiment 6.
NR 46
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U1 2
U2 4
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 MAR 1
PY 2011
VL 217
IS 2
BP 399
EP 407
DI 10.1016/j.bbr.2010.11.018
PG 9
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 712WZ
UT WOS:000286698300018
PM 21074569
ER
PT J
AU Buchanan, RW
Keefe, RSE
Lieberman, JA
Barch, DM
Csernansky, JG
Goff, DC
Gold, JM
Green, MF
Jarskog, LF
Javitt, DC
Kimhy, D
Kraus, MS
McEvoy, JP
Mesholam-Gately, RI
Seidman, LJ
Ball, MP
McMahon, RP
Kern, RS
Robinson, J
Marder, SR
AF Buchanan, Robert W.
Keefe, Richard S. E.
Lieberman, Jeffrey A.
Barch, Deanna M.
Csernansky, John G.
Goff, Donald C.
Gold, James M.
Green, Michael F.
Jarskog, L. Fredrik
Javitt, Daniel C.
Kimhy, David
Kraus, Michael S.
McEvoy, Joseph P.
Mesholam-Gately, Raquelle I.
Seidman, Larry J.
Ball, M. Patricia
McMahon, Robert P.
Kern, Robert S.
Robinson, James
Marder, Stephen R.
TI A Randomized Clinical Trial of MK-0777 for the Treatment of Cognitive
Impairments in People with Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Clinical trial; cognition; functional capacity; gamma-aminobutyric acid;
schizophrenia; symptoms
ID WORKING-MEMORY; PREFRONTAL CORTEX; GENE-EXPRESSION; RATING-SCALE;
PYRAMIDAL NEURONS; AXON TERMINALS; MESSENGER-RNA; DEFICITS; MATRICS;
BATTERY
AB Background: In a previous pilot study, MK-0777-a gamma-aminobutyric acid (GABA)(A) alpha(2)/alpha(3) partial agonist-was reported to improve delayed memory and cognitive measures of prefrontal cortical function in people with schizophrenia. The current study was designed to further examine the efficacy and safety of MK-0777 for the treatment of cognitive impairments in schizophrenia.
Methods: Sixty people with DSM-IV schizophrenia entered a 4-week, multi-center, double-blind, placebo-controlled, randomized clinical trial. Participants were randomized to: MK-0777 3 mg b.i.d. (n = 18); MK-0777 8 mg b.i.d. (n = 21); or placebo (n = 21). Participants were clinically stable. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, AX-Continuous Performance Test, and N-Back were used to assess cognition. The University of California San Diego (UCSD) Performance Based Skills Assessment-2 and the Schizophrenia Cognition Rating Scale assessed functional capacity and served as functional outcome coprimary measures.
Results: There were no significant group differences on the primary outcome measure, the MATRICS Consensus Cognitive Battery composite score. Secondary analyses suggested that participants randomized to placebo performed significantly better on visual memory and reasoning/problem-solving tests than participants assigned to either MK-0777 dose. There were no significant group differences on the AX-Continuous Performance Test or N-Back d prime scores or UCSD Performance-Based Skills Assessment-2 and Schizophrenia Cognition Rating Scale total scores. In general, MK-0777 was well-tolerated with minimal side effects.
Conclusions: The study results suggest that MK-0777 has little benefit for cognitive impairments in people with schizophrenia. The GABA(A) receptor remains a promising target, but a more potent partial agonist with greater intrinsic activity at the GABA(A) alpha 2 site might be needed for cognitive enhancement in schizophrenia.
C1 [Buchanan, Robert W.; Gold, James M.; Ball, M. Patricia; McMahon, Robert P.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA.
[Keefe, Richard S. E.; Kraus, Michael S.; McEvoy, Joseph P.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[Lieberman, Jeffrey A.; Jarskog, L. Fredrik; Kimhy, David] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, New York, NY 10027 USA.
[Lieberman, Jeffrey A.; Jarskog, L. Fredrik; Kimhy, David] Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA.
[Javitt, Daniel C.; Robinson, James] NYU, Sch Med, Dept Psychiat, Nathan S Kline Inst Psychiat Res, New York, NY USA.
[Barch, Deanna M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Csernansky, John G.] NW Feinberg Sch Med, Dept Psychiat, Chicago, IL USA.
[Mesholam-Gately, Raquelle I.; Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Goff, Donald C.; Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Green, Michael F.; Kern, Robert S.; Marder, Stephen R.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA.
[Green, Michael F.; Kern, Robert S.; Marder, Stephen R.] VA VISN 22 Mental Illness Res Educ & Clin Ctr, Los Angeles, CA USA.
RP Buchanan, RW (reprint author), Univ Maryland, Sch Med, Grounds Spring Grove Hosp, Dept Psychiat, Maple & Locust St,POB 21247, Baltimore, MD 21228 USA.
EM rwbuchanan@mprc.umaryland.edu
RI McMahon, Robert/C-5462-2009;
OI Kimhy, David/0000-0001-7735-9378
FU National Institute of Mental Health [HHSN278200441003C]; McDonnell
Center for Higher Brain Function; National Alliance for Research on
Schizophrenia and Depression; Allon; Novartis; Janssen Pharmaceutica;
Eli Lilly; Sanofi Aventis; Pfizer; Janssen; GlaxoSmithKline; Department
of Veterans Affairs; Singapore National Medical Research Council;
AstraZeneca; MATRICS Assessment; Otsuka; VivoMetrics; Merck; Sepracor;
Targacept; Wyeth; Schering Plough; Bristol Meyers Squibb; Roche;
Lundbeck; Acadia; Jazz Pharmaceuticals
FX This study was funded by National Institute of Mental Health Contract
HHSN278200441003C to the University of California, Los Angeles (SRM,
Principal Investigator). Double-blind medications were provided by Merck
and Company. We wish to thank the following for their assistance in the
conduct of the study: New York State Psychiatric Institute and College
of Physicians and Surgeons, Columbia University: Marlene Carlson; Duke
University Medical Center: Trina Walker and Leslie Yusko; Massachusetts
General Hospital, Harvard Medical School: Shannon Sorenson and Joanne
Wojcik; Maryland Psychiatric Research Center: Sharon August and Ilene
Verovsky; Washington University in St. Louis School of Medicine: Meghan
Flatley and Emily Thomason and UCLA Semel Institute for Neuroscience and
Human Behavior: Ayala Ofek and Ewa Witt.; Ms. Ball reported consultant
services with ePharmaLearning to provide training fora Pfizer trial. Dr.
Barch disclosed the receipt of research funding from the National
Institute of Mental Health, the McDonnell Center for Higher Brain
Function, National Alliance for Research on Schizophrenia and
Depression, Allon, and Novartis. Dr. Buchanan has served as a Data and
Safety Monitoring Board member for Cephalon, Otsuka, and Pfizer; a
consultant to Abbott, GlaxoSmithKline, Sanofi-Aventis, Scherring-Plough;
and an Advisory Board member for Abbott, AstraZeneca, Cypress
Bioscience, Merck, Pfizer, Roche, Solvay Pharmaceuticals, and Wyeth. He
has received grant support from Janssen Pharmaceutica. Dr. Csernansky
reported receipt of honoraria for service on Data Monitoring Committees
for clinical trials sponsored by Eli Lilly and Sanofi Aventis. Dr. Goff
has served as consultant and/or adviser to: Xytis, Forest Laboratories,
Pfizer, Indevus Pharmaceuticals, H. Lundbeck, Schering-Plough, Eli
Lilly, Takeda, Biovail, Solvay, Hoffman-La Roche, and Dianippon
Sumitomo; served on a Data and Safety Monitoring Board for Otsuka and
Wyeth; and received research funding from Pfizer, Janssen, Novartis, and
GlaxoSmithKline. Dr. Gold disclosed royalties from the brief assessment
of cognition in schizophrenia (BACS) and has served as a consultant for
Pfizer, Solvay, GlaxoSmithKline, AstraZeneca, and Merck. Dr. Green has
been a consultant to Abbot Laboratories, Astellas, Cypress Bioscience,
Dainippon Sumitomo Pharma, GlaxoSmithKline, Lundbeck, Otsuka, Sanofi
Aventis, Takeda, and Wyeth and a speaker for Janssen Cilag. Dr. Jarskog
has received grant support from Novartis and GlaxoSmithKline. Dr. Javitt
serves as Chair, scientific advisory board, and major shareholder of
Glytech and Amino Acids Solutions. Over the past 2 years, Dr. Javitt has
served as a consultant for pharmaceutical companies, including Sanofi
Aventis, Solvay, Organon, Lundbeck, AstraZeneca, NPS Pharmaceuticals,
Takeda, and Sepracor. He currently serves on a new treatment development
advisory board for Pfizer, serves on the Scientific Advisory Board for
Promentis Pharmaceuticals, and has received research support from the
pharmaceutical industry, including, in the past year, Pfizer, Roche, and
Jazz Pharmaceuticals. Dr. Keefe reports having received
investigator-initiated research funding support from the National
Institute of Mental Health, Department of Veterans Affairs, Allon,
GlaxoSmithKline, Novartis, and the Singapore National Medical Research
Council and an unrestricted educational grant from AstraZeneca. He
disclosed receiving honoraria and served as a consultant or advisory
board member for Abbott, Acadia, AstraZeneca, BiolioneRx, BrainCells,
Bristol-Myers Squibb, CHDI, Cypress Bioscience, Dainippon Sumitomo
Pharma, Eli Lilly, En Vivo, Johnson & Johnson, Lundbeck, Memory
Pharmaceuticals, Merck, Neurosearch, NeuroCog Trials, Novartis,
Orexigen, Orion, Otsuka, Pfizer, Prophase, Roche, SanofiAventis, Shire,
Solvay, Takeda, Wyeth, and Xenoport. Dr. Keefe reports being a
shareholder in NeuroCog Trials as well as receiving royalties from the
BACS testing battery and the MATRICS Consensus Cognitive Battery (BA CS
Symbol Coding). Dr. Kern receives financial support from MATRICS
Assessment, a nonprofit organization that facilitates the distribution
of the MATRICS Consensus Cognitive Battery. He also has received
consultation fees from Otsuka. Dr. Kimhy has received an instrument
grant from VivoMetrics. Dr.; Lieberman received grant/research funding
from Allon, GlaxoSmithKline, Merck, Novartis, Pfizer Sepracor, and
Targacept and also served on advisory boards for Bioline, Eli Lilly,
GlaxoSmithKline, Intracellular Therapies, Pierre Fabre and Psychogenics;
and he holds a patent for Repligen. Dr. Marder reports having received
consulting fees from the following companies: Wyeth, Otsuka, Pfizer,
Schering Plough, Bristol Meyers Squibb, Roche, Lundbeck, Sanofi Aventis,
and Acadia. He received research support from Novartis and
GlaxoSmithKline. Dr. McEvoy has received grants from GlaxoSmithKline,
Pfizer, and Novartis as well as honoraria from Eli Lilly. Dr. Larry J.
Seidman reports no financial disclosures or conflicts of interest for
the past 2 years. He has been a speaker for Shire Pharmaceuticals and
received an unrestricted education grant from Janssen Pharmaceuticals in
the past 5 years. All other authors report no biomedical financial
interests or potential conflicts of interest.
NR 47
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PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 1
PY 2011
VL 69
IS 5
BP 442
EP 449
DI 10.1016/j.biopsych.2010.09.052
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 727SO
UT WOS:000287822000008
PM 21145041
ER
PT J
AU Pulsipher, MA
Young, NS
Tolar, J
Risitano, AM
Deeg, HJ
Anderlini, P
Calado, R
Kojima, S
Eapen, M
Harris, R
Scheinberg, P
Savage, S
Maciejewski, JP
Tiu, RV
DiFronzo, N
Horowitz, MM
Antin, JH
AF Pulsipher, Michael A.
Young, Neal S.
Tolar, Jakub
Risitano, Antonio M.
Deeg, H. Joachim
Anderlini, Paolo
Calado, Rodrigo
Kojima, Seiji
Eapen, Mary
Harris, Richard
Scheinberg, Phillip
Savage, Sharon
Maciejewski, Jaroslaw P.
Tiu, Ramon V.
DiFronzo, Nancy
Horowitz, Mary M.
Antin, Joseph H.
TI Optimization of Therapy for Severe Aplastic Anemia Based on Clinical,
Biologic, and Treatment Response Parameters: Conclusions of an
International Working Group on Severe Aplastic Anemia Convened by the
Blood and Marrow Transplant Clinical Trials Network, March 2010
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Severe aplastic anemia; Blood and marrow transplantation;
Immunosuppressive therapy; Telomeres
ID STEM-CELL TRANSPLANTATION; ALTERNATIVE DONOR TRANSPLANTS; HIGH-DOSE
CYCLOPHOSPHAMIDE; ANTI-THYMOCYTE GLOBULIN; TERM-FOLLOW-UP; ANTITHYMOCYTE
GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; CONDITIONING REGIMEN; BONE-MARROW;
ANTILYMPHOCYTE GLOBULIN
AB Although recent advances in therapy offer the promise for improving survival in patients with severe aplastic anemia (SAA), the small size of the patient population, lack of a mechanism in North America for longitudinal follow-up of patients, and inadequate cooperation among hematologists, scientists, and transplant physicians remain obstacles to conducting large studies that would advance the field. To address this issue, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a group of international experts in March 2010 to define the most important questions in the basic science, immunosuppressive therapy (IST), and bone marrow transplantation (BMT) of SAA and propose initiatives to facilitate clinical and biologic research. Key conclusions of the working group were: ( 1) new patients should obtain accurate, expert diagnosis and early identification of biologic risk; (2) a population-based SAA outcomes registry should be established in North America to collect data on patients longitudinally from diagnosis through and after treatment; (3) a repository of biologic samples linked to the clinical data in the outcomes registry should be developed; (4) innovative approaches to unrelated donor BMT that decrease graft-versus-host disease are needed; and (5) alternative donor transplantation approaches for patients lacking HLA-matched unrelated donors must be improved. A partnership of BMT, IST, and basic science researchers will develop initiatives and partner with advocacy and funding organizations to address these challenges. Collaboration with similar study groups in Europe and Asia will be pursued. Biol Blood Marrow Transplant 17: 291-299 (2011) (C) 2011 American Society fin. Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [Pulsipher, Michael A.] Univ Utah, Sch Med, Primary Childrens Med Ctr, Salt Lake City, UT 84113 USA.
[Young, Neal S.; Calado, Rodrigo; Scheinberg, Phillip] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Tolar, Jakub] Univ Minnesota, Minneapolis, MN USA.
[Risitano, Antonio M.] Univ Naples Federico 2, Naples, Italy.
[Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Kojima, Seiji] Childrens Med Ctr, Nagoya, Aichi, Japan.
[Eapen, Mary; Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Harris, Richard] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Savage, Sharon] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Maciejewski, Jaroslaw P.; Tiu, Ramon V.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Pulsipher, MA (reprint author), Univ Utah, Sch Med, Primary Childrens Med Ctr, 100 N Mario Capecchi Dr, Salt Lake City, UT 84113 USA.
EM michael.pulsipher@hsc.utah.edu
RI Calado, Rodrigo/G-2619-2011; Kojima, Seiji/I-1601-2012
FU Blood and Marrow Transplant Clinical Trials Network; National Heart,
Lung, and Blood Institute; National Cancer Institute; Genzyme
FX Financial disclosure: This International Working Group was supported by
the Blood and Marrow Transplant Clinical Trials Network, the National
Heart, Lung, and Blood Institute, the National Cancer Institute, and a
grant from Genzyme. The authors gratefully acknowledge the participating
centers and co-investigators of the BMT CTN 0301 study.
NR 49
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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 MAR
PY 2011
VL 17
IS 3
BP 291
EP 299
DI 10.1016/j.bbmt.2010.10.028
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 725GM
UT WOS:000287633200002
PM 21034841
ER
PT J
AU Zilberberg, J
Friedman, TM
Dranoff, G
Korngold, R
AF Zilberberg, Jenny
Friedman, Thea M.
Dranoff, Glenn
Korngold, Robert
TI Treatment with GM-CSF Secreting Myeloid Leukemia Cell Vaccine Prior to
Autologous-BMT Improves the Survival of Leukemia-Challenged Mice
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE AML; Autologous BMT; Immunotherapy
ID COLONY-STIMULATING FACTOR; BONE-MARROW-TRANSPLANTATION;
VERSUS-HOST-DISEASE; MINOR HISTOCOMPATIBILITY ANTIGENS; POTENT ANTITUMOR
IMMUNITY; BEARING DENDRITIC CELLS; T-CELLS; LANGERHANS CELLS;
IMMUNOTHERAPY; RESPONSES
AB Vaccination with irradiated autologous tumor cells, engineered to secrete granulocyte macrophage-colony stimulating factor (GM-CSF) (GM tumor), can generate potent antitumor effects when combined with autologous bone marrow transplantation (BMT). That notwithstanding, the post-BMT milieu, characterized by marked cytopenia, can pose a challenge to the implementation of vaccine immunotherapies. To bypass this problem, partial post-BMT immune reconstitution has been allowed to develop prior to vaccination. However, delaying vaccination can also potentially allow the expansion of residual tumor cells. Other approaches have used reinfusion of "primed" autologous lymphocytes and multiple administrations of GM tumor cells, which required the processing of large amounts of tumor. Utilizing the MMB3.19 murine myeloid leukemia model, we tested whether a single dose of GM tumor cells, 7 days prior to syngeneic BMT, could be a curative treatment in MMB3.19-challenged recipient mice. This vaccination protocol significantly improved survival of mice by eliciting long-lasting host immune responses that survived lethal irradiation, and were even protective against post-BMT tumor rechallenge. Furthermore, we demonstrated that mature donor lymphocytes can also play a limited role in mounting the antitumor response, but our pre-BMT vaccination strategy obviated the need for either established de novo immune reconstitution or the use of multiple post-BMT immunizations. Biol Blood Marrow Transplant 17: 330-340 (2011) (C) 2011 American Society for Blood and Marrow Transplantation
C1 [Zilberberg, Jenny; Friedman, Thea M.; Korngold, Robert] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ 07601 USA.
[Dranoff, Glenn] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Zilberberg, J (reprint author), Hackensack Univ, Med Ctr, John Theurer Canc Ctr, 30 Prospect Ave, Hackensack, NJ 07601 USA.
EM jzilberberg@humed.com
FU NIH [U19-AI029530]
FX We thank Eugenia Dziopa and Kristin Vazzana for help with the BMT
experiments, and Themaba Nyirenda, PhD, for consultation on statistical
analysis. This work was supported by Project 3 of NIH Grant U19-AI029530
(R.K).
NR 38
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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 MAR
PY 2011
VL 17
IS 3
BP 330
EP 340
DI 10.1016/j.bbmt.2010.09.020
PG 11
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 725GM
UT WOS:000287633200006
PM 20946965
ER
PT J
AU Issa, NC
Marty, FM
Gagne, LS
Koo, S
Verrill, KA
Alyea, EP
Cutler, CS
Koreth, J
Armand, P
Ho, VT
Antin, JH
Soiffer, RJ
Baden, LR
AF Issa, Nicolas C.
Marty, Francisco M.
Gagne, Lisa S.
Koo, Sophia
Verrill, Kelly A.
Alyea, Edwin P.
Cutler, Corey S.
Koreth, John
Armand, Philippe
Ho, Vincent T.
Antin, Joseph H.
Soiffer, Robert J.
Baden, Lindsey R.
TI Seroprotective Titers against 2009 H1N1 Influenza A Virus after
Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation
Recipients
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Immune response; Swine Influenza; rituximab; bone marrow transplantation
ID MARROW-TRANSPLANTATION; INFECTIONS; RESPONSES; IMMUNIZATION; EXPERIENCE
AB Little data are available regarding the safety and immunologic response to pandemic H1N1 influenza vaccine in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). We measured serum antibody titers against A/California/7/2009 H1N1 using a hemagglutination inhibition assay in 82 allogeneic HSCT recipients who received the 2009 H1N1 vaccine between November 2009 and January 2010 after it became available at our institution. The median time between HSCT and vaccination was 19 months (range, 2.5-94 months), and the median time from vaccination to specimen collection was 56 days (range, 14-140 days). Seroprotective antibody titers (hemagglutination inhibition titer >= 1:40) against 2009 H1N1 influenza A virus were detected in 51% of patients. The presence of chronic graft-versus-host disease and type of conditioning regimen did not affect the rate of detection of seroprotective titers after vaccination. Patients were more likely to have a seroprotective titer the farther away from HSCT they were (adjusted odds ratio, 1.79 per year; 95% confidence interval, 1.12-2.85). Rituximab administration in the year before vaccination was associated with a lack of seroprotective titer (adjusted odds ratio, 0.11; 95% confidence interval, 0.01-0.97). The vaccine was safe and well tolerated. Strategies are needed to improve the influenza vaccine response in this population, especially those receiving immunotherapy. Biol Blood Marrow Transplant 17: 434-438 (2011) (C) 2011 American Society fir Blood and Marrow Transplantation
C1 [Issa, Nicolas C.; Marty, Francisco M.; Gagne, Lisa S.; Koo, Sophia; Verrill, Kelly A.; Cutler, Corey S.; Baden, Lindsey R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Issa, Nicolas C.; Marty, Francisco M.; Koo, Sophia; Alyea, Edwin P.; Cutler, Corey S.; Koreth, John; Armand, Philippe; Ho, Vincent T.; Antin, Joseph H.; Soiffer, Robert J.; Baden, Lindsey R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
RP Issa, NC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A-4, Boston, MA 02115 USA.
EM nissa@partners.org
OI Koo, Sophia/0000-0002-4973-7439
FU National Cancer Institute [CA142106]; Jock and Bunny Adams Education and
Research Fund
FX We thank David W. Kubiak, PharmD, BCPS, Anne McDonnell, PharmD, Emily
Mui, PharmD, and Juliette Kim, PharmD for their help in retrieving
pharmacy data on vaccine administration oseltamivir, intravenous
immunoglobulin, rituximab, and alemtuzumab use. This study was supported
in part by National Cancer Institute Grant CA142106 and the Jock and
Bunny Adams Education and Research Fund.
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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 MAR
PY 2011
VL 17
IS 3
BP 434
EP 438
DI 10.1016/j.bbmt.2010.10.002
PG 5
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 725GM
UT WOS:000287633200018
PM 20950701
ER
PT J
AU Kuranov, RV
Qiu, JZ
McElroy, AB
Estrada, A
Salvaggio, A
Kiel, J
Dunn, AK
Duong, TQ
Milner, TE
AF Kuranov, Roman V.
Qiu, Jinze
McElroy, Austin B.
Estrada, Arnold
Salvaggio, Anthony
Kiel, Jeffrey
Dunn, Andrew K.
Duong, Timothy Q.
Milner, Thomas E.
TI Depth-resolved blood oxygen saturation measurement by dual-wavelength
photothermal (DWP) optical coherence tomography
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID SIGNALS; SCATTERING; SPECTROSCOPY; ABSORPTION; RESOLUTION; VELOCITY;
OXIMETRY; TISSUE; CORTEX; MEDIA
AB Non-invasive depth-resolved measurement of hemoglobin oxygen saturation (SaO(2)) levels in discrete blood vessels may have implications for diagnosis and treatment of various pathologies. We introduce a novel Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) for non-invasive depth-resolved measurement of SaO(2) levels in a blood vessel phantom. DWP OCT SaO(2) is linearly correlated with blood-gas SaO(2) measurements. We demonstrate 6.3% precision in SaO(2) levels measured a phantom blood vessel using DWP-OCT with 800 and 765 nm excitation wavelengths. Sources of uncertainty in SaO(2) levels measured with DWP-OCT are identified and characterized. (C) 2011 Optical Society of America
C1 [Kuranov, Roman V.; Kiel, Jeffrey; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Kuranov, Roman V.; Qiu, Jinze; McElroy, Austin B.; Estrada, Arnold; Salvaggio, Anthony; Dunn, Andrew K.; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
[Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Kuranov, RV (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA.
EM kuranov@uthscsa.edu
RI Qiu, Jinze /I-2272-2013; Dunn, Andrew/I-9527-2014
OI Qiu, Jinze /0000-0001-8466-1460;
FU NIH [UL1RR025767, KL2RR025766, R01 EY018855, R01 EY014211]; San Antonio
Area Foundation [130977]; Department of Veterans Affairs
FX This research was partially supported by NIH KL2 training grants (parent
grants UL1RR025767 and KL2RR025766), San Antonio Area Foundation grant
130977 to RVK, Department of Veterans Affairs (VA MERIT Award) to T. Q.
Duong and NIH (R01 EY018855 and R01 EY014211) to T. Q. Duong.
NR 41
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PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD MAR 1
PY 2011
VL 2
IS 3
BP 491
EP 504
DI 10.1364/BOE.2.000491
PG 14
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 886SW
UT WOS:000299875200009
PM 21412455
ER
PT J
AU Dehaes, M
Grant, PE
Sliva, DD
Roche-Labarbe, N
Pienaar, R
Boas, DA
Franceschini, MA
Selb, J
AF Dehaes, Mathieu
Grant, P. Ellen
Sliva, Danielle D.
Roche-Labarbe, Nadege
Pienaar, Rudolph
Boas, David A.
Franceschini, Maria Angela
Selb, Juliette
TI Assessment of the frequency-domain multi-distance method to evaluate the
brain optical properties: Monte Carlo simulations from neonate to adult
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID NEAR-INFRARED SPECTROSCOPY; TIME-RESOLVED REFLECTANCE; HIGHLY SCATTERING
MEDIA; CEREBRAL BLOOD-VOLUME; PHOTON MIGRATION; INFANT BRAIN; HUMAN
HEAD; NONINVASIVE DETERMINATION; HEMODYNAMIC-RESPONSE; NEWBORN-INFANTS
AB The near infrared spectroscopy (NIRS) frequency-domain multi-distance (FD-MD) method allows for the estimation of optical properties in biological tissue using the phase and intensity of radiofrequency modulated light at different source-detector separations. In this study, we evaluated the accuracy of this method to retrieve the absorption coefficient of the brain at different ages. Synthetic measurements were generated with Monte Carlo simulations in magnetic resonance imaging (MRI)-based heterogeneous head models for four ages: newborn, 6 and 12 month old infants, and adult. For each age, we determined the optimal set of source-detector separations and estimated the corresponding errors. Errors arise from different origins: methodological (FD-MD) and anatomical (curvature, head size and contamination by extra-cerebral tissues). We found that the brain optical absorption could be retrieved with an error between 8-24% in neonates and infants, while the error increased to 19-44% in adults over all source-detector distances. The dominant contribution to the error was found to be the head curvature in neonates and infants, and the extra-cerebral tissues in adults. (C) 2011 Optical Society of America
C1 [Dehaes, Mathieu; Grant, P. Ellen; Sliva, Danielle D.; Pienaar, Rudolph] Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA.
[Dehaes, Mathieu; Grant, P. Ellen; Sliva, Danielle D.; Pienaar, Rudolph] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Grant, P. Ellen; Roche-Labarbe, Nadege; Boas, David A.; Franceschini, Maria Angela; Selb, Juliette] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Grant, P. Ellen; Roche-Labarbe, Nadege; Boas, David A.; Franceschini, Maria Angela; Selb, Juliette] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Dehaes, M (reprint author), Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, 300 Longwood Ave, Boston, MA 02115 USA.
EM mathieu.dehaes@childrens.harvard.edu
RI Roche-Labarbe, Nadege/N-9101-2015
OI Roche-Labarbe, Nadege/0000-0002-5010-0400
FU NIH/NICHD [R01-HD042908, R21-HD058725]; NIH/NCRR [P41-RR14075]; Fonds
Quebecois de la Recherche sur la Nature et les Technologies (FQRNT-B3,
Canada)
FX The authors thank Myong-Sun Choe (CHB) and Lilla Zollei (MGH). This work
was supported by the NIH/NICHD grants # R01-HD042908 and R21-HD058725,
the NIH/NCRR grant # P41-RR14075 and the Fonds Quebecois de la Recherche
sur la Nature et les Technologies (FQRNT-B3, Canada).
NR 45
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PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD MAR 1
PY 2011
VL 2
IS 3
BP 552
EP 567
DI 10.1364/BOE.2.000552
PG 16
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 886SW
UT WOS:000299875200015
PM 21412461
ER
PT J
AU Dehaes, M
Gagnon, L
Lesage, F
Pelegrini-Issac, M
Vignaud, A
Valabregue, R
Grebe, R
Wallois, F
Benali, H
AF Dehaes, Mathieu
Gagnon, Louis
Lesage, Frederic
Pelegrini-Issac, Melanie
Vignaud, Alexandre
Valabregue, Romain
Grebe, Reinhard
Wallois, Fabrice
Benali, Habib
TI Quantitative investigation of the effect of the extra-cerebral
vasculature in diffuse optical imaging: a simulation study
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID NEAR-INFRARED SPECTROSCOPY; PRIMARY VISUAL-CORTEX; ADULT HUMAN HEAD;
BRAIN ACTIVATION; TISSUE OXYGENATION; INDOCYANINE GREEN; PHOTON
MIGRATION; FOCAL CHANGES; BLOOD-FLOW; MODEL
AB Diffuse optical imaging (DOI) is a non invasive technique allowing the recovery of hemodynamic changes in the brain. Due to the diffusive nature of photon propagation in turbid media and the fact that cerebral tissues are located around 1.5 cm under the adult human scalp, DOI measurements are subject to partial volume errors. DOI measurements are also sensitive to large pial vessels because oxygenated and deoxygenated hemoglobin are the dominant chromophores in the near infrared window. In this study, the effect of the extra-cerebral vasculature in proximity of the sagittal sinus was investigated for its impact on DOI measurements simulated over the human adult visual cortex. Numerical Monte Carlo simulations were performed on two specific models of the human head derived from magnetic resonance imaging (MRI) scans. The first model included the extra-cerebral vasculature in which constant hemoglobin concentrations were assumed while the second did not. The screening effect of the vasculature was quantified by comparing recovered hemoglobin changes from each model for different optical arrays and regions of activation. A correction factor accounting for the difference between the recovered and the simulated hemoglobin changes was computed in each case. The results show that changes in hemoglobin concentration are better estimated when the extra-cerebral vasculature is modeled and the correction factors obtained in this case were at least 1.4-fold lower. The effect of the vasculature was also examined in a high-density diffuse optical tomography configuration. In this case, the difference between changes in hemoglobin concentration recovered with each model was reduced down to 10%. (C) 2011 Optical Society of America
C1 [Dehaes, Mathieu; Pelegrini-Issac, Melanie; Benali, Habib] Univ Paris 06, INSERM, UMR S 678, LIF & LINeM, Paris, France.
[Dehaes, Mathieu; Grebe, Reinhard; Wallois, Fabrice] Univ Picardie Jules Verne, GRAMFC, EA 4293, Amiens, France.
[Gagnon, Louis] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Gagnon, Louis] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Lesage, Frederic] Ecole Polytech, Dept Genie Elect, Montreal, PQ H3C 3A7, Canada.
[Vignaud, Alexandre] Siemens Healthcare, St Denis, France.
[Valabregue, Romain] Univ Paris 06, INSERM, UMR S 975, CRICM CENIR, Paris, France.
RP Dehaes, M (reprint author), Childrens Hosp Boston, Dept Med, Div Newborn Med, 300 Longwood Ave, Boston, MA 02115 USA.
EM mathieu.dehaes@childrens.harvard.edu
FU Regional Council of Picardie (France); European Regional Development
Fund (ERDF); Fonds Quebecois de la Recherche sur la Nature et les
Technologies [FQRNT-B3]; MIT; National Sciences and Engineering Research
Council (NSERC) of Canada
FX The authors thank David A. Boas, Ph.D. for helpful discussions on the
methodology proposed in this work. They acknowledge funds from the
Regional Council of Picardie (France), the European Regional Development
Fund (ERDF), the Fonds Quebecois de la Recherche sur la Nature et les
Technologies (FQRNT-B3), the IDEA-squared program at MIT and the
National Sciences and Engineering Research Council (NSERC) of Canada.
NR 54
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U2 3
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD MAR 1
PY 2011
VL 2
IS 3
BP 680
EP 695
DI 10.1364/BOE.2.000680
PG 16
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 886SW
UT WOS:000299875200026
PM 21412472
ER
PT J
AU Marques, L
LeBlanc, N
Weingarden, H
Greenberg, JL
Traeger, LN
Keshaviah, A
Wilhelm, S
AF Marques, Luana
LeBlanc, Nicole
Weingarden, Hilary
Greenberg, Jennifer L.
Traeger, Lara N.
Keshaviah, Aparna
Wilhelm, Sabine
TI Body dysmorphic symptoms: Phenomenology and ethnicity
SO BODY IMAGE
LA English
DT Article
DE BDD; Ethnic differences; Body parts; Compensatory behaviors
ID OBSESSIVE-COMPULSIVE SCALE; POPULATION-BASED SURVEY; COLLEGE-STUDENTS;
ASIAN-AMERICAN; FOLLOW-UP; DISORDER; PREVALENCE; RELIABILITY; SAMPLE;
IMAGE
AB Differences in the presentation of clinical features of body dysmorphic disorder (BDD) across ethnic groups have received little investigation. The current study assessed BDD symptoms in an ethnically diverse sample of adults (n=401) using an online survey. Participants completed self-report measures assessing BDD symptoms, body parts of concern and BDD behaviors. Compared to Caucasian participants, no significant differences were found in body parts or behaviors reported by Latino or African American participants. Significant group differences did emerge between Asian and Caucasian participants. Specifically, Asians reported more concern with straight hair and dark skin and fewer body shape concerns than Caucasians. Asians also endorsed lower rates of grooming, touching body parts, and camouflaging and higher rates of exercise compared to Caucasians. Although most clinical features of BDD appear similar across ethnic groups, results showed some differences in body parts and behaviors between Caucasians and Asian Americans with BDD symptoms. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Marques, Luana] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorder,Sch Med, Boston, MA 02114 USA.
[Marques, Luana; LeBlanc, Nicole; Weingarden, Hilary; Greenberg, Jennifer L.; Traeger, Lara N.; Keshaviah, Aparna; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[LeBlanc, Nicole; Weingarden, Hilary] Tufts Univ, Medford, MA 02155 USA.
RP Marques, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorder,Sch Med, 1 Bowdoin Sq, Boston, MA 02114 USA.
EM lmarques@partners.org
NR 34
TC 10
Z9 10
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1740-1445
J9 BODY IMAGE
JI Body Image
PD MAR
PY 2011
VL 8
IS 2
BP 163
EP 167
DI 10.1016/j.bodyim.2010.12.006
PG 5
WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary
SC Psychology; Psychiatry
GA 758AK
UT WOS:000290131600009
PM 21354876
ER
PT J
AU Saless, N
Litscher, SJ
Vanderby, R
Demant, P
Blank, RD
AF Saless, Neema
Litscher, Suzanne J.
Vanderby, Ray
Demant, Peter
Blank, Robert D.
TI Linkage mapping of principal components for femoral biomechanical
performance in a reciprocal HCB-8 x HCB-23 intercross
SO BONE
LA English
DT Article
DE Principal components; Biomechanics; Linkage; Recombinant congenic mice;
Osteoporosis
ID QUANTITATIVE TRAIT LOCI; RECOMBINANT CONGENIC STRAINS; INBRED MOUSE
STRAINS; BONE-MINERAL DENSITY; MICE; PRECISION; C57BL/6J; STRENGTH;
GEOMETRY; CROSSES
AB Studies of bone genetics have addressed an array of related phenotypes, including various measures of biomechanical performance, bone size, bone, shape, and bone mineral density. These phenotypes are not independent, resulting in redundancy of the information they provide. Principal component (PC) analysis transforms multiple phenotype data to a new set of orthogonal "synthetic" phenotypes. We performed PC analysis on 17 femoral biomechanical, anatomic, and body size phenotypes in a reciprocal intercross of HcB-8 and HcB-23, accounting for 80% of the variance in 4 PCs. Three of the 4 PCs were mapped in the cross. The linkage analysis revealed a quantitative trait locus (QTL) with LOD = 4.7 for PC2 at 16 cM on chromosome 19 that was not detected using the directly measured phenotypes. The chromosome 19 QTL falls within a similar to 10 megabase interval, with Osf1 as a positional candidate gene. PC QTLs were also found on chromosomes 1, 2, 4, 6, and 10 that coincided with those identified for directly measured or calculated material property phenotypes. The novel chromosome 19 QTL illustrates the power advantage that attends use of PC phenotypes for linkage mapping. Constraint of the chromosome 19 candidate interval illustrates an important advantage of experimental crosses between recombinant congenic mouse strains. Published by Elsevier Inc.
C1 [Saless, Neema; Blank, Robert D.] Univ Wisconsin, Cellular & Mol Biol Program, Madison, WI USA.
[Litscher, Suzanne J.] Univ Wisconsin, Dept Med, Madison, WI USA.
[Vanderby, Ray] Univ Wisconsin, Dept Orthoped Surg, Madison, WI USA.
[Demant, Peter] Roswell Pk Canc Inst, Dept Genet, Buffalo, NY 14263 USA.
[Blank, Robert D.] Univ Wisconsin, Dept Med, Madison, WI USA.
[Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, GRECC Serv, Madison, WI USA.
RP Blank, RD (reprint author), H4-556 CSC 5148,600 Highland Ave, Madison, WI 53792 USA.
EM rdb@medicine.wisc.edu
FU Office of Research and Development, Biomedical Laboratory R&D Service,
Department of Veterans Affairs (RDB); NIH [AR-54753]
FX This material is based upon work supported by the Office of Research and
Development, Biomedical Laboratory R&D Service, Department of Veterans
Affairs (RDB) and performed in the Geriatrics Research, Education, and
Clinical Center at the William S. Middleton Memorial Veterans Hospital.
This report is Madison GRECC manuscript 2010-09. This work is supported
by NIH grant AR-54753 (R.D.B.).
NR 42
TC 11
Z9 11
U1 0
U2 1
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 MAR 1
PY 2011
VL 48
IS 3
BP 647
EP 653
DI 10.1016/j.bone.2010.10.165
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 740EG
UT WOS:000288773800029
PM 20969983
ER
PT J
AU Bastepe, M
Altug-Teber, O
Agarwal, C
Oberfield, SE
Bonin, M
Juppner, H
AF Bastepe, Murat
Altug-Teber, Oezge
Agarwal, Chhavi
Oberfield, Sharon E.
Bonin, Michael
Juppner, Harald
TI Paternal uniparental isodisomy of the entire chromosome 20 as a
molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib)
SO BONE
LA English
DT Article
DE Pseudohypoparathyroidism; Parathyroid hormone; Stimulatory G protein;
GNAS; Imprinting
ID ALBRIGHTS HEREDITARY OSTEODYSTROPHY; GNAS LOCUS; AUTOSOMAL-DOMINANT;
EPIGENETIC DEFECTS; DISOMY; METHYLATION; FEATURES; DELETION; ELEMENT;
20Q
AB Pseudohypoparathyoridism type Ib (PHP-Ib) typically defines the presence of end-organ resistance to parathyroid hormone in the absence of Albright's hereditary osteodystrophy. Patients affected by this disorder present with imprinting defects in the complex GNAS locus. Microdeletions within STX16 or GNAS have been identified in familial cases with PHP-Ib, but the molecular cause of the GNAS imprinting defects in sporadic PHP-Ib cases remains poorly defined. We now report a case with sporadic PHP-Ib for whom a SNPlex analysis revealed loss of the maternal GNAS allele. Further analysis of the entire genome with a 100 K SNP chip identified a paternal uniparental isodisomy affecting the entire chromosome 20 without evidence for another chromosomal abnormality. Our findings explain the observed GNAS methylation changes and the patient's hormone resistance, and furthermore suggest that chromosome 20 harbors, besides GNAS, no additional imprinted region that contributes to the clinical and laboratory phenotype. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Bastepe, Murat; Juppner, Harald] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA.
[Bastepe, Murat; Juppner, Harald] Harvard Univ, Sch Med, Boston, MA USA.
[Altug-Teber, Oezge; Bonin, Michael] Univ Clin Tubingen, Dept Med Genet, Tubingen, Germany.
[Agarwal, Chhavi; Oberfield, Sharon E.] Columbia Univ, Med Ctr, Dept Pediat Endocrinol Diabet & Metab, New York, NY USA.
RP Juppner, H (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA.
EM jueppner@helix.mgh.harvard.edu
FU National Institutes of Diabetes and Digestive and Kidney Disease [R01
DK073911, R37 DK46718]
FX The authors would like to thank Michael P. Goldman, BS, for his help in
reviewing the patient's clinical and laboratory findings. This work was
funded by research grants from National Institutes of Diabetes and
Digestive and Kidney Disease R01 DK073911 to MB and R37 DK46718 to HJ.
NR 25
TC 33
Z9 33
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD MAR 1
PY 2011
VL 48
IS 3
BP 659
EP 662
DI 10.1016/j.bone.2010.10.168
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 740EG
UT WOS:000288773800031
PM 20965295
ER
PT J
AU Wasif, N
Etzioni, D
Maggard, MA
Tomlinson, JS
Ko, CY
AF Wasif, Nabil
Etzioni, David
Maggard, Melinda A.
Tomlinson, James S.
Ko, Clifford Y.
TI Trends, Patterns, and Outcomes in the Management of Malignant Colonic
Polyps in the General Population of the United States
SO CANCER
LA English
DT Article
DE malignant colon polyps; lymph nodes; survival; colon cancer; surgical
resection
ID COLORECTAL-CANCER; QUALITY MEASURES; RISK-FACTORS; SURVEILLANCE;
POLYPECTOMY; COLECTOMY; SOCIETY
AB BACKGROUND: Colonoscopic screening has increased detection of malignant colonic polyps (MPs). The goal of this study was to analyze trends and patterns in the surgical treatment of MPs and to assess outcomes as measured by lymph node retrieval and patient survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was queried to identify 19,743 patients with MPs from 1988 to 2003. RESULTS: The majority of MPs were present in the sigmoid and descending colon (54%), and 38% were tubular, 40% were tubulovillous, and 22% were villous. During the study period, the incidence of MPs increased from 29% to 42% and surgical resection (SR) was increasingly used for treatment, from 54% to 70%. Predictors of SR were aged <70 years (odds ratio [OR], 1.3; 95% confidence interval [95% CI], 1.2-1.4), high-grade tumors (OR, 1.5; 95% Cl, 1.2-1.9), diagnosis in 1999 through 2003 (OR, 1.7; 95% Cl, 1.5-1.9), villous subtype (OR, 2.3; 95% Cl, 2.0-2.6), and right colon location (OR, 8.1; 95% Cl, 7.0-9.4). In patients undergoing SR, the mean and median number of lymph nodes was only 4 and 1, respectively. A significant percentage of patients (49%) had no lymph nodes retrieved and a worse overall survival at 5 years compared with patients who had at least 1 lymph node examined (64% vs 74%; P<001). CONCLUSIONS: MPs appear to be increasing in incidence, and there is a trend toward increased use of SR for treatment. However, patients undergoing SR for MPs undergo suboptimal assessment of lymph nodes, with a detrimental impact on survival. Adequate lymphadenectomy and lymph node evaluation are crucial to improve outcomes in patients with these potentially curable lesions. Cancer 2011;117:931-7. (C) 2010 American Cancer Society
C1 [Wasif, Nabil] St Johns Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA USA.
[Wasif, Nabil; Etzioni, David] Mayo Clin Scottsdale, Dept Surg, Scottsdale, AZ USA.
[Maggard, Melinda A.; Tomlinson, James S.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA.
[Tomlinson, James S.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA.
RP Wasif, N (reprint author), Mayo Clin, Dept Surg, 5777 E Mayo Blvd, Phoenix, AZ 85054 USA.
EM wasif.nabil@mayo.edu
NR 19
TC 12
Z9 12
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 1
PY 2011
VL 117
IS 5
BP 931
EP 937
DI 10.1002/cncr.25657
PG 7
WC Oncology
SC Oncology
GA 725LM
UT WOS:000287646200010
PM 20960490
ER
PT J
AU Cramer, DW
Bast, RC
Berg, CD
Diamandis, EP
Godwin, AK
Hartge, P
Lokshin, AE
Lu, KH
McIntosh, MW
Mor, G
Patriotis, C
Pinsky, PF
Thornquist, MD
Scholler, N
Skates, SJ
Sluss, PM
Srivastava, S
Ward, DC
Zhang, Z
Zhu, CS
Urban, N
AF Cramer, Daniel W.
Bast, Robert C., Jr.
Berg, Christine D.
Diamandis, Eleftherios P.
Godwin, Andrew K.
Hartge, Patricia
Lokshin, Anna E.
Lu, Karen H.
McIntosh, Martin W.
Mor, Gil
Patriotis, Christos
Pinsky, Paul F.
Thornquist, Mark D.
Scholler, Nathalie
Skates, Steven J.
Sluss, Patrick M.
Srivastava, Sudhir
Ward, David C.
Zhang, Zhen
Zhu, Claire S.
Urban, Nicole
TI Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and
Ovarian Cancer Screening Trial Specimens
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID BIOTINYLATED RECOMBINANT ANTIBODIES; DIAGNOSTIC MARKERS; SERUM;
MANAGEMENT
AB Establishing a cancer screening biomarker's intended performance requires "phase III" specimens obtained in asymptomatic individuals before clinical diagnosis rather than "phase II" specimens obtained from symptomatic individuals at diagnosis. We used specimens from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to evaluate ovarian cancer biomarkers previously assessed in phase II sets. Phase II specimens from 180 ovarian cancer cases and 660 benign disease or general population controls were assembled from four Early Detection Research Network or Ovarian Cancer Specialized Program of Research Excellence sites and used to rank 49 biomarkers. Thirty-five markers, including 6 additional markers from a fifth site, were then evaluated in PLCO proximate specimens from 118 women with ovarian cancer and 474 matched controls. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40. Except for transthyretin, these markers had similar or better sensitivity when moving to phase III specimens that had been drawn within 6 months of the clinical diagnosis. Performance of all markers declined in phase III specimens more remote than 6 months from diagnosis. Despite many promising new markers for ovarian cancer, CA125 remains the single-best biomarker in the phase II and phase III specimens tested in this study. Cancer Prev Res; 4(3); 365-74. (C)2011 AACR.
C1 [Cramer, Daniel W.] Brigham & Womens Hosp, Div Epidemiol, Boston, MA 02115 USA.
[Bast, Robert C., Jr.; Lu, Karen H.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Berg, Christine D.; Pinsky, Paul F.; Zhu, Claire S.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Diamandis, Eleftherios P.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Lokshin, Anna E.] Univ Pittsburgh, Pittsburgh, PA USA.
[McIntosh, Martin W.; Thornquist, Mark D.; Urban, Nicole] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Mor, Gil] Yale Univ, New Haven, CT USA.
[Patriotis, Christos; Srivastava, Sudhir] NCI, Canc Biomarker Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Scholler, Nathalie] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Skates, Steven J.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ward, David C.] Univ Honolulu, Canc Res Ctr, Honolulu, HI USA.
[Zhang, Zhen] Johns Hopkins Univ, Baltimore, MD USA.
RP Cramer, DW (reprint author), Brigham & Womens Hosp, Div Epidemiol, 221 Longwood Ave,RFB 365, Boston, MA 02115 USA.
EM dcramer@partners.org
RI Bast, Robert/E-6585-2011; Berg , Christine/K-1047-2014; Scholler,
Nathalie/O-9003-2014;
OI Bast, Robert/0000-0003-4621-8462; Diamandis,
Eleftherios/0000-0002-1589-820X
FU Ovarian Cancer SPOREs at FHCRC [P50 CA083636]; MDACC [P50 CA83639];
FCCC/UPenn [P50 CA083638]; NCI [N01-CN-43309]; EDRN CVC [5U01 CA113916];
Ovarian Cancer SPORE at BWH [P50 CA105009]; EDRN [5U01 CA86381]; Golfers
Against Cancer; Wiley Mossy Foundation
FX This work was supported in part by the Ovarian Cancer SPOREs at FHCRC
(P50 CA083636), to N. Urban, MDACC (P50 CA83639) to R. C. Bast and
FCCC/UPenn (P50 CA083638), an NCI contract (N01-CN-43309), an EDRN CVC
(5U01 CA113916) to A. K. Godwin; an Ovarian Cancer SPORE at BWH (P50
CA105009) and an EDRN (5U01 CA86381) to D. W. Cramer; and grants from
Golfers Against Cancer and the Wiley Mossy Foundation to R. C. Bast.
NR 26
TC 118
Z9 126
U1 1
U2 16
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 365
EP 374
DI 10.1158/1940-6207.CAPR-10-0195
PG 10
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800013
PM 21372036
ER
PT J
AU Zhu, CS
Pinsky, PF
Cramer, DW
Ransohoff, DF
Hartge, P
Pfeiffer, RM
Urban, N
Mor, G
Bast, RC
Moore, LE
Lokshin, AE
McIntosh, MW
Skates, SJ
Vitonis, A
Zhang, Z
Ward, DC
Symanowski, JT
Lomakin, A
Fung, ET
Sluss, PM
Scholler, N
Lu, KH
Marrangoni, AM
Patriotis, C
Srivastava, S
Buys, SS
Berg, CD
AF Zhu, Claire S.
Pinsky, Paul F.
Cramer, Daniel W.
Ransohoff, David F.
Hartge, Patricia
Pfeiffer, Ruth M.
Urban, Nicole
Mor, Gil
Bast, Robert C., Jr.
Moore, Lee E.
Lokshin, Anna E.
McIntosh, Martin W.
Skates, Steven J.
Vitonis, Allison
Zhang, Zhen
Ward, David C.
Symanowski, James T.
Lomakin, Aleksey
Fung, Eric T.
Sluss, Patrick M.
Scholler, Nathalie
Lu, Karen H.
Marrangoni, Adele M.
Patriotis, Christos
Srivastava, Sudhir
Buys, Saundra S.
Berg, Christine D.
CA PLCO Project Team
TI A Framework for Evaluating Biomarkers for Early Detection: Validation of
Biomarker Panels for Ovarian Cancer
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID SCREENING TRIAL; PROTEOMIC PATTERNS; TUMOR-MARKERS; PROSTATE; SERUM;
LUNG; POPULATION; PREDICTION; DESIGN
AB A panel of biomarkers may improve predictive performance over individual markers. Although many biomarker panels have been described for ovarian cancer, few studies used prediagnostic samples to assess the potential of the panels for early detection. We conducted a multisite systematic evaluation of biomarker panels using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial.
Using a nested case-control design, levels of 28 biomarkers were measured laboratory-blinded in 118 serum samples obtained before cancer diagnosis and 951 serum samples from matched controls. Five predictive models, each containing 6 to 8 biomarkers, were evaluated according to a predetermined analysis plan. Three sequential analyses were conducted: blinded validation of previously established models (step 1); simultaneous split-sample discovery and validation of models (step 2); and exploratory discovery of new models (step 3). Sensitivity, specificity, sensitivity at 98% specificity, and AUC were computed for the models and CA125 alone among 67 cases diagnosed within one year of blood draw and 476 matched controls. In step 1, one model showed comparable performance to CA125, with sensitivity, specificity, and AUC at 69.2%, 96.6%, and 0.892, respectively. Remaining models had poorer performance than CA125 alone. In step 2, we observed a similar pattern. In step 3, a model derived from all 28 markers failed to show improvement over CA125.
Thus, biomarker panels discovered in diagnostic samples may not validate in prediagnostic samples; utilizing prediagnostic samples for discovery may be helpful in developing validated early detection panels. Cancer Prev Res; 4(3); 375-83. (C)2011 AACR.
C1 [Berg, Christine D.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Cramer, Daniel W.; Vitonis, Allison] Brigham & Womens Hosp, Ob Gyn Epidemiol Ctr, Boston, MA 02115 USA.
[Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Ransohoff, David F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Hartge, Patricia; Pfeiffer, Ruth M.; Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Urban, Nicole; McIntosh, Martin W.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Mor, Gil] Yale Univ, Sch Med, Dept Obstet & Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT USA.
[Bast, Robert C., Jr.; Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX USA.
[Lokshin, Anna E.; Marrangoni, Adele M.] Univ Pittsburgh, Inst Med, Hillman Canc Ctr, Pittsburgh, PA USA.
[Skates, Steven J.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Zhang, Zhen] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD USA.
[Ward, David C.] Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
[Symanowski, James T.] Nevada Canc Inst, Las Vegas, NV USA.
[Lomakin, Aleksey] MIT, Boston, MA USA.
[Fung, Eric T.] Vermillion Inc, Fremont, CA USA.
[Scholler, Nathalie] Univ Penn, Sch Med, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA.
[Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA.
RP Berg, CD (reprint author), NCI, Canc Prevent Div, NIH, 6130 Execut Blvd,Rm 3112, Bethesda, MD 20892 USA.
EM bergc@mail.nih.gov
RI Bast, Robert/E-6585-2011; Pfeiffer, Ruth /F-4748-2011; Berg ,
Christine/K-1047-2014; Scholler, Nathalie/O-9003-2014
OI Bast, Robert/0000-0003-4621-8462;
FU National Cancer Institute; National Cancer Institute [P50 CA083636, P50
CA083639, 5U01 CA86381, R01 CA127913, U01 CA084986]; Golfers Against
Cancer; Wiley Mossy Foundation
FX This work was supported in part by contracts from the National Cancer
Institute to 10 PLCO screening centers, a coordinating center and a
central analytic laboratory; grants from the National Cancer Institute
(P50 CA083636 to NU, P50 CA083639 to R. C. Bast, 5U01 CA86381 to DWC,
R01 CA127913 and U01 CA084986 to G. Mor); and grants from Golfers
Against Cancer and the Wiley Mossy Foundation to R. C. Bast.
NR 29
TC 92
Z9 93
U1 2
U2 17
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2011
VL 4
IS 3
BP 375
EP 383
DI 10.1158/1940-6207.CAPR-10-0193
PG 9
WC Oncology
SC Oncology
GA 729PV
UT WOS:000287963800014
PM 21372037
ER
PT J
AU Demers, M
Ho-Tin-Noe, B
Schatzberg, D
Yang, JJ
Wagner, DD
AF Demers, Melanie
Ho-Tin-Noe, Benoit
Schatzberg, Daphne
Yang, Janie J.
Wagner, Denisa D.
TI Increased Efficacy of Breast Cancer Chemotherapy in Thrombocytopenic
Mice
SO CANCER RESEARCH
LA English
DT Article
ID INTERSTITIAL FLUID PRESSURE; ANTI-ANGIOGENIC THERAPY; ANTIANGIOGENIC
THERAPY; MONOCLONAL-ANTIBODY; MAMMARY-TUMOR; INFLAMMATION; HEMORRHAGE;
RESISTANCE; PLATELETS; PROTEINS
AB Platelets contribute to homeostasis of the tumor vasculature by helping prevent hemorrhage. Thus, we hypothesized that inducing thrombocytopenia would increase tumor vascular leakiness and facilitate the effective delivery of chemotherapeutic agents to tumors. In a mammary carcinoma murine model, platelet depletion induced bleeding specifically at the tumor site, favoring the accumulation of fluorescently labeled microspheres only in the tumor. Moreover, induction of thrombocytopenia in tumor-bearing mice before injection of paclitaxel increased its intratumoral accumulation and reduced growth of both slow- and fast-growing tumors, compared with mice with normal platelet counts that were treated only with paclitaxel. Histologic analysis confirmed the expectation of an increase in tumor apoptosis and a reduction in tumor proliferation in thrombocytopenic mice receiving chemotherapy. No increased toxicity was seen in other organs or blood cells. Taken together, our results indicate that low platelet count selectively induces leakiness of tumor vessels and favors the delivery of chemotherapy to tumor sites, enhancing its tumoricidal effects. Cancer Res; 71(5); 1540-9. (C)2011 AACR.
C1 [Demers, Melanie; Ho-Tin-Noe, Benoit; Schatzberg, Daphne; Yang, Janie J.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Demers, Melanie; Ho-Tin-Noe, Benoit; Schatzberg, Daphne; Yang, Janie J.; Wagner, Denisa D.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02115 USA.
[Demers, Melanie; Ho-Tin-Noe, Benoit; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
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, R01 41002]; Terry Fox Foundation through the
Canadian Cancer Society [TF-018748]
FX This work was supported by the National Heart, Lung, and Blood Institute
of the National Institutes of Health grants P01 HL066105 and R01 41002
(to D.D. Wagner). M. Demers was supported by a fellowship from the Terry
Fox Foundation through the Canadian Cancer Society (TF-018748).
NR 32
TC 24
Z9 24
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 1
PY 2011
VL 71
IS 5
BP 1540
EP 1549
DI 10.1158/0008-5472.CAN-10-2038
PG 10
WC Oncology
SC Oncology
GA 728AH
UT WOS:000287845300006
PM 21212409
ER
PT J
AU Tanwar, PS
Zhang, LH
Roberts, DJ
Teixeira, JM
AF Tanwar, Pradeep S.
Zhang, LiHua
Roberts, Drucilla J.
Teixeira, Jose M.
TI Stromal Deletion of the APC Tumor Suppressor in Mice Triggers
Development of Endometrial Cancer
SO CANCER RESEARCH
LA English
DT Article
ID BETA-CATENIN; INTESTINAL TUMORIGENESIS; BREAST CARCINOMAS; UTERINE
STROMA; GROWTH-FACTOR; ER-BETA; ESTROGEN; CELLS; MICROENVIRONMENT;
DIFFERENTIATION
AB The contribution of the stromal microenvironment to the progression of endometrial cancer has not been well explored. We have conditionally expressed a mutant allele of adenomatous polyposis coli (APC(cKO)) in murine uterine stroma cells to study its effect on uterine development and function. In addition to metrorrhagia, the mice develop complex atypical endometrial gland hyperplasia that progresses to endometrial carcinoma in situ and endometrial adenocarcinoma as evidenced by myometrial invasion. Stromal cells subjacent to the carcinoma cells express alpha-smooth muscle actin (alpha SMA) with fewer cells expressing platelet-derived growth factor alpha compared with normal stromal cells, suggesting that the mutant stromal cells have acquired a more myofibroblastic phenotype, which have been described as cancer-associated fibroblasts and have been shown to induce carcinogenesis in other organ systems. Analyses of human endometrial cancer specimens showed substantial alpha SMA expression in the stroma compared with normal endometrial stroma cells. We also show that APC(cKO) mutant uteri and human endometrial cancer have decreased stromal levels of transforming growth factor beta and bone morphogenetic protein activities and that the mutant uteri failed to respond to exogenous estradiol stimulation. The mutant stroma cells also had higher levels of vascular endothelial growth factor and stromal derived factor signaling components and diminished expression of estrogen receptor a and progesterone receptor, which is common in advanced stages of human endometrial cancer and is an indicator of poor prognosis. Our results indicate that de novo mutation or loss of heterozygosity in stromal APC is sufficient to induce endometrial hyperplasia and endometrial carcinogenesis by mechanisms that are consistent with unopposed estrogen signaling in the endometrial epithelium. Cancer Res; 71(5); 1584-96. (C)2011 AACR.
C1 [Tanwar, Pradeep S.; Zhang, LiHua; Teixeira, Jose M.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA.
[Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Teixeira, Jose M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Teixeira, JM (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol Thier 931, 55 Fruit St, Boston, MA 02114 USA.
EM teixeira@helix.mgh.harvard.edu
OI Teixeira, Jose/0000-0002-6438-5064
FU NICHD [HD057201]; Vincent Memorial Research Fund
FX These studies were supported in part by a grant from NICHD, HD057201,
and by the Vincent Memorial Research Fund to J.M. Texeira.
NR 56
TC 29
Z9 30
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 1
PY 2011
VL 71
IS 5
BP 1584
EP 1596
DI 10.1158/0008-5472.CAN-10-3166
PG 13
WC Oncology
SC Oncology
GA 728AH
UT WOS:000287845300010
PM 21363919
ER
PT J
AU Mahida, S
Lubitz, SA
Rienstra, M
Milan, DJ
Ellinor, PT
AF Mahida, Saagar
Lubitz, Steven A.
Rienstra, Michiel
Milan, David J.
Ellinor, Patrick T.
TI Monogenic atrial fibrillation as pathophysiological paradigms
SO CARDIOVASCULAR RESEARCH
LA English
DT Review
DE Atrial fibrillation; Mutation; Family; Genetics
ID LONG-QT SYNDROME; OF-FUNCTION MUTATION; DOMINANT DILATED CARDIOMYOPATHY;
SYSTEM GENE POLYMORPHISMS; GAP-JUNCTION DISTRIBUTION;
CONGESTIVE-HEART-FAILURE; OUTWARD K+ CURRENT; I-KS CHANNELS;
SODIUM-CHANNEL; NATRIURETIC-PEPTIDE
AB Atrial fibrillation (AF) is the most common cardiac rhythm abnormality and represents a major burden, both to patients and to health-care systems. In recent years, increasing evidence from population-based studies has demonstrated that AF is a heritable condition. Although familial forms of AF have been recognized for many years, they represent a rare subtype of the arrhythmia. However, despite their limited prevalence, the identification of mutations in monogenic AF kindreds has provided valuable insights into the molecular pathways underlying the arrhythmia and a framework for investigating AF encountered in the general population. In contrast to these rare families, the typical forms of AF occurring in the community are likely to be multigenic and have significant environmental influences. Recently, genome-wide association studies have uncovered common sequence variants that confer increased susceptibility to the arrhythmia. In the future, the elucidation of the genetic substrate underlying both familial and more typical forms of AF will hopefully lead to the development of novel diagnostic tools as well as more targeted rhythm control strategies. In this article, we will focus on monogenic forms of AF and also provide an overview of case-control association studies for AF.
C1 [Mahida, Saagar; Lubitz, Steven A.; Rienstra, Michiel; Milan, David J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Milan, David J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
EM pellinor@partners.org
OI Rienstra, Michiel/0000-0002-2581-070X
FU Netherlands Organization of Scientific Research (Rubicon) [825.09.020];
National Institutes of Health [T32 HL007575, R21HL096009, R21DA026982,
R01HL104156, R21DA027021, R01HL092577, K24HL105780).]
FX This work was supported by a grant from the Netherlands Organization of
Scientific Research to M. R. (Rubicon Grant 825.09.020), grants from the
National Institutes of Health to S.A.L. (T32 HL007575), D.J.M.
(R21HL096009 and R21DA026982), and P. T. E. (R01HL104156, R21DA027021,
R01HL092577, and K24HL105780).
NR 134
TC 47
Z9 47
U1 2
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 MAR
PY 2011
VL 89
IS 4
BP 692
EP 700
DI 10.1093/cvr/cvq381
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 723DV
UT WOS:000287487400002
PM 21123219
ER
PT J
AU Sinner, MF
Ellinor, PT
Meitinger, T
Benjamin, EJ
Kaab, S
AF Sinner, Moritz F.
Ellinor, Patrick T.
Meitinger, Thomas
Benjamin, Emelia J.
Kaeaeb, Stefan
TI Genome-wide association studies of atrial fibrillation: past, present,
and future
SO CARDIOVASCULAR RESEARCH
LA English
DT Review
DE Atrial fibrillation; Genetics; Genome-wide association study; Single
nucleotide polymorphism; Arrhythmia
ID TRANSCRIPTION FACTOR ATBF1; CA2+-ACTIVATED K+ CHANNEL; QT INTERVAL
DURATION; LEFT-RIGHT ASYMMETRY; SMALL-CONDUCTANCE; CHROMOSOME 4Q25;
COMMON VARIANTS; RISK-FACTORS; PR INTERVAL; HEART-RATE
AB Genome-wide association studies (GWAS) for atrial fibrillation (AF) have identified three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 that are associated with the arrhythmia. Susceptibility loci also have been identified by GWAS for PR interval duration, a quantitative phenotype related to AF. In this review article, we have sought to summarize the latest findings for population-based genetic studies of AF, to highlight ongoing functional studies, and to explore the future directions of genetic research on AF.
C1 [Sinner, Moritz F.; Kaeaeb, Stefan] Univ Hosp Munich, Dept Med 1, D-81377 Munich, Germany.
[Sinner, Moritz F.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Sinner, Moritz F.; Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA.
[Sinner, Moritz F.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med,Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med,Prevent Med Sect, Boston, MA 02118 USA.
RP Kaab, S (reprint author), Univ Hosp Munich, Dept Med 1, Campus Grosshadern,Marchioninistr 15, D-81377 Munich, Germany.
EM skaab@med.lmu.de
RI Meitinger, Thomas/O-1318-2015;
OI Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health [1R01HL092577, 1RC1HL101056, 1R01HL102214,
1R01HL104156, 5R21DA027021, 1K24HL105780]; Bundesministerium fur Bildung
und Forschung BMBF (German Competence Network on AF AFNET [01 GI
0204/N]; German National Genome Research Network NGFN [01GS0499,
01GS0838]; Leducq Foundation [07-CVD 03]; LMU Excellence Initiative
[557/569]; German Heart Foundation
FX This work was supported by the National Institutes of Health
(1R01HL092577 to E.J.B. and P.T.E.; 1RC1HL101056, 1R01HL102214 to E.J.B;
1R01HL104156, 5R21DA027021, 1K24HL105780 to P.T.E.); Bundesministerium
fur Bildung und Forschung BMBF (German Competence Network on AF AFNET 01
GI 0204/N, German National Genome Research Network NGFN 01GS0499,
01GS0838 to S. K.; Leducq Foundation (07-CVD 03 to E.J.B., P. T. E. and
S. K.); LMU Excellence Initiative to S. K.; LMU Research grant (FoFoLe
557/569 to M.F.S.). M.F.S. is supported by the German Heart Foundation.
NR 77
TC 43
Z9 44
U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR
PY 2011
VL 89
IS 4
BP 701
EP 709
DI 10.1093/cvr/cvr001
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 723DV
UT WOS:000287487400003
PM 21245058
ER
PT J
AU Schon, A
Madani, N
Smith, AB
Lalonde, JM
Freire, E
AF Schoen, Arne
Madani, Navid
Smith, Amos B.
Lalonde, Judith M.
Freire, Ernesto
TI Some Binding-Related Drug Properties are Dependent on Thermodynamic
Signature
SO CHEMICAL BIOLOGY & DRUG DESIGN
LA English
DT Article
DE binding affinity; enthalpy; entropy; isothermal titration calorimetry;
thermodynamic optimization
ID PROTEIN-PROTEIN INTERACTIONS; SMALL-MOLECULE INHIBITORS; HIV-1 GP120;
RECEPTOR; CD4; ANTIBODY; NEUTRALIZATION; RETROVIRUS; REDUCTASE; LIGANDS
AB The binding affinity is determined by the Gibbs energy of binding (Delta G) which is the sum of enthalpic (Delta H) and entropic (-T Delta S) contributions. Because the enthalpy and entropy contribute in an additive way to the binding energy, the same binding affinity can be achieved by many different combinations of enthalpic and entropic contributions; however, do compounds with similar binding affinities but different thermodynamic signatures (i.e., different Delta H, -T Delta S combinations) exhibit the same functional effects? Are there characteristics of compounds that can be modulated by modifying their thermodynamic signatures? In this paper, we consider the minimization of unwanted conformational effects arising during the development of CD4/gp120 inhibitors, a new class of HIV-1 cell entry inhibitors. Competitive inhibitors of protein/protein interactions run the risk of triggering the very same signals that they are supposed to inhibit. Here, we show that for CD4/gp120 inhibitors, the magnitude of those unwanted effects is related to the proportion in which the enthalpy and entropy changes contribute to the binding affinity. The thermodynamic optimization plot (TOP) previously proposed to optimize binding affinity can also be used to obtain appropriate enthalpy/entropy combinations for drug candidates.
C1 [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Madani, Navid] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Madani, Navid] Harvard Univ, Div Aids, Dept Pathol, Sch Med, Boston, MA 02115 USA.
[Smith, Amos B.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
[Lalonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA.
RP Freire, E (reprint author), Johns Hopkins Univ, Dept Biol, 3400 N Charles, Baltimore, MD 21218 USA.
EM ef@jhu.edu
FU National Institutes of Health [GM56550, GM57144]; National Science
Foundation [MCB0641252]
FX This work was supported by grants from the National Institutes of Health
(GM56550 and GM57144) and the National Science Foundation (MCB0641252).
NR 27
TC 18
Z9 18
U1 0
U2 9
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1747-0277
J9 CHEM BIOL DRUG DES
JI Chem. Biol. Drug Des.
PD MAR
PY 2011
VL 77
IS 3
BP 161
EP 165
DI 10.1111/j.1747-0285.2010.01075.x
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 718SJ
UT WOS:000287146200001
PM 21288305
ER
PT J
AU Suh, WM
Seto, AH
Margey, RJP
Cruz-Gonzalez, I
Jang, IK
AF Suh, William M.
Seto, Arnold H.
Margey, Ronan J. P.
Cruz-Gonzalez, Ignacio
Jang, Ik-Kyung
TI Intravascular Detection of the Vulnerable Plaque
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE atherosclerosis; acute coronary syndrome; cardiac imaging techniques
ID OPTICAL COHERENCE TOMOGRAPHY; CORONARY-ARTERY-DISEASE; RADIOFREQUENCY
DATA-ANALYSIS; NEAR-INFRARED SPECTROSCOPY; IN-VIVO CHARACTERIZATION;
ATHEROSCLEROTIC PLAQUES; VIRTUAL HISTOLOGY; TISSUE CHARACTERIZATION;
MAGNETIC-RESONANCE; RAMAN-SPECTROSCOPY
C1 [Suh, William M.; Seto, Arnold H.; Margey, Ronan J. P.; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Cruz-Gonzalez, Ignacio] Univ Hosp Salamanca, Div Cardiol, Salamanca, Spain.
RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,GRB800, Boston, MA 02114 USA.
EM ijang@partners.org
RI 2011, Secribsal/D-9425-2012
FU LightLab/St Jude; Medtronic; Abbott Vascular
FX Dr Jang has received research grants from LightLab/St Jude, Medtronic,
and Abbott Vascular.
NR 62
TC 51
Z9 55
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD MAR
PY 2011
VL 4
IS 2
BP 169
EP 178
DI 10.1161/CIRCIMAGING.110.958777
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 734WC
UT WOS:000288370500016
PM 21406663
ER
PT J
AU Cheng, EM
Cunningham, WE
Towfighi, A
Sanossian, N
Bryg, RJ
Anderson, TL
Guterman, JJ
Gross-Schulman, SG
Beanes, S
Jones, AS
Liu, HH
Ettner, SL
Saver, JL
Vickrey, BG
AF Cheng, Eric M.
Cunningham, William E.
Towfighi, Amytis
Sanossian, Nerses
Bryg, Robert J.
Anderson, Thomas L.
Guterman, Jeffrey J.
Gross-Schulman, Sandra G.
Beanes, Sylvia
Jones, Andrea S.
Liu, Honghu
Ettner, Susan L.
Saver, Jeffrey L.
Vickrey, Barbara G.
TI Randomized, Controlled Trial of an Intervention to Enable Stroke
Survivors Throughout the Los Angeles County Safety Net to "Stay With the
Guidelines"
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE stroke; secondary prevention; risk factors; self-management; care
coordination
ID TRANSIENT ISCHEMIC ATTACK; IMPROVING PRIMARY-CARE; RISK-FACTORS;
BLOOD-PRESSURE; GROUP VISITS; SECONDARY PREVENTION; SELF-MANAGEMENT;
CHRONIC ILLNESS; CHRONIC DISEASE; WARNING SIGNS
AB Background-Stroke is the leading cause of adult disability. Inpatient programs optimize secondary stroke prevention care at the time of hospital discharge, but such care may not be continued after hospital discharge.
Methods-To improve the delivery of secondary stroke preventive services after hospital discharge, we have designed a chronic care model-based program called SUSTAIN (Systemic Use of STroke Averting INterventions). This care intervention includes group clinics, self-management support, report cards, decision support through care guides and protocols, and coordination of ongoing care. The first specific aim is to test, in a randomized, controlled trial, whether SUSTAIN improves blood pressure control among an analytic sample of 268 patients with a recent stroke or transient ischemic attack discharged from 4 Los Angeles County public hospitals. Secondary outcomes consist of control of other stroke risk factors, lifestyle habits, medication adherence, patient perceptions of care quality, functional status, and quality of life. A second specific aim is to conduct a cost analysis of SUSTAIN from the perspective of the Los Angeles County Department of Health Services by using direct costs of the intervention, cost equivalents of associated utilization of county system resources, and cost equivalents of the observed and predicted averted vascular events.
Conclusions-If SUSTAIN is effective, we will have the expertise and findings to advocate for its continued support at Los Angeles County hospitals and to disseminate the SUSTAIN program to other settings serving indigent, minority populations.
C1 [Cheng, Eric M.] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, VA Greater Angeles UCLA, Los Angeles, CA 90073 USA.
[Cheng, Eric M.; Vickrey, Barbara G.] VA Greater Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA.
[Cunningham, William E.; Guterman, Jeffrey J.; Liu, Honghu; Ettner, Susan L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA.
[Towfighi, Amytis] Rancho Los Amigos Natl Rehabil Ctr, Dept Neurol, Los Angeles, CA USA.
[Towfighi, Amytis; Sanossian, Nerses] Univ So Calif, Dept Neurol, Los Angeles, CA USA.
[Bryg, Robert J.] Olive View UCLA Med Ctr, Dept Med, Sylmar, CA 91342 USA.
[Anderson, Thomas L.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Neurol, Torrance, CA 90509 USA.
[Guterman, Jeffrey J.; Gross-Schulman, Sandra G.] Olive View UCLA Med Ctr, Los Angeles Cty Dept Hlth Serv, Sylmar, CA 91342 USA.
[Beanes, Sylvia] Amer Heart Assoc, Los Angeles, CA USA.
[Jones, Andrea S.] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA.
RP Cheng, EM (reprint author), Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, VA Greater Angeles UCLA, 11301 Wilshire Blvd,ML 127, Los Angeles, CA 90073 USA.
EM eric.cheng@va.gov
OI Saver, Jeffrey/0000-0001-9141-2251
FU American Heart Association; National Institutes of Health/National
Institute of Neurological Disorders and Stroke [K23NS058571]; UCLA/DREW
[P20MD000148/P20MD000182]; UCLA Center for Health Improvement of
Minority Elderly/Resource Centers for Minority Aging Research (National
Institute on Aging) [P30AG021684]
FX This work was supported by an award from the American Heart Association
Pharmaceutical Roundtable and David and Stevie Spina. There are no
sponsor-imposed restrictions on publication of this article and any
subsequent articles about this study. Dr Eric Cheng is supported by a
Career Development Award from the National Institutes of Health/National
Institute of Neurological Disorders and Stroke (K23NS058571). Drs Cheng
and Cunningham also received partial support from the UCLA/DREW project
EXPORT (NCMHD grants No. P20MD000148/P20MD000182). Dr Cunningham also
receives partial support from the UCLA Center for Health Improvement of
Minority Elderly/Resource Centers for Minority Aging Research (National
Institute on Aging grant No. P30AG021684).
NR 50
TC 13
Z9 13
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAR
PY 2011
VL 4
IS 2
BP 229
EP 234
DI 10.1161/CIRCOUTCOMES.110.951012
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 734WN
UT WOS:000288372200016
PM 21406671
ER
PT J
AU Dhingra, R
Gaziano, JM
Djousse, L
AF Dhingra, Ravi
Gaziano, J. Michael
Djousse, Luc
TI Chronic Kidney Disease and the Risk of Heart Failure in Men
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE heart failure; congestive; epidemiology; renal disease
ID LEFT-VENTRICULAR HYPERTROPHY; STAGE RENAL-DISEASE;
CARDIOVASCULAR-DISEASE; PHYSICIANS HEALTH; MORTALITY RISK; SERUM
PHOSPHORUS; BLOOD-PRESSURE; LIFETIME RISK; CYSTATIN-C; VITAMINS E
AB Background-The relations between chronic kidney disease (CKD) and incident heart failure remain unclear.
Methods and Results-We related CKD to incident nonfatal heart failure and cardiovascular (CVD) death (as separate and combined end points) in 10 181 male participants (mean age, 67 years). Kidney function was assessed by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation in clinically relevant categories of <60 and >= 60 mL . min(-1) . 1.73 m(-2) (referent) and <45, 45 to 60, 60 to 90, and >= 90 mL . min(-1) . 1.73 m(-2) (referent). During follow-up (mean, 10.1 years; range, 0.03 to 12.2), 439 developed heart failure and 832 had CVD death/heart failure. In multivariable models, men with eGFR <60 mL . min(-1) . 1.73 m(-2) had a 2-fold risk of heart failure (95% confidence interval, 1.62 to 2.56, P < 0.0001) compared with referent category. The hazard ratio (with corresponding 95% confidence interval) for development of heart failure according to eGFR categories of 60 to 90, 45 to 60, and <45 mL . min(-1) . 1.73 m(-2) compared with referent category were 1.24 (0.98 to 1.56), 2.58 (1.91 to 3.49), and 1.52 (0.92 to 2.76), respectively. In the analyses restricted to subgroup of nondiabetic individuals and normotensive individuals at baseline (n = 7545), men with eGFR <60 mL . min(-1) . 1.73 m(-2) had a 2.2-fold risk of heart failure (95% confidence interval, 1.66 to 2.95), compared with men with eGFR >= 60 mL . min(-1) . 1.73 m(-2). Additionally, risk of heart failure or CVD death was >2.5-fold higher among individuals with eGFR 45 to 60 and <45 mL . min(-1) . 1.73 m(-2), compared with referent category.
Conclusions-Moderate level of CKD, even in absence of diabetes and hypertension at baseline, is associated with a higher risk of development of heart failure and CVD death/heart failure in men. (Circ Heart Fail. 2011;4:138-144.)
C1 [Dhingra, Ravi] Dartmouth Hitchcock Med Ctr, Cardiol Sect, Lebanon, NH 03756 USA.
[Dhingra, Ravi; Gaziano, J. Michael; Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA.
RP Dhingra, R (reprint author), Dartmouth Hitchcock Med Ctr, Cardiol Sect, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM ravi.dhingra@hitchcock.org
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU National Institutes of Health, Bethesda, MD [CA-34944, CA-40360,
CA-097193, HL-26490, HL-34595]; National Institutes of Health; Veterans
Administration, Veroscience; Amgen; Biomedical Research Institute,
Brigham and Women's Hospital
FX The Physicians' Health Study is supported by grants CA-34944, CA-40360,
CA-097193, HL-26490, and HL-34595 from the National Institutes of
Health, Bethesda, MD.; Dr Gaziano reported receiving
investigator-initiated research funding from the National Institutes of
Health, the Veterans Administration, Veroscience, and Amgen; serving as
a consultant or receiving honoraria from Bayer AG and serving as an
expert witness for Merck. Dr Djousse reported that he is currently the
recipient of investigator-initiated grants from the National Institutes
of Health and that over the past 5 years he has received an
investigator-initiated grant from the Biomedical Research Institute,
Brigham and Women's Hospital.
NR 42
TC 18
Z9 21
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 MAR
PY 2011
VL 4
IS 2
BP 138
EP 144
DI 10.1161/CIRCHEARTFAILURE.109.899070
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 735UM
UT WOS:000288445300007
PM 21216838
ER
PT J
AU Gao, ZJ
Xu, XY
McClane, B
Zeng, Q
Litkouhi, B
Welch, WR
Berkowitz, RS
Mok, SC
Garner, EIO
AF Gao, Zhijian
Xu, Xiaoyin
McClane, Bruce
Zeng, Qing
Litkouhi, Babak
Welch, William R.
Berkowitz, Ross S.
Mok, Samuel C.
Garner, Elizabeth I. O.
TI C Terminus of Clostridium perfringens Enterotoxin Downregulates CLDN4
and Sensitizes Ovarian Cancer Cells to Taxol and Carboplatin
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TIGHT JUNCTION PROTEINS; EPITHELIAL-CELLS; GENE-EXPRESSION; CLAUDIN-4;
CARCINOMA; FRAGMENT; STRANDS; PACLITAXEL; RECEPTORS; DIVISION
AB Purpose: We have previously shown that CLDN4 (encoding claudin-4), a cell tight junction (TJ) protein, is highly expressed in human epithelial ovarian carcinomas (EOC) but undetectable in normal ovaries. CLDN4 has been identified as a specific receptor for C terminus of Clostridium perfringens enterotoxin (C-CPE), a nontoxic molecule that may disrupt TJ barrier function and enhance cellular absorption. The purpose of this study was to determine the potential clinical applications of C-CPE and its effects on CLDN4 expression in EOC.
Experimental Design: Using a 3-dimensional culture model and monolayer culture of EOC cells, we examined the effects of C-CPE on CLDN4 expression by quantitative real-time PCR, immunofluorescence, and Western blot. The synergistic effect of C-CPE to clinically relevant chemotherapies (Taxol and Carboplatin) was observed in EOC culture and xenograft mice. Furthermore, we determined through oligonucleotide microarray analysis that the transcript profile alterations dysregulated as a consequence of C-CPE treatment.
Results: C-CPE treatment decreased protein expression and relocated CLDN4 from cell-cell contact regions to the cytoplasm. Particularly, C-CPE sensitized EOC cells to chemotherapeutic administration at low dosages and significantly inhibited tumor growth in a nontoxic manner. Furthermore, we provided genome-wide molecular evidence that C-CPE treatment is involved in the stimulation of the ubiquitin-proteasome pathway and the inhibition of cell metabolism in EOC cells.
Conclusions: The addition of C-CPE can enhance the effectiveness of Taxol or Carboplatin and significantly inhibited EOC cell growth in a CLDN4-dependent manner, suggesting that C-CPE may have promising therapeutic potential for EOC. Clin Cancer Res; 17(5); 1065-74. (C)2010 AACR.
C1 [Gao, Zhijian; Litkouhi, Babak; Berkowitz, Ross S.; Garner, Elizabeth I. O.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA 02115 USA.
[Xu, Xiaoyin; Zeng, Qing] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[McClane, Bruce] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA.
[Welch, William R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Berkowitz, Ross S.; Garner, Elizabeth I. O.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA.
[Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
RP Gao, ZJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA 02115 USA.
EM zhijian_gao@yahoo.com
FU Dana-Farber/Harvard Cancer Center Ovarian Cancer SPORE, National
Institute of Health [P50CA105009]; Robert Wood Johnson; The University
of Texas MD Anderson Ovarian Cancer SPORE, National Institutes of Health
[P50CA083639, RO1CA133057]; University of Pittsburgh School of Medicine,
National Institutes of Health [R37 AI19844]
FX This study was supported in part by Dana-Farber/Harvard Cancer Center
Ovarian Cancer SPORE Grant P50CA105009 from the National Institute of
Health, Harold Amos Minority Faculty Development Award from Robert Wood
Johnson, The University of Texas MD Anderson Ovarian Cancer SPORE grants
P50CA083639 and RO1CA133057 from the National Institutes of Health, and
University of Pittsburgh School of Medicine Grant R37 AI19844 from the
National Institutes of Health.
NR 39
TC 21
Z9 22
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 1
PY 2011
VL 17
IS 5
BP 1065
EP 1074
DI 10.1158/1078-0432.CCR-10-1644
PG 10
WC Oncology
SC Oncology
GA 728ZT
UT WOS:000287914400013
PM 21123456
ER
PT J
AU Janne, PA
Boss, DS
Camidge, DR
Britten, CD
Engelman, JA
Garon, EB
Guo, F
Wong, S
Liang, J
Letrent, S
Millham, R
Taylor, I
Eckhardt, SG
Schellens, JHM
AF Jaenne, Pasi A.
Boss, David S.
Camidge, D. Ross
Britten, Carolyn D.
Engelman, Jeffrey A.
Garon, Edward B.
Guo, Feng
Wong, Steven
Liang, Jane
Letrent, Stephen
Millham, Robert
Taylor, Ian
Eckhardt, S. Gail
Schellens, Jan H. M.
TI Phase I Dose-Escalation Study of the Pan-HER Inhibitor, PF299804, in
Patients with Advanced Malignant Solid Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER;
ACQUIRED-RESISTANCE; MUTATIONS; GEFITINIB; ERBB2; EGFR; HKI-272; CI-1033
AB Purpose: PF299804 is a potent, orally available, irreversible inhibitor of tyrosine kinase human epidermal growth factor receptors (HER) 1 (EGFR), HER2, and HER4. This first-in-human study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF299804 in patients with advanced solid malignancies.
Experimental Design: PF299804 was administered once daily continuously (schedule A) and intermittently (schedule B). Dose escalation proceeded until intolerable toxicities occurred. Skin biopsies were taken predose and after 14 days of treatment to establish a pharmacokinetic/pharmacodynamic relationship. Tumor response was measured once every 2 cycles. Efficacy was correlated with tumor genotypes in non-small cell lung cancer (NSCLC) patients.
Results: 121 patients were included (111 in schedule A, 10 in schedule B). The maximum tolerated dose (MTD) was 45 mg/d. Dose-limiting toxicities included stomatitis and skin toxicities. Most adverse events were mild and comprised skin toxicities, fatigue, and gastrointestinal side-effects including diarrhea, nausea, and vomiting. Pharmacokinetic analyses revealed dose-dependent increases in PF299804 exposure associated with target inhibition in skin biopsy samples. Fifty-seven patients with non-small cell lung cancer (NSCLC) were treated in this study. Four patients, all previously treated with gefitinib or erlotinib (2 with exon 19 deletions, 1 with exon 20 insertion, 1 mutational status unknown), had a partial response to PF299804.
Conclusions: The MTD of PF299804 is 45 mg/d. Both continuous and intermittent treatment schedules were well tolerated, and encouraging signs of antitumor activity were observed in gefitinib/erlotinib treated NSCLC patients. Clin Cancer Res; 17(5); 1131-9. (C)2011 AACR.
C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Boss, David S.; Schellens, Jan H. M.] Netherlands Canc Inst, Div Clin Pharmacol, Amsterdam, Netherlands.
[Camidge, D. Ross; Eckhardt, S. Gail] Univ Colorado, Aurora, CO USA.
[Britten, Carolyn D.; Garon, Edward B.; Wong, Steven] Univ Calif Los Angeles, UCLA Med Ctr, Los Angeles, CA USA.
[Guo, Feng] Pfizer China Res & Dev Ctr, Shanghai, Peoples R China.
[Liang, Jane; Millham, Robert; Taylor, Ian] Pfizer Oncol, New London, CT USA.
[Letrent, Stephen] Pfizer Oncol, Clin Dev & Med Affairs, San Diego, CA USA.
[Schellens, Jan H. M.] Univ Utrecht, Fac Pharmaceut Sci, Div Drug Toxicol, Utrecht, Netherlands.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820,44 Binney St, Boston, MA 02115 USA.
EM pjanne@partners.org
FU Pfizer Inc.; National Institutes of Health [R01CA135257]; National
Cancer Institute Lung [SPORE P50CA090578]; Pfizer
FX This study was funded by Pfizer Inc. and supported in part by grants
from the National Institutes of Health R01CA135257 (P.A. Janne and J.A.
Engelman) and the National Cancer Institute Lung SPORE P50CA090578 (P.A.
Janne and J.A. Engelman).; P.A. Janne: commercial research grant,
Pfizer; ownership interest, Gatekeeper Pharmaceuticals;
consultant/advisor, Boeringher Ingelheim, AVEO Pharmaceuticals, Pfizer,
Roche, Astra Zeneca, and OSI Pharmaceuticals; royalties from DFCI owned
patent on EGFR mutations licensed to Genzyme. C.D. Britten and J.H.M.
Schellens: commercial research grant, Pfizer. J.A. Engelmann: ownership
interest, Gatekeeper Pharmaceuticals; consultant/advisor, Roche, AVEO
Pharmaceuticals, and OSI Pharmaceuticals. F. Guo, J. Liang, S. Letrent,
R. Milham, and I. Taylor: employment and ownership interest, Pfizer.
S.G. Eckhardt: commercial research grant and consultant/advisor, Pfizer.
NR 22
TC 85
Z9 88
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 1
PY 2011
VL 17
IS 5
BP 1131
EP 1139
DI 10.1158/1078-0432.CCR-10-1220
PG 9
WC Oncology
SC Oncology
GA 728ZT
UT WOS:000287914400020
PM 21220471
ER
PT J
AU Abu Dayyeh, BK
Lautz, DB
Thompson, CC
AF Abu Dayyeh, Barham K.
Lautz, David B.
Thompson, Christopher C.
TI Gastrojejunal Stoma Diameter Predicts Weight Regain After Roux-en-Y
Gastric Bypass
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Weight Loss; Obesity; Surgery; ROC; PPV
ID VERTICAL BANDED GASTROPLASTY; BARIATRIC SURGERY; DILATED
GASTROJEJUNOSTOMY; ENERGY-EXPENDITURE; FOOD-INTAKE; FOLLOW-UP;
REDUCTION; GHRELIN; SCLEROTHERAPY; METAANALYSIS
AB BACKGROUND & AIMS: Weight regain after Roux-en-Y gastric bypass (RYGB) is associated with reductions in health status and quality of life. We evaluated whether gastrojejunal stoma diameter is a risk factor for weight regain after RYGB. METHODS: We examined data collected over 4 years from consecutive patients referred to a tertiary care bariatric center for upper endoscopy after RYGB. We used linear regression analysis to determine the association between the gastrojejunal stoma diameter and weight regain. We applied a logistic regression model using clinical and endoscopic parameters to develop a prediction rule for weight gain after RYGB. RESULTS: Among 165 patients included in our study, 59% had significant weight regain (>= 20% of maximum weight lost after the RYGB) and 41% did not. The mean percentage of maximal weight lost after RYGB that was regained in the entire cohort was 30% +/- 22%. Gastrojejunal stoma diameter was associated significantly with weight regain after RYGB surgery in univariate analysis (beta = .31, P < .0001). This association remained significant after adjusting for several known or purported risk factors for weight regain (beta = .19, P = .003). We developed a simple prediction rule for weight regain after RYGB using a 7-point scoring system that includes the gastrojejunal stoma diameter, race, and percentage of maximal body weight lost after RYGB; a cut-off score of 4 or more points had an area under receiver operating characteristic curve of 0.76 and a positive predictive value of 75%. CONCLUSIONS: Increased gastrojejunal stoma diameter is a risk factor for weight regain after RYGB and can be incorporated in a novel prediction rule.
C1 [Thompson, Christopher C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Abu Dayyeh, Barham K.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Abu Dayyeh, Barham K.; Thompson, Christopher C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Lautz, David B.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St,Thorn 14, Boston, MA 02115 USA.
EM christopher_thompson@hms.harvard.edu
FU NIDDK NIH HHS [T32 DK007191, P30 DK034854, T32 DK007191-36, T32
DK007533, T32DK007191]
NR 40
TC 25
Z9 25
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 MAR
PY 2011
VL 9
IS 3
BP 228
EP 233
DI 10.1016/j.cgh.2010.11.004
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 737FY
UT WOS:000288555700015
PM 21092760
ER
PT J
AU Musher, DM
Sampath, R
Rodriguez-Barradas, MC
AF Musher, Daniel M.
Sampath, Rahul
Rodriguez-Barradas, Maria C.
TI The Potential Role for Protein-Conjugate Pneumococcal Vaccine in Adults:
What Is the Supporting Evidence?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID HIV-INFECTED ADULTS; RENAL-TRANSPLANT RECIPIENTS; COST-EFFECTIVENESS
ANALYSIS; PLACEBO-CONTROLLED TRIAL; POLYSACCHARIDE VACCINE;
STREPTOCOCCUS-PNEUMONIAE; DOUBLE-BLIND; OLDER-ADULTS; CAPSULAR
POLYSACCHARIDES; HEMOPHILUS-INFLUENZAE
AB Vaccination with protein-conjugate pneumococcal vaccine (PCV) provides children with extraordinary protection against pneumococcal disease, although the protective effect may be blunted by the emergence of replacement strains. Studies in adults have compared PCV with pneumococcal polysaccharide vaccine (PPV) using surrogate markers of protection, namely, serum anticapsular IgG antibody and opsonic activity. Results suggest that PCV is at least as effective as PPV for the strains covered, but a definitive and consistent advantage has not been demonstrated. Unfortunately, persons who are most in need of vaccine do not respond as well as otherwise healthy adults to either vaccine. Newer formulations of PCV will protect against the most prevalent of the current replacement strains, but replacement strains will create a moving target for PCVs. Unless an ongoing trial comparing 13-valent PCV with placebo (not to PPV) demonstrates a clearly better effect than that seen in the past with PPV, cost-effectiveness considerations are likely to prevent widespread use of PCV in adults.
C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Med Care Line Infect Dis Sect, Houston, TX 77030 USA.
Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA.
Baylor Coll Med, Dept Microbiol, Houston, TX 77030 USA.
RP Musher, DM (reprint author), Michael E DeBakey VAMC, Infect Dis Sect, Houston, TX 77030 USA.
EM dmusher@bcm.edu
NR 65
TC 44
Z9 44
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 1
PY 2011
VL 52
IS 5
BP 633
EP 640
DI 10.1093/cid/ciq207
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 716RR
UT WOS:000286991700017
PM 21292668
ER
PT J
AU Gupta, K
Hooton, TM
Naber, KG
Wullt, B
Colgan, R
Miller, LG
Moran, GJ
Nicolle, LE
Raz, R
Schaeffer, AJ
Soper, DE
AF Gupta, Kalpana
Hooton, Thomas M.
Naber, Kurt G.
Wullt, Bjorn
Colgan, Richard
Miller, Loren G.
Moran, Gregory J.
Nicolle, Lindsay E.
Raz, Raul
Schaeffer, Anthony J.
Soper, David E.
TI International Clinical Practice Guidelines for the Treatment of Acute
Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the
Infectious Diseases Society of America and the European Society for
Microbiology and Infectious Diseases
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID URINARY-TRACT-INFECTION; TRIMETHOPRIM-SULFAMETHOXAZOLE RESISTANCE;
EXTENDED-RELEASE CIPROFLOXACIN; RANDOMIZED CONTROLLED-TRIAL; SINGLE-DOSE
FOSFOMYCIN; ESCHERICHIA-COLI; DOUBLE-BLIND; ANTIBIOTIC-RESISTANCE; 400
MG; ANTIMICROBIAL SUSCEPTIBILITY
AB A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.
C1 [Gupta, Kalpana] Vet Affairs Boston Hlth Care Syst, Dept Med, Boston, MA USA.
[Gupta, Kalpana] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Hooton, Thomas M.] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA.
[Colgan, Richard] Univ Maryland, Dept Family & Community Med, Baltimore, MD 21201 USA.
[Miller, Loren G.] Harbor UCLA Med Ctr, Div Infect Dis, Torrance, CA 90509 USA.
[Moran, Gregory J.] Olive View UCLA Med Ctr, Dept Emergency Med, Slymar, CA USA.
[Moran, Gregory J.] Olive View UCLA Med Ctr, Div Infect Dis, Slymar, CA USA.
[Schaeffer, Anthony J.] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA.
[Soper, David E.] Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA.
[Soper, David E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Nicolle, Lindsay E.] Univ Manitoba, Dept Internal Med, Winnipeg, MB, Canada.
[Nicolle, Lindsay E.] Univ Manitoba, Dept Med Mirobiol, Winnipeg, MB, Canada.
[Naber, Kurt G.] Tech Univ Munich, Munich, Germany.
[Wullt, Bjorn] Univ Lund Hosp, S-22185 Lund, Sweden.
[Raz, Raul] HaEmek Med Ctr, Infect Dis Unit, Afula, Israel.
[Raz, Raul] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel.
RP Gupta, K (reprint author), VA Boston HCS, 1400 VFW Pkwy,111 Med, W Roxbury, MA 02132 USA.
EM kalpana.gupta@va.gov
FU The Infectious Diseases Society of America; UpToDate; American
Urological Association; Bionorica; Daiichi; Sankyo; Janssen Cilag;
Johnson Johnson; OM Pharma; Pierre Fabre; Sanofi Aventis; Zambon;
Mer-Lion Pharmaceuticals; Rosen Pharma; Cubist; Pfizer Pharmaceuticals
FX Financial support. The Infectious Diseases Society of America.; K.G.
(Chair) has served as a consultant to Pfizer and Pinnacle
Pharmaceutical. A.J.S. has served as a consultant to Novabay
Pharmaceuticals, Pfizer, Propagate Pharmaceuticals, Hagen/Sinclair
Research Recruiting, Swiss Precision Diagnostics Development Company,
and FlashPointMedica; has received honoraria from BMJ Group (British
Medical Journal) and Advanstar Communications; received a royalty
payment from UpToDate; and received remuneration from the American
Urological Association. G.J.M. has served as a consultant to Cerexa,
Cubist, Eisai, Forest, Merck, Ortho-McNeil, Pfizer, and Schering-Plough
and has received honoraria from Cubist and Merck. K.G.N. has received
remuneration as consultant or speaker from Bionorica, Daiichi Sankyo,
Janssen Cilag, Johnson & Johnson, OM Pharma, Pierre Fabre, Sanofi
Aventis, and Zambon and has received research grants from Mer-Lion
Pharmaceuticals, Rosen Pharma, and OM Pharma. L.E.N. has served as a
consultant to Pfizer, Leo pharmaceuticals, Cerexa, and Johnson & Johnson
and served on the advisory board for Leo Pharmaceuticals and Cerexa.
L.G.M. has served as a consultant to Forest and Theravance Laboratories
and received research grants from Cubist and Pfizer Pharmaceuticals.
T.M.H. has served as a consultant to Pfizer, Alita Pharmaceuticals, and
Pinnacle Pharmaceuticals All other authors: no conflicts.
NR 62
TC 476
Z9 494
U1 10
U2 39
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 1
PY 2011
VL 52
IS 5
BP E103
EP E120
DI 10.1093/cid/ciq257
PG 18
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 716RR
UT WOS:000286991700001
PM 21292654
ER
PT J
AU Dolan, MM
Heyworth, BE
Bedi, A
Duke, G
Kelly, BT
AF Dolan, Mark M.
Heyworth, Benton E.
Bedi, Asheesh
Duke, Gavin
Kelly, Bryan T.
TI CT Reveals a High Incidence of Osseous Abnormalities in Hips with Labral
Tears
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID FEMORO-ACETABULAR IMPINGEMENT; FEMOROACETABULAR IMPINGEMENT;
RADIOGRAPHIC EVALUATION; OSTEOARTHRITIS; ANTEVERSION; RETROVERSION;
NECK; YOUNG; ARTHROSCOPY; EPIPHYSIS
AB Acetabular labral tears are being diagnosed with increasing frequency and there is a growing consensus that these tears rarely occur in the absence of osseous abnormalities.
We therefore determined the presence of structural abnormalities in patients with acetabular labral tears using a standardized CT protocol.
We evaluated 135 consecutive patients with labral tears diagnosed by MRI with CT scans of the symptomatic hip. The CT scans were evaluated in a standardized fashion to determine acetabular and femoral pathomorphologic features. Acetabular evaluation included version measurements and anterior and lateral center-edge angles. Femoral parameters evaluated included version, alpha angle, and neck-shaft angle.
One hundred twenty-two (90%) of the 135 hips had structural abnormalities. One hundred two (76%) had an alpha angle greater than 50A degrees, 18 (13%) had femoral version less than 5A degrees, 22 (16%) had femoral version greater than 25A(0), and five (4%) had coxa valga. Fifty-eight (43%) patients had acetabular retroversion and five (4%) had a lateral center-edge angle less than 20A(0). Of the 58 patients with acetabular retroversion, 23 had isolated cranial retroversion, 12 had isolated central retroversion, and 23 had combined cranial and central retroversion. Sixty-seven of the 121 hips (55%) with bony abnormalities had a combination of abnormalities.
Ninety percent of patients with labral tears had structural abnormalities seen on CT scans. These structural abnormalities frequently occur in combination, and understanding these underlying morphologic features of the hip can help guide treatment.
Level IV, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
C1 [Dolan, Mark M.] NW Orthopaed Inst, Chicago, IL 60611 USA.
[Dolan, Mark M.] Northwestern Univ, Feinberg Sch Med, Dept Orthopaed Surg, Chicago, IL 60611 USA.
[Heyworth, Benton E.] Massachusetts Gen Hosp, Dept Sports Med, Boston, MA 02114 USA.
[Bedi, Asheesh] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA.
[Duke, Gavin] New York Presbyterian Hosp, New York, NY USA.
[Kelly, Bryan T.] Hosp Special Surg, Ctr Hip Pain & Preservat, New York, NY 10021 USA.
RP Dolan, MM (reprint author), NW Orthopaed Inst, 680 N Lake Shore Dr,Suite 924, Chicago, IL 60611 USA.
EM markmdolan@gmail.com
NR 34
TC 41
Z9 42
U1 0
U2 4
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 MAR
PY 2011
VL 469
IS 3
BP 831
EP 838
DI 10.1007/s11999-010-1539-6
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 716BJ
UT WOS:000286939600030
PM 20886325
ER
PT J
AU Hatsukami, DK
Jorenby, DE
Gonzales, D
Rigotti, NA
Glover, ED
Oncken, CA
Tashkin, DP
Reus, VI
Akhavain, RC
Fahim, REF
Kessler, PD
Niknian, M
Kalnik, MW
Rennard, SI
AF Hatsukami, D. K.
Jorenby, D. E.
Gonzales, D.
Rigotti, N. A.
Glover, E. D.
Oncken, C. A.
Tashkin, D. P.
Reus, V. I.
Akhavain, R. C.
Fahim, R. E. F.
Kessler, P. D.
Niknian, M.
Kalnik, M. W.
Rennard, S. I.
TI Immunogenicity and Smoking-Cessation Outcomes for a Novel Nicotine
Immunotherapeutic
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID CONJUGATE VACCINE; IMMUNIZATION; RATS; RECOMMENDATIONS; BRAIN
AB NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-mu g doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-mu g dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.
C1 [Hatsukami, D. K.] Univ Minnesota, Dept Psychiat, Tobacco Use Programs, Minneapolis, MN 55455 USA.
[Jorenby, D. E.] Univ Wisconsin, Dept Med, Madison, WI USA.
[Gonzales, D.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Rigotti, N. A.] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Glover, E. D.] Univ Maryland, Dept Behav & Community Hlth, Sch Publ Hlth, College Pk, MD 20742 USA.
[Oncken, C. A.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Tashkin, D. P.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Reus, V. I.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Akhavain, R. C.; Fahim, R. E. F.; Kessler, P. D.; Niknian, M.; Kalnik, M. W.] Nabi Biopharmaceut, Rockville, MD USA.
[Rennard, S. I.] Univ Nebraska Med Ctr, Dept Med, Omaha, NE USA.
RP Hatsukami, DK (reprint author), Univ Minnesota, Dept Psychiat, Tobacco Use Programs, Minneapolis, MN 55455 USA.
EM hatsu001@umn.edu
RI reus, victor/I-7923-2015;
OI reus, victor/0000-0002-8193-5697; Gonzales, David/0000-0002-4323-198X
FU NIDA NIH HHS [R01 DA017894, R01 DA017894-01A1, 1R01DA017894-01A1]
NR 19
TC 86
Z9 86
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2011
VL 89
IS 3
BP 392
EP 399
DI 10.1038/clpt.2010.317
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 722NS
UT WOS:000287439600019
PM 21270788
ER
PT J
AU von Kanel, R
Carney, RM
Zhao, SJ
Whooley, MA
AF von Kaenel, Roland
Carney, Robert M.
Zhao, Shoujun
Whooley, Mary A.
TI Heart rate variability and biomarkers of systemic inflammation in
patients with stable coronary heart disease: findings from the Heart and
Soul Study
SO CLINICAL RESEARCH IN CARDIOLOGY
LA English
DT Article
DE Autonomic nervous system; Biomarkers; Cardiac autonomic function;
Cardiovascular disease; Heart rate variability; Inflammation
ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; ARTERY-DISEASE;
CARDIOVASCULAR-DISEASES; AUTONOMIC FUNCTION; PROGNOSTIC VALUE;
ANGINA-PECTORIS; UNSTABLE ANGINA; INTERLEUKIN-6; MARKERS
AB Chronic low-grade systemic inflammation is a key component in atherogenesis. Decreased heart rate variability (HRV), a strong predictor of cardiovascular events, has been associated with elevations in circulating levels of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen in apparently healthy individuals. We investigated whether decreased HRV is associated with inflammatory markers in patients with coronary heart disease (CHD).
We studied the relationship between HRV and CRP, IL-6, and fibrinogen in 862 outpatients with CHD. All participants provided fasting blood samples and underwent 24-h ambulatory monitoring to assess time-domain measures of HRV (MeanNN, SDNN, SDANN, and RMSSD). Regression analyses were adjusted for age, sex, ethnicity, body mass index, smoking, diabetes, beta blocker use, and cardiopulmonary history.
MeanNN, SDNN, and SDANN were significantly and inversely associated with CRP and IL-6 levels in age-adjusted models and after adjustment for all covariates (p a parts per thousand currency sign 0.02). MeanNN, SDNN, and SDANN were also inversely associated with fibrinogen levels in age-adjusted models (p < 0.03), but not significantly so in multivariable-adjusted models. Reduced vagal modulation of heart rate (RMSSD) was not significantly associated with any inflammatory measures.
Reduced cardiac autonomic control is associated with increased systemic inflammation in patients with stable CHD. This relationship was largely independent of important covariates.
C1 [von Kaenel, Roland] Univ Bern, Dept Gen Internal Med, Div Psychosomat Med, Inselspital,Bern Univ Hosp, CH-3010 Bern, Switzerland.
[Carney, Robert M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Zhao, Shoujun] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Whooley, Mary A.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA.
[Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP von Kanel, R (reprint author), Univ Bern, Dept Gen Internal Med, Div Psychosomat Med, Inselspital,Bern Univ Hosp, CH-3010 Bern, Switzerland.
EM roland.vonkaenel@insel.ch
FU Department of Veterans Affairs, Washington, DC; Robert Wood Johnson
Foundation, Princeton, New Jersey; American Federation for Aging
Research, New York, NY; Ischemia Research and Education Foundation, San
Bruno, CA
FX The Heart and Soul Study was supported by grants from the Department of
Veterans Affairs (Epidemiology Merit Review Program), Washington, DC;
The Robert Wood Johnson Foundation (Generalist Physician Faculty
Scholars Program), Princeton, New Jersey; the American Federation for
Aging Research Paul Beeson Faculty Scholars in Aging Research Program),
New York, NY; and the Ischemia Research and Education Foundation, San
Bruno, CA.
NR 45
TC 23
Z9 23
U1 2
U2 9
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1861-0684
EI 1861-0692
J9 CLIN RES CARDIOL
JI Clin. Res. Cardiol.
PD MAR
PY 2011
VL 100
IS 3
BP 241
EP 247
DI 10.1007/s00392-010-0236-5
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 723KQ
UT WOS:000287505800008
PM 20857123
ER
PT J
AU Trinh, NHT
Shyu, I
McGrath, PJ
Clain, A
Baer, L
Fava, M
Yeung, A
AF Trinh, Nhi-Ha T.
Shyu, Irene
McGrath, Patrick J.
Clain, Alisabet
Baer, Lee
Fava, Maurizio
Yeung, Albert
TI Examining the role of race and ethnicity in relapse rates of major
depressive disorder
SO COMPREHENSIVE PSYCHIATRY
LA English
DT Article
ID MINORITY PATIENTS; PRIMARY-CARE; ANXIETY DISORDERS; AFRICAN-AMERICAN;
ASIAN-AMERICANS; UNITED-STATES; BELIEFS; STIGMA; DRUG
AB Objective: We test the hypothesis that racial or ethnic differences exist in relapse rates to fluoxetine discontinuation in major depressive disorder (MDD).
Method: Data are from a prospective study examining the relapse rates secondary to fluoxetine discontinuation in MDD. Subjects in the discontinuation phase consisted of 255 adults aged 18 to 65: 214 subjects who self-identified as white, 22 as African American, 13 as Latino American, and 6 as Asian American.
Results: In both the fluoxetine and placebo groups, no statistically significant differences emerged when comparing time to relapse for minority groups as compared to the white population. Adjusting for statistically significant predictors of relapse (symptom severity, neurovegetative symptom pattern, sex) and for educational level did not change the outcome of the survival analyses.
Conclusions: Although the size of minority groups in this sample was modest, in a randomized, controlled trial setting, minority and white patients may have similar rates of relapse in MDD. This finding reinforces the importance of maintenance treatment in relapse for both minority as well as white patients with MDD. Given the self-selecting nature of clinical trials, future studies are needed to further examine the potential influence of underlying cultural factors on clinical outcomes in minority populations. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Trinh, Nhi-Ha T.; Shyu, Irene; Clain, Alisabet; Baer, Lee; Fava, Maurizio; Yeung, Albert] Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA.
[McGrath, Patrick J.] New York State Psychiat Inst & Hosp, Dept Psychiat, Depress Evaluat Serv, New York, NY 10032 USA.
RP Trinh, NHT (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA.
EM ntrinh@partners.org
FU NIMH NIH HHS [R10 MH056057, R10 MH056057-05]
NR 27
TC 2
Z9 2
U1 1
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 0010-440X
J9 COMPR PSYCHIAT
JI Compr. Psychiat.
PD MAR-APR
PY 2011
VL 52
IS 2
BP 151
EP 155
DI 10.1016/j.comppsych.2010.05.004
PG 5
WC Psychiatry
SC Psychiatry
GA 725MB
UT WOS:000287647700006
PM 21295221
ER
PT J
AU Potts, BC
Albitar, MX
Anderson, KC
Baritaki, S
Berkers, C
Bonavida, B
Chandra, J
Chauhan, D
Cusack, JC
Fenical, W
Ghobrial, IM
Groll, M
Jensen, PR
Lam, KS
Lloyd, GK
McBride, W
McConkey, DJ
Miller, CP
Neuteboom, STC
Oki, Y
Ovaa, H
Pajonk, F
Richardson, PG
Roccaro, AM
Sloss, CM
Spear, MA
Valashi, E
Younes, A
Palladino, MA
AF Potts, B. C.
Albitar, M. X.
Anderson, K. C.
Baritaki, S.
Berkers, C.
Bonavida, B.
Chandra, J.
Chauhan, D.
Cusack, J. C., Jr.
Fenical, W.
Ghobrial, I. M.
Groll, M.
Jensen, P. R.
Lam, K. S.
Lloyd, G. K.
McBride, W.
McConkey, D. J.
Miller, C. P.
Neuteboom, S. T. C.
Oki, Y.
Ovaa, H.
Pajonk, F.
Richardson, P. G.
Roccaro, A. M.
Sloss, C. M.
Spear, M. A.
Valashi, E.
Younes, A.
Palladino, M. A.
TI Marizomib, a Proteasome Inhibitor for All Seasons: Preclinical Profile
and a Framework for Clinical Trials
SO CURRENT CANCER DRUG TARGETS
LA English
DT Review
DE Proteasome inhibitor; marizomib; bortezomib; NF-kappa B; multiple
myeloma; pharmacodynamics; combination therapy
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NF-KAPPA-B; PANCREATIC-CANCER CELLS;
ADVANCED SOLID TUMORS; ACTINOMYCETE SALINISPORA-TROPICA;
SALINOSPORAMIDE-A NPI-0052; MULTIPLE-MYELOMA CELLS; GROWTH-FACTOR
RECEPTOR; NON-HODGKINS-LYMPHOMA; ACID-BASED PROTEASOME
AB The proteasome has emerged as an important clinically relevant target for the treatment of hematologic malignancies. Since the Food and Drug Administration approved the first-in-class proteasome inhibitor bortezomib (Velcade (R)) for the treatment of relapsed/refractory multiple myeloma (MM) and mantle cell lymphoma, it has become clear that new inhibitors are needed that have a better therapeutic ratio, can overcome inherent and acquired bortezomib resistance and exhibit broader anti-cancer activities. Marizomib (NPI-0052; salinosporamide A) is a structurally and pharmacologically unique beta-lactone-gamma-lactam proteasome inhibitor that may fulfill these unmet needs. The potent and sustained inhibition of all three proteolytic activities of the proteasome by marizomib has inspired extensive preclinical evaluation in a variety of hematologic and solid tumor models, where it is efficacious as a single agent and in combination with biologics, chemotherapeutics and targeted therapeutic agents. Specifically, marizomib has been evaluated in models for multiple myeloma, mantle cell lymphoma, Waldenstrom's macroglobulinemia, chronic and acute lymphocytic leukemia, as well as glioma, colorectal and pancreatic cancer models, and has exhibited synergistic activities in tumor models in combination with bortezomib, the immunomodulatory agent lenalidomide (Revlimid (R)), and various histone deacetylase inhibitors. These and other studies provided the framework for ongoing clinical trials in patients with MM, lymphomas, leukemias and solid tumors, including those who have failed bortezomib treatment, as well as in patients with diagnoses where other proteasome inhibitors have not demonstrated significant efficacy. This review captures the remarkable translational studies and contributions from many collaborators that have advanced marizomib from seabed to bench to bedside.
C1 [Potts, B. C.; Lam, K. S.; Lloyd, G. K.; Neuteboom, S. T. C.; Spear, M. A.; Palladino, M. A.] Nereus Pharmaceut Inc, San Diego, CA 92121 USA.
[Albitar, M. X.] Quest Diagnost Inc, Dept Hematopathol, San Juan Capistrano, CA 92675 USA.
[Anderson, K. C.; Chauhan, D.; Ghobrial, I. M.; Richardson, P. G.; Roccaro, A. M.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
[Anderson, K. C.; Chauhan, D.; Ghobrial, I. M.; Richardson, P. G.; Roccaro, A. M.] Harvard Univ, Sch Med, Jerome Lipper Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA.
[Baritaki, S.; Bonavida, B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Berkers, C.; Ovaa, H.] Netherlands Canc Inst, Div Cell Biol, Amsterdam, Netherlands.
[Chandra, J.; Miller, C. P.] Univ Texas Houston, Childrens Canc Hosp MD Anderson, Dept Pediat Res, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Cusack, J. C., Jr.; Sloss, C. M.] Harvard Univ, Massachusetts Gen Hosp, Div Surg Oncol, Sch Med, Boston, MA 02114 USA.
[Fenical, W.; Jensen, P. R.] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, San Diego, CA 92093 USA.
[Groll, M.] Tech Univ Munich, Ctr Integrated Prot Sci, Dept Chem, Lehrstuhl Biochem, D-85747 Garching, Germany.
[McBride, W.; Pajonk, F.; Valashi, E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA.
[McConkey, D. J.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Oki, Y.; Younes, A.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA.
RP Potts, BC (reprint author), Nereus Pharmaceut Inc, 10480 Wateridge Circle, San Diego, CA 92121 USA.
EM bpotts@nereuspharm.com; mpalladino@nereuspharm.com
RI Pajonk, Frank/E-4247-2010; Groll, Michael/F-5572-2015; Berkers,
Celia/I-3848-2016
FU NIH [SPORE-P50100707, PO1-CA078378, NIH RO1CA050947, NIH R01CA98871, F31
CA123645, NIH R01CA115811, NCI R37CA044848]
FX We gratefully acknowledge the contributions of the many individuals
whose research findings are captured in this review and whose efforts
have contributed to the extensive body of knowledge on marizomib. We
thank SR Potts for contributing Fig. (1). This work was supported by NIH
grants SPORE-P50100707, PO1-CA078378, and NIH RO1CA050947 to DC and KCA;
NIH R01CA98871 to JCC; F31 CA123645 to CPM; NIH R01CA115811 to JC; and
NCI R37CA044848 to WF.
NR 208
TC 94
Z9 94
U1 8
U2 21
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1568-0096
EI 1873-5576
J9 CURR CANCER DRUG TAR
JI Curr. Cancer Drug Targets
PD MAR
PY 2011
VL 11
IS 3
BP 254
EP 284
PG 31
WC Oncology
SC Oncology
GA 743BF
UT WOS:000288989700003
PM 21247382
ER
PT J
AU Singh, JA
Reddy, SG
Kundukulam, J
AF Singh, Jasvinder A.
Reddy, Supriya G.
Kundukulam, Joseph
TI Risk factors for gout and prevention: a systematic review of the
literature
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
DE alcohol; chronic diseases; diet; gout; gouty arthritis; medications;
risk factors; systematic review
ID URIC-ACID LEVEL; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH;
INCIDENT GOUT; FOLLOW-UP; TAIWAN ABORIGINES; PROSPECTIVE COHORT; HIGH
PREVALENCE; RENAL-FAILURE; DIURETIC USE
AB Purpose of review
Our objective was to perform a systematic review of risk factors and prevention of gout. We searched Medline for fully published reports in English using keywords including but not limited to 'gout', 'epidemiology', 'primary prevention', 'secondary prevention', 'risk factors'. Data from relevant articles meeting inclusion criteria were extracted using standardized forms.
Recent findings
Of the 751 titles and abstracts, 53 studies met the criteria and were included in the review. Several risk factors were studied. Alcohol consumption increased the risk of incident gout, especially beer and hard liquor. Several dietary factors increased the risk of incident gout, including meat intake, seafood intake, sugar sweetened soft drinks, and consumption of foods high in fructose. Diary intake, folate intake, and coffee consumption were each associated with a lower risk of incident gout and in some cases a lower rate of gout flares. Thiazide and loop diuretics were associated with higher risk of incident gout and higher rate of gout flares. Hypertension, renal insufficiency, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, diabetes, obesity, and early menopause were each associated with a higher risk of incident gout and/or gout flares.
Summary
Several dietary risk factors for incident gout and gout flares are modifiable. Prevention and optimal management of comorbidities are likely to decreased risk of gout. Research in preventive strategies for the treatment of gout is needed.
C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.
[Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA.
[Singh, Jasvinder A.; Reddy, Supriya G.; Kundukulam, Joseph] Univ Alabama, Dept Med, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] Univ Alabama, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA.
[Reddy, Supriya G.] Univ Alabama, Dept Hlth Sci, Tuscaloosa, AL USA.
RP Singh, JA (reprint author), Univ Alabama, Dept Med, Sch Publ Hlth, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.
EM Jasvinder.md@gmail.com
OI singh, jasvinder/0000-0003-3485-0006
FU Allergan; Takeda; Savient; Wyeth; Amgen; URL pharmaceuticals; Novartis;
Birmingham VA Medical Center, Alabama, USA
FX We thank Louise Falzon, of the Cochrane Library, for performing and
updating the search for this systematic review and April DeMedicis, of
the Birmingham VA Medical Center, for reviewing titles and abstracts
prior to conducting the full text review as well as assisting with the
data abstraction process. This material is the result of work supported
with the resources and the use of facilities at the Birmingham VA
Medical Center, Alabama, USA.; There are no financial conflicts related
to this work. J.A.S. has received speaker honoraria from Abbott;
research and travel grants from Allergan, Takeda, Savient, Wyeth and
Amgen; and consultant fees from Savient, URL pharmaceuticals and
Novartis.
NR 73
TC 43
Z9 60
U1 4
U2 56
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8711
J9 CURR OPIN RHEUMATOL
JI Curr. Opin. Rheumatol.
PD MAR
PY 2011
VL 23
IS 2
BP 192
EP 202
DI 10.1097/BOR.0b013e3283438e13
PG 11
WC Rheumatology
SC Rheumatology
GA 715JB
UT WOS:000286879200013
PM 21285714
ER
PT J
AU LoCascio, SA
Spinelli, J
Kurtz, J
AF LoCascio, Samuel A.
Spinelli, Joia
Kurtz, Josef
TI Hematopoietic Stem Cell Transplantation for the Treatment of
Autoimmunity in Type 1 Diabetes
SO CURRENT STEM CELL RESEARCH & THERAPY
LA English
DT Review
DE Diabetes; tolerance; chimerism; allogeneic; hematopoietic
ID BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; IMMUNOLOGICAL
SELF-TOLERANCE; NOD MICE; COSTIMULATORY BLOCKADE; HYGIENE HYPOTHESIS;
MIXED CHIMERISM; APOPTOSIS RESISTANCE; SUSCEPTIBILITY GENES; ANTI-CD154
ANTIBODY
AB Type 1 diabetes (T1D) is an autoimmune disease that leads to the destruction of the insulin-producing pancreatic beta cells. While there is no current cure, recent work in the field of allogeneic hematopoietic stem cell transplantation (HSCT) and the induction of mixed chimerism, a state in which multilineage hematopoietic populations of both recipient and donor co-exist, has demonstrated that it is possible to provide protection from disease onset, as well as reverse the autoimmune state in spontaneously diabetic mice. Furthermore, the establishment of mixed chimerism induces donor-specific tolerance, providing the potential to normalize glucose regulation via pancreatic islet transplantation without the requirement of life-long immunosuppression. Current studies are aimed at understanding the mechanisms involved in both the reversal of autoimmunity and the induction of tolerance, with the aim of moving this promising approach to curing T1D into the clinic.
C1 [LoCascio, Samuel A.; Spinelli, Joia; Kurtz, Josef] Univ Cambridge Emmanuel Coll, Boston, MA 02115 USA.
[LoCascio, Samuel A.; Kurtz, Josef] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA.
RP Kurtz, J (reprint author), Univ Cambridge Emmanuel Coll, 400 Fenway, Boston, MA 02115 USA.
EM kurtzj@emmanuel.edu
NR 76
TC 9
Z9 9
U1 0
U2 2
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1574-888X
J9 CURR STEM CELL RES T
JI Curr. Stem Cell Res. Ther.
PD MAR
PY 2011
VL 6
IS 1
BP 29
EP 37
PG 9
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 910LN
UT WOS:000301638700005
PM 20955158
ER
PT J
AU Shivakumar, G
Brandon, AR
Snell, PG
Santiago-Munoz, P
Johnson, NL
Trivedi, MH
Freeman, MP
AF Shivakumar, Geetha
Brandon, Anna R.
Snell, Peter G.
Santiago-Munoz, Patricia
Johnson, Neysa L.
Trivedi, Madhukar H.
Freeman, Marlene P.
TI ANTENATAL DEPRESSION: A RATIONALE FOR STUDYING EXERCISE
SO DEPRESSION AND ANXIETY
LA English
DT Review
DE exercise; physical activity; pregnancy; postpartum; mood; depression;
gestational diabetes; preeclampsia
ID GESTATIONAL DIABETES-MELLITUS; TIME PHYSICAL-ACTIVITY;
ADULT-NEUROGENESIS; PREGNANT-WOMEN; ANTIDEPRESSANT TREATMENT; POSTPARTUM
DEPRESSION; PERINATAL DEPRESSION; AMERICAN-COLLEGE; AEROBIC EXERCISE;
CONTROLLED-TRIAL
AB Background: Major depressive disorder (MDD) in pregnancy or antenatal depression poses unique treatment challenges and has serious consequences for mothers, unborn babies, and families when untreated. This review presents current knowledge on exercise during pregnancy, antidepressant effects of exercise, and the rationale for the specific study of exercise for antenatal depression. Method: A systematic literature review was performed using English language articles published in Medline, PsycINFO, CINAHL, and the Cochrane Library from 1985 to January 2010. Results: There is a broad literature supporting the antidepressant effects of exercise, but a paucity of studies specifically for antenatal depression. A small number of observational studies have reported that regular physical activities improve self-esteem and reduce symptoms of anxiety and depression during pregnancy. To date, there have not been randomized controlled studies of exercise for the treatment of MDD in pregnant women. Conclusions: Systematic studies are needed to assess exercise as a treatment alternative for MDD during pregnancy. In consideration of the benefits of exercise for the mother and baby, and the burden of depression, studies are needed to determine the role of exercise for pregnant women with depression. Depression and Anxiety 28:234-242, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [Shivakumar, Geetha] Dallas VA Med Ctr, Mental Hlth Trauma Serv, Dallas, TX 75216 USA.
[Shivakumar, Geetha; Brandon, Anna R.; Johnson, Neysa L.; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Snell, Peter G.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA.
[Santiago-Munoz, Patricia; Johnson, Neysa L.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
[Freeman, Marlene P.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA.
RP Shivakumar, G (reprint author), Dallas VA Med Ctr, Mental Hlth Trauma Serv, 4500 S Lancaster Rd,Mail Code 116A, Dallas, TX 75216 USA.
EM Geetha.Shivakumar@va.gov
FU NIH [1 UL1 RR024982-01]; NIMH [1K23MH085007-02, 5R01MH067692-04]; Glaxo
Smith Kline; Eli Lilly; Forest
FX The authors disclose the following financial relationships within the
past 3 years: Contract grant sponsor: NIH; Contract grant number: 1 UL1
RR024982-01; Contract grant sponsor: NIMH; Contract grant numbers:
1K23MH085007-02; 5R01MH067692-04.; Dr. Geetha Shivakumar acknowledges 12
months support from NIH (1 UL1 RR024982-01). Dr. Anna Brandon reports
current support from the NIMH (1K23MH085007-02) and the NIH (1 UL1
RR024982-01). Drs. Peter Snell, Patricia Santiago-Munoz, and Neysa
Johnson have no disclosures to report. Dr. Marlene Freeman acknowledges
support in last 12 months from Glaxo Smith Kline, Eli Lilly, Forest;
Honorarium for CME content: Pam Lab. Dr. Madhukar Trivedi acknowledges
NIMH 5R01MH067692-04 for his work on this manuscript.
NR 72
TC 18
Z9 19
U1 2
U2 23
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2011
VL 28
IS 3
BP 234
EP 242
DI 10.1002/da.20777
PG 9
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 734JZ
UT WOS:000288331700008
PM 21394856
ER
PT J
AU Killgore, WDS
Britton, JC
Price, LM
Gold, AL
Deckersbach, T
Rauch, SL
AF Killgore, William D. S.
Britton, Jennifer C.
Price, Lauren M.
Gold, Andrea L.
Deckersbach, Thilo
Rauch, Scott L.
TI NEURAL CORRELATES OF ANXIETY SENSITIVITY DURING MASKED PRESENTATION OF
AFFECTIVE FACES
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE FMRI; neuroimaging; anxiety sensitivity; ASI; insula; specific phobia;
healthy controls
ID PANIC DISORDER; BRAIN ACTIVATION; PHYSIOLOGICAL CONDITION; HIERARCHICAL
STRUCTURE; INSULAR CORTEX; CO2 CHALLENGE; AMYGDALA; PHOBIA;
INTEROCEPTION; INDEX
AB Background: Anxiety Sensitivity (AS), the tendency to fear the thoughts, symptoms, and social consequences associated with the experience of anxiety, is associated with increased risk for developing anxiety disorders. Some evidence suggests that higher scores on the Anxiety Sensitivity Index (ASI), a measure of the AS construct, are associated with activation of the anterior insular cortex during overt emotion perception. Although the ASI provides subscale scores measuring Physical, Mental Incapacitation, and Social Concerns of AS, no study has examined the relationship between these factors and regional brain activation during affect processing. We hypothesized that insular responses to fear-related stimuli would be primarily related to the Physical Concerns subscale of the ASI, particularly for a sample of subjects with specific phobias. Methods: Adult healthy controls (HC; n = 22) and individuals with specific phobia, small animal subtype (SAP; n = 17), completed the ASI and underwent functional magnetic resonance imaging while engaged in a backward-masked affect perception task that presents emotional facial stimuli below the threshold of conscious perception. Results: Groups did not differ in ASI, state or trait anxiety scores, or insula activation. Total ASI scores were positively correlated with activation in the right middle/anterior insula for the combined sample and for the HC and SAP groups separately. Multiple regression analysis revealed that the relationship between AS and insular activation was primarily accounted for by Physical Concerns only. Conclusions: Findings support the hypothesized role of the right anterior insula in the visceral/interoceptive aspects of AS, even in response to masked affective stimuli. Depression and Anxiety 28:243-249, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Killgore, William D. S.] Harvard Univ, McLean Hosp, Sch Med, Affect Neurosci Lab,Neuroimaging Ctr, Belmont, MA 02478 USA.
[Britton, Jennifer C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Deckersbach, Thilo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Belmont, MA 02478 USA.
[Deckersbach, Thilo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Belmont, MA 02478 USA.
[Gold, Andrea L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
RP Killgore, WDS (reprint author), Harvard Univ, McLean Hosp, Sch Med, Affect Neurosci Lab,Neuroimaging Ctr, 115 Mill St, Belmont, MA 02478 USA.
EM killgore@mclean.harvard.edu
RI Britton, Jennifer/J-4501-2013;
OI Gold, Andrea/0000-0003-4447-776X; Killgore, William/0000-0002-5328-0208
FU NIMH [R01 MH070730-04]; National Institute of Health
FX The authors disclose the following financial relationships within the
past 3 years: Contract grant sponsor: NIMH; Contract grant number: R01
MH070730-04; Contract grant sponsor: National Institute of Health.
NR 41
TC 15
Z9 15
U1 6
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2011
VL 28
IS 3
BP 243
EP 249
DI 10.1002/da.20788
PG 7
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 734JZ
UT WOS:000288331700009
PM 21308886
ER
PT J
AU Nostro, MC
Sarangi, F
Ogawa, S
Holtzinger, A
Corneo, B
Li, XL
Micallef, SJ
Park, IH
Basford, C
Wheeler, MB
Daley, GQ
Elefanty, AG
Stanley, EG
Keller, G
AF Nostro, M. Cristina
Sarangi, Farida
Ogawa, Shinichiro
Holtzinger, Audrey
Corneo, Barbara
Li, Xueling
Micallef, Suzanne J.
Park, In-Hyun
Basford, Christina
Wheeler, Michael B.
Daley, George Q.
Elefanty, Andrew G.
Stanley, Edouard G.
Keller, Gordon
TI Stage-specific signaling through TGF beta family members and WNT
regulates patterning and pancreatic specification of human pluripotent
stem cells
SO DEVELOPMENT
LA English
DT Article
DE Endoderm differentiation; Human embryonic stem cells; Human induced
pluripotent stem cells; beta-Cell; Pancreas
ID NODAL-RELATED SIGNALS; ISLET-LIKE CLUSTERS; DIRECTED DIFFERENTIATION;
DEFINITIVE ENDODERM; PRIMITIVE STREAK; IN-VIVO; MOUSE; INSULIN;
GASTRULATION; GENERATION
AB The generation of insulin-producing beta-cells from human pluripotent stem cells is dependent on efficient endoderm induction and appropriate patterning and specification of this germ layer to a pancreatic fate. In this study, we elucidated the temporal requirements for TGF beta family members and canonical WNT signaling at these developmental stages and show that the duration of nodal/activin A signaling plays a pivotal role in establishing an appropriate definitive endoderm population for specification to the pancreatic lineage. WNT signaling was found to induce a posterior endoderm fate and at optimal concentrations enhanced the development of pancreatic lineage cells. Inhibition of the BMP signaling pathway at specific stages was essential for the generation of insulin-expressing cells and the extent of BMP inhibition required varied widely among the cell lines tested. Optimal stage-specific manipulation of these pathways resulted in a striking 250-fold increase in the levels of insulin expression and yielded populations containing up to 25% C-peptide+cells.
C1 [Nostro, M. Cristina; Sarangi, Farida; Ogawa, Shinichiro; Holtzinger, Audrey; Keller, Gordon] Univ Hlth Network, McEwen Ctr Regenerat Med, Toronto, ON M5G 1L7, Canada.
[Corneo, Barbara] New York Neural Stem Cell Inst, Rensselaer, NY 12144 USA.
[Li, Xueling; Micallef, Suzanne J.; Elefanty, Andrew G.; Stanley, Edouard G.] Monash Univ, Monash Immunol & Stem Cell Labs, Clayton, Vic 3800, Australia.
[Park, In-Hyun] Yale Univ, Sch Med, Dept Genet, Yale Stem Cell Ctr, New Haven, CT 06520 USA.
[Basford, Christina; Wheeler, Michael B.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada.
[Daley, George Q.] Childrens Hosp, Cell Transplantat Program, Div Pediat Hematol Oncol, Manton Ctr Orphan Dis Res,Howard Hughes Med Inst, Boston, MA 02115 USA.
[Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Keller, G (reprint author), Univ Hlth Network, McEwen Ctr Regenerat Med, Toronto, ON M5G 1L7, Canada.
EM gkeller@uhnresearch.ca
RI Stanley, Ed/A-2985-2013; Elefanty, Andrew/A-6066-2008;
OI Stanley, Ed/0000-0002-6389-3665; Wheeler, Michael/0000-0002-7480-7267
FU NIH/NIDDK [U01-DK072513]; JDRF; ASCC; NHMRC (Australia)
FX We would like to thank members of the Keller laboratory, Dr Nadeem
Moghal and Dr Benjamin Neel for comments on the manuscript. This work
was supported by a grant from NIH/NIDDK (U01-DK072513) to G.K. M.C.N.
was supported by a JDRF postdoctoral fellowship. A.G.E., E.G.S., X.L.
and S.J.M. are supported by grants from the JDRF, the ASCC and the NHMRC
(Australia). A.G.E. and E.G.S. are Senior Research Fellows of the NHMRC.
Deposited in PMC for release after 12 months.
NR 63
TC 170
Z9 172
U1 2
U2 28
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD MAR 1
PY 2011
VL 138
IS 5
BP 861
EP 871
DI 10.1242/dev.055236
PG 11
WC Developmental Biology
SC Developmental Biology
GA 724KX
UT WOS:000287576100007
PM 21270052
ER
PT J
AU Bacci, S
Rizza, S
Prudente, S
Spoto, B
Powers, C
Facciorusso, A
Pacilli, A
Lauro, D
Testa, A
Zhang, YY
Di Stolfo, G
Mallamaci, F
Tripepi, G
Xu, R
Mangiacotti, D
Aucella, F
Lauro, R
Gervino, EV
Hauser, TH
Copetti, M
De Cosmo, S
Pellegrini, F
Zoccali, C
Federici, M
Doria, A
Trischitta, V
AF Bacci, Simonetta
Rizza, Stefano
Prudente, Sabrina
Spoto, Belinda
Powers, Christine
Facciorusso, Antonio
Pacilli, Antonio
Lauro, Davide
Testa, Alessandra
Zhang, Yuan-Yuan
Di Stolfo, Giuseppe
Mallamaci, Francesca
Tripepi, Giovanni
Xu, Rui
Mangiacotti, Davide
Aucella, Filippo
Lauro, Renato
Gervino, Ernest V.
Hauser, Thomas H.
Copetti, Massimiliano
De Cosmo, Salvatore
Pellegrini, Fabio
Zoccali, Carmine
Federici, Massimo
Doria, Alessandro
Trischitta, Vincenzo
TI The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk
Individuals Evidence for Interaction With Obesity in Diabetic Patients
SO DIABETES
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; BODY-MASS INDEX; INSULIN-RESISTANCE; K121Q
POLYMORPHISM; MYOCARDIAL-INFARCTION; METABOLIC SYNDROME; REVERSE
EPIDEMIOLOGY; HEART-DISEASE; ASSOCIATION; GENE
AB OBJECTIVE-Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals.
RESEARCH DESIGN AND METHODS-A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; n = 330 with type 2 diabetes and coronary artery disease), the Tor Vergata. Atherosclerosis Study (TVAS; n = 141 who had MI), and the Cardiovascular Risk Extended Evaluation in Dialysis (CREED) database (n = 266 with end-stage renal disease). Age at MI was investigated in cross-sectional studies of 339 type 2 diabetic patients (n = 169 from Italy, n = 170 from the U.S.).
RESULTS-Incidence of cardiovascular events per 100 person-years was 4.2 in GHS, 10.8 in TVAS, and 11.7 in CREED. Hazard ratios (HRs) for KQ+QQ versus individuals carrying the K121/K121 genotype (KK) individuals were 1.47 (95% CI 0.80-2.70) in GHS, 2.31 (95% CI 1.22-4.34) in TVAS, and 1.36 (95% CI 0.88-2.10) in CREED, and 1.56 (95% CI 1.15-2.12) in the three cohorts combined. In the 395 diabetic patients, the Q121 variant predicted cardiovascular events among obese but not among nonobese individuals (HR 5.94 vs. 0.62, P = 0.003 for interaction). A similar synergism was observed in cross-sectional studies, with age at MI being 3 years younger in Q121 carriers than in KK homozygotes among obese but not among nonobese patients (P = 0.035 for interaction).
CONCLUSIONS-The ENPP1 K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding. Diabetes 60:1000-1007, 2011
C1 [Mangiacotti, Davide; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy.
[Bacci, Simonetta; Pacilli, Antonio; De Cosmo, Salvatore] IRCCS Casa Sollievo Sofferenza, Unit Endocrinol, San Giovanni Rotondo, Italy.
[Rizza, Stefano; Lauro, Davide; Lauro, Renato; Federici, Massimo] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy.
[Prudente, Sabrina] IRCCS Casa Sollievo Sofferenza, Mendel Lab, San Giovanni Rotondo, Italy.
[Spoto, Belinda; Testa, Alessandra; Mallamaci, Francesca; Tripepi, Giovanni; Zoccali, Carmine] CNR IBIM, Res Unit Clin Epidemiol & Physiopathol Renal Dis, Reggio Di Calabria, Italy.
[Powers, Christine; Zhang, Yuan-Yuan; Xu, Rui; Doria, Alessandro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Facciorusso, Antonio; Di Stolfo, Giuseppe] IRCCS Casa Sollievo Sofferenza, Unit Cardiol, San Giovanni Rotondo, Italy.
[Zhang, Yuan-Yuan; Xu, Rui; Gervino, Ernest V.; Hauser, Thomas H.; Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Aucella, Filippo] IRCCS Casa Sollievo Sofferenza, Unit Nepluol & Dialysis, San Giovanni Rotondo, Italy.
[Gervino, Ernest V.; Hauser, Thomas H.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA.
[Copetti, Massimiliano; Pellegrini, Fabio] IRCCS Casa Sollievo Sofferenza, Unit Biostat, San Giovanni Rotondo, Italy.
[Pellegrini, Fabio] Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Chieti, Italy.
[Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy.
RP Trischitta, V (reprint author), IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy.
EM v.trischitta@operapadrepio.it
RI Federici, Massimo/G-9940-2012; Prudente, Sabrina/H-2886-2016; De Cosmo,
Salvatore/J-7420-2016; Trischitta, Vincenzo/K-1487-2016; Copetti,
Massimiliano/K-3186-2016;
OI Federici, Massimo/0000-0003-4989-5194; Prudente,
Sabrina/0000-0001-9220-8981; Zoccali, Carmine/0000-0002-6616-1996; De
Cosmo, Salvatore/0000-0001-8787-8286; Trischitta,
Vincenzo/0000-0003-1174-127X; Copetti, Massimiliano/0000-0002-7960-5947;
TESTA, ALESSANDRA/0000-0002-0529-6571; Lauro, Davide/0000-0002-8597-4415
FU Italian Ministry of Health; Fondazione Roma; National Institutes of
Health [HL73168, DK36836]
FX This study was partly supported by the Italian Ministry of Health
("Ricerca Corrente 2009 and 2010") (to S.P. and V.T.), by Fondazione
Roma ("Sostegno alla ricerca scientifica biomedica 2008") (to V.T.), and
by the National Institutes of Health Grants HL73168 (to A.D.) and
DK36836 to the Genetics Core of the Diabetes & Endocrinology Research
Center at the Joslin Diabetes Center.
NR 54
TC 19
Z9 20
U1 2
U2 12
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAR
PY 2011
VL 60
IS 3
BP 1000
EP 1007
DI 10.2337/db10-1300
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730UM
UT WOS:000288060300035
PM 21282363
ER
PT J
AU Goebel-Fabbri, AE
Anderson, BJ
Fikkan, J
Franko, DL
Pearson, K
Weinger, K
AF Goebel-Fabbri, Ann E.
Anderson, Barbara J.
Fikkan, Janna
Franko, Debra L.
Pearson, Kimberly
Weinger, Katie
TI Improvement and Emergence of Insulin Restriction in Women With Type 1
Diabetes
SO DIABETES CARE
LA English
DT Article
ID CLINICAL EATING-DISORDERS; MICROVASCULAR COMPLICATIONS; MELLITUS;
BEHAVIOR; INVENTORY; OMISSION; FEMALES; ADULTS; GIRLS; IDDM
AB OBJECTIVE To determine the distinguishing characteristics of women who report stopping insulin restriction at 11 years of follow-up from those continuing to endorse insulin restriction as well as those characteristics differing in patients who continue to Use insulin appropriately from new insulin restrictors.
RESEARCH DESIGN AND METHODS This is an 11-year follow-up study of 207 women with type 1 diabetes. Insulin restriction, diabetes self-care behaviors, diabetes-specific distress, and psychiatric and eating disorder symptoms were assessed using self-report surveys.
RESULTS Of the original sample, 57% participated in the follow-up study. Mean age was 44 +/- 12 years, diabetes duration was 28 +/- 11 years, and A1C was 7.9 +/- 1.3%. At follow-up, 20 of 60 baseline insulin restrictors had stopped restriction. Women who stopped reported improved diabetes self-care and distress, fewer problems with diabetes self-management, and lower levels of psychologic distress and eating disorder symptoms. Logistic regression indicated that lower levels of fear of weight gain with improved blood glucose and fewer problems with diabetes self-management predicted stopping restriction. At follow-up, 34 women (23%) reported new restriction, and a larger proportion of new insulin restrictors, relative to nonrestrictors, endorsed fear of weight gain with improved blood glucose.
CONCLUSIONS Findings indicate that fear of weight gain associated with improved blood glucose and problems with diabetes self-care are core issues related to both the emergence and resolution of insulin restriction. Greater attention to these concerns may help treatment teams to better meet the unique treatment needs of women struggling with insulin restriction. Diabetes Care 34:545-550, 2011
C1 [Goebel-Fabbri, Ann E.; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Goebel-Fabbri, Ann E.; Pearson, Kimberly; Weinger, Katie] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Anderson, Barbara J.] Texas Childrens Hosp, Dept Pediat, Houston, TX 77030 USA.
[Fikkan, Janna] Duke Univ, Med Ctr, Durham, NC USA.
[Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA.
[Pearson, Kimberly] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Weinger, K (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA.
EM katie.weinger@joslin.harvard.edu
FU Center of Excellence in Women's Health; Harvard Medical School; National
Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-060115,
P30-DK-36836]; National Institutes of Health; Herbert Graetz Fund
FX This project was funded by a grant from the Center of Excellence in
Women's Health, Harvard Medical School and the National Institute of
Diabetes and Digestive and Kidney Diseases (R01-DK-060115 and
P30-DK-36836). The original work was supported by grants from the
National Institutes of Health-supported Diabetes and Endocrinology
Research Center at Joslin Diabetes Center and the Herbert Graetz Fund.
NR 19
TC 8
Z9 8
U1 4
U2 11
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 MAR
PY 2011
VL 34
IS 3
BP 545
EP 550
DI 10.2337/dc10-1547
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 731YA
UT WOS:000288145400003
PM 21266653
ER
PT J
AU Markowitz, SM
Park, ER
Delahanty, LM
O'Brien, KE
Grant, RW
AF Markowitz, Sarah M.
Park, Elyse R.
Delahanty, Linda M.
O'Brien, Kelsey E.
Grant, Richard W.
TI Perceived Impact of Diabetes Genetic Risk Testing Among Patients at High
Phenotypic Risk for Type 2 Diabetes
SO DIABETES CARE
LA English
DT Article
ID INTERVENTIONS; METAANALYSIS; PERCEPTIONS; PREDICTION; VARIANTS;
MELLITUS; OUTCOMES
AB OBJECTIVE-Rapid advances in diabetes genetic epidemiology may lead to a new era of "personalized medicine" based on individual genetic risk assessment. There is minimal experience to guide how best to clinically implement such testing so that results (e.g., "higher" or "lower" relative genetic risk) improve rather than reduce patient motivation for behavior change.
RESEARCH DESIGN AND METHODS-Between November 2009 and May 2010, we conducted in-depth interviews with 22 overweight participants at high phenotypic risk for type 2 diabetes to explore perceptions of diabetes genetic risk testing compared with currently available prediction using nongenetic risk factors (e.g., family history, abnormal fasting glucose, obesity). We used hypothetical scenarios to specifically investigate the impact of both "higher" and "lower" relative genetic risk results on participants' views about diabetes prevention.
RESULTS-Many participants conferred a unique value on personal genetic risk information relative to nongenetic risk based on the perceived scientific certainty and durability of genetic results. In contrast, other participants considered their genetic risk within the overall context of their other measured risk factors. Reactions to diabetes genetic test results differed by current motivation levels. Whereas most subjects reported that "higher" risk results would motivate behavior change, subjects with lower current motivation often reported that "lower" genetic risk results would further reduce their motivation to engage in diabetes prevention behaviors.
CONCLUSIONS-To be effective, future clinical implementation of type 2 diabetes genetic risk testing should be individualized based on each patient's risk perception and current level of motivation to prevent diabetes.
C1 [Park, Elyse R.; Delahanty, Linda M.; O'Brien, Kelsey E.; Grant, Richard W.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Markowitz, Sarah M.] Wells Coll, Aurora, NY USA.
[Park, Elyse R.] Mongan Inst Hlth Policy, Boston, MA USA.
[Delahanty, Linda M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[O'Brien, Kelsey E.; Grant, Richard W.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA.
RP Grant, RW (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
EM rgrant@partners.org
OI Grant, Richard/0000-0002-6164-8025
FU NIDDK NIH HHS [R21 DK084527-01, R21 DK084527]
NR 24
TC 22
Z9 23
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 MAR
PY 2011
VL 34
IS 3
BP 568
EP 573
DI 10.2337/dc10-1960
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 731YA
UT WOS:000288145400007
PM 21285385
ER
PT J
AU Fiallo-Scharer, R
Cheng, J
Beck, RW
Buckingham, BA
Chase, HP
Kollman, C
Laffel, L
Lawrence, JM
Mauras, N
Tamborlane, WV
Wilson, DM
Wolpert, H
Bode, B
Ruedy, KJ
Weinzimer, S
Xing, DY
AF Fiallo-Scharer, Rosanna
Cheng, Jing
Beck, Roy W.
Buckingham, Bruce A.
Chase, H. Peter
Kollman, Craig
Laffel, Lori
Lawrence, Jean M.
Mauras, Nelly
Tamborlane, William V.
Wilson, Darrell M.
Wolpert, Howard
Bode, Bruce
Ruedy, Katrina J.
Weinzimer, Stuart
Xing, Dongyuan
CA JDRF Continuous Glucose Monitoring
TI Factors Predictive of Severe Hypoglycemia in Type 1 Diabetes Analysis
from the Juvenile Diabetes Research Foundation continuous glucose
monitoring randomized control trial dataset
SO DIABETES CARE
LA English
DT Article
ID BLOOD-GLUCOSE; CHILDREN; VALIDATION; ACCURACY; THERAPY; RISK
AB OBJECTIVE-Identify factors predictive of severe hypoglycemia (SH) and assess the clinical utility of continuous glucose monitoring (CGM) to warn of impending SH.
RESEARCH DESIGN AND METHODS-In a multicenter randomized clinical trial, 436 children and adults with type 1 diabetes were randomized to a treatment group that used CGM (N = 224), or a control group that used standard home blood glucose monitoring (N = 212) and completed 12 months of follow-up. After 6 months, the original control group initiated CGM while the treatment group continued use of CGM for 6 months. Baseline risk factors for SH were evaluated over 12 months of follow-up using proportional hazards regression. CGM-derived indices of hypoglycemia were used to predict episodes of SH over a 24-h time horizon.
RESULTS-The SH rate was 17.9 per 100 person-years, and a higher rate was associated with the occurrence of SH in the prior 6 months and female sex. SH frequency increased eightfold when 30% of CGM values were <= 70 mg/dL on the prior day (4.5 vs. 0.5%; P < 0.001), but the positive predictive value (PPV) was low (< 5%). Results were similar for hypoglycemic area under the curve and the low blood glucose index calculated by CGM.
CONCLUSIONS-SH in the 6 months prior to the study was the strongest predictor of SH during the study. CGM-measured hypoglycemia over a 24-h span is highly associated with SH the following day (P < 0.001), but the PPV is low.
C1 [Cheng, Jing; Beck, Roy W.; Kollman, Craig; Ruedy, Katrina J.; Xing, Dongyuan] Jaeb Ctr Hlth Res, Tampa, FL USA.
[Fiallo-Scharer, Rosanna; Chase, H. Peter] Barbara Davis Ctr Childhood Diabet, Aurora, CO USA.
[Buckingham, Bruce A.; Wilson, Darrell M.] Stanford Univ, Stanford, CA 94305 USA.
[Laffel, Lori; Wolpert, Howard] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Lawrence, Jean M.] Kaiser Permanente, San Diego, CA USA.
[Mauras, Nelly] Nemours Childrens Clin, Jacksonville, FL USA.
[Tamborlane, William V.; Weinzimer, Stuart] Yale Univ, New Haven, CT USA.
[Bode, Bruce] Atlanta Diabet Associates, Atlanta, GA USA.
RP Beck, RW (reprint author), Jaeb Ctr Hlth Res, Tampa, FL USA.
EM jdrfapp@jaeb.org
FU JDRF [22-2006-1107, 22-2006-1117, 22-2006-1112, 22-2006-1123,
01-2006-8031]; Medtronic MiniMed, Inc.; DexCom, Inc.; Abbott Diabetes
Care, Inc.
FX The study funding was provided by JDRF (grant numbers 22-2006-1107,
22-2006-1117, 22-2006-1112, 22-2006-1123, and 01-2006-8031).; B.B.
reports having received consulting fees, honoraria, travel
reimbursement, and research funds from Medtronic MiniMed, Inc. and grant
support from DexCom, Inc. B.A.B. reports having received grant support
and serving on the Medical Advisory Board for Medtronic MiniMed, Inc.,
grant support and a speaker honorarium from Abbott Diabetes Care, Inc.,
and grant support from DexCom, Inc. C.K. reports having received
consulting fees from Medtronic MiniMed, Inc. L.L. reports having
received consulting fees and a speaker honorarium from Abbott Diabetes
Care, Inc., and consulting fees and research funding from Medtronic
MiniMed, Inc. W.V.T. reports having received consulting fees from
Medtronic MiniMed, Inc. S.W. reports having received research support, a
speaker honorarium and travel reimbursement from Medtronic MiniMed,
Inc., and a speaker honorarium from Animas Corp/LifeScan, Inc. No other
potential conflicts of interest relevant to this article were reported.
NR 20
TC 22
Z9 22
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2011
VL 34
IS 3
BP 586
EP 590
DI 10.2337/dc10-1111
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 731YA
UT WOS:000288145400010
ER
PT J
AU Cheng, PY
Neugaard, B
Foulis, P
Conlin, PR
AF Cheng, Peiyao
Neugaard, Britta
Foulis, Philip
Conlin, Paul R.
TI Hemoglobin A(1c) as a Predictor of Incident Diabetes
SO DIABETES CARE
LA English
DT Article
ID CARDIOVASCULAR-DISEASE; US POPULATION; RISK; A1C; PREVALENCE; HBA(1C);
ADULTS; ASSOCIATION; DIAGNOSIS; VETERANS
AB OBJECTIVE-Several studies have suggested that HbA(1c) levels may predict incident diabetes. With new recommendations for use of HbA(1c) in diagnosing diabetes, many patients with HbA(1c) results below the diagnostic threshold will be identified. Clinicians will need to categorize risk for a subsequent diabetic diagnosis in such patients. The objective of this study was to determine the ability of HbA(1c) to predict the incidence of a diabetic diagnosis.
RESEARCH DESIGN AND METHODS-We performed a historical cohort study using electronic medical record data from two Department of Veterans Affairs Medical Centers. Patients (n = 12,589) were identified with a baseline HbA(1c) < 6.5% between January 2000 and December 2001 and without a diagnosis of diabetes. Patients (12,375) had at least one subsequent follow-up visit. These patients were tracked for 8 years for a subsequent diagnosis of diabetes.
RESULTS-During an average follow-up of 4.4 years, 3,329 (26.9%) developed diabetes. HbA(1c) >= 5.0% carried a significant risk for developing diabetes during follow-up. When compared with the reference group (HbA(1c) < 4.5%), HbA(1c) increments of 0.5% between 5.0 and 6.4% had adjusted odds ratios of 1.70(5.0-5.4%), 4.87 (5.5-5.9%), and 16.06(6.0-6.4%) (P < 0.0001). Estimates of hazard ratios similarly showed significant increases for HbA(1c) >= 5.0% A risk model for incident diabetes within 5 years was developed and validated using HbA(1c), age, BMI, and systolic blood pressure.
CONCLUSIONS-The incidence of diabetes progressively and significantly increased among patients with an HbA(1c) >= 5.0%, with substantially expanded risk for those with HbA(1c) 6.0-6.4%.
C1 [Conlin, Paul R.] VA Boston Healthcare Syst, Boston, MA USA.
[Cheng, Peiyao; Neugaard, Britta; Foulis, Philip] Dept Vet Affairs Med Ctr, Tampa, FL USA.
[Neugaard, Britta] Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, Tampa, FL USA.
[Neugaard, Britta; Foulis, Philip] Univ S Florida, Coll Med, Dept Pathol & Cell Biol, Tampa, FL USA.
[Conlin, Paul R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Conlin, PR (reprint author), VA Boston Healthcare Syst, Boston, MA USA.
EM paul.conlin@va.gov
FU VA Health Services Research and Development Service [TEL-02-100,
IIR-04-045]; National Institutes of Health [K24-DK063214]; Tosoh
Bioscience
FX Funding for this work was provided by the VA Health Services Research
and Development Service. (Grants TEL-02-100 and IIR-04-045), the
National Institutes of Health (Grant K24-DK063214), and Tosoh
Bioscience.
NR 23
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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 MAR
PY 2011
VL 34
IS 3
BP 610
EP 615
DI 10.2337/dc10-0625
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 731YA
UT WOS:000288145400017
PM 21289229
ER
PT J
AU Lautz, D
Halperin, F
Goebel-Fabbri, A
Goldfine, AB
AF Lautz, David
Halperin, Florencia
Goebel-Fabbri, Ann
Goldfine, Allison B.
TI The Great Debate: Medicine or Surgery What is best for the patient with
type 2 diabetes?
SO DIABETES CARE
LA English
DT Review
ID GASTRIC-BYPASS-SURGERY; BARIATRIC SURGICAL-PROCEDURES; DUODENAL-JEJUNAL
EXCLUSION; LIFE-STYLE INTERVENTION; BODY-MASS INDEX; WEIGHT-LOSS;
HYPERINSULINEMIC HYPOGLYCEMIA; CARDIOVASCULAR OUTCOMES; LONGITUDINAL
ASSESSMENT; GLYCEMIC CONTROL
C1 [Lautz, David; Halperin, Florencia; Goldfine, Allison B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lautz, David] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Halperin, Florencia; Goebel-Fabbri, Ann; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Halperin, Florencia; Goldfine, Allison B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Goebel-Fabbri, Ann] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Goldfine, AB (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM allison.goldfine@joslin.harvard.edu
FU National Institutes of Health [1RC1-DK-086918, KL2-RR-025757]; DERC
[P30-DK-36836]; Covidien; Nestle; LifeScan, a Division of Johnson
Johnson; Mercodia; National Institutes of Health/National Institute of
Diabetes and Digestive and Kidney Diseases
FX This research was supported by National Institutes of Health Grants
1RC1-DK-086918 and KL2-RR-025757 (to F.H.), and DERC P30-DK-36836.;
Additional funds and supplies to support the trial are provided by
Covidien; Nestle; LifeScan, a Division of Johnson & Johnson; and
Mercodia. D.L. has worked occasionally as a consultant for Covidien,
largely reviewing their instrumentation; this has always been less than
$2000/year and has always been vetted by the Brigham and Women's
Hospital Corporate Sponsored Research office. Neither D.L. nor A.B.G.
has personal financial interest in Covidien. No other potential
conflicts of interest relevant to this article were reported. The
authors note they are conducting an investigator-initiated clinical
trial sponsored by the National Institutes of Health/National Institute
of Diabetes and Digestive and Kidney Diseases (clinical trials
identifier NCT01073020).
NR 61
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U1 0
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PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2011
VL 34
IS 3
BP 763
EP 770
DI 10.2337/dc10-1859
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 731YA
UT WOS:000288145400048
PM 21357363
ER
PT J
AU Boyko, EJ
Meigs, JB
AF Boyko, Edward J.
Meigs, James B.
TI Does Diabetes Always Confer Coronary Heart Disease Risk Equivalent to a
Prior Myocardial Infarction? Implications for prevention
SO DIABETES CARE
LA English
DT Editorial Material
ID BLOOD-GLUCOSE CONTROL; SCIENTIFIC STATEMENT; TYPE-2; COMPLICATIONS;
ASPIRIN; INTERVENTION; METAANALYSIS; ASSOCIATION; INFORMATION; METFORMIN
C1 [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Div Gen Med, Boston, MA USA.
RP Boyko, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
EM eboyko@uw.edu
FU NIDDK NIH HHS [P30 DK017047, P30-DK17047, K24-DK080140, K24 DK080140]
NR 17
TC 8
Z9 8
U1 1
U2 4
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 MAR
PY 2011
VL 34
IS 3
BP 782
EP 784
DI 10.2337/dc10-1958
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 731YA
UT WOS:000288145400051
PM 21357366
ER
PT J
AU Bains, SS
Egede, LE
AF Bains, Sujeev S.
Egede, Leonard E.
TI Associations Between Health Literacy, Diabetes Knowledge, Self-Care
Behaviors, and Glycemic Control in a Low Income Population with Type 2
Diabetes
SO DIABETES TECHNOLOGY & THERAPEUTICS
LA English
DT Article
ID MEDICATION ADHERENCE; MORTALITY; OUTCOMES; EDUCATION; DISEASE; RISK;
COMPLICATIONS; METAANALYSIS; MELLITUS; PEOPLE
AB Objective: This study assessed associations among health literacy, diabetes knowledge, self-care, and glycemic control in a low income, predominately minority population with type 2 diabetes.
Methods: One hundred twenty-five adults with diabetes were recruited from a primary care clinic. Subjects completed validated surveys to measure health literacy, diabetes knowledge, and self-care (medication adherence, diet, exercise, blood sugar testing, and foot care). Hemoglobin A1c values were extracted from the medical record. Spearman's correlation and multiple linear regression were used to assess the relationship among health literacy, diabetes knowledge, self-care, and glycemic control controlling for covariates.
Results: Cronbach's alpha was 0.95 for the Revised Rapid Estimate of Adult Literacy in Medicine. The majority of the sample was < 65 years old (50.7%), female (72.5%), and African American (71.4%), had less than a high school education (68.2%) and a household income <$15,000 (64.2%), and reported their health status as worse than last year (73.9%). In adjusted models that examined the associations among health literacy, diabetes knowledge, medication adherence, and self-care, health literacy was only significantly associated with diabetes knowledge (beta = 0.55; 95% confidence interval [CI] 0.29, 0.82). In the final adjusted model for independent factors associated with glycemic control, both diabetes knowledge (beta = 0.12; 95% CI 0.01, 0.23) and perceived health status (beta = 1.14; 95% CI 0.13, 2.16) were significantly associated with glycemic control, whereas health literacy was not associated with glycemic control (beta = -0.03; 95% CI -0.19, 0.13).
Conclusions: Diabetes knowledge and perceived health status are the most important factors associated with glycemic control in this population. Health literacy appears to exert its influence through diabetes knowledge and is not directly related to self-care or medication adherence.
C1 [Bains, Sujeev S.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
[Bains, Sujeev S.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA.
RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA.
EM egedel@musc.edu
FU NIDDK NIH HHS [R01 DK081121, T35 DK007431]
NR 50
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U1 2
U2 23
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1520-9156
J9 DIABETES TECHNOL THE
JI Diabetes Technol. Ther.
PD MAR
PY 2011
VL 13
IS 3
BP 335
EP 341
DI 10.1089/dia.2010.0160
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 727KO
UT WOS:000287798200007
PM 21299402
ER
PT J
AU Xing, DY
Kollman, C
Beck, RW
Tamborlane, WV
Laffel, L
Buckingham, BA
Wilson, DM
Weinzimer, S
Fiallo-Scharer, R
Ruedy, KJ
AF Xing, Dongyuan
Kollman, Craig
Beck, Roy W.
Tamborlane, William V.
Laffel, Lori
Buckingham, Bruce A.
Wilson, Darrell M.
Weinzimer, Stuart
Fiallo-Scharer, Rosanna
Ruedy, Katrina J.
CA Juvenile Diabet Res Fdn Continuous
TI Optimal Sampling Intervals to Assess Long-Term Glycemic Control Using
Continuous Glucose Monitoring
SO DIABETES TECHNOLOGY & THERAPEUTICS
LA English
DT Article
ID TRIAL; ACCURACY; CHILDREN; SYSTEM
AB Aims and Hypothesis: The optimal duration and frequency of short-term continuous glucose monitoring (CGM) to reflect long-term glycemia have not been determined. The Juvenile Diabetes Research Foundation CGM randomized trials provided a large dataset of longitudinal CGM data for this type of analysis.
Methods: The analysis included 185 subjects who had 334 3-month intervals of CGM data meeting specific criteria. For various glucose indices, correlations (r(2)) were computed for the entire 3-month interval versus selected sampling periods ranging from 3 to 15 days. Other computed agreement measures included median relative absolute difference, values within +/- 10% and +/- 20% of full value, and median absolute difference.
Results: As would be expected, the more days of glucose data that were sampled, the higher the correlation with the full 3 months of data. For 3 days of sampling, the r(2) value ranged from 0.32 to 0.47, evaluating mean glucose, percentage of values 71-180 mg/dL, percentage of values > 180mg/dL, percentage of values <= 70mg/dL, and coefficient of variation; in contrast, for 15 days of sampling, the r(2) values ranged from 0.66 to 0.75. The results were similar when the analysis intervals were stratified by age group (8-14, 15-24, and >= 25 years), by baseline hemoglobin A1c level (< 7.0% and >= 7.0%), and by CGM device type.
Conclusions and Interpretation: Our data suggest that a 12-15-day period of monitoring every 3 months may be needed to optimally assess overall glucose control. Shorter periods of sampling can be useful, but the correlation with 3-month measures of glycemic control is lower.
C1 [Xing, Dongyuan; Kollman, Craig; Beck, Roy W.; Ruedy, Katrina J.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
[Tamborlane, William V.; Weinzimer, Stuart] Yale Univ, Dept Pediat, New Haven, CT 06520 USA.
[Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Buckingham, Bruce A.; Wilson, Darrell M.] Stanford Univ, Stanford, CA 94305 USA.
[Fiallo-Scharer, Rosanna] Barbara Davis Ctr, Aurora, CO USA.
RP Xing, DY (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA.
EM jdrfapp@jaeb.org
FU Juvenile Diabetes Research Foundation, Inc. [22-2006-1107, 22-2006-1117,
22-2006-1112, 22-2006-1123, 01-2006-8031]; Medical Advisory Board for
Medtronic MiniMed, Inc.; Abbott Diabetes Care, Inc.; DexCom, Inc.;
Medtronic MiniMed, Inc.
FX The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring
Study Group would like to recognize the efforts of the subjects and
their families and thank them for their participation. Study funding was
provided by the Juvenile Diabetes Research Foundation, Inc. with grant
numbers 22-2006-1107, 22-2006-1117, 22-2006-1112, 22-2006-1123, and
01-2006-8031.; Continuous glucose monitors and sensors were purchased at
a bulk discount price from DexCom, Inc. (San Diego, CA), Medtronic
MiniMed, Inc. (Northridge, CA), and Abbott Diabetes Care, Inc. (Alameda,
CA). Home glucose meters and test strips were provided to the study by
LifeScan, Inc. and Abbott Diabetes Care, Inc. The companies had no
involvement in the design, conduct, or analysis of the trial or the
manuscript preparation. Below is a listing of relationships of the
investigators with companies that make products relevant to the article
between July 1, 2006 and present; research funds where listed below were
provided to the legal entity that employs the individual and not
directly to the individual: B.A.B. reports having received grant support
and serving on the Medical Advisory Board for Medtronic MiniMed, Inc.,
grant support and a speaker honorarium from Abbott Diabetes Care, Inc.,
and grant support from DexCom, Inc.; C.K. reports having received
consulting fees from Medtronic MiniMed, Inc.; L.L. reports having
received consulting fees and a speaker honorarium from Abbott Diabetes
Care, Inc. and consulting fees and research funding from Medtronic
MiniMed, Inc.; W.V.T. reports having received consulting fees from
Medtronic MiniMed, Inc.; and S.W. reports having received research
support, a speaker honorarium, and travel reimbursement from Medtronic
MiniMed, Inc. and a speaker honorarium from Animas Corp./Lifescan, Inc.
NR 14
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U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1520-9156
J9 DIABETES TECHNOL THE
JI Diabetes Technol. Ther.
PD MAR
PY 2011
VL 13
IS 3
BP 351
EP 358
DI 10.1089/dia.2010.0156
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 727KO
UT WOS:000287798200009
PM 21299401
ER
PT J
AU Aguayo-Mazzucato, C
Koh, A
El Khattabi, I
Li, WC
Toschi, E
Jermendy, A
Juhl, K
Mao, K
Weir, GC
Sharma, A
Bonner-Weir, S
AF Aguayo-Mazzucato, C.
Koh, A.
El Khattabi, I.
Li, W. -C.
Toschi, E.
Jermendy, A.
Juhl, K.
Mao, K.
Weir, G. C.
Sharma, A.
Bonner-Weir, S.
TI Mafa expression enhances glucose-responsive insulin secretion in
neonatal rat beta cells
SO DIABETOLOGIA
LA English
DT Article
DE Beta cell development; Insulin secretion; MAFA; Maturation
ID EMBRYONIC STEM-CELLS; ENDOCRINE PANCREAS; IN-VIVO; GENE; TRANSCRIPTION;
ISLETS; PDX-1; MATURATION; HORMONE; DIFFERENTIATION
AB Neonatal beta cells lack glucose-stimulated insulin secretion and are thus functionally immature. We hypothesised that this lack of glucose responsiveness results from a generalised low expression of genes characteristic of mature functional beta cells. Important glucose-responsive transcription factors, Mafa and Pdx1, regulate genes involved in insulin synthesis and secretion, and have been implicated in late beta cell development. The aim of this study was to assess whether Mafa and/or Pdx1 regulates the postnatal functional maturation of beta cells.
By quantitative PCR we evaluated expression of these and other beta cell genes over the first month compared with adult. After infection with adenovirus expressing MAFA, Pdx1 or green fluorescent protein (Gfp), P2 rat islets were evaluated by RT-PCR and insulin secretion with static incubation and reverse haemolytic plaque assay (RHPA).
At P2 most beta cell genes were expressed at about 10% of adult, but by P7 Pdx1 and Neurod1 no longer differ from adult; by contrast, Mafa expression remained significantly lower than adult through P21. Overexpression of Pdx1 increased Mafa, Neurod1, glucokinase (Gck) mRNA and insulin content but failed to enhance glucose responsiveness. Similar overexpression of MAFA resulted in increased Neurod1, Nkx6-1, Gck and Glp1r mRNAs and no change in insulin content but, importantly, acquisition of glucose-responsive insulin secretion. Both the percentage of secreting beta cells and the amount of insulin secreted per beta cell increased, approaching that of adult beta cells.
In the process of functional maturation acquiring glucose-responsive insulin secretion, neonatal beta cells undergo a coordinated gene expression programme in which Mafa plays a crucial role.
C1 [Aguayo-Mazzucato, C.; Koh, A.; El Khattabi, I.; Li, W. -C.; Toschi, E.; Jermendy, A.; Juhl, K.; Mao, K.; Weir, G. C.; Sharma, A.; Bonner-Weir, S.] Harvard Univ, Sch Med, Sect Islet Cell & Regenerat Biol, Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Sharma, A (reprint author), Harvard Univ, Sch Med, Sect Islet Cell & Regenerat Biol, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM arun.sharma@joslin.harvard.edu; susan.bonner-weir@joslin.harvard.edu
FU NIH [R01 DK 66056, R01 DK 60127]; Joslin Diabetes and Endocrinology
Research Center (DERC) [P30 DK36836]; Juvenile Diabetes Research
Foundation; Diabetes Research and Wellness Foundation; Graetz Fund;
Joslin [T32 DK007260]; JDRF; Singapore National Medical Research
Council; Lundbeckfonden fellowship
FX The authors thank J. Lock, T. Salameh and C. Cahill, all of the Joslin
Diabetes Center, for their expert technical assistance. This study was
supported by NIH R01 DK 66056 (S. Bonner-Weir), R01 DK 60127 (A.
Sharma), P30 DK36836 Joslin Diabetes and Endocrinology Research Center
(DERC) Advanced Microscopy Core grants as well as the Juvenile Diabetes
Research Foundation, Diabetes Research and Wellness Foundation, the
Graetz Fund and an important group of private donors. I. El Khattabi was
supported by Joslin T32 DK007260, W. C. Li by a JDRF Post doctoral
fellowship, A. Koh by a Singapore National Medical Research Council
Research fellowship grant, and K. Juhl by a Lundbeckfonden fellowship.
NR 40
TC 52
Z9 53
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD MAR
PY 2011
VL 54
IS 3
BP 583
EP 593
DI 10.1007/s00125-010-2026-z
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 716PX
UT WOS:000286987000016
PM 21190012
ER
PT J
AU Jermendy, A
Toschi, E
Aye, T
Koh, A
Aguayo-Mazzucato, C
Sharma, A
Weir, GC
Sgroi, D
Bonner-Weir, S
AF Jermendy, A.
Toschi, E.
Aye, T.
Koh, A.
Aguayo-Mazzucato, C.
Sharma, A.
Weir, G. C.
Sgroi, D.
Bonner-Weir, S.
TI Rat neonatal beta cells lack the specialised metabolic phenotype of
mature beta cells
SO DIABETOLOGIA
LA English
DT Article
DE Glucose responsiveness; Immature function; Mitochondrial shuttles;
Neonatal islet
ID STIMULATED INSULIN-SECRETION; LASER-CAPTURE MICRODISSECTION;
GENE-EXPRESSION; PANCREATIC-ISLETS; MITOCHONDRIAL METABOLISM;
PYRUVATE-CARBOXYLASE; NEWBORN RATS; GLUCOSE; FETAL; SHUTTLE
AB Fetal and neonatal beta cells have poor glucose-induced insulin secretion and only gain robust glucose responsiveness several weeks after birth. We hypothesise that this unresponsiveness is due to a generalised immaturity of the metabolic pathways normally found in beta cells rather than to a specific defect.
Using laser-capture microdissection we excised beta cell-enriched cores of pancreatic islets from day 1 (P1) neonatal and young adult Sprague-Dawley rats in order to compare their gene-expression profiles using Affymetrix U34A microarrays (neonatal, n = 4; adult, n = 3).
Using dChip software for analysis, 217 probe sets for genes/38 expressed sequence tags (ESTs) were significantly higher and 345 probe sets for genes/33 ESTs significantly lower in beta cell-enriched cores of neonatal islets compared with those of adult islets. Among the genes lower in the neonatal beta cells were key metabolic genes including mitochondrial shuttles (malate dehydrogenase, glycerol-3-phosphate dehydrogenase and glutamate oxalacetate transaminase), pyruvate carboxylase and carnitine palmitoyl transferase 2. Differential expression of these enzyme genes was confirmed by quantitative PCR on RNA from isolated neonatal (P2 until P28) and adult islets and with immunostaining of pancreas. Even by 28 days of age some of these genes were still expressed at lower levels than in adults.
The lack of glucose responsiveness in neonatal islets is likely to be due to a generalised immaturity of the metabolic specialisation of pancreatic beta cells.
C1 [Jermendy, A.; Toschi, E.; Aye, T.; Koh, A.; Aguayo-Mazzucato, C.; Sharma, A.; Weir, G. C.; Bonner-Weir, S.] Harvard Univ, Sch Med, Sect Islet Cell & Regenerat Biol, Res Div,Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA.
[Jermendy, A.] Semmelweis Univ, Dept Pediat 1, H-1085 Budapest, Hungary.
[Sgroi, D.] Harvard Univ, Sch Med, Mol Pathol Unit, Massachusetts Gen Hosp,Dept Pathol, Boston, MA 02215 USA.
RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Sect Islet Cell & Regenerat Biol, Res Div,Joslin Diabet Ctr,Dept Med, 1 Joslin Pl, Boston, MA 02215 USA.
EM Susan.Bonner-Weir@joslin.harvard.edu
FU National Institutes of Health [R01 DK 66056]; Beta-cell Biology
Consortium [DK 61251]; Advanced Microscopy, Genomics and Bioinformatics
cores of Joslin Diabetes and Endocrinology Research Center [P30 DK
36836]; Juvenile Diabetes Research Foundation [JDRF 1-2004-120];
Diabetes Research and Wellness Foundation; Graetz Fund;
Hungarian-American Enterprise Scholarship Fund; Singapore National
Medical Research Council; Lawson-Wilkins Fellowship; Endocrine Fellow
Foundation; [TAMOP-4.2.2-08/01/KMR-2008-2004]
FX The authors thank J. Lock (Joslin Diabetes Center) for her expert
technical assistance, J. Schroeder and I-H. Wu (Joslin Diabetes Center)
for help with bioinformatics. This study was supported by National
Institutes of Health Grants R01 DK 66056 (S. Bonner-Weir), DK 61251
beta-cell Biology Consortium (D. Sgroi), the Advanced Microscopy,
Genomics and Bioinformatics cores of Joslin Diabetes and Endocrinology
Research Center (P30 DK 36836) as well as the Juvenile Diabetes Research
Foundation (JDRF 1-2004-120 to S. Bonner-Weir), Diabetes Research and
Wellness Foundation, the Graetz Fund, and an important group of private
donors. A. Jermendy was supported partially by the Hungarian-American
Enterprise Scholarship Fund and TAMOP-4.2.2-08/01/KMR-2008-2004 research
grant, A. Koh by a Singapore National Medical Research Council Research
fellowship grant, and T. Aye by a Lawson-Wilkins Fellowship and an
Endocrine Fellow Foundation award. The data discussed in this
publication have been deposited in NCBI Gene Expression Omnibus [46] and
are accessible through GEO Series accession number GSE24790
(www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE24790).
NR 46
TC 42
Z9 42
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD MAR
PY 2011
VL 54
IS 3
BP 594
EP 604
DI 10.1007/s00125-010-2036-x
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 716PX
UT WOS:000286987000017
PM 21240476
ER
PT J
AU Borsook, D
Becerra, L
Hargreaves, R
AF Borsook, David
Becerra, Lino
Hargreaves, Richard
TI Biomarkers for Chronic Pain and Analgesia. Part 1: The Need, Reality,
Challenges, and Solutions
SO DISCOVERY MEDICINE
LA English
DT Article
AB Chronic pain remains a significant clinical problem that has few effective therapies. Currently the success rate for treating chronic pain with analgesics is around 30%. Both treatment and research into chronic pain are greatly compromised by the fact that there is no objective diagnostic test that can complement the subjective assessment of chronic pain conditions. Chronic pain is now considered to be a disease of the central nervous system. Since behavior (including pain or analgesia) results from activity in brain circuits through the participation of many brain regions, we suggest that specific measures for the disease state and for drug effects can be defined using functional brain imaging. Tremendous advances have been made in functional imaging in the field of pain and analgesics and the development of CNS imaging biomarkers for pain may be close at hand. The successful identification of functional brain "signatures" for both drug action (analgesia) and disease state (neuropathic pain) when qualified could provide objective biomarkers to guide for drug development and clinical practice. In this two-part review, we discuss the potential of biomarkers for chronic pain including functional neuroimaging together with the challenges and limitations that are likely to be faced during the implementation of this strategy. The fit-for-purpose, scientific validation, and clinical qualification of novel CNS biomarkers for chronic pain could dramatically change the current outlook for treatment of chronic pain and research into its etiology. [Discovery Medicine 11(58):197-207, March 2011]
C1 [Borsook, David; Becerra, Lino] Harvard Univ, Sch Med, McLean Hosp, PAIN Grp,Massachusetts Gen Hosp, Belmont, MA 02478 USA.
[Borsook, David; Becerra, Lino] Harvard Univ, Sch Med, Childrens Hosp, Belmont, MA 02478 USA.
[Hargreaves, Richard] Merck & Co Inc, Merck Res Labs, West Point, PA 19486 USA.
RP Borsook, D (reprint author), Harvard Univ, Sch Med, McLean Hosp, PAIN Grp,Massachusetts Gen Hosp, Belmont, MA 02478 USA.
EM dborsook@partners.org
FU NINDS [K24 (NS064050)]; Herlands Fund
FX Supported by NINDS K24 (NS064050) to D.B. and the L. Herlands Fund to
the P.A.I.N. group (D.B., L.B.). We thank Gautam Pendse, M.A., M.S., for
his contribution to Figure 3.
NR 63
TC 44
Z9 44
U1 0
U2 2
PU DISCOVERY MEDICINE
PI TIMONIUM
PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA
SN 1539-6509
EI 1944-7930
J9 DISCOV MED
JI Discov. Med.
PD MAR
PY 2011
VL 11
IS 58
BP 197
EP 207
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA V27UY
UT WOS:000208639300003
PM 21447279
ER
PT J
AU Borsook, D
Becerra, L
Hargreaves, R
AF Borsook, David
Becerra, Lino
Hargreaves, Richard
TI Biomarkers for Chronic Pain and Analgesia. Part 2: How, Where, and What
to Look for Using Functional Imaging
SO DISCOVERY MEDICINE
LA English
DT Article
AB Rapid advances in brain imaging chronic pain patients have yielded exciting data sets that could provide the basis for the development of chronic pain biomarkers that could increase the probability of success in analgesic drug development, aid clinicians in understanding, tracking, and treating disease, and link patients to the most effective therapies for their pain conditions. This review explores the potential of brain imaging techniques to detect functional, morphometric, and chemical changes that could serve as biomarkers for disease state and therapeutic efficacy. An important area for future research is to image clinical ongoing pain to further our knowledge of brain function in different pain states and the effects of treatment. [Discovery Medicine 11(58):209-219, March 2011]
C1 [Borsook, David; Becerra, Lino] Harvard Univ, Sch Med, McLean Hosp, PAIN Grp,Massachusetts Gen Hosp, Belmont, MA 02478 USA.
[Borsook, David; Becerra, Lino] Harvard Univ, Sch Med, Childrens Hosp, Belmont, MA 02478 USA.
[Hargreaves, Richard] Merck & Co Inc, Merck Res Labs, West Point, PA 19486 USA.
RP Borsook, D (reprint author), Harvard Univ, Sch Med, McLean Hosp, PAIN Grp,Massachusetts Gen Hosp, Belmont, MA 02478 USA.
EM dborsook@partners.org
FU NINDS [K24 (NS064050)]; Herlands Fund
FX Supported by NINDS K24 (NS064050) to D.B. and the L. Herlands Fund to
the P.A.I.N. group (D.B., L.B.).
NR 116
TC 32
Z9 32
U1 0
U2 2
PU DISCOVERY MEDICINE
PI TIMONIUM
PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA
SN 1539-6509
EI 1944-7930
J9 DISCOV MED
JI Discov. Med.
PD MAR
PY 2011
VL 11
IS 58
BP 209
EP 219
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA V27UY
UT WOS:000208639300004
PM 21447280
ER
PT J
AU Hildebrandt, T
Lai, JK
Langenbucher, JW
Schneider, M
Yehuda, R
Pfaff, DW
AF Hildebrandt, Tom
Lai, Justine K.
Langenbucher, James W.
Schneider, Melanie
Yehuda, Rachel
Pfaff, Donald W.
TI The diagnostic dilemma of pathological appearance and performance
enhancing drug use
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Review
DE Anabolic-androgenic steroids; Appearance and performance enhancing
drugs; Substance use disorder; Diagnosis; Body image disturbance;
Compulsive exercise
ID ANDROGENIC STEROID USE; SUBSTANCE USE DISORDERS; MALE NORMAL VOLUNTEERS;
ITEM RESPONSE THEORY; OF-THE-LITERATURE; ANABOLIC-STEROIDS;
EXERCISE-DEPENDENCE; DSM-V; MUSCLE DYSMORPHIA; BODY-IMAGE
AB Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance or achievement, dietary control, and frequent exercise. A number of existing reviews and conceptual papers have defined pathological forms of APED use within the APED class of anabolic-androgenic steroids (AASs) and using the framework of AAS dependence. We review published data on APED use including human studies of AAS users and identified three defining phenomenological features associated with increased health risk and pathology. These features included (1) polypharmacy or the concurrent use of several pharmacologically distinct substances used to change outward appearance or increase likelihood of personal achievement: (2) significant body image disturbance: (3) rigid practices and preoccupations with diet and exercise. Investigations into the latent structure of APED use suggest these features cluster together in a homogenous group of APED users who have the highest health risk and most psychopathology. These features are discussed in the context of AAS dependence and problems with defining classic tolerance-withdrawal symptoms among APED users. Suggestions for a resolution and outline for future research needed to determine the best system for identifying and diagnosing pathological APED use are discussed. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Hildebrandt, Tom; Lai, Justine K.] Mt Sinai Sch Med, Eating & Weight Disorders Program, New York, NY 10029 USA.
[Langenbucher, James W.; Schneider, Melanie] Rutgers State Univ, Piscataway, NJ 08854 USA.
[Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA.
[Pfaff, Donald W.] Rockefeller Univ, New York, NY 10128 USA.
RP Hildebrandt, T (reprint author), Mt Sinai Sch Med, Eating & Weight Disorders Program, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
EM tom.hildebrandt@mssm.edu
OI Hildebrandt, Thomas/0000-0001-7054-9590
FU National Institute on Drug Abuse [K23 024034]
FX Dr. Hildebrandt's time was supported by National Institute on Drug Abuse
grant K23 024034.
NR 146
TC 12
Z9 12
U1 16
U2 24
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD MAR 1
PY 2011
VL 114
IS 1
BP 1
EP 11
DI 10.1016/j.drugalcdep.2010.09.018
PG 11
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 734CZ
UT WOS:000288312100001
PM 21115306
ER
PT J
AU Puzanov, I
Flaherty, KT
Sosman, JA
Grippo, JF
Su, F
Nolop, K
Lee, RJ
Bollag, G
AF Puzanov, I.
Flaherty, K. T.
Sosman, J. A.
Grippo, J. F.
Su, F.
Nolop, K.
Lee, R. J.
Bollag, G.
TI VEMURAFENIB B-raf Kinase Inhibitor Oncolytic
SO DRUGS OF THE FUTURE
LA English
DT Article
DE PLX-4032; R-7204; RG-7204; RO-5185426
ID THYROID-CARCINOMA CELLS; METASTATIC MELANOMA; DRUG-RESISTANCE; BRAF;
PLX4032; PATHWAY; MUTATIONS; GROWTH; PROLIFERATION; ACTIVATION
AB Vemurafenib (RG-7204, PLX-4032) is a potent inhibitor of the V600E mutation-positive B-raf kinase. Mutations in this protein have been implicated in approximately 50% of melanomas, 30-70% of thyroid tumors, 30% of serous low-grade ovarian tumors and 10% of colorectal cancers. Vemurafenib has shown promising preclinical and clinical efficacy against mutant BRAF cell lines and tumors. Vemurafenib exhibits selectivity over a broad range of kinases, which has translated into cellular selectivity for cancer cell lines expressing BRAF(V600E), BRAF(V600D) and BRAF(V600R), with no activity against cells lacking oncogenic B-raf. Pharmacokinetic analyses have shown that exposure increases with dose from 160 mg to 1,120 mg twice daily, and a dose of 960 mg twice daily was selected for phase II and III evaluation. Phase I and II clinical data have demonstrated promising activity, with the recently reported BRIM-2 study in patients with metastatic melanoma having met its primary endpoint, demonstrating a best overall response rate of > 50% in the context of manageable side effects.
C1 [Puzanov, I.; Sosman, J. A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Puzanov, I.; Sosman, J. A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Flaherty, K. T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Grippo, J. F.; Su, F.; Lee, R. J.] Hoffmann La Roche, Nutley, NJ USA.
[Nolop, K.; Bollag, G.] Plexxikon Inc, Berkeley, CA USA.
RP Puzanov, I (reprint author), Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
EM igor.puzanov@vanderbilt.edu
NR 39
TC 6
Z9 6
U1 2
U2 12
PU PROUS SCIENCE, SA-THOMSON REUTERS
PI BARCELONA
PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN
SN 0377-8282
J9 DRUG FUTURE
JI Drug Future
PD MAR
PY 2011
VL 36
IS 3
BP 191
EP 199
DI 10.1358/dof.2011.36.3.1590788
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 781TP
UT WOS:000291959700003
ER
PT J
AU van Ryn, M
Burgess, DJ
Dovidio, JF
Phelan, SM
Saha, S
Malat, J
Griffin, JM
Fu, SS
Perry, S
AF van Ryn, Michelle
Burgess, Diana J.
Dovidio, John F.
Phelan, Sean M.
Saha, Somnath
Malat, Jennifer
Griffin, Joan M.
Fu, Steven S.
Perry, Sylvia
TI THE IMPACT OF RACISM ON CLINICIAN COGNITION, BEHAVIOR, AND CLINICAL
DECISION MAKING
SO DU BOIS REVIEW-SOCIAL SCIENCE RESEARCH ON RACE
LA English
DT Article
DE Racial Inequity; Health Care Disparities; Racial Bias; Providers;
Racism; Stereotypes; Discrimination; Interracial Interaction
ID HEALTH-CARE DISPARITIES; IMPLICIT ASSOCIATION TEST; STEREOTYPE THREAT;
CULTURAL COMPETENCE; PHYSICIANS PERCEPTIONS; AFRICAN-AMERICANS; AVERSIVE
RACISM; PUBLIC-HEALTH; ATTITUDES; RACE
AB Over the past two decades, thousands of studies have demonstrated that Blacks receive lower quality medical care than Whites, independent of disease status, setting, insurance, and other clinically relevant factors. Despite this, there has been little progress towards eradicating these inequities. Almost a decade ago we proposed a conceptual model identifying mechanisms through which clinicians' behavior, cognition, and decision making might be influenced by implicit racial biases and explicit racial stereotypes, and thereby contribute to racial inequities in care. Empirical evidence has supported many of these hypothesized mechanisms, demonstrating that White medical care clinicians: (1) hold negative implicit racial biases and explicit racial stereotypes, (2) have implicit racial biases that persist independently of and in contrast to their explicit (conscious) racial attitudes, and (3) can be influenced by racial bias in their clinical decision making and behavior during encounters with Black patients. This paper applies evidence from several disciplines to further specify our original model and elaborate on the ways racism can interact with cognitive biases to affect clinicians' behavior and decisions and in turn, patient behavior and decisions. We then highlight avenues for intervention and make specific recommendations to medical care and grant-making organizations.
C1 [van Ryn, Michelle; Phelan, Sean M.] Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN 55414 USA.
[Burgess, Diana J.; Griffin, Joan M.; Fu, Steven S.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55414 USA.
[Dovidio, John F.; Perry, Sylvia] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Saha, Somnath] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97201 USA.
[Saha, Somnath] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA.
[Malat, Jennifer] Univ Cincinnati, Dept Sociol, Cincinnati, OH 45221 USA.
[Burgess, Diana J.; Griffin, Joan M.; Fu, Steven S.] Univ Minnesota, Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55414 USA.
RP van Ryn, M (reprint author), Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Room 221,925 Delaware St SE, Minneapolis, MN 55414 USA.
EM vanry001@umn.edu
RI Burgess, Diana/A-1946-2016
FU NHLBI NIH HHS [R01 HL085631]
NR 89
TC 41
Z9 42
U1 12
U2 43
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1742-058X
J9 DU BOIS REV
JI Du Bois Rev.
PD SPR
PY 2011
VL 8
IS 1
SI SI
BP 199
EP 218
DI 10.1017/S1742058X11000191
PG 20
WC Ethnic Studies; Sociology
SC Ethnic Studies; Sociology
GA 051ZD
UT WOS:000312166600015
PM 24761152
ER
PT J
AU Kind, A
Anderson, P
Hind, J
Robbins, J
Smith, M
AF Kind, Amy
Anderson, Paul
Hind, Jacqueline
Robbins, JoAnne
Smith, Maureen
TI Omission of Dysphagia Therapies in Hospital Discharge Communications
SO DYSPHAGIA
LA English
DT Article
DE Care management; Communication; Continuity of care; Hospital discharge;
Deglutition; Deglutition disorders
ID MEDICAL REHABILITATION REPORT; RANDOMIZED CONTROLLED-TRIAL; UNIFORM DATA
SYSTEM; GENERAL-PRACTITIONERS; ACUTE STROKE; ALZHEIMERS-DISEASE; PATIENT
SAFETY; CLINICAL-TRIAL; HIP FRACTURE; FOLLOW-UP
AB Despite the wide implementation of dysphagia therapies, it is unclear whether these therapies are successfully communicated beyond the inpatient setting. The aim of this study was to examine the rate of dysphagia recommendation omissions in hospital discharge summaries for high-risk subacute care (i.e., skilled nursing facility, rehabilitation, long-term care) populations. We performed a retrospective cohort study that included all stroke and hip fracture patients billed for inpatient dysphagia evaluations by speech-language pathologists (SLPs) and discharged to subacute care from 2003 through 2005 from a single large academic medical center (N = 187). Dysphagia recommendations from final SLP hospital notes and from hospital (physician) discharge summaries were abstracted, coded, and compared for each patient. Recommendation categories included dietary (food and liquid), postural/compensatory techniques (e.g., chin tuck), rehabilitation (e.g., exercise), meal pacing (e.g., small bites), medication delivery (e.g., crush pills), and provider/supervision (e.g., 1-to-1 assist). Forty-five percent of discharge summaries omitted all SLP dysphagia recommendations. Forty-seven percent (88/186) of patients with SLP dietary recommendations, 82% (93/114) with postural, 100% (16/16) with rehabilitation, 90% (69/77) with meal pacing, 95% (21/22) with medication, and 79% (96/122) with provider/supervision recommendations had these recommendations completely omitted from their discharge summaries. Discharge summaries omitted all categories of SLP recommendations at notably high rates. Improved post-hospital communication strategies are needed for discharges to subacute care.
C1 [Kind, Amy] Univ Wisconsin, Geriatr Sect, Dept Med, Sch Med & Publ Hlth, Madison, WI 53705 USA.
[Kind, Amy; Anderson, Paul; Hind, Jacqueline; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, United States Dept Vet Affairs, Geriatr Res Educ & Clin Ctr GRECC, Madison, WI 53705 USA.
[Kind, Amy] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI 53705 USA.
[Hind, Jacqueline; Robbins, JoAnne] Univ Wisconsin, Gastroenterol & Hepatol Sect, Dept Med, Sch Med & Publ Hlth, Madison, WI 53705 USA.
[Smith, Maureen] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI 53726 USA.
[Smith, Maureen] Univ Wisconsin, Dept Family Med, Sch Med & Publ Hlth, Madison, WI 53726 USA.
RP Kind, A (reprint author), Univ Wisconsin, Geriatr Sect, Dept Med, Sch Med & Publ Hlth, 2500 Overlook Terrace, Madison, WI 53705 USA.
EM ajk@medicine.wisc.edu
FU University of Wisconsin (UW) Hartford Center of Excellence in
Geriatrics; UW Health Innovation Program; UW Shapiro Summer Medical
Student Research Fellowship; K-L2 through the NIH [1KL2RR025012-01];
Community-Academic Partnerships core of the University of Wisconsin
Institute for Clinical and Translational Research (UW ICTR); National
Center for Research Resources, National Institutes of Health
[IUL1RR025011]
FX Special thanks to UW Health Innovation Program staff Geoff Wodtke and
Wen-Jan Tuan for data management and cleaning, Inna Larsen for
administrative support, Colleen Brown and Kristin Slovenkay for
manuscript formatting, and Peggy Munson for IRB assistance, and to Bruce
Grau and Tim Kamps for assistance with data collection. Funding for this
project was provided by the University of Wisconsin (UW) Hartford Center
of Excellence in Geriatrics, the UW Health Innovation Program, and the
UW Shapiro Summer Medical Student Research Fellowship. Dr. Kind is
supported by a K-L2 through the NIH grant 1KL2RR025012-01 [Institutional
Clinical and Translational Science Award (UW-Madison) (KL2)]. This
project was also supported by the Community-Academic Partnerships core
of the University of Wisconsin Institute for Clinical and Translational
Research (UW ICTR), grant IUL1RR025011 from the Clinical and
Translational Science Award (CTSA) program of the National Center for
Research Resources, National Institutes of Health. The UW Health
Innovation Program provided assistance with IRB application, Medicare
outcomes variable creation and linkage, data management and cleaning,
and manuscript formatting. No other funding source had a role in the
design or conduct data collection, management, analysis, or
interpretation; or preparation, review, or approval of the manuscript.
NR 73
TC 14
Z9 14
U1 5
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0179-051X
J9 DYSPHAGIA
JI Dysphagia
PD MAR
PY 2011
VL 26
IS 1
BP 49
EP 61
DI 10.1007/s00455-009-9266-4
PG 13
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 732VQ
UT WOS:000288218200008
PM 20098999
ER
PT J
AU Tritos, NA
AF Tritos, Nicholas A.
TI Serum Dehydroepiandrosterone Sulfate in the Diagnosis of Adrenal
Insufficiency: Ready for Prime Time?
SO ENDOCRINE PRACTICE
LA English
DT Editorial Material
ID SEPTIC SHOCK; ACTH STIMULATION; CORTISOL-LEVELS; AXIS; HYDROCORTISONE;
CORTICOTROPIN; DYSFUNCTION
C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA.
EM ntritos@partners.org
NR 22
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
EI 1934-2403
J9 ENDOCR PRACT
JI Endocr. Pract.
PD MAR-APR
PY 2011
VL 17
IS 2
BP 167
EP 169
DI 10.4158/EP10385.ED
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V28XV
UT WOS:000208714400010
PM 21247840
ER
PT J
AU Park, JH
Daheron, L
Kantarci, S
Lee, BS
Teixeira, JM
AF Park, Joo Hyun
Daheron, Laurence
Kantarci, Sibel
Lee, Byung Seok
Teixeira, Jose M.
TI Human Endometrial Cells Express Elevated Levels of Pluripotent Factors
and Are More Amenable to Reprogramming into Induced Pluripotent Stem
Cells
SO ENDOCRINOLOGY
LA English
DT Article
ID SMALL-MOLECULE COMPOUNDS; HUMAN AMNIOTIC-FLUID; HUMAN SOMATIC-CELLS;
DEFINED FACTORS; GENERATION; INDUCTION; FIBROBLASTS; EFFICIENCY; OCT4
AB The human endometrium is a tissue with remarkable plasticity and regenerative capacity. Additionally, endometrial cells can be retrieved using minimally invasive procedures, which makes them an ideal source for reprogramming into a pluripotent state. Endometrial cells were obtained from donors in their fifth decade and reprogrammed into induced pluripotent stem (iPS) cells using retroviral transduction with SOX2, OCT4, KLF4, and MYC. The human endometrial cells displayed accelerated expression of endogenous NANOG and OCT4 during reprogramming compared with neonatal skin fibroblasts. As a result, iPS cell colonies that could be subcultured and propagated were established as early as 12 d after transduction rather than the usually reported 3-4 wk for other cell types. After 3 wk of reprogramming, the human endometrial cells also yielded significantly higher numbers of iPS colonies in comparison with the neonatal skin fibroblasts. Although the efficiency of iPS colony formation varied depending on the donor, the basal level of endogenous expression of the defined factors was positively correlated with reprogramming efficiency. The reprogramming resulted in an average colony-forming efficiency of 0.49 +/- 0.10%, with a range from 0.31-0.66%, compared with the neonatal skin fibroblasts, resulting in an average efficiency of 0.03 +/- 0.00% per transduction, with a range from 0.02-0.03%. Our studies show that the human endometrium expresses elevated levels of pluripotent factors, which with additional defined factors, results in significantly more efficient and accelerated generation of induced pluripotent stem cells compared with conventional somatic cells. (Endocrinology 152: 1080-1089, 2011)
C1 [Park, Joo Hyun; Teixeira, Jose M.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Daheron, Laurence; Teixeira, Jose M.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Kantarci, Sibel] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Lee, Byung Seok] Yonsei Univ, Coll Med, Dept Obstet & Gynecol, Severance Hosp, Seoul 120752, South Korea.
RP Teixeira, JM (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol Their 931, 55 Fruit St, Boston, MA 02114 USA.
EM teixeira@helix.mgh.harvard.edu
OI Teixeira, Jose/0000-0002-6438-5064
FU National Institute of Child Health and Human Development [HD052701];
Vincent Memorial research funds
FX These studies were supported in part by a grant from the National
Institute of Child Health and Human Development (HD052701) and by
Vincent Memorial research funds to J.M.T.
NR 40
TC 19
Z9 22
U1 3
U2 6
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAR
PY 2011
VL 152
IS 3
BP 1080
EP 1089
DI 10.1210/en.2010-1072
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 723QC
UT WOS:000287520900033
PM 21209016
ER
PT J
AU Hershman, JM
Okunyan, A
Rivina, Y
Cannon, S
Hogen, V
AF Hershman, Jerome M.
Okunyan, Armen
Rivina, Yelena
Cannon, Sophie
Hogen, Victor
TI Prevention of DNA Double-Strand Breaks Induced by Radioiodide-I-131 in
FRTL-5 Thyroid Cells
SO ENDOCRINOLOGY
LA English
DT Article
ID REPAIR; RADIATION; CANCER; REARRANGEMENT; CHROMOSOMES; SYMPORTER; IODIDE
AB Radioiodine-131 released from nuclear reactor accidents has dramatically increased the incidence of papillary thyroid cancer in exposed individuals. The deposition of ionizing radiation in cells results in double-strand DNA breaks (DSB) at fragile sites, and this early event can generate oncogenic rearrangements that eventually cause cancer. The aims of this study were to develop a method to show DNA DSBs induced by I-131 in thyroid cells; to test monovalent anions that are transported by the sodium/iodide symporter to determine whether they prevent I-131-induced DSB; and to test other radioprotective agents for their effect on irradiated thyroid cells. Rat FRTL-5 thyroid cells were incubated with I-131. DSBs were measured by nuclear immunofluorescence using antibodies to p53-binding protein 1 or gamma H2AX. Incubation with 1-10 mu Ci I-131 per milliliter for 90 min resulted in a dose-related increase of DSBs; the number of DSBs increased from a baseline of 4-15% before radiation to 65-90% after radiation. GH3 or CHO cells that do not transport iodide did not develop DSBs when incubated with I-131. Incubation with 20-100 mu M iodide or thiocyanate markedly attenuated DSBs. Perchlorate was about 6 times more potent than iodide or thiocyanate. The effects of the anions were much greater when each was added 30-120 min before the I-131. Two natural organic compounds recently shown to provide radiation protection partially prevented DSBs caused by I-131 and had an additive effect with perchlorate. In conclusion, we developed a thyroid cell model to quantify the mitogenic effect of I-131. I-131 causes DNA DSBs in FRTL-5 cells and had no effect on cells that do not transport iodide. Perchlorate, iodide, and thiocyanate protect against DSBs induced by I-131. (Endocrinology 152: 1130-1135, 2011)
C1 [Hershman, Jerome M.] W Los Angeles Vet Affairs Med Ctr, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA.
RP Hershman, JM (reprint author), W Los Angeles Vet Affairs Med Ctr, Endocrinol & Diabet Div, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM jhershmn@ucla.edu
FU University of California, Los Angeles, Center of Biological
Radioprotectors; National Institutes of Health
FX This work was supported by a research grant from the University of
California, Los Angeles, Center of Biological Radioprotectors and the
National Institutes of Health.
NR 20
TC 7
Z9 7
U1 1
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAR
PY 2011
VL 152
IS 3
BP 1130
EP 1135
DI 10.1210/en.2010-1163
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 723QC
UT WOS:000287520900038
PM 21190956
ER
PT J
AU Liu, YY
Nakatani, T
Kogai, T
Mody, K
Brent, GA
AF Liu, Yan-Yun
Nakatani, Teruyo
Kogai, Takahiko
Mody, Kaizeen
Brent, Gregory A.
TI Thyroid Hormone and COUP-TF1 Regulate Kallikrein-Binding Protein (KBP)
Gene Expression
SO ENDOCRINOLOGY
LA English
DT Article
ID PROMOTER-TRANSCRIPTION FACTORS; HUMAN TISSUE KALLIKREIN; RECEPTOR
DNA-BINDING; COREPRESSOR N-COR; NEGATIVE REGULATION; RETINOIC ACID;
HISTONE DEACETYLASE; ESTROGEN-RECEPTOR; RESPONSE ELEMENTS;
GROWTH-HORMONE
AB Kallikrein-binding protein (KBP) is a component of the kallikrein-kinin system that mediates vasodilation and inhibits tumor growth by antagonizing vascular endothelial growth factor-mediated angiogenesis. We demonstrate that KBP gene expression is repressed by T(3) and modulated by the orphan nuclear receptor, chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1). In hypothyroid mice, KBP mRNA expression in the testis was increased 2.1-fold compared with euthyroid mice. We have identified two negative thyroid hormone response elements (nTREs) in the mouse KBP gene, nTRE1 located in the 5' flanking region (-53 to -29) and nTRE2, located in the first intron (104-132). We used functional assays, cofactor knockdown, and chromatin immunoprecipitation assays to characterize nTRE1 and nTRE2 in hepatic (HepG2) and testes (GC-1spg) cell lines. Reporter expression directed by both elements was enhanced with addition of thyroid hormone receptor and repressed with the addition of T(3). COUP-TF1 enhanced basal expression of both elements but blunted unliganded thyroid hormone receptor enhancement and T(3) repression of nTRE1 but not nTRE2. Both nTREs bound nuclear corepressor and binding increased in response to T(3). Nuclear corepressor knockdown resulted in loss of T(3) repression of both nTRE1 and nTRE2. COUP-TF1, which usually represses T(3) induction of positive thyroid hormone response elements, reverses T(3) repression mediated by nTRE1 in the mouse KBP gene. Endogenous KBP expression is repressed by T(3) and two functional nTREs, both of which are required, have been characterized in the KBP gene. COUP-TF1 may be an important factor to modulate expression of genes that are repressed by T(3). (Endocrinology 152: 1143-1153, 2011)
C1 [Brent, Gregory A.] Vet Affairs Greater Los Angeles Hlth Care Syst, Mol Endocrinol Lab, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, Dept Physiol, David Geffen Sch Med, Los Angeles, CA 90073 USA.
RP Brent, GA (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst, Mol Endocrinol Lab, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM gbrent@ucla.edu
FU Department of Veterans Affairs; National Institutes of Health [RO1
DK67233]
FX This work was supported by Merit Review funds from the Department of
Veterans Affairs and Grant RO1 DK67233 from the National Institutes of
Health.
NR 63
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Z9 4
U1 0
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAR
PY 2011
VL 152
IS 3
BP 1143
EP 1153
DI 10.1210/en.2010-0580
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 723QC
UT WOS:000287520900040
PM 21266512
ER
PT J
AU Garavalia, L
Ho, PM
Garavalia, B
Foody, JM
Kruse, H
Spertus, JA
Decker, C
AF Garavalia, Linda
Ho, P. Michael
Garavalia, Brian
Foody, JoAnne M.
Kruse, Heather
Spertus, John A.
Decker, Carole
TI Clinician-patient discord: Exploring differences in perspectives for
discontinuing clopidogrel
SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING
LA English
DT Article
DE Myocardial infarction; Medication discontinuance; Patient-provider
communication; Qualitative research
ID ACUTE CORONARY SYNDROMES; HEALTH BELIEF MODEL; PREMATURE
DISCONTINUATION; MEDICATION; PHYSICIANS; ADHERENCE; OUTCOMES; THERAPY;
COMMUNICATION; METAANALYSIS
AB Background: Premature stopping of anti-platelet therapy has potentially fatal consequences for myocardial infarction (MI) patients who have received a drug-eluting stent (DES). Exploring multiple perspectives to identify contributing factors to the problem is essential.
Aim: We gained patient and clinician perspectives as to why MI patients prematurely stop anti-platelet therapy (clopidogrel) after DES implantation.
Methods: This qualitative, descriptive study of DES-treated MI patients (n=22) and of clinicians (physicians and nurse practitioners; n=17) from multiple U.S. cities used content analysis of interview data. Findings across patients and clinicians were then compared to examine congruent and contrasting reasons for premature clopidogrel discontinuance.
Findings: Patients frequently identified communication and education (e.g. unaware they should be taking clopidogrel, unaware of intended duration of therapy) as the primary reasons for having stopped. Patients rarely cited cost, while clinicians most commonly cited cost as a reason for premature stopping.
Conclusions: The discrepancy in perceptions of patients and clinicians as to the primary reason for early discontinuance suggests an important opportunity for improving persistence. Rather than focusing on the high costs of medications, something outside of their control, physicians should consider communicating more effectively the importance and intended duration of clopidogrel to their patients. (C) 2010 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
C1 [Garavalia, Brian; Spertus, John A.; Decker, Carole] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Garavalia, Linda] Univ Missouri Kansas City, Sch Pharm, Kansas City, MO USA.
[Ho, P. Michael] Univ Colorado Denver, Denver VA Med Ctr, Denver, CO USA.
[Ho, P. Michael] Hlth Sci Ctr, San Antonio, TX USA.
[Foody, JoAnne M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Kruse, Heather] Univ Missouri Kansas City, Dept Psychol, Kansas City, MO USA.
[Spertus, John A.] Univ Missouri Kansas City, Sch Med, Kansas City, MO USA.
[Decker, Carole] Univ Missouri Kansas City, Sch Nursing, Kansas City, MO USA.
RP Decker, C (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA.
EM cldecker@saint-lukes.org
FU Sanofi-Aventis; NIH SCCOR [P50 HL077113]
FX Funding was received from Sanofi-Aventis and NIH SCCOR (P50 HL077113)
grants. The sponsors were not involved in the conduct of the study,
analysis of the data, or preparation of the manuscript.
NR 29
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U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1474-5151
J9 EUR J CARDIOVASC NUR
JI Eur. J. Cardiovasc. Nurs.
PD MAR
PY 2011
VL 10
IS 1
BP 50
EP 55
DI 10.1016/j.ejcnurse.2010.04.002
PG 6
WC Cardiac & Cardiovascular Systems; Nursing
SC Cardiovascular System & Cardiology; Nursing
GA 734TL
UT WOS:000288361600008
PM 20483665
ER
PT J
AU Carroll, DL
AF Carroll, D. L.
TI Needs of older patients and their spouses after a cardiovascular
procedure
SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING
LA English
DT Meeting Abstract
C1 [Carroll, D. L.] Massachusetts Gen Hospitla, Boston, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1474-5151
J9 EUR J CARDIOVASC NUR
JI Eur. J. Cardiovasc. Nurs.
PD MAR
PY 2011
VL 10
SU 1
BP S44
EP S44
DI 10.1016/S1474-5151(11)60153-9
PG 1
WC Cardiac & Cardiovascular Systems; Nursing
SC Cardiovascular System & Cardiology; Nursing
GA 048GO
UT WOS:000311899300140
ER
PT J
AU Matura, LA
McDonough, AJ
Carroll, DL
AF Matura, L. A.
McDonough, A. J.
Carroll, D. L.
TI Symptom burden and symptom clusters in pulmonary arterial hypertension:
a pilot study
SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING
LA English
DT Meeting Abstract
C1 [Matura, L. A.] Northeastern Univ, Boston, MA 02115 USA.
[McDonough, A. J.] Univ Massachusetts Lowell, Lowell, MA USA.
[Carroll, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1474-5151
J9 EUR J CARDIOVASC NUR
JI Eur. J. Cardiovasc. Nurs.
PD MAR
PY 2011
VL 10
SU 1
BP S38
EP S38
DI 10.1016/S1474-5151(11)60136-9
PG 1
WC Cardiac & Cardiovascular Systems; Nursing
SC Cardiovascular System & Cardiology; Nursing
GA 048GO
UT WOS:000311899300123
ER
PT J
AU Hsia, TY
Ringewald, JM
Stroud, RE
Forbus, GA
Bradley, SM
Chung, WK
Spinale, FG
AF Hsia, Tain-Yen
Ringewald, Jeremy M.
Stroud, Robert E.
Forbus, Geoffrey A.
Bradley, Scott M.
Chung, Wendy K.
Spinale, Francis G.
TI Determinants of extracellular matrix remodelling are differentially
expressed in paediatric and adult dilated cardiomyopathy
SO EUROPEAN JOURNAL OF HEART FAILURE
LA English
DT Article
DE Cardiomyopathy; Extracellular matrix; Matrix metalloproteinase;
Paediatrics
ID LEFT-VENTRICULAR FUNCTION; CONGESTIVE-HEART-FAILURE; TISSUE INHIBITORS;
METALLOPROTEINASE INHIBITION; CARDIOPULMONARY BYPASS; RELEASE;
FIBROBLASTS; MYOCARDITIS; INDUCTION; SYSTEM
AB Aims The left ventricular phenotype of idiopathic dilated cardiomyopathy (DCM) can appear similar in paediatric and adult patients. However, the aetiology of paediatric DCM is usually idiopathic, and often leads an aggressive clinical course. A structural underpinning of DCM is extracellular matrix changes, which are determined by a balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). This study tested the hypothesis that different MMP/TIMP profiles occur in paediatric and adult DCM patients.
Methods and results Left ventricular samples from paediatric (age 9 +/- 5 years; n = 10) and adult (age 62 +/- 3 years; n = 20) DCM (at time of transplant) were subjected to an MMP/TIMP multiplex array and immunoassay in order to measure the MMP subclasses; collagenases (MMP-8, -13), gelatinases (MMP-2, -9), stromelysin/matrilysin (MMP-3, -7), membrane type (MT1-MMP), as well as for the four known TIMPs. MMP-8 and -9 levels increased by over 150% (P < 0.05), whereas MMP-3 and -7 levels decreased by over 30% (P < 0.05) in paediatric DCM when compared with adult DCM. TIMP-1 and -2 levels increased two-fold (P < 0.05), but TIMP-3 fell by 41% (P < 0.05) in paediatric DCM. Myocardial levels of specific interleukins (IL-1beta, IL-2, IL-8) were increased by approximately 50% in paediatric DCM.
Conclusions These unique findings demonstrated that a specific MMP/TIMP profile occurs in paediatric DCM when compared with adult DCM, and that local cytokine induction may contribute to this process. These distinct differences in the determinants of myocardial matrix structure and function may contribute to the natural history of DCM in children.
C1 [Hsia, Tain-Yen; Ringewald, Jeremy M.; Stroud, Robert E.; Forbus, Geoffrey A.; Bradley, Scott M.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29403 USA.
[Hsia, Tain-Yen; Ringewald, Jeremy M.; Stroud, Robert E.; Forbus, Geoffrey A.; Bradley, Scott M.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Chung, Wendy K.] Columbia Univ, Dept Pediat, New York, NY 10027 USA.
RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, 114 Doughty St, Charleston, SC 29403 USA.
EM wilburnm@musc.edu
FU NIH [HL059165-09, HL057952-08]; Veterans' Affairs Health Administration;
Children's Cardiomyopathy Foundation, USA
FX This work was supported by NIH grants HL059165-09, HL057952-08, a Merit
Award from the Veterans' Affairs Health Administration and the
Children's Cardiomyopathy Foundation, USA.
NR 33
TC 6
Z9 7
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1388-9842
J9 EUR J HEART FAIL
JI Eur. J. Heart Fail.
PD MAR
PY 2011
VL 13
IS 3
BP 271
EP 277
DI 10.1093/eurjhf/hfq184
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 723HG
UT WOS:000287496800007
PM 21147820
ER
PT J
AU Yakimchuk, K
Roura-Mir, C
Magalhaes, KG
de Jong, A
Kasmar, AG
Granter, SR
Budd, R
Steere, A
Pena-Cruz, V
Kirschning, C
Cheng, TY
Moody, DB
AF Yakimchuk, Konstantin
Roura-Mir, Carme
Magalhaes, Kelly G.
de Jong, Annemieke
Kasmar, Anne G.
Granter, Scott R.
Budd, Ralph
Steere, Allen
Pena-Cruz, Victor
Kirschning, Carsten
Cheng, Tan-Yun
Moody, D. Branch
TI Borrelia burgdorferi infection regulates CD1 expression in human cells
and tissues via IL1-beta
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE CD1; DC; IL-1; Lyme disease; T cells
ID HUMAN DENDRITIC CELLS; KILLER T-CELLS; EARLY LYME-DISEASE; CLASS-II
TRANSPORT; NF-KAPPA-B; MYCOBACTERIUM-TUBERCULOSIS; ANTIGEN PRESENTATION;
HUMAN MONOCYTES; CUTTING EDGE; INFLAMMASOME ACTIVATION
AB The appearance of group 1 CD1 proteins (CD1a, CD1b and CD1c) on maturing myeloid DC is a key event that converts myeloid DC to effective lipid APC. Here, we show that Borrelia burgdorferi, the causative agent of Lyme disease, triggers appearance of group 1 CD1 proteins at high density on the surface of human myeloid DC during infection. Within human skin, CD1b and CD1c expression was low or absent prior to infection, but increased significantly after experimental infections and in erythema migrans lesions from Lyme disease patients. The induction of CD1 was initiated by borrelial lipids acting through TLR-2 within minutes, but required 3 days for maximum effect. The delay in CD1 protein appearance involved a multi-step process whereby TLR-2 stimulated cells release soluble factors, which are sufficient to transfer the CD1-inducing effect in trans to other cells. Analysis of these soluble factors identified IL-1 beta as a previously unknown pathway leading to group 1 CD1 protein function. This study establishes that upregulation of group 1 CD1 proteins is an early event in B. burgdorferi infection and suggests a stepwise mechanism whereby bacterial cell walls, TLR activation and cytokine release cause DC precursors to express group 1 CD1 proteins.
C1 [Yakimchuk, Konstantin; Roura-Mir, Carme; Magalhaes, Kelly G.; de Jong, Annemieke; Kasmar, Anne G.; Cheng, Tan-Yun; Moody, D. Branch] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Granter, Scott R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Granter, Scott R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Budd, Ralph] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Steere, Allen] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
[Pena-Cruz, Victor] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kirschning, Carsten] Univ Duisburg Essen, Inst Med Microbiol, Essen, Germany.
RP Moody, DB (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Smith Bldg,Room 514,1 Jimmy Fund Way, Boston, MA 02115 USA.
EM bmoody@rics.bwh.harvard.edu
RI Roura-Mir, Carme/D-4538-2013
OI Roura-Mir, Carme/0000-0003-0514-337X
FU NIH [AI R01049313, AR R01048632, AR R0120358]; Pew Foundation; Burroughs
Wellcome Fund for Translational Research; Cancer Research Institute and
Centers for Disease Control and Prevention [CCU110 291]; The English;
Bonter; Mitchell Foundation; Eshe Fund; Lyme/Arthritis Research Fund at
Massachusetts General Hospital
FX This work was supported by grants from the NIH (AI R01049313, AR
R01048632, AR R0120358), the Pew Foundation Scholars in the Biomedical
Sciences Program, The Burroughs Wellcome Fund for Translational
Research, the Cancer Research Institute and Centers for Disease Control
and Prevention, (CCU110 291), The English, Bonter, Mitchell Foundation,
the Eshe Fund, and the Lyme/Arthritis Research Fund at Massachusetts
General Hospital. The authors thank Justin D. Radolf for providing B.
burgdorferi strains and advice, Sam Behar and Steve Porcelli for
providing antibodies to CD1, Nitin Damle and Vijay Sikand for performing
the skin biopsies, and Jenny Shin for cutting sections of the EM biopsy
samples.
NR 63
TC 19
Z9 19
U1 1
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD MAR
PY 2011
VL 41
IS 3
BP 694
EP 705
DI 10.1002/eji.201040808
PG 12
WC Immunology
SC Immunology
GA 731HU
UT WOS:000288097700015
PM 21246541
ER
PT J
AU Sandoval, KE
Farr, SA
Banks, WA
Niehoff, ML
Morley, JE
Crider, AM
Witt, KA
AF Sandoval, Karin E.
Farr, Susan A.
Banks, William A.
Niehoff, Michael L.
Morley, John E.
Crider, Albert M.
Witt, Ken A.
TI Chronic peripheral administration of somatostatin receptor subtype-4
agonist NNC 26-9100 enhances learning and memory in SAMP8 mice
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE Somatostatin subtype-4 receptor agonist; NNC 26-9100; Alzheimer's
disease; Learning; Memory
ID AMYLOID-BETA PEPTIDE; BLOOD-BRAIN-BARRIER; FOOTSHOCK AVOIDANCE
ACQUISITION; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE;
SENILE-DEMENTIA; A-BETA; PROTEIN; NEPRILYSIN; RETENTION
AB Selective somatostatin receptor subtype agonists have been proposed as a means to mitigate learning and memory loss associated with Alzheimer's disease. The first aim of this study evaluated blood-to-brain transport and regional brain distribution of NNC 26-9100, a selective somatostatin subtype-4 (sst4) receptor agonist. The entry rate of I-131-NNC 26-9100 was K-i = 0.25 mu l/g min, with an similar to 93% association with the parenchymal component. The second goal of this study was to evaluate the effect of chronic NNC 26-9100 administration (i.p.) on learning and memory, brain A beta(x-42) levels, and protein expression of sst4 receptor and amyloid precursor protein (APP) in the senescence-accelerated mouse p8 (SAMP8) model of Alzheimer's disease. Mice chronically treated with NNC 26-9100 showed improved learning (day 21) and memory (day 28) using the T-maze paradigm (20 and 200 mu g). Ex vivo tissue analyses showed a decline in A beta(x-42) levels at the 20 mu g dose, while no alterations were observed in sst4 receptor or APP protein expression compared to vehicle controls. These findings indicate NNC 26-9100 is taken up into key brain regions associated with learning and memory. Furthermore, chronic administration of NNC 26-9100 improved learning and memory and decreased A beta(x-42) brain levels. These results suggest sst4 receptor agonists may provide a viable therapy in the treatment of Alzheimer's disease and other forms of cognitive impairment. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Witt, Ken A.] So Illinois Univ, Sch Pharm, Dept Pharmaceut Sci, Edwardsville, IL 62026 USA.
[Farr, Susan A.; Niehoff, Michael L.; Morley, John E.] Vet Affairs Med Ctr St Louis, Ctr Geriatr Res Educ & Clin, St Louis, MO USA.
[Farr, Susan A.; Niehoff, Michael L.; Morley, John E.] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr, St Louis, MO 63103 USA.
[Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA.
[Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA.
RP Witt, KA (reprint author), So Illinois Univ, Sch Pharm, Dept Pharmaceut Sci, Campus Box 2000, Edwardsville, IL 62026 USA.
EM kwitt@siue.edu
RI morley, john/F-9177-2011
OI morley, john/0000-0001-6444-2965
FU Alzheimer's Drug Discovery Foundation [261105.01]; VA; National
Institutes of Health National Institute on Aging [R21AG029318]
FX This work was supported by the Alzheimer's Drug Discovery Foundation
(Grant: 261105.01), VA merit review, and the National Institutes of
Health National Institute on Aging (Grant: R21AG029318).
NR 42
TC 11
Z9 13
U1 2
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD MAR 1
PY 2011
VL 654
IS 1
BP 53
EP 59
DI 10.1016/j.ejphar.2010.12.013
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 720OY
UT WOS:000287291200008
PM 21185826
ER
PT J
AU Bubber, P
Hartounian, V
Gibson, GE
Blass, JP
AF Bubber, P.
Hartounian, V.
Gibson, G. E.
Blass, J. P.
TI Abnormalities in the tricarboxylic acid (TCA) cycle in the brains of
schizophrenia patients
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Mitochondria; Tricarboxylic acid cycle; Energy metabolism; Postmortem
interval; Schizophrenia
ID ALPHA-KETOGLUTARATE DEHYDROGENASE; MITOCHONDRIAL DYSFUNCTION;
ALZHEIMERS-DISEASE; OXIDATIVE STRESS; GLUCOSE-TOLERANCE; PREFRONTAL
CORTEX; ENZYMES; METABOLISM; COMPLEX; GLYCOLYSIS
AB Images of brain metabolism and measurements of activities of components of the electron transport chain support earlier studies that suggest that brain glucose oxidation is inherently abnormal in a significant proportion of persons with schizophrenia. Therefore, we measured the activities of enzymes of the tricarboxylic (TCA) cycle in dorsolateral-prefrontal-cortex from schizophrenia patients (N=13) and non-psychiatric disease controls (N=13): the pyruvate dehydrogenase complex (PDHC), citrate synthase (CS), aconitase, isocitrate dehydrogenase (ICDH), the alpha-ketoglutarate dehydrogenase complex (KGDHC), succinate thiokinase (STH), succinate dehydrogenase (SDH), fumarase and malate dehydrogenase (MDH). Activities of aconitase (18.4%, p<0.05), KGDHC (26%) and STH (28.2%, p<0.05), enzymes in the first half of the TCA cycle, were lower, but SDH (18.3%, p<0.05) and MDH (34%, p<0.005), enzymes in the second half, were higher than controls. PDHC, CS, ICDH and fumarase activities were unchanged. There were no significant correlations between enzymes of TCA cycle and cognitive function, age or choline acetyl transferase activity, except for aconitase activity which decreased slightly with age (r = 0.55, p = 003). The increased activities of dehydrogenases in the second half of the TCA cycle may reflect a compensatory response to reduced activities of enzymes in the first half. Such alterations in the components of TCA cycle are adequate to alter the rate of brain metabolism. These results are consistent with the imaging studies of hypometabolism in schizophrenia. They suggest that deficiencies in mitochondrial enzymes can be associated with mental disease that takes the form of schizophrenia. (C) 2010 Elsevier B.V. and ECNP. All rights reserved.
C1 [Gibson, G. E.] Cornell Univ, Weill Cornell Med Sch, Burke Med Res Inst, Weill Med Coll, White Plains, NY 10605 USA.
[Hartounian, V.] Mt Sinai Sch Med, New York, NY USA.
[Hartounian, V.] Bronx Vet Affairs Med Ctr, MIRECC, Bronx, NY 10468 USA.
RP Gibson, GE (reprint author), Cornell Univ, Weill Cornell Med Sch, Burke Med Res Inst, Weill Med Coll, 785 Mamaroneck Ave, White Plains, NY 10605 USA.
EM ggibson@med.cornell.edu
FU Burke Medical Research Institute; NIH [AG14600, AG11921, AG14930];
[MH064673]; [MH066392]
FX This work was supported by grants MH064673 and MH066392, AG14600,
AG11921, AG14930, AG11921 and Burke Medical Research Institute. The
funding sources were not involved in study design, collection analysis
or interpretation of the data, the writing of the report nor submission
to Schizophrenia Research.; This work was supported by NIH grants
AG14600, AG11921 and AG14930.
NR 49
TC 28
Z9 29
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD MAR
PY 2011
VL 21
IS 3
BP 254
EP 260
DI 10.1016/j.euroneuro.2010.10.007
PG 7
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 728UU
UT WOS:000287900800005
PM 21123035
ER
PT J
AU Vickers, A
Savage, C
Bianco, F
Mulhall, J
Sandhu, J
Guillonneau, B
Cronin, A
Scardino, P
AF Vickers, Andrew
Savage, Caroline
Bianco, Fernando
Mulhall, John
Sandhu, Jaspreet
Guillonneau, Bertrand
Cronin, Angel
Scardino, Peter
TI Cancer Control and Functional Outcomes After Radical Prostatectomy as
Markers of Surgical Quality: Analysis of Heterogeneity Between Surgeons
at a Single Cancer Center
SO EUROPEAN UROLOGY
LA English
DT Article
DE Prostate cancer; Radical prostatectomy; Surgeon heterogeneity; Erectile
funcion; Urinary function
ID VOLUME; CURVE
AB Background: Previous studies have shown that complications and biochemical recurrence rates after radical prostatectomy (RP) vary between different surgeons to a greater extent than might be expected by chance. Data on urinary and erectile outcomes, however, are lacking.
Objective: In this study, we examined whether between-surgeon variation, known as heterogeneity, exists for urinary and erectile outcomes after RP.
Design, setting, and participants: Our study consisted of 1910 RP patients who were treated by 1 of 11 surgeons between January 1999 and July 2007.
Intervention: All patients underwent RP at Memorial Sloan-Kettering Cancer Center.
Measurements: Patients were evaluated for functional outcome 1 yr after surgery. Multivariable random effects models were used to evaluate the heterogeneity in erectile or urinary outcome between surgeons, after adjustment for case mix (age, prostate-specific antigen, pathologic stage and grade, comorbidities) and year of surgery.
Results and limitations: We found significant heterogeneity in functional outcomes after RP (p < 0.001 for both urinary and erectile function). Four surgeons had adjusted rates of full continence <75%, whereas three had rates >85%. For erectile function, two surgeons in our series had adjusted rates <20%; another two had rates >45%. We found some evidence suggesting that surgeons' erectile and urinary outcomes were correlated. Contrary to the hypothesis that surgeons "trade off" functional outcomes and cancer control, better rates of functional preservation were associated with lower biochemical recurrence rates.
Conclusions: A patient's likelihood of recovering erectile and urinary function may differ depending on which of two surgeons performs his RP. Functional preservation does not appear to come at the expense of cancer control; rather, both are related to surgical quality. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Vickers, Andrew] Mem Sloan Kettering Canc Ctr, Hlth Outcomes Res Grp, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Vickers, Andrew; Savage, Caroline; Mulhall, John; Sandhu, Jaspreet; Guillonneau, Bertrand; Scardino, Peter] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
[Bianco, Fernando] Columbia Univ, Div Urol, Mt Sinai Med Ctr, New York, NY USA.
[Mulhall, John; Sandhu, Jaspreet; Guillonneau, Bertrand; Scardino, Peter] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA.
[Cronin, Angel] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Vickers, A (reprint author), Mem Sloan Kettering Canc Ctr, Hlth Outcomes Res Grp, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA.
EM vickersa@mskcc.org
OI Vickers, Andrew/0000-0003-1525-6503
FU Prostate Cancer Foundation; Sidney Kimmel Center for Prostate and
Urologic Cancers; National Cancer Institute [P50-CA92629]
FX Supported in part by funds from David H. Koch provided through the
Prostate Cancer Foundation, the Sidney Kimmel Center for Prostate and
Urologic Cancers, and a P50-CA92629 SPORE grant from the National Cancer
Institute to Peter Scardino.
NR 11
TC 52
Z9 55
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD MAR
PY 2011
VL 59
IS 3
BP 317
EP 322
DI 10.1016/j.eururo.2010.10.045
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 712IA
UT WOS:000286658600007
PM 21095055
ER
PT J
AU Ament, JD
Stryjewski, TP
Pujari, S
Siddique, S
Papaliodis, GN
Chodosh, J
Dohlman, CH
AF Ament, J. D.
Stryjewski, T. P.
Pujari, S.
Siddique, S.
Papaliodis, G. N.
Chodosh, J.
Dohlman, C. H.
TI Cost effectiveness of the type II Boston keratoprosthesis
SO EYE
LA English
DT Article
DE decision analysis; cost utility; cost effectiveness; keratoprosthesis;
autoimmune diseases
ID OSTEO-ODONTO-KERATOPROSTHESIS; STEVENS-JOHNSON-SYNDROME; OCULAR SURFACE
DISEASE; TOTAL HIP-ARTHROPLASTY; PENETRATING KERATOPLASTY; EFFECTIVENESS
THRESHOLD; CATARACT-SURGERY; UTILITY ANALYSIS; CHEMOPROPHYLAXIS;
DECISIONS
AB Purpose Despite demonstrated cost effectiveness, not all corneal disorders are amenable to type I Boston keratoprosthesis (KPro) implantation. This includes patients with autoimmune diseases, such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Type II KPro is implanted through the eyelids in severe dry eye and cicatricial diseases, and its cost effectiveness was sought.
Patients and methods In a retrospective chart review, 29 patients who underwent type II KPro surgery at the Massachusetts Eye and Ear Infirmary between the years 2000 and 2009 were identified. A total of 11 patients had 5-year follow-up data. Average cost effectiveness was determined by cost-utility analysis, comparing type II KPro surgery with no further intervention.
Results Using the current parameters, the cost utility of KPro from third-party insurer (Medicare) perspective was 63 196 $/quality-adjusted life year.
Conclusion Efforts to refer those less likely to benefit from traditional corneal transplantation or type I KPro, for type II KPro surgery, may decrease both patient and societal costs. Eye (2011) 25, 342-349; doi:10.1038/eye.2010.197; published online 24 December 2010
C1 [Ament, J. D.; Stryjewski, T. P.; Pujari, S.; Siddique, S.; Papaliodis, G. N.; Chodosh, J.; Dohlman, C. H.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Ament, JD (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM jaredament@post.harvard.edu
FU Dr Dohlman's research and development fund
FX Dr Dohlman receives no personal profits from the sale of the Boston
Keratoprosthesis. Proceeds go to the Massachusetts Eye and Ear
Infirmary, and are used to support research and development. The authors
are/were employees of the Massachusetts Eye and Ear Infirmary, and
receive no financial benefit from the publication of this data. Dr Ament
is a Clinical Research Fellow who is paid directly from Dr Dohlman's
research and development fund.
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U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-222X
EI 1476-5454
J9 EYE
JI Eye
PD MAR
PY 2011
VL 25
IS 3
BP 342
EP 349
DI 10.1038/eye.2010.197
PG 8
WC Ophthalmology
SC Ophthalmology
GA 733DG
UT WOS:000288240500010
PM 21183944
ER
PT J
AU Jia, WW
Wang, SW
Horner, JW
Wang, N
Wang, HY
Gunther, EJ
DePinho, RA
Zhu, JY
AF Jia, Wenwen
Wang, Shuwen
Horner, James W.
Wang, Ning
Wang, Huayan
Gunther, Edward J.
DePinho, Ronald A.
Zhu, Jiyue
TI A BAC transgenic reporter recapitulates in vivo regulation of human
telomerase reverse transcriptase in development and tumorigenesis
SO FASEB JOURNAL
LA English
DT Article
DE transgenic mouse; hTERT gene; mammary tumor; bioluminescent imaging
ID MOUSE TELOMERASE; STEM-CELLS; CATALYTIC SUBUNIT; IMMORTAL CELLS; HTERT
GENE; C-MYC; CANCER; EXPRESSION; MICE; ACTIVATION
AB Telomerase is tightly regulated in humans relative to mice, owing to the differential regulation of TERT genes. To explore hTERT regulation in vivo, we engineered mice with a 160-kb transgenic bacterial artificial chromosome (BAC) spanning the hTERT locus with a Renilla luciferase (Rluc) cassette downstream of its promoter. Analysis of multiple founder lines revealed that the Rluc expression profile from the transgenic hTERT reporter locus reproduced that of the native hTERT gene in all tissues and organs examined, demonstrating that genetic sequence determined the species-specific developmental regulation of the hTERT gene and that mouse epigenetic and transcription machineries faithfully regulated hTERT transcription. Thus, these mice allowed detailed analyses of developmental hTERT regulation. Both the transgenic hTERT reporter and the endogenous mTERT locus were expressed in early embryonic stages, and their mRNA levels progressively decreased throughout embryonic and postnatal development. Whereas hTERT transcription was much lower than mTERT expression in most organs, it increased significantly during postnatal development of thymus, testis, and ovary. In testis, the Rluc mRNA was enriched in elongating spermatids of seminiferous tubules. In addition, the transcription of transgenic hTERT reporter, but surprisingly not the endogenous mTERT gene, was activated during Wnt1-induced mammary tumorigenesis, allowing the monitoring of tumor development via noninvasive bioluminescent imaging. Collectively, our results demonstrate that the hTERT transgenic reporter system recapitulates the developmental regulation of the hTERT gene in a chromosomal position-independent manner and serves as a legitimate model to explore telomerase regulation in the development of normal and neoplastic tissues in vivo.-Jia, W., Wang, S., Horner, J. W., Wang, N., Wang, H., Gunther, E. J., DePinho, R. A., Zhu, J. A BAC transgenic reporter recapitulates in vivo regulation of human telomerase reverse transcriptase in development and tumorigenesis. FASEB J. 25, 979-989 (2011). www.fasebj.org
C1 [Jia, Wenwen; Wang, Huayan] NW Agr & Forestry A&F Univ, Coll Vet Med, Shaanxi Ctr Stem Cell Engn & Technol, Yangling, Shaanxi, Peoples R China.
[Jia, Wenwen; Wang, Shuwen; Wang, Ning; Zhu, Jiyue] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA.
[Gunther, Edward J.] Penn State Univ, Coll Med, Jake Gittlen Canc Res Fdn, Hershey, PA 17033 USA.
[Horner, James W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
RP Zhu, JY (reprint author), Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, 500 Univ Dr,C4605, Hershey, PA 17033 USA.
EM jozl@psu.edu
FU U.S. National Institutes of Health [R21CA106470, R01GM071725]; Chinese
National Programs for Fundamental Research and Development
[2009CB941002]; Chinese Ministry of Education
FX The authors thank Longgui Chen for technical assistance, Aimin Liu for
RNA in situ hybridization, and Kang Li for the preparation of tissue
cryosections. The authors also thank the Macromolecular and Molecular
Genetics Core Facilities at Penn State College of Medicine for the
excellent services. The work was supported in part by U.S. National
Institutes of Health grants R21CA106470 and R01GM071725 (J.Z.), a 973
grant (2009CB941002) from the Chinese National Programs for Fundamental
Research and Development (H.W.), and a Ph.D. student scholarship from
the Chinese Ministry of Education (W.J.). None of the authors have
professional or financial affiliations that can be perceived to bias the
presentation of this work.
NR 50
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U1 0
U2 5
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD MAR
PY 2011
VL 25
IS 3
BP 979
EP 989
DI 10.1096/fj.10-173989
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 727MZ
UT WOS:000287806200018
PM 21135040
ER
PT J
AU Bhattacharya, A
Lustgarten, M
Shi, Y
Liu, YH
Jang, YC
Pulliam, D
Jernigan, AL
Van Remmen, H
AF Bhattacharya, Arunabh
Lustgarten, Michael
Shi, Yun
Liu, Yuhong
Jang, Youngmok C.
Pulliam, Daniel
Jernigan, Amanda L.
Van Remmen, Holly
TI Increased mitochondrial matrix-directed superoxide production by fatty
acid hydroperoxides in skeletal muscle mitochondria
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Oxidative stress; Superoxide; Fatty acid hydroperoxides; Hydrogen
peroxide; Mitochondria; Free radicals
ID ELECTRON-TRANSPORT CHAIN; RAT-HEART MITOCHONDRIA; NADH-UBIQUINONE
OXIDOREDUCTASE; OXYGEN SPECIES PRODUCTION; REACTIVE OXYGEN; COMPLEX-I;
ARACHIDONIC-ACID; OXIDATIVE STRESS; BRAIN MITOCHONDRIA; RESPIRATORY
CHAIN
AB Previous studies have shown that muscle atrophy is associated with mitochondrial dysfunction and an increased rate of mitochondrial reactive oxygen species production. We recently demonstrated that fatty acid hydroperoxides (FA-OOHs) are significantly elevated in mitochondria isolated from atrophied muscles. The purpose of this study was to determine whether FA-OOHs can alter skeletal muscle mitochondrial function. We found that FA-OOHs (at low-micromolar concentrations) induce mitochondrial dysfunction assessed by a decrease in the rate of ATP production, oxygen consumption, and activity of respiratory chain complexes land Ill. Using methods to distinguish superoxide release toward the matrix and toward the intermembrane space, we demonstrate that FA-OOHs significantly elevate oxidative stress in the mitochondrial matrix (and not the intermembrane space), with complex I as the major site of superoxide production (most probably from a site upstream of the ubiquinone binding site but downstream from the flavin binding site the-iron sulfur clusters). Our results are the first to indicate that FA-OOHs are, important modulators of mitochondrial function and oxidative stress in skeletal muscle mitochondria and may play an important role in muscle atrophies that are associated with increased generation of FA-OOHs, e.g., denervation-induced muscle atrophy. (C) 2010 Published by Elsevier Inc.
C1 [Bhattacharya, Arunabh; Lustgarten, Michael; Shi, Yun; Liu, Yuhong; Jang, Youngmok C.; Pulliam, Daniel; Jernigan, Amanda L.; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Bhattacharya, Arunabh; Liu, Yuhong; Pulliam, Daniel; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Shi, Yun; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
EM vanremmen@uthscsa.edu
FU National Institute of Aging [AG20591]; Muscular Dystrophy Association
[MDA 10047]
FX This work was supported by the National Institute of Aging (Grant
AG20591 to H.V.R.) and the Muscular Dystrophy Association (Grant MDA
10047 to H.V.R.). We greatly appreciate the editorial support provided
by Ms. Corinne Price.
NR 67
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Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD MAR 1
PY 2011
VL 50
IS 5
BP 592
EP 601
DI 10.1016/j.freeradbiomed.2010.12.014
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 719BQ
UT WOS:000287174700005
PM 21172427
ER
PT J
AU Chan, AT
Ogino, S
Giovannucci, EL
Fuchs, CS
AF Chan, Andrew T.
Ogino, Shuji
Giovannucci, Edward L.
Fuchs, Charles S.
TI Inflammatory Markers Are Associated With Risk of Colorectal Cancer and
Chemopreventive Response to Anti-Inflammatory Drugs
SO GASTROENTEROLOGY
LA English
DT Article
DE Colon Cancer; Prevention; Inflammation; Chemoprevention
ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; CORONARY-HEART-DISEASE;
NATIONAL DEATH INDEX; FACTOR-ALPHA; ASPIRIN USE; DIABETES-MELLITUS;
CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE
AB BACKGROUND & AIMS: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) lower the risk of colorectal cancer (CRC). We investigated whether plasma inflammatory markers were associated with risk of CRC and if use of anti-inflammatory drugs was differentially associated with risk of CRC according to levels of inflammatory markers. METHODS: We measured levels of high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, and the soluble tumor necrosis factor receptor 2 (sTNFR-2) in blood samples from 32,826 women, collected from 1989 to 1990. Through 2004, we documented 280 cases of incident CRC; each case was matched for age to 2 randomly selected participants without cancer (controls). Information on anti-inflammatory drug (aspirin and NSAIDs) use was collected biennially. RESULTS: Compared with women in the lowest quartile of plasma levels of sTNFR-2, women in the highest quartile had an increased risk of CRC (multivariate relative risk [RR], 1.67; 95% confidence interval [CI], 1.05-2.68; P for trend = .03). Among women with high baseline levels of sTNFR-2, those who initiated aspirin/NSAID use after blood collection had significant reductions in subsequent risk of CRC (multivariate RR, 0.39; 95% CI, 0.18-0.86). In contrast, among women with low baseline levels of sTNFR-2, initiation of aspirin/NSAID use was not associated with significant risk reduction (multivariate RR, 0.86; 95% CI, 0.41-1.79). Plasma levels of CRP and IL-6 were not significantly associated with CRC risk. CONCLUSIONS: Plasma levels of sTNFR-2, but not CRP or IL-6, are associated with an increased risk of CRC. Anti-inflammatory drugs appear to reduce risk of CRC among women with high, but not low, baseline levels of sTNFR-2. Certain subsets of the population, defined by inflammatory markers, may obtain different benefits from anti-inflammatory drugs.
C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Chan, Andrew T.; Ogino, Shuji; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA.
[Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med 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 Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 722, Boston, MA 02114 USA.
EM achan@partners.org
FU National Institutes of Health [P01CA87969, P01CA55075, P50CA127003];
[R01 137178]; [U01 CA049449]
FX Supported by grants R01 137178, U01 CA049449. P01CA87969, P01CA55075,
and P50CA127003 from the National Institutes of Health. Dr Chan is a
Damon Runyon Cancer Research Foundation Clinical Investigator.
NR 59
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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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2011
VL 140
IS 3
BP 799
EP U183
DI 10.1053/j.gastro.2010.11.041
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730EC
UT WOS:000288014700021
ER
PT J
AU Lok, AS
Everhart, JE
Wright, EC
Di Bisceglie, AM
Kim, HY
Sterling, RK
Everson, GT
Lindsay, KL
Lee, WM
Bonkovsky, HL
Dienstag, JL
Ghany, MG
Morishima, C
Morgan, TR
AF Lok, Anna S.
Everhart, James E.
Wright, Elizabeth C.
Di Bisceglie, Adrian M.
Kim, Hae-Young
Sterling, Richard K.
Everson, Gregory T.
Lindsay, Karen L.
Lee, William M.
Bonkovsky, Herbert L.
Dienstag, Jules L.
Ghany, Marc G.
Morishima, Chihiro
Morgan, Timothy R.
CA Halt-C Trial Grp
TI Maintenance Peginterferon Therapy and Other Factors Associated With
Hepatocellular Carcinoma in Patients With Advanced Hepatitis C
SO GASTROENTEROLOGY
LA English
DT Article
DE Interferon Therapy; Hepatitis C Clinical Trial; Interferon
Nonresponders; Liver Cancer
ID SUSTAINED VIROLOGICAL RESPONSE; LOW-DOSE PEGINTERFERON;
INTERFERON-ALPHA; PROLONGED THERAPY; RISK-FACTORS; CIRRHOSIS; TRIAL;
METAANALYSIS; PROGRESSION; SURVIVAL
AB BACKGROUND & AIMS: Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance therapy with pegylated interferon (peginterferon) does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer posttreatment follow-up period. METHODS: The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores >= 3) who did not have a sustained virologic response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7) years. RESULTS: Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.24-0.83); in treated and control patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44; 95% CI, 0.77-2.69). Treated patients with a >= 2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03). CONCLUSIONS: Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk of HCC than controls.
C1 [Lok, Anna S.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Wright, Elizabeth C.] NIDDK, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA.
[Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA.
[Sterling, Richard K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA.
[Everson, Gregory T.] Univ Colorado, Denver Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Aurora, CO USA.
[Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
RP Lok, AS (reprint author), Univ Michigan Hlth Syst, Div Gastroenterol, 3912 Taubman Ctr,SPC 5362, Ann Arbor, MI 48109 USA.
EM aslok@umich.edu
OI Yang, Shuman/0000-0002-9638-0890
FU University of Massachusetts Medical Center, Worcester, Massachusetts
[N01-DK-9-2326]; University of Connecticut Health Center, Farmington,
Connecticut [M01RR-06192]; Saint Louis University School of Medicine, St
Louis, Missouri [N01-DK-9-2324]; Massachusetts General Hospital, Boston,
Massachusetts (Harvard Clinical and Translational Science Center)
[N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; University of Colorado
Denver School of Medicine, Aurora, Colorado [N01-DK-9-2327, M01RR-00051,
1 UL1 RR 025780-01]; University of California-Irvine, Irvine, California
[N01-DK-9-2320, M01RR-00827]; University of Texas Southwestern Medical
Center, Dallas, Texas (North and Central Texas Clinical and
Translational Science Initiative) [N01-DK-9-2321, M01RR-00633, 1 UL1
RR024982-01]; University of Southern California, Los Angeles, California
[N01-DK-9-2325, M01RR-00043]; University of Michigan Medical Center, Ann
Arbor, Michigan (Michigan Center for Clinical and Health Research)
[N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia Commonwealth
University Health System, Richmond, Virginia [N01-DK-9-2322,
M01RR-00065]; University of Washington, Seattle, Washington
[N01-DK-9-2318]; New England Research Institutes, Watertown,
Massachusetts [N01-DK-9-2328]; Hoffmann-La Roche, Inc; National
Institute of Diabetes and Digestive and Kidney Diseases; National Center
for Research Resources, National Institutes of Health; National
Institutes of Health
FX In addition to the authors of this manuscript, the following individuals
were instrumental in the planning, conduct, and/or care of patients
enrolled in this study at each of the participating institutions:
University of Massachusetts Medical Center, Worcester, Massachusetts
(contract N01-DK-9-2326): Gyongyi Szabo, MD, Barbara F. Banner, MD,
Maureen Cormier, RN, and Donna Giansiracusa, RN; University of
Connecticut Health Center, Farmington, Connecticut (grant M01RR-06192):
Gloria Borders, RN, and Michelle Kelley, RN, ANP; Saint Louis University
School of Medicine, St Louis, Missouri (contract N01-DK-9-2324): Bruce
Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth M. Brunt, MD, and
Debra King, RN; Massachusetts General Hospital, Boston, Massachusetts
(contract N01-DK-9-2319, grant M01RR-01066; grant 1 UL1 RR025758-01,
Harvard Clinical and Translational Science Center): Raymond T. Chung,
MD, Andrea E. Reid, MD, Atul K. Bhan, MD, Wallis A. Molchen, and David
P. Lundmark; University of Colorado Denver School of Medicine, Aurora,
Colorado (contract N01-DK-9-2327, grant M01RR-00051, grant 1 UL1 RR
025780-01): Thomas Trouillot, MD, Marcelo Kugelmas, MD, S. Russell Nash,
MD, Jennifer DeSanto, RN, and Carol McKinley, RN; University of
California-Irvine, Irvine, California (contract N01-DK-9-2320, grant
M01RR-00827): John C. Hoefs, MD, John R. Craig, MD, M. Mazen Jamal, MD,
MPH, Muhammad Sheikh, MD, and Choon Park, RN; University of Texas
Southwestern Medical Center, Dallas, Texas (contract N01-DK-9-2321,
grant M01RR-00633, grant 1 UL1 RR024982-01, North and Central Texas
Clinical and Translational Science Initiative): Thomas E. Rogers, MD,
Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN, Rivka Elbein,
RN, BSN, and Nancy Liston, MPH; University of Southern California, Los
Angeles, California (contract N01-DK-9-2325, grant M01RR-00043):
Sugantha Govindarajan, MD, Carol B. Jones, RN, and Susan L. Milstein,
RN; University of Michigan Medical Center, Ann Arbor, Michigan (contract
N01-DK-9-2323, grant M01RR-00042, grant 1 UL1 RR024986, Michigan Center
for Clinical and Health Research): Robert J. Fontana, MD, Joel K.
Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, and R. Tess Bonham, BS;
Virginia Commonwealth University Health System, Richmond, Virginia
(contract N01-DK-9-2322, grant M01RR-00065): Mitchell L. Shiffman, MD,
Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, and
Paula Smith, RN; Liver Diseases Branch, National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health,
Bethesda, Maryland: T. Jake Liang, MD, David Kleiner, MD, PhD, Yoon
Park, RN, Elenita Rivera, RN, and Vanessa Haynes-Williams, RN; National
Institute of Diabetes and Digestive and Kidney Diseases, Division of
Digestive Diseases and Nutrition, Bethesda, Maryland: Leonard B. Seeff,
MD, Patricia R. Robuck, PhD, and Jay H. Hoofnagle, MD; University of
Washington, Seattle, Washington (contract N01-DK-9-2318): David R.
Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC,
ASCP, and Natalia Antonov, MEd; New England Research Institutes,
Watertown, Massachusetts (contract N01-DK-9-2328): Kristin K. Snow, MSc,
ScD, Anne M. Stoddard, ScD, and Margaret C. Bell, MS, MPH; Inova Fairfax
Hospital, Falls Church, Virginia: Zachary D. Goodman, MD, PhD, Fanny
Monge, and Michelle Parks; Data and Safety Monitoring Board Members:
Gary L. Davis, MD (Chair), Guadalupe Garcia-Tsao, MD, Michael Kutner,
PhD, Stanley M. Lemon, MD, and Robert P. Perrillo, MD.; The authors
disclose the following: Dr Lok is a consultant and receives research
support from Hoffmann-La Roche, Inc; Dr Di Bisceglie is a consultant and
receives research support from Hoffmann-La Roche, Inc; Dr Sterling is a
consultant and receives research support from Hoffmann-La Roche, Inc; Dr
Everson is a consultant and receives research support from Hoffmann-La
Roche, Inc; Dr Lindsay was a consultant and received research support
from Hoffmann-La Roche, Inc, during this study and is now an employee of
Tibotec, Inc (a subsidiary of Johnson and Johnson; Titusville, NJ); Dr
Lee receives research support from Hoffmann-La Roche, Inc; Dr Bonkovsky
receives research support from Hoffmann-La Roche, Inc; and Dr Morgan
receives research support from Hoffmann-La Roche, Inc. The remaining
authors disclose no conflicts.; Supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (contract numbers are listed
in the acknowledgments). Additional support was provided by the National
Institute of Allergy and Infectious Diseases, the National Cancer
Institute, the National Center for Minority Health and Health
Disparities, and General Clinical Research Center and Clinical and
Translational Science Center grants from the National Center for
Research Resources, National Institutes of Health (grant numbers are
listed in the acknowledgments). The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Center for Research Resources or the National Institutes of
Health. Additional funding to conduct this study was supplied by
Hoffmann-La Roche, Inc, through a Cooperative Research and Development
Agreement with the National Institutes of Health.
NR 29
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U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2011
VL 140
IS 3
BP 840
EP U230
DI 10.1053/j.gastro.2010.11.050
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730EC
UT WOS:000288014700025
PM 21129375
ER
PT J
AU Parekkadan, B
Upadhyay, R
Dunham, J
Iwamoto, Y
Mizoguchi, E
Mizoguchi, A
Weissleder, R
Yarmush, ML
AF Parekkadan, Biju
Upadhyay, Rabi
Dunham, Joshua
Iwamoto, Yoshiko
Mizoguchi, Emiko
Mizoguchi, Atsushi
Weissleder, Ralph
Yarmush, Martin L.
TI Bone Marrow Stromal Cell Transplants Prevent Experimental Enterocolitis
and Require Host CD11b(+) Splenocytes
SO GASTROENTEROLOGY
LA English
DT Article
DE Crohn's Disease; Mesenchymal Stem Cells; Monocyte; Imaging
ID MESENCHYMAL STEM-CELLS; INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS;
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IMMUNE-RESPONSE; IN-VIVO;
THERAPY; INFUSION; MICE; DIFFERENTIATION
AB BACKGROUND & AIMS: Bone marrow stromal cells (MSCs) are being evaluated as a cellular therapeutic for immune-mediated diseases. We investigated the effects of MSCs in mice with chemically induced colitis and determined the effects of CD11b(+) cells based on the hypothesis that MSCs increase numbers of regulatory T cells. METHODS: Colitis was induced in mice using trinitrobenzene sulfonic acid; symptoms were monitored as a function of MSC delivery. An immunomodulatory response was determined by measuring numbers of regulatory T cells in mesenteric lymph nodes. In vitro cocultures were used to assess the interaction of MSCs with regulatory T cells and CD11b(+) cells; findings were supported using near-infrared tracking of MSCs in vivo. We chemically and surgically depleted splenic CD11b(+) cells before colitis was induced with trinitrobenzene sulfonic acid to monitor the effects of MSCs. We adoptively transferred CD11b(+) cells that were cocultured with MSCs into mice with colitis. RESULTS: Intravenous grafts of MSCs prevented colitis and increased survival times of mice. Numbers of Foxp3(+) regulatory T cells increased in mesenteric lymph nodes in mice given MSCs. MSCs increased the numbers of Foxp3(+) splenocytes in a CD11b(+) cell-dependent manner. Transplanted MSCs colocalized near splenic CD11b(+) cells in vivo. Loss of CD11b(+) cells eliminated the therapeutic effect of MSCs. MSCs increased the anticolitis effects of CD11b(+) cells in mice. CONCLUSIONS: MSC transplants, delivered by specific parameters, reduce colitis in mice. Interactions between MSC and CD11b(+) regulatory T cells might be used to develop potency assays for MSCs, to identify nonresponders to MSC therapy, and to create new cell grafts that are composed of CD11b(+) cells preconditioned by MSCs.
C1 [Parekkadan, Biju; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA.
[Parekkadan, Biju; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA.
[Upadhyay, Rabi; Dunham, Joshua; Iwamoto, Yoshiko; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Mizoguchi, Atsushi] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA.
RP Parekkadan, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA.
EM biju_parekkadan@hms.harvard.edu
FU National Institutes of Health [5R01DK059766-06, R01 DK80070,
U24CA092782]; Broad Foundation [BMRP498382]; Shriners Hospitals for
Children
FX This work was partially supported by grants from the National Institutes
of Health (5R01DK059766-06, R01 DK80070, and U24CA092782), the Broad
Medical Research Program of the Broad Foundation (BMRP498382), and the
Shriners Hospitals for Children.
NR 34
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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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2011
VL 140
IS 3
BP 966
EP U385
DI 10.1053/j.gastro.2010.10.013
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730EC
UT WOS:000288014700037
PM 20955701
ER
PT J
AU Lugea, A
Tischler, D
Nguyen, J
Gong, J
Gukovsky, I
French, SW
Gorelick, FS
Pandol, SJ
AF Lugea, Aurelia
Tischler, David
Nguyen, Janie
Gong, Jun
Gukovsky, Ilya
French, Samuel W.
Gorelick, Fred S.
Pandol, Stephen J.
TI BASIC-LIVER, PANCREAS, AND BILIARY TRACT
SO GASTROENTEROLOGY
LA English
DT Article
DE Alcohol Disease; Transcription Factors; ER Protein Folding; Organelle
ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; OXIDATIVE
STRESS; TRANSCRIPTION FACTOR; ER STRESS; TRANSLATIONAL CONTROL;
IN-VITRO; ETHANOL; XBP1; CELL
AB BACKGROUND & AIMS: Endoplasmic reticulum (ER) stress responses (collectively known the unfolded protein response [UPR]) have important roles in several human disorders, but their contribution to alcoholic pancreatitis is not known. We investigated the role of X-box binding protein 1 (XBP1), a UPR regulator, in prevention of alcohol-induced ER stress in the exocrine pancreas. METHODS: Wild-type and Xbp1(+/-) mice were fed control or ethanol diets for 4 weeks. Pancreatic tissue samples were then examined by light and electron microscopy to determine pancreatic alterations; UPR regulators were analyzed biochemically. RESULTS: In wild-type mice, ethanol activated a UPR, increasing pancreatic levels of XBP1 and XBP1 targets such as protein disulfide isomerase (PDI). In these mice, pancreatic damage was minor. In ethanol-fed Xbp1(+/-) mice, XBP1 and PDI levels were significantly lower than in ethanol-fed-wild-type mice. The combination of XBP1 deficiency and ethanol feeding reduced expression of regulators of ER function and the up-regulation of proapoptotic signals. Moreover, ethanol feeding induced oxidation of PDI, which might compromise PDI-mediated disulfide bond formation during ER protein folding. In ethanol-fed Xbp1(+/-) mice, ER stress was associated with disorganized and dilated ER, loss of zymogen granules, accumulation of autophagic vacuoles, and increased acinar cell death. CONCLUSIONS: Long-term ethanol feeding causes oxidative ER stress, which activates a UPR and increases XBP1 levels and activity. A defective UPR due to XBP1 deficiency results in ER dysfunction and acinar cell pathology.
C1 [Lugea, Aurelia; Tischler, David; Nguyen, Janie; Gong, Jun; Gukovsky, Ilya; Pandol, Stephen J.] Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA 90073 USA.
[French, Samuel W.] Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA.
[Gorelick, Fred S.] Yale Univ, VA Med Ctr, West Haven, CT USA.
RP Lugea, A (reprint author), Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, So Calif Res Ctr ALPD & Cirrhosis, 11301 Wilshire Blvd,Bldg 258,R339, Los Angeles, CA 90073 USA.
EM alugea@ucla.edu
FU National Institute on Alcohol Abuse and Alcoholism [R21 AA016010];
National Center for Complementary and Alternative Medicine
[1P01AT003960]
FX Supported by the National Institute on Alcohol Abuse and Alcoholism
(grant R21 AA016010) and the National Center for Complementary and
Alternative Medicine (grant 1P01AT003960).
NR 53
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U1 0
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2011
VL 140
IS 3
BP 987
EP U415
DI 10.1053/j.gastro.2010.11.038
PG 19
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 730EC
UT WOS:000288014700039
PM 21111739
ER
PT J
AU Zatzick, D
Rivara, F
Jurkovich, G
Russo, J
Trusz, SG
Wang, J
Wagner, A
Stephens, K
Dunn, C
Uehara, E
Petrie, M
Engel, C
Davydow, D
Katon, W
AF Zatzick, Douglas
Rivara, Frederick
Jurkovich, Gregory
Russo, Joan
Trusz, Sarah Geiss
Wang, Jin
Wagner, Amy
Stephens, Kari
Dunn, Chris
Uehara, Edwina
Petrie, Megan
Engel, Charles
Davydow, Dimitri
Katon, Wayne
TI Enhancing the population impact of collaborative care interventions:
mixed method development and implementation of stepped care targeting
posttraumatic stress disorder and related comorbidities after acute
trauma
SO GENERAL HOSPITAL PSYCHIATRY
LA English
DT Article
DE PTSD; Stepped collaborative care; Acute care; Population impact;
Traumatic injury
ID RANDOMIZED CONTROLLED-TRIAL; POST-CABG DEPRESSION; FUNCTIONAL OUTCOMES;
ANXIETY DISORDERS; PREVENTIVE INTERVENTIONS; BEHAVIORAL ACTIVATION;
CLINICAL-RESEARCH; PHYSICAL INJURY; ALCOHOL-ABUSE; FOLLOW-UP
AB Objective: The objective of the study was to develop and implement a stepped collaborative care intervention targeting posttraumatic stress disorder (PTSD) and related comorbidities to enhance the population impact of early trauma-focused interventions.
Method: We describe the design and implementation of the Trauma Survivors Outcomes and Support study. An interdisciplinary treatment development team was composed of trauma surgical, clinical psychiatric and mental health services "change agents" who spanned the boundaries between frontline trauma center clinical care and acute care policy. Mixed method clinical epidemiologic and clinical ethnographic studies informed the development of PTSD screening and intervention procedures.
Results: Two hundred seven acutely injured trauma survivors with high early PTSD symptom levels were randomized into the study. The stepped collaborative care model integrated care management (i.e., posttraumatic concern elicitation and amelioration, motivational interviewing and behavioral activation) with cognitive behavioral therapy and pharmacotherapy targeting PTSD. The model was feasibly implemented by frontline acute care masters in social work and nurse practioner providers.
Conclusions: Stepped care protocols targeting PTSD may enhance the population impact of early interventions developed for survivors of individual and mass trauma by extending the reach of collaborative care interventions to acute care medical settings and other nonspecialty posttraumatic contexts. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Zatzick, Douglas; Dunn, Chris] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA.
[Rivara, Frederick] Univ Washington, Sch Med, Dept Pediat, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA.
[Jurkovich, Gregory] Univ Washington, Sch Med, Dept Surg, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA.
[Russo, Joan; Davydow, Dimitri; Katon, Wayne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Trusz, Sarah Geiss; Stephens, Kari; Petrie, Megan] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA.
[Wang, Jin] Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA.
[Wagner, Amy] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97207 USA.
[Uehara, Edwina] Univ Washington, Sch Med, Sch Social Work, Seattle, WA 98104 USA.
[Engel, Charles] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
RP Zatzick, D (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA.
EM dzatzick@u.washington.edu
FU National Institute of Mental Health [MH073613, MH086814]
FX This work was funded by grants MH073613 and MH086814 from the National
Institute of Mental Health. The authors thank Jeffrey Love, B.A., for
his assistance with the preparation of the manuscript. The views
expressed in this article are those of the authors and do not reflect
official policy or position of the Department of the Army, The
Department of Defense, or any other U.S. Government agency or
department.
NR 138
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U1 12
U2 34
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0163-8343
J9 GEN HOSP PSYCHIAT
JI Gen. Hosp. Psych.
PD MAR-APR
PY 2011
VL 33
IS 2
BP 123
EP 134
DI 10.1016/j.genhosppsych.2011.01.001
PG 12
WC Psychiatry
SC Psychiatry
GA 745RP
UT WOS:000289183700006
PM 21596205
ER
PT J
AU Ogino, S
Chan, AT
Fuchs, CS
Giovannucci, E
AF Ogino, Shuji
Chan, Andrew T.
Fuchs, Charles S.
Giovannucci, Edward
TI Molecular pathological epidemiology of colorectal neoplasia: an emerging
transdisciplinary and interdisciplinary field
SO GUT
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; BODY-MASS INDEX; LIFE-STYLE FACTORS; III
COLON-CANCER; TUMOR MICROSATELLITE INSTABILITY; K-RAS MUTATIONS;
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MGMT PROMOTER METHYLATION;
ONE-CARBON METABOLISM; SINGLE NUCLEOTIDE POLYMORPHISM
AB Colorectal cancer is a complex disease resulting from somatic genetic and epigenetic alterations, including locus-specific CpG island methylation and global DNA or LINE-1 hypomethylation. Global molecular characteristics such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), global DNA hypomethylation, and chromosomal instability cause alterations of gene function on a genome-wide scale. Activation of oncogenes including KRAS, BRAF and PIK3CA affects intracellular signalling pathways and has been associated with CIMP and MSI. Traditional epidemiology research has investigated various factors in relation to an overall risk of colon and/or rectal cancer. However, colorectal cancers comprise a heterogeneous group of diseases with different sets of genetic and epigenetic alterations. To better understand how a particular exposure influences the carcinogenic and pathologic process, somatic molecular changes and tumour biomarkers have been studied in relation to the exposure of interest. Moreover, an investigation of interactive effects of tumour molecular changes and the exposures of interest on tumour behaviour (prognosis or clinical outcome) can lead to a better understanding of tumour molecular changes, which may be prognostic or predictive tissue biomarkers. These new research efforts represent 'molecular pathologic epidemiology', which is a multidisciplinary field of investigations of the interrelationship between exogenous and endogenous (eg, genetic) factors, tumoural molecular signatures and tumour progression. Furthermore, integrating genome-wide association studies (GWAS) with molecular pathological investigation is a promising area (GWAS-MPE approach). Examining the relationship between susceptibility alleles identified by GWAS and specific molecular alterations can help elucidate the function of these alleles and provide insights into whether susceptibility alleles are truly causal. Although there are challenges, molecular pathological epidemiology has unique strengths, and can provide insights into the pathogenic process and help optimise personalised prevention and therapy. In this review, we overview this relatively new field of research and discuss measures to overcome challenges and move this field forward.
C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA.
[Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ogino, Shuji; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Canc Epidemiol Program, Boston, MA USA.
[Ogino, Shuji; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Dana Farber Harvard Canc Ctr, Gastrointestinal Malignancies Program, Boston, MA USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Fuchs, Charles S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Pathol, 44 Binney St,Room JF 215C, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
FU U.S. National Institute of Health [P01 CA87969, P01 CA55075, P50
CA127003, R01 CA137178, K07 CA122826, R01 CA151993]
FX This work was supported by U.S. National Institute of Health (P01
CA87969, to S. E. Hankinson; P01 CA55075, to W. C. Willett; P50
CA127003, to CSF; R01 CA137178, to ATC; K07 CA122826, to SO; and R01
CA151993, to SO).
NR 308
TC 199
Z9 202
U1 8
U2 39
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD MAR
PY 2011
VL 60
IS 3
BP 397
EP 411
DI 10.1136/gut.2010.217182
PG 15
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 716LJ
UT WOS:000286969800019
PM 21036793
ER
PT J
AU Sinner, MF
Lubitz, SA
Pfeufer, A
Makino, S
Beckmann, BM
Lunetta, KL
Steinbeck, G
Perz, S
Rahman, R
Sonni, A
Greenberg, SM
Furie, KL
Wichmann, HE
Meitinger, T
Peters, A
Benjamin, EJ
Rosand, J
Ellinor, PT
Kaab, S
AF Sinner, Moritz F.
Lubitz, Steven A.
Pfeufer, Arne
Makino, Seiko
Beckmann, Britt-Maria
Lunetta, Kathryn L.
Steinbeck, Gerhard
Perz, Siegfried
Rahman, Rosanna
Sonni, Akshata
Greenberg, Steven M.
Furie, Karen L.
Wichmann, H. -Erich
Meitinger, Thomas
Peters, Annette
Benjamin, Emelia J.
Rosand, Jonathan
Ellinor, Patrick T.
Kaeaeb, Stefan
TI Lack of replication in polymorphisms reported to be associated with
atrial fibrillation
SO HEART RHYTHM
LA English
DT Article
DE Atrial fibrillation; Arrhythmia; Genetics; Single nucleotide
polymorphism; Replication; Meta-analysis
ID GENOME-WIDE ASSOCIATION; GENETIC SUSCEPTIBILITY; FAMILIAL AGGREGATION;
CHROMOSOME 4Q25; COMMON VARIANTS; CHANNEL GENES; HEART-DISEASE;
RISK-FACTORS; LONE; POPULATION
AB BACKGROUND Atrial fibrillation (AF) is the most common sustained arrhythmia and has a substantial heritable component. Numerous associations between single nucleotide polymorphisms (SNPs) and AF have been described, but few have been replicated.
OBJECTIVE We sought to systematically replicate SNPs that are reported to be associated with AF in two large study samples of European descent.
METHODS We searched PubMed for studies reporting associations between SNPs and AF published before July 1, 2007. SNPs were genotyped in two independent case-control samples from Germany and the United States. Associations between SNPs and AF were assessed using logistic regression models adjusting for age, sex, and hypertension. A meta-analysis of the results from the two studies was performed.
RESULTS We identified 21 SNPs and the angiotensin-converting enzyme insertion/deletion polymorphism that were reported to be associated with AF in the literature. Nine of these genetic variants were not represented on common genome-wide SNP arrays. We successfully genotyped 21 of these 22 variants in 2,145 cases with AF from the German Competence Network for Atrial Fibrillation and 4,073 controls from the KORA S4 study and 16 variants in 790 cases and 1,330 controls from the Massachusetts General Hospital. None of the SNPs replicated in independent populations with AF.
CONCLUSION Our results suggest that previously reported associations to AF were likely false positives and highlight the need for systematic replication of genetic associations in large, independent cohorts to accurately detect variants associated with disease.
C1 [Sinner, Moritz F.; Beckmann, Britt-Maria; Steinbeck, Gerhard; Kaeaeb, Stefan] LMU Munchen, Univ Hosp Grosshadern, Dept Med 1, D-81366 Munich, Germany.
[Sinner, Moritz F.; Lubitz, Steven A.; Makino, Seiko; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Lubitz, Steven A.; Meitinger, Thomas] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Pfeufer, Arne; Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, Munich, Germany.
[Pfeufer, Arne] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Perz, Siegfried] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Neuherberg, Germany.
[Rahman, Rosanna; Sonni, Akshata; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA.
[Rahman, Rosanna; Sonni, Akshata; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Wichmann, H. -Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Wichmann, H. -Erich] LMU Munchen, IBE, Chair Epidemiol, D-81366 Munich, Germany.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Whitaker Cardiovasc Inst,Cardiol Div, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Whitaker Cardiovasc Inst,Prevent Med Div, Boston, MA 02118 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
RP Kaab, S (reprint author), LMU Munchen, Klinikum Grosshadern, Dept Med 1, D-81366 Munich, Germany.
EM Stefan.Kaab@med.uni-muenchen.de
RI Kaab, Stefan/H-3915-2012; Pfeufer, Arne/B-6634-2013; Peters,
Annette/A-6117-2011; Meitinger, Thomas/O-1318-2015;
OI Lunetta, Kathryn/0000-0002-9268-810X; Benjamin,
Emelia/0000-0003-4076-2336
FU LMU [577/569]; German National Genome Research Network NGFN [01 GS 0499,
01 GS 0838]; German Federal Ministry of research [01 EZ 0874]; German
Competence Network on AF (AFNET) [01 GI 0204/N]; Leducq Foundation
[07-CVD 03]; LMU Excellence Initiative; BMBF German Federal Ministry of
research [01EZ0874]; Deane Institute for Integrative Research in Atrial
Fibrillation and Stroke; National Institutes of Health [R01NS059727,
5P50NS051343, T32HL007575, R01HL092577]; BMBF; State of Bavaria
FX MF Sinner, SA Lubitz, PT Ellinor, and S Kaab contributed equally to this
study. This study was funded by an LMU Research Grant FoFoLe 577/569 to
Dr. Sinner; the German National Genome Research Network NGFN 01 GS 0499,
01 GS 0838, German Federal Ministry of research 01 EZ 0874, German
Competence Network on AF (AFNET) 01 GI 0204/N, Leducq Foundation 07-CVD
03, and LMU Excellence Initiative to Dr. Kaab; the German National
Genome Research Network NGFN 01GR0803 and the BMBF German Federal
Ministry of research 01EZ0874 to Dr. Pfeufer; the Deane Institute for
Integrative Research in Atrial Fibrillation and Stroke to Dr. Ellinor;
and the National Institutes of Health to Dr. Rosand (R01NS059727), Dr.
Furie (5P50NS051343), Dr. Lubitz (T32HL007575), and Drs. Ellinor and
Benjamin (R01HL092577). The KORA platform is funded by the BMBF and by
the State of Bavaria.
NR 48
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U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD MAR
PY 2011
VL 8
IS 3
BP 403
EP 409
DI 10.1016/j.hrthm.2010.11.003
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 726PA
UT WOS:000287736200018
PM 21056700
ER
PT J
AU Martins, PN
Chang, S
Mahadevapa, B
Martins, AB
Sheiner, P
AF Martins, Paulo N.
Chang, Sue
Mahadevapa, Basant
Martins, Ann-Britt
Sheiner, Patricia
TI Liver grafts from selected older donors do not have significantly more
ischaemia reperfusion injury
SO HPB
LA English
DT Article
DE liver; transplantation; ischaemia reperfusion injury; outcomes; aging
ID SINGLE-CENTER EXPERIENCE; HEAT-SHOCK RESPONSE; EXTENDED CRITERIA; COLD
ISCHEMIA; RISK-FACTORS; ORGAN-TRANSPLANTATION; PRIMARY NONFUNCTION;
IMMUNE-RESPONSE; AGE; SURVIVAL
AB Background:
There is a general concern that aged organs are more susceptible to ischaemia. In the light of recent proposals to change the liver allocation system by expanding regional sharing, it is feared that increased cold ischaemia time of grafts from older donors may reduce graft survival. The aim of this study was to correlate donor age and the patterns of ischaemia reperfusion injury and synthetic function early after liver transplantation.
Methods:
We performed a retrospective study of first transplants using a single-centre electronic database. Patterns of liver injury (based on transaminases and post-reperfusion biopsy), synthetic function (international normalized ratio [INR]), and graft and patient survival in recipients receiving liver grafts from donors aged >= 65 years (group 1, n = 50) were compared with equivalent patterns in a matched cohort of recipients transplanted with grafts from donors aged < 65 years (group 2, n = 50).
Results:
There was no significant difference in transaminase levels from day 0 to day 6 after transplantation. When groups 1 and 2 were subdivided into two subgroups based on the duration of graft cold ischaemia time (< 8 h and >= 8 h), there was no statistical difference in transaminase levels during the first 7 days. There were two cases (4%) of primary non-function in group 1 and one (2%) in group 2. Initial poor function did not differ significantly between the groups (26% vs. 24%; P = 0.81). In addition, there was no difference in histological changes in post-reperfusion biopsies (21% vs. 34%; P = 0.078) and rate of acute rejection episodes in the first year (30% vs. 32%; P = 0.99). There was no significant difference between groups 1 and 2 in 1-year patient and graft survivals (78% vs. 90% [P = 0.17]; 88% vs. 94% [P = 0.48], respectively).
Conclusions:
Judiciously selected livers from aged donors are not associated with major increased susceptibility to ischaemia reperfusion injury.
C1 [Martins, Paulo N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Ctr, Boston, MA 02114 USA.
[Chang, Sue; Mahadevapa, Basant; Martins, Ann-Britt; Sheiner, Patricia] New York Med Coll, Dept Surg, Div Hepatobiliary Surg & Transplantat, New York, NY USA.
RP Martins, PN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Ctr, 55 Fruit St, Boston, MA 02114 USA.
EM pnmartins@partners.org
NR 56
TC 9
Z9 11
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1365-182X
J9 HPB
JI HPB
PD MAR
PY 2011
VL 13
IS 3
BP 212
EP 220
DI 10.1111/j.1477-2574.2010.00275.x
PG 9
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 719VY
UT WOS:000287240800012
PM 21309940
ER
PT J
AU Kuijk, EW
Lopes, SMCDS
Geijsen, N
Macklon, N
Roelen, BAJ
AF Kuijk, Ewart W.
Lopes, Susana M. Chuva de Sousa
Geijsen, Niels
Macklon, Nick
Roelen, Bernard A. J.
TI The different shades of mammalian pluripotent stem cells
SO HUMAN REPRODUCTION UPDATE
LA English
DT Review
DE pluripotency; embryonic stem cells; epigenetics; germ cells; iPS cells
ID PRIMORDIAL GERM-CELLS; LEUKEMIA INHIBITORY FACTOR; PREIMPLANTATION MOUSE
EMBRYOS; CHROMATIN REMODELING COMPLEX; MARMOSET CALLITHRIX-JACCHUS;
EARLY LINEAGE SEGREGATION; LONG-TERM PROLIFERATION; PATERNAL
X-CHROMOSOME; SELF-RENEWAL; IN-VITRO
AB BACKGROUND: Pluripotent stem cells have been derived from a variety of sources such as from the inner cell mass of preimplantation embryos, from primordial germ cells, from teratocarcinomas and from male germ cells. The recent development of induced pluripotent stem cells demonstrates that somatic cells can be reprogrammed to a pluripotent state in vitro.
METHODS: This review summarizes our current understanding of the origins of mouse and human pluripotent cells. We pay specific attention to transcriptional and epigenetic regulation in pluripotent cells and germ cells. Furthermore, we discuss developmental aspects in the germline that seem to be of importance for the transition of germ cells towards pluripotency. This review is based on literature from the Pubmed database, using Boolean search statements with relevant keywords on the subject.
RESULTS: There are distinct molecular mechanisms involved in the generation and maintenance of the various pluripotent cell types. Furthermore, there are important similarities and differences between the different categories of pluripotent cells in terms of phenotype and epigenetic modifications. Pluripotent cell lines from various origins differ in growth characteristics, developmental potential, transcriptional activity and epigenetic regulation. Upon derivation, pluripotent stem cells generally acquire new properties, but they often also retain a 'footprint' of their tissue of origin.
CONCLUSIONS: In order to further our knowledge of the mechanisms underlying self-renewal and pluripotency, a thorough comparison between different pluripotent stem cell types is required. This will progress the use of stem cells in basic biology, drug discovery and future clinical applications.
C1 [Roelen, Bernard A. J.] Univ Utrecht, Fac Vet Med, Dept Farm Anim Hlth, NL-3584 CM Utrecht, Netherlands.
[Kuijk, Ewart W.; Macklon, Nick] Univ Med Ctr Utrecht, Dept Reprod Med & Gynaecol, Utrecht, Netherlands.
[Kuijk, Ewart W.; Geijsen, Niels] Hubrecht Inst KNAW, Utrecht, Netherlands.
[Lopes, Susana M. Chuva de Sousa] Leiden Univ, Med Ctr, Dept Anat & Embryol, Leiden, Netherlands.
[Geijsen, Niels] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA.
[Geijsen, Niels] Harvard Univ, Harvard Stem Cell Inst, Boston, MA USA.
[Macklon, Nick] Univ Southampton, Princess Anne Hosp, Div Dev Origins Adult Dis, Dept Obstet & Gynaecol, Southampton, Hants, England.
RP Roelen, BAJ (reprint author), Univ Utrecht, Fac Vet Med, Dept Farm Anim Hlth, Yalelaan 104, NL-3584 CM Utrecht, Netherlands.
EM b.a.j.roelen@uu.nl
OI Kuijk, Ewart/0000-0002-1385-6516
FU Nederlands Organization for Scientific Research [VENI 916.76.015]; Dutch
Science Organization NWO; National Institutes of Health
FX SCDSL was funded by the Nederlands Organization for Scientific Research
(VENI 916.76.015 grant), N.G. was funded by the Dutch Science
Organization NWO and the National Institutes of Health.
NR 216
TC 18
Z9 18
U1 1
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1355-4786
J9 HUM REPROD UPDATE
JI Hum. Reprod. Update
PD MAR-APR
PY 2011
VL 17
IS 2
BP 254
EP 271
DI 10.1093/humupd/dmq035
PG 18
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 723FH
UT WOS:000287491400010
PM 20705693
ER
PT J
AU Subramanian, S
Yates, M
Vandenbark, AA
Offner, H
AF Subramanian, Sandhya
Yates, Melissa
Vandenbark, Arthur A.
Offner, Halina
TI Oestrogen-mediated protection of experimental autoimmune
encephalomyelitis in the absence of Foxp3+regulatory T cells implicates
compensatory pathways including regulatory B cells
SO IMMUNOLOGY
LA English
DT Article
DE B cells; experimental autoimmune encephalomyelitis; Foxp3-DTR; Foxp3;
oestrogen
ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; PRODUCE
CXCL13; CUTTING EDGE; MICE; INDUCTION; TOLERANCE; ARTHRITIS; RESPONSES;
SEVERITY
AB P>Oestrogen (17 beta-oestradiol, E(2)) is a highly effective treatment for experimental autoimmune encephalomyelitis (EAE) that may potentiate Foxp3+ regulatory T (Treg) cells, which in turn limit the expansion of encephalitogenic T-cell specificities. To determine if Treg cells constitute the major non-redundant protective pathway for E(2), we evaluated E(2) protection of EAE after targeted deletion of Foxp3 expression in Foxp3-DTR mice. Unexpectedly, E(2)-treated Foxp3-deficient mice were completely protected against clinical and histological myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide-induced EAE before succumbing to diphtheria toxin-induced mortality. This finding indicated the presence of alternative E(2)-dependent EAE-protective pathways that could compensate for the lack of Treg cells. Further investigation revealed that E(2) treatment inhibited proliferation and expression of CCL2 and CXCL2, but enhanced secretion of interleukin-10 (IL-10) and IL-13 by MOG-35-55-specific spleen cells. These changes occurred concomitantly with increased expression of several chemokines and receptors, including CXCL13 and CXCR5, and the negative co-activation molecules, PD-L1 and B7.2, by B cells and dendritic cells. Furthermore, E(2) treatment resulted in higher percentages of spleen and lymph node T cells expressing IL-17, interferon-gamma and tumour necrosis factor-alpha, but with lower expression of CCR6, suggesting sequestration of MOG-35-55 peptide-specific T cells in peripheral immune organs. Taken together, these data suggest that E(2)-induced mechanisms that provide protection against EAE in the absence of Foxp3+ Treg cells include induction of regulatory B cells and peripheral sequestration of encephalitogenic T cells.
C1 [Subramanian, Sandhya; Yates, Melissa; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA.
[Yates, Melissa; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
[Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA.
RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM offnerva@ohsu.edu
FU National Institutes of Health [NS45445, NS49210]; National Multiple
Sclerosis Society [RG3405-C-6, FG1832-A-1]; Biomedical Laboratory R&D
Service, Department of Veterans' Affairs
FX The authors wish to thank Dr Sushmita Sinha for helpful discussions and
Ms Eva Niehaus for assistance with manuscript preparation. This work was
supported by National Institutes of Health grants NS45445 and NS49210;
National Multiple Sclerosis Society grant RG3405-C-6; and the Biomedical
Laboratory R&D Service, Department of Veterans' Affairs. Dr Melissa
Yates is a Postdoctoral Fellow of the National Multiple Sclerosis
Society and this work was supported in part by the National Multiple
Sclerosis Society Postdoctoral Fellowship FG1832-A-1.
NR 37
TC 23
Z9 27
U1 1
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD MAR
PY 2011
VL 132
IS 3
BP 340
EP 347
DI 10.1111/j.1365-2567.2010.03380.x
PG 8
WC Immunology
SC Immunology
GA 714WI
UT WOS:000286839300004
PM 21091909
ER
PT J
AU Marley, CS
Lerner, LB
Panagopoulos, G
Kavaler, E
AF Marley, Clara S.
Lerner, Lori B.
Panagopoulos, Georgia
Kavaler, Elizabeth
TI Personal, Professional and Financial Satisfaction among American Women
Urologists
SO INTERNATIONAL BRAZ J UROL
LA English
DT Article
DE urology; urologists; women; clinical practice
ID CAREER SATISFACTION; SURGICAL SUBSPECIALTY; GENDER-DIFFERENCES;
SURGEONS; PHYSICIANS
AB Purpose: Although nearly half of American medical school classes are comprised of women, less than 5% of female medical students enter the surgical subspecialties compared to nearly 20% of male students. Many women are concerned that a career in a surgical field will limit their personal choices. In an effort to evaluate if urology is conducive to a satisfying lifestyle, we surveyed all 365 board certified women urologists in the United States in 2007 to find out how satisfied they are with their choice of urology.
Materials and Methods: A 114 item anonymous survey was mailed to all 365 American Board Certified female urologists in 2007. Results were analyzed.
Results: Of the 244 women (69%) who responded, 86.8% (211) reported being satisfied with their decision to enter urology. Given the choice to repeat the decision, 81% (198) said that they would remain in medicine and 91.4% (222) would choose a surgical subspecialty again. The majority of respondents who stated they would choose a career outside of medicine also stated their family life had been significantly compromised by their career. Those who did not think their family life was compromised reported they would remain in medicine. There was a positive correlation between the level of satisfaction with the work itself and with income level (p = 0.006).
Conclusions: Despite the small number of women who choose a career in urology, the number of satisfied women indicates urology is a career conducive to having a balanced and fulfilling life; professionally, personally and financially.
C1 [Marley, Clara S.; Panagopoulos, Georgia; Kavaler, Elizabeth] Lenox Hill Hosp, Dept Urol, New York, NY 10075 USA.
[Lerner, Lori B.] VA Boston Healthcare Syst, W Roxbury, MA USA.
RP Marley, CS (reprint author), Lenox Hill Hosp, Dept Urol, 100 E 77th St, New York, NY 10075 USA.
EM ciaramarley@hotmail.com
NR 14
TC 3
Z9 3
U1 0
U2 2
PU BRAZILIAN SOC UROL
PI RIO DE JANEIRO
PA RUA BAMBINA, 153, RIO DE JANEIRO, 2251-050, BRAZIL
SN 1677-5538
J9 INT BRAZ J UROL
JI Int. Braz J Urol
PD MAR-APR
PY 2011
VL 37
IS 2
BP 187
EP 192
DI 10.1590/S1677-55382011000200005
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 773RF
UT WOS:000291325900013
PM 21557835
ER
PT J
AU Bleier, BS
Schlosser, RJ
AF Bleier, Benjamin S.
Schlosser, Rodney J.
TI Endoscopic anatomy of the postganglionic pterygopalatine innervation of
the posterolateral nasal mucosa
SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
LA English
DT Article; Proceedings Paper
CT 56th Annual Fall Scientific Meeting of the American-Rhinologic-Society
(ARS)
CY SEP 25-28, 2010
CL Boston, MA
SP Amer Rhinol Soc (ARS)
DE vidian neurectomy; vasomotor rhinitis; neurogenic rhinitis;
pterygopalatine fossa; parasympathetic innervation
ID VIDIAN NEURECTOMY; GANGLION EFFERENTS; CHRONIC RHINITIS
AB Background: Recent anatomic dissections have redefined the sinonasal parasympathetic pathway suggesting that individual rami project from the pterygopalatine ganglion (PPG) to innervate the nasal mucosa via multiple small nerve fascicles. The purpose of this study is correlate these anatomic descriptions with endoscopic findings and to define the pattern and location of the posterolateral neurovascular rami.
Methods: Eight cadaver heads were utilized for a total of 16 individual sides. A lateral nasal submucosal flap was elevated while preserving all neurovascular bundles perforating the palatine bone. All nerves were traced proximally to confirm their origin.
Results: Excluding the sphenopalatine foraminal contents, accessory posterolateral nerves were noted in 87.5%(14/16) of specimens, 50% (7/14) of which contained greater than one. All nerves could be traced directly to the PPG or greater palatine nerve. Of the 25 accessory nerves identified, the most common location was posterosuperior to the horizontal attachment of the inferior turbinate (40%, 10/25).
Conclusion: This study supports prior work suggesting that neurons project from the PPG via multiple individual postganglionic rami to supply the nasal mucosa. This new anatomic insight may be exploited to selectively lesion these nerve fascicles in patients with vasomotor rhinitis to improve outcomes while avoiding the morbidities associated with vidian neurectomy. (C) 2011 ARS-AAOA, LLC.
C1 [Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA.
[Schlosser, Rodney J.] Med Univ S Carolina, Charleston, SC 29425 USA.
RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA.
EM bleierb@gmail.com
NR 14
TC 8
Z9 8
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2042-6976
J9 INT FORUM ALLERGY RH
JI Int. Forum Allergy Rhinol.
PD MAR-APR
PY 2011
VL 1
IS 2
BP 113
EP 117
DI 10.1002/alr.20011
PG 5
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 007TW
UT WOS:000308912300007
PM 22287329
ER
PT J
AU Shima, K
Nosho, K
Baba, Y
Cantor, M
Meyerhardt, JA
Giovannucci, EL
Fuchs, CS
Ogino, S
AF Shima, Kaori
Nosho, Katsuhiko
Baba, Yoshifumi
Cantor, Mami
Meyerhardt, Jeffrey A.
Giovannucci, Edward L.
Fuchs, Charles S.
Ogino, Shuji
TI Prognostic significance of CDKN2A (p16) promoter methylation and loss of
expression in 902 colorectal cancers: cohort study and literature review
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE colon cancer; CDKN2A; epigenetics; hypermethylation; prognosis; clinical
outcome; survival
ID POPULATION-BASED SERIES; MICROSATELLITE INSTABILITY; COLON-CANCER;
PHENOTYPE CIMP; CLINICOPATHOLOGICAL FEATURES; LINE-1 HYPOMETHYLATION;
INVERSE CORRELATIONS; SHORTER SURVIVAL; DNA METHYLATION; POOR-PROGNOSIS
AB A cyclin-dependent kinase inhibitor CDKN2A (p16/Ink4a) is a tumor suppressor and upregulated in cellular senescence. CDKN2A promoter methylation and gene silencing are associated with the CpG island methylator phenotype ((IMP) in colon cancer. However, prognostic significance of CDKN2A methylation or loss of CDKN2A (p16) expression independent of CIMP status remains uncertain. Using a database of 902 colorectal cancers in 2 independent cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study), we quantified CDKN2A promoter methylation and detected hypermethylation in 269 tumors (30%). By immunohistochemistry, we detected loss of CDKN2A (p16) expression in 25% (200/804) of tumors. We analyzed for LINE-1 hypomethylation and hypermethylation at 7 (IMP-specific CpG islands (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); microsatellite instability (MSI); KRAS, BRAF and PIK3CA mutations; and expression of TP53 (p53), CTNNB1 (beta-catenin), CDKN1A (p21), CDKN1B (p27), CCND1 (cyclin D1), FASN (fatty acid synthase) and PTGS2 (cyclooxygenase-2). CDKN2A promoter methylation and loss of CDKN2A (p16) were associated with shorter overall survival in univariate Cox regression analysis [hazard ratio (HR): 1.36, 95% Cl: 1.10-1.66, p = 0.0036 for CDKN2A methylation; HR: 1.30, 95% Cl: 1.03-1.63, p = 0.026 for CDKN2A (p16) loss] but not in multivariate analysis that adjusted for clinical and tumor variables, including (IMP, MSI and LINE-1 methylation. Neither CDKN2A promoter methylation nor toss of CDKN2A (p16) was associated with colorectal cancer-specific mortality in uni- or multivariate analysis. Despite its well-established role in carcinogenesis, CDKN2A (p16) promoter methylation or loss of expression in colorectal cancer is not independently associated with patient prognosis.
C1 [Ogino, Shuji] Harvard Univ, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch,Dept Med Oncol, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Harvard Univ, Ctr Mol Oncol Pathol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch,Dept Med Oncol, 44 Binney St,Room JF-215C, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
FU U.S. National Institute of Health [P01 CA87969, P01 CA55075, P50
CA127003, K07 CA122826]; The Bennett Family Fund; Entertainment Industry
Foundation through National Colorectal Cancer Research Alliance; Japan
Society for Promotion of Science
FX Grant sponsor: U.S. National Institute of Health; Grant numbers: P01
CA87969, P01 CA55075, P50 CA127003, K07 CA122826; Grant sponsors: The
Bennett Family Fund, the Entertainment Industry Foundation through
National Colorectal Cancer Research Alliance, the Japan Society for
Promotion of Science; This work was supported by U.S. National Institute
of Health (NIH) grants (to S.H., W.W., C.S.F. and S.O.), and in part by
grants from The Bennett Family Fund and from the Entertainment Industry
Foundation through National Colorectal Cancer Research Alliance. K.N.
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 NCI or NIH. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. No conflicts of
interest exist.
NR 61
TC 43
Z9 46
U1 1
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2011
VL 128
IS 5
BP 1080
EP 1094
DI 10.1002/ijc.25432
PG 15
WC Oncology
SC Oncology
GA 716HS
UT WOS:000286960300008
PM 20473920
ER
PT J
AU Yang, HY
Magpayo, N
Held, KD
AF Yang, Hongying
Magpayo, Nicole
Held, Kathryn D.
TI Targeted and non-targeted effects from combinations of low doses of
energetic protons and iron ions in human fibroblasts
SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
LA English
DT Article
DE targeted effects; non-targeted effects; energetic protons; iron ions
ID MEDIATED INTERCELLULAR COMMUNICATION; INDUCED GENOMIC INSTABILITY;
IRRADIATED GLIOMA-CELLS; C3H 10T(1)/(2) CELLS; BYSTANDER RESPONSES;
IONIZING-RADIATION; NITRIC-OXIDE; ADAPTIVE RESPONSE; CELLULAR
COMMUNICATION; UNIRRADIATED CELLS
AB Purpose: In space, astronauts are exposed to mixed radiation fields consisting of energetic protons and high atomic number, high energy (HZE) particles at low dose rates. Therefore, it is critical to understand effects of combinations of low doses of different radiation types at the cellular level.
Materials and methods: AG01522 normal human skin fibroblasts and a transwell insert co-culture system were used. Irradiations used were 1 GeV/amu (gigaelectron volt/atomic mass unit) protons and 1 GeV/amu iron (Fe) ions. DNA damage was measured as micronucleus (MN) formation and p53 binding protein 1 (53BP1) foci induction.
Results: The same magnitude of DNA damage was induced in cells sequentially exposed to 1 cGy protons and 1 cGy Fe ions as in cells irradiated with either protons or Fe ions alone. The same magnitude of DNA damage was also observed in non-irradiated bystander cells sharing medium with cells irradiated with either 1 cGy protons or iron ions or protons plus iron ions. However, when the 'bystander' cells were exposed to 1 cGy protons up to 3 h before co-culture with Fe ion-irradiated cells, no DNA damage in the 'bystander' cells was observed.
Conclusions: These data provide the first evidence of interactions between targeted and non-targeted DNA damage caused by dual exposure to low doses of energetic protons and iron ions.
C1 [Yang, Hongying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA.
RP Yang, HY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, R4406,Bldg 149,CNY, Charlestown, MA 02129 USA.
EM hyang5@partners.org
FU NSRL; Medical and Biology Departments of Brookhaven National Laboratory;
NASA [NNX07AE40G]
FX The authors acknowledge the excellent assistance from the support
personnel at NSRL and in the Medical and Biology Departments of
Brookhaven National Laboratory. In particular, the authors thank Drs
Adam Rusek, I-Hung Chiang and Michael Sivertz for their invaluable
physics and dosimetry support at NSRL. The authors thank Drs Kevin M.
Prise, Howard L. Liber and Robert W. Redmond for many helpful
discussions. This research was supported by NASA grant # NNX07AE40G.
NR 49
TC 12
Z9 12
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0955-3002
J9 INT J RADIAT BIOL
JI Int. J. Radiat. Biol.
PD MAR
PY 2011
VL 87
IS 3
BP 311
EP 319
DI 10.3109/09553002.2010.537431
PG 9
WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Nuclear Science &
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 728GI
UT WOS:000287862200008
PM 21158498
ER
PT J
AU Fan, BJ
Wang, DY
Pasquale, LR
Haines, JL
Wiggs, JL
AF Fan, Bao Jian
Wang, Dan Yi
Pasquale, Louis R.
Haines, Jonathan L.
Wiggs, Janey L.
TI Genetic Variants Associated with Optic Nerve Vertical Cup-to-Disc Ratio
Are Risk Factors for Primary Open Angle Glaucoma in a US Caucasian
Population
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID INTRAOCULAR-PRESSURE; OCULAR HYPERTENSION; HERITABILITY; HEAD; SIZE;
EYE; ANOPHTHALMIA; PREVALENCE; EXPRESSION; PREVENTION
AB PURPOSE. Genetically complex disorders, such as primary open angle glaucoma (POAG), may include highly heritable quantitative traits as part of the overall phenotype, and mapping genes influencing the related quantitative traits may effectively identify genetic risk factors predisposing to the complex disease. Recent studies have identified SNPs associated with optic nerve area and vertical cup-to-disc ratio (VCDR). The purpose of this study was to evaluate the association between these SNPs and POAG in a US Caucasian case-control sample.
METHODS. Five SNPs previously associated with optic disc area, or VCDR, were genotyped in 539 POAG cases and 336 controls. Genotype data were analyzed for single SNP associations and SNP interactions with VCDR and POAG.
RESULTS. SNPs associated with VCDR rs1063192 (CDKN2B) and rs10483727 (SIX1/SLX6) were also associated with POAG (P = 0.0006 and P = 0.0043 for rs1063192 and rs10483727, respectively). rs1063192, associated with smaller VCDR, had a protective effect (odds ratio [OR] = 0.73; 95% confidence interval [CH 0.58-0.90), whereas rs10483727, associated with larger VCDR, increased POAG risk (OR = 1.33; 95% CI, 1.08-1.65). POAG risk associated with increased VCDR was significantly influenced by the C allele of rs1900004 (ATOH7), associated with increased optic nerve area (P-interaction = 0.025; OR = 1.89; 95% CI, 1.22-2.94).
CONCLUSIONS. Genetic variants influencing VCDR are associated with POAG in a US Caucasian population. Variants associated with optic nerve area are not independently associated with disease but can influence the effects of VCDR variants suggesting that increased optic disc area can significantly contribute to POAG risk when coupled with risk factors controlling VCDR. (Incest Ophthalmol Vis Sci.. 2011; 52:1788-1792) DOI:10.1167/iovs.10-6339
C1 [Fan, Bao Jian; Wang, Dan Yi; Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
[Haines, Jonathan L.] Vanderbilt Univ Sch Med, Ctr Human Genet Res, Nashville, TN USA.
RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM janey_wiggs@meei.harvard.edu
RI Haines, Jonathan/C-3374-2012;
OI Fan, Baojian/0000-0002-6851-2737
FU National Institutes of Health [EY015872, P30EY014104]; Massachusetts
Lions Eye Research Fund; Research to Prevent Blindness
FX Supported in part by National Institutes of Health Grants EY015872 and
P30EY014104, the Massachusetts Lions Eye Research Fund, and Research to
Prevent Blindness.
NR 28
TC 61
Z9 63
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2011
VL 52
IS 3
BP 1788
EP 1792
DI 10.1167/iovs.10-6339
PG 5
WC Ophthalmology
SC Ophthalmology
GA 742SR
UT WOS:000288965300071
PM 21398277
ER
PT J
AU Kim, EH
Bird, JA
Kulis, M
Laubach, S
Pons, L
Shreffler, W
Steele, P
Kamilaris, J
Vickery, B
Burks, AW
AF Kim, Edwin H.
Bird, J. Andrew
Kulis, Michael
Laubach, Susan
Pons, Laurent
Shreffler, Wayne
Steele, Pamela
Kamilaris, Janet
Vickery, Brian
Burks, A. Wesley
TI Sublingual immunotherapy for peanut allergy: Clinical and immunologic
evidence of desensitization
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Peanut allergy; sublingual immunotherapy; desensitization; food allergy
ID ANAPHYLACTIC REACTIONS; FOOD ALLERGY; DOUBLE-BLIND; KIWI FRUIT; EXTRACT;
FATALITIES; MECHANISMS; CELLS
AB Background: There are no treatments currently available for peanut allergy. Sublingual immunotherapy (SLIT) is a novel approach to the treatment of peanut allergy.
Objective: We sought to investigate the safety, clinical effectiveness, and immunologic changes with SLIT in children with peanut allergy.
Methods: In this double-blind, placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge.
Results: Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median, 1,710 vs 85 mg; P = .011). Mechanistic studies demonstrated a decrease in skin prick test wheal size (P = .020) and decreased basophil responsiveness after stimulation with 10(-2) mu g/mL (P = .009) and 10(-3) mu g/mL (P = .009) of peanut. Peanut-specific IgE levels increased over the initial 4 months (P = .002) and then steadily decreased over the remaining 8 months (P = .003), whereas peanut-specific IgG4 levels increased during the 12 months (P = .014). Lastly, IL-5 levels decreased after 12 months (P = .015). No statistically significant changes were found in IL-13 levels, the percentage of regulatory T cells, or IL-10 and IFN-gamma production.
Conclusion: Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy, with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance. (J Allergy Clin Immunol 2011;127:640-6.)
C1 [Kim, Edwin H.; Bird, J. Andrew; Kulis, Michael; Laubach, Susan; Pons, Laurent; Steele, Pamela; Kamilaris, Janet; Vickery, Brian; Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA.
[Shreffler, Wayne] Massachusetts Gen Hosp, Food Allergy Ctr MGH, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
RP Burks, AW (reprint author), Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Box 2644, Durham, NC 27710 USA.
EM wesley.burks@duke.edu
OI Bird, John/0000-0003-3772-6078
FU National Institutes of Health [NCCAM R01-AT004435-03, 5T32-AI007062-32];
American Academy of Allergy, Asthma & Immunology/Food Allergy
Initiative; Wallace Research Foundation [WRF2010.01]; National Center
for Research Resources (NCRR), a component of the National Institutes of
Health (NIH) [UL1RR024128]; NIH Roadmap for Medical Research; NIAID;
NIH/NIAID; Thrasher Research Fund; American Lung Association; Cephalon;
Anaphylaxis Network (FAAN); Wallace Research Foundation
FX Supported by the National Institutes of Health: NCCAM R01-AT004435-03,
5T32-AI007062-32; the American Academy of Allergy, Asthma &
Immunology/Food Allergy Initiative Howard Gittis Memorial 3rd Year/4th
Year Fellowship/Instructor Award (J. A. B.); and the Wallace Research
Foundation (WRF2010.01). Additional support for the project was provided
by grant UL1RR024128 from the National Center for Research Resources
(NCRR), a component of the National Institutes of Health (NIH) and the
NIH Roadmap for Medical Research, and its contents are solely the
responsibility of the authors and do not necessarily represent the
official view of NCRR or NIH.; J. A. Bird has received research support
from the American Academy of Allergy, Asthma & Immunology and the Food
Allergy Initiative. M. Kulis has received research support from the
National Institutes of Health (NIH)/National Institute of Allergy and
Infectious Diseases (NIAID). W. Shreffler has received research support
from the NIAID. B. Vickery has received research support from the
NIH/NIAID, Thrasher Research Fund, American Lung Association, and
Cephalon. A. W. Burks has consulted for ActoGeniX NV, Intelliject,
McNeil Nutritionals, Novartis, and Schering-Plough; is a minority
stockholder in Allertein and MastCell, Inc; is on an advisory board for
Dannon Co Probiotics; is on an expert panel for Nutricia; has received
research support from the NIH, Food Allergy and Anaphylaxis Network
(FAAN), and Wallace Research Foundation; and is on the medical board of
directors of FAAN. The rest of the authors have declared that they have
no conflict of interest.
NR 27
TC 144
Z9 150
U1 2
U2 18
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2011
VL 127
IS 3
BP 640
EP U153
DI 10.1016/j.jaci.2010.12.1083
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 730FG
UT WOS:000288018400013
PM 21281959
ER
PT J
AU Marshall-Berenz, EC
Vujanovic, AA
Zvolensky, MJ
AF Marshall-Berenz, Erin C.
Vujanovic, Anka A.
Zvolensky, Michael J.
TI Main and interactive effects of a nonclinical panic attack history and
distress tolerance in relation to PTSD symptom severity
SO JOURNAL OF ANXIETY DISORDERS
LA English
DT Article
DE PTSD; Distress tolerance; Panic attacks; Anxiety
ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY;
PSYCHOMETRIC PROPERTIES; ANXIETY DISORDERS; SCALE; TRAUMA;
QUESTIONNAIRE; RELIABILITY; VALIDATION; EXPOSURE
AB The current study investigated the main and interactive effects of a nonclinical panic attack history and distress tolerance in relation to PTSD symptoms. The sample consisted of 91 adults (62.6% women; M(age) = 23.45, SD = 9.56) who met DSM-IV criteria for trauma exposure, 53.8% of whom met criteria for a recent (past 2 years) history of nonclinical panic attacks. Results indicated that distress tolerance, as measured by the Distress Tolerance Scale (Simons & Gaher, 2005), was significantly related to all PTSD symptom clusters, and a nonclinical panic attack history was significantly related to PTSD re-experiencing and hyperarousal symptoms. The interaction of a nonclinical panic attack history and distress tolerance significantly predicted unique variance in only PTSD hyperarousal symptoms. Implications and future directions are discussed for the role of nonclinical panic attacks and distress tolerance in PTSD symptom expression. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Marshall-Berenz, Erin C.; Zvolensky, Michael J.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA.
[Vujanovic, Anka A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA.
[Vujanovic, Anka A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Zvolensky, MJ (reprint author), Univ Vermont, Dept Psychol, 2 Colchester Ave,John Dewey Hall, Burlington, VT 05405 USA.
EM Michael.Zvolensky@uvm.edu
FU NIDA NIH HHS [1 R01 DA027533-01, R01 DA027533]; NIMH NIH HHS [1 F31
MH080453-01A1, 1 R01 MH076629-01, F31 MH080453, R01 MH076629, R01
MH076629-01A2]
NR 43
TC 12
Z9 12
U1 5
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0887-6185
J9 J ANXIETY DISORD
JI J. Anxiety Disord.
PD MAR
PY 2011
VL 25
IS 2
BP 185
EP 191
DI 10.1016/j.janxdis.2010.09.001
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 716YJ
UT WOS:000287009100005
PM 20888732
ER
PT J
AU Wu, XX
Patki, A
Lara-Castro, C
Cui, XQ
Zhang, K
Walton, RG
Osier, MV
Gadbury, GL
Allison, DB
Martin, M
Garvey, WT
AF Wu, Xuxia
Patki, Amit
Lara-Castro, Cristina
Cui, Xiangqin
Zhang, Kui
Walton, R. Grace
Osier, Michael V.
Gadbury, Gary L.
Allison, David B.
Martin, Mitchell
Garvey, W. Timothy
TI Genes and biochemical pathways in human skeletal muscle affecting
resting energy expenditure and fuel partitioning
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE microarray; human; skeletal muscle; G protein-coupled receptor;
ubiquitin; protein phosphatase 2A; mitochondrial function; respiratory
quotient
ID BODY-WEIGHT GAIN; BROWN ADIPOSE-TISSUE; BETA-ADRENERGIC-BLOCKADE;
PROTEIN MESSENGER-RNA; METABOLIC-RATE; UNCOUPLING PROTEINS; RESPIRATORY
QUOTIENT; UBIQUITIN-PROTEASOME; INSULIN-RESISTANCE; DIABETES-MELLITUS
AB Wu X, Patki A, Lara-Castro C, Cui X, Zhang K, Walton RG, Osier MV, Gadbury GL, Allison DB, Martin M, Garvey WT. Genes and biochemical pathways in human skeletal muscle affecting resting energy expenditure and fuel partitioning. J Appl Physiol 110: 746-755, 2011. First published November 25, 2010; doi:10.1152/japplphysiol.00293.2010.-Genes influencing resting energy expenditure (REE) and respiratory quotient (RQ) represent candidate genes for obesity and the metabolic syndrome because of the involvement of these traits in energy balance and substrate oxidation. We aim to explore the molecular basis for individual variation in REE and fuel partitioning as reflected by RQ. We performed microarray studies in human vastus lateralis muscle biopsies from 40 healthy subjects with measured REE and RQ values. We identified 2,392 and 1,115 genes significantly correlated with REE and RQ, respectively. Genes correlated with REE and RQ encompass a broad array of functions, including carbohydrate and lipid metabolism, gene expression, mitochondrial processes, and membrane transport. Microarray pathway analysis revealed that REE was positively correlated with upregulation of G protein-coupled receptor signaling (meet criteria/total genes: 65 of 283) involved in autonomic nervous system functions, including those receptors mediating adrenergic, dopamine, gamma-aminobutyric acid (GABA), neuropeptide Y (NPY), and serotonin action (meet criteria/total genes: 46 of 176). Reduced REE was associated with an increase in genes participating in ubiquitin-proteasome-dependent proteolytic pathways (58 of 232). Serine-type peptidase activity (9 of 76) was positively correlated with RQ, while genes involved in the protein phosphatase type 2A complex (4 of 9), mitochondrial function and cellular respiration (38 of 315), and unfolded protein binding (19 of 97) were associated with reduced RQ values and a preference for lipid fuel metabolism. Individual variations in whole body REE and RQ are regulated by differential expressions of specific genes and pathways intrinsic to skeletal muscle.
C1 [Wu, Xuxia; Lara-Castro, Cristina; Walton, R. Grace; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Patki, Amit; Cui, Xiangqin; Zhang, Kui; Allison, David B.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Osier, Michael V.] Rochester Inst Technol, Sch Biol & Med Sci, Rochester, NY 14623 USA.
[Gadbury, Gary L.] Kansas State Univ, Dept Stat, Manhattan, KS 66506 USA.
[Martin, Mitchell] Roche, Mol Med Labs, Nutley, NJ USA.
RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 1675 Univ Blvd, Birmingham, AL 35294 USA.
EM garveyt@uab.edu
OI Cui, Xiangqin/0000-0003-0621-9313; Allison, David/0000-0003-3566-9399
FU National Institutes of Health [DK-038764, DK-083562, HL-055782];
American Heart Association; Department of Veterans Affairs; University
of Alabama at Birmingham (UAB) Center for Clinical and Translational
Science [UL1-RR-025777]; UAB Nutrition and Obesity Research Center
[P30-DK-56336]; UAB Diabetes Research and Training Center
[P60-DK-079626]
FX This work was supported by grants from the National Institutes of Health
(DK-038764, DK-083562, and HL-055782 to W. T. Garvey), by an American
Heart Association Beginning Grant-in-Aid (X. Wu), and by the Merit
Review program of the Department of Veterans Affairs (W. T. Garvey). We
gratefully acknowledge the support of the research core facilities of
the University of Alabama at Birmingham (UAB) Center for Clinical and
Translational Science (UL1-RR-025777), the UAB Nutrition and Obesity
Research Center (P30-DK-56336), and the UAB Diabetes Research and
Training Center (P60-DK-079626).
NR 78
TC 7
Z9 7
U1 0
U2 9
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
EI 1522-1601
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD MAR
PY 2011
VL 110
IS 3
BP 746
EP 755
DI 10.1152/japplphysiol.00293.2010
PG 10
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 731RN
UT WOS:000288127100023
PM 21109598
ER
PT J
AU Porterfield, JE
Larson, ER
Jenkins, JT
Escobedo, D
Valvano, JW
Pearce, JA
Feldman, MD
AF Porterfield, John E.
Larson, Erik R.
Jenkins, James T.
Escobedo, Daniel
Valvano, Jonathan W.
Pearce, John A.
Feldman, Marc D.
TI Left ventricular epicardial admittance measurement for detection of
acute LV dilation
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE early detection of heart failure; bioimpedance; left ventricular
preload; end-diastolic volume; conductance
ID CHRONIC HEART-FAILURE; CARDIAC-RESYNCHRONIZATION; IMPLANTABLE
DEFIBRILLATOR; CONDUCTANCE CATHETER; HEMODYNAMIC MONITOR; VOLUME;
SYSTEM; ALPHA; RESISTIVITY; FEASIBILITY
AB There are two implanted heart failure warning systems incorporated into biventricular pacemakers/automatic implantable cardiac defibrillators and tested in clinical trials: right heart pressures, and lung conductance measurements. However, both warning systems postdate measures of the earliest indicator of impending heart failure: left ventricular (LV) volume. There are currently no proposed implanted technologies that can perform LV blood volume measurements in humans. We propose to solve this problem by incorporating an admittance measurement system onto currently deployed biventricular and automatic implantable cardiac defibrillator leads. This study will demonstrate that an admittance measurement system can detect LV blood conductance from the epicardial position, despite the current generating and sensing electrodes being in constant motion with the heart, and with dynamic removal of the myocardial component of the returning voltage signal. Specifically, in 11 pigs, it will be demonstrated that 1) a physiological LV blood conductance signal can be derived; 2) LV dilation in response to dose-response intravenous neosynephrine can be detected by blood conductance in a similar fashion to the standard of endocardial crystals when admittance is used, but not when only traditional conductance is used; 3) the physiological impact of acute left anterior descending coronary artery occlusion and resultant LV dilation can be detected by blood conductance, before the anticipated secondary rise in right ventricular systolic pressure; and 4) a pleural effusion simulated by placing saline outside the pericardium does not serve as a source of artifact for blood conductance measurements.
C1 [Jenkins, James T.; Escobedo, Daniel; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78248 USA.
[Porterfield, John E.; Larson, Erik R.; Valvano, Jonathan W.; Pearce, John A.] Univ Texas Austin, Austin, TX 78712 USA.
[Jenkins, James T.; Escobedo, Daniel; Feldman, Marc D.] S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA.
RP Feldman, MD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Rm 5-642,7703 Floyd Curl Dr, San Antonio, TX 78248 USA.
EM feldmanm@uthscsa.edu
FU National Institutes of Health [R21 HL 079926]; National Center for
Research Resources [UL 1RR025767]; University of Texas Health Science
Center in San Antonio (Biscoe Division of Cardiology and South Texas
Technology Management); Medtronic Corporation (Minneapolis, MN)
FX This study was supported in part by National Institutes of Health Grant
R21 HL 079926, Grant UL 1RR025767 from the National Center for Research
Resources, and grants from the University of Texas Health Science Center
in San Antonio (Biscoe Division of Cardiology and South Texas Technology
Management). Research was funded in part by a grant given by Medtronic
Corporation (Minneapolis, MN).
NR 33
TC 3
Z9 3
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD MAR
PY 2011
VL 110
IS 3
BP 799
EP 806
DI 10.1152/japplphysiol.01047.2010
PG 8
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 731RN
UT WOS:000288127100029
PM 21148342
ER
PT J
AU Sabatini, ME
Wolkovich, AM
Macklin, EA
Wright, DL
Souter, I
Toth, TL
AF Sabatini, Mary E.
Wolkovich, Ann M.
Macklin, Eric A.
Wright, Diane L.
Souter, Irene
Toth, Thomas L.
TI Pronuclear embryo cryopreservation experience: outcomes for reducing the
risk of ovarian hyperstimulation syndrome and for fertility preservation
in cancer patients
SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
LA English
DT Article
DE Ovarian hyperstimulation syndrome; OHSS; IVF; Cancer; Fertility
preservation
ID IN-VITRO FERTILIZATION; ELECTIVE CRYOPRESERVATION; SUBSEQUENT TRANSFER;
PREGNANCY RATE; FRESH EMBRYOS; PREVENTION; WOMEN; OHSS; EFFICIENCY;
PROTOCOL
AB Purpose To evaluate pregnancy rate (PR) and live birth rate (LBR) after freezing pronuclear (PN) embryos for two purposes: to reduce the risk of ovarian hyperstimulation syndrome (OHSS) and to bank embryos for cancer patients anticipating gametotoxic chemotherapy/radiotherapy.
Methods Data from 3,621 consecutive IVF cycles were retrospectively analyzed. PN freezing was offered to patients at risk for OHSS and for those wishing to preserve fertility prior to cancer therapy. Primary outcomes evaluated were PR and LBR. Outcomes were compared to patients who underwent fresh embryo transfer (ET) in 2006.
Results Sixty-six patients froze PN embryos. Thirty-eight were at risk for OHSS. The LBR was 34.3% after one transfer, and 51.4% after a mean of 1.4 transfers. Twenty-eight cancer patients froze embryos. The LBR was 16.7% after one transfer and 25.0% after a mean of 1.5 transfers. The LBR was 35.5% for patients who underwent fresh ET.
Conclusion PN freezing with delayed ET is an effective tool for achieving pregnancy for patients at risk of OHSS and for cancer patients wishing to preserve fertility.
C1 [Sabatini, Mary E.; Wolkovich, Ann M.; Wright, Diane L.; Souter, Irene; Toth, Thomas L.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA.
[Sabatini, Mary E.; Macklin, Eric A.; Souter, Irene; Toth, Thomas L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
RP Sabatini, ME (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, 55 Fruit St, Boston, MA 02114 USA.
EM msabatini@partners.org
RI Macklin, Eric/E-2955-2013
OI Macklin, Eric/0000-0003-1618-3502
NR 36
TC 5
Z9 6
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1058-0468
J9 J ASSIST REPROD GEN
JI J. Assist. Reprod. Genet.
PD MAR
PY 2011
VL 28
IS 3
BP 279
EP 284
DI 10.1007/s10815-010-9515-3
PG 6
WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
GA 778BL
UT WOS:000291674000015
PM 21107899
ER
PT J
AU Zhao, XF
Burger, M
Liu, Y
Das, MK
Combs, W
Wenk, JF
Guccione, JM
Kassab, GS
AF Zhao, Xuefeng
Burger, Mike
Liu, Yi
Das, Mithilesh K.
Combs, William
Wenk, Jonathan F.
Guccione, Julius M.
Kassab, Ghassan S.
TI Simulation of LV Pacemaker Lead in Marginal Vein: Potential Risk Factors
for Acute Dislodgement
SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME
LA English
DT Article
DE pacing lead; lead dislodgement; dynamic analysis
ID CORONARY-SINUS; STABILITY; MODEL
AB Although left ventricular (LV) coronary sinus lead dislodgement remains a problem, the risk factors for dislodgement have not been clearly defined. In order to identify potential risk factors for acute lead dislodgement, we conducted dynamic finite element simulations of pacemaker lead dislodgement in marginal LV vein. We considered factors such as mismatch in lead and vein diameters, velocity of myocardial motion, branch angle between the insertion vein and the coronary sinus, degree of slack, and depth of insertion. The results show that large lead-to-vein diameter mismatch, rapid myocardial motion, and superficial insertion are potential risk factors for lead dislodgement. In addition, the degree of slack presents either a positive or negative effect on dislodgement risk depending on the branch angle. The prevention of acute lead dislodgment can be enforced by inducing as much static friction force as possible at the lead-vein interface, while reducing the external force. If the latter exceeds the former, dislodgement will occur. The present findings underscore the major risk factors for lead dislodgment, which may improve implantation criterion and future lead design. [DOI: 10.1115/1.4003323]
C1 [Kassab, Ghassan S.] Indiana Univ Purdue Univ Indianapolis, Dept Surg, Indianapolis, IN 46202 USA.
[Kassab, Ghassan S.] Indiana Univ Purdue Univ Indianapolis, Dept Biomed Engn, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA.
[Burger, Mike] Livermore Software Technol Corp, Livermore, CA 94550 USA.
[Das, Mithilesh K.] Indiana Univ Sch Med, Roudebush VA Med Ctr, Krannert Inst Cardiol, Indianapolis, IN 46202 USA.
[Wenk, Jonathan F.; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94121 USA.
[Wenk, Jonathan F.; Guccione, Julius M.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Kassab, GS (reprint author), Indiana Univ Purdue Univ Indianapolis, Dept Surg, Indianapolis, IN 46202 USA.
EM gkassab@iupui.edu
RI Zhao, Xuefeng/A-3260-2013
OI Zhao, Xuefeng/0000-0003-3834-9091
NR 10
TC 2
Z9 2
U1 0
U2 0
PU ASME
PI NEW YORK
PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA
SN 0148-0731
J9 J BIOMECH ENG-T ASME
JI J. Biomech. Eng.-Trans. ASME
PD MAR
PY 2011
VL 133
IS 3
AR 031006
DI 10.1115/1.4003323
PG 7
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 718BY
UT WOS:000287096100006
ER
PT J
AU McCurdy, MR
Sharafkhaneh, A
Abdel-Monem, H
Rojo, J
Tittel, FK
AF McCurdy, Matthew R.
Sharafkhaneh, Amir
Abdel-Monem, Hanan
Rojo, Javier
Tittel, Frank K.
TI Exhaled nitric oxide parameters and functional capacity in chronic
obstructive pulmonary disease
SO JOURNAL OF BREATH RESEARCH
LA English
DT Article
ID COPD; ASTHMA; EXCHANGE; BIOMARKERS; DIFFUSION; MARKERS; MODEL; AIR
AB The extended exhaled nitric oxide (eNO) parameters, including peripheral or alveolar eNO, are investigational biomarkers in COPD. In this study, the hypothesis was tested that elevated peripheral eNO correlates with decreased functional capacity and lower global health status. Twenty-seven subjects with the Global Initiative for Chronic Obstructive Lung Disease stage 3 and 4 COPD were enrolled. Functional capacity and health status were tested using the 6 min walk test and St George's Respiratory Questionnaire (SGRQ) respectively. eNO parameters were estimated using multiple exhalation flow rates and were corrected for axial diffusion. The extended NO measurements were FE(NO)0.05 14.2 ppb (range 5.1-23.2), C(ANO) 4.6 ppb (2.2-6.9), D(awNO) 8.8 ml s(-1) (4.8-12.9), C(awNO) 83.2 ppb (29.9-128.7) and J'(awNO) 405 pl s(-1) (111-731). The distance traveled in the 6 min walk test was correlated with peripheral nitric oxide (r = -0.59, p = 0.03). SGRQ symptom score was correlated with maximum airway NO flux (r = -0.73, p = 0.01). SGRQ total score was correlated with maximum airway NO flux (r = -0.56, p = 0.05). In this study of subjects with severe COPD, peripheral nitric oxide correlated with functional capacity while large airway NO parameters correlated with symptom scores.
C1 [McCurdy, Matthew R.; Tittel, Frank K.] Rice Univ, Rice Quantum Inst, Houston, TX 77251 USA.
[McCurdy, Matthew R.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Radiat Oncol, Houston, TX 77030 USA.
[Sharafkhaneh, Amir; Abdel-Monem, Hanan] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Pulm Crit Care & Sleep Med, Houston, TX 77030 USA.
[Rojo, Javier] Rice Univ, Dept Stat, Houston, TX 77251 USA.
RP Tittel, FK (reprint author), Rice Univ, Rice Quantum Inst, Houston, TX 77251 USA.
EM fkt@rice.edu
NR 34
TC 28
Z9 28
U1 0
U2 4
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 1752-7155
J9 J BREATH RES
JI J. Breath Res.
PD MAR
PY 2011
VL 5
IS 1
AR 016003
DI 10.1088/1752-7155/5/1/016003
PG 6
WC Biochemical Research Methods; Respiratory System
SC Biochemistry & Molecular Biology; Respiratory System
GA 732SM
UT WOS:000288210000004
PM 21378438
ER
PT J
AU Rojas, CA
Jaimes, CE
El-Sherief, AH
Medina, HM
Chung, JH
Ghoshhajra, B
Abbara, S
AF Rojas, Carlos A.
Jaimes, Camilo E.
El-Sherief, Ahmed H.
Medina, Hector M.
Chung, Jonathan H.
Ghoshhajra, Brian
Abbara, Suhny
TI Cardiac CT of non-shunt pathology of the interatrial septum
SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY
LA English
DT Article
DE Interatrial septum; Interatrial septal aneurysm; Lipomatous hypertrophy
of the interatrial septum
AB The development and anatomy of the interatrial septum is complex. With the increasing use of cardiac CT and its precise delineation of the anatomy, it is important for the cardiac imager to become familiar with the normal anatomic structures that compose the interatrial septum and their variants. Furthermore, it is important to recognize pathologic processes occurring in this region other than atrial septal defects and potential imaging pitfalls. This pictorial essay provides a detailed review of these topics with emphasis in CT appearance and related technical aspects. (C) 2011 Society of Cardiovascular Computed Tomography. All rights reserved.
C1 [Rojas, Carlos A.; El-Sherief, Ahmed H.; Medina, Hector M.; Chung, Jonathan H.; Ghoshhajra, Brian; Abbara, Suhny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiac Imaging, Boston, MA 02114 USA.
[Jaimes, Camilo E.] Univ Rosario, Sch Med & Hlth Sci, Bogota, Colombia.
RP Rojas, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiac Imaging, 165 Cambridge St, Boston, MA 02114 USA.
EM caranrojas@gmail.com
RI Ghoshhajra, Brian/J-2114-2016
OI Ghoshhajra, Brian/0000-0002-3865-3432
NR 30
TC 1
Z9 1
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-5925
J9 J CARDIOVASC COMPUT
JI J. Cardiovasc. Comput. Tomogr.
PD MAR-APR
PY 2011
VL 5
IS 2
BP 93
EP 100
DI 10.1016/j.jcct.2010.10.011
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA V34CH
UT WOS:000209064000004
PM 21130061
ER
PT J
AU Shih, YYI
Wey, HY
De La Garza, BH
Duong, TQ
AF Shih, Yen-Yu I.
Wey, Hsiao-Ying
De La Garza, Bryan H.
Duong, Timothy Q.
TI Striatal and cortical BOLD, blood flow, blood volume, oxygen
consumption, and glucose consumption changes in noxious forepaw
electrical stimulation
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE CBF; CBV; CMRglc; CMRO(2); high-field fMRI; striatum
ID FUNCTIONAL MRI; BASAL GANGLIA; SOMATOSENSORY STIMULATION;
NEURONAL-ACTIVITY; NEURAL ACTIVITY; RAT; FMRI; ORGANIZATION; ARTERIAL;
DYNAMICS
AB Recent reports showed noxious forepaw stimulation in rats evoked an unexpected sustained decrease in cerebral blood volume (CBV) in the bilateral striatum, whereas increases in spike activity and Fos-immunoreactive cells were observed. This study aimed to further evaluate the hemodynamic and metabolic needs in this model and the sources of negative functional magnetic resonance imaging (fMRI) signals by measuring blood oxygenation-level-dependent (BOLD), cerebral-blood-flow (CBF), CBV, and oxygen-consumption (i.e., cerebral metabolic rate of oxygen (CMRO(2))) changes using an 11.7-T MRI scanner, and glucose-consumption (i.e., cerebral metabolic rate of glucose (CMRglc)) changes using micro-positron emission tomography. In the contralateral somatosensory cortex, BOLD, CBF, CBV, CMRO(2) (n = 7, P < 0.05), and CMRglc (n = 5, P < 0.05) increased. In contrast, in the bilateral striatum, BOLD, CBF, and CBV decreased (P < 0.05), CMRO(2) decreased slightly, although not significantly from baseline, and CMRglc was not statistically significant from baseline (P > 0.05). These multimodal functional imaging findings corroborate the unexpected negative hemodynamic changes in the striatum during noxious forepaw stimulation, and support the hypothesis that striatal hemodynamic response is dominated by neurotransmitter-mediated vasoconstriction, overriding the stimulus-evoked fMRI signal increases commonly accompany elevated neuronal activity. Multimodal functional imaging approach offers a means to probe the unique attributes of the striatum, providing novel insights into the neurovascular coupling in the striatum. These findings may have strong implications in fMRI studies of pain. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 832-841; doi:10.1038/jcbfm.2010.173; published online 13 October 2010
C1 [Shih, Yen-Yu I.; Wey, Hsiao-Ying; De La Garza, Bryan H.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Wey, Hsiao-Ying; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Duong, Timothy Q.] SW Natl Primate Res Ctr, San Antonio, TX USA.
RP Shih, YYI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM shihy@uthscsa.edu; duongt@uthscsa.edu
RI Duong, Timothy/B-8525-2008; Wey, Hsiao-Ying/G-3031-2012;
OI Shih, Yen-Yu Ian/0000-0001-6529-911X
FU NIH [R01-NS45879]; American Heart Association [10POST4290091]; San
Antonio Area Foundation; Defense Advanced Research Projects Agency
[HR0011-07-C-0027]; NIH/NCRR [S10 RR023038]
FX This work is supported by NIH R01-NS45879 to TQD, American Heart
Association (10POST4290091), and San Antonio Area Foundation to YYIS.;
The authors acknowledge Dr Fuqiang Zhao and Dr Ai-Ling Lin for valuable
discussion and Mr David A Lewis and Dr Kihak Lee for their assistance
with the PET scans. The authors acknowledge the resource supports of the
Defense Advanced Research Projects Agency (Comprehensive Facility for
Animal Imaging Research (CFAIR), HR0011-07-C-0027) and NIH/NCRR (S10
RR023038).
NR 42
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Z9 26
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD MAR
PY 2011
VL 31
IS 3
BP 832
EP 841
DI 10.1038/jcbfm.2010.173
PG 10
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 727ZS
UT WOS:000287842700006
PM 20940730
ER
PT J
AU Pallais, JC
Kemp, EH
Bergwitz, C
Kantham, L
Slovik, DM
Weetman, AP
Brown, EM
AF Pallais, J. Carl
Kemp, E. Helen
Bergwitz, Clemens
Kantham, Lakshmi
Slovik, David M.
Weetman, Anthony P.
Brown, Edward M.
TI Autoimmune Hypocalciuric Hypercalcemia Unresponsive to Glucocorticoid
Therapy in a Patient with Blocking Autoantibodies against the
Calcium-Sensing Receptor
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PARATHYROID-HORMONE LEVELS; ACQUIRED HYPOPARATHYROIDISM; ANTIBODIES;
HYPERPARATHYROIDISM; CORTICOSTEROIDS; TARGET; CELLS
AB Context: Autoantibodies directed against the calcium-sensing receptor (CaSR) have been reported in several individuals with various autoimmune disorders and PTH-mediated hypercalcemia. Previously, glucocorticoid treatment has been shown to decrease the CaSR autoantibody titers and normalize the hypercalcemia in a patient with autoimmune hypocalciuric hypercalcemia (AHH).
Objective: The objective of the study was to evaluate a patient with AHH for the presence of blocking autoantibodies against the CaSR and to monitor her biochemical and serological responses to a trial of glucocorticoid therapy.
Results: Glucocorticoid treatment had no effect on serum total or ionized calcium concentration or serum PTH levels, all of which remained at higher than normal levels. In contrast, on prednisone, urinary calcium excretion increased from overtly hypocalciuric levels to normal values. Anti-CaSR autoantibodies were detected at similar levels in the patient's serum before, during, and after glucocorticoid treatment. Functional testing of these antibodies showed that they inhibited the stimulatory effect of extracellular Ca2+ on ERK1/2 but did not suppress the calcium-induced accumulation of inositol-1-phosphate.
Conclusions: We report a patient with AHH with frankly elevated PTH levels who was found to have autoantibodies against the CaSR. The hypercalcemia and CaSR autoantibody titers failed to respond to glucocorticoid therapy, unlike a previously reported patient with similar clinical and biochemical features. The anti-CaSR antibody-mediated inhibition of CaSR-stimulated ERK1/2 activity, but not of inositol-1-phosphate accumulation, suggests that ERK1/2 may mediate, at least in part, the regulation of PTH secretion and urinary calcium excretion by the CaSR. (J Clin Endocrinol Metab 96: 672-680, 2011)
C1 [Pallais, J. Carl; Bergwitz, Clemens; Slovik, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
[Kemp, E. Helen; Weetman, Anthony P.] Univ Sheffield, Sch Med, Dept Human Metab, Sheffield S10 2JF, S Yorkshire, England.
[Kantham, Lakshmi; Brown, Edward M.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Kantham, Lakshmi; Brown, Edward M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Pallais, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
EM jpallais@partners.org
RI Kemp, Elizabeth Helen/D-1665-2011
OI Kemp, Elizabeth Helen/0000-0002-0313-8916
FU National Institutes of Health [DK078331]; Athena Diagnostics, Inc.;
calcimimetic, cinacalcet, through NPS Pharmaceuticals, Inc.
FX E.M.B. is supported by Grant DK078331 from the National Institutes of
Health.; J.C.P., E.H.K., C.B., L.K., D.M.S., and A.P.W. have nothing to
declare. E.M.B. has received lecture fees from Athena Diagnostics, Inc.
and has a financial interest in the calcimimetic, cinacalcet, through
NPS Pharmaceuticals, Inc.
NR 27
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Z9 7
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2011
VL 96
IS 3
BP 672
EP 680
DI 10.1210/jc.2010-1739
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730GA
UT WOS:000288020600036
PM 21159843
ER
PT J
AU Makimura, H
Stanley, TL
Sun, N
Hrovat, MI
Systrom, DM
Grinspoon, SK
AF Makimura, Hideo
Stanley, Takara L.
Sun, Noelle
Hrovat, Mirko I.
Systrom, David M.
Grinspoon, Steven K.
TI The Association of Growth Hormone Parameters with Skeletal Muscle
Phosphocreatine Recovery in Adult Men
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID MAGNETIC-RESONANCE-SPECTROSCOPY; FAT-FREE MASS; MITOCHONDRIAL
RESPIRATION; FACTOR-I; EXERCISE; INSULIN; GH; PROTECTION; TURNOVER;
CHILDREN
AB Context: Previous studies have suggested a relationship between GH and mitochondrial function. However, little is known about the relationship of specific GH indices and in vivo measures of mitochondrial function in humans.
Objective: The objective of this study was to determine the association between GH, IGF-I, and phosphocreatine (PCr) recovery, a measure of mitochondrial function, in otherwise healthy adults.
Design: Thirty-seven healthy men and women were studied at a single university medical center. Subjects underwent GH stimulation testing with GH releasing hormone-arginine and measurement of IGF-I. Mitochondrial function was determined by PCr recovery after submaximal exercise by (31)Phosphorous magnetic resonance spectroscopy. Subjects underwent assessment of lean and fat mass with use of dual energy X-ray absorptiometry.
Results: There were no differences in PCr recovery between men and women (men 20.7 +/- 1.5 vs. women 24.8 +/- 1.4 mM/min; P > 0.05). IGF-I (r = 0.33; P = 0.04) was associated with PCr recovery in all subjects. Among men, IGF-I (r = 0.69; P = 0.003), peak stimulated GH (r = 0.52; P = 0.04), and GH area under the curve (AUC) (r = 0.53; P = 0.04) were significantly associated with PCr recovery. However, neither IGF-I, peak stimulated GH, nor GH AUC (all P > 0.05) were associated with PCr recovery in women. After adjusting for age, race, and physical activity, IGF-I remained significantly associated with PCr recovery (beta = 0.10; P = 0.02) among men.
Conclusions: IGF-I, peak stimulated GH, and GH AUC are associated with skeletal muscle PCr recovery in men. (J Clin Endocrinol Metab 96: 817-823, 2011)
C1 [Makimura, Hideo; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
[Makimura, Hideo; Stanley, Takara L.; Sun, Noelle; Grinspoon, Steven K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Stanley, Takara L.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Hrovat, Mirko I.; Systrom, David M.] Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA.
[Hrovat, Mirko I.] Mirtech Inc, Brockton, MA 02301 USA.
RP Makimura, H (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 211, Boston, MA 02114 USA.
EM hmakimura@partners.org
OI Systrom, David/0000-0002-9610-6330
FU National Institutes of Health [1R01HL085268-01A1, K24DK064545-06,
K23DK087857-01A1]; Boston Nutrition Obesity Research Center
[3P30DK046200, UL1RR025758]; National Center for Research Resources;
Center for Functional Neuroimaging Technologies [P41RR14075]
FX This work was supported by National Institutes of Health Grant
1R01HL085268-01A1 (to S. G.), K24DK064545-06 (to S. G.),
K23DK087857-01A1 (to H. M.), Boston Nutrition Obesity Research Center
Pilot and Feasibility Grant 3P30DK046200 (to H. M.), UL1RR025758 to the
Harvard Clinical and Translational Science Center from the National
Center for Research Resources, and P41RR14075 from the Center for
Functional Neuroimaging Technologies to the Athinoula A. Martinos Center
for Biomedical Imaging where the 31P-MRS imaging studies were
conducted. The content is solely the responsibility of the authors and
does not necessarily represent the offical views of the National Center
for Research Resources or the National Institutes of Health.
NR 26
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Z9 10
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2011
VL 96
IS 3
BP 817
EP 823
DI 10.1210/jc.2010-2264
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730GA
UT WOS:000288020600053
PM 21177784
ER
PT J
AU Hegedus, L
Moses, AC
Zdravkovic, M
Tu, LT
Daniels, GH
AF Hegedus, Laszlo
Moses, Alan C.
Zdravkovic, Milan
Tu Le Thi
Daniels, Gilbert H.
TI GLP-1 and Calcitonin Concentration in Humans: Lack of Evidence of
Calcitonin Release from Sequential Screening in over 5000 Subjects with
Type 2 Diabetes or Nondiabetic Obese Subjects Treated with the Human
GLP-1 Analog, Liraglutide
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID MEDULLARY-THYROID CARCINOMA; C-CELL HYPERPLASIA; OPEN-LABEL TRIAL;
JAPANESE PATIENTS; GLYCEMIC CONTROL; PARALLEL-GROUP; METFORMIN;
EFFICACY; SAFETY; SULFONYLUREA
AB Background: Serum calcitonin (CT) is a well-accepted marker of C-cell proliferation, particularly in medullary thyroid carcinoma. Chronic glucagon-like peptide-1 (GLP-1) receptor agonist administration in rodents has been associated with increased serum CT levels and C-cell tumor formation. There are no longitudinal studies measuring CT in humans without medullary thyroid carcinoma or a family history of medullary thyroid carcinoma and no published studies on the effect of GLP-1 receptor agonists on human serum CT concentrations.
Aim: The aim of the study was to determine serum CT response over time to the GLP-1 receptor agonist liraglutide in subjects with type 2 diabetes mellitus or nondiabetic obese subjects.
Methods: Unstimulated serum CT concentrations were measured at 3-month intervals for no more than 2 yr in a series of trials in over 5000 subjects receiving liraglutide or control therapy.
Results: Basal mean CT concentrations were at the low end of normal range in all treatment groups and remained low throughout the trials. At 2 yr, estimated geometric mean values were no greater than 1.0 ng/liter, well below upper normal ranges for males and females. Proportions of subjects whose CT levels increased above a clinically relevant cutoff of 20 ng/liter were very low in all groups. There was no consistent dose or time-dependent relationship and no consistent difference between treatment groups.
Conclusions: These data do not support an effect of GLP-1 receptor activation on serum CT levels in humans and suggest that findings previously reported in rodents may not apply to humans. However, the long-term consequences of GLP-1 receptor agonist treatment are a subject of further studies. (J Clin Endocrinol Metab 96: 853-860, 2011)
C1 [Hegedus, Laszlo] Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense, Denmark.
[Moses, Alan C.] Novo Nordisk Inc, Princeton, NJ 08540 USA.
[Zdravkovic, Milan; Tu Le Thi] Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark.
[Daniels, Gilbert H.] Massachusetts Gen Hosp, Thyroid Unit, Endocrine Tumor Ctr, Boston, MA 02114 USA.
[Daniels, Gilbert H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Daniels, Gilbert H.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Hegedus, L (reprint author), Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense, Denmark.
EM Laszlo.Hegedus@ouh.regionsyddanmark.dk
FU Novo Nordisk A/S
FX Writing assistance for this manuscript was provided by Watermeadow
Medical, which was sponsored by Novo Nordisk A/S.; L. H. has received
consulting fees from and has served on an advisory council for Novo
Nordisk A/S. A.C.M., M.Z., and T.L.T. are employees of and shareholders
in Novo Nordisk. G. H. D. has acted as a consultant for Novo Nordisk,
currently serves on a steering committee, has received honoraria as a
consultant, and has provided Food and Drug Administration testimony as a
consultant.
NR 22
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U1 0
U2 7
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2011
VL 96
IS 3
BP 853
EP 860
DI 10.1210/jc.2010-2318
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730GA
UT WOS:000288020600058
PM 21209033
ER
PT J
AU Shaw, ND
Seminara, SB
Welt, CK
Au, MG
Plummer, L
Hughes, VA
Dwyer, AA
Martin, KA
Quinton, R
Mericq, V
Merino, PM
Gusella, JF
Crowley, WF
Pitteloud, N
Hall, JE
AF Shaw, Natalie D.
Seminara, Stephanie B.
Welt, Corrine K.
Au, Margaret G.
Plummer, Lacey
Hughes, Virginia A.
Dwyer, Andrew A.
Martin, Kathryn A.
Quinton, Richard
Mericq, Veronica
Merino, Paulina M.
Gusella, James F.
Crowley, William F., Jr.
Pitteloud, Nelly
Hall, Janet E.
TI Expanding the Phenotype and Genotype of Female GnRH Deficiency
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC
HYPOGONADISM; FOLLICLE-STIMULATING-HORMONE; KALLMANN-SYNDROME;
LUTEINIZING-HORMONE; RECEPTOR MUTATIONS; GENE-MUTATIONS; SECRETION;
SPECTRUM; PROKINETICIN-2
AB Context: GnRH deficiency is a rare genetic disorder of absent or partial pubertal development. The clinical and genetic characteristics of GnRH-deficient women have not been well-described.
Objective: Todetermine the phenotypic and genotypic spectrum of a large series of GnRH-deficient women.
Design, Setting, and Subjects: Retrospective study of 248 females with GnRH deficiency evaluated at an academic medical center between 1980 and 2010.
Main Outcome Measures: Clinical presentation, baseline endogenous GnRH secretory activity, and DNA sequence variants in 11 genes associated with GnRH deficiency.
Results: Eighty-eight percent had undergone pubarche, 51% had spontaneous thelarche, and 10% had 1-2 menses. Women with spontaneous thelarche were more likely to demonstrate normal pubarche (P = 0.04). In 27% of women, neuroendocrine studies demonstrated evidence of some endogenous GnRH secretory activity. Thirty-six percent (a large excess relative to controls) harbored a rare sequence variant in a gene associated with GnRH deficiency (87% heterozygous and 13% biallelic), with variants in FGFR1 (15%), GNRHR (6.6%), and PROKR2 (6.6%) being most prevalent. One woman had a biallelic variant in the X-linked gene, KAL1, and nine women had heterozygous variants.
Conclusions: The clinical presentation of female GnRH deficiency varies from primary amenorrhea and absence of any secondary sexual characteristics to spontaneous breast development and occasional menses. In this cohort, rare sequence variants were present in all of the known genes associated with GnRH deficiency, including the novel identification of GnRH-deficient women with KAL1 variants. The pathogenic mechanism through which KAL1 variants disrupt female reproductive development requires further investigation. (J Clin Endocrinol Metab 96: E566-E576, 2011)
C1 [Hall, Janet E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA.
[Shaw, Natalie D.; Seminara, Stephanie B.; Welt, Corrine K.; Au, Margaret G.; Plummer, Lacey; Hughes, Virginia A.; Dwyer, Andrew A.; Martin, Kathryn A.; Crowley, William F., Jr.; Pitteloud, Nelly; Hall, Janet E.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Shaw, Natalie D.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Quinton, Richard] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Mericq, Veronica] Univ Chile, Fac Med, Inst Maternal & Child Res, Santiago 7, Chile.
[Merino, Paulina M.] Univ Chile, Fac Med, Dept Pediat, Santiago 7, Chile.
RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX-5,55 Fruit St, Boston, MA 02114 USA.
EM jehall@partners.org
RI Mericq, Veronica/F-3927-2010; Dwyer, Andrew/D-8099-2012; PITTELOUD,
Nelly/K-2709-2014;
OI Dwyer, Andrew/0000-0002-7023-6794; Welt, Corrine/0000-0002-8219-5504;
Mericq, Veronica/0000-0003-2287-0181; Shaw, Natalie/0000-0002-0847-9170
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development/National Institutes of Health [R01 HD42708, U54 HD028138];
National Institutes of Health/National Center for Research Resources,
General Clinical Research Centers [M01-RR-01066]; Developmental Genome
Anatomy Project [GM061354]; National Institutes of Health [5T32
HD007396]; Harvard Clinical and Translational Science Center [UL1 RR
025758]; Harvard University
FX This work was supported by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development/National Institutes of Health
through R01 HD42708 and cooperative agreement U54 HD028138 as part of
the Specialized Cooperative Centers Program in Reproduction and
Infertility Research and M01-RR-01066 National Institutes of
Health/National Center for Research Resources, General Clinical Research
Centers Program. Dr. Gusella received support from the Developmental
Genome Anatomy Project (GM061354). Dr. Shaw received fellowship support
from the National Institutes of Health (5T32 HD007396) and from the
Scholars in Clinical Science program of Harvard Catalyst [The Harvard
Clinical and Translational Science Center (Award #UL1 RR 025758) and
financial contributions from Harvard University and its affiliated
academic health care centers]. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
Harvard Catalyst, Harvard University and its affiliated academic health
care centers, the National Center for Research Resources, or the
National Institutes of Health.
NR 57
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U1 0
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2011
VL 96
IS 3
BP E566
EP E576
DI 10.1210/jc.2010-2292
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 730GA
UT WOS:000288020600019
PM 21209029
ER
PT J
AU Kim, HY
Eyheramonho, MB
Pichavant, M
Cambaceres, CG
Matangkasombut, P
Cervio, G
Kuperman, S
Moreiro, R
Konduru, K
Manangeeswaran, M
Freeman, GJ
Kaplan, GG
DeKruyff, RH
Umetsu, DT
Rosenzweig, SD
AF Kim, Hye Young
Belen Eyheramonho, Maria
Pichavant, Muriel
Gonzalez Cambaceres, Carlos
Matangkasombut, Ponpan
Cervio, Guillermo
Kuperman, Silvina
Moreiro, Rita
Konduru, Krishnamurthy
Manangeeswaran, Mohanraj
Freeman, Gordon J.
Kaplan, Gerardo G.
DeKruyff, Rosemarie H.
Umetsu, Dale T.
Rosenzweig, Sergio D.
TI A polymorphism in TIM1 is associated with susceptibility to severe
hepatitis A virus infection in humans
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID KILLER T-CELLS; ACUTE LIVER-FAILURE; AIRWAY HYPERREACTIVITY; MUCIN
DOMAIN; NKT CELLS; PHOSPHATIDYLSERINE RECEPTOR; FULMINANT-HEPATITIS;
APOPTOTIC CELLS; HIV-1 INFECTION; ATOPIC DISEASE
AB During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However,, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy.
C1 [Kim, Hye Young; Pichavant, Muriel; Matangkasombut, Ponpan; DeKruyff, Rosemarie H.; Umetsu, Dale T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat,Div Immunol, Boston, MA 02115 USA.
[Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Immunol, Buenos Aires, DF, Argentina.
[Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Liver Transplantat, Buenos Aires, DF, Argentina.
[Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Transfus Med, Buenos Aires, DF, Argentina.
[Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Lab Med, Buenos Aires, DF, Argentina.
[Konduru, Krishnamurthy; Manangeeswaran, Mohanraj; Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Rosenzweig, Sergio D.] NIAID, Infect Dis Susceptibil Unit, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Umetsu, DT (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Immunol,Karp Labs, Rm 10127,1 Blackfan Circle, Boston, MA 02115 USA.
EM dale.umetsu@childrens.harvard.edu; srosenzweig@niaid.nih.gov
FU Fortabat Endowment of the David Rockefeller Center for Latin American
Studies at Harvard University; NIH [P01 AI054456]; FDA
FX We thank Leslie Kalish for help with the statistical analysis; and Mirta
Ciocca, Miriam Cuarterolo, Oscar Imventarza, Javier Goni, Ana Del Pozo,
Jorge Sasbon, Stefania Pittaluga, and Maria T. de Davila for valuable
comments and support. These studies were supported by the de Fortabat
Endowment of the David Rockefeller Center for Latin American Studies at
Harvard University, by a grant from the NIH (P01 AI054456), and with FDA
intramural funds. The findings and conclusions in this article have not
been formally disseminated by the FDA and should not be construed to
represent any Agency determination or policy.
NR 47
TC 36
Z9 38
U1 1
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAR
PY 2011
VL 121
IS 3
BP 1111
EP 1118
DI 10.1172/JCI44182
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 729YQ
UT WOS:000287991000029
PM 21339644
ER
PT J
AU Pardanani, A
Gotlib, JR
Jamieson, C
Cortes, JE
Talpaz, M
Stone, RM
Silverman, MH
Gilliland, DG
Shorr, J
Tefferi, A
AF Pardanani, Animesh
Gotlib, Jason R.
Jamieson, Catriona
Cortes, Jorge E.
Talpaz, Moshe
Stone, Richard M.
Silverman, Michael H.
Gilliland, D. Gary
Shorr, Jolene
Tefferi, Ayalew
TI Safety and Efficacy of TG101348, a Selective JAK2 Inhibitor, in
Myelofibrosis
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID INTERNATIONAL-WORKING-GROUP; PROGNOSTIC SCORING SYSTEM;
MYELOPROLIFERATIVE NEOPLASMS; POLYCYTHEMIA-VERA; MYELOID METAPLASIA;
ESSENTIAL THROMBOCYTHEMIA; MUTATIONS; JAK2V617F; CRITERIA; CELLS
AB Purpose Myelofibrosis is a myeloid malignancy associated with anemia, splenomegaly, and constitutional symptoms. Patients frequently harbor JAK-STAT activating mutations that are sensitive to TG101348, a selective small-molecule Janus kinase 2 (JAK2) inhibitor.
Patients and Methods In a multicenter phase I trial, oral TG101348 was administered once a day to patients with high-or intermediate-risk primary or post-polycythemia vera/essential thrombocythemia myelofibrosis.
Results Fifty-nine patients were treated, including 28 in the dose-escalation phase. The maximum-tolerated dose was 680 mg/d, and dose-limiting toxicity was a reversible and asymptomatic increase in the serum amylase level. Forty-three patients (73%) continued treatment beyond six cycles; the median cumulative exposure to TG101348 was 380 days. Adverse events included nausea, vomiting, diarrhea, anemia, and thrombocytopenia; corresponding grades 3 to 4 incidence rates were 3%, 3%, 10%, 35%, and 24%. TG101348 treatment had modest effect on serum cytokine levels, but greater than half of the patients with early satiety, night sweats, fatigue, pruritus, and cough achieved rapid and durable improvement in these symptoms. By six and 12 cycles of treatment, 39% and 47% of patients, respectively, had achieved a spleen response per International Working Group criteria. The majority of patients with leukocytosis or thrombocytosis at baseline (n = 28 and n = 10, respectively) achieved normalization of blood counts after six (57% and 90%, respectively) and 12 (56% and 88%, respectively) cycles. A significant decrease in JAK2 V617F allele burden was observed at 6 months in mutation-positive patients (n = 51; P = .04), particularly in the subgroup with allele burden greater than 20% (n = 23; P < .01); the decrease was durable at 12 months.
Conclusion TG101348 is well tolerated and produces significant reduction in disease burden and durable clinical benefit in patients with myelofibrosis. J Clin Oncol 29:789-796. (C) 2011 by American Society of Clinical Oncology
C1 [Tefferi, Ayalew] Mayo Clin, Div Hematol, Rochester, MN 55905 USA.
Stanford Univ, Sch Med, Stanford, CA 94305 USA.
Univ Calif San Diego, San Diego, CA 92103 USA.
TargeGen, San Diego, CA USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Biostrateg Consulting, Marblehead, MA USA.
Merck, N Wales, PA USA.
RP Tefferi, A (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA.
EM tefferi.ayalew@mayo.edu
FU TargeGen; Cytopia
FX Research Funding: Animesh Pardanani, TargeGen, Cytopia; Jason R. Gotlib,
TargeGen; Catriona Jamieson, TargeGen; Jorge E. Cortes, TargeGen; Moshe
Talpaz, TargeGen; Ayalew Tefferi, TargeGen.
NR 26
TC 226
Z9 233
U1 1
U2 15
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
BP 789
EP 796
DI 10.1200/JCO.2010.32.8021
PG 8
WC Oncology
SC Oncology
GA 726NO
UT WOS:000287729900018
PM 21220608
ER
PT J
AU Horan, JT
Logan, BR
Agovi-Johnson, MA
Lazarus, HM
Bacigalupo, AA
Ballen, KK
Bredeson, CN
Carabasi, MH
Gupta, V
Hale, GA
Khoury, HJ
Juckett, MB
Litzow, MR
Martino, R
McCarthy, PL
Smith, FO
Rizzo, JD
Pasquini, MC
AF Horan, John T.
Logan, Brent R.
Agovi-Johnson, Manza-A.
Lazarus, Hillard M.
Bacigalupo, Andrea A.
Ballen, Karen K.
Bredeson, Christopher N.
Carabasi, Matthew H.
Gupta, Vikas
Hale, Gregory A.
Khoury, Hanna Jean
Juckett, Mark B.
Litzow, Mark R.
Martino, Rodrigo
McCarthy, Philip L.
Smith, Franklin O.
Rizzo, J. Douglas
Pasquini, Marcelo C.
TI Reducing the Risk for Transplantation-Related Mortality After Allogeneic
Hematopoietic Cell Transplantation: How Much Progress Has Been Made?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; ACUTE
MYELOID-LEUKEMIA; ACUTE GRAFT; FLUCONAZOLE PROPHYLAXIS;
PERIPHERAL-BLOOD; RECIPIENTS; METHOTREXATE; INFECTIONS; CHILDREN
AB Purpose Transplantation-related mortality (TRM) is a major barrier to the success of allogeneic hematopoietic cell transplantation (HCT).
Patients and Methods We assessed changes in the incidence of TRM and overall survival from 1985 through 2004 in 5,972 patients younger than age 50 years who received myeloablative conditioning and HCT for acute myeloid leukemia (AML) in first complete remission (CR1) or second complete remission (CR2).
Results Among HLA-matched sibling donor transplantation recipients, the relative risks (RRs) for TRM were 0.5 and 0.3 for 2000 to 2004 compared with those for 1985 to 1989 in patients in CR1 and CR2, respectively (P < .001). The RRs for all causes of mortality in the latter period were 0.73 (P < .001) and 0.60 (P = .005) for the CR1 and CR2 groups, respectively. Among unrelated donor transplantation recipients, the RRs for TRM were 0.73 (P = .095) and 0.58 (P < .001) for 2000 to 2004 compared with those in 1990 to 1994 in the CR1 and CR2 groups, respectively. Reductions in mortality were observed in the CR2 group (RR, 0.74; P = .03) but not in the CR1 group.
Conclusion Our results suggest that innovations in transplantation care since the 1980s and 1990s have reduced the risk of TRM in patients undergoing allogeneic HCT for AML and that this reduction has been accompanied by improvements in overall survival. J Clin Oncol 29:805-813. (C) 2011 by American Society of Clinical Oncology
C1 [Pasquini, Marcelo C.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
Emory Univ Hosp, Childrens Healthcare Atlanta Egleston, Atlanta, GA 30322 USA.
Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USA.
Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA.
Univ Hosp Case Med Ctr, Cleveland, OH USA.
Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
Univ Cincinnati, Coll Med, Cincinnati, OH USA.
Osped San Martino Genova, Genoa, Italy.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA.
Mayo Clin Rochester, Rochester, MN USA.
Hosp Santa Creu & Sant Pau, Barcelona, Spain.
Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
RP Pasquini, MC (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA.
EM mpasquin@mcw.edu
NR 35
TC 62
Z9 63
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
BP 805
EP 813
DI 10.1200/JCO.2010.32.5001
PG 9
WC Oncology
SC Oncology
GA 726NO
UT WOS:000287729900020
PM 21220593
ER
PT J
AU Aplenc, R
Blaney, SM
Strauss, LC
Balis, FM
Shusterman, S
Ingle, AM
Agrawal, S
Sun, JF
Wright, JJ
Adamson, PC
AF Aplenc, Richard
Blaney, Susan M.
Strauss, Lewis C.
Balis, Frank M.
Shusterman, Suzanne
Ingle, Ashish Mark
Agrawal, Shruti
Sun, Junfeng
Wright, John J.
Adamson, Peter C.
TI Pediatric Phase I Trial and Pharmacokinetic Study of Dasatinib: A Report
From the Children's Oncology Group Phase I Consortium
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; CYTOGENETIC RESPONSES; IMATINIB-RESISTANT
AB Purpose Dasatinib is an orally available tyrosine kinase inhibitor with low nanomolar activity against SRC family kinases, BCR-ABL, c-KIT, EPHA2, and the PDGF-beta receptor. Dasatinib was found to have selective activity in several tumor models in the Pediatric Preclinical Testing Program.
Patients and Methods A phase I study of dasatinib in pediatric patients with refractory solid tumors or imatinib-refractory, Philadelphia chromosome-positive leukemia was performed. Dose levels of 50, 65, 85, and 110 mg/m(2)/dose, administered orally twice daily for 28 days, with courses repeated without interruption, were studied. Pharmacokinetic studies were performed with the initial dose.
Results A total of 39 patients (solid tumors, n = 28; chronic myeloid leukemia [CML], n = 9; acute lymphoblastic leukemia, n = 2) were enrolled. No dose-limiting toxicities (DLTs) were observed at the 50, 65, and 85 mg/m(2) dose levels. At 110 mg/m(2), two of six patients experienced DLT including grade 2 diarrhea and headache. In children with leukemia, grade 4 hypokalemia (50 mg/m(2)), grade 3 diarrhea (85 mg/m(2)), and grade 2 creatinine elevation (50 mg/m(2)) were observed. DLT in later courses included pleural effusions, hemangiomatosis, and GI hemorrhage. There were three complete cytogenetic responses, three partial cytogenetic responses, and two partial/minimal cytogenetic responses observed in evaluable patients with CML.
Conclusion Overall, drug disposition and tolerability of dasatinib were similar to those observed in adult patients. J Clin Oncol 29:839-844. (C) 2011 by American Society of Clinical Oncology
C1 [Aplenc, Richard] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
Baylor Coll Med, Houston, TX 77030 USA.
Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA USA.
Stat & Data Ctr, Childrens Oncol Grp, Arcadia, CA USA.
Univ Nebraska Med Ctr, Omaha, NE USA.
NCI, Canc Therapeut & Evaluat Program, Bethesda, MD 20892 USA.
RP Aplenc, R (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, 4018 CTRB,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM raplenc@mail.med.upenn.edu
FU National Cancer Institute [U01 CA97452]; NCRR [M01 RR00188]
FX Supported by National Cancer Institute Grants No. U01 CA97452 and NCRR
M01 RR00188.
NR 12
TC 41
Z9 45
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
BP 839
EP 844
DI 10.1200/JCO.2010.30.7231
PG 6
WC Oncology
SC Oncology
GA 726NO
UT WOS:000287729900024
PM 21263099
ER
PT J
AU Kulke, MH
Siu, LL
Tepper, JE
Fisher, G
Jaffe, D
Haller, DG
Ellis, LM
Benedetti, JK
Bergsland, EK
Hobday, TJ
Van Cutsem, E
Pingpank, J
Oberg, K
Cohen, SJ
Posner, MC
Yao, JC
AF Kulke, Matthew H.
Siu, Lillian L.
Tepper, Joel E.
Fisher, George
Jaffe, Deborah
Haller, Daniel G.
Ellis, Lee M.
Benedetti, Jacqueline K.
Bergsland, Emily K.
Hobday, Timothy J.
Van Cutsem, Eric
Pingpank, James
Oberg, Kjell
Cohen, Steven J.
Posner, Mitchell C.
Yao, James C.
TI Future Directions in the Treatment of Neuroendocrine Tumors: Consensus
Report of the National Cancer Institute Neuroendocrine Tumor Clinical
Trials Planning Meeting
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PROGRESSION-FREE SURVIVAL; NUCLEOTIDE POLYMORPHISM ANALYSIS; METASTATIC
CARCINOID-TUMORS; PANCREATIC ENDOCRINE TUMORS; PHASE-II; SOMATOSTATIN
ANALOG; ALLELIC ALTERATIONS; PROGNOSTIC-FACTORS; GRADING SYSTEM;
OCTREOTIDE LAR
AB Neuroendocrine tumors (NETs) arise from a variety of anatomic sites and share the capacity for production of hormones and vasoactive peptides. Because of their perceived rarity, NETs have not historically been a focus of rigorous clinical research. However, the diagnosed incidence of NETs has been increasing, and the estimated prevalence in the United States exceeds 100,000 individuals. The recent completion of several phase III studies, including those evaluating octreotide, sunitinib, and everolimus, has demonstrated that rigorous evaluation of novel agents in this disease is both feasible and can lead to practice-changing outcomes. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trials planning meeting to identify key unmet needs, develop appropriate study end points, standardize clinical trial inclusion criteria, and formulate priorities for future NET studies for the US cooperative group program. Emphasis was placed on the development of well-designed clinical trials with clearly defined efficacy criteria. Key recommendations include the evaluation of pancreatic NET separately from NETs of other sites and the exclusion of patients with poorly differentiated histologies from trials focused on low-grade histologies. Studies evaluating novel agents for the control of hormonal syndromes should avoid somatostatin analog washout periods when possible and should include quality-of-life end points. Because of the observed long survival after progression of many patients, progression-free survival is recommended as a feasible and relevant primary end point for both phase III studies and phase II studies where a delay in progression is expected in the absence of radiologic responses. J Clin Oncol 29: 934-943. (C) 2011 by American Society of Clinical Oncology
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA.
Stanford Univ, Sch Med, Stanford, CA 94305 USA.
Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
NCI, Coordinating Ctr Clin Trials, Off Director, Rockville, MD USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Yao, James C.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, Houston, TX 77030 USA.
Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98104 USA.
Mayo Clin, Coll Med, Rochester, MN USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
Univ Hosp, Uppsala, Sweden.
RP Yao, JC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM jyao@mdanderson.org
FU National Cancer Institute, Bethesda, MD; Novartis; Pfizer; Genentech;
Ipsen; sanofi-aventis; Lexicon
FX Supported in part by a grant from the National Cancer Institute,
Bethesda, MD.; Research Funding: Lillian L. Siu, Novartis, Pfizer;
George Fisher, Genentech, Ipsen, Novartis, sanofi-aventis; Emily K.
Bergsland, Novartis, Genentech, Lexicon; Timothy J. Hobday, Novartis;
Eric Van Cutsem, Novartis, Pfizer; James C. Yao, Novartis, Genentech
NR 49
TC 129
Z9 135
U1 0
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
BP 934
EP 943
DI 10.1200/JCO.2010.33.2056
PG 10
WC Oncology
SC Oncology
GA 726NO
UT WOS:000287729900037
PM 21263089
ER
PT J
AU Alharbi, H
Choueiri, TK
Kollmannsberger, CK
North, S
MacKenzie, MJ
Knox, JJ
Rini, BI
Heng, DY
AF Alharbi, H.
Choueiri, T. K.
Kollmannsberger, C. K.
North, S.
MacKenzie, M. J.
Knox, J. J.
Rini, B. I.
Heng, D. Y.
TI Brain metastases in patients treated with targeted therapy for
metastatic renal cell carcinoma (mRCC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada.
Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
London Reg Canc Program, London, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 326
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700325
PM 27968642
ER
PT J
AU Arvold, ND
Catalano, PJ
Sweeney, C
Hoffman, KE
Nguyen, PL
Balboni, TA
Fossa, SD
Travis, LB
Beard, C
AF Arvold, N. D.
Catalano, P. J.
Sweeney, C.
Hoffman, K. E.
Nguyen, P. L.
Balboni, T. A.
Fossa, S. D.
Travis, L. B.
Beard, C.
TI Physician and patient factors influencing management recommendations in
stage I testicular seminoma: A survey among radiation oncologists in the
United States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Radiat Oncol Program, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
Oslo Univ Hosp, Div Canc Med & Radiotherapy, Oslo, Norway.
Univ Rochester, Rochester, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 225
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700226
PM 27968685
ER
PT J
AU Arvold, ND
Chen, M
Moul, JW
Moran, BJ
Dosoretz, DE
Banez, LL
Katin, MJ
Braccioforte, MH
D'Amico, AV
AF Arvold, N. D.
Chen, M.
Moul, J. W.
Moran, B. J.
Dosoretz, D. E.
Banez, L. L.
Katin, M. J.
Braccioforte, M. H.
D'Amico, A. V.
TI Risk of death from prostate cancer after radical prostatectomy or
brachytherapy in men with low-or intermediate-risk disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Radiat Oncol Program, Boston, MA USA.
Univ Connecticut, Storrs, CT USA.
Duke Univ, Med Ctr, Durham, NC USA.
Prostate Canc Fdn Chicago, Westmont, IL USA.
21st Century Oncol, Ft Myers, FL USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 198
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700199
PM 27968470
ER
PT J
AU Baskin-Bey, ES
Holtkamp, GM
Smith, MR
Ouatas, T
Phung, D
Tombal, B
AF Baskin-Bey, E. S.
Holtkamp, G. M.
Smith, M. R.
Ouatas, T.
Phung, D.
Tombal, B.
TI A phase II, open-label, single-arm, efficacy, and safety study of
MDV3100 in patients with hormone-naive prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Astellas Pharma Europe, Staines, Surrey, England.
Astellas Pharma Europe BV, Leiderdorp, Netherlands.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Clin Univ St Luc, B-1200 Brussels, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 177
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700178
PM 27968436
ER
PT J
AU Beard, C
Chen, M
Arvold, ND
Nguyen, PL
Ng, AK
Hoffman, KE
AF Beard, C.
Chen, M.
Arvold, N. D.
Nguyen, P. L.
Ng, A. K.
Hoffman, K. E.
TI Long-term survival and competing causes of death in men with stage I
seminoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Connecticut, Storrs, CT USA.
Harvard Radiat Oncol Program, Boston, MA USA.
Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 226
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700227
PM 27968699
ER
PT J
AU Campbell, MT
Jung, J
Philips, S
Mohammadi, Y
Carr, KA
Davis, TL
Li, L
Sweeney, C
Skaar, TC
Hahn, NM
AF Campbell, M. T.
Jung, J.
Philips, S.
Mohammadi, Y.
Carr, K. A.
Davis, T. L.
Li, L.
Sweeney, C.
Skaar, T. C.
Hahn, N. M.
TI Germ-line single nucleotide polymorphism (SNP) predictors of
progression-free survival and overall survival in patients with advanced
prostate cancer treated with androgen-deprivation therapy (ADT).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Indiana Univ, Indianapolis, IN 46204 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 51
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700052
PM 27968396
ER
PT J
AU Choueiri, TK
Vaishampayan, UN
Yu, EY
Quinn, DI
Hahn, NM
Hutson, TE
Ross, RW
Rosenberg, JE
Jacobus, SJ
Kantoff, PW
AF Choueiri, T. K.
Vaishampayan, U. N.
Yu, E. Y.
Quinn, D. I.
Hahn, N. M.
Hutson, T. E.
Ross, R. W.
Rosenberg, J. E.
Jacobus, S. J.
Kantoff, P. W.
TI A double-blind randomized trial of docetaxel plus vandetanib versus
docetaxel plus placebo in platinum-pretreated advanced urothelial cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Univ Washington, Seattle, WA 98195 USA.
Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Texas Oncol PA, Baylor Sammons Canc Ctr, Dallas, TX USA.
Dana Farber Canc Inst, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA LBA239
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700240
PM 27968416
ER
PT J
AU Coen, J
Paly, JJ
Weyman, EA
Rodrigues, A
Shipley, WU
Zietman, AL
Efstathiou, JA
Talcott, JA
AF Coen, J.
Paly, J. J.
Weyman, E. A.
Rodrigues, A.
Shipley, W. U.
Zietman, A. L.
Efstathiou, J. A.
Talcott, J. A.
TI Long-term QOL outcome after proton beam monotherapy for localized
prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 68
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700069
PM 27968351
ER
PT J
AU Davis, TL
Jung, J
Carr, KA
Philips, S
Mohammadi, Y
Campbell, MT
Li, L
Sweeney, C
Skaar, TC
Hahn, NM
AF Davis, T. L.
Jung, J.
Carr, K. A.
Philips, S.
Mohammadi, Y.
Campbell, M. T.
Li, L.
Sweeney, C.
Skaar, T. C.
Hahn, N. M.
TI Androgen pathway constitutional polymorphism predictors of
progression-free and overall survivals in advanced castrate-resistant
prostate cancer (CRPC) patients treated with ketoconazole (KC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Indiana Univ, Indianapolis, IN 46204 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 54
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700055
PM 27968400
ER
PT J
AU Efstathiou, JA
Paly, JJ
Lu, H
Athar, BS
Niemierko, A
Bekelman, JE
Coen, J
Shipley, WU
Zietman, AL
Paganetti, H
AF Efstathiou, J. A.
Paly, J. J.
Lu, H.
Athar, B. S.
Niemierko, A.
Bekelman, J. E.
Coen, J.
Shipley, W. U.
Zietman, A. L.
Paganetti, H.
TI Adjuvant radiation therapy for early-stage seminoma: Proton-photon
comparison and second cancer risk
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 228
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700229
PM 27968695
ER
PT J
AU Galsky, MD
Hahn, NM
Rosenberg, JE
Sonpavde, G
Oh, WK
Dreicer, R
Vogelzang, NJ
Sternberg, CN
Bajorin, DF
Bellmunt, J
AF Galsky, M. D.
Hahn, N. M.
Rosenberg, J. E.
Sonpavde, G.
Oh, W. K.
Dreicer, R.
Vogelzang, N. J.
Sternberg, C. N.
Bajorin, D. F.
Bellmunt, J.
CA Cisplatin Ineligibility Bladder
TI Defining "cisplatin ineligible" patients with metastatic bladder cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Baylor Coll Med, Texas Oncol, Houston, TX 77030 USA.
Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA.
Comprehens Canc Ctr Nevada, Las Vegas, NV USA.
San Camillo Hosp, Rome, Italy.
Forlanini Hosp, Rome, Italy.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Hosp del Mar, Barcelona, Spain.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 238
PG 2
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700239
PM 27968673
ER
PT J
AU Hahn, NM
Jung, J
Philips, S
Patel, YR
Carr, KA
Mohammadi, Y
Magjuka, D
Li, L
Sweeney, C
Skaar, TC
AF Hahn, N. M.
Jung, J.
Philips, S.
Patel, Y. R.
Carr, K. A.
Mohammadi, Y.
Magjuka, D.
Li, L.
Sweeney, C.
Skaar, T. C.
TI Use of germ-line single nucleotide polymorphisms (SNPs) in drug
transporters (ABCG2/ABCB1) and tubulin (TUBB4) to predict survival in
patients with metastatic castrate-resistant prostate cancer (CRPC)
receiving docetaxel
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
Indiana Univ, Sch Publ Hlth, Indianapolis, IN 46204 USA.
Indiana Univ, Indianapolis, IN 46204 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 58
PG 2
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700059
PM 27968403
ER
PT J
AU Harzstark, AL
Beer, TM
Weinberg, VK
Higano, CS
Nordquist, LT
Rosenberg, JE
Alumkal, JJ
Yu, EY
Mi, J
Small, EJ
AF Harzstark, A. L.
Beer, T. M.
Weinberg, V. K.
Higano, C. S.
Nordquist, L. T.
Rosenberg, J. E.
Alumkal, J. J.
Yu, E. Y.
Mi, J.
Small, E. J.
TI Intermittent chemotherapy (ICh) for metastatic castration-resistant
prostate cancer (mCRPC): Results of a prospective randomized phase II
trial of the DoD Prostate Cancer Clinical Trials Consortium
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
Univ Washington, Sch Med, Seattle, WA USA.
Oncol Hematol West PC, Omaha, NE USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 133
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700134
PM 27968494
ER
PT J
AU Heng, DY
MacKenzie, MJ
Vaishampayan, UN
Knox, JJ
Bjarnason, GA
Tan, M
Wood, L
Donskov, F
Rini, BI
Choueiri, TK
AF Heng, D. Y.
MacKenzie, M. J.
Vaishampayan, U. N.
Knox, J. J.
Bjarnason, G. A.
Tan, M.
Wood, L.
Donskov, F.
Rini, B. I.
Choueiri, T. K.
CA Int mRCC Database Consortium
TI Primary anti-VEGF-refractory metastatic renal cell carcinoma (mRCC):
Clinical characteristics, risk factors, and subsequent therapy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
London Reg Canc Program, London, ON, Canada.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Natl Canc Ctr Singapore, Singapore, Singapore.
Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark.
Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 305
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700305
ER
PT J
AU Higano, CS
Beer, TM
Taplin, M
Efstathiou, E
Anand, A
Hirmand, M
Fleisher, M
Scher, HI
AF Higano, C. S.
Beer, T. M.
Taplin, M.
Efstathiou, E.
Anand, A.
Hirmand, M.
Fleisher, M.
Scher, H. I.
CA Prostate Canc Clinical Trials Cons
TI Antitumor activity of MDV3100 in pre- and post-docetaxel advanced
prostate cancer: Long-term follow-up of a phase I/II study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Washington, Sch Med, Seattle, WA USA.
Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Medivation Inc, San Francisco, CA USA.
RI Anand, Aseem/P-1214-2014
OI Anand, Aseem/0000-0002-3606-540X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 134
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700135
PM 27968506
ER
PT J
AU Hoffman, KE
Chen, M
Nguyen, PL
Bennett, CL
Sartor, AO
Stein, K
Kuban, DA
D'Amico, AV
AF Hoffman, K. E.
Chen, M.
Nguyen, P. L.
Bennett, C. L.
Sartor, A. O.
Stein, K.
Kuban, D. A.
D'Amico, A. V.
TI Factors associated with a delay in diagnosis of recurrent prostate
cancer after radical prostatectomy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
Univ Connecticut, Storrs, CT USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
South Carolina Coll Pharm, Charleston, SC USA.
Hollings Canc Ctr, Charleston, SC USA.
Tulane Univ, New Orleans, LA 70118 USA.
Eisai Pharmaceut, Woodcliff Lake, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 208
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700209
PM 27968624
ER
PT J
AU Jardim, DLF
Je, Y
Schutz, FA
Choueiri, TK
AF Jardim, D. L. Fontes
Je, Y.
Schutz, F. A.
Choueiri, T. K.
TI Hematologic toxicities in renal cell carcinoma and other malignancies
treated with bevacizumab: A meta-analysis of clinical trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 336
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700335
ER
PT J
AU Khambati, H
Choueiri, TK
Kollmannsberger, CK
North, S
Bjarnason, GA
Vaishampayan, UN
Wood, L
MacKenzie, MJ
Rini, BI
Heng, DY
AF Khambati, H.
Choueiri, T. K.
Kollmannsberger, C. K.
North, S.
Bjarnason, G. A.
Vaishampayan, U. N.
Wood, L.
MacKenzie, M. J.
Rini, B. I.
Heng, D. Y.
CA Int mRCC Database Consortium
TI Efficacy of targeted drug therapy for metastatic renal cell carcinoma in
the elderly patient population
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada.
Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
London Reg Canc Program, London, ON, Canada.
Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 318
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700317
PM 27968644
ER
PT J
AU Lu-Yao, GL
Kim, S
Moore, D
Shih, W
Lin, Y
DiPaola, RS
Zietman, AL
Yao, S
AF Lu-Yao, G. L.
Kim, S.
Moore, D.
Shih, W.
Lin, Y.
DiPaola, R. S.
Zietman, A. L.
Yao, S.
TI Is radiation therapy superior to conservative management in men with
localized prostate cancer?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA.
Univ Med & Dent New Jersey, Sch Publ Hlth, Canc Inst New Jersey, New Brunswick, NJ USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 73
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700074
PM 27968334
ER
PT J
AU Martin, NE
Chen, M
Nguyen, PL
Beard, C
Kantoff, PW
D'Amico, AV
AF Martin, N. E.
Chen, M.
Nguyen, P. L.
Beard, C.
Kantoff, P. W.
D'Amico, A. V.
TI Biopsy Gleason score and the duration of testosterone suppression among
men treated with external beam radiation and six months of combined
androgen blockade
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Connecticut, Storrs, CT USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RI Martin, Neil/E-2193-2014
OI Martin, Neil/0000-0002-8164-8516
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 191
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700192
PM 27968475
ER
PT J
AU Michaelson, MD
Cohen, DP
Li, S
Motzer, RJ
Escudier, B
Barrios, CH
Burnett, PE
Puzanov, I
AF Michaelson, M. D.
Cohen, D. P.
Li, S.
Motzer, R. J.
Escudier, B.
Barrios, C. H.
Burnett, P. E.
Puzanov, I.
TI Hand-foot syndrome (HFS) as a potential biomarker of efficacy in
patients (pts) with metastatic renal cell carcinoma (mRCC) treated with
sunitinib (SU)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Pfizer Oncol, La Jolla, CA USA.
Pfizer Oncol, Shanghai, Peoples R China.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Inst Gustave Roussy, Villejuif, France.
Pontificia Univ Catolica Rio Grande do Sul, Hosp Sao Lucas, Porto Alegre, RS, Brazil.
Vanderbilt Univ, Med Ctr, Nashville, TN USA.
RI Barrios, Carlos/G-8525-2015
NR 0
TC 3
Z9 3
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 320
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700319
ER
PT J
AU Mitin, T
Chen, M
Moran, BJ
Dosoretz, DE
Katin, MJ
Braccioforte, MH
Salenius, S
D'Amico, AV
AF Mitin, T.
Chen, M.
Moran, B. J.
Dosoretz, D. E.
Katin, M. J.
Braccioforte, M. H.
Salenius, S.
D'Amico, A. V.
TI Diabetes mellitus, race, and the odds of high-grade prostate cancer in
men diagnosed with prostate cancer in the United States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Univ Connecticut, Storrs, CT USA.
Prostate Canc Fdn Chicago, Westmont, IL USA.
21st Century Oncol, Ft Myers, FL USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 180
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700181
PM 27968485
ER
PT J
AU Morgans, AK
Hancock, ML
Barnette, G
Steiner, MS
Morton, RA
Smith, MR
AF Morgans, A. K.
Hancock, M. L.
Barnette, G.
Steiner, M. S.
Morton, R. A.
Smith, M. R.
TI Racial differences in bone mineral density and fractures in men
receiving androgen deprivation therapy for prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
GTx Inc, Memphis, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 212
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700213
PM 27968614
ER
PT J
AU Nguyen, PL
Chen, M
Chen, RC
Hoffman, KE
Hu, JC
Bennett, CL
Kattan, MW
Sartor, AO
Stein, K
D'Amico, AV
AF Nguyen, P. L.
Chen, M.
Chen, R. C.
Hoffman, K. E.
Hu, J. C.
Bennett, C. L.
Kattan, M. W.
Sartor, A. O.
Stein, K.
D'Amico, A. V.
CA COMPARE Registry Steering Comm
TI Comorbidity and treatment regret in men with recurrent prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Connecticut, Storrs, CT USA.
Univ N Carolina, Chapel Hill, NC USA.
Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
South Carolina Coll Pharm, Charleston, SC USA.
Hollings Canc Ctr, Charleston, SC USA.
Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
Tulane Univ, New Orleans, LA 70118 USA.
Eisai Pharmaceut, Woodcliff Lake, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 187
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700188
PM 27968480
ER
PT J
AU Petrylak, DP
Kantoff, PW
Rotshteyn, Y
Israel, RJ
Olson, WC
Ramakrishna, T
Morris, S
AF Petrylak, D. P.
Kantoff, P. W.
Rotshteyn, Y.
Israel, R. J.
Olson, W. C.
Ramakrishna, T.
Morris, S.
TI Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A
phase I trial in taxane-refractory prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Columbia Univ, Med Ctr, New York, NY USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Progen Pharmaceut Inc, New York, NY USA.
Progen Pharmaceut Inc, Tarrytown, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 158
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700159
PM 27968566
ER
PT J
AU Prasad, SM
Gu, X
Lipsitz, SR
Nguyen, PL
Hu, JC
AF Prasad, S. M.
Gu, X.
Lipsitz, S. R.
Nguyen, P. L.
Hu, J. C.
TI Inappropriate utilization of radiographic imaging in men with newly
diagnosed prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 120
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700121
PM 27968524
ER
PT J
AU Psutka, SP
Daha, A
Gervais, D
Feldman, AS
AF Psutka, S. P.
Daha, A.
Gervais, D.
Feldman, A. S.
TI Effect of salvage radiofrequency ablation on local control of recurrent
renal cell carcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 355
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700353
PM 27968664
ER
PT J
AU Richards, CJ
Je, Y
Schutz, FA
Dallabrida, SM
Moslehi, JJ
Choueiri, TK
AF Richards, C. J.
Je, Y.
Schutz, F. A.
Dallabrida, S. M.
Moslehi, J. J.
Choueiri, T. K.
TI Incidence and risk of congestive heart failure risk in renal cell cancer
(RCC) and non-RCC patients treated with sunitinib
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
Dana Farber Canc Inst, Dept Cardiol, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 316
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700315
PM 27968315
ER
PT J
AU Saylor, PJ
Hancock, ML
Barnette, G
Steiner, MS
Morton, RA
Smith, MR
AF Saylor, P. J.
Hancock, M. L.
Barnette, G.
Steiner, M. S.
Morton, R. A.
Smith, M. R.
TI Factors associated with vertebral fractures in men treated with
androgen-deprivation therapy (ADT) for prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
GTx Inc, Memphis, TN USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 205
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700206
PM 27968643
ER
PT J
AU Schutz, FA
Je, Y
Choueiri, TK
AF Schutz, F. A.
Je, Y.
Choueiri, T. K.
TI Hematologic toxicities in cancer patients treated with the multityrosine
Kinase sorafenib: A meta-analysis of clinical trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 352
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700350
PM 27968648
ER
PT J
AU Schutz, FA
Xie, W
Heng, DY
Donskov, F
Wood, L
Vaishampayan, UN
Tan, M
MacKenzie, MJ
Kollmannsberger, CK
Choueiri, TK
AF Schutz, F. A.
Xie, W.
Heng, D. Y.
Donskov, F.
Wood, L.
Vaishampayan, U. N.
Tan, M.
MacKenzie, M. J.
Kollmannsberger, C. K.
Choueiri, T. K.
TI The effect of low serum sodium on treatment outcome to vascular
endothelial growth factor (VEGF)-targeted therapy in metastatic renal
cell carcinoma: Results from a large international collaboration
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark.
Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Canc Ctr Singapore, Singapore, Singapore.
London Reg Canc Program, London, ON, Canada.
British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 322
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700321
PM 27968635
ER
PT J
AU Shipley, WU
Hunt, D
Lukka, HR
Major, P
Heney, NM
Grignon, D
Patel, M
Bahary, J
Lawton, CA
Sandler, HM
AF Shipley, W. U.
Hunt, D.
Lukka, H. R.
Major, P.
Heney, N. M.
Grignon, D.
Patel, M.
Bahary, J.
Lawton, C. A.
Sandler, H. M.
TI Initial report of RTOG 9601, a phase III trial in prostate cancer:
Effect of anti-androgen therapy (AAT) with bicalutamide during and after
radiation therapy (RT) on freedom from progression and incidence of
metastatic disease in patients following radical prostatectomy (RP) with
pT2-3,N0 disease and elevated PSA levels
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Amer Coll Radiol, Philadelphia, PA USA.
McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada.
Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada.
Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
Univ Montreal, Dept Radiat Oncol, Ctr Hosp Univ Montreal, Montreal, PQ, Canada.
Med Coll Wisconsin, Milwaukee, WI 53226 USA.
Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 1
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700002
ER
PT J
AU Smith, DC
Smith, MR
Small, EJ
Sweeney, C
Kurzrock, R
Gordon, MS
Vogelzang, NJ
Scheffold, C
Ballinger, MD
Hussain, M
AF Smith, D. C.
Smith, M. R.
Small, E. J.
Sweeney, C.
Kurzrock, R.
Gordon, M. S.
Vogelzang, N. J.
Scheffold, C.
Ballinger, M. D.
Hussain, M.
TI Phase II study of XL184 in a cohort of patients (pts) with
castration-resistant prostate cancer (CRPC) and measurable soft tissue
disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Pinnacle Oncol Arizona, Scottsdale, AZ USA.
Comprehens Canc Ctr Nevada, Las Vegas, NV USA.
Exelixis, San Francisco, CA USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 127
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700128
PM 27968542
ER
PT J
AU Smith, MR
Klotz, L
van der Meulen, E
Colli, E
Tanko, LB
AF Smith, M. R.
Klotz, L.
van der Meulen, E.
Colli, E.
Tanko, L. B.
TI Association of baseline risk factors with cardiovascular (CV) events
during long-term degarelix therapy in men with prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
Ferring Pharmaceut, Copenhagen, Denmark.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 190
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700191
PM 27968474
ER
PT J
AU Talcott, JA
Zietman, AL
Kaplan, ID
Clark, JA
D'Amico, AV
AF Talcott, J. A.
Zietman, A. L.
Kaplan, I. D.
Clark, J. A.
D'Amico, A. V.
TI Evaluation of a prostate brachytherapy technique designed to reduce
short- and long-term urinary dysfunction: 5-year results of a
multi-institutional comparative cohort study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Charlestown, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Boston Univ, Sch Publ Hlth, Boston, MA USA.
Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2011
VL 29
IS 7
SU S
MA 70
PG 1
WC Oncology
SC Oncology
GA V31JU
UT WOS:000208880700071
PM 27968332
ER
PT J
AU Gallucci, GO
Grutter, L
Chuang, SK
Belser, UC
AF Gallucci, German O.
Gruetter, Linda
Chuang, Sung-Kiang
Belser, Urs C.
TI Dimensional changes of peri-implant soft tissue over 2 years with
single-implant crowns in the anterior maxilla
SO JOURNAL OF CLINICAL PERIODONTOLOGY
LA English
DT Article
DE dental implants; DIM; emergence profile; interproximal papilla;
peri-implant soft tissue; single-implant crown
ID TITANIUM IMPLANTS; TOOTH IMPLANTS; TEETH; ABUTMENTS; BONE; AESTHETICS;
HUMANS; MUCOSA; PINK
AB P>Objective
To compare the peri-implant soft tissue dimensions after insertion of single-implant crowns in the anterior maxilla.
Materials and Methods
Twenty patients were accepted according to well-defined inclusion criteria and randomized to porcelain-fused-to-metal (PFM) or all-ceramic groups. Follow-up was at: Baseline (B), Crown Insertion (CI), 1-year (1Y), and 2-year (2Y). The following parameters were statistically analysed: distance implant shoulder to marginal peri-implant mucosa (DIM), papilla height (PH), width of keratinized mucosa (KM), crestal bone level (CBL), full mouth plaque score (FMPS), full mouth bleeding score (FMBS), and probing pocket depth.
Results
Between groups measurements for DIM, PH, KM, CBL, FMPS, and FMBS showed no statistically significant differences except the distal CBLs to adjacent tooth. DIM (mid-facial) decreased from B to CI remaining stable at 1Y and 2Y (p-value 0.0014). DIM mesial and distal aspects significantly increased from B to CI showing signs of stability at the 2Y. PH between B and CI increased at the mesial site and at the distal site, thereafter, peri-implant soft tissues were stable at the 2Y.
Conclusion
The insertion of an implant crown affects the peri-implant mucosa morphology by an apical displacement at the mid-facial aspect and coronal at mesial and distal sites.
C1 [Gallucci, German O.] Harvard Univ, Dept Restorat Dent & Biomat Sci, Sch Dent Med, Boston, MA 02115 USA.
[Chuang, Sung-Kiang] Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA.
[Gruetter, Linda; Belser, Urs C.] Univ Geneva, Sch Dent Med, Dept Fixed Prosthodont & Occlus, Geneva, Switzerland.
RP Gallucci, GO (reprint author), Harvard Univ, Dept Restorat Dent & Biomat Sci, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA.
EM german_gallucci@hsdm.harvard.edu
RI Gallucci, German/H-4505-2011
FU ITI Foundation, Basel, Switzerland [362]
FX This study was funded by the ITI Foundation, Grant 362, Basel,
Switzerland.
NR 26
TC 18
Z9 19
U1 0
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0303-6979
J9 J CLIN PERIODONTOL
JI J. Clin. Periodontol.
PD MAR
PY 2011
VL 38
IS 3
BP 293
EP 299
DI 10.1111/j.1600-051X.2010.01686.x
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 715MD
UT WOS:000286887700013
PM 21219391
ER
PT J
AU Caroff, SN
Davis, VG
Miller, DD
Davis, SM
Rosenheck, RA
McEvoy, JP
Campbell, EC
Saltz, BL
Riggio, S
Chakos, MH
Swartz, MS
Keefe, RSE
Stroup, TS
Lieberman, JA
AF Caroff, Stanley N.
Davis, Vicki G.
Miller, Del D.
Davis, Sonia M.
Rosenheck, Robert A.
McEvoy, Joseph P.
Campbell, E. Cabrina
Saltz, Bruce L.
Riggio, Silvana
Chakos, Miranda H.
Swartz, Marvin S.
Keefe, Richard S. E.
Stroup, T. Scott
Lieberman, Jeffrey A.
CA CATIE Investigators
TI Treatment Outcomes of Patients With Tardive Dyskinesia and Chronic
Schizophrenia
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID OUTPATIENT HEALTH OUTCOMES; FOLLOW-UP; 2ND-GENERATION ANTIPSYCHOTICS;
RANDOMIZED-TRIAL; HALOPERIDOL; CATIE; OLANZAPINE; CLOZAPINE; BLIND;
RISPERIDONE
AB Objective: We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD.
Method: This analysis compared 200 patients with DSM-IV defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with chi(2) tests. Data were collected from January 2001 to December 2004.
Results: Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (chi(2)(1) = 0.11, P=.743). Changes in PANSS scores were not significantly different (F-1,F-974 = 0.82, P=.366), but patients with TD showed less improvement in neurocognitive scores (F-1,F-359=6.53, P=.011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F-3,F-151 = 0.32, P=.811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a >= 50% decrease in AIMS score, and 7% showed a >= 50% increase in AIMS score.
Conclusions: Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. Trial Registration: clinicaltrials.gov Identifier: NCT00014001 J Clin Psychiatry 2011;72(3):295-303 (C) Copyright 2010 Physicians Postgraduate Press, Inc.
C1 [Caroff, Stanley N.; Campbell, E. Cabrina] Dept Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA.
[Caroff, Stanley N.; Campbell, E. Cabrina] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Davis, Vicki G.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA.
[Miller, Del D.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA.
[Davis, Sonia M.] Quintiles Inc, Res Triangle Pk, NC USA.
[Davis, Sonia M.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Rosenheck, Robert A.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA.
[McEvoy, Joseph P.] Duke Univ, Med Ctr, Dept Biol Psychiat, John Umstead Hosp, Durham, NC USA.
[McEvoy, Joseph P.; Swartz, Marvin S.; Keefe, Richard S. E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[Saltz, Bruce L.] Mental Hlth Advocates Inc, Boca Raton, FL USA.
[Riggio, Silvana] James J Peter Vet Affairs Med Ctr, New York, NY USA.
[Riggio, Silvana] Mt Sinai Sch Med, New York, NY USA.
[Chakos, Miranda H.] SUNY Hlth Sci Ctr, Dept Psychiat, Brooklyn, NY 11203 USA.
[Stroup, T. Scott; Lieberman, Jeffrey A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY USA.
RP Caroff, SN (reprint author), Vet Affairs Med Ctr 116A, Univ & Woodland Ave, Philadelphia, PA 19104 USA.
EM stanley.caroff@va.gov
RI Stroup, Thomas/F-9188-2014
OI Stroup, Thomas/0000-0002-3123-0672
FU National Institute of Mental Health [NO1 MH90001]; Department of
Veterans Affairs, Veterans Health Administration, Office of Research
Development; Pfizer; Bristol-Myers Squibb; Ortho-McNeil Neurologics;
National Institute of Mental Health; Foundation for the National
Institute of Health; Eli Lilly; Janssen; AstraZeneca; Wyeth; Forest;
Dainippon Sumitomo; Indevus; Cephalon; Novartis; Solvay; Roche; Organon;
Allon; Singapore National Medical Research Council
FX Dr Caroff has been a consultant for Eli Lilly and has received
grant/research support from Pfizer, Bristol-Myers Squibb, and
Ortho-McNeil Neurologics. Dr V. G. Davis is an employee of the
Collaborative Studies Coordinating Center in the Department of
Biostatistics, University of North Carolina. Dr Miller has been a
consultant for Otsuka, Hoffmann-La Roche, and Schering Plough and has
received research funds from the National Institute of Mental Health and
the Foundation for the National Institute of Health. Dr S. M. Davis is
an employee of Quintiles. Dr Rosenheck has been a consultant for Eli
Lilly, GlaxoSmithKline, Bristol-Myers Squibb, Organon, and Janssen; has
received research support from Bristol-Myers Squibb, Eli Lilly, Janssen,
AstraZeneca, and Wyeth; and provided expert testimony for the plaintiffs
in UFCW Local 1776 and Participating Employers Health and Welfare Fund,
et al vs Eli Lilly and Company; for the respondent in Eli Lilly Canada
Inc vs Novapharm Ltd and Minister of Health, respondent; and for the
Patent Medicines Prices Review Board, Canada, in the matter of Janssen
Ortho Inc. and "Risperdal Consta." Dr McEvoy has received research
funding from AstraZeneca, Forest, Eli Lilly, Janssen, Pfizer,
Sanofi-Aventis, and Dainippon Sumitomo; consulting or advisory board
fees from Pfizer, Bristol-Myers Squibb, Indevus, and Eli Lilly; lecture
fees from Janssen and Bristol-Myers Squibb; and honoraria from Eli
Lilly. Dr Saltz has received research funds from Cephalon, AstraZeneca,
and Novartis and lecture fees from Janssen and Novartis. Dr Chakos has
been a consultant for Roche and has received grant/research support from
Pfizer, Solvay, AstraZeneca, Janssen, Roche, and Organon. Dr Swartz has
received consulting and education fees from AstraZeneca, Bristol-Myers
Squibb, Pfizer, Eli Lilly, and Comprehensive Neuroscience and has
received grant/research support and honoraria from Eli Lilly. Dr Keefe
is currently receiving or in the past 12 months has received
investigator-initiated research funding support from the National
Institute of Mental Health, Allon, Novartis, and the Singapore National
Medical Research Council and an unrestricted educational grant from
AstraZeneca; and has received honoraria from or served as a consultant
or advisory board member for Abbott, AstraZeneca, BiolineRx,
Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo, Eli Lilly, Johnson &
Johnson, Lundbeck, Memory, Merck, Neurosearch, Orion, Orexigen, Otsuka,
Pfizer, Roche, Targacept, Sanofi-Aventis, Shire, Wyeth, and Xenoport. In
the past, he has received honoraria from or served as a consultant or
advisory board member for Acadia, Cortex, Cyberonics, Forest, Gabriel,
GlaxoSmithKline, Repligen, Saegis, and Schering Plough and has received
research funding from AstraZeneca, Eli Lilly, Janssen, and Pfizer. He
receives royalties from the Brief Assessment of Cognition in
Schizophrenia (BACS) testing battery and the MATRICS Battery (BACS
Symbol Coding). Dr Stroup has received research funding from Eli Lilly
and consulting fees from Janssen, Eli Lilly, Lundbeck, Solvay,
GlaxoSmithKline, and Bristol-Myers Squibb. Dr Lieberman has received
research funding from AstraZeneca, Bristol-Myers Squibb,
GlaxoSmithKline, Janssen, and Pfizer and consulting and educational fees
from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest,
GlaxoSmithKline, Janssen, Novartis, Pfizer, and Solvay. Drs Campbell and
Riggio report no financial or other relationship relevant to the subject
of this article.; Supported by the Clinical Antipsychotic Trials of
Intervention Effectiveness project, National Institute of Mental Health
(NO1 MH90001). This article was based on results from the Clinical
Antipsychotic Trials of Intervention Effectiveness project, supported by
the National Institute of Mental Health (NO1 MH90001). The aim of this
project is to examine the comparative effectiveness of antipsychotic
drugs in conditions for which their use is clinically indicated
including schizophrenia and Alzheimer's disease. The project was carried
out by principal investigators from Columbia University, the University
of North Carolina, Duke University, the University of Southern
California, the University of Rochester, and Yale University in
association with Quintiles, Inc.; the program staff of the Division of
Interventions and Services Research of the National Institute of Mental
Health; and investigators from 57 sites in the United States (CATIE
Investigators Group). AstraZeneca Pharmaceuticals LP, Bristol-Myers
Squibb Company, Forest Pharmaceuticals, Inc., Janssen Pharmaceutics
Products, L.P., Eli Lilly and Company, Otsuka Pharmaceutical Co., Ltd.,
Pfizer Inc., and Zenith Goldline Pharmaceuticals, Inc., provided
medications for the studies. This material is based upon work also
supported in part by the Department of Veterans Affairs, Veterans Health
Administration, Office of Research Development, with resources and the
use of facilities at the Philadelphia Veterans Affairs Medical Center.
NR 53
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PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD MAR
PY 2011
VL 72
IS 3
BP 295
EP 303
DI 10.4088/JCP.09m05793yel
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 741BM
UT WOS:000288838100004
PM 20816031
ER
PT J
AU Klein, RL
Carter, RE
Jenkins, AJ
Lyons, TJ
Baker, NL
Gilbert, GE
Virella, G
Lopes-Virella, MF
AF Klein, Richard L.
Carter, Rickey E.
Jenkins, Alicia J.
Lyons, Timothy J.
Baker, Nathaniel L.
Gilbert, Gregory E.
Virella, Gabriel
Lopes-Virella, Maria F.
CA DCCT-EDIC Res Grp
TI LDL-containing immune complexes in the DCCT/EDIC cohort: associations
with lipoprotein subclasses
SO JOURNAL OF DIABETES AND ITS COMPLICATIONS
LA English
DT Article
DE Diabetes; Lipoprotein subclasses; LDL autoantibodies; Intima-media
thickness; Statistical mediation analysis
ID INTIMA-MEDIA THICKNESS; CORONARY-ARTERY-DISEASE;
LOW-DENSITY-LIPOPROTEIN; OXIDIZED LDL; ATHEROSCLEROTIC LESIONS;
DIABETES-MELLITUS; HUMAN MACROPHAGES; COMPLICATIONS; ANTIBODIES;
GLYCOXIDATION
AB Immune complexes containing modified LDL (LDL-IC) and NMR-detennined Total LDL particle concentrations are significantly associated with intima-media thickness (IMT). We analyzed the associations between concentrations of NMR-determined lipoprotein subclasses and LDL-IC in the DCCT/EDIC cohort. LDL-IC concentrations in women and men of the DCCT/EDIC cohort did not differ significantly and were positively associated with Total LDL particle concentrations in men and women (r=0.34, r=0.32, respectively; P<.01) and with Small LDL concentration (r=0.22, r=0.13, respectively; P<.01). In women, Large LDL concentrations were also associated with LDL-IC (r=0.20, P<.01) while in men, the association was more modest (r=0.11, P<.05). Thus, both Small and Large LDL are associated with LDL-IC formation. Based on the results from statistical mediation analyses, we concluded that plasma concentrations of LDL-1C may provide a physiological link between the statistically significant association of Total LDL particle concentration with carotid artery IMT in subjects with Type 1 diabetes. Furthermore, after adjusting for conventional risk factors, there was a decrease in LDL-1C concentration even in the presence of high Total LDL particle concentrations in those women with high concentrations of Large HDL, but the association was not evident in men. This suggests that the associations between Large HDL and Total LDL particle concentrations, and their associations with LDL-IC levels, differ by gender and suggest that LDL-1C partially mediate the contribution of Total LDL particle concentration to increased carotid IMT in diabetic men. Published by Elsevier Inc.
C1 [Klein, Richard L.; Jenkins, Alicia J.; Lopes-Virella, Maria F.] Med Univ S Carolina, Div Endocrinol Metab & Med Genet, Dept Med, Charleston, SC 29403 USA.
[Klein, Richard L.; Lopes-Virella, Maria F.] Vet Affairs Med Ctr, Res Serv, Ralph H Johnson Dept, Charleston, SC 29403 USA.
[Carter, Rickey E.; Baker, Nathaniel L.; Gilbert, Gregory E.] Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29403 USA.
[Jenkins, Alicia J.] Univ Melbourne, Dept Med, St Vincents Hosp, Fitzroy, Vic 3065, Australia.
[Jenkins, Alicia J.; Lyons, Timothy J.] Univ Oklahoma, Hlth Sci Ctr, Endocrinol Sect, Oklahoma City, OK USA.
[Jenkins, Alicia J.; Lyons, Timothy J.] Univ Oklahoma, Hlth Sci Ctr, Harold Hamm Diabet Ctr, Oklahoma City, OK USA.
[Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29403 USA.
[DCCT-EDIC Res Grp] Box NDIC DCCT, Bethesda, MD USA.
RP Klein, RL (reprint author), Med Univ S Carolina, Div Endocrinol Metab & Med Genet, Dept Med, 114 Doughty St,STB 501, Charleston, SC 29403 USA.
EM kleinrl@musc.edu
RI Jenkins, Alicia/N-2482-2015; Gilbert, Gregory/C-7735-2016
OI Gilbert, Gregory/0000-0003-0879-5496
FU American Diabetes Association; Juvenile Diabetes Research Foundation
[4-1998-272, 996001]; National Institutes of Health [PO1 HL55782];
Diabetes Research and Wellness Foundation (Fairfax, VA, USA); Department
of Veterans Affairs; National Institute of Diabetes, Endocrinology and
Metabolic Diseases of the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK)
FX This research was supported by funding by the American Diabetes
Association, Juvenile Diabetes Research Foundation (4-1998-272, 996001),
National Institutes of Health (PO1 HL55782), The Diabetes Research and
Wellness Foundation (Fairfax, VA, USA), and the Merit Review Program of
the Department of Veterans Affairs. The DCCT/EDIC Research Group is
sponsored through research contracts from the National Institute of
Diabetes, Endocrinology and Metabolic Diseases of the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National
Institutes of Health.
NR 30
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1056-8727
J9 J DIABETES COMPLICAT
JI J. Diabetes Complications
PD MAR-APR
PY 2011
VL 25
IS 2
BP 73
EP 82
DI 10.1016/j.jdiacomp.2010.03.001
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 736WH
UT WOS:000288525200001
PM 20605479
ER
PT J
AU Truong, QA
Charipar, EM
Ptaszek, LM
Taylor, C
Fontes, JD
Kriegel, M
Irlbeck, T
Mahabadi, AA
Blankstein, R
Hoffmann, U
AF Truong, Quynh A.
Charipar, Elizabeth M.
Ptaszek, Leon M.
Taylor, Carolyn
Fontes, Joao D.
Kriegel, Matthias
Irlbeck, Thomas
Mahabadi, Amir A.
Blankstein, Ron
Hoffmann, Udo
TI Usefulness of electrocardiographic parameters as compared with computed
tomography measures of left atrial volume enlargement: from the ROMICAT
trial
SO JOURNAL OF ELECTROCARDIOLOGY
LA English
DT Article; Proceedings Paper
CT 37th International Congress on Electrocardiology
CY JUN, 2010
CL Lund, SWEDEN
DE Left atrium; Left atrial volume; Left atrial enlargement; Computed
tomography; Electrocardiogram
ID P-WAVE; MYOCARDIAL-INFARCTION; DIAGNOSIS; ECHOCARDIOGRAPHY; CRITERIA;
FORCE; HEART; PREDICTOR; SIZE
AB Introduction: The 12-lead surface electrocardiogram (ECG) is commonly used as a noninvasive modality to assess for left atrial enlargement (LAE), but data comparing ECG against cardiac computed tomography (CT) for LAE is lacking. We aimed to determine the diagnostic performance of 6 ECG criteria for LAE as compared with CT left atrial volume (LAV) and index to body surface area (LAVI) as the reference standard.
Materials and Methods: In 339 patients (age: mean +/- mean, 53 +/- 12 years; 63% male), we evaluated the quantitative ECG parameters of P duration, P to PR segment ratio, P wave area, and P terminal force in lead VI. We also assessed qualitatively the morphology of bifid and biphasic P waves. Patients were stratified into top and lowest quartile of LAV and LAVI by CT.
Results: Of the 6 ECG criteria, patients with P duration greater than 110 milliseconds had a 2 1/2-fold increase likelihood of being in the top quartile of LAV (adjusted odds ratio [OR], 2.51; P = .01) and LAVI (adjusted OR, 2.74; P = .007) as measured by CT. For this ECG criterion, the sensitivity and specificity were 71% and 55% for CT LAE by LAV and 61% and 55% for LAVI. The remaining ECG parameters of LAE assessed (P to PR segment ratio, P terminal force in lead VI, P wave area, bifid, and biphasic P wave) were not associated with LAE by CT-based LAV or LAVI (all P >= .20).
Discussion: Only P duration greater than 110 milliseconds was independently associated with LAE based on CT-derived LA volume and index. However, none of the established ECG parameters of LAE have sufficient diagnostic accuracies for predicting volumetric enlargement by CT, thus limiting its clinical utility. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Truong, Quynh A.; Charipar, Elizabeth M.; Taylor, Carolyn; Fontes, Joao D.; Kriegel, Matthias; Irlbeck, Thomas; Mahabadi, Amir A.; Blankstein, Ron; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol,Med Sch, Boston, MA 02114 USA.
[Truong, Quynh A.; Ptaszek, Leon M.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, Boston, MA 02114 USA.
[Blankstein, Ron] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
RP Truong, QA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol,Med Sch, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM qtruong@partners.org
FU NHLBI NIH HHS [L30HL093896, K23 HL098370, K24 HL113128, L30 HL093806,
L30 HL093806-01, R01 HL080053, R01 HL080053-03, T32 HL076136, T32
HL076136-05, T32HL076136]
NR 27
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U2 3
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 0022-0736
J9 J ELECTROCARDIOL
JI J. Electrocardiol.
PD MAR-APR
PY 2011
VL 44
IS 2
BP 257
EP 264
DI 10.1016/j.jelectrocard.2010.04.011
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 733SK
UT WOS:000288282900032
PM 20537347
ER
PT J
AU Sarkar, U
Schillinger, D
Lopez, A
Sudore, R
AF Sarkar, Urmimala
Schillinger, Dean
Lopez, Andrea
Sudore, Rebecca
TI Validation of Self-Reported Health Literacy Questions Among Diverse
English and Spanish-Speaking Populations
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE health literacy; limited English proficiency; Hispanic American;
validation studies
ID VULNERABLE PATIENTS; HOSPITAL ADMISSION; MANAGEMENT SUPPORT; DIABETES
PATIENTS; IDENTIFY PATIENTS; LIMITED LITERACY; GLYCEMIC CONTROL;
PRIMARY-CARE; KNOWLEDGE; RISK
AB Limited health literacy (HL) contributes to poor health outcomes and disparities, and direct measurement is often time-intensive. Self-reported HL questions have not been validated among Spanish-speaking and diverse English-speaking populations.
To evaluate three self-reported questions:1 "How confident are you filling out medical forms?";2 "How often do you have problems learning about your medical condition because of difficulty understanding written information?"; and3 "How often do you have someone help you read hospital materials?" Answers were based on a 5-point Likert scale.
This was a validation study nested within a trial of diabetes self-management support in the San Francisco Department of Public Health.
English and Spanish-speaking adults with type 2 diabetes receiving primary care.
Using the Test of Functional Health Literacy in Adults (s-TOFHLA) in English and Spanish as the reference, we classified HL as inadequate, marginal, or adequate. We calculated the C-index and test characteristics of the three questions and summative scale compared to the s-TOFHLA and assessed variations in performance by language, race/ethnicity, age, and education.
Of 296 participants, 48% were Spanish-speaking; 9% were White, non-Hispanic; 47% had inadequate HL and 12% had marginal HL. Overall, 57% reported being confident with forms "somewhat" or less. The "confident with forms" question performed best for detecting inadequate (C-index = 0.82, (0.77-0.87)) and inadequate plus marginal HL (C index = 0.81, (0.76-0.86); p < 0.01 for differences from other questions), and performed comparably to the summative scale. The "confident with forms" question and scale also performed best across language, race/ethnicity, educational attainment, and age.
A single self-reported HL question about confidence with forms and a summative scale of three questions discriminated between Spanish and English speakers with adequate HL and those with inadequate and/or inadequate plus marginal HL. The "confident with forms" question or the summative scale may be useful for estimating HL in clinical research involving Spanish-speaking and English-speaking, chronically-ill, diverse populations.
C1 [Sarkar, Urmimala; Schillinger, Dean; Lopez, Andrea] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Sarkar, Urmimala; Schillinger, Dean; Lopez, Andrea] Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco Ctr Vulnerable Populat, San Francisco, CA 94143 USA.
[Sudore, Rebecca] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94143 USA.
RP Sarkar, U (reprint author), Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Box 1364,1001 Potrero,Bldg 10,3rd Floor, San Francisco, CA 94143 USA.
EM usarkar@medsfgh.ucsf.edu
FU San Francisco Veterans' Affairs Medical Center; National Center for
Research Resources [KL2RR024130]; Agency for Healthcare Research and
Quality [R18 HS01726101, K08 HS017594]; NIH [ULRR024131]; Veterans
Affairs; Pfizer
FX We gratefully acknowledge the data analysis performed by Kathy Z. Fung,
MS, (funded by the San Francisco Veterans' Affairs Medical Center) and
the biostatistical advice provided by John Boscardin, Ph.D (funded by
the National Center for Research Resources KL2RR024130). Funds were
provided by Agency for Healthcare Research and Quality R18 HS01726101
(to DS), a NIH Clinical and Translational Science Award ULRR024131 (to
DS), the National Center for Research Resources KL2RR024130 (to US.) and
Agency for Healthcare Research and Quality K08 HS017594 (to US), a
Veterans Affairs Career Development Award and a Pfizer Fellowship in
Clear Health Communication (RS). None of the funders had any role in
study design; in the collection, analysis, and interpretation of data;
in the writing of the manuscript; or in the decision to submit the
manuscript for publication.
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PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAR
PY 2011
VL 26
IS 3
BP 265
EP 271
DI 10.1007/s11606-010-1552-1
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 725QV
UT WOS:000287661800013
PM 21057882
ER
PT J
AU Celi, LAG
Tang, RJ
Villarroel, MC
Davidzon, GA
Lester, WT
Chueh, HC
AF Celi, Leo Anthony G.
Tang, Robin J.
Villarroel, Mauricio C.
Davidzon, Guido A.
Lester, William T.
Chueh, Henry C.
TI A Clinical Database-Driven Approach to Decision Support: Predicting
Mortality Among Patients with Acute Kidney Injury
SO JOURNAL OF HEALTHCARE ENGINEERING
LA English
DT Article
DE modeling; data mining; collective experience; decision support; ICU;
mortality prediction; acute kidney injury
ID CRITICALLY-ILL PATIENTS; ACUTE-RENAL-FAILURE; RIFLE; CLASSIFICATION;
MULTICENTER
AB In exploring an approach to decision support based on information extracted from a clinical database, we developed mortality prediction models of intensive care unit (ICU) patients who had acute kidney injury (AKI) and compared them against the Simplified Acute Physiology Score (SAPS). We used MIMIC, a public de-identified database of ICU patients admitted to Beth Israel Deaconess Medical Center, and identified 1400 patients with an ICD9 diagnosis of AKI and who had an ICU stay >= 3 days. Multivariate regression models were built using the SAPS variables from the first 72 hours of ICU admission. All the models developed on the training set performed better than SAPS (AUC = 0.64, Hosmer-Lemeshow p < 0.001) on an unseen test set; the best model had an AUC = 0.74 and Hosmer-Lemeshow p = 0.53. These findings suggest that local customized modeling might provide more accurate predictions. This could be the first step towards an envisioned individualized point-of-care probabilistic modeling using one's clinical database.
C1 [Celi, Leo Anthony G.] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA.
[Tang, Robin J.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Villarroel, Mauricio C.] Univ Oxford, Dept Engn Sci, Inst Biomed Engn, Oxford OX1 3PJ, England.
[Davidzon, Guido A.] Stanford Univ, Med Ctr, Dept Radiol Nucl Med, Stanford, CA 94305 USA.
[Lester, William T.; Chueh, Henry C.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA.
RP Celi, LAG (reprint author), Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, 330 Brookline Ave, Boston, MA 02215 USA.
EM lceli@bidmc.harvard.edu; rjt2112@columbia.edu; villarroel@eng.ox.ac.uk;
davidzon@stan-ford.edu; wlester@partners.org; hchueh@partners.org
OI Lester, William/0000-0003-4086-9280; Davidzon, Guido/0000-0001-5579-6825
FU National Library of Medicine (NLM) Training Grant [2T15LM007092-16];
National Institute of Health (NIH); National Institute of Biomedical
Imaging and Bioengineering (NIBIB) [2R01 EB001659]
FX This work is supported by National Library of Medicine (NLM) Training
Grant # 2T15LM007092-16. The MIMIC II database was funded by the
National Institute of Health (NIH), and its National Institute of
Biomedical Imaging and Bioengineering (NIBIB) under Grant 2R01 EB001659.
NR 11
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U1 1
U2 6
PU MULTI-SCIENCE PUBL CO LTD
PI BRENTWOOD
PA 5 WATES WAY, BRENTWOOD CM15 9TB, ESSEX, ENGLAND
SN 2040-2295
J9 J HEALTHC ENG
JI J. Healthc. Eng.
PD MAR
PY 2011
VL 2
IS 1
BP 97
EP 109
DI 10.1260/2040-2295.2.1.97
PG 13
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 045BJ
UT WOS:000311668900007
PM 22844575
ER
PT J
AU Pol, S
Ghalib, RH
Rustgi, VK
Martorell, C
Everson, GT
Tatum, HA
Hezode, C
Lim, JK
Bronowicki, JP
Abrams, GA
Brau, N
Morris, DW
Thuluvath, P
Reindollar, R
Yin, PD
Diva, U
Hindes, R
McPhee, F
Gao, M
Thiry, A
Schnittman, S
Hughes, EA
AF Pol, S.
Ghalib, R. H.
Rustgi, V. K.
Martorell, C.
Everson, G. T.
Tatum, H. A.
Hezode, C.
Lim, J. K.
Bronowicki, J. -P.
Abrams, G. A.
Brau, N.
Morris, D. W.
Thuluvath, P.
Reindollar, R.
Yin, P. D.
Diva, U.
Hindes, R.
McPhee, F.
Gao, M.
Thiry, A.
Schnittman, S.
Hughes, E. A.
TI FIRST REPORT OF SVR12 FOR A NS5A REPLICATION COMPLEX INHIBITOR,
BMS-790052 IN COMBINATION WITH PEG-IFN alpha-2A AND RBV: PHASE 2A TRIAL
IN TREATMENT-NAIVE HCV-GENOTYPE-1 SUBJECTS
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 46th Annual Meeting of the
European-Association-for-the-Study-of-the-Liver (EASL)
CY 2011
CL Berlin, GERMANY
SP European Assoc Study Liver (EASL)
C1 [Pol, S.] Hop Cochin, F-75674 Paris, France.
[Ghalib, R. H.] Methodist Hlth Syst, Liver Inst, Dallas, TX USA.
[Rustgi, V. K.] Metropolitan Res, Fairfax, VA USA.
[Martorell, C.] Res Inst, Springfield, MA USA.
[Everson, G. T.] Univ Colorado, Aurora, CO USA.
[Tatum, H. A.] Opt Hlth Res LLC, Tulsa, OK USA.
[Hezode, C.] CHU Henri Mondor, F-94010 Creteil, France.
[Lim, J. K.] Yale Univ, Sch Med, New Haven, CT USA.
[Bronowicki, J. -P.] Hop Adultes Braboios, Vandoeuvre Les Nancy, France.
[Abrams, G. A.] Alabama Liver & Digest Specialists, Montgomery, AL USA.
[Brau, N.] James J Peters VAMC, Bronx, NY USA.
[Morris, D. W.] Healthcare Res Consultants, Tulsa, OK USA.
[Thuluvath, P.] St Johns Mercy Med Ctr, Baltimore, MD USA.
[Reindollar, R.] Carolinas Ctr Liver Dis Res Dept, Statesville, NC USA.
[Yin, P. D.; Diva, U.; Hindes, R.; McPhee, F.; Gao, M.; Thiry, A.; Schnittman, S.; Hughes, E. A.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
EM stanislas.pol@cch.aphp.fr
NR 0
TC 10
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2011
VL 54
SU 1
MA 1373
BP S544
EP S545
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 856GC
UT WOS:000297625603057
ER
PT J
AU Chang, LM
Maheshwari, P
Werth, S
Schaffer, L
Head, SR
Kovarik, C
Werth, VP
AF Chang, Laura M.
Maheshwari, Prateesh
Werth, Sheila
Schaffer, Lana
Head, Steven R.
Kovarik, Carrie
Werth, Victoria P.
TI Identification and Molecular Analysis of Glycosaminoglycans in Cutaneous
Lupus Erythematosus and Dermatomyositis
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE chondroitin sulfate; cutaneous lupus erythematosus; dermatomyositis;
glycosaminoglycans; hyaluronan
ID CHONDROITIN-SULFATE; HUMAN SKIN; HYALURONAN METABOLISM;
MONOCLONAL-ANTIBODIES; CD44; CELLS; EXPRESSION; ADHESION; INJURY;
PROTEOGLYCANS
AB Glycosaminoglycans (GAGs), also known histologically as dermal mucin, accumulate in several inflammatory skin conditions. Because different GAG species have distinct immunologic effects, the authors examined two GAGs, hyaluronan (HA) and chondroitin sulfate (CS), using specific stains in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). In the dermis of one CLE subtype, tumid LE (TLE), they found only increased HA, but both HA and CS were significantly elevated in another CLE subtype, discoid LE (DLE). DM lesional dermis accumulated mainly CS but not HA. The authors then used glycomic gene expression microarrays to assess the expression of HA-and CS-related genes in CLE skin. Real-time quantitative PCR confirmed significantly increased expression of HAS2, CHSY1, and C4ST1 in the combined groups of CLE lesions (n = 8) compared to healthy controls (n = 4). Thus, the increase in HA in CLE presumably results from upregulation of HAS2, whereas CHSY1 and C4ST1 appear to contribute to increased CS. Based on their known immunomodulatory effects in other systems, HA and CS may thus participate in the pathophysiology of these inflammatory skin conditions. (J Histochem Cytochem 59:336-345, 2011)
C1 [Chang, Laura M.; Maheshwari, Prateesh; Werth, Sheila; Kovarik, Carrie; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Chang, Laura M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Maheshwari, Prateesh] Univ Penn, Coll Arts & Sci, Philadelphia, PA 19104 USA.
[Kovarik, Carrie; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA.
[Schaffer, Lana; Head, Steven R.] Consortium Funct Glyc, DNA Array Core Facil, La Jolla, CA USA.
[Schaffer, Lana; Head, Steven R.] Scripps Res Inst, La Jolla, CA 92037 USA.
RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, 2 Maloney Bldg,3400 Spruce St, Philadelphia, PA 19104 USA.
EM werth@mail.med.upenn.edu
FU Lupus Foundation of American; Department of Veterans Affairs Veterans
Health Administration, Office of Research and Development, Biomedical
Laboratory Research and Development; National Institutes of Health [NIH
K24-AR 02207, NIH T32-AR007465-25, GM-62116]
FX The author(s) disclosed receipt of the following financial support for
the research and/or authorship of this article: This work was supported
by the Lupus Foundation of American; in part by a Merit Review Grant
from the Department of Veterans Affairs Veterans Health Administration,
Office of Research and Development, Biomedical Laboratory Research and
Development; the National Institutes of Health (grant number NIH K24-AR
02207) to VPW; the National Institutes of Health training grant (grant
number NIH T32-AR007465-25) to LMC; and the Consortium for Functional
Glycomics Grant (grant number GM-62116) from the National Institutes of
Health.
NR 44
TC 10
Z9 10
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0022-1554
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD MAR
PY 2011
VL 59
IS 3
BP 336
EP 345
DI 10.1369/0022155410398000
PG 10
WC Cell Biology
SC Cell Biology
GA 805CC
UT WOS:000293703000010
PM 21378287
ER
PT J
AU Zhou, XY
Shapiro, L
Fellingham, G
Willardson, BM
Burton, GF
AF Zhou, Xueyuan
Shapiro, Leland
Fellingham, Gilbert
Willardson, Barry M.
Burton, Gregory F.
TI HIV Replication in CD4(+) T Lymphocytes in the Presence and Absence of
Follicular Dendritic Cells: Inhibition of Replication Mediated by
alpha-1-Antitrypsin through Altered I kappa B alpha Ubiquitination
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR NECROSIS FACTOR; TRANSCRIPTION
FACTORS; INFECTION; TYPE-1; ACTIVATION; ACTIN; PATHOGENESIS; PROTEINS;
NUCLEUS
AB Follicular dendritic cells (FDCs) increase HIV replication and virus production in lymphocytes by increasing the activation of NF-kappa B in infected cells. Because alpha-1-antitrypsin (AAT) decreases HIV replication in PBMCs and monocytic cells and decreases NF-kappa B activity, we postulated that AAT might also block FDC-mediated HIV replication. Primary CD4(+) T cells were infected with HIV and cultured with FDCs or their supernatant with or without AAT, and ensuing viral RNA and p24 production were monitored. NF-kappa B activation in the infected cells was also assessed. Virus production was increased in the presence of FDC supernatant, but the addition of AAT at concentrations >0.5 mg/ml inhibited virus replication. AAT blocked the nuclear translocation of NF-kappa B p50/p65 despite an unexpected elevation in associated phosphorylated and ubiquitinated I kappa B alpha (Ub-I kappa B alpha). In the presence of AAT, degradation of cytoplasmic I kappa B alpha was dramatically inhibited compared with control cultures. AAT did not inhibit the proteasome; however, it altered the pattern of ubiquitination of I kappa B alpha. AAT decreased I kappa B alpha polyubiquitination linked through ubiquitin lysine residue 48 and increased ubiquitination linked through lysine residue 63. Moreover, lysine reside 63-linked Ub-I kappa B alpha degradation was substantially slower than lysine residue 48-linked Ub-I kappa B alpha in the presence of AAT, correlating altered ubiquitination with a prolonged I kappa B alpha t(1/2). Because AAT is naturally occurring and available clinically, examination of its use as an inhibitory agent in HIV-infected subjects may be informative and lead to the development of similar agents that inhibit HIV replication using a novel mechanism. The Journal of Immunology, 2011, 186: 3148-3155.
C1 [Zhou, Xueyuan; Willardson, Barry M.; Burton, Gregory F.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA.
[Shapiro, Leland] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.
[Shapiro, Leland] Univ Colorado, Div Infect Dis, Dept Med, Denver, CO 80220 USA.
[Fellingham, Gilbert] Brigham Young Univ, Dept Stat, Provo, UT 84602 USA.
RP Burton, GF (reprint author), Brigham Young Univ, Dept Chem & Biochem, Room C104B BNSN, Provo, UT 84602 USA.
EM gburton@chem.byu.edu
FU National Institute of Allergy and Infectious Disease [AI39963, AI91517];
National Institute of General Medical Sciences [GM078550]; Campbell
Foundation; College of Physical and Mathematical Sciences
FX This work was supported by Public Health Service Grants AI39963 and
AI91517 from the National Institute of Allergy and Infectious Disease
(to G.F.B.), GM078550 from the National Institute of General Medical
Sciences (to B.M.W.), the Campbell Foundation (to L.S.), and by a
Brigham Young University grant from the College of Physical and
Mathematical Sciences (to G.F.B.).
NR 35
TC 19
Z9 20
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2011
VL 186
IS 5
BP 3148
EP 3155
DI 10.4049/jimmunol.1001358
PG 8
WC Immunology
SC Immunology
GA 721LT
UT WOS:000287356900053
PM 21263074
ER
PT J
AU Cassol, E
Rossouw, T
Seebregts, C
Cassol, S
AF Cassol, Edana
Rossouw, Theresa
Seebregts, Chris
Cassol, Sharon
TI Microbial Translocation: A Marker of Advanced HIV-1 Infection and a
Predictor of Treatment Failure?
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
ID IMMUNE ACTIVATION; GENE-EXPRESSION; PROGRESSION; DISEASE; AFRICA
C1 [Cassol, Edana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Cassol, Sharon] Univ Pretoria, Fac Hlth Sci, MRC Unit Inflammat & Immun, ZA-0002 Pretoria, South Africa.
[Rossouw, Theresa] Univ Pretoria, Dept Family Med, ZA-0002 Pretoria, South Africa.
[Seebregts, Chris] Med Res Counts, Ehlth Res & Innovat Platform, Biomed Informat Res, Tygerberg, South Africa.
RP Cassol, E (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, CLS 1017,450 Brookline Ave, Boston, MA 02215 USA.
EM edana_cassol@dfci.harvard.edu
NR 12
TC 4
Z9 4
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2011
VL 203
IS 5
BP 747
EP 748
DI 10.1093/infdis/jiq109
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 717FD
UT WOS:000287028000024
PM 21278212
ER
PT J
AU Luo, S
Chaplin, AC
Langley, RGB
Njauw, CN
Duncan, LM
Miller, RA
Tsao, H
AF Luo, Su
Chaplin, Anna C.
Langley, Richard G. B.
Njauw, Ching-Ni
Duncan, Lyn M.
Miller, Robert A.
Tsao, Hensin
TI Agminated Segmental Nevi Demonstrating Intranevic Concordance of BRAF
Status
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
ID FACIO-CUTANEOUS SYNDROME; MUTATIONS; SKIN; NRAS
C1 [Luo, Su; Njauw, Ching-Ni; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Luo, Su] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Chaplin, Anna C.; Langley, Richard G. B.; Miller, Robert A.] Dalhousie Univ, Dept Med, Div Dermatol, Halifax, NS, Canada.
[Duncan, Lyn M.] Harvard Univ, Sch Med, Dept Pathol, MGH Dermatopathol Unit, Boston, MA 02115 USA.
[Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA.
RP Luo, S (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM htsao@partners.org
RI Njauw, Ching-Ni/H-8046-2012
FU NCI NIH HHS [P50 CA093683-09, K24 CA149202, P50 CA-93683, K24
CA149202-01, P50 CA093683]
NR 12
TC 4
Z9 4
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2011
VL 131
IS 3
BP 788
EP 790
DI 10.1038/jid.2010.380
PG 4
WC Dermatology
SC Dermatology
GA 719SQ
UT WOS:000287229700036
PM 21160499
ER
PT J
AU Warren, HS
AF Warren, H. Shaw
TI Control issues in sepsis: what modulates apoptosis?
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Editorial Material
DE entotoxin shock; serum; modulation; lymphocytes; monocytes
ID DEFINITIONS; MACROPHAGES; DEPLETION; HUMANS; SHOCK
C1 Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA.
RP Warren, HS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA.
EM swarren1@partners.org
FU PHS HHS [A1059010]
NR 13
TC 1
Z9 1
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2011
VL 89
IS 3
BP 325
EP 326
DI 10.1189/jlb.1110612
PG 2
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 727NL
UT WOS:000287807700002
PM 21357246
ER
PT J
AU Gee, MS
Harisinghani, MG
AF Gee, Michael S.
Harisinghani, Mukesh G.
TI MRI in Patients With Inflammatory Bowel Disease
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Review
DE MRI; MR enterography; Crohn's disease; ulcerative colitis; imaging
ID MULTIDETECTOR ROW CT; ORAL CONTRAST-MEDIA; CROHNS-DISEASE;
COMPUTED-TOMOGRAPHY; IMAGING EVALUATION; CAPSULE ENDOSCOPY;
FOLLOW-THROUGH; CANCER-RISKS; RADIATION; ENTEROCLYSIS
AB Inflammatory bowel disease (IBD) affects approximate to 1.4 million people in North America and, because of its typical early age of onset and episodic disease course, IBD patients often undergo numerous imaging studies over the course of their lifetimes. Computed tomography (CT) has become the standard imaging modality for assessment of IBD patients because of its widespread availability, rapid image acquisition, and ability to evaluate intraluminal and extraluminal disease. However, repetitive CT imaging has been associated with a significant ionizing radiation risk to patients, making MRI an appealing alternative IBD Imaging modality. Pelvic MRI is currently the imaging gold standard for detecting perianal disease, while recent studies indicate that MRI bowel-directed techniques (enteroclysis, enterography, colonography) can accurately evaluate bowel inflammation in IBD. With recent technical innovations leading to faster and higher resolution body MRI, the role of MRI in IBD evaluation is likely to continue to expand. Future applications include surveillance Imaging. detection of mural fibrosis, and early assessment of therapy response.
C1 [Gee, Michael S.; Harisinghani, Mukesh G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA.
[Gee, Michael S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Pediat Imaging, Boston, MA 02114 USA.
RP Harisinghani, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM mharisinghani@partners.org
FU National Institutes of Health; Harvard Medical School [UL1 RR025758-02]
FX Contract grant sponsor: National Institutes of Health and Harvard
Medical School; Contract grant number: Clinical and translational
science award UL1 RR025758-02 (to M.S.G. and M.G.H.).
NR 46
TC 28
Z9 29
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD MAR
PY 2011
VL 33
IS 3
BP 527
EP 534
DI 10.1002/jmri.22504
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 729LL
UT WOS:000287951100002
PM 21512607
ER
PT J
AU Milbury, CA
Chen, CC
Mamon, H
Liu, PF
Santagata, S
Makrigiorgos, GM
AF Milbury, Coren A.
Chen, Clark C.
Mamon, Harvey
Liu, Pingfang
Santagata, Sandro
Makrigiorgos, G. Mike
TI Multiplex Amplification Coupled with COLD-PCR and High Resolution
Melting Enables Identification of Low-Abundance Mutations in Cancer
Samples with Low DNA Content
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID CELL LUNG-CANCER; WHOLE-GENOME AMPLIFICATION; REAL-TIME PCR; P53
MUTATIONS; GENETIC PATHWAYS; CLINICAL-IMPLICATIONS; SENSITIVE DETECTION;
DYE CONCENTRATION; CODING SEQUENCES; CURVE ANALYSIS
AB Thorough screening of cancer-specific biomarkers, such as DNA mutations, can require large amounts of genomic material; however, the amount of genomic material obtained from some specimens (such as biopsies, fine-needle aspirations, circulating-DNA or tumor cells, and histological slides) may limit the analyses that can be performed. Furthermore, mutant alleles may be at low-abundance relative to wild-type DNA, reducing detection ability. We present a multiplex-PCR approach tailored to amplify targets of interest from small amounts of precious specimens, for extensive downstream detection of low-abundance alleles. Using 3 ng of DNA (1000 genome-equivalents), we amplified the 1 coding exons (2-11) of TP53 via multiplex-PCR. Following multiplex-PCR, we performed COLD-PCR (co-amplification of major and minor alleles at lower denaturation temperature) to enrich low-abundance variants and high resolution melting (HRM) to screen for aberrant melting profiles. Mutation-positive samples were sequenced. Evaluation of mutation-containing dilutions revealed improved sensitivities after COLD-PCR over conventional-PCR. COLD-PCR improved HRM sensitivity by approximately threefold to sixfold. Similarly, COLD-PCR improved mutation identification in sequence-chromatograms over conventional PCR. In clinical specimens, eight mutations were detected via conventional-PCR-HRM, whereas 12 were detected by COLD-PCR-HRM, yielding a 33% improvement in mutation detection. In summary, we demonstrate an efficient approach to increase screening capabilities from limited DNA material via multiplex-PCR and improve mutation detection sensitivity via COLD-PCR amplification. (J Mol Dingo 2011, 13:220-232; DOI: 10.1016/j.jmoldx.2010.10.008)
C1 [Milbury, Coren A.; Chen, Clark C.; Mamon, Harvey; Liu, Pingfang; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA.
[Chen, Clark C.] Beth Israel Deaconess Med Ctr, Div Neurosurg, Boston, MA 02215 USA.
[Santagata, Sandro] Harvard Univ, Med Sch Boston, Brigham & Womens Hosp, Dept Pathol, Cambridge, MA 02138 USA.
RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Level L2,75 Francis St, Boston, MA 02115 USA.
EM mmakrigiorgos@partners.org
RI Chen, Clark/C-8714-2013
OI Chen, Clark/0000-0001-6258-9277
FU NCI [T32-CA009078]; NIH [CA-138280, CA-111994]
FX Supported by grants T32-CA009078 from the NCI (C.A.M.), and NIH grants
CA-138280 and CA-111994.
NR 62
TC 13
Z9 14
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD MAR
PY 2011
VL 13
IS 2
BP 220
EP 232
DI 10.1016/j.jmoldx.2010.10.008
PG 13
WC Pathology
SC Pathology
GA 865JD
UT WOS:000298306300015
PM 21354058
ER
PT J
AU Munger, KL
Chitnis, T
Frazier, AL
Giovannucci, E
Spiegelman, D
Ascherio, A
AF Munger, Kassandra L.
Chitnis, Tanuja
Frazier, A. Lindsay
Giovannucci, Edward
Spiegelman, Donna
Ascherio, Alberto
TI Dietary intake of vitamin D during adolescence and risk of multiple
sclerosis
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Multiple sclerosis; Vitamin D; Cohort study; Epidemiology
ID BREAST-CANCER; ENVIRONMENTAL-FACTORS; US WOMEN; CONSUMPTION; CHILDHOOD;
MILK; MS; REPRODUCIBILITY; EXPOSURE; COHORTS
AB Adolescence may be an important etiological period in the development of multiple sclerosis (MS), and studies suggest that adequate vitamin D nutrition is protective. Here, the authors examined whether dietary intake of vitamin D during adolescence decreases the risk of MS in adulthood. In 1986 in the Nurses' Health Study and in 1998 in the Nurses' Health Study II (NHSII), women completed a food frequency questionnaire regarding their dietary intake during adolescence. From this, daily intake of vitamin D was calculated. Adolescent diet was available for 379 incident MS cases confirmed over the combined 44 years of follow-up in both cohorts, and for 67 prevalent cases in the NHSII who had MS at baseline (1989). Cox proportional hazards models were used to calculate relative risk estimates and 95% confidence intervals. Total vitamin D intake during adolescence was not associated with MS risk. Intake of a parts per thousand yen400 IU/day of vitamin D from multivitamins was associated with a non-statistically significant reduced risk (RR compared to no intake = 0.73, 95% CI: 0.50-1.07, P = 0.11), whereas intake of whole milk, an important source of dietary vitamin D, was associated with an increased risk. The possibility of opposite effects of vitamin D and milk intake on MS risk should be considered in future studies.
C1 [Munger, Kassandra L.; Giovannucci, Edward; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chitnis, Tanuja] Harvard Univ, Brigham & Womens Hosp, Sch Med, Partners Multiple Sclerosis Ctr,Dept Neurol, Boston, MA 02115 USA.
[Frazier, A. Lindsay] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA.
[Frazier, A. Lindsay; Giovannucci, Edward; Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Giovannucci, Edward; Spiegelman, Donna; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Munger, KL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,3rd Fl, Boston, MA 02115 USA.
EM kgorham@hsph.harvard.edu
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health [NS047467]
FX This work was supported by the National Institute of Neurological
Disorders and Stroke at the National Institutes of Health (grant
NS047467). We thank K. Claire Simon, ScD, and Leslie Unger for technical
support. The authors have no financial conflicts of interest to
disclose.
NR 29
TC 26
Z9 27
U1 1
U2 11
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD MAR
PY 2011
VL 258
IS 3
BP 479
EP 485
DI 10.1007/s00415-010-5783-1
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 729BZ
UT WOS:000287924200018
PM 20945071
ER
PT J
AU Mendez, MF
Shapira, JS
AF Mendez, Mario F.
Shapira, Jill S.
TI Internet Pornography and Frontotemporal Dementia
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Letter
ID SEXUAL-BEHAVIOR; DEGENERATION
C1 [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Neurol, Los Angeles, CA 90095 USA.
Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
RP Mendez, MF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Neurol, Los Angeles, CA 90095 USA.
NR 5
TC 0
Z9 0
U1 1
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0895-0172
J9 J NEUROPSYCH CLIN N
JI J. Neuropsychiatr. Clin. Neurosci.
PD SPR
PY 2011
VL 23
IS 2
BP E3
EP E3
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 777VF
UT WOS:000291652500093
ER
PT J
AU Fung, SJ
Xi, MC
Zhang, JH
Torterolo, P
Sampogna, S
Morales, FR
Chase, MH
AF Fung, Simon J.
Xi, MingChu
Zhang, JianHua
Torterolo, Pablo
Sampogna, Sharon
Morales, Francisco R.
Chase, Michael H.
TI Projection Neurons From the Central Nucleus of the Amygdala to the
Nucleus Pontis Oralis
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Article
DE amygdalofugal projection; glutamate; cholera toxin B; retrograde;
reticular formation
ID VESICULAR GLUTAMATE TRANSPORTER-2; TRIGEMINAL MOTOR NUCLEUS; ACTIVE REM
SLEEP; RETICULAR-FORMATION; BRAIN-STEM; HYPOGLOSSAL MOTONEURONS;
MEDULLA-OBLONGATA; PARADOXICAL SLEEP; GUINEA-PIG; RAT
AB The present retrograde labeling study was designed to determine the presence and pattern of projections from individual subdivisions of the central nucleus of the amygdala (CNA) to the nucleus pontis oralis (NPO), which is a critical brainstem site involved in the generation and maintenance of active (REM) sleep. Projections from the CNA were labeled with the retrograde tracer cholera toxin B-subunit (CTB), which was injected, unilaterally, via microiontophoresis, into the NPO. Sections of the amygdala were immunostained in order to identify CTB-labeled CNA neurons and CNA neurons that contained CTB plus the vesicular glutamate transporter 2 (VGLUT2), which is a marker for glutamatergic neurons. Histological analyses revealed that retrogradely labeled neurons that project to the NPO were localized, ipsilaterally, within the medial, lateral, and capsular subdivisions of the CNA. In addition, a substantial proportion (24%) of all retrogradely labeled CNA neurons also exhibited VGLUT2 immunoreactivity. The present study demonstrates that glutamatergic neurons, which are present within various subdivisions of the CNA, project directly to the NPO. These data lend credence to the hypothesis that NPO neurons that are involved in the control of active sleep are activated by glutamatergic projections from the amygdala. (C) 2010 Wiley-Liss, Inc.
C1 [Fung, Simon J.; Xi, MingChu; Zhang, JianHua; Torterolo, Pablo; Sampogna, Sharon; Morales, Francisco R.; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA.
[Fung, Simon J.; Xi, MingChu; Zhang, JianHua; Chase, Michael H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Torterolo, Pablo; Morales, Francisco R.; Chase, Michael H.] Univ Republica, Dept Fisiol, Fac Med, Montevideo, Uruguay.
[Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA.
RP Fung, SJ (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA.
EM sfung@websciences.org
FU NIH [NS 60917]
FX Contract grant sponsor: NIH; Contract grant number: NS 60917.
NR 51
TC 14
Z9 14
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD MAR
PY 2011
VL 89
IS 3
BP 429
EP 436
DI 10.1002/jnr.22554
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 717RG
UT WOS:000287064500015
PM 21259329
ER
PT J
AU Morasco, BJ
Corson, K
Turk, DC
Dobscha, SK
AF Morasco, Benjamin J.
Corson, Kathryn
Turk, Dennis C.
Dobscha, Steven K.
TI Association Between Substance Use Disorder Status and Pain-Related
Function Following 12 Months of Treatment in Primary Care Patients With
Musculoskeletal Pain
SO JOURNAL OF PAIN
LA English
DT Article
DE Chronic pain; substance use disorder; pain functioning; treatment;
collaborative care intervention
ID LOW-BACK-PAIN; MORRIS DISABILITY QUESTIONNAIRE; CHRONIC NONMALIGNANT
PAIN; CHRONIC NONCANCER PAIN; ABUSE SCREENING-TEST;
METHADONE-MAINTENANCE; COLLABORATIVE CARE; DEPENDENT PATIENTS;
RANDOMIZED-TRIAL; PERSISTENT PAIN
AB The goal of this study was to examine relationships between substance use disorder (SUD) history and 12-month outcomes among primary care patients with chronic noncancer pain (CNCP). Patients were enrolled in a randomized trial of collaborative care intervention (CCI) versus treatment as usual (TAU) to improve pain-related physical and emotional function. At baseline, 72 of 362 patients (20.0%) had a history of SUD. Compared to CNCP patients without SUD, those with comorbid SUD had poorer pain-related function and were more likely to meet criteria for current major depression and post-traumatic stress disorder (all P values <.05). Logistic regression analyses were conducted to examine whether SUD status was associated with clinically significant change over 12 months in pain-related function (30% reduction in Roland Morris Disability Questionnaire Score). The overall model was not significant in the CCI group. However, within the TAU group, participants with a SUD history were significantly less likely to show improvements in pain-related function (OR = .30, 95% CI = .11-.82). CNCP patients with comorbid SUD reported greater functional impairment at baseline. Patients with SUD who received usual care were 70% less likely to have clinically significant improvements in pain-related function 12 months postbaseline, and SUD status did not impede improvement for the CCI group.
Perspective: Chronic noncancer pain patients with a history of a substance use disorder (SUD) report poorer pain-related functioning and are less likely to experience clinically significant improvements from usual pain treatment. Providers should assess for SUD status and provide more intensive interventions for these patients. (C) 2011 by the American Pain Society
C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA.
[Corson, Kathryn; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Med & Psychiat, Portland, OR USA.
[Morasco, Benjamin J.; Corson, Kathryn; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
[Turk, Dennis C.] Univ Washington, Sch Med, Dept Anesthesiol & Pain Med, Seattle, WA USA.
RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hop Rd, Portland, OR 97239 USA.
EM benjamin.morasco@va.gov
FU Department of Veterans Affairs, Veterans Health Administration; Health
Services Research and Development Service Projects [PMI 03-195,
RCD04129]; National Institute on Drug Abuse [K23DA023467]; Endo; Johnson
Johnson; Philips Respironics; National Institutes of Health; Eli Lilly;
Empi; Pfizer; SK Life Science; Oregon Clinical and Translational
Research Institute at OHSU; National Center for Research Resources, a
component of the National Institutes of Health and NIH Roadmap for
Medical Research [UI1RR024140]
FX Supported in part by the Department of Veterans Affairs, Veterans Health
Administration, and Health Services Research and Development Service
Projects PMI 03-195 and RCD04129, awarded to Dr Dobscha. Dr Morasco also
received support from award K23DA023467 from the National Institute on
Drug Abuse. During the past 12 months, Dr Turk has received research
support from Endo, Johnson & Johnson, Philips Respironics, and the
National Institutes of Health, and consulting fees from Eli Lilly, Empi,
Johnson & Johnson, Pfizer, Philips Respironics, and SK Life Science. He
is also a Special Government Employee of the U.S. Food and Drug
Administration. The authors also appreciate support provided from the
Oregon Clinical and Translational Research Institute at OHSU, grant
number UI1RR024140 from the National Center for Research Resources, a
component of the National Institutes of Health and NIH Roadmap for
Medical Research.
NR 49
TC 14
Z9 14
U1 2
U2 6
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD MAR
PY 2011
VL 12
IS 3
BP 352
EP 359
DI 10.1016/j.jpain.2010.07.010
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 738HS
UT WOS:000288631500006
PM 20851057
ER
PT J
AU Wood, GJ
Morrison, RS
AF Wood, Gordon J.
Morrison, R. Sean
TI Writing Abstracts and Developing Posters for National Meetings
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID STRUCTURED ABSTRACTS; PUBLICATION; PRESENTATIONS; ELABORATION;
EXPLANATION; PRESENTERS; ARTICLES; CONSORT; TRIALS; IMPACT
AB Presenting posters at national meetings can help fellows and junior faculty members develop a national reputation. They often lead to interesting and fruitful networking and collaboration opportunities. They also help with promotion in academic medicine and can reveal new job opportunities. Practically, presenting posters can help justify funding to attend a meeting. Finally, this process can be invaluable in assisting with manuscript preparation. This article provides suggestions and words of wisdom for palliative care fellows and junior faculty members wanting to present a poster at a national meeting describing a case study or original research. It outlines how to pick a topic, decide on collaborators, and choose a meeting for the submission. It also describes how to write the abstract using examples that present a general format as well as writing tips for each section. It then describes how to prepare the poster and do the presentation. Sample poster formats are provided as are talking points to help the reader productively interact with those that visit the poster. Finally, tips are given regarding what to do after the meeting. The article seeks to not only describe the basic steps of this entire process, but also to highlight the hidden curriculum behind the successful abstracts and posters. These tricks of the trade can help the submission stand out and will make sure the reader gets the most out of the hard work that goes into a poster presentation at a national meeting.
C1 [Wood, Gordon J.] Univ Pittsburgh, Sch Med, Inst Enhance Palliat Care, Sect Palliat Care & Med Eth,Dept Med, Pittsburgh, PA 15213 USA.
[Morrison, R. Sean] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA.
[Morrison, R. Sean] James J Peters VA, Bronx, NY USA.
RP Wood, GJ (reprint author), Univ Pittsburgh, Sch Med, Inst Enhance Palliat Care, Sect Palliat Care & Med Eth,Dept Med, 200 Lothrop St,Suite 933 W, Pittsburgh, PA 15213 USA.
EM woodgj@upmc.edu
FU National Institute on Aging [K24 AG022345]; National Palliative Care
Research Center
FX Dr. Morrison is supported by a Mid-Career Investigator Award in Patient
Oriented Research from the National Institute on Aging (K24 AG022345). A
portion of this work was funded by the National Palliative Care Research
Center.
NR 31
TC 5
Z9 5
U1 0
U2 11
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
J9 J PALLIAT MED
JI J. Palliat. Med.
PD MAR
PY 2011
VL 14
IS 3
BP 353
EP 359
DI 10.1089/jpm.2010.0171
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 728ZZ
UT WOS:000287915700021
PM 21241194
ER
PT J
AU Rosen, AK
Mull, HJ
Kaafarani, H
Nebeker, J
Shimada, S
Helwig, A
Nordberg, B
Long, B
Savitz, LA
Shanahan, CW
Itani, K
AF Rosen, Amy K.
Mull, Hillary J.
Kaafarani, Haytham
Nebeker, Jonathan
Shimada, Stephanie
Helwig, Amy
Nordberg, Brian
Long, Brenna
Savitz, Lucy A.
Shanahan, Christopher W.
Itani, Kamal
TI Applying Trigger Tools to Detect Adverse Events Associated With
Outpatient Surgery
SO JOURNAL OF PATIENT SAFETY
LA English
DT Article
DE patient safety; adverse events; triggers; outpatient surgery; quality
AB Objective: The objective of this study is to evaluate the performance of 5 triggers to detect adverse events (AEs) associated with outpatient surgery. Triggers use surveillance algorithms derived from clinical logic to flag cases where AEs have most likely occurred. Current efforts to detect AEs have focused primarily on the inpatient setting, despite the increase in outpatient surgery in all health care settings.
Methods: Using trigger logic, we retrospectively evaluated data from 3 large health care systems' electronic medical records. Patients were eligible for inclusion if they had an outpatient (same-day) surgery in 2007 and at least 1 clinical note in the 6 months after the surgery. Two nurse abstractors reviewed a sample of trigger-flagged cases from each health care system. After reaching interrater reliability targets (k > 0.60), we calculated the positive predictive value (PPV) of each trigger and the confidence interval of the estimate.
Results: The surgical triggers flagged between 1% and 22% of the outpatient surgery cases, with a wide range in PPVs (6.0%-62.0%). The pulmonary embolism and deep vein thrombosis and emergency department triggers had the lowest proportion of flagged cases along with the highest PPVs, showing the most promise for screening cases with a high probability of AE occurrence.
Conclusions: Triggers may be useful in identifying a narrow set of surgeries for further review to determine if a surgical AE occurred, complementing existing tools and initiatives used to detect AEs. Improved detection of AEs in outpatient surgery should help target potential areas for quality improvement.
C1 [Rosen, Amy K.; Mull, Hillary J.] VA Boston Healthcare Syst, Ctr Org, Leadership, Management Res, Boston, MA USA.
[Rosen, Amy K.; Mull, Hillary J.; Shimada, Stephanie] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Kaafarani, Haytham] Tufts Med Ctr, Dept Surg, Boston, MA USA.
[Kaafarani, Haytham] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Nebeker, Jonathan; Nordberg, Brian; Long, Brenna] VA Salt Lake City Geriatr Res Educ & Clin Ctr, Salt Lake City, UT USA.
[Nebeker, Jonathan; Savitz, Lucy A.] Univ Utah, Salt Lake City, UT USA.
[Shimada, Stephanie] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Helwig, Amy] Agcy Healthcare Res & Qual, Rockville, MD USA.
[Savitz, Lucy A.] Intermt Healthcare, Salt Lake City, UT USA.
[Shanahan, Christopher W.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Shanahan, Christopher W.] Boston Med Ctr, Boston, MA USA.
[Itani, Kamal] VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA USA.
[Itani, Kamal] Harvard Univ, Sch Med, Boston, MA USA.
RP Rosen, AK (reprint author), VA Boston Healthcare Syst 152M, 150 S Huntington Ave, Boston, MA 02130 USA.
EM akrosen@bu.edu
RI Shanahan, Christopher/H-6592-2015
OI Shanahan, Christopher/0000-0001-9067-5922
FU Agency for Healthcare Research and Quality [HHSA290200600012]
FX This project was supported by the Agency for Healthcare Research and
Quality (Contract No. HHSA290200600012).
NR 32
TC 7
Z9 7
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1549-8417
J9 J PATIENT SAF
JI J. Patient Saf.
PD MAR
PY 2011
VL 7
IS 1
BP 45
EP 59
DI 10.1097/PTS.0b013e31820d164b
PG 15
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA V27KL
UT WOS:000208612000008
PM 21921867
ER
PT J
AU Smaldone, A
Ritholz, MD
AF Smaldone, Arlene
Ritholz, Marilyn D.
TI Perceptions of Parenting Children With Type 1 Diabetes Diagnosed in
Early Childhood
SO JOURNAL OF PEDIATRIC HEALTH CARE
LA English
DT Article
DE Parenting; type 1 diabetes; teamwork; qualitative
ID DIFFICULT CONVERSATIONS; HEALTH-CARE; MELLITUS; KETOACIDOSIS; TRENDS;
YOUTH; HOME
AB Introduction: The purpose of this study was to explore perceptions of psychosocial adaptations in parenting young children with type 1 diabetes (T1DM) from diagnosis through childhood.
Method: Fourteen parents of 11 children with T1DM who were diagnosed at age five years or younger participated in semi-structured interviews. Data were analyzed using content analysis.
Results: Three significant themes were identified. In the theme "Diagnostic Experiences: Frustrations, Fears, and Doubts,'' parents described inadequate diagnostic experiences with pediatricians where concerns were minimized and diagnosis was sometimes delayed. Although hospitalization occurred abruptly, communication with specialists was more satisfactory. In the theme "Adapting to Diabetes,'' parents described isolation in caring for their child's T1DM. Family and friends had minimal understanding of T1DM care. Support groups lessened mothers' isolation, but fathers were less positive about this experience. Parental adaptation was more effective when responsibility for diabetes decision making was shared. All parents reported never mastering diabetes management. The theme "Negotiating Developmental Transitions'' revealed that normative childhood events were stressful, requiring that parents balance concerns to foster their child's participation.
Conclusions: Pediatric providers can improve diagnostic and treatment experiences for parents of children with T1DM by recognizing feelings of isolation and lack of mastery, providing attentive communication, encouraging parental teamwork, and offering ongoing anticipatory guidance. J Pediatr Health Care. (2011) 25, 87-95.
C1 [Smaldone, Arlene] Columbia Univ, Sch Nursing, New York, NY 10032 USA.
[Ritholz, Marilyn D.] Childrens Hosp Boston, Boston, MA USA.
[Ritholz, Marilyn D.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Ritholz, Marilyn D.] Harvard Univ, Sch Med, Boston, MA USA.
RP Smaldone, A (reprint author), Columbia Univ, Sch Nursing, 617 W 168th St, New York, NY 10032 USA.
EM ams130@columbia.edu
FU National Institutes of Health/National Institute of Nursing Research
[5P20 NR007799]
FX Supported by National Institutes of Health/National Institute of Nursing
Research grant No. 5P20 NR007799 (Arlene Smaldone, DNSc, CPNP, CDE,
principal investigator of project pilot).
NR 35
TC 27
Z9 28
U1 1
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5245
J9 J PEDIATR HEALTH CAR
JI J. Pediatr. Health Care
PD MAR-APR
PY 2011
VL 25
IS 2
BP 87
EP 95
DI 10.1016/j.pedhc.2009.09.003
PG 9
WC Health Policy & Services; Nursing; Pediatrics
SC Health Care Sciences & Services; Nursing; Pediatrics
GA 797QU
UT WOS:000293143200005
PM 21320680
ER
PT J
AU Fung, EB
Humphrey, ML
Gildengorin, G
Goldstein, N
Hoffinger, SA
AF Fung, Ellen B.
Humphrey, Marcie L.
Gildengorin, Ginny
Goldstein, Natalie
Hoffinger, Scott A.
TI Rapid Remineralization of the Distal Radius After Forearm Fracture in
Children
SO JOURNAL OF PEDIATRIC ORTHOPAEDICS
LA English
DT Article
DE DXA; bone mineral content; bone mineral density; forearm fracture;
children
ID BONE-MINERAL DENSITY; REFRACTURES; ADOLESCENTS; POPULATION; CHILDHOOD;
MASS
AB Background: Bone mineral content (BMC) and density (BMD) have been shown to diminish after fracture and immobilization in adults. Distal radius fractures are common in children, and unlike adults, there is a low incidence of refracture. The primary aim of this study was to assess the change in radial BMC and BMD after upper extremity fracture and casting in healthy pediatric patients.
Methods: Patients were recruited at the time of distal radius fractures casting. The nonfractured (non-Fx) distal radius was initially scanned by dual energy x-ray absorptiometry (baseline), and then both arms were scanned at the time of cast removal (CastOff), and 4, 8, 12, 24, and 52 weeks post CastOff.
Results: Twenty-one patients were enrolled (13 male, 13 Caucasian; 10.4 +/- 2.5 y) with an average length of casting of 38 +/- 11 days. Eighteen patients (86%) completed all protocol requirements. At CastOff, there was no significant difference in total BMC or BMD between the Fx and non-Fx arms. From CastOff to 24 weeks, the overall change in BMC and BMD for the non-Fx arm was + 4.2% and + 0.2%, respectively, whereas for the Fx arm, the change was + 8.3% and + 3.4%, respectively. By 24 weeks, the difference in the overall change in BMD between the Fx and non-Fx arms was statistically significant (greater than instrumental error; P < 0.05). However, by 52 weeks, these differences were no longer significant. The increased mineralization was unrelated to age, sex, arm dominance, or calcium intake.
Conclusions: These data show that there is rapid remineralization after a simple forearm fracture in children, with a transient elevation in BMD in the Fx arm after casting. This novel finding suggests that bone may be stronger around the site of fracture and could significantly change how we counsel young patients recovering from forearm fracture. Future research should focus on children immobilized for varying lengths of time and those with repeat fractures, using volumetric techniques of bone geometry and strength assessment.
C1 [Fung, Ellen B.] Childrens Hosp & Res Ctr, HEDCO Hlth Sci Ctr, Dept Hematol, Oakland, CA 94609 USA.
[Humphrey, Marcie L.; Hoffinger, Scott A.] Childrens Hosp & Res Ctr, Dept Orthoped, Oakland, CA 94609 USA.
[Gildengorin, Ginny] Childrens Hosp & Res Ctr, Pediat Clin Res Ctr, Oakland, CA 94609 USA.
[Goldstein, Natalie] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Fung, EB (reprint author), Childrens Hosp & Res Ctr, HEDCO Hlth Sci Ctr, Dept Hematol, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA.
EM efung@mail.cho.org
FU National Center for Research Resources [M01 RR01271, UL1-RR024131]
FX This publication was supported in part by the following grants: M01
RR01271 and UL1-RR024131 from the National Center for Research
Resources.
NR 21
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-6798
J9 J PEDIATR ORTHOPED
JI J. Pediatr. Orthop.
PD MAR
PY 2011
VL 31
IS 2
BP 138
EP 143
DI 10.1097/BPO.0b013e3182093ddd
PG 6
WC Orthopedics; Pediatrics
SC Orthopedics; Pediatrics
GA 719GS
UT WOS:000287190800008
PM 21307706
ER
PT J
AU Gutierrez, OM
Isakova, T
Enfield, G
Wolf, M
AF Gutierrez, Orlando M.
Isakova, Tamara
Enfield, Gwen
Wolf, Myles
TI Impact of Poverty on Serum Phosphate Concentrations in the Third
National Health and Nutrition Examination Survey
SO JOURNAL OF RENAL NUTRITION
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; SURVEY NHANES-III; FAST-FOOD; MINERAL
METABOLISM; PHOSPHORUS INTAKE; RENAL-DISEASE; UNITED-STATES;
HYPERPHOSPHATEMIA; HEMODIALYSIS; ASSOCIATION
AB Objective: Increased serum phosphate is associated with adverse health outcomes. High intake of inexpensive processed and fast foods is common in impoverished communities, and is linked with excessive dietary phosphorus intake and elevated serum phosphate concentrations in chronic kidney disease patients. We examined the impact of socioeconomic status on dietary phosphorus intake and serum phosphate concentrations in the general population.
Design: Cross-sectional study.
Participants: A total of 14,261 adult participants in the Third National Health and Nutrition Examination Survey.
Predictors and Outcomes: Poverty to income ratio (PIR; family income indexed to the federal poverty level) was the primary index of socioeconomic status. Serum phosphate was the primary outcome variable.
Results: Although estimated phosphorus intake decreased with decreasing quartiles of PIR (P < .001), serum phosphate was inversely associated with PIR (P = .003). The relationship between lower PIR and higher serum phosphate remained significant after adjustment for demographic, laboratory, and dietary intake characteristics (P - .02). Compared with participants in the highest PIR quartile (income >300% of the federal poverty level), participants in the lowest quartile (income < the federal poverty level) had more than twice the odds of hyperphosphatemia (>= 4.4 mg/dL) in unadjusted and multivariable-adjusted logistic regression analyses (OR, 2.2; 95% CI, 1.5 to 3.2).
Conclusions: Although lower income was associated with decreased estimated phosphorus intake, increasing poverty was independently linked with increased serum phosphate and higher likelihood of hyperphosphatemia. These findings may indicate that conventional dietary instruments underestimate phosphorus intake, especially among impoverished individuals. Further studies are needed to explore these possibilities. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved.
C1 [Gutierrez, Orlando M.; Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA.
[Isakova, Tamara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Nephrol, Boston, MA USA.
[Enfield, Gwen] Univ Miami, Miller Sch Med, Clin Res Ctr, Miami, FL 33136 USA.
RP Gutierrez, OM (reprint author), Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, 1120 NW 14th St,CRB C-221,Room 815, Miami, FL 33136 USA.
EM ogutierrez2@med.miami.edu
FU American Kidney Fund Clinical Scientist in Nephrology Fellowship;
National Institutes of Health [K23DK081673, R01DK076116, R01DK081374]
FX This study was supported by the American Kidney Fund Clinical Scientist
in Nephrology Fellowship (to Dr. Isakova) and grants K23DK081673 (to Dr.
Gutierrez), R01DK076116 and R01DK081374 (to Dr. Wolf) from the National
Institutes of Health.
NR 42
TC 20
Z9 20
U1 0
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1051-2276
J9 J RENAL NUTR
JI J. Renal Nutr.
PD MAR
PY 2011
VL 21
IS 2
BP 140
EP 148
DI 10.1053/j.jrn.2010.03.001
PG 9
WC Nutrition & Dietetics; Urology & Nephrology
SC Nutrition & Dietetics; Urology & Nephrology
GA 722YQ
UT WOS:000287471600005
PM 20537917
ER
PT J
AU Crane, DA
Little, JW
Burns, SP
AF Crane, Deborah A.
Little, James W.
Burns, Stephen P.
TI Weight gain following spinal cord injury: a pilot study
SO JOURNAL OF SPINAL CORD MEDICINE
LA English
DT Article
DE Spinal cord injury; Obesity
ID BODY-MASS INDEX; ENERGY-EXPENDITURE; DISEASE RISK; FAT MASS; OBESITY;
ADULTS; PARAPLEGIA; COMMUNITY; TIME; MEN
AB Study design: Retrospective chart review.
Objective: To define the temporal course of weight gain in persons with new spinal cord injury (SCI), and to identify predictors of weight gain in this population.
Setting: A United States Department of Veterans Affairs (VA) SCI Unit.
Methods: A retrospective chart review in a VA SCI Unit was conducted. Participants (n = 85) included all persons with new SCI completing initial rehabilitation at the center between 1998 and 2006. Outcome measures were mean change in body mass index (BMI) between rehabilitation admission and final follow-up, time of greatest BMI change, and distribution of participants by BMI classification. These measures were also examined relative to SCI level, American Spinal Injury Association Impairment Scale (AIS) grade, primary mode of mobility, and age at rehabilitation admission.
Results: Mean BMI increased by 2.3 kg/m(2) between rehabilitation admission (mean 45 days post-injury) and final follow-up (mean 5 years post-injury). The distribution of participants shifted from lower BMI classifications at rehabilitation admission to higher BMI classifications at final follow-up. For participants transitioning from normal to overweight or obese, the greatest increase occurred during the first year after acute rehabilitation. Neurological level, impairment category, primary mode of mobility, and age at rehabilitation admission did not significantly predict BMI change. BMI at rehabilitation admission correlated significantly with BMI at final follow-up (P < 0.0005).
Conclusions: These findings confirm a significant increase in BMI after new SCI and suggest that persons with new SCI are at greatest weight gain risk during the first year following acute rehabilitation.
C1 [Crane, Deborah A.; Little, James W.; Burns, Stephen P.] Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Seattle, WA 98104 USA.
[Crane, Deborah A.; Little, James W.; Burns, Stephen P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Crane, DA (reprint author), Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Box 359740,325 9th Ave, Seattle, WA 98104 USA.
EM dacrane@uw.edu
NR 22
TC 10
Z9 10
U1 0
U2 1
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 1079-0268
J9 J SPINAL CORD MED
JI J. Spinal Cord. Med.
PD MAR
PY 2011
VL 34
IS 2
BP 227
EP 232
DI 10.1179/2045772311Y.0000000001
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 744FR
UT WOS:000289080800011
PM 21675361
ER
PT J
AU Patti, JA
AF Patti, John A.
TI Radiology-Centric Medicine and the Need for Practice Transformation
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA.
EM jpatti@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD MAR
PY 2011
VL 8
IS 3
BP 149
EP 150
DI 10.1016/j.jacr.2011.01.014
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 961FH
UT WOS:000305449000001
PM 21371659
ER
PT J
AU Byers, E
Gomez, MA
Sheridan, RM
Orr, NW
Hirsch, JA
AF Byers, Ernest
Gomez, Max A., II
Sheridan, Robert M.
Orr, Nelson W.
Hirsch, Joshua A.
TI Radiofrequency Identification for Inventory in Neurointerventional
Practice
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE RFID; interventional radiology; medical inventory; patient billing;
human factor
AB Implementations of radiofrequency identification (RFID) systems within hospital settings are not unique or without controversy. To date, little consideration has been given to use of this technology in clinical interventional radiologic practice. The potential financial advantages coupled with benefits to quality and safety and increases in staff satisfaction are considerable. The authors outline these advantages by enabling readers to broadly consider the systemic perspective of implementing RFID technology with art associated vision toward downstream growth. Furthermore, the authors demonstrate the benefits of RFID technology integration in reducing cost and increasing quality assurance and the on-time delivery of services. Implementing RFID requires commitment from frontline technologist staff members to work collaboratively with management and external vendors. Ultimately, the authors believe this technology can positively influence patient care.
C1 [Byers, Ernest; Gomez, Max A., II; Sheridan, Robert M.; Orr, Nelson W.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA.
RP Sheridan, RM (reprint author), Massachusetts Gen Hosp, Dept Imaging, 175 Cambridge St,Suite 200, Boston, MA 02114 USA.
EM rmsheridan@partners.org
NR 7
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD MAR
PY 2011
VL 8
IS 3
BP 191
EP 198
DI 10.1016/j.jacr.2010.09.006
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 961FH
UT WOS:000305449000012
PM 21371670
ER
PT J
AU Okura, T
Plassman, BL
Steffens, DC
Llewellyn, DJ
Potter, GG
Langa, KM
AF Okura, Toru
Plassman, Brenda L.
Steffens, David C.
Llewellyn, David J.
Potter, Guy G.
Langa, Kenneth M.
TI Neuropsychiatric Symptoms and the Risk of Institutionalization and
Death: The Aging, Demographics, and Memory Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE neuropsychiatric symptoms; caregiver distress; institutionalization;
mortality
ID MILD COGNITIVE IMPAIRMENT; NURSING-HOME PLACEMENT; ALZHEIMERS-DISEASE;
OLDER-ADULTS; DEMENTIA CARE; UNITED-STATES; FOLLOW-UP; PREVALENCE;
MORTALITY; DEPRESSION
AB OBJECTIVES
To examine the association between neuropsychiatric symptoms and risk of institutionalization and death.
DESIGN
Analysis of longitudinal data.
SETTING
The Aging, Demographics, and Memory Study (ADAMS).
PARTICIPANTS
Five hundred thirty-seven adults aged 71 and older with cognitive impairment drawn from the Health and Retirement Study (HRS).
MEASUREMENTS
Neuropsychiatric symptoms (delusions, hallucinations, agitation, depression, apathy, elation, anxiety, disinhibition, irritation, and aberrant motor behaviors) and caregiver distress were identified using the Neuropsychiatric Inventory. A consensus panel in the ADAMS assigned cognitive category. Date of nursing home placement and information on death, functional limitations, medical comorbidity, and sociodemographic characteristics were obtained from the HRS and ADAMS.
RESULTS
Overall, the presence of one or more neuropsychiatric symptoms was not associated with a significantly higher risk for institutionalization or death during the 5-year study period, although when assessing each symptom individually, depression, delusions, and agitation were each associated with a significantly higher risk of institutionalization (hazard rate (HR)=3.06, 95% confidence interval (CI)=1.09-8.59 for depression; HR=5.74, 95% CI=1.94-16.96 for clinically significant delusions; HR=4.70, 95% CI=1.07-20.70 for clinically significant agitation). Caregiver distress mediated the association between delusions and agitation and institutionalization. Depression and hallucinations were associated with significantly higher mortality (HR=1.56, 95% CI=1.08-2.26 for depression; HR=2.59, 95% CI=1.09-6.16 for clinically significant hallucinations).
CONCLUSION
Some, but not all, neuropsychiatric symptoms are associated with a higher risk of institutionalization and death in people with cognitive impairment, and caregiver distress also influences institutionalization. Interventions that better target and treat depression, delusions, agitation, and hallucinations, as well as caregiver distress, may help delay or prevent these negative clinical outcomes.
C1 [Okura, Toru] Bajikoen Clin, Geriatr Sect, Tokyo 1580098, Japan.
[Steffens, David C.] Duke Univ, Med Ctr, Div Geriatr Psychiat, Durham, NC USA.
[Potter, Guy G.] Duke Univ, Med Ctr, Div Med Psychol, Durham, NC USA.
[Plassman, Brenda L.; Steffens, David C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[Llewellyn, David J.] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England.
[Langa, Kenneth M.] Univ Michigan, Dept Internal Med, Div Gen Med, Ann Arbor, MI 48109 USA.
[Langa, Kenneth M.] US Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA.
RP Okura, T (reprint author), Bajikoen Clin, Geriatr Sect, 1-22-23 Kami Yoga Setagaya Ward, Tokyo 1580098, Japan.
EM t-ohkura@t3.rim.or.jp
FU National Institute on Aging (NIA) [R01 AG027010, R01 AG030155]
FX Conflict of Interest: The National Institute on Aging (NIA) provided
funding for the HRS and the ADAMS (U01 AG09740). Additional funding
support was provided by NIA Grants R01 AG027010 and R01 AG030155.
NR 45
TC 36
Z9 37
U1 2
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAR
PY 2011
VL 59
IS 3
BP 473
EP 481
DI 10.1111/j.1532-5415.2011.03314.x
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 732UQ
UT WOS:000288215600012
PM 21391937
ER
PT J
AU Rosolowsky, ET
Skupien, J
Smiles, AM
Niewczas, M
Roshan, B
Stanton, R
Eckfeldt, JH
Warram, JH
Krolewski, AS
AF Rosolowsky, Elizabeth T.
Skupien, Jan
Smiles, Adam M.
Niewczas, Monika
Roshan, Bijan
Stanton, Robert
Eckfeldt, John H.
Warram, James H.
Krolewski, Andrzej S.
TI Risk for ESRD in Type 1 Diabetes Remains High Despite Renoprotection
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID TERM ANTIHYPERTENSIVE TREATMENT; CONVERTING ENZYME-INHIBITION; IMPROVED
GRAFT-SURVIVAL; CHRONIC KIDNEY-DISEASE; RENAL-TRANSPLANTATION;
NEPHROPATHY; PROGRESSION; MELLITUS; MICROALBUMINURIA; PROTEINURIA
AB Historically, patients with type 1 diabetes and macroalbuminuria had high competing risks: cardiovascular death or renal failure. Here, we assessed these risks in patients receiving therapies implemented during the last 30 years. Between 1991 and 2004, we enrolled 423 white patients with type 1 diabetes who developed macroalbuminuria (albumin excretion rate, >= 300 mu g/min). With follow-up for 98% through 2008, ESRD developed in 172 patients (incidence rate, 5.8/100 person-years), and 29 died without ESRD (mortality rate, 1/100 person-years). The majority of these outcomes occurred between ages 36 and 52 years with durations of diabetes of 21 to 37 years. The 15-year cumulative risks were 52% for ESRD and 11% for pre-ESRD death. During the 15 years of follow-up, the use of renoprotective treatment increased from 56 to 82%, and BP and lipid levels improved significantly; however, the risks for both ESRD and pre-ESRD death did not change over the years analyzed. There were 70 post-ESRD deaths, and the mortality rate was very similar during the 1990s and the 2000s (11/100 person-years versus 12/100 person-years, respectively). Mortality was low in patients who received a pre-emptive kidney transplant (1/100 person-years), although these patients did not differ from dialyzed patients with regard to predialysis eGFR, sex, age at onset of ESRD, or duration of diabetes. In conclusion, despite the widespread adoption of renoprotective treatment, patients with type 1 diabetes and macroalbuminuria remain at high risk for ESRD, suggesting that more effective therapies are desperately needed.
C1 [Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA.
[Rosolowsky, Elizabeth T.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Skupien, Jan; Niewczas, Monika; Krolewski, Andrzej S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Roshan, Bijan; Stanton, Robert] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Renal, Boston, MA 02215 USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Rosolowsky, Elizabeth T.; Skupien, Jan; Smiles, Adam M.; Niewczas, Monika; Roshan, Bijan; Stanton, Robert; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Clin Div, Boston, MA 02215 USA.
RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM Andrzej.Krolewski@joslin.harvard.edu
FU JDRF [1-2008-1018, 3-2009-397]; National Institutes of Health [DK41526,
DK067638]; National Institutes of Health Child Health Services [HS00063]
FX This project was supported through JDRF research grant 1-2008-1018
(A.S.K.) and National Institutes of Health grants DK41526 (A.S.K.) and
DK067638 (A.S.K.) and National Institutes of Health Child Health
Services Research Training Program, grant HS00063 (E.T.R.), and JDRF
fellowship grant 3-2009-397 (J.S.).
NR 33
TC 84
Z9 87
U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2011
VL 22
IS 3
BP 545
EP 553
DI 10.1681/ASN.2010040354
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 740GE
UT WOS:000288778800022
PM 21355053
ER
PT J
AU Boger, CA
Chen, MH
Tin, A
Olden, M
Koettgen, A
de Boer, IH
Fuchsberger, C
O'Seaghdha, CM
Pattaro, C
Teumer, A
Liu, CT
Glazer, NL
Li, M
O'Conne, JR
Tanaka, T
Peralta, CA
Kutalik, Z
Luan, J
Zhao, JH
Hwang, SJ
Akylbekova, E
Kramer, H
van der Harst, P
Smith, AV
Lohman, K
de Andrade, M
Hayward, C
Kollerits, B
Tonjes, A
Aspelund, T
Ingelsson, E
Eiriksdottir, G
Launer, LJ
Harris, TB
Shuldiner, AR
Mitchell, BD
Arking, DE
Franceschini, N
Boerwinkle, E
Egan, J
Hernandez, D
Reilly, M
Townsend, RR
Lumley, T
Siscovick, DS
Psaty, BM
Kestenbaum, B
Haritunians, T
Bergmann, S
Vollenweider, P
Waeber, G
Mooser, V
Waterworth, D
Johnson, AD
Florez, JC
Meigs, JB
Lu, XN
Turner, ST
Atkinson, EJ
Leak, TS
Aasarod, K
Skorpen, F
Syvanen, AC
Illig, T
Baumert, J
Koenig, W
Kramer, BK
Devuyst, O
Mychaleckyj, JC
Minelli, C
Bakker, SJL
Kedenko, L
Paulweber, B
Coassin, S
Endlich, K
Kroemer, HK
Biffar, R
Stracke, S
Volzke, H
Stumvol, M
Magi, R
Campbell, H
Vitart, V
Hastie, ND
Gudnason, V
Kardia, SLR
Liu, YM
Polasek, O
Curhan, G
Kronenberg, F
Prokopenko, I
Rudan, I
Arnlov, J
Hallan, S
Navis, G
Parsa, A
Ferrucci, L
Coresh, J
Shlipak, MG
Bul, SB
Paterson, AD
Wichmann, HE
Wareham, NJ
Loos, RJF
Rotter, JI
Pramstaller, PP
Cupples, LA
Beckmann, JS
Yang, QO
Heid, IM
Rettig, R
Dreisbach, AW
Bochud, M
Fox, CS
Kao, WHL
AF Boeger, Carsten A.
Chen, Ming-Huei
Tin, Adrienne
Olden, Matthias
Koettgen, Anna
de Boer, Ian H.
Fuchsberger, Christian
O'Seaghdha, Conall M.
Pattaro, Cristian
Teumer, Alexander
Liu, Ching-Ti
Glazer, Nicole L.
Li, Man
O'Conne, Jeffrey R.
Tanaka, Toshiko
Peralta, Carmen A.
Kutalik, Zoltan
Luan, Jian'an
Zhao, Jing Hua
Hwang, Shih-Jen
Akylbekova, Ermeg
Kramer, Holly
van der Harst, Pim
Smith, Albert V.
Lohman, Kurt
de Andrade, Mariza
Hayward, Caroline
Kollerits, Barbara
Toenjes, Anke
Aspelund, Thor
Ingelsson, Erik
Eiriksdottir, Gudny
Launer, Lenore J.
Harris, Tamara B.
Shuldiner, Alan R.
Mitchell, Braxton D.
Arking, Dan E.
Franceschini, Nora
Boerwinkle, Eric
Egan, Josephine
Hernandez, Dena
Reilly, Muredach
Townsend, Raymond R.
Lumley, Thomas
Siscovick, David S.
Psaty, Bruce M.
Kestenbaum, Bryan
Haritunians, Talin
Bergmann, Sven
Vollenweider, Peter
Waeber, Gerard
Mooser, Vincent
Waterworth, Dawn
Johnson, Andrew D.
Florez, Jose C.
Meigs, James B.
Lu, Xiaoning
Turner, Stephen T.
Atkinson, Elizabeth J.
Leak, Tennille S.
Aasarod, Knut
Skorpen, Frank
Syvaenen, Ann-Christine
Illig, Thomas
Baumert, Jens
Koenig, Wolfgang
Kraemer, Bernhard K.
Devuyst, Olivier
Mychaleckyj, Josyf C.
Minelli, Cosetta
Bakker, Stephan J. L.
Kedenko, Lyudmyla
Paulweber, Bernhard
Coassin, Stefan
Endlich, Karlhans
Kroemer, Heyo K.
Biffar, Reiner
Stracke, Sylvia
Voelzke, Henry
Stumvol, Michael
Maegi, Reedik
Campbell, Harry
Vitart, Veronique
Hastie, Nicholas D.
Gudnason, Vilmundur
Kardia, Sharon L. R.
Liu, Yongmei
Polasek, Ozren
Curhan, Gary
Kronenberg, Florian
Prokopenko, Inga
Rudan, Igor
Aernloev, Johan
Hallan, Stein
Navis, Gerjan
Parsa, Afshin
Ferrucci, Luigi
Coresh, Josef
Shlipak, Michael G.
Bul, Shelley B.
Paterson, Andrew D.
Wichmann, H. -Erich
Wareham, Nicholas J.
Loos, Ruth J. F.
Rotter, Jerome I.
Pramstaller, Peter P.
Cupples, L. Adrienne
Beckmann, Jacques S.
Yang, Qiong
Heid, Iris M.
Rettig, Rainer
Dreisbach, Albert W.
Bochud, Murielle
Fox, Caroline S.
Kao, W. H. L.
CA CKDGen Consortium
DCCT EDIC
TI CUBN Is a Gene Locus for Albuminuria
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; TYPE-1
DIABETES-MELLITUS; LOW-GRADE ALBUMINURIA; RENAL-FUNCTION;
ALBUMIN/CREATININE RATIO; ATHEROSCLEROSIS RISK; LINKAGE ANALYSIS;
PROXIMAL TUBULE; DESIGN
AB Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
C1 [Hwang, Shih-Jen; Johnson, Andrew D.; Fox, Caroline S.] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA.
[Boeger, Carsten A.; Olden, Matthias] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Tin, Adrienne; Koettgen, Anna; Li, Man; Kao, W. H. L.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Tin, Adrienne; Koettgen, Anna; Li, Man; Kao, W. H. L.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Olden, Matthias; Heid, Iris M.] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, Regensburg, Germany.
[Koettgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany.
[de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA.
[Fuchsberger, Christian; Pattaro, Cristian; Minelli, Cosetta; Pramstaller, Peter P.] European Acad Bolzano Bozen EURAC, Inst Med Genet, Bolzano, Italy.
[Fuchsberger, Christian; Pattaro, Cristian; Minelli, Cosetta; Pramstaller, Peter P.] Med Univ Lubeck, Affiliated Inst, D-23538 Lubeck, Germany.
[O'Seaghdha, Conall M.] Harvard Univ, Sch Med, Boston, MA USA.
[O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA.
[Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfaculty Inst Genet & Funct Genom, Greifswald, Germany.
[Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] NHLBIs Framingham Heart Study, Boston, MA USA.
[Glazer, Nicole L.; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Glazer, Nicole L.; Lumley, Thomas] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[O'Conne, Jeffrey R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Tanaka, Toshiko] Medstar Res Inst, Baltimore, MD USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco Med Sch, San Francisco, CA 94143 USA.
[Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Kutalik, Zoltan; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Luan, Jian'an; Zhao, Jing Hua; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Akylbekova, Ermeg] Jackson State Univ, Jackson, MS USA.
[Hwang, Shih-Jen; Johnson, Andrew D.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Kramer, Holly] Loyola Univ, Maywood, IL USA.
[van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Holtasmara, Kopavogur, Iceland.
[Lohman, Kurt; Liu, Yongmei] Wake Forest Univ, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[de Andrade, Mariza; Atkinson, Elizabeth J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Hayward, Caroline; Vitart, Veronique; Hastie, Nicholas D.] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Kollerits, Barbara; Coassin, Stefan; Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Innsbruck, Austria.
[Toenjes, Anke; Stumvol, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Geriatr Res & Educ Clin Ctr, Vet Adm Med Ctr, Baltimore, MD 21201 USA.
[Arking, Dan E.] Johns Hopkins Med Inst, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Franceschini, Nora] Univ N Carolina, Chapel Hill, NC USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Egan, Josephine] NIA, Lab Clin Invest, Baltimore, MD 21224 USA.
[Hernandez, Dena] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Reilly, Muredach] Univ Penn, Div Cardiol, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA.
[Townsend, Raymond R.] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Dept Epidemiol, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Dept Hlth Serv, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Vollenweider, Peter; Waeber, Gerard] Univ Vaudois, Ctr Hosp, Dept Internal Med, Lausanne, Switzerland.
[Mooser, Vincent; Waterworth, Dawn] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA.
[Turner, Stephen T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA.
[Leak, Tennille S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Aasarod, Knut; Hallan, Stein] St Olavs Univ Hosp, Trondheim, Norway.
[Aasarod, Knut; Skorpen, Frank; Hallan, Stein] Norwegian Univ Sci & Technol, Fac Med, N-7034 Trondheim, Norway.
[Syvaenen, Ann-Christine] Uppsala Univ, Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
[Illig, Thomas; Baumert, Jens; Wichmann, H. -Erich; Heid, Iris M.] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Koenig, Wolfgang] Univ Ulm Klinikum, Zentrum Innere Med, Med Klin Kardiol 2, Ulm, Germany.
[Kraemer, Bernhard K.] Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany.
[Devuyst, Olivier] Catholic Univ Louvain, Sch Med, NEER Unit, B-1200 Brussels, Belgium.
[Mychaleckyj, Josyf C.] Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Bakker, Stephan J. L.; Navis, Gerjan] Univ Groningen, Dept Internal Med, Univ Med Ctr, Groningen, Netherlands.
[Kedenko, Lyudmyla; Paulweber, Bernhard] Paracelsus Med Univ, Dept Internal Med 1, Salzburg, Austria.
[Endlich, Karlhans] Ernst Moritz Arndt Univ Greifswald, Inst Anat & Cell Biol, Greifswald, Germany.
[Kroemer, Heyo K.] Ernst Moritz Arndt Univ Greifswald, Inst Pharmacol, Greifswald, Germany.
[Biffar, Reiner] Ernst Moritz Arndt Univ Greifswald, Clin Prosthodont Dent Gerostomatol & Mat Sci, Greifswald, Germany.
[Stracke, Sylvia] Ernst Moritz Arndt Univ Greifswald, Nephrol Clin Internal Med A, Greifswald, Germany.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Maegi, Reedik; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
[Maegi, Reedik; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX1 2JD, England.
[Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Polasek, Ozren] Gen Info Ltd, Zagreb, Croatia.
[Curhan, Gary] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Sch Med, Edinburgh, Midlothian, Scotland.
[Aernloev, Johan] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Shlipak, Michael G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Bul, Shelley B.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth, Toronto, ON M5G 1X5, Canada.
[Paterson, Andrew D.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Beckmann, Jacques S.] Univ Lausanne, Lausanne, Switzerland.
[Beckmann, Jacques S.] Univ Vaudois, Ctr Hosp, Serv Med Genet, Lausanne, Switzerland.
[Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany.
[Dreisbach, Albert W.] Univ Mississippi, Div Nephrol, Jackson, MS 39216 USA.
[Bochud, Murielle] Univ Lausanne, IUMSP, Lausanne, Switzerland.
[Bochud, Murielle] Univ Vaudois, Ctr Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBIs Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov; wkao@jhsph.edu
RI Singleton, Andrew/C-3010-2009; Giallauria, Francesco/B-5681-2013;
Endlich, Karlhans/G-5485-2013; Johnson, Andrew/G-6520-2013; Colaus,
PsyColaus/K-6607-2013; Fuchsberger, Christian/C-9646-2010; Aspelund,
Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Beckmann, Jacques S
/A-9772-2008; Arnlov, Johan/N-9886-2013; Kottgen, Anna/D-2920-2012;
Cavalieri, Margherita/G-8053-2012; Rudan, Igor/I-1467-2012; Kronenberg,
Florian/B-1736-2008; Yang, Qiong/G-5438-2014; Pramstaller,
Peter/C-2357-2008; Bakker, Stephan/J-4023-2015; Gudnason,
Vilmundur/K-6885-2015; Bull, Shelley/A-1920-2013; Polasek,
Ozren/B-6002-2011; Prokopenko, Inga/H-3241-2014; Paterson,
Andrew/A-4088-2011; Smith, Albert/K-5150-2015; Hayward,
Caroline/M-8818-2016; Feitosa, Mary/K-8044-2012;
OI Mitchell, Braxton/0000-0003-4920-4744; Bergmann,
Sven/0000-0002-6785-9034; Giallauria, Francesco/0000-0003-4119-9397;
Aspelund, Thor/0000-0002-7998-5433; Beckmann, Jacques S
/0000-0002-9741-1900; Rudan, Igor/0000-0001-6993-6884; Felix,
Janine/0000-0002-9801-5774; Magi, Reedik/0000-0002-2964-6011; Kramer,
Holly/0000-0002-6374-837X; Cupples, L. Adrienne/0000-0003-0273-7965;
Zgaga, Lina/0000-0003-4089-9703; Kronenberg,
Florian/0000-0003-2229-1120; Bakker, Stephan/0000-0003-3356-6791;
Gudnason, Vilmundur/0000-0001-5696-0084; Polasek,
Ozren/0000-0002-5765-1862; Prokopenko, Inga/0000-0003-1624-7457;
Paterson, Andrew/0000-0002-9169-118X; Smith, Albert/0000-0003-1942-5845;
Hayward, Caroline/0000-0002-9405-9550; Feitosa,
Mary/0000-0002-0933-2410; Fuchsberger, Christian/0000-0002-5918-8947
FU NIH [R01 AG18728, R01 HL088119, U01 GM074518-04, U01 HL072515-06, U01
HL084756, NIH K12RR023250, NIH P30 DK072488, NIH P60 DK079637,
HHSN268200625226C]; University of Maryland General Clinical Research
Center [M01 RR 16500]; Baltimore Veterans Administration Medical Center
Geriatrics Research and Education Clinical Center; Paul Beeson Physician
Faculty; National Heart, Lung, and Blood Institute [N01-HC-55015,
N01-HC55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, N01-HC-85079,
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, U01 HL080295, R01 HL087652, R01 AG027002]; National Human
Genome Research Institute [U01HG004402]; National Institutes of Health
and NIH Roadmap for Medical Research [ULIRR025005]; National Center for
Research Resources [M01RR00425]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; Medical Research Council UK;
Cancer Research UK
FX AMISH: The Amish studies are supported by grants and contracts from the
NIH including R01 AG18728 (Amish Longevity Study), R01 HL088119 (Amish
Calcification Study), U01 GM074518-04 (PAPI Study), U01 HL072515-06
(HAPI Study), U01 HL084756 and NIH K12RR023250 (University of Maryland
MCRDP), NIH P30 DK072488 (Clinical Nutrition Research Unit of Maryland),
and NIH P60 DK079637 (Baltimore Diabetes Research and Training Center).
The University of Maryland General Clinical Research Center, grant M01
RR 16500, the Baltimore Veterans Administration Medical Center
Geriatrics Research and Education Clinical Center, and the Paul Beeson
Physician Faculty Scholars in Aging Program. We thank our Amish research
volunteers for their long-standing partnership in research, and the
research staff at the Amish Research Clinic for their hard work and
dedication.; ARIC: The Atherosclerosis Risk in Communities study is
carried out as a collaborative study supported by National Heart, Lung,
and Blood Institute contracts N01-HC-55015, N01-HC55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641,
R01HL59367, and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and National Institutes of Health contract
HHSN268200625226C. The authors thank the staff and participants of the
ARIC study for their important contributions. Infrastructure was partly
supported by grant numbers ULIRR025005, a component of the National
Institutes of Health and NIH Roadmap for Medical Research.; CHS: The
Cardiovascular Health Study (CHS) research reported in this article was
supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129,
N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133, grants U01
HL080295 and R01 HL087652, and R01 AG027002 from the National Heart,
Lung and Blood Institute, with additional contribution from the National
Institute of Neurologic Disorders and Stroke. A full list of principal
CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was
supported in part by National Center for Research Resources grant
M01RR00425 to the Cedars-Sinai General Clinical Research Center
Genotyping core and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center.; CoLaus: The CoLaus authors thank Mande
Barreau, Mathieu Firmann, Vladimir Mayor, Anne-Lise Bastian, Binasa
Ramie, Martine Moranville, Martine Baumer, Marcy Sagette, Jeanne
Ecoffey, and Sylvie Mermoud for data collection. The CoLaus study
received financial contributions from GlaxoSmithKline, the Faculty of
Biology and Medicine of Lausanne, the Swiss National Science Foundation
(33CSCO-122661, 3200BO-111361/2, 3100AO-116323/1, and 310000-112552),
the Swiss School of Public Health Plus, the Giorgi-Cavaglieri
Foundation, and the European Framework Project 6 (EuroDia, AnEuploidy,
and Hypergenes projects).; EPIC: The EPIC Norfolk Study is funded by
program grants from the Medical Research Council UK and Cancer Research
UK, and by additional support from the European Union, Stroke
Association, British Heart Foundation, Department of Health, Food
Standards Agency, and the Wellcome Trust.
NR 81
TC 85
Z9 87
U1 5
U2 13
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2011
VL 22
IS 3
BP 555
EP 570
DI 10.1681/ASN.2010060598
PG 16
WC Urology & Nephrology
SC Urology & Nephrology
GA 740GE
UT WOS:000288778800023
PM 21355061
ER
PT J
AU Salanitro, AH
Safford, MM
Houston, TK
Williams, JH
Ovalle, F
Payne-Foster, P
Allison, JJ
Estrada, CA
AF Salanitro, Amanda H.
Safford, Monika M.
Houston, Thomas K.
Williams, Jessica H.
Ovalle, Fernando
Payne-Foster, Pamela
Allison, Jeroan J.
Estrada, Carlos A.
TI Patient Complexity and Diabetes Quality of Care in Rural Settings
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Article
DE diabetes; quality of care; primary care
AB Purpose: Even though pay-for-performance programs are being rapidly implemented, little is known about how patient complexity affects practice-level performance assessment in rural settings. We sought to determine the association between patient complexity and practice-level performance in the rural United States.
Basic procedures: Using baseline data from a trial aimed at improving diabetes care, we determined factors associated with a practice's proportion of patients having controlled diabetes (hemoglobin A(lc) <= 7%): patient socioeconomic factors, clinical factors, difficulty with self-testing of blood glucose, and difficulty with keeping appointments. We used linear regression to adjust the practice-level proportion with A(lc) controlled for these factors. We compared practice rankings using observed and expected performance and classified practices into hypothetical pay-for-performance categories.
Main Findings: Rural primary care practices (n = 135) in 11 southeastern states provided information for 1641 patients with diabetes. For practices in the best quartile of observed control, 76.1% of patients had controlled diabetes vs 19.3% of patients in the worst quartile. After controlling for other variables, proportions of diabetes control were 10% lower in those practices whose patients had the greatest difficulty with either self testing or appointment keeping (p < .05 for both). Practice rankings based on observed and expected proportion of AI, control showed only moderate agreement in pay-for-performance categories (kappa = 0.47; 95% confidence interval, 0.32-0.56; p < .001).
Principal Conclusions: Basing public reporting and resource allocation on quality assessment that does not account for patient characteristics may further harm this vulnerable group of patients and physicians.
C1 [Salanitro, Amanda H.] Vanderbilt Univ, VA Tennessee Valley Geriatr Res Educ & Clin Ctr, Nashville, TN USA.
[Salanitro, Amanda H.] Vanderbilt Univ, Sect Hosp Med, Nashville, TN USA.
[Estrada, Carlos A.] Univ Alabama, Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA.
[Estrada, Carlos A.] Univ Alabama, Ctr Surg Med Acute Care Res & Transit CSMART, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Houston, Thomas K.; Allison, Jeroan J.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Payne-Foster, Pamela] Univ Alabama, Tuscaloosa, AL USA.
RP Salanitro, AH (reprint author), Room A-414,1310 24th Ave S, Nashville, TN 37212 USA.
EM amanda.salanitro@vanderbilt.edu
RI Houston, Thomas/F-2469-2013;
OI Allison, Jeroan/0000-0003-4472-2112
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[5R18DK065001]; Veterans Affairs
FX Dr Allison was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK, 5R18DK065001). Dr Salanitro was
supported by a Veterans Affairs National Quality Scholars fellowship.
NR 1
TC 3
Z9 3
U1 1
U2 2
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD MAR
PY 2011
VL 103
IS 3
BP 234
EP 240
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 755UO
UT WOS:000289964400006
PM 21671526
ER
PT J
AU Reiner, AP
Kahn, A
Eisner, BH
Pletcher, MJ
Sadetsky, N
Williams, OD
Polak, JF
Jacobs, DR
Stoller, ML
AF Reiner, Alexander P.
Kahn, Arnold
Eisner, Brian H.
Pletcher, Mark J.
Sadetsky, Natalia
Williams, O. Dale
Polak, Joseph F.
Jacobs, David R., Jr.
Stoller, Marshall L.
TI Kidney Stones and Subclinical Atherosclerosis in Young Adults: The
CARDIA Study
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urolithiasis; atherosclerosis
ID UNITED-STATES; NEPHROLITHIASIS; HYPERTENSION; RISK; ASSOCIATION;
POPULATION; OBESITY
AB Purpose: Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. To our knowledge there has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease. We studied the relationship between nephrolithiasis, and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from the CARDIA study.
Materials and Methods: The CARDIA study is a United States, population based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985 to 1986.
Results: By the year 20 examination 200 (3.9%) CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 examination, particularly of the internal carotid/bulb region. Using a composite dichotomous end point of carotid stenosis and/or the upper quartile of internal carotid/bulb wall thickness, the association of kidney stones with carotid atherosclerosis was significant (OR 1.6, 95% CI 1.1-2.3, p = 0.01), even after adjusting for major atherosclerotic risk factors.
Conclusions: The association between a history of kidney stones and subclinical carotid atherosclerosis in young adults adds further support to the notion that nephrolithiasis and atherosclerosis share common systemic risk factors and/or pathophysiology.
C1 [Pletcher, Mark J.; Sadetsky, Natalia; Stoller, Marshall L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA.
[Pletcher, Mark J.; Sadetsky, Natalia; Stoller, Marshall L.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Reiner, Alexander P.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA.
[Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Polak, Joseph F.] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA.
[Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Kahn, Arnold] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Williams, O. Dale] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
RP Stoller, ML (reprint author), Univ Calif San Francisco, Dept Urol, Box 0738, San Francisco, CA 94143 USA.
EM mstoller@urology.ucsf.edu
FU CARDIA [N01-HC-48047 - N01-HC-48050, N01-HC-95095]; CARDIA Ultrasound
Reading Center [HHSN268200425204C]; CARDIA Computed Tomography Reading
Center [N01-HC-05187, HHSN268200425205C]; Boston Scientific Corporation;
PercSys; Ravine Group
FX Supported by the CARDIA contract (N01-HC-48047 - N01-HC-48050 and
N01-HC-95095), CARDIA Ultrasound Reading Center HHSN268200425204C, and
CARDIA Computed Tomography Reading Center N01-HC-05187 and
HHSN268200425205C.; Financial interest and/or other relationship with
Boston Scientific Corporation, PercSys and the Ravine Group.
NR 19
TC 41
Z9 42
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD MAR
PY 2011
VL 185
IS 3
BP 920
EP 925
DI 10.1016/j.juro.2010.10.086
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 718OM
UT WOS:000287133900056
PM 21251678
ER
PT J
AU Lim, CS
Qiao, XY
Reslan, OM
Xia, Y
Raffetto, JD
Paleolog, E
Davies, AH
Khalil, RA
AF Lim, Chung S.
Qiao, Xiaoying
Reslan, Ossama M.
Xia, Yin
Raffetto, Joseph D.
Paleolog, Ewa
Davies, Alun H.
Khalil, Raouf A.
TI Prolonged mechanical stretch is associated with upregulation of
hypoxia-inducible factors and reduced contraction in rat inferior vena
cava
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 22nd Annual Meeting of the American-Venous-Forum
CY FEB 10-13, 2010
CL Amelia Isl, FL
SP Amer Venous Forum
ID SMOOTH-MUSCLE-CELLS; VARICOSE-VEIN FORMATION; FACTOR-KAPPA-B;
NITRIC-OXIDE; MATRIX METALLOPROTEINASES; SUPEROXIDE-PRODUCTION; INDUCED
ANGIOGENESIS; VASCULAR-DISEASE; MMP-9 EXPRESSION; SKELETAL-MUSCLE
AB Background: Decreased venous tone and vein wall dilation may contribute to varicose vein formation. We have shown that prolonged vein wall stretch is associated with upregulation of matrix metalloproteases (MMPs) and decreased contraction. Because hypoxia-inducible factors (HIFs) expression also increases with mechanical stretch, this study tested whether upregulation of HIFs is an intermediary mechanism linking prolonged vein wall stretch to the changes in MMP expression and venous contraction.
Methods: Segments of rat inferior vena cava (IVC) were suspended in tissue bath under 0.5-g basal tension for 1 hour, and a control contraction to phenylephrine (PHE, 10(-5)M) and KCl (96mM) was elicited. The veins were then exposed to prolonged 18 hours of tension at 0.5 g, 2 g, 2 g plus HIF inhibitor U0126 (10(-5)M), 17-[2-(dimethylamino)ethyl] amino-17-desmethoxygeldanamycin (17-DMAG, 10(-5)M), or echinomycin (10(-6)M), or 2 g plus dimethyloxallyl glycine (DMOG; 10(-4)M), a prolyl-hydroxylase inhibitor that stabilizes HIF. The fold-change in PHE and KCl contraction was compared with the control contraction at 0.5-g tension for 1 hour. Vein tissue homogenates were analyzed for HIF-1 alpha, HIF-2 alpha, MMF-2, and MMP-9 messenger RNA (mRNA) and protein amount using real-time reverse transcription polymerase chain reaction and Western blots.
Results: Compared with control IVC contraction at 0.5-g tension for 1 hour, the PHE and KCl contraction after prolonged 0.5-g tension was 2.0 +/- 0.35 and 1.1 +/- 0.06, respectively. Vein contraction to PHE and KCl after prolonged 2-g tension was significantly reduced (0.87 +/- 0.13 and 0.72 +/- 0.05, respectively). PHE-induced contraction was restored in IVC exposed to prolonged 2-g tension plus the HIF inhibitor U0126 (1.38 +/- 0.15) or echinomycin (1.99 +/- 0.40). U0126 and echinomycin also restored KCl-induced contraction in NC exposed to prolonged 2-g tension (1.14 +/- 0.05 and 1.11 +/- 0.15, respectively). Treatment with DMOG further reduced PHE- and KCl-induced contraction in veins subjected to prolonged 2-g tension (0.47 +/- 0.06 and 0.57 +/- 0.01, respectively). HIF-1 alpha and HIF-2 alpha inRNA were overexpressed in NC exposed to prolonged 2-g tension, and the overexpression was reversed by U0126. The overexpression of HIF-1 alpha and HIF-2 alpha in stretched NC was associated with increased MMP-2 and MMP-9 mRNA. The protein amount of HIf-1 alpha, HIF-2 alpha, MMP-2, and MMP-9 was also increased in NC exposed to prolonged 2-g wall tension.
Conclusions:Prolonged increases in vein wall tension are associated with overexpression of HIF-1 alpha and HIF-2 alpha, increased MMP-2 and MMP-9 expression, and reduced venous contraction in rat IVC. Together with our report that MMP-2 and MMP-9 inhibit NC contraction, the data suggest that increased vein wall tension induces HIF overexpression and causes an increase in MMP expression and reduction of venous contraction, leading to progressive venous dilation and varicose vein formation. (J Vase Surg 2011;53:764-73.)
C1 [Lim, Chung S.; Paleolog, Ewa; Davies, Alun H.] Univ London Imperial Coll Sci Technol & Med, Imperial Vasc Unit, London SW7 2AZ, England.
[Lim, Chung S.; Paleolog, Ewa; Davies, Alun H.] Univ London Imperial Coll Sci Technol & Med, Cytokine Biol Vessels Grp, Dept Surg & Canc, London SW7 2AZ, England.
[Lim, Chung S.; Paleolog, Ewa; Davies, Alun H.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Kennedy Inst Rheumatol, London SW7 2AZ, England.
[Lim, Chung S.; Qiao, Xiaoying; Reslan, Ossama M.; Xia, Yin; Raffetto, Joseph D.; Khalil, Raouf A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02115 USA.
[Raffetto, Joseph D.] VA Boston Healthcare Syst, W Roxbury, MA USA.
RP Khalil, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Vasc Surg, 75 Francis St, Boston, MA 02115 USA.
EM raouf_khalil@hms.harvard.edu
FU NHLBI NIH HHS [HL-70659, R01 HL065998-10, R01 HL065998, R01 HL070659-05,
R01 HL070659, HL-65998]; NICHD NIH HHS [HD-60702, R03 HD060702-02, R03
HD060702]
NR 48
TC 21
Z9 21
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD MAR
PY 2011
VL 53
IS 3
BP 764
EP 773
DI 10.1016/j.jvs.2010.09.018
PG 10
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 727HF
UT WOS:000287788200036
PM 21106323
ER
PT J
AU Jones, EG
AF Jones, Elizabeth Geiger
TI Recognizing Hospital-Acquired Burn Injury in Patients After Coronary
Artery Bypass Surgery
SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING
LA English
DT Article
AB BACKGROUND: Nosocomial injury is a constant threat in the hospital setting. While there is growing awareness surrounding hospital-acquired pressure ulcers, little information is available on burns associated with intraoperative procedures.
CASES: We identified perineal lesions on 4 patients who underwent coronary artery bypass with grafting. These injuries were initially classified as pressure ulcers but subsequent investigation revealed that the injuries were intraoperative burns attributable to pooling of isopropyl alcohol underneath patients who were placed on intraoperative heating pads.
CONCLUSIONS: Differentiating between hospital-acquired pressure ulcers and burns can be difficult. Our facility's experience with intraoperative burn injuries now mandates that this etiologic factor be considered in the differential diagnosis of postoperative patients with atypical cutaneous injuries.
C1 Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA.
RP Jones, EG (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA.
EM Gwammyliz@heavi.tv
NR 12
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1071-5754
J9 J WOUND OSTOMY CONT
JI J. Wound Ostomy Cont. Nurs.
PD MAR-APR
PY 2011
VL 38
IS 2
BP 193
EP 195
DI 10.1097/WON.0b013e31820bc479
PG 3
WC Nursing
SC Nursing
GA 732PZ
UT WOS:000288201900014
PM 21389831
ER
PT J
AU Davies, JK
Barbon, CM
Voskertchian, AR
Nadler, LM
Guinan, EC
AF Davies, Jeff K.
Barbon, Christine M.
Voskertchian, Annie R.
Nadler, Lee M.
Guinan, Eva C.
TI Induction of Alloantigen-specific Anergy in Human Peripheral Blood
Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal
Blockade
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Immunology; Issue 49; Allogeneic stem cell transplantation;
alloreactivity; Graft-versus-Host Disease; T cell costimulation; anergy;
mixed lymphocyte reaction
AB Allogeneic hematopoietic stem cell transplantation (AHSCT) offers the best chance of cure for many patients with congenital and acquired hematologic diseases. Unfortunately, transplantation of alloreactive donor T cells which recognize and damage healthy patient tissues can result in Graft-versus-Host Disease (GvHD)(1). One challenge to successful AHSCT is the prevention of GvHD without associated impairment of the beneficial effects of donor T cells, particularly immune reconstitution and prevention of relapse. GvHD can be prevented by non-specific depletion of donor T cells from stem cell grafts or by administration of pharmacological immunosuppression. Unfortunately these approaches increase infection and disease relapse(2-4). An alternative strategy is to selectively deplete alloreactive donor T cells after allostimulation by recipient antigen presenting cells (APC) before transplant. Early clinical trials of these allodepletion strategies improved immune reconstitution after HLA-mismatched HSCT without excess GvHD(5, 6). However, some allodepletion techniques require specialized recipient APC production(6,7)and some approaches may have off-target effects including depletion of donor pathogen-specific T cells(8)and CD4 T regulatory cells(9). One alternative approach is the inactivation of alloreactive donor T cells via induction of alloantigen-specific hyporesponsiveness. This is achieved by stimulating donor cells with recipient APC while providing blockade of CD28-mediated co-stimulation signals(10). This "alloanergization" approach reduces alloreactivity by 1-2 logs while preserving pathogen-and tumor-associated antigen T cell responses in vitro(11). The strategy has been successfully employed in 2 completed and 1 ongoing clinical pilot studies in which alloanergized donor T cells were infused during or after HLA-mismatched HSCT resulting in rapid immune reconstitution, few infections and less severe acute and chronic GvHD than historical control recipients of unmanipulated HLA-mismatched transplantation(12). Here we describe our current protocol for the generation of peripheral blood mononuclear cells (PBMC) which have been alloanergized to HLA-mismatched unrelated stimulator PBMC. Alloanergization is achieved by allostimulation in the presence of monoclonal antibodies to the ligands B7.1 and B7.1 to block CD28-mediated costimulation. This technique does not require the production of specialized stimulator APC and is simple to perform, requiring only a single and relatively brief ex vivo incubation step. As such, the approach can be easily standardized for clinical use to generate donor T cells with reduced alloreactivity but retaining pathogen-specific immunity for adoptive transfer in the setting of AHSCT to improve immune reconstitution without excessive GvHD.
C1 [Davies, Jeff K.; Barbon, Christine M.; Voskertchian, Annie R.; Nadler, Lee M.; Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Davies, Jeff K.; Nadler, Lee M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Guinan, Eva C.] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA.
RP Guinan, EC (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA.
EM eva_guinan@dfci.harvard.edu
FU National Institutes of Health [U19 CA100625, R21 CA137645]; Leukemia &
Lymphoma Society; American Society of Blood and Marrow
Transplantation/OtsukaNew Investigator Award
FX Supported by the National Institutes of Health (U19 CA100625 and R21
CA137645). JKD was supported by the Leukemia & Lymphoma Society and the
American Society of Blood and Marrow Transplantation/OtsukaNew
Investigator Award.
NR 12
TC 0
Z9 0
U1 0
U2 0
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD MAR
PY 2011
IS 49
AR UNSP e2673
DI 10.3791/2673
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36LY
UT WOS:000209214600048
ER
PT J
AU Villablanca, EJ
Mora, JR
AF Villablanca, Eduardo J.
Mora, J. Rodrigo
TI Competitive Homing Assays to Study Gut-tropic T Cell Migration
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Editorial Material
C1 [Villablanca, Eduardo J.; Mora, J. Rodrigo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Cambridge, MA 02138 USA.
RP Mora, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Cambridge, MA 02138 USA.
EM j_rodrigo_mora@hms.harvard.edu
RI Villablanca, Eduardo/E-1380-2016
OI Villablanca, Eduardo/0000-0001-9522-9729
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD MAR
PY 2011
IS 49
DI 10.3791/2619
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36LY
UT WOS:000209214600014
ER
PT J
AU Ratnam, KK
Feng, XB
Chuang, PY
Verma, V
Lu, TC
Wang, JS
Jin, YM
Farias, EF
Napoli, JL
Chen, N
Kaufman, L
Takano, T
D'Agati, VD
Klotman, PE
He, JC
AF Ratnam, Krishna K.
Feng, Xiaobei
Chuang, Peter Y.
Verma, Vikram
Lu, Ting-Chi
Wang, Jinshan
Jin, Yuanmeng
Farias, Eduardo F.
Napoli, Joseph L.
Chen, Nan
Kaufman, Lewis
Takano, Tomoko
D'Agati, Vivette D.
Klotman, Paul E.
He, John C.
TI Role of the retinoic acid receptor-alpha in HIV-associated nephropathy
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE HIV; kidney disease; podocytes; proteinuria; retinoic acid receptor
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; IN-VITRO; HIV-1-ASSOCIATED
NEPHROPATHY; PATHOLOGICAL CLASSIFICATION; PODOCYTE PROLIFERATION;
ANTIRETROVIRAL THERAPY; GLOMERULAR-DISEASE; EXPRESSION; MICE;
DIFFERENTIATION
AB All-trans retinoic acid protects against the development of HIV-associated nephropathy (HIVAN) in HIV-1 transgenic mice (Tg26). In vitro, all-trans retinoic acid inhibits HIV-induced podocyte proliferation and restores podocyte differentiation markers by activating its receptor-alpha (RAR alpha). Here, we report that Am580, a water-soluble RAR alpha-specific agonist, attenuated proteinuria, glomerosclerosis, and podocyte proliferation, and restored podocyte differentiation markers in kidneys of Tg26 mice. Furthermore, RAR alpha-/- Tg26 mice developed more severe kidney and podocyte injury than did RAR alpha-/- Tg26 mice. Am580 failed to ameliorate kidney injury in RAR alpha-/- Tg26 mice, confirming our hypothesis that Am580 acts through RAR alpha. Although the expression of RAR alpha-target genes was suppressed in the kidneys of Tg26 mice and of patients with HIVAN, the expression of RAR alpha in the kidney was not different between patients with HIVAN and minimal change disease. However, the tissue levels of retinoic acid were reduced in the kidney cortex and isolated glomeruli of Tg26 mice. Consistent with this, the expression of two key enzymes in the retinoic acid synthetic pathway, retinol dehydrogenase type 1 and 9, and the overall enzymatic activity for retinoic acid synthesis were significantly reduced in the glomeruli of Tg26 mice. Thus, a defect in the endogenous synthesis of retinoic acid contributes to loss of the protection by retinoic acid in HIVAN. Hence, RAR alpha agonists may be potential agents for the treatment of HIVAN. Kidney International (2011) 79, 624-634; doi: 10.1038/ki.2010.470; published online 8 December 2010
C1 [He, John C.] Mt Sinai Sch Med, Dept Med Nephrol, Div Nephrol, New York, NY 10029 USA.
[Feng, Xiaobei; Jin, Yuanmeng; Chen, Nan] Shanghai Jiao Tong Univ, RuiJin Hosp, Sch Med, Shanghai 200030, Peoples R China.
[Wang, Jinshan; Napoli, Joseph L.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Farias, Eduardo F.] Mt Sinai Sch Med, Dept Med, Div Hematol, New York, NY 10029 USA.
[Takano, Tomoko] McGill Univ, Ctr Hlth, Div Nephrol, Montreal, PQ, Canada.
[D'Agati, Vivette D.] Columbia Univ, Dept Pathol, New York, NY USA.
[He, John C.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
[He, John C.] James J Peters VA Med Ctr, New York, NY USA.
RP He, JC (reprint author), Mt Sinai Sch Med, Dept Med Nephrol, Div Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA.
EM cijiang.he@mssm.edu
FU National Institutes of Health [R01 DK078897, K08DK082760]; VA
[1I01BX000345]
FX This work was supported by National Institutes of Health grant R01
DK078897 to JCH. JCH is also supported by a VA Merit Award
(1I01BX000345). PYC is a recipient of the NIH career development award
(K08DK082760).
NR 42
TC 31
Z9 31
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAR
PY 2011
VL 79
IS 6
BP 624
EP 634
DI 10.1038/ki.2010.470
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 727MO
UT WOS:000287804600007
PM 21150871
ER
PT J
AU Mollenhauer, B
Locascio, JJ
Schulz-Schaeffer, W
Sixel-Doring, F
Trenkwalder, C
Schlossmacher, MG
AF Mollenhauer, Brit
Locascio, Joseph J.
Schulz-Schaeffer, Walter
Sixel-Doering, Friederike
Trenkwalder, Claudia
Schlossmacher, Michael G.
TI alpha-Synuclein and tau concentrations in cerebrospinal fluid of
patients presenting with parkinsonism: a cohort study
SO LANCET NEUROLOGY
LA English
DT Article
ID MULTIPLE SYSTEM ATROPHY; ALZHEIMERS-DISEASE; LEWY BODIES;
CLINICAL-DIAGNOSIS; RESEARCH CRITERIA; TASK-FORCE; DEMENTIA; CSF;
BIOMARKERS; QUANTIFICATION
AB Background Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy are brain disorders characterised by intracellular alpha-synuclein deposits. We aimed to assess whether reduction of alpha-synudein concentrations in CSF was a marker for alpha-synuclein deposition in the brain, and therefore diagnostic of synucleinopathies.
Methods We assessed potential extracellular-fluid markers of alpha-synuclein deposition in the brain (total alpha-synuclein and total tau in CSF, and total alpha-synuclein in serum) in three cohorts: a cross-sectional training cohort of people with Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, Alzheimer's disease, or other neurological disorders; a group of patients with autopsy-confirmed dementia with Lewy bodies, Alzheimer's disease, or other neurological disorders (CSF specimens were drawn ante mortem during clinical investigations); and a validation cohort of patients who between January, 2003, and December, 2006, were referred to a specialised movement disorder hospital for routine inpatient admission under the working diagnosis of parkinsonism. CSF and serum samples were assessed by ELISA, and clinical diagnoses were made according to internationally established criteria. Mean differences in biomarkers between diagnostic groups were assessed with conventional parametric and non-parametric statistics.
Findings In our training set, people with Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies had lower CSF alpha-synuclein concentrations than patients with Alzheimer's disease and other neurological disorders. CSF alpha-synuclein and tau values separated participants with synucleinopathies well from those with other disorders (p<0.0001; area under the receiver operating characteristic curve [AUC]=0.908). In the autopsy-confirmed cases, CSF alpha-synuclein discriminated between dementia with Lewy bodies and Alzheimer's disease (p=0-0190; AUC=0.687); in the validation cohort, CSF alpha-synuclein discriminated Parkinson's disease and dementia with Lewy bodies versus progressive supranuclear palsy, normal-pressure hydrocephalus, and other neurological disorders (p<0.0001; AUC=0.711). Other predictor variables tested in this cohort included CSF tau (p=0.0798), serum alpha-synuclein (p=0.0502), and age (p=0.0335). CSF alpha-synuclein concentrations of 1.6 pg/p.I. or lower showed 70.72% sensitivity (95% CI 65-3-76.1%) and 52.83% specificity (39.4-66.3%) for the diagnosis of Parkinson's disease. At this cutoff, the positive predictive value for any synucleinopathy was 90.7% (95% CI 87.3-94.2%) and the negative predictive value was 20.4% (13.7-27.2%).
Interpretation Mean CSF alpha-synuclein concentrations as measured by ELISA are significantly lower in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy than in other neurological diseases. Although specificity was low, the high positive predictive value of CSF alpha-synuclein concentrations in patients presenting with synucleinopathy-type parkinsonism might be useful in stratification of patients in future clinical trials.
C1 [Mollenhauer, Brit; Sixel-Doering, Friederike; Trenkwalder, Claudia] Paracelsus Elena Klin, D-34128 Kassel, Germany.
[Mollenhauer, Brit; Trenkwalder, Claudia] Georg August Univ Goettingen, Dept Neurol, Gottingen, Germany.
[Mollenhauer, Brit; Trenkwalder, Claudia] Georg August Univ Goettingen, Dept Clin Neurophysiol, Gottingen, Germany.
[Locascio, Joseph J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Schulz-Schaeffer, Walter] Univ Gottingen, Dept Neuropathol, Gottingen, Germany.
[Schlossmacher, Michael G.] Ottawa Hosp, Div Neurosci, Res Inst, Dept Med, Ottawa, ON, Canada.
[Schlossmacher, Michael G.] Univ Ottawa, Dept Cellular & Mol Med, OHRI Neurosci, Ottawa, ON K1H 8M5, Canada.
[Mollenhauer, Brit; Schlossmacher, Michael G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA.
RP Mollenhauer, B (reprint author), Paracelsus Elena Klin, Klin Str 16, D-34128 Kassel, Germany.
EM brit.mollenhauer@pk-mx.de; mschlossmacher@ohri.ca
FU TEVA-Pharma; Desitin; Boehringer Ingelheim; GE Healthcare; TEVA
Neuroscience; VolkswagenStiftung; Deutsche Forschungsgemeinschaft;
Alberta Prion Research Institut, Canada; European Union; Bayer Schering
Pharma; German Parkinson Patient Foundation; Orion Phamia; UCB/Schwarz
Pharma; Solvay
FX BM has received grants from TEVA-Pharma, Desitin, Boehringer Ingelheim
and GE Healthcare and honoraria for consultancy from Bayer Schering
Pharma AG and for presentations from GlaxoSmithKline and Orion Pharma as
well as travel and meeting expenses from Boehringer-Ingelheim and
Novartis. MGS has served as an ad hoc, paid consultant for FoldRx,
Genzyme, Johnson and Johnson, Amicus Therapeutics, Elan Pharmaceuticals,
Novartis, and LINK Medicine, has received payment for a lecture from
TEVA Neuroscience, and has a scientific collaboration with Covance,
Epitomics, and the Michael J Fox Foundation. CT is employed by
Paracelsus, provides expert testimony for Axxonis, serves as a
consultant for TEVA Pharma, Boerhinger-Ingelheim, UCB, Solvay, Novartis,
Mundipharm, Viofor Pharma, and Cephalon, and has received honoraria for
presentations and lectures from TEVA Pharma, Boehringer-Ingelheim, UCB,
Viofor Pharma, and Cephalon. WS-S serves as consultant for Bayer
Schering Pharma; he has received grants from the VolkswagenStiftung,
Deutsche Forschungsgemeinschaft, Alberta Prion Research Institut,
Canada, and the European Union, and has received payment for lectures
from Bayer Schering Pharma. FS-D has received a grant from the German
Parkinson Patient Foundation and honoraria from advisory board meetings
from Orion Pharma, as well as payment for lectures by
Boehringer-Ingelheim, Orion Phamia, UCB/Schwarz Pharma, and Solvay. JJL
declares no conflicts of interest. BM and MGS are listed as co-inventors
in a patent application to the US Patent Office related to the
quantification of alpha-synuclein in biological fluids for the purpose
of improved diagnosis.
NR 42
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U1 2
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD MAR
PY 2011
VL 10
IS 3
BP 230
EP 240
DI 10.1016/S1474-4422(11)70014-X
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 736HR
UT WOS:000288482200011
PM 21317042
ER
PT J
AU Gianni, L
Dafni, U
Gelber, RD
Azambuja, E
Muehlbauer, S
Goldhirsch, A
Untch, M
Smith, I
Baselga, J
Jackisch, C
Cameron, D
Mano, M
Pedrini, JL
Veronesi, A
Mendiola, C
Pluzanska, A
Semiglazov, V
Vrdoljak, E
Eckart, MJ
Shen, ZZ
Skiadopoulos, G
Procter, M
Pritchard, KI
Piccart-Gebhart, MJ
Bell, R
AF Gianni, Luca
Dafni, Urania
Gelber, Richard D.
Azambuja, Evandro
Muehlbauer, Susanne
Goldhirsch, Aron
Untch, Michael
Smith, Ian
Baselga, Jose
Jackisch, Christian
Cameron, David
Mano, Max
Pedrini, Jose Luiz
Veronesi, Andrea
Mendiola, Cesar
Pluzanska, Anna
Semiglazov, Vladimir
Vrdoljak, Eduard
Eckart, Michael J.
Shen, Zhenzhou
Skiadopoulos, George
Procter, Marion
Pritchard, Kathleen I.
Piccart-Gebhart, Martine J.
Bell, Richard
CA Herceptin Adjuvant HERA Trial Stud
TI Treatment with trastuzumab for 1 year after adjuvant chemotherapy in
patients with HER2-positive early breast cancer: a 4-year follow-up of a
randomised controlled trial
SO LANCET ONCOLOGY
LA English
DT Article
ID 1ST-LINE TREATMENT; CLINICAL-TRIALS; OVARIAN-CANCER; PHASE-II; EFFICACY;
SAFETY; ONCOGENE; ANTIBODY; PLUS
AB Background Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial.
Methods The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48.4 months (IQR 42.0-56.5) and assess the effect of the extensive crossover to trastuzumab. Our analysis was by intention-to-treat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11.
Findings The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78.6%) compared with the observation group (4-year disease-free survival 72.2%; hazard ratio [HR] 0.76; 95% CI 0.66-0.87; p<0.0001). Intention-to-treat analysis of overall survival showed no significant difference in the risk of death (4-year overall survival 89.3% vs 87.7%, respectively; HR 0.85; 95% CI 0.70-1.04; p=0.11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22.8 months (range 4.5-52.7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group (adjusted HR 0.68; 95% CI 0.51-0.90; p=0.0077). Higher incidences of grade 3-4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhoea.
Interpretation Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort.
C1 [Gianni, Luca] San Raffaele Inst, Dept Med Oncol, Milan, Italy.
[Dafni, Urania] Univ Athens, Lab Biostat, Athens, Greece.
[Dafni, Urania; Skiadopoulos, George] Frontier Sci Fdn Hellas, Athens, Greece.
[Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Azambuja, Evandro] Univ Libre Bruxelles, Med Oncol Clin, Inst Jules Bordet, Brussels, Belgium.
[Azambuja, Evandro] Univ Libre Bruxelles, Breast European Adjuvant Study Team BrEAST, Ctr Data, Inst Jules Bordet, Brussels, Belgium.
[Muehlbauer, Susanne] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland.
[Goldhirsch, Aron] European Inst Oncol, Dept Med, Milan, Italy.
[Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland.
[Untch, Michael] Helios Klinikum Berlin Buch, Dept Obstet & Gynaecol, Berlin, Germany.
[Untch, Michael] Helios Klinikum Berlin Buch, Multidisciplinary Breast Canc Ctr, Berlin, Germany.
[Smith, Ian] Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England.
[Smith, Ian] Inst Canc Res, London SW3 6JB, England.
[Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA.
[Jackisch, Christian] Klinikum Offenbach, Dept Gynecol & Obstet, Offenbach, Germany.
[Cameron, David] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Cameron, David] Western Gen Hosp, Dept Oncol, Edinburgh EH4 2XU, Midlothian, Scotland.
[Mano, Max] Univ Sao Paulo, Dept Med Oncol, Inst Canc Estado Sao Paulo, BR-05508 Sao Paulo, Brazil.
[Pedrini, Jose Luiz] Hosp Nossa Senhora Conceicao, Minist Saude, Unity Mastol, Porto Alegre, RS, Brazil.
[Veronesi, Andrea] Natl Canc Inst, Ctr Riferimento Oncol, Div Med Oncol C, Aviano, Italy.
[Mendiola, Cesar] Hosp Ruber Int, Madrid, Spain.
[Pluzanska, Anna] Reg Oncol Ctr, Oncol Chemotherapy Clin, Lodz, Poland.
[Semiglazov, Vladimir] Petrov Res Inst Oncol, St Petersburg, Russia.
[Vrdoljak, Eduard] Univ Hosp Split, Split, Croatia.
[Eckart, Michael J.] Onkol Schwerpunktpraxis & Tagesklin, Erlangen, Germany.
[Shen, Zhenzhou] Fudan Univ, Canc Hosp, Shanghai 200433, Peoples R China.
[Procter, Marion] Frontier Sci Scotland, Kingussie, Kincraig, Scotland.
[Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Piccart-Gebhart, Martine J.] Univ Libre Bruxelles, Dept Med, Inst Jules Bordet, Brussels, Belgium.
[Piccart-Gebhart, Martine J.] Univ Libre Bruxelles, BrEAST Data Ctr, Inst Jules Bordet, Brussels, Belgium.
[Bell, Richard] Geelong Hosp, Andrew Love Canc Ctr, Geelong, Vic, Australia.
RP Gianni, L (reprint author), Fdn San Raffaele, Via Olgettina 68, I-20132 Milan, Italy.
EM gianni.luca@hsr.it
RI Mano, Max /C-6917-2012; Pritchard, Kathleen/I-2184-2014
OI Semiglazov, Vladimir/0000-0003-0077-9619; Pritchard,
Kathleen/0000-0003-0758-9666
FU Roche; Michelangelo Foundation
FX LG has received payments for membership of advisory boards for Roche.
RDG was provided with financial support through Roche's support for the
International Breast Cancer Study Group and Breast International Group.
IS has received speaker's honoraria from Roche. CJ has received
consultancy fees from Roche in relation to the HERA trial, and travel
expenses and speaker's honoraria. EA has received consultancy fees from
Roche in relation to the HERA trial and speaker's honoraria. MM has
received travel expenses from Roche in relation to the HERA trial and
speaker's honoraria. CM and EV have received consultancy fees from Roche
in relation to the HERA trial, and travel expenses and speaker's
honoraria. EV has received consultancy fees and payments for advisory
board membership, speaking engagements, and related travel expenses. CM
has received consultancy fees, payment for speaking engagements, and
related travel expenses. GS's institution received funding from Roche in
relation to the HERA study. JP received travel expenses from Roche to
attend HERA-related meetings. AV has received research funding and
travel expenses from Roche. DC and RB have received research funding
from Roche in relation to the HERA trial, honoraria for speaking
engagements, and consultancy fees and travel expenses from Roche. MJP-G
and JB have received consultancy fees from Roche for work unrelated to
this study. KIP has received consultancy fees from Roche in relation to
the HERA trial. SM is an employee of F Hoffmann-La Roche and has stock
options in the company. The other authors declare that they have no
conflicts of interest.; We thank the women who participated in the
study; the Breast European Adjuvant Study Team Data Centre; the Frontier
Science Team; the Breast International Group Secretariat; the HERA
steering committee; the Independent Data Monitoring Committee; the
Cardiac Advisory Board; the Pathology Laboratory, Kassel, Germany; F
Hoffmann-La Roche; and all the doctors who participated in HERA. Medical
writing assistance was provided by Alan Russell of Complete HealthVizion
and funded by the Michelangelo Foundation.
NR 25
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAR
PY 2011
VL 12
IS 3
BP 236
EP 244
DI 10.1016/S1470-2045(11)70033-X
PG 9
WC Oncology
SC Oncology
GA 736HY
UT WOS:000288483500022
PM 21354370
ER
PT J
AU Ghobrial, IM
Weller, E
Vij, R
Munshi, NC
Banwait, R
Bagshaw, M
Schlossman, R
Leduc, R
Chuma, S
Kunsman, J
Laubach, J
Jakubowiak, AJ
Maiso, P
Roccaro, A
Armand, P
Dollard, A
Warren, D
Harris, B
Poon, T
Sam, A
Rodig, S
Anderson, KC
Richardson, PG
AF Ghobrial, Irene M.
Weller, Edie
Vij, Ravi
Munshi, Nikhil C.
Banwait, Ranjit
Bagshaw, Meghan
Schlossman, Robert
Leduc, Renee
Chuma, Stacey
Kunsman, Janet
Laubach, Jacob
Jakubowiak, Andrzej J.
Maiso, Patricia
Roccaro, Aldo
Armand, Philippe
Dollard, Akari
Warren, Diane
Harris, Brianna
Poon, Tiffany
Sam, Amy
Rodig, Scott
Anderson, Kenneth C.
Richardson, Paul G.
TI Weekly bortezomib in combination with temsirolimus in relapsed or
relapsed and refractory multiple myeloma: a multicentre, phase 1/2,
open-label, dose-escalation study
SO LANCET ONCOLOGY
LA English
DT Article
ID MAMMALIAN TARGET; SYNERGISTIC ACTIVITY; INHIBITOR RAPAMYCIN; AKT
ACTIVITY; II TRIAL; MTOR; CCI-779; CELLS; PATHWAYS; KINASE
AB Background Multiple myeloma is the second most prevalent haematological malignancy and is incurable. Our aim was to assess the response and safety of the combination of temsirolimus (an mTOR inhibitor) and bortezomib in patients with relapsed or refractory multiple myeloma.
Methods We did an open-label, dose-escalation study in three centres in the USA. Patients were enrolled from June, 2007, to December, 2009. Eligible patients were aged 18 years or older with relapsed or relapsed and refractory multiple myeloma after one or more treatment (including lenalidomide, bortezomib, or thalidomide), with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were assigned a dose level in the order of their entry into the study. Phase 1 was to assess the safety and establish the maximum tolerated dose (MTD) of the combination and phase 2 was to assess overall response rate at the MTD. Intravenous temsirolimus was given at 15 or 25 mg and intravenous bortezomib at 1.3 or 1.6 mg/m(2) once a week, with dose escalation until dose-limiting adverse events were recorded in two of the three people in the dose cohort. Use of steroids were not permitted. The primary endpoint was the proportion of patients with a partial response or better. Analyses were done on an intention-to-treat basis, with all patients who had been enrolled included. The study is registered with ClinicalTrials.gov, number NCT00483262.
Findings 20 patients were enrolled into the phase 1 study and 43 into phase 2. All patients were heavily pretreated (median five lines in the phase 1 cohort, and four lines in the phase 2 cohort). The MTD was determined to be 1.6 mg/m(2) bortezomib on days 1, 8, 15, and 22 in combination with 25 mg temsirolimus on days 1, 8, 15, 22, and 29, for a cycle of 35 days. In the phase 2 study, the proportion of patients with a partial response or better was 33% (14 of 43; 90% CI 21-47). Long-term follow-up of patients is ongoing. There were three deaths during treatment in the phase 1 and 2 studies: one patient died of septic shock in the phase 1 study; one patient died with H1N1 influenza infection and one died with cardiac amyloid and ventricular arrhythmia unrelated to treatment in the phase 2 study. In the phase 1 study, the most common treatment-related grade 3-4 adverse events were thrombocytopenia (13 patients), lymphopenia (ten), neutropenia (nine), leucopenia (seven), and anaemia (five). In the phase 2 study, the most common treatment-related grade 3-4 adverse events were thrombocytopenia (25 patients), lymphopenia (24), neutropenia (17), leucopenia (ten), anaemia (seven), and diarrhoea (five). Four patients in the phase 1 study had sensory peripheral neuropathy (grade 2 or less); in the phase 2 study, 11 had sensory peripheral neuropathy (all grade 2 or less) and seven motor peripheral neuropathy (one grade 3, six grade 2 or less).
Interpretation mTOR inhibitors could have a role in combination with weekly bortezomib for the treatment of patients with relapsed and refractory multiple myeloma without the addition of steroids.
C1 [Ghobrial, Irene M.; Weller, Edie; Munshi, Nikhil C.; Banwait, Ranjit; Bagshaw, Meghan; Schlossman, Robert; Leduc, Renee; Chuma, Stacey; Kunsman, Janet; Laubach, Jacob; Maiso, Patricia; Roccaro, Aldo; Armand, Philippe; Warren, Diane; Harris, Brianna; Poon, Tiffany; Sam, Amy; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Vij, Ravi] Washington Univ, Sch Med, Sect Bone Marrow Transplant & Leukemia, St Louis, MO USA.
[Munshi, Nikhil C.] Boston Veteran Affairs Hlth Care Syst, Dept Med, Boston, MA USA.
[Jakubowiak, Andrzej J.] Univ Michigan, Dept Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA.
[Dollard, Akari] MMRC, Norwalk, CT USA.
[Rodig, Scott] Brigham & Women Hosp, Dept Pathol, Boston, MA USA.
RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM irene_ghobrial@dfci.hatvard.edu
OI Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128;
Harris, Brianna/0000-0001-6229-9907
FU Millennium; Bristol-Myers Squibb; Celgene; Onyx
FX IMG has received payment as a member of advisory boards for Millennium,
Celgene, Novartis, Genzyme, and Onyx; and has received research support
from Millennium and Bristol-Myers Squibb. RV has received payment for
being a member of speaker bureaus for Celgene and Millennium; advisory
boards for Millennium, Celgene, and Onyx; and has received research
support from Celgene and Onyx. NCM has received payment for being a
member of advisory boards for Millennium, Celgene, Onyx, and Novartis.
At has been a consultant without honoraria for Millennium, Bristol-Myers
Squibb, and Onyx. KCA has received payment for being a member of
advisory boards for Millennium, Celgene, Johnson get Johnson,
Bristol-Myers Squibb, Onyx, and Novartis; and is the founder and a share
holder of Acetylon Inc. PGR has received payment for being a member of
advisory boards for Millennium, Celgene, Johnson & Johnson,
Bristol-Myers Squibb, and Novartis. The other authors declare no
conflicts of interest.
NR 33
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD MAR
PY 2011
VL 12
IS 3
BP 263
EP 272
DI 10.1016/S1470-2045(11)70028-6
PG 10
WC Oncology
SC Oncology
GA 736HY
UT WOS:000288483500025
PM 21345726
ER
PT J
AU Tanaka, M
Kinoshita, M
Yoshihara, Y
Shinomiya, N
Seki, S
Nemoto, K
Hamblin, MR
Morimoto, Y
AF Tanaka, Masamitsu
Kinoshita, Manabu
Yoshihara, Yasuo
Shinomiya, Nariyoshi
Seki, Shuhji
Nemoto, Koichi
Hamblin, Michael R.
Morimoto, Yuji
TI Photodynamic Therapy Using Intra-Articular Photofrin for Murine MRSA
Arthritis: Biphasic Light Dose Response for Neutrophil-Mediated
Antibacterial Effect
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE photoinactivation; antimicrobial effect; neutrophil-mediated host
defense; chemokine; macrophage inflammatory protein-2
ID RESISTANT STAPHYLOCOCCUS-AUREUS; IN-VIVO; INFECTIONS; MICE; MODEL
AB Background and Objective: Bacterial arthritis does not respond well to antibiotics and moreover multidrug resistance is spreading. We previously tested photodynamic therapy (PDT) mediated by systemic Photofrin (R) in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) arthritis, but found that neutrophils were killed by PDT and therefore the infection was potentiated.
Study Design/Materials and Methods: The present study used an intra-articular injection of Photofrin (R) and optimized the light dosimetry in order to maximize bacterial killing and minimize killing of host neutrophils. MRSA (5 x 10(7) CFU) was injected into the mouse knee followed 3 days later by 1 mu g of Photofrin (R) and 635-nm diode laser illumination with a range of fluences within 5 minutes. Synovial fluid was sampled 6 hours or 1-3, 5, and 7 days after PDT to determine MRSA colony-forming units (CFU), neutrophil numbers, and levels of cytokines.
Results: A biphasic light dose response was observed with the greatest reduction of MRSA CFU seen with a fluence of 20 J cm(-2), whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. Consistent with these results, a significantly higher concentration of macrophage inflammatory protein-2, a CXC chemokine, and greater accumulation of neutrophils were seen in the infected knee joint after PDT with a fluence of 20 J cm(-2) compared to fluences of 5 or 70 J cm(-2).
Conclusion: PDT for murine MRSA arthritis requires appropriate light dosimetry to simultaneously maximize bacterial killing and neutrophil accumulation into the infected site, while too little light does not kill sufficient bacteria and too much light kills neutrophils and damages host tissue as well as bacteria and allows bacteria to grow unimpeded by host defense. Lasers Surg. Med. 43:221-229, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Shinomiya, Nariyoshi; Morimoto, Yuji] Natl Def Med Coll, Dept Integrat Physiol & Bionano Med, Tokorozawa, Saitama 3598513, Japan.
[Tanaka, Masamitsu; Yoshihara, Yasuo; Nemoto, Koichi] Natl Def Med Coll, Dept Orthoped Surg, Tokorozawa, Saitama 3598513, Japan.
[Kinoshita, Manabu; Seki, Shuhji] Natl Def Med Coll, Dept Immunol & Microbiol, Tokorozawa, Saitama 3598513, Japan.
[Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Morimoto, Y (reprint author), Natl Def Med Coll, Dept Integrat Physiol & Bionano Med, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan.
EM moyan@ndmc.ac.jp
OI Hamblin, Michael/0000-0001-6431-4605
FU US NIH [RO1AI050875]; US Air Force MFEL program [FA9550-04-1-0079];
Center for Integration of Medicine and Innovative Technology
[DAMD17-02-2-0006]; Congressionally Directed Medical Research Program
[W81XWH-09-1-0514]; Young Scholar Encouragement Program of National
Defense Medical College
FX This work was supported by the Young Scholar Encouragement Program of
National Defense Medical College. M. R. H. was supported by US NIH
(grant RO1AI050875), US Air Force MFEL program (contract
FA9550-04-1-0079), Center for Integration of Medicine and Innovative
Technology (DAMD17-02-2-0006), Congressionally Directed Medical Research
Program (W81XWH-09-1-0514).
NR 34
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U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD MAR
PY 2011
VL 43
IS 3
BP 221
EP 229
DI 10.1002/lsm.21037
PG 9
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 735EC
UT WOS:000288395200006
PM 21412806
ER
PT J
AU Grabher, C
Payne, EM
Johnston, AB
Bolli, N
Lechman, E
Dick, JE
Kanki, JP
Look, AT
AF Grabher, C.
Payne, E. M.
Johnston, A. B.
Bolli, N.
Lechman, E.
Dick, J. E.
Kanki, J. P.
Look, A. T.
TI Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb
SO LEUKEMIA
LA English
DT Article
DE miR-126; miR-150; c-myb; thrombocyte; hematopoiesis; zebrafish
ID ACUTE MYELOID-LEUKEMIA; STEM-CELLS; TRANSCRIPTIONAL REGULATION;
DEFINITIVE HEMATOPOIESIS; AORTIC ENDOTHELIUM; T-ALL; EXPRESSION; TARGET;
PROGENITOR; MEGAKARYOPOIESIS
AB Precise regulatory mechanisms are required to appropriately modulate the cellular levels of transcription factors controlling cell fate decisions during blood cell development. In this study, we show that miR-126 is a novel physiological regulator of the proto-oncogene c-myb during definitive hematopoiesis. We show that knockdown of miR-126 results in increased c-Myb levels and promotes erythropoiesis at the expense of thrombopoiesis in vivo. We further provide evidence that specification of thrombocyte versus erythrocyte cell lineages is altered by the concerted activities of the microRNAs (miRNAs) miR-126 and miR-150. Both miRNAs are required but not sufficient individually to precisely regulate the cell fate decision between erythroid and megakaryocytic lineages during definitive hematopoiesis in vivo. These results support the notion that miRNAs not only function to provide precision to developmental programs but also are essential determinants in the control of variable potential functions of a single gene during hematopoiesis. Leukemia (2011) 25, 506-514; doi:10.1038/leu.2010.280; published online 16 November 2010
C1 [Grabher, C.; Payne, E. M.; Johnston, A. B.; Bolli, N.; Kanki, J. P.; Look, A. T.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Payne, E. M.] Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, Inst Canc, London, England.
[Lechman, E.; Dick, J. E.] Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Canc Res, Div Stem Cell & Dev Biol, Toronto, ON, Canada.
[Lechman, E.; Dick, J. E.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Look, A. T.] Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol,Dept Pediat, Boston, MA 02115 USA.
RP Grabher, C (reprint author), Karlsruhe Inst Technol, Inst Toxicol & Genet, Hermann von Helmholtz Pl 1, D-76344 Eggenstein Leopoldshafen, Germany.
EM clemens.grabher@kit.edu
RI Grabher, Clemens/H-2064-2013; Bolli, Niccolo/D-4057-2011;
OI Bolli, Niccolo/0000-0002-1018-5139; Dick, John/0000-0002-9527-8317
FU NIH [CA93152]; Leukemia and Lymphoma Research UK
FX We thank R Hoffmans, U Pyati and N Bushati for critical comments on the
manuscript and L Zon for the Tg(c-myb:EGFP) zebrafish line. This work
was supported by the NIH grant CA93152 (ATL). EMP is the recipient of a
Clinical Research Training Fellowship from Leukemia and Lymphoma
Research UK. NB is a Special Fellow of the Leukemia and Lymphoma
Society.
NR 52
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U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAR
PY 2011
VL 25
IS 3
BP 506
EP 514
DI 10.1038/leu.2010.280
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 732CB
UT WOS:000288159500014
PM 21079614
ER
PT J
AU Stone, RM
Moser, B
Sanford, B
Schulman, P
Kolitz, JE
Allen, S
Stock, W
Galinsky, I
Vij, R
Marcucci, G
Hurd, D
Larson, RA
AF Stone, Richard M.
Moser, Barry
Sanford, Ben
Schulman, Philip
Kolitz, Jonathan E.
Allen, Steven
Stock, Wendy
Galinsky, Ilene
Vij, Ravi
Marcucci, Guido
Hurd, David
Larson, Richard A.
CA Canc & Leukemia Grp B
TI High dose cytarabine plus gemtuzumab ozogamicin for patients with
relapsed or refractory acute myeloid leukemia: Cancer and Leukemia Group
B study 19902
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Gemtuzumab ozogamicin; Acute myeloid leukemia; Cytarabine; Relapse
ID ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; DISEASE-FREE
SURVIVAL; INDUCTION CHEMOTHERAPY; FINAL REPORT; PHASE-I; G-CSF;
MITOXANTRONE; COMBINATION; ADULTS
AB Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate, was combined with high dose cytarabine (HiDAC; cytarabine 3 g/m(2) over 3 h daily for 5 days) for adults with relapsed or refractory AML. HiDAC plus GO 9mg/m(2) on day 7 and 4.5mg/m(2) on day 14 was not tolerated, but HiDAC followed by GO 9mg/m(2) on day 7 was safe: 12/37 (32%) patients with relapsed AML achieved complete remission. Median overall survival was 8.9 months. No grade 4 hepatic veno-occlusive disease was observed. This regimen merits further study, both in this setting and as a remission consolidation therapy. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Stone, Richard M.; Galinsky, Ilene] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Moser, Barry; Sanford, Ben] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA.
[Schulman, Philip] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Kolitz, Jonathan E.; Allen, Steven] N Shore Long Isl Jewish Hlth Syst, New Hyde Pk, NY USA.
[Stock, Wendy; Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA.
[Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA.
[Marcucci, Guido] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
[Hurd, David] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
RP Stone, RM (reprint author), Dana Farber Canc Inst, 44 Binney St,M1B-17, Boston, MA 02115 USA.
EM rstone@partners.org
OI Allen, Steven/0000-0002-3482-3182; Larson, Richard/0000-0001-9168-3203
FU National Cancer Institute [CA31946]; Cancer and Leukemia Group B; CALGB
Statistical Center [CA33601]
FX The research for CALGB 19902 was supported, in part, by grants from the
National Cancer Institute (CA31946) to the Cancer and Leukemia Group B
(Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center
(Stephen George, PhD, CA33601). The content of this manuscript is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Cancer Institute. The following
institutions participated in this study: Christiana Care Health
Services, Inc. CCOP, Wilmington, DE - Stephen Grubbs, MD, supported by
CA45418; Hematology-Oncology Associates of Central New York CCOP,
Syracuse, NY - Jeffrey Kirshner, MD, supported by CA45389; Kansas City
Community Clinical Oncology Program CCOP, Kansas City, MO - Rakesh Gaur,
MD; Dana-Farber Cancer Institute, Boston, MA Harold J. Burstein, MD,
supported by CA32291; North Shore Long Island Jewish Health System, New
Hyde Park, NY - Daniel Budman, MD, supported by CA35279; Rhode Island
Hospital, Providence, RI - William Sikov, MD, supported by CA08025; The
Ohio State University Medical Center, Columbus, OH - Clara D.
Bloomfield, MD, supported by CA77658; University of Chicago, Chicago, IL
- Hedy L Kindler, MD, supported by CA41287; University of Illinois
MBCCOP, Chicago, IL - David J. Peace, MD, supported by CA74811;
University of Iowa, Iowa City, IA - Daniel A. Vaena, MD, supported by
CA47642; University of Vermont, Burlington, VT - Hyman B. Muss, MD,
supported by CA77406; Wake Forest University School of Medicine,
Winston-Salem, NC - David D. Hurd, MD, supported by CA03927; Washington
University School of Medicine, St. Louis, MO - Nancy Bartlett, MD,
supported by CA77440; and Western Pennsylvania Cancer Institute,
Pittsburgh, PA - Richard K. Shadduck, MD.
NR 28
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U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD MAR
PY 2011
VL 35
IS 3
BP 329
EP 333
DI 10.1016/j.leukres.2010.07.017
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 729QH
UT WOS:000287965100017
PM 20688393
ER
PT J
AU Rogal, SS
Landsittel, D
Surman, O
Chung, RT
Rutherford, A
AF Rogal, Shari S.
Landsittel, Douglas
Surman, Owen
Chung, Raymond T.
Rutherford, Anna
TI Pretransplant Depression, Antidepressant Use, and Outcomes of Orthotopic
Liver Transplantation
SO LIVER TRANSPLANTATION
LA English
DT Article
ID RENAL-TRANSPLANTATION; HEART-TRANSPLANTATION; MORBIDITY; PREDICTORS;
MORTALITY; DISEASE; RISK
AB Depression is a common problem among patients awaiting organ transplantation, but little is known about the impact of depression and its treatment on the outcomes of liver transplantation. In this retrospective cohort analysis, we studied all patients over 18 years of age who underwent liver transplantation during a 5-year period (2004-2008) at a single center. Among 179 recipients, 65 patients had depression, as defined by a health care provider assessment, before transplantation. Depression was defined as past or active depression or an adjustment disorder. The associations between pretransplant depression and various outcomes (time to death, graft failure, first acute cellular rejection episode, first infection, and first rehospitalization) were assessed. In the entire sample, more patients with depression required posttransplant psychiatric care (37% versus 18%); the adjusted hazard ratio was 2.28 (1.27-4.11). The rates of other outcomes, including hospital readmission, acute cellular rejection, graft failure, mortality, and infection, were similar for patients with depression and patients without depression. Among those with depression, patients on antidepressants at the time of transplantation had acute cellular rejection less frequently than those not taking antidepressants (13% versus 40%); the adjusted hazard ratio was 0.14 (0.03-0.62). The rates of other outcomes were similar between these 2 groups. These data indicate that depression affects posttransplant psychiatric morbidity but not other medical outcomes of liver transplantation. Pharmacological treatment of depression may significantly reduce the incidence of acute cellular rejection in patients undergoing liver transplantation. However, future prospective studies of mental health and liver transplantation are required to definitively assess the effects of antidepressant medications on medical outcomes. Liver Transpl 17:251-260, 2011. (C) 2011 AASLD.
C1 [Rogal, Shari S.] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA.
[Rutherford, Anna] Brigham & Womens Hosp, Div Gastroenterol & Hepatol, Boston, MA 02115 USA.
[Landsittel, Douglas] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA.
[Surman, Owen] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol & Hepatol, Boston, MA 02114 USA.
RP Rogal, SS (reprint author), Univ Pittsburgh, Med Ctr, Presbyterian Univ Hosp, Div Gastroenterol Hepatol & Nutr, C Wing,200 Lothrop St, Pittsburgh, PA 15261 USA.
EM shari.rogal@gmail.com
FU National Center for Research Resources a component of the National
Institutes of Health [5UL1 RR024153-04]; Roadmap for Medical Research
FX Contributions from Douglas Landsittel were made possible by grant 5UL1
RR024153-04 from the National Center for Research Resources (a component
of the National Institutes of Health) and the Roadmap for Medical
Research.
NR 20
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U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1527-6465
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD MAR
PY 2011
VL 17
IS 3
BP 251
EP 260
DI 10.1002/lt.22231
PG 10
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA 732IL
UT WOS:000288178100005
PM 21384507
ER
PT J
AU Paulus, JK
Zhou, W
Kraft, P
Johnson, BE
Lin, XH
Christiani, DC
AF Paulus, Jessica K.
Zhou, Wei
Kraft, Peter
Johnson, Bruce E.
Lin, Xihong
Christiani, David C.
TI Haplotypes of estrogen receptor-beta and risk of non-small cell lung
cancer in women
SO LUNG CANCER
LA English
DT Article
DE Non-small cell lung cancer; Estrogen receptor-beta (ESR2); Molecular
epidemiology; Tobacco; Parity; Women
ID HORMONE REPLACEMENT THERAPY; CIGARETTE-SMOKING; UNRELATED INDIVIDUALS;
POSTMENOPAUSAL WOMEN; REPRODUCTIVE FACTORS; PROSTATE-CANCER;
SEX-DIFFERENCES; BREAST-CANCER; EXPRESSION; COHORT
AB Epidemiologic and biologic evidence suggests that lung cancer has different clinical and biological characteristics in women, and that estrogen may contribute to the pathogenesis of non-small cell lung cancer (NSCLC). We investigated whether germline variation in the estrogen receptor-beta gene (ESR2) is associated with lung cancer risk among 1021 female cases and 826 female controls enrolled in the Lung Cancer Susceptibility Study at the Massachusetts General Hospital from 1992 to 2004. Four haplotype-tagging polymorphisms (htSNPs) (rs3020450, rs1256031, rs1256049, rs4986938) captured the common genetic variation across the ESR2 locus from a set of markers culled from healthy controls from a public database and sequencing the coding regions of 95 breast cancer cases. Using the expectation-maximization algorithm, five common haplotypes were resolved (CCGC (43%), TCAT (287%), TCAC (11%), CCAC (9%) and CCAT (6%)). Multivariate logistic regression was used to estimate adjusted odds ratios (OR) and their 95% confidence intervals (95% CI) for individual htSNPs and haplotype scores. Neither the four individual htSNPs nor their resolved haplotypes were associated with lung cancer risk in the entire population, nor in strata defined by parity (yes versus no), age (< 50 years versus >= 50 years) or smoking history (current-, former-, never-smokers). Our findings indicate that ESR2 is not associated with risk of lung cancer in women. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Paulus, Jessica K.; Kraft, Peter; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Zhou, Wei] Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA.
[Kraft, Peter; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Paulus, JK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM jpaulus@hsph.harvard.edu
FU NIH [R01CA98924, R01CA74386, T32ES07069]; MGH; HSPH
FX This study was funded by NIH grants: R01CA98924, R01CA74386 and
T32ES07069. We are indebted to the Lung Cancer Susceptibility and
Survival Study participants and the assistance of the study support
teams at MGH and HSPH.
NR 52
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U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD MAR
PY 2011
VL 71
IS 3
BP 258
EP 263
DI 10.1016/j.lungcan.2010.06.011
PG 6
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 735LS
UT WOS:000288416700003
PM 20655613
ER
PT J
AU Lane, MA
McDonald, JR
Zeringue, AL
Caplan, L
Curtis, JR
Ranganathan, P
Eisen, SA
AF Lane, Michael A.
McDonald, Jay R.
Zeringue, Angelique L.
Caplan, Liron
Curtis, Jeffrey R.
Ranganathan, Prabha
Eisen, Seth A.
TI TNF-alpha Antagonist Use and Risk of Hospitalization for Infection in a
National Cohort of Veterans With Rheumatoid Arthritis
SO MEDICINE
LA English
DT Article
ID ANTITUMOR-NECROSIS-FACTOR; MODIFYING ANTIRHEUMATIC DRUGS; SERIOUS
BACTERIAL-INFECTIONS; BRITISH-SOCIETY; ELDERLY-PATIENTS; FACTOR THERAPY;
AFFAIRS; BIOLOGICS; PNEUMONIA; MORTALITY
AB Medications used to treat rheumatoid arthritis (RA) may confer an increased risk of infection. We conducted a retrospective cohort study of veterans with RA followed in the United States Department of Veterans Affairs health care system from October 1998 through September 2005. Risk of hospitalization for infection associated with tumor necrosis factor (TNF)-alpha antagonists therapy was measured using an extension of Cox proportional hazards regression, adjusting for demographic characteristics, comorbid illnesses, and other medications used to treat RA.
A total of 20,814 patients met inclusion criteria, including 3796 patients who received infliximab, etanercept, or adalimumab. Among the study cohort, 1465 patients (7.0%) were hospitalized at least once for infection. There were 1889 hospitalizations for infection. The most common hospitalized infections were pneumonia, bronchitis, and cellulitis. Age and several comorbid medical conditions were associated with hospitalization for infection. Prednisone (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.88Y2.43) and TNF-alpha antagonist use (HR, 1.24; 95% CI, 1.02-1.50) were associated with hospitalization for infection, while the use of disease-modifying antirheumatic drugs (DMARDs) other than TNF-alpha antagonists was not. Compared to etanercept, infliximab was associated with risk for hospitalization for infection (HR, 1.51; 95% CI, 1.14-2.00), while adalimumab use was not (HR, 0.95; 95% CI, 0.68-1.33). In all treatment groups, rate of hospitalization for infection was highest in the first 8 months of therapy.
We conclude that patients with RA who are treated with TNF-alpha antagonists are at higher risk for hospitalization for infection than those treated with other DMARDs. Prednisone use is also a risk factor for hospitalization for infection.
C1 [Lane, Michael A.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[McDonald, Jay R.; Zeringue, Angelique L.] St Louis Vet Affairs Med Ctr, St Louis, MO USA.
[Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Curtis, Jeffrey R.] Univ Alabama, Ctr Educ & Res Therapeut, Birmingham, AL USA.
[Eisen, Seth A.] Vet Affairs Hlth Serv Res & Dev, Washington, DC USA.
RP Lane, MA (reprint author), Washington Univ, Sch Med, 660 S Euclid Ave,Campus Box 8051, St Louis, MO 63110 USA.
EM mlane@dom.wustl.edu
RI Zeringue, Angelique/I-1755-2012;
OI Lane, Michael/0000-0003-2426-8186
FU Department of Veterans Affairs; Veterans Health Administration; Health
Services Research and Development [IAF 06-026]; Goldfarb Patient Safety
& Quality Fellowship; Barnes-Jewish Hospital Foundation; NIH
[K12RR023249, KL2RR024994]; VA [07-221]
FX The research reported here was supported by the Department of Veterans
Affairs, Veterans Health Administration, Health Services Research and
Development Service project number IAF 06-026 (PI: Dr. McDonald). Dr.
Lane has received career development support from the Goldfarb Patient
Safety & Quality Fellowship program and the Barnes-Jewish Hospital
Foundation. The career development of Dr. McDonald has been supported by
NIH K12RR023249 and KL2RR024994. Dr. Caplan is supported by VA HSR&D
Career Development Award 07-221.
NR 35
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U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7974
J9 MEDICINE
JI Medicine (Baltimore)
PD MAR
PY 2011
VL 90
IS 2
BP 139
EP 145
DI 10.1097/MD.0b013e318211106a
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 729BC
UT WOS:000287920600007
PM 21358439
ER
PT J
AU Ren, XF
Akiyoshi, K
Vandenbark, AA
Hurn, PD
Offner, H
AF Ren, Xuefang
Akiyoshi, Kozaburo
Vandenbark, Arthur A.
Hurn, Patricia D.
Offner, Halina
TI CD4(+)FoxP3(+) regulatory T-cells in cerebral ischemic stroke
SO METABOLIC BRAIN DISEASE
LA English
DT Article
DE Cerebral ischemia; T lymphocyte; T regulatory cells; Middle cerebral
artery occlusion; Stroke
AB Experimental cerebral ischemic stroke is exacerbated by inflammatory T-cells and is accompanied by systemic increases in CD4(+)CD25(+)Foxp3(+) regulatory T-cells (Treg). To determine their effect on ischemic brain injury, Treg were depleted in Foxp3(DTR) mice prior to stroke induction. In contrast to a recent Nature Medicine report, our results demonstrate unequivocally that Treg depletion did not affect stroke infarct volume, thus failing to implicate this regulatory pathway in limiting stroke damage.
C1 [Ren, Xuefang; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, R&D 31, Portland, OR 97239 USA.
[Ren, Xuefang; Akiyoshi, Kozaburo; Hurn, Patricia D.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA.
[Vandenbark, Arthur A.; Hurn, Patricia D.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM offnerva@ohsu.edu
RI wu, peihua/F-8818-2012
FU NIH [NR03521]; Biomedical Laboratory R&D Service, Department of Veterans
Affairs
FX The authors wish to thank Dr. Sushmita Sinha, Ms. Sandhya Subramanian
and Dr. Suzan Dziennis for helpful discussions and Ms. Eva Niehaus and
Heather Hoem for assistance in preparing the manuscript. This work was
supported by NIH grant NR03521 and the Biomedical Laboratory R&D
Service, Department of Veterans Affairs.
NR 7
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U1 2
U2 11
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7490
J9 METAB BRAIN DIS
JI Metab. Brain Dis.
PD MAR
PY 2011
VL 26
IS 1
BP 87
EP 90
DI 10.1007/s11011-010-9226-6
PG 4
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 745DR
UT WOS:000289146100010
PM 21082336
ER
PT J
AU Spires-Jones, TL
de Calignon, A
Meyer-Luehmann, M
Bacskai, BJ
Hyman, BT
AF Spires-Jones, Tara L.
de Calignon, Alix
Meyer-Luehmann, Melanie
Bacskai, Brian J.
Hyman, Bradley T.
TI Monitoring protein aggregation and toxicity in Alzheimer's disease mouse
models using in vivo imaging
SO METHODS
LA English
DT Article
DE Alzheimer; Tau; Plaque; Multiphoton; In vivo imaging
ID AMYLOID PRECURSOR PROTEIN; TANGLE-BEARING NEURONS; A-BETA-PLAQUES;
TRANSGENIC MICE; MULTIPHOTON MICROSCOPY; NEURITE TRAJECTORIES; CASPASE
ACTIVATION; SPINE LOSS; TAU; PATHOLOGY
AB Aggregation of amyloid beta peptide into senile plaques and hyperphosphorylated tau protein into neurofibrillary tangles in the brain are the pathological hallmarks of Alzheimer's disease. Despite over a century of research into these lesions, the exact relationship between pathology and neurotoxicity has yet to be fully elucidated. In order to study the formation of plaques and tangles and their effects on the brain, we have applied multiphoton in vivo imaging of transgenic mouse models of Alzheimer's disease. This technique allows longitudinal imaging of pathological aggregation of proteins and the subsequent changes in surrounding neuropil neurodegeneration and recovery after therapeutic interventions. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Spires-Jones, Tara L.; de Calignon, Alix; Meyer-Luehmann, Melanie; Bacskai, Brian J.; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
RP Spires-Jones, TL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA.
EM tspires@partners.org
OI Spires-Jones, Tara/0000-0003-2530-0598; Meyer-Luehmann,
Melanie/0000-0003-3661-2220
FU Alzheimer's Association; NIH [AG08487, K99AG33670, EB000768, AG026249]
FX We gratefully acknowledge funding from the Alzheimer's Association
Zenith Award, NIH Grants AG08487, K99AG33670, EB000768, and AG026249.
NR 45
TC 13
Z9 13
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
J9 METHODS
JI Methods
PD MAR
PY 2011
VL 53
IS 3
BP 201
EP 207
DI 10.1016/j.ymeth.2010.12.009
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736VN
UT WOS:000288523200004
PM 21163350
ER
PT J
AU Berra, L
Sampson, J
Fumagalli, J
Panigada, M
Kolobow, T
AF Berra, L.
Sampson, J.
Fumagalli, J.
Panigada, M.
Kolobow, T.
TI Alternative approaches to ventilator-associated pneumonia prevention
SO MINERVA ANESTESIOLOGICA
LA English
DT Review
DE Pneumonia, ventilator-associated; Respiration, artificial; Cross
infection
ID COATED ENDOTRACHEAL-TUBES; BACTERIAL-COLONIZATION; TRACHEAL TUBE;
MINERVA ANESTESIOLOGICA; MUCUS SHAVER; ASPIRATION; TRIAL; FEASIBILITY;
ORIENTATION; INTUBATION
AB Ventilator-associated pneumonia (VAP), which develops in patients receiving mechanical ventilation, is the most common nosocomial infection in patients with acute respiratory failure. The major mechanism of lower respiratory tract colonization is aspiration of bacteria-colonized secretions from the oropharynx into the lower airways. The hydrostatic pressure of the secretions that collect in the subglottic space, which is the area above the endotracheal tube (ETT) cuff, or aerosolization of bacteria from the secretions collected within the respiratory tubing may facilitate the leakage into the lower airways. Ideally, the elimination of the mechanisms responsible for aspiration would decrease the incidence of VAP. Several preventive measures have been tested in clinical trials with little success.Here we present the results of our efforts to develop novel approaches for the prevention of VAP Specifically, we found that keeping ventilated patients in a lateral position, which eliminates gravitational forces, is feasible and possibly advantageous. Additionally, several novel medical devices have been recently developed to prevent bacterial biofilm formation from the ETT and breathing tubing. These devices include coated ETTs, mucus shavers and mucus slurpers. Prevention of ETT bacterial colonization showed decreased bacterial colonization of the respiratory circuit and of the lower respiratory tract in laboratory studies and clinical trials. Future large studies should be designed to test the hypothesis that VAP can be prevented with these novel strategies. While there is a current focus on the use of respiratory devices to prevent biofilm formation and microaspiration, it is important to remember that lower respiratory tract colonization is multifactorial. Prevention of VAP cannot be achieved solely by eliminating bacterial biofilm on respiratory devices, and more comprehensive care of the intubated patient needs to be implemented. (Minerva Anestesiol 2011;77:323-33)
C1 [Berra, L.; Sampson, J.; Fumagalli, J.; Panigada, M.; Kolobow, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
RP Berra, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA.
EM lberra@partners.org
RI Lee, H/E-7918-2010; Panigada, Mauro/K-4650-2014
OI Panigada, Mauro/0000-0003-4841-9794
NR 30
TC 12
Z9 15
U1 0
U2 5
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0375-9393
EI 1827-1596
J9 MINERVA ANESTESIOL
JI Minerva Anestesiol.
PD MAR
PY 2011
VL 77
IS 3
BP 323
EP 333
PG 11
WC Anesthesiology; Critical Care Medicine
SC Anesthesiology; General & Internal Medicine
GA 751CA
UT WOS:000289593900012
PM 21150848
ER
PT J
AU Liu, W
Hasserjian, RP
Hu, Y
Zhang, LP
Miranda, RN
Medeiros, LJ
Wang, SA
AF Liu, Wei
Hasserjian, Robert P.
Hu, Ying
Zhang, Liping
Miranda, Roberto N.
Medeiros, L. Jeffrey
Wang, Sa A.
TI Pure erythroid leukemia: a reassessment of the entity using the 2008
World Health Organization classification
SO MODERN PATHOLOGY
LA English
DT Article
DE acute erythroleukemia; cytogenetics; erythroid predominance;
myelodysplastic syndromes; pure erythroid leukemia; survival
ID ACUTE ERYTHROLEUKEMIA; E-CADHERIN; AML; PROERYTHROBLASTS; CYTOGENETICS;
GLYCOPHORIN; EXPRESSION; CRITERIA; VARIANT; CELLS
AB Pure erythroid leukemia (PEL) is rare, characterized by a neoplastic proliferation of erythroblasts. Given recent incorporation of molecular genetic findings and clinical features in the revised 2008 World Health Organization classification scheme of acute myeloid leukemia, we questioned if PEL still remains as a distinct subtype of acute myeloid leukemia. In this retrospective study, we identified 18 cases of acute leukemia with morphologic and immunophenotypic features of PEL. Following the current World Health Organization classification algorithm, these cases were classified as: 13 acute myeloid leukemia with myelodysplasia-related changes, 3 therapy-related acute myeloid leukemia, and 1 chronic myelogenous leukemia blast crisis, and one unclassifiable due to insufficient clinical information. All 16 cases with cytogenetic data harbored an extremely complex karyotype and the median overall survival of the 18 patients was 3 months (range, 1-7 months). This survival was significantly shorter than that of patients with acute erythroid leukemia, erythroid/myeloid subtype, or acute myeloid leukemia with myelodysplasia-related changes with erythroid predominance (P < 0.001). PEL is characterized as a neoplastic erythroid hyperproliferation with maturation arrest. E-cadherin emerged as the most sensitive and specific marker for immature erythroblasts, and was helpful in distinguishing PEL from other erythroid proliferations. Our study showed that the criteria for acute myeloid leukemia in the 2008 World Health Organization system facilitate reclassification of PEL cases into other acute myeloid leukemia categories, mainly of acute myeloid leukemia with myelodysplasia-related changes. These new assigned categories fail to capture the distinct features of PEL, where the phenotype of PEL correlates with a very complex karyotype and an extremely aggressive clinical course. Modern Pathology (2011) 24, 375-383; doi:10.1038/modpathol.2010.194; published online 19 November 2010
C1 [Liu, Wei; Hu, Ying; Miranda, Roberto N.; Medeiros, L. Jeffrey; Wang, Sa A.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA.
[Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Zhang, Liping] Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA USA.
RP Liu, W (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM swang5@mdanderson.org
OI Miranda, Roberto/0000-0002-8467-5464
FU NCI NIH HHS [P30 CA016672]
NR 27
TC 19
Z9 20
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD MAR
PY 2011
VL 24
IS 3
BP 375
EP 383
DI 10.1038/modpathol.2010.194
PG 9
WC Pathology
SC Pathology
GA 729XC
UT WOS:000287986600005
PM 21102413
ER
PT J
AU Seward, RJ
Drouin, EE
Steere, AC
Costello, CE
AF Seward, Robert J.
Drouin, Elise E.
Steere, Allen C.
Costello, Catherine E.
TI Peptides Presented by HLA-DR Molecules in Synovia of Patients with
Rheumatoid Arthritis or Antibiotic-Refractory Lyme Arthritis
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID CYCLIC CITRULLINATED PEPTIDE; T-CELL RECOGNITION; MASS-SPECTROMETRY;
BOUND PEPTIDES; CLASS-I; ANTIGENIC DETERMINANTS; HLA-DRB1 ALLELES;
ASSOCIATION; CYSTEINE; DISEASE
AB Disease-associated HLA-DR molecules, which may present autoantigens, constitute the greatest genetic risk factor for rheumatoid arthritis (RA) and antibiotic-refractory Lyme arthritis (LA). The peptides presented by HLA-DR molecules in synovia have not previously been defined. Using tandem mass spectrometry, rigorous database searches, and manual spectral interpretation, we identified 1,427 HLA-DR-presented peptides (220-464 per patient) from the synovia of four patients, two diagnosed with RA and two diagnosed with LA. The peptides were derived from 166 source proteins, including a wide range of intracellular and plasma proteins. A few epitopes were found only in RA or LA patients. However, two patients with different diseases who had the same HLA allele had the largest number of epitopes in common. In one RA patient, peptides were identified as originating from source proteins that have been reported to undergo citrullination under other circumstances, yet neither this post-translational modification nor anti-cyclic citrullinated peptide antibodies were detected. Instead, peptides with the post-translational modification of S-cysteinylation were identified. We conclude that a wide range of proteins enter the HLA-DR pathway of antigen-presenting cells in the patients' synovial tissue, and their HLA-DR genotype, not the disease type, appears to be the primary determinant of their HLA-DR-peptide repertoire. New in-sights into the naturally presented HLA-DR epitope repertoire in target tissues may allow the identification of pathogenic T cell epitopes, and this could lead to innovative therapeutic interventions. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.002477, 1-14, 2011.
C1 [Seward, Robert J.; Costello, Catherine E.] Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Dept Biochem, Boston, MA 02118 USA.
[Seward, Robert J.; Drouin, Elise E.; Steere, Allen C.] Harvard Univ, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Med Sch, Boston, MA 02114 USA.
RP Costello, CE (reprint author), Boston Univ, Sch Med, Ctr Biomed Mass Spectrometry, Dept Biochem, 670 Albany St,Rm 511, Boston, MA 02118 USA.
EM cecmsms@bu.edu
OI Costello, Catherine/0000-0003-1594-5122
FU National Institutes of Health [P41 RR010888, S10 RR015942, S10 RR020946,
N01 HV028178, R01 AR020358]; Dana Foundation; Mathers Foundation;
English, Bonter, Mitchell Foundation; Eshe Fund; Massachusetts General
Hospital
FX This work was supported, in whole or in part, by National Institutes of
Health Grants P41 RR010888, S10 RR015942, and S10 RR020946 and Contract
N01 HV028178 (to C. E. C.) and by Grant R01 AR020358 (to A. C. S.). This
work was also supported by a grant from the Dana Foundation (to A. C. S.
and C. E. C.) and grants from the Mathers Foundation; the English,
Bonter, Mitchell Foundation; the Eshe Fund; and the Lyme/Arthritis
Research Fund at Massachusetts General Hospital (to A. C. S.).
NR 56
TC 9
Z9 9
U1 1
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
EI 1535-9484
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD MAR
PY 2011
VL 10
IS 3
AR M110.002477
DI 10.1074/mcp.M110.002477
PG 14
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 728AY
UT WOS:000287847200010
PM 21081667
ER
PT J
AU Whiteman, NK
Groen, SC
Chevasco, D
Bear, A
Beckwith, N
Gregory, TR
Denoux, C
Mammarella, N
Ausubel, FM
Pierce, NE
AF Whiteman, Noah K.
Groen, Simon C.
Chevasco, Daniela
Bear, Ashley
Beckwith, Noor
Gregory, T. Ryan
Denoux, Carine
Mammarella, Nicole
Ausubel, Frederick M.
Pierce, Naomi E.
TI Mining the plant-herbivore interface with a leafmining Drosophila of
Arabidopsis
SO MOLECULAR ECOLOGY
LA English
DT Review
DE Arabidopsis; Drosophila; gene expression; herbivory; jasmonate; model
system
ID CARDAMINE-CORDIFOLIA GRAY,A.; HOST PLANTS; INSECT INTERACTIONS;
MOLECULAR-PATTERNS; DEFENSE RESPONSES; HAWAIIAN DROSOPHILIDAE;
PSEUDOMONAS-SYRINGAE; LARVAL PERFORMANCE; PARKINSONS-DISEASE; NATIVE
CRUCIFER
AB Experimental infections of Arabidopsis thaliana (Arabidopsis) with genomically characterized plant pathogens such as Pseudomonas syringae have facilitated the dissection of canonical eukaryotic defence pathways and parasite virulence factors. Plants are also attacked by herbivorous insects, and the development of an ecologically relevant genetic model herbivore that feeds on Arabidopsis will enable the parallel dissection of host defence and reciprocal resistance pathways such as those involved in xenobiotic metabolism. An ideal candidate is Scaptomyza flava, a drosophilid fly whose leafmining larvae are true herbivores that can be found in nature feeding on Arabidopsis and other crucifers. Here, we describe the life cycle of S. flava on Arabidopsis and use multiple approaches to characterize the response of Arabidopsis to S. flava attack. Oviposition choice tests and growth performance assays on different Arabidopsis ecotypes, defence-related mutants, and hormone and chitin-treated plants revealed significant differences in host preference and variation in larval performance across Arabidopsis accessions. The jasmonate and glucosinolate pathways in Arabidopsis are important in mediating quantitative resistance against S. flava, and priming with jasmonate or chitin resulted in increased resistance. Expression of xenobiotic detoxification genes was reduced in S. flava larvae reared on Arabidopsis jasmonate signalling mutants and increased in plants pretreated with chitin. These results and future research directions are discussed in the context of developing a genetic model system to analyse insect-plant interactions.
C1 [Whiteman, Noah K.; Groen, Simon C.; Chevasco, Daniela; Bear, Ashley; Beckwith, Noor; Pierce, Naomi E.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02478 USA.
[Whiteman, Noah K.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
[Gregory, T. Ryan] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
[Denoux, Carine; Mammarella, Nicole; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Denoux, Carine; Mammarella, Nicole; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
RP Whiteman, NK (reprint author), Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02478 USA.
EM whiteman@email.arizona.edu
RI Groen, Simon/G-2443-2012;
OI Beckwith, Noor/0000-0001-6025-8642
FU National Institutes of Health [F32AI069732, GM48707]; National Science
Foundation [MCB-0519898, SES-0750480]; Harvard University; Harvard
University Science and Engineering Committee
FX NKW was supported by a Kirschstein National Research Service Award
(NRSA) from the National Institutes of Health (F32AI069732 to NKW), FMA
was supported by a grant from the National Science Foundation (grant
MCB-0519898 to FMA) and a grant from the National Institutes of Health
(grant GM48707 to FMA), and NEP was supported by a grant from the
National Science Foundation (grant SES-0750480 to NEP). NKW, SCG, FMA
and NEP were supported by a grant from the Harvard University's Provost
Fund for Interfaculty Collaboration and a grant from the Harvard
University Science and Engineering Committee Seed Fund for
Interdisciplinary Science. We thank Jen Bush for advice on culturing of
Arabidopsis, Andrew Brownjohn, Benjamin Goldman-Huertas, Sondra Lavigne,
Christopher Meehan and Matan Shelomi for assistance with laboratory work
and culturing of Scaptomyza flava. We thank Mark Beilstein for advice on
the phylogenetic analyses and William Gelbart, Patrick O'Grady and
Therese Markow for useful discussions of Drosophila biology. We thank
Gabe Miller for photographs of Arabidopsis. We thank Paul H. Williams
for telling NEP about leafmining flies of Arabidopsis in a meeting
hosted by Ed and Kyoko Jones as part of the Japan Fulbright Masters
Teacher Program in 2004.
NR 132
TC 30
Z9 30
U1 3
U2 39
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0962-1083
EI 1365-294X
J9 MOL ECOL
JI Mol. Ecol.
PD MAR
PY 2011
VL 20
IS 5
BP 995
EP 1014
DI 10.1111/j.1365-294X.2010.04901.x
PG 20
WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology
SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology;
Evolutionary Biology
GA 721ZN
UT WOS:000287397600013
PM 21073583
ER
PT J
AU Ko, S
Ahn, J
Song, CS
Kim, S
Knapczyk-Stwora, K
Chatterjee, B
AF Ko, Soyoung
Ahn, Jungmi
Song, Chung S.
Kim, Soyoung
Knapczyk-Stwora, Katarzyna
Chatterjee, Bandana
TI Lysine Methylation and Functional Modulation of Androgen Receptor by
Set9 Methyltransferase
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID PROSTATE-CANCER; COACTIVATOR COMPLEX; HISTONE H3; ACETYLATION;
EXPRESSION; BINDING; ALPHA; AKT; P53; MYB
AB Lysine methyltransferases modulate activities of transcription factors and transcription coregulators by methylating specific lysine residue(s). We report that the androgen receptor (AR) is methylated at lysine-630 by Set9, which was originally identified as a histone H3K4 monomethyltransferase. Alanine substitution of lysine-630 prevented AR methylation in vitro and in vivo. Set9 methylated the nuclear and cytoplasmic AR utilizing the cofactor S-adenosyl-methionine. A panmethyllysine antibody recognized endogenous AR, and Set9 coimmunoprecipitated with nuclear and cytoplasmic AR. Set9 overexpression potentiated AR-mediated transactivation of the probasin promoter, whereas Set9 depletion inhibited AR activity and target gene expression. Similar to AR, chromatin occupancy of Set9 at androgen response elements (AREs) was androgen dependent, and associated with methylated histone H3K4 chromatin activation marks and p300/CBP associated factor acetyltransferase recruitment. Set9 depletion increased the histone H3K9-dimethyl repressive mark at AREs and reduced histone activation marks and occupancy of p300/CBP associated factor. K630A mutation reduced amino-and carboxy-terminal (N-C) interaction in Set9-intact cells, whereas N-C interaction for wild-type AR was reduced upon Set9 depletion. The K630A mutant was resistant to loss of activity from Set9 silencing and to increase of activity from Set9 overexpression. The K630 dependence of Set9-regulated N-C interaction and AR activity suggests that Set9 directly acts on AR at the amino acid level. Chromatin recruitment of Set9 to AREs is suggestive of its additional role as a transcriptional coactivator. Because the cellular metabolic state determines the level of S-adenosylmethionine and consequently the activity of Set9, the enhanced activity of methylated AR may have special significance in certain metabolic contexts. (Molecular Endocrinology 25: 433-444, 2011)
C1 [Ko, Soyoung; Ahn, Jungmi; Song, Chung S.; Kim, Soyoung; Knapczyk-Stwora, Katarzyna; Chatterjee, Bandana] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78245 USA.
[Chatterjee, Bandana] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Chatterjee, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, Inst Biotechnol, 15355 Lambda Dr, San Antonio, TX 78245 USA.
EM chatterjee@uthscsa.edu
FU National Institutes of Health [R01-AG10486, R01-AG19660]; Veterans
Affairs; Department of Defense [XWH-08-1-0067]; Clinical and
Translational Science Award-Translational Science Training predoctoral
fellowship
FX The study was supported by National Institutes of Health Grants
R01-AG10486 and R01-AG19660; a Veterans Affairs Merit-Review grant, a
Department of Defense predoctoral fellowship, XWH-08-1-0067 (to S. Ko.);
and a Clinical and Translational Science Award-Translational Science
Training predoctoral fellowship (to J.A.).
NR 26
TC 34
Z9 35
U1 1
U2 8
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD MAR
PY 2011
VL 25
IS 3
BP 433
EP 444
DI 10.1210/me.2010-0482
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 726CX
UT WOS:000287697500006
PM 21273441
ER
PT J
AU Rosenquist, JN
Fowler, JH
Christakis, NA
AF Rosenquist, J. N.
Fowler, J. H.
Christakis, N. A.
TI Social network determinants of depression
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE depression; social networks; sociology; social norms; mood
ID HEALTH; SYMPTOMS; SPREAD
AB The etiology of depression has long been thought to include social environmental factors. To quantitatively explore the novel possibility of person-to-person spread and network-level determination of depressive symptoms, analyses were performed on a densely interconnected social network of 12 067 people assessed repeatedly over 32 years as part of the Framingham Heart Study. Longitudinal statistical models were used to examine whether depressive symptoms in one person were associated with similar scores in friends, co-workers, siblings, spouses and neighbors. Depressive symptoms were assessed using CES-D scores that were available for subjects in three waves measured between 1983 and 2001. Results showed both low and high CES-D scores (and classification as being depressed) in a given period were strongly correlated with such scores in one's friends and neighbors. This association extended up to three degrees of separation (to one's friends' friends' friends). Female friends appear to be especially influential in the spread of depression from one person to another. The results are robust to multiple network simulation and estimation methods, suggesting that network phenomena appear relevant to the epidemiology of depression and would benefit from further study. Molecular Psychiatry (2011) 16, 273-281; doi:10.1038/mp.2010.13; published online 16 March 2010
C1 [Rosenquist, J. N.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Rosenquist, J. N.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Fowler, J. H.] Univ Calif San Diego, Dept Polit Sci, San Diego, CA 92103 USA.
[Christakis, N. A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA.
[Christakis, N. A.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA.
RP Rosenquist, JN (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM jrosenqu@gmail.com
RI Fowler, James/C-2750-2008
OI Fowler, James/0000-0001-7795-1638
FU NIA NIH HHS [P01 AG031093, P01 AG031093-01]; NIGMS NIH HHS [P41
GM103504]
NR 44
TC 86
Z9 88
U1 3
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD MAR
PY 2011
VL 16
IS 3
BP 273
EP 281
DI 10.1038/mp.2010.13
PG 9
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 723AT
UT WOS:000287479100008
PM 20231839
ER
PT J
AU Osborn, MJ
McElmurry, RT
Lees, CJ
DeFeo, AP
Chen, ZY
Kay, MA
Naldini, L
Freeman, G
Tolar, J
Blazar, BR
AF Osborn, Mark J.
McElmurry, Ron T.
Lees, Christopher J.
DeFeo, Anthony P.
Chen, Zhi-Ying
Kay, Mark A.
Naldini, Luigi
Freeman, Gordon
Tolar, Jakub
Blazar, Bruce R.
TI Minicircle DNA-based Gene Therapy Coupled With Immune Modulation Permits
Long-term Expression of alpha-L-Iduronidase in Mice With
Mucopolysaccharidosis Type I
SO MOLECULAR THERAPY
LA English
DT Article
ID EPISOMAL TRANSGENE EXPRESSION; NAKED PLASMID DNA; ENDOGENOUS MICRORNA;
HUMAN GENOME; FACTOR-VIII; VECTOR; VIVO; LIVER; TOLERANCE; ELEMENTS
AB Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease characterized by mutations to the alpha-L-iduronidase (IDUA) gene resulting in inactivation of the IDUA enzyme. The loss of IDUA protein results in the progressive accumulation of glycosaminoglycans within the lysosomes resulting in severe, multi-organ system pathology. Gene replacement strategies have relied on the use of viral or nonviral gene delivery systems. Drawbacks to these include laborious production procedures, poor efficacy due to plasmid-borne gene silencing, and the risk of insertional mutagenesis. This report demonstrates the efficacy of a nonintegrating, minicircle (MC) DNA vector that is resistant to epigenetic gene silencing in vivo. To achieve sustained expression of the immunogenic IDUA protein we investigated the use of a tissue-specific promoter in conjunction with microRNA target sequences. The inclusion of microRNA target sequences resulted in a slight improvement in long-term expression compared to their absence. However, immune modulation by costimulatory blockade was required and permitted for IDUA expression in MPS I mice that resulted in the biochemical correction of pathology in all of the organs analyzed. MC gene delivery combined with costimulatory pathway blockade maximizes safety, efficacy, and sustained gene expression and is a new approach in the treatment of lysosomal storage disease.
C1 [Osborn, Mark J.; McElmurry, Ron T.; Lees, Christopher J.; DeFeo, Anthony P.; Tolar, Jakub; Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Bone Marrow Transplant, Minneapolis, MN 55455 USA.
[Osborn, Mark J.; McElmurry, Ron T.; Lees, Christopher J.; DeFeo, Anthony P.; Tolar, Jakub; Blazar, Bruce R.] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA.
[Chen, Zhi-Ying; Kay, Mark A.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
[Chen, Zhi-Ying; Kay, Mark A.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Naldini, Luigi] San Raffaele Telethon Inst Gene Therapy, Milan, Italy.
[Naldini, Luigi] Univ Vita Salute San Raffaele, Milan, Italy.
[Freeman, Gordon] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA.
RP Osborn, MJ (reprint author), Univ Minnesota, Dept Pediat, Div Bone Marrow Transplant, 420 Delaware St SE,MMC 366, Minneapolis, MN 55455 USA.
EM osbor026@umn.edu
RI Naldini, Luigi/E-9083-2012;
OI Tolar, Jakub/0000-0002-0957-4380
FU National MPS Society; Minnesota Medical Foundation; Children's Cancer
Research Fund; Fondazione Telethon
FX We are grateful to Katherine P. Ponder (Washington University) for
helpful discussions in developing the IDUA enzymatic assay. We thank
Andrew P. Price and John Oleksowicz (University of Minnesota) for
excellent technical assistance. M.J.O. is supported by a grant from the
National MPS Society. M.J.O., J.T., & B.R.B. are also supported by the
Minnesota Medical Foundation and the Children's Cancer Research Fund.
NR 47
TC 49
Z9 50
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAR
PY 2011
VL 19
IS 3
BP 450
EP 460
DI 10.1038/mt.2010.249
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 728YY
UT WOS:000287911600004
PM 21081900
ER
PT J
AU Boulting, GL
Kiskinis, E
Croft, GF
Amoroso, MW
Oakley, DH
Wainger, BJ
Williams, DJ
Kahler, DJ
Yamaki, M
Davidow, L
Rodolfa, CT
Dimos, JT
Mikkilineni, S
MacDermott, AB
Woolf, CJ
Henderson, CE
Wichterle, H
Eggan, K
AF Boulting, Gabriella L.
Kiskinis, Evangelos
Croft, Gist F.
Amoroso, Mackenzie W.
Oakley, Derek H.
Wainger, Brian J.
Williams, Damian J.
Kahler, David J.
Yamaki, Mariko
Davidow, Lance
Rodolfa, Christopher T.
Dimos, John T.
Mikkilineni, Shravani
MacDermott, Amy B.
Woolf, Clifford J.
Henderson, Christopher E.
Wichterle, Hynek
Eggan, Kevin
TI A functionally characterized test set of human induced pluripotent stem
cells
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID MOTOR-NEURONS; DIRECTED DIFFERENTIATION; NEURAL CONVERSION; IPS CELLS;
HUMAN ES; DISEASE; BLASTOCYSTS; TISSUE; LINES; ALS
AB Human induced pluripotent stem cells (iPSCs) present exciting opportunities for studying development and for in vitro disease modeling. However, reported variability in the behavior of iPSCs has called their utility into question. We established a test set of 16 iPSC lines from seven individuals of varying age, sex and health status, and extensively characterized the lines with respect to pluripotency and the ability to terminally differentiate. Under standardized procedures in two independent laboratories, 13 of the iPSC lines gave rise to functional motor neurons with a range of efficiencies similar to that of human embryonic stem cells (ESCs). Although three iPSC lines were resistant to neural differentiation, early neuralization rescued their performance. Therefore, all 16 iPSC lines passed a stringent test of differentiation capacity despite variations in karyotype and in the expression of early pluripotency markers and transgenes. This iPSC and ESC test set is a robust resource for those interested in the basic biology of stem cells and their applications.
C1 [Boulting, Gabriella L.; Kiskinis, Evangelos; Yamaki, Mariko; Eggan, Kevin] Howard Hughes Med Inst, Cambridge, MA USA.
[Boulting, Gabriella L.; Kiskinis, Evangelos; Yamaki, Mariko; Davidow, Lance; Mikkilineni, Shravani; Eggan, Kevin] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Boulting, Gabriella L.; Rodolfa, Christopher T.; Dimos, John T.; Mikkilineni, Shravani; Eggan, Kevin] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Croft, Gist F.; Amoroso, Mackenzie W.; Oakley, Derek H.; Henderson, Christopher E.; Wichterle, Hynek] Columbia Univ, Jenifer Estess Lab Stem Cell Res, Project ALS, New York, NY USA.
[Croft, Gist F.; Amoroso, Mackenzie W.; Oakley, Derek H.; Henderson, Christopher E.; Wichterle, Hynek] Columbia Univ, Ctr Motor Neuron Biol & Dis MNC, Dept Pathol, New York, NY USA.
[Croft, Gist F.; Amoroso, Mackenzie W.; Oakley, Derek H.; Henderson, Christopher E.; Wichterle, Hynek] Columbia Univ, Ctr Motor Neuron Biol & Dis MNC, Dept Neurol & Neurosci, New York, NY USA.
[Croft, Gist F.; Amoroso, Mackenzie W.; Oakley, Derek H.; Henderson, Christopher E.; Wichterle, Hynek] Columbia Stem Cell Initiat CSCI, New York, NY USA.
[Wainger, Brian J.; Woolf, Clifford J.] Childrens Hosp, Program Neurobiol, Boston, MA 02115 USA.
[Wainger, Brian J.; Woolf, Clifford J.] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
[Wainger, Brian J.; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Wainger, Brian J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Williams, Damian J.; MacDermott, Amy B.] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY USA.
[Williams, Damian J.; MacDermott, Amy B.] Columbia Univ, Dept Neurosci, New York, NY USA.
[Kahler, David J.] New York Stem Cell Fdn Inc, New York, NY USA.
RP Eggan, K (reprint author), Howard Hughes Med Inst, Cambridge, MA USA.
EM hw350@columbia.edu; keggan@scrb.harvard.edu
RI Williams, Damian/K-4023-2014;
OI Weygandt Amoroso, Mackenzie/0000-0001-7368-4456; Henderson,
Christopher/0000-0002-9936-3279
FU A.L.S.; P2ALS; NYSTEM; National Institutes of Health (NIH) [1RC2
NS069395-01, 5T32GM007592]; National Institute of Neurological Disorders
and Stroke; National Institute of Child Health and Development
FX We thank H. Mitsumoto, J. Montes, P. Kaufmann and J. Andrews for
collecting skin biopsies; K. Koszka, A. Sproul, A. Hon and A.
Garcia-Diaz for technical assistance; M. Park, A. Meissner and C. Bock
for manuscript assistance, as well as S. Brenner-Morton and T. Jessell
for providing Islet antibodies. This work was funded by Project A.L.S.,
P2ALS, NYSTEM and the National Institutes of Health (NIH) GO
grant 1RC2 NS069395-01. G. L. B. is a Harvard Stem Cell Institute/NIH
Trainee. E. K. is an EMBO Postdoctoral Fellow. B.J.W. is supported by
NIH Training Grant 5T32GM007592. C.J.W. is supported by grants from the
National Institute of Neurological Disorders and Stroke and the National
Institute of Child Health and Development. K. E. is a Howard Hughes
Medical Institute early career scientist.
NR 24
TC 238
Z9 248
U1 4
U2 47
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD MAR
PY 2011
VL 29
IS 3
BP 279
EP U147
DI 10.1038/nbt.1783
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 732RL
UT WOS:000288206700024
PM 21293464
ER
PT J
AU Anderson, CA
Boucher, G
Lees, CW
Franke, A
D'Amato, M
Taylor, KD
Lee, JC
Goyette, P
Imielinski, M
Latiano, A
Lagace, C
Scott, R
Amininejad, L
Bumpstead, S
Baidoo, L
Baldassano, RN
Barclay, M
Bayless, TM
Brand, S
Buning, C
Colombel, JF
Denson, LA
De Vos, M
Dubinsky, M
Edwards, C
Ellinghaus, D
Fehrmann, RSN
Floyd, JAB
Florin, T
Franchimont, D
Franke, L
Georges, M
Glas, J
Glazer, NL
Guthery, SL
Haritunians, T
Hayward, NK
Hugot, JP
Jobin, G
Laukens, D
Lawrance, I
Lemann, M
Levine, A
Libioulle, C
Louis, E
McGovern, DP
Milla, M
Montgomery, GW
Morley, KI
Mowat, C
Ng, A
Newman, W
Ophoff, RA
Papi, L
Palmieri, O
Peyrin-Biroulet, L
Panes, J
Phillips, A
Prescott, NJ
Proctor, DD
Roberts, R
Russell, R
Rutgeerts, P
Sanderson, J
Sans, M
Schumm, P
Seibold, F
Sharma, Y
Simms, LA
Seielstad, M
Steinhart, AH
Targan, SR
van den Berg, LH
Vatn, M
Verspaget, H
Walters, T
Wijmenga, C
Wilson, DC
Westra, HJ
Xavier, RJ
Zhao, ZZ
Ponsioen, CY
Andersen, V
Torkvist, L
Gazouli, M
Anagnou, NP
Karlsen, TH
Kupcinskas, L
Sventoraityte, J
Mansfield, JC
Kugathasan, S
Silverberg, MS
Halfvarson, J
Rotter, JI
Mathew, CG
Griffiths, AM
Gearry, R
Ahmad, T
Brant, SR
Chamaillard, M
Satsangi, J
Cho, JH
Schreiber, S
Daly, MJ
Barrett, JC
Parkes, M
Annese, V
Hakonarson, H
Radford-Smith, G
Duerr, RH
Vermeire, S
Weersma, RK
Rioux, JD
AF Anderson, Carl A.
Boucher, Gabrielle
Lees, Charlie W.
Franke, Andre
D'Amato, Mauro
Taylor, Kent D.
Lee, James C.
Goyette, Philippe
Imielinski, Marcin
Latiano, Anna
Lagace, Caroline
Scott, Regan
Amininejad, Leila
Bumpstead, Suzannah
Baidoo, Leonard
Baldassano, Robert N.
Barclay, Murray
Bayless, Theodore M.
Brand, Stephan
Buening, Carsten
Colombel, Jean-Frederic
Denson, Lee A.
De Vos, Martine
Dubinsky, Marla
Edwards, Cathryn
Ellinghaus, David
Fehrmann, Rudolf S. N.
Floyd, James A. B.
Florin, Timothy
Franchimont, Denis
Franke, Lude
Georges, Michel
Glas, Juergen
Glazer, Nicole L.
Guthery, Stephen L.
Haritunians, Talin
Hayward, Nicholas K.
Hugot, Jean-Pierre
Jobin, Gilles
Laukens, Debby
Lawrance, Ian
Lemann, Marc
Levine, Arie
Libioulle, Cecile
Louis, Edouard
McGovern, Dermot P.
Milla, Monica
Montgomery, Grant W.
Morley, Katherine I.
Mowat, Craig
Ng, Aylwin
Newman, William
Ophoff, Roel A.
Papi, Laura
Palmieri, Orazio
Peyrin-Biroulet, Laurent
Panes, Julian
Phillips, Anne
Prescott, Natalie J.
Proctor, Deborah D.
Roberts, Rebecca
Russell, Richard
Rutgeerts, Paul
Sanderson, Jeremy
Sans, Miquel
Schumm, Philip
Seibold, Frank
Sharma, Yashoda
Simms, Lisa A.
Seielstad, Mark
Steinhart, A. Hillary
Targan, Stephan R.
van den Berg, Leonard H.
Vatn, Morten
Verspaget, Hein
Walters, Thomas
Wijmenga, Cisca
Wilson, David C.
Westra, Harm-Jan
Xavier, Ramnik J.
Zhao, Zhen Z.
Ponsioen, Cyriel Y.
Andersen, Vibeke
Torkvist, Leif
Gazouli, Maria
Anagnou, Nicholas P.
Karlsen, Tom H.
Kupcinskas, Limas
Sventoraityte, Jurgita
Mansfield, John C.
Kugathasan, Subra
Silverberg, Mark S.
Halfvarson, Jonas
Rotter, Jerome I.
Mathew, Christopher G.
Griffiths, Anne M.
Gearry, Richard
Ahmad, Tariq
Brant, Steven R.
Chamaillard, Mathias
Satsangi, Jack
Cho, Judy H.
Schreiber, Stefan
Daly, Mark J.
Barrett, Jeffrey C.
Parkes, Miles
Annese, Vito
Hakonarson, Hakon
Radford-Smith, Graham
Duerr, Richard H.
Vermeire, Severine
Weersma, Rinse K.
Rioux, John D.
TI Meta-analysis identifies 29 additional ulcerative colitis risk loci,
increasing the number of confirmed associations to 47
SO NATURE GENETICS
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY
LOCI; CROHNS-DISEASE; COMMON VARIANTS; GENE-EXPRESSION; CELLS; MULTIPLE;
PROTEIN; ENRICHMENT
AB Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 x 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.
C1 [Anderson, Carl A.; Bumpstead, Suzannah; Floyd, James A. B.; Morley, Katherine I.; Barrett, Jeffrey C.] Wellcome Trust Sanger Inst, Cambridge, England.
[Boucher, Gabrielle; Goyette, Philippe; Lagace, Caroline; Jobin, Gilles; Rioux, John D.] Univ Montreal, Montreal, PQ, Canada.
[Boucher, Gabrielle; Goyette, Philippe; Lagace, Caroline; Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada.
[Lees, Charlie W.; Satsangi, Jack] Univ Edinburgh, Western Gen Hosp, Gastrointestinal Unit, Mol Med Ctr, Edinburgh, Midlothian, Scotland.
[Franke, Andre; Ellinghaus, David; Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
[D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
[Taylor, Kent D.; McGovern, Dermot P.; Targan, Stephan R.] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA.
[Lee, James C.; Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Gastroenterol Res Unit, Cambridge CB2 2QQ, England.
[Imielinski, Marcin; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Latiano, Anna; Palmieri, Orazio; Annese, Vito] IRCCS CSS Hosp, Gastroenterol Unit, San Giovanni Rotondo, Italy.
[Scott, Regan; Baidoo, Leonard; Duerr, Richard H.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Amininejad, Leila; Franchimont, Denis] Free Univ Brussels, Erasmus Hosp, Dept Gastroenterol, Brussels, Belgium.
[Baldassano, Robert N.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Dept Pediat, Ctr Pediat Inflammatory Bowel Dis, Philadelphia, PA 19104 USA.
[Barclay, Murray; Roberts, Rebecca; Gearry, Richard] Univ Otago, Dept Med, Christchurch, New Zealand.
[Bayless, Theodore M.; Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Meyerhoff Inflammatory Bowel Dis Ctr, Baltimore, MD 21205 USA.
[Brand, Stephan; Glas, Juergen] Univ Hosp Munich, Dept Med 2, Munich, Germany.
[Buening, Carsten] Univ Med Berlin, Dept Gastroenterol, Charite, Berlin, Germany.
[Colombel, Jean-Frederic] Univ Lille, Dept Hepatogastroenterol, Lille, France.
[Denson, Lee A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[De Vos, Martine; Laukens, Debby] Ghent Univ Hosp, Dept Gastroenterol & Hepatol, B-9000 Ghent, Belgium.
[Dubinsky, Marla] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA.
[Edwards, Cathryn] Torbay Hosp, Dept Gastroenterol, Torquay, Devon, England.
[Fehrmann, Rudolf S. N.; Franke, Lude; Wijmenga, Cisca; Westra, Harm-Jan] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands.
[Florin, Timothy] Dept Gastroenterol, Mater Hlth Serv, Brisbane, Qld, Australia.
[Georges, Michel] Univ Liege, Dept Genet, Fac Vet Med, Liege, Belgium.
[Glazer, Nicole L.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Internal Med, Seattle, WA 98195 USA.
[Guthery, Stephen L.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Haritunians, Talin; McGovern, Dermot P.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Hayward, Nicholas K.] Queensland Inst Med Res, Oncogenom Lab, Brisbane, Qld 4006, Australia.
[Lemann, Marc] Univ Paris Diderot, GETAID Grp, Paris, France.
[Jobin, Gilles] Hop Maison Neuve Rosemont, Dept Gastroenterol, Montreal, PQ H1T 2M4, Canada.
[Lawrance, Ian] Univ Western Australia, Sch Med & Pharmacol, Fremantle, WA, Australia.
[Levine, Arie] Tel Aviv Univ, Pediat Gastroenterol Unit, Wolfson Med Ctr, IL-69978 Tel Aviv, Israel.
[Levine, Arie] Sackler Sch Med, Tel Aviv, Israel.
[Libioulle, Cecile; Louis, Edouard] Ctr Hosp Univ Univ Liege, Div Gastroenterol, Liege, Belgium.
[Milla, Monica; Annese, Vito] Azienda Ospeda Univ AOU Careggi, Unit Gastroenterol SOD2, Florence, Italy.
[Montgomery, Grant W.; Zhao, Zhen Z.] Queensland Inst Med Res, Mol Epidemiol, Brisbane, Qld 4006, Australia.
[Mowat, Craig; Phillips, Anne] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med, Dundee DD1 9SY, Scotland.
[Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA.
[Ng, Aylwin; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Newman, William] Univ Manchester, Dept Med Genet, Manchester, Lancs, England.
[Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Papi, Laura] Univ Florence, Inst Human Genet, Florence, Italy.
[Peyrin-Biroulet, Laurent] Univ Hosp Nancy, Dept Hepatogastroenterol, Vandoeuvre Les Nancy, France.
[Panes, Julian; Sans, Miquel] Hosp Clin Barcelona, Dept Gastroenterol, IDIBAPS, CIBERehd, Barcelona, Spain.
[Prescott, Natalie J.; Mathew, Christopher G.] Kings Coll London, Sch Med, Dept Med & Mol Genet, Guys Hosp, London WC2R 2LS, England.
[Proctor, Deborah D.; Sharma, Yashoda; Cho, Judy H.] Yale Univ, Dept Med, Sect Digest Dis, New Haven, CT 06520 USA.
[Russell, Richard; Wilson, David C.] Royal Hosp Sick Children, Glasgow G3 8SJ, Lanark, Scotland.
[Rutgeerts, Paul; Vermeire, Severine] Univ Hosp Gasthuisberg, Div Gastroenterol, B-3000 Louvain, Belgium.
[Sanderson, Jeremy] St Thomas Hosp, Dept Gastroenterol, Guys & St Thomas NHS Fdn Trust, London, England.
[Schumm, Philip] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Seibold, Frank] Univ Bern, Inselspital, Div Gastroenterol, CH-3010 Bern, Switzerland.
[Simms, Lisa A.; Radford-Smith, Graham] Queensland Inst Med Res, Inflammatory Bowel Dis, Brisbane, Qld 4006, Australia.
[Seielstad, Mark] Genome Inst Singapore, Singapore, Singapore.
[Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Steinhart, A. Hillary; Silverberg, Mark S.] Univ Toronto, Mt Sinai Hosp, Ctr Inflammatory Bowel Dis, Toronto, ON M5G 1X5, Canada.
[van den Berg, Leonard H.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands.
[Vatn, Morten; Karlsen, Tom H.] Univ Hosp, Rikshosp, Dept Med, Oslo, Norway.
[Verspaget, Hein] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Walters, Thomas; Griffiths, Anne M.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Wilson, David C.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Ponsioen, Cyriel Y.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands.
[Andersen, Vibeke] Viborg Reg Hosp, Dept Med, Viborg, Denmark.
[Torkvist, Leif] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
[Gazouli, Maria; Anagnou, Nicholas P.] Univ Athens, Dept Biol, Sch Med, GR-15701 Athens, Greece.
[Kupcinskas, Limas; Sventoraityte, Jurgita] Kaunas Univ Med, Dept Gastroenterol, Kaunas, Lithuania.
[Mansfield, John C.] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England.
[Kugathasan, Subra] Emory Sch Med, Dept Genet, Atlanta, GA USA.
[Kugathasan, Subra] Emory Sch Med, Dept Pediat, Atlanta, GA USA.
[Halfvarson, Jonas] Orebro Univ Hosp, Dept Med, Orebro, Sweden.
[Ahmad, Tariq] Peninsula Coll Med & Dent, Exeter, Devon, England.
[Chamaillard, Mathias] INSERM, U1019, F-59045 Lille, France.
[Cho, Judy H.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Schreiber, Stefan] Univ Kiel, Dept Gen Internal Med, Kiel, Germany.
[Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Weersma, Rinse K.] Univ Med Ctr Groningen, Dept Gastroenterol, NL-9713 AV Groningen, Netherlands.
RP Anderson, CA (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England.
EM carl.anderson@sanger.ac.uk; john.david.rioux@umontreal.ca
RI Mathew, Christopher/G-3434-2015; Palmieri, Orazio/J-7697-2012; Morley,
Katherine/A-2986-2011; Franke, Lude/P-7036-2016; Latiano,
Anna/R-1965-2016; Franke, Andre/B-2151-2010; Ellinghaus,
David/G-4467-2012; Anderson, Carl/B-8327-2013; Silverberg,
Mark/B-4183-2008; Wijmenga, Cisca/D-2173-2009; hayward,
nicholas/C-1367-2015; Chamaillard, Mathias/L-6542-2013; Rioux,
John/A-9599-2015; Schreiber, Stefan/B-6748-2008; Fehrmann,
Rudolf/E-2551-2011; Prescott, Natalie/F-6490-2011; Hugot,
Jean-Pierre/F-6594-2012; D'Amato, Mauro/F-2450-2010; Montgomery,
Grant/B-7148-2008
OI Gearry, Richard/0000-0002-2298-5141; Halfvarson,
Jonas/0000-0003-0122-7234; Andersen, Vibeke/0000-0002-0127-2863; Newman,
William/0000-0002-6382-4678; Papi, Laura/0000-0003-4552-9517; Panes,
Julian/0000-0002-4971-6902; Wijmenga, Cisca/0000-0002-5635-1614;
Barrett, Jeffrey/0000-0002-1152-370X; Lee, James/0000-0001-5711-9385;
Mathew, Christopher/0000-0003-4178-1838; Palmieri,
Orazio/0000-0002-0019-7929; Morley, Katherine/0000-0002-2725-5535;
Franke, Lude/0000-0002-5159-8802; Latiano, Anna/0000-0003-3719-2061;
Franke, Andre/0000-0003-1530-5811; Duerr, Richard/0000-0001-6586-3905;
Laukens, Debby/0000-0002-1984-5850; Seielstad, Mark/0000-0001-5783-1401;
Vermeire, Severine/0000-0001-9942-3019; Anderson,
Carl/0000-0003-1719-7009; hayward, nicholas/0000-0003-4760-1033;
Chamaillard, Mathias/0000-0002-0243-9717; Rioux,
John/0000-0001-7560-8326; Schreiber, Stefan/0000-0003-2254-7771;
Fehrmann, Rudolf/0000-0002-7516-315X; Prescott,
Natalie/0000-0002-5901-7371; D'Amato, Mauro/0000-0003-2743-5197;
Montgomery, Grant/0000-0002-4140-8139
FU German Ministry of Education and Research through the National Genome
Research Network; Italian Group for IBD; Italian Society for Paediatric
Gastroenterology, Hepatology and Nutrition; Royal Brisbane and Women's
Hospital Foundation; University of Queensland; National Health and
Medical Research Council, Australia; European Community; National
Association for Colitis and Crohn's disease; Medical Research Council
UK; Peninsular College of Medicine and Dentistry, Exeter; Wellcome Trust
[083948/Z/07/Z, WT091745/Z/10/Z, WT089120/Z/09/Z]; Crohn's and Colitis
Foundation of America; US National Institutes of Health (NIH)/NIDDK
[DK064869]; National Center for Research Resources (NCRR) [M01-RR00425];
NIH/NIDDK [P01-DK046763, DK 063491]; Cedars-Sinai Medical Center;
Deutsche Forschungsgemeinschaft (DFG) [BR 1912/5-1]; Else
Kroner-Fresenius-Stiftung [P50/05/EKMS05/62]; Programme Hospitalier de
Recherche Clinique; Netherlands Organization for Scientific Research
(NWO) [90.700.281, 918.66.620]; Celiac Disease Consortium [BSIK03009];
Prinses Beatrix Fonds; Adessium Foundation; Amyotrophic Lateral
Sclerosis Association; Netherlands Genomics Initiative [93519031]; NWO
(ZonMW) [916.10.135]; National Institute for Health Research (NIHR)
Biomedical Research Centre; Helmsley Foundation; Primary Children's
Medical Center Foundation; [DK062431]; [DK062422]; [DK062420];
[DK062432]; [DK062423]; [DK062413]; [DK076984]; [DK084554];
[DK062429]; [DK069513]; [DK83756]; [AI062773]; [DK043351]
FX We thank all the subjects who contributed samples and the physicians and
nursing staff who helped with recruitment globally. This study was
supported by the German Ministry of Education and Research through the
National Genome Research Network, the Popgen biobank and infrastructure
support through the Deutsche Forschungsgemeinschaft (DFG) cluster of
excellence 'Inflammation at Interfaces'. Italian case collections were
supported by the Italian Group for IBD and the Italian Society for
Paediatric Gastroenterology, Hepatology and Nutrition. We acknowledge
funding provided by the Royal Brisbane and Women's Hospital Foundation,
University of Queensland (Ferguson Fellowship), National Health and
Medical Research Council, Australia and by the European Community (5th
PCRDT). UK case collections were supported by the National Association
for Colitis and Crohn's disease, Wellcome Trust, Medical Research
Council UK and Peninsular College of Medicine and Dentistry, Exeter.
Activities in Sweden were supported by the Swedish Society of Medicine,
the Bengt Ihre Foundation, the Karolinska Institutet, the Swedish
National Program for IBD Genetics, the Swedish Organization for IBD, the
Swedish Medical Research Council, the Soderbergh Foundation and the
Swedish Cancer Foundation. Support for genotyping and genetic data
analysis was provided by the Agency for Science Technology and Research
(A*STAR), Singapore. We are grateful to the funders and investigators of
the Epidemiological Investigation of Rheumatoid Arthritis for providing
genotype data from healthy Swedish individuals.; The Wellcome Trust Case
Control Consortium 2 project was supported by Wellcome Trust grant
083948/Z/07/Z. We also acknowledge the National Institute for Health
Research (NIHR) Biomedical Research Centre awards to Guy's & St. Thomas'
National Health Service (NHS) Trust, King's College London and to
Addenbrooke's Hospital, University of Cambridge School of Clinical
Medicine and to the University of Manchester and Central Manchester
Foundation Trust. The NIDDK IBD Genetics Consortium is funded by the
following grants: DK062431 (S. R. B.), DK062422 (J.H.C.), DK062420 (R.
H. D.), DK062432 (J.D.R.), DK062423 (M. S. S.), DK062413 (D. P. M.),
DK076984 (M.J.D.), DK084554 (M.J.D. and D. P. M.) and DK062429 (J.H.C.).
J.H.C. is also funded by the Crohn's and Colitis Foundation of America;
S. L. G. by DK069513 and Primary Children's Medical Center Foundation;
and J.D.R. by US National Institutes of Health (NIH)/NIDDK grant
DK064869. Cedars-Sinai is supported by National Center for Research
Resources (NCRR) grant M01-RR00425, NIH/NIDDK grant P01-DK046763, DK
063491 and Cedars-Sinai Medical Center Inflammatory Bowel Disease
Research Funds. E. L., D. F. and S. V. are senior clinical investigators
for the Funds for Scientific Research (FWO/FNRS) Belgium. S. Brand was
supported by Deutsche Forschungsgemeinschaft (DFG BR 1912/5-1) and Else
Kroner-Fresenius-Stiftung (P50/05/EKMS05/62). M. C. was supported by the
Programme Hospitalier de Recherche Clinique. C. A. A. is supported by
Wellcome Trust grant WT091745/Z/10/Z. J.C.B. is supported by Wellcome
Trust grant WT089120/Z/09/Z. R. K. W. is supported by a clinical
fellowship grant (90.700.281) from the Netherlands Organization for
Scientific Research (NWO). C. W. is supported by grants from the Celiac
Disease Consortium (BSIK03009) and The Netherlands Organization for
Scientific Research (NWO, VICI grant 918.66.620). L.H.v.d.B.
acknowledges funding from the Prinses Beatrix Fonds, the Adessium
Foundation and the Amyotrophic Lateral Sclerosis Association. L. F.
received a Horizon Breakthrough grant from the Netherlands Genomics
Initiative (93519031) and a VENI grant from NWO (ZonMW grant
916.10.135). R.J.X. and A.N. are funded by DK83756, AI062773, DK043351
and the Helmsley Foundation.
NR 53
TC 609
Z9 614
U1 4
U2 66
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD MAR
PY 2011
VL 43
IS 3
BP 246
EP U94
DI 10.1038/ng.764
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 726BR
UT WOS:000287693800016
PM 21297633
ER
PT J
AU Nakahira, K
Haspel, JA
Rathinam, VAK
Lee, SJ
Dolinay, T
Lam, HC
Englert, JA
Rabinovitch, M
Cernadas, M
Kim, HP
Fitzgerald, KA
Ryter, SW
Choi, AMK
AF Nakahira, Kiichi
Haspel, Jeffrey Adam
Rathinam, Vijay A. K.
Lee, Seon-Jin
Dolinay, Tamas
Lam, Hilaire C.
Englert, Joshua A.
Rabinovitch, Marlene
Cernadas, Manuela
Kim, Hong Pyo
Fitzgerald, Katherine A.
Ryter, Stefan W.
Choi, Augustine M. K.
TI Autophagy proteins regulate innate immune responses by inhibiting the
release of mitochondrial DNA mediated by the NALP3 inflammasome
SO NATURE IMMUNOLOGY
LA English
DT Article
ID FRANCISELLA-TULARENSIS; AIM2 INFLAMMASOME; INTRACELLULAR DNA; OXIDATIVE
STRESS; ENDOTOXIC-SHOCK; HOST-DEFENSE; ACTIVATION; IL-1-BETA; DISEASE;
MECHANISMS
AB Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. Here we demonstrate that depletion of the autophagic proteins LC3B and beclin 1 enhanced the activation of caspase-1 and secretion of interleukin 1 (IL-1 beta) and IL-18. Depletion of autophagic proteins promoted the accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial reactive oxygen species (ROS). Cytosolic mtDNA contributed to the secretion of IL-1 beta and IL-18 in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity.
C1 [Nakahira, Kiichi; Haspel, Jeffrey Adam; Lee, Seon-Jin; Dolinay, Tamas; Lam, Hilaire C.; Englert, Joshua A.; Cernadas, Manuela; Kim, Hong Pyo; Ryter, Stefan W.; Choi, Augustine M. K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Haspel, Jeffrey Adam] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA.
[Rathinam, Vijay A. K.; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA USA.
[Rabinovitch, Marlene] Stanford Univ, Sch Med, Wall Ctr Pulm Vasc Dis, Stanford, CA 94305 USA.
[Kim, Hong Pyo] Univ Ulsan, Coll Nat Sci, Sch Biol Sci, Ulsan 680749, South Korea.
RP Choi, AMK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
EM amchoi@rics.bwh.harvard.edu
FU National Institutes of Health [HL079904-12, HL08554, HL060234-10,
HL097005, AI083713, AI067497]; New England Regional Center of Excellence
for Biodefense and Emerging Infectious Diseases (National Institute of
Allergy and Infectious Diseases of the National Institutes of Health)
[AI057159]
FX We thank B. Levine (University of Texas Southwestern Medical Center) for
Becn1+/-mice; and E. Ifedigbo for technical assistance.
Supported by National Institutes of Health (HL079904-12, HL08554,
HL060234-10 and HL097005 to A. M. K. C., and AI083713 and AI067497 to K.
A. F.) and the New England Regional Center of Excellence for Biodefense
and Emerging Infectious Diseases (National Institute of Allergy and
Infectious Diseases of the National Institutes of Health; AI057159 to
V.A.K.R).
NR 48
TC 789
Z9 831
U1 29
U2 156
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD MAR
PY 2011
VL 12
IS 3
BP 222
EP U57
DI 10.1038/ni.1980
PG 10
WC Immunology
SC Immunology
GA 721KZ
UT WOS:000287354400009
PM 21151103
ER
PT J
AU Chin, L
Andersen, JN
Futreal, PA
AF Chin, Lynda
Andersen, Jannik N.
Futreal, P. Andrew
TI Cancer genomics: from discovery science to personalized medicine
SO NATURE MEDICINE
LA English
DT Article
ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; ANAPLASTIC LYMPHOMA KINASE;
EML4-ALK FUSION GENE; SOMATIC MUTATIONS; ALK KINASE; ACTIVATING
MUTATIONS; MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; RENAL-CARCINOMA
AB Recent advances in genome technologies and the ensuing outpouring of genomic information related to cancer have accelerated the convergence of discovery science and clinical medicine. Successful examples of translating cancer genomics into therapeutics and diagnostics reinforce its potential to make possible personalized cancer medicine. However, the bottlenecks along the path of converting a genome discovery into a tangible clinical endpoint are numerous and formidable. In this Perspective, we emphasize the importance of establishing the biological relevance of a cancer genomic discovery in realizing its clinical potential and discuss some of the major obstacles to moving from the bench to the bedside.
C1 [Chin, Lynda; Andersen, Jannik N.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Chin, Lynda] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Futreal, P. Andrew] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England.
RP Chin, L (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
EM lynda_chin@dfci.harvard.edu
OI Andersen, Jannik/0000-0003-4528-2120
NR 67
TC 207
Z9 211
U1 11
U2 76
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2011
VL 17
IS 3
BP 297
EP 303
DI 10.1038/nm.2323
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 730XF
UT WOS:000288070000040
PM 21383744
ER
PT J
AU Namekawa, SH
Lee, JT
AF Namekawa, Satoshi H.
Lee, Jeannie T.
TI Detection of nascent RNA, single-copy DNA and protein localization by
immunoFISH in mouse germ cells and preimplantation embryos
SO NATURE PROTOCOLS
LA English
DT Article
ID X-CHROMOSOME INACTIVATION; HISTONE MODIFICATIONS; CHROMATIN; MICE;
METHYLATION
AB Dynamic reprogramming of the genome takes place during the gamete-to-embryo transition. This transition defines a period of continuous and global change but has been difficult to study because of extremely limited material and varying degrees of chromatin compaction. Improved methods of detecting chromatin and gene expression changes in the germ line and in the preimplantation embryo would greatly enhance the understanding of this crucial developmental transition. Here we describe a protocol developed and used by us that improves the sensitivity of existing fluorescence in situ hybridization ( FISH) methods; the protocol described here has enabled us to visualize single-copy DNA targets and corresponding nascent RNA transcripts in preimplantation embryos and during spermatogenesis. Major improvements over alternative methods involve fixation and permeabilization steps. Chromatin epitopes can be visualized simultaneously by combining FISH with immunofluorescence; multicopy and repetitive element expression can also be reliably measured. This procedure ( sample preparation and staining) requires 1-1.5 d to complete and will facilitate detailed examination of spatial relationships between chromatin epitopes, DNA and RNA during the dynamic transition from gamete to embryo.
C1 [Namekawa, Satoshi H.; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA.
[Namekawa, Satoshi H.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA.
EM satoshi.namekawa@cchmc.org; lee@molbio.mgh.harvard.edu
FU National Institutes of Health [R01-GM58839]; Japan Society for the
Promotion of Science (JSPS); Charles King Trust
FX We thank K. Hyunh, B. Payer and L.- F. Zhang for their assistance to
optimize experimental conditions during the initial phases of these
works. The studies have been supported by National Institutes of Health
grant R01-GM58839 to J.T.L. S.H.N. was supported by the research
fellowships of the Japan Society for the Promotion of Science (JSPS) and
the Charles King Trust. J.T.L. is an Investigator of the Howard Hughes
Medical Institute.
NR 34
TC 27
Z9 27
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD MAR
PY 2011
VL 6
IS 3
DI 10.1038/nprot.2010.195
PG 15
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 729PA
UT WOS:000287961700002
PM 21372809
ER
PT J
AU Altfeld, M
Fadda, L
Frleta, D
Bhardwaj, N
AF Altfeld, Marcus
Fadda, Lena
Frleta, Davor
Bhardwaj, Nina
TI DCs and NK cells: critical effectors in the immune response to HIV-1
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATURAL-KILLER-CELLS;
PLASMACYTOID-DENDRITIC-CELLS; CD4(+) T-CELLS; MHC CLASS-I;
INTERFERON-ALPHA EXPRESSION; HIV-1-INFECTED PATIENTS; INHIBITORY
RECEPTORS; TYPE-1 INFECTION; HLA-B
AB Dendritic cells (DCs) and natural killer (NK) cells have central roles in antiviral immunity by shaping the quality of the adaptive immune response to viruses and by mediating direct antiviral activity. HIV-1 infection is characterized by a severe dysregulation of the antiviral immune response that starts during early infection. This Review describes recent insights into how HIV-1 infection affects DC and NK cell function, and the roles of these innate immune cells in HIV-1 pathogenesis. The importance of understanding DC and NK cell crosstalk during HIV infection for the development of effective antiviral strategies is also discussed.
C1 [Altfeld, Marcus; Fadda, Lena] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA.
[Frleta, Davor; Bhardwaj, Nina] NYU, Langone Med Ctr, Inst Canc, New York, NY 10016 USA.
RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA.
EM maltfeld@partners.org; Nina.Bhardwaj@nyumc.org
FU Science Foundation Ireland; Irish Research Council for Science,
Engineering Technology; Health Research Board Ireland
FX The authors would like to thank their respective funding bodies:
L.A.O'N. is supported by Science Foundation Ireland, F.J.S. was
supported by the Irish Research Council for Science, Engineering &
Technology and C.E.M. is supported by a Health Research Board
Ireland/Marie Curie fellowship.
NR 127
TC 104
Z9 107
U1 2
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD MAR
PY 2011
VL 11
IS 3
BP 176
EP 186
DI 10.1038/nri2935
PG 11
WC Immunology
SC Immunology
GA 726OG
UT WOS:000287732500011
PM 21350578
ER
PT J
AU Neuwelt, EA
Bauer, B
Fahlke, C
Fricker, G
Iadecola, C
Janigro, D
Leybaert, L
Molnar, Z
O'Donnell, ME
Povlishock, JT
Saunders, NR
Sharp, F
Stanimirovic, D
Watts, RJ
Drewes, LR
AF Neuwelt, Edward A.
Bauer, Bjoern
Fahlke, Christoph
Fricker, Gert
Iadecola, Constantino
Janigro, Damir
Leybaert, Luc
Molnar, Zoltan
O'Donnell, Martha E.
Povlishock, John T.
Saunders, Norman R.
Sharp, Frank
Stanimirovic, Danica
Watts, Ryan J.
Drewes, Lester R.
TI Engaging neuroscience to advance translational research in brain barrier
biology
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID CENTRAL-NERVOUS-SYSTEM; BINDING CASSETTE TRANSPORTERS; P-GLYCOPROTEIN
EXPRESSION; HUMAN BLOOD-BRAIN; HEREDITARY CEREBRAL-HEMORRHAGE; GREEN
FLUORESCENT PROTEIN; AMINO-ACID TRANSPORTERS; NECROSIS-FACTOR-ALPHA;
INDUCED UP-REGULATION; MULTIPLE-SCLEROSIS
AB The delivery of many potentially therapeutic and diagnostic compounds to specific areas of the brain is restricted by brain barriers, of which the most well known are the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier. Recent studies have shown numerous additional roles of these barriers, including an involvement in neurodevelopment, in the control of cerebral blood flow, and-when barrier integrity is impaired-in the pathology of many common CNS disorders such as Alzheimer's disease, Parkinson's disease and stroke.
C1 [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Neuwelt, Edward A.] Portland VA Med Ctr, Portland, OR 97239 USA.
[Bauer, Bjoern] Univ Minnesota, Coll Pharm, Duluth, MN 55812 USA.
[Fahlke, Christoph] Hannover Med Sch, Inst Neurophysiol, OE 4230, D-30625 Hannover, Germany.
[Fricker, Gert] Univ Heidelberg, Abt Pharmazeut Technol & Pharmakol Neuenheimer, D-69120 Heidelberg, Germany.
[Iadecola, Constantino] Weill Cornell Med Coll, Div Neurobiol, New York, NY 10065 USA.
[Janigro, Damir] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Leybaert, Luc] Univ Ghent, Dept Basic Med Sci, B-9000 Ghent, Belgium.
[Molnar, Zoltan] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
[O'Donnell, Martha E.] Univ Calif Davis, Sch Med, Dept Physiol & Membrane Biol, Davis, CA 95616 USA.
[Povlishock, John T.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA.
[Saunders, Norman R.] Univ Melbourne, Dept Pharmacol Parkville, Melbourne, Vic 3010, Australia.
[Sharp, Frank] Univ Calif Davis, UC Davis MIND Inst, Sacramento, CA 95817 USA.
[Stanimirovic, Danica] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R7, Canada.
[Watts, Ryan J.] Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA.
[Drewes, Lester R.] Univ Minnesota, Sch Med, Duluth, MN 55812 USA.
RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,L603, Portland, OR 97239 USA.
EM neuwelte@ohsu.edu
RI Fahlke, Christoph/G-3635-2013; Leybaert, Luc/F-4079-2015;
OI Fahlke, Christoph/0000-0001-8602-9952; Janigro,
Damir/0000-0003-2165-5826; Leybaert, Luc/0000-0001-6452-6982; Molnar,
Zoltan/0000-0002-6852-6004; Saunders, Norman/0000-0001-6660-7639
FU US National Institutes of Health [5 R13 CA086959-10]
FX The meeting on which this report was based was partially funded by an
R13 grant from the US National Institutes of Health (Grant 5 R13
CA086959-10). We would like to thank all of the people who attended the
Engaging Neuroscience to Advance Brain Barriers Translational Research
meeting (March 19-21, 2009), Gleneden Beach, Oregon, USA. Special thanks
to Lester Drewes, Martha O'Donnell, Leslie Muldoon and Aliana Kim who
were instrumental in the development of this report.
NR 218
TC 192
Z9 197
U1 2
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD MAR
PY 2011
VL 12
IS 3
BP 169
EP 182
DI 10.1038/nrn2995
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 722ZM
UT WOS:000287474900004
PM 21331083
ER
PT J
AU Upadhyay, A
Larson, MG
Guo, CY
Vasan, RS
Lipinska, I
O'Donnell, CJ
Kathiresan, S
Meigs, JB
Keaney, JF
Rong, JA
Benjamin, EJ
Fox, CS
AF Upadhyay, Ashish
Larson, Martin G.
Guo, Chao-Yu
Vasan, Ramachandran S.
Lipinska, Izabella
O'Donnell, Christopher J.
Kathiresan, Sekar
Meigs, James B.
Keaney, John F., Jr.
Rong, Jian
Benjamin, Emelia J.
Fox, Caroline S.
TI Inflammation, kidney function and albuminuria in the Framingham
Offspring cohort
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE albuminuria; chronic kidney disease; C-reactive protein; inflammation
ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; CARDIOVASCULAR MORTALITY;
RENAL-INSUFFICIENCY; TISSUE DISTRIBUTION; OXIDATIVE STRESS; ALL-CAUSE;
BIOMARKERS; RISK; ASSOCIATION
AB Background. Inflammation and chronic kidney disease (CKD) are both associated with cardiovascular disease (CVD). Whether inflammatory biomarkers are associated with kidney function and albuminuria after accounting for traditional CVD risk factors is not completely understood.
Methods. The sample comprised Framingham Offspring cohort participants (n = 3294, mean age 61, 53% women) who attended the seventh examination cycle (1998-2001). Inflammatory biomarkers [C-reactive protein (CRP), tumour necrosis factor (TNF)-alpha, interleukin-6, TNF receptor 2 (TNFR2), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), P-selectin, CD-40 ligand, osteoprotegerin, urinary isoprostanes, myeloperoxidase and fibrinogen] were measured on fasting blood samples. Serum creatinine-based estimated glomerular filtration rate (eGFR) and serum cystatin C concentration were used to assess kidney function. Urinary albumin-to-creatinine ratio (UACR) was used to assess albuminuria. Linear or logistic regression was used to test associations between biomarkers and kidney measures.
Results. Chronic kidney disease (CKD), defined as eGFR < 59/64 mL/min/1.73 m(2) in women/men, was present in 8.8% (n = 291) of participants. TNF-alpha, interleukin-6, TNFR2, MCP-1, osteoprotegerin, myeloperoxidase and fibrinogen were higher among individuals with CKD; all biomarkers except for urinary isoprostanes were elevated in higher cystatin C quartiles; and TNF-alpha, interleukin-6, TNFR2, ICAM-1 and osteoprotegerin were elevated in higher UACR quartiles-all assessed after multivariable adjustment. Almost 6% and 17% of variability in TNFR2 were explained by CKD status and higher cystatin C quartiles, respectively.
Conclusions. Biomarkers of inflammation are associated with kidney function and albuminuria. In particular, substantial variability in soluble TNFR2 is explained by CKD and cystatin C.
C1 [Upadhyay, Ashish] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
[Upadhyay, Ashish] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Larson, Martin G.; Guo, Chao-Yu; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Rong, Jian; Benjamin, Emelia J.; Fox, Caroline S.] Boston Univ, Framingham, MA USA.
[Larson, Martin G.; Guo, Chao-Yu; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Rong, Jian; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Lipinska, Izabella] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA.
[Lipinska, Izabella; O'Donnell, Christopher J.; Kathiresan, Sekar; Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Keaney, John F., Jr.] UMass Mem Hlth Care, Div Cardiovasc Med, Worcester, MA USA.
[Rong, Jian; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
RP Upadhyay, A (reprint author), Tufts Med Ctr, Div Nephrol, Boston, MA USA.
EM aupadhyay@tuftsmedicalcenter.org
OI Larson, Martin/0000-0002-9631-1254; Upadhyay,
Ashish/0000-0002-0536-5776; Ramachandran, Vasan/0000-0001-7357-5970;
Benjamin, Emelia/0000-0003-4076-2336
FU NHLBI NIH HHS [R01 HL064753, N01 HC025195, N01-HC-25195, R01
HL043302-10, R01 HL064753-01, R01 HL076784, R01 HL076784-01,
R01-HL-076784, R01-HL-64753, R01-HL04334, R01-HL70139]; NIA NIH HHS
[AG028321, R01 AG028321, R01 AG028321-01]; NIDDK NIH HHS [K24 DK080140,
K24 DK080140-01, K24-DK080140]
NR 32
TC 56
Z9 59
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD MAR
PY 2011
VL 26
IS 3
BP 920
EP 926
DI 10.1093/ndt/gfq471
PG 8
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 726SN
UT WOS:000287746500024
PM 20682604
ER
PT J
AU Reardon, DA
Galanis, E
DeGroot, JF
Cloughesy, TF
Wefel, JS
Lamborn, KR
Lassman, AB
Gilbert, MR
Sampson, JH
Wick, W
Chamberlain, MC
Macdonald, DR
Mehta, MP
Vogelbaum, MA
Chang, SM
Van den Bent, MJ
Wen, PY
AF Reardon, David A.
Galanis, Evanthia
DeGroot, John F.
Cloughesy, Timothy F.
Wefel, Jeffrey S.
Lamborn, Kathleen R.
Lassman, Andrew B.
Gilbert, Mark R.
Sampson, John H.
Wick, Wolfgang
Chamberlain, Marc C.
Macdonald, David R.
Mehta, Minesh P.
Vogelbaum, Michael A.
Chang, Susan M.
Van den Bent, Martin J.
Wen, Patrick Y.
TI Clinical trial end points for high-grade glioma: the evolving landscape
SO NEURO-ONCOLOGY
LA English
DT Review
DE clinical trials; malignant glioma; end point
ID PROGRESSION-FREE SURVIVAL; QUALITY-OF-LIFE; RECURRENT MALIGNANT GLIOMA;
PHASE-II TRIAL; GLIOBLASTOMA-MULTIFORME; TUMOR PROGRESSION;
BRAIN-TUMORS; NEUROCOGNITIVE FUNCTION; DISEASE PROGRESSION; RESPONSE
ASSESSMENT
AB To review the strengths and weaknesses of primary and auxiliary end points for clinical trials among patients with high-grade glioma (HGG). Recent advances in outcome for patients with newly diagnosed and recurrent HGG, coupled with the development of multiple promising therapeutics with myriad antitumor actions, have led to significant growth in the number of clinical trials for patients with HGG. Appropriate clinical trial design and the incorporation of optimal end points are imperative to efficiently and effectively evaluate such agents and continue to advance outcome. Growing recognition of limitations weakening the reliability of traditional clinical trial primary end points has generated increasing uncertainty of how best to evaluate promising therapeutics for patients with HGG. The phenomena of pseudoprogression and pseudoresponse have made imaging-based end points, including overall radiographic response and progression-free survival, problematic. Although overall survival is considered the "gold-standard" end point, recently identified active salvage therapies such as bevacizumab may diminish the association between presalvage therapy and overall survival. Finally, advances in imaging as well as the assessment of patient function and well being have strengthened interest in auxiliary end points assessing these aspects of patient care and outcome. Better appreciation of the strengths and limitations of primary end points will lead to more effective clinical trial strategies. Technical advances in imaging as well as improved survival for patients with HGG support the further development of auxiliary end points evaluating novel imaging approaches as well as measures of patient function and well being.
C1 [Reardon, David A.; Sampson, John H.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[Galanis, Evanthia] Mayo Clin, Dept Med Oncol, Rochester, MN USA.
[DeGroot, John F.; Wefel, Jeffrey S.; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Neurooncol Program, Los Angeles, CA 90095 USA.
[Lamborn, Kathleen R.; Chang, Susan M.] Univ Calif San Francisco, Dept Neurol Surg, Div Neurooncol, San Francisco, CA 94143 USA.
[Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
[Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA.
[Wick, Wolfgang] Univ Heidelberg, Dept Neurooncol, Heidelberg, Germany.
[Chamberlain, Marc C.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Macdonald, David R.] Univ Western Ontario, Dept Oncol, London, ON N6A 3K7, Canada.
[Macdonald, David R.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON N6A 3K7, Canada.
[Macdonald, David R.] London Reg Canc Program, London, ON, Canada.
[Mehta, Minesh P.] Univ Wisconsin, Sch Med, Dept Human Oncol, Madison, WI 53706 USA.
[Vogelbaum, Michael A.] Cleveland Clin Fdn, Brain Tumor & NeuroOncol Ctr, Cleveland, OH 44195 USA.
[Van den Bent, Martin J.] Erasmus Univ Hosp Rotterdam, Neurooncol Unit, Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands.
[Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurol, Boston, MA 02115 USA.
RP Reardon, DA (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Box 3624, Durham, NC 27710 USA.
EM reard003@mc.duke.edu
RI Gilbert, Mark/J-7494-2016;
OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713
NR 73
TC 54
Z9 56
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD MAR
PY 2011
VL 13
IS 3
BP 353
EP 361
DI 10.1093/neuonc/noq203
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 732AA
UT WOS:000288151400010
PM 21310734
ER
PT J
AU Leung, E
Guo, L
Bu, J
Maloof, M
El Khoury, J
Geula, C
AF Leung, Elaine
Guo, Ling
Bu, Jing
Maloof, Marie
El Khoury, Joseph
Geula, Changiz
TI Microglia activation mediates fibrillar amyloid-beta toxicity in the
aged primate cortex
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyloid toxicity; Microglia; Fibrillar; Neuronal loss; Non-human primate
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CENTRAL-NERVOUS-SYSTEM;
ALZHEIMERS-DISEASE; SCAVENGER RECEPTOR; BONE-MARROW; IN-VITRO; HUMAN
MONOCYTES; PROTEIN; NEUROTOXICITY; TUFTSIN
AB The amyloid-beta peptide (A beta) plays a central role in the pathogenesis of Alzheimer's disease (AD). The fibrillar form of A beta (fA beta) exerts toxic effects on neurons through mechanisms not well understood. We have shown that the aged primate cortex is selectively vulnerable to fA beta toxicity at low concentrations. In addition to neuronal loss, fA beta induced massive activation of microglia in the aged rhesus cortex. We now demonstrate that inhibition of microglia activation abolishes fA beta toxicity. Injection or pump delivery of macrophage/microglia inhibitory factor (MIF) significantly reduced activation of microglia and the volume of damage caused by fA beta. Microglia isolated from aged rhesus cortex produced substantial reactive oxygen species when stimulated by fA beta, which was inhibited by MIF in a dose-dependent manner. This is the first definitive in vivo demonstration that the fA beta-induced microglia activation and inflammation mediate, at least in part, its toxic effects on neurons. Combined with our earlier observations, these findings suggest that aged primate microglia may display an exaggerated inflammatory response to fA beta when compared with young microglia. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Leung, Elaine; Guo, Ling; Bu, Jing; Maloof, Marie; Geula, Changiz] Northwestern Univ, Feinberg Sch Med, Lab Cognit & Mol Morphometry, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA.
[Leung, Elaine; Bu, Jing; Maloof, Marie; El Khoury, Joseph; Geula, Changiz] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Leung, Elaine; Bu, Jing; Maloof, Marie; Geula, Changiz] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA.
[El Khoury, Joseph] Massachusetts Gen Hosp, Div Infect Dis, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
RP Geula, C (reprint author), Northwestern Univ, Feinberg Sch Med, Lab Cognit & Mol Morphometry, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA.
EM c-geula@northwestern.edu
FU Alzheimer's Association; Dana Foundation; Illinois Department of Public
Health Alzheimer's Disease; Northwestern University Alzheimer's Disease
Center [P30 AGO 13854]
FX We thank Naima Gedi and Nicholas Nagykery for expert technical
assistance. This work was supported in part by grants from the
Alzheimer's Association, the Dana Foundation Neuroimmunology Program and
the Illinois Department of Public Health Alzheimer's Disease Fund and
the Northwestern University Alzheimer's Disease Center (P30 AGO 13854).
NR 59
TC 19
Z9 19
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD MAR
PY 2011
VL 32
IS 3
BP 387
EP 397
DI 10.1016/j.neurobiolaging.2009.02.025
PG 11
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 755PE
UT WOS:000289944800004
PM 19349094
ER
PT J
AU Rozkalne, A
Hyman, BT
Spires-Jones, TL
AF Rozkalne, Anete
Hyman, Bradley T.
Spires-Jones, Tara L.
TI Calcineurin inhibition with FK506 ameliorates dendritic spine density
deficits in plaque-bearing Alzheimer model mice
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Alzheimer; Dendritic spine; FK506; Tacrolimus; Synapse; Transgenic
ID PROTEIN TRANSGENIC MICE; DISEASE MOUSE MODEL; AMYLOID-BETA; IN-VIVO;
LIVER-TRANSPLANTATION; SYNAPTIC PLASTICITY; EXPERIMENTAL STROKE; MEMORY;
OLIGOMERS; IMMUNOSUPPRESSION
AB Synapse loss is the strongest correlate of cognitive decline in Alzheimer's disease, and synapses are an attractive therapeutic target due to their plastic nature that allows for potential recovery with intervention. We have previously demonstrated in transgenic mice that form senile plaques that dendrites surrounding plaques become dystrophic and lose postsynaptic dendritic spines. Furthermore, we found strong evidence that plaque-associated dendritic changes are mediated by calcineurin, a calcium-dependent phosphatase involved in cell signaling, using in vitro models and genetically encoded inhibitors in mouse models. In this study, we pharmacologically inhibited calcineurin with FK506 treatment to test the hypothesis that calcineurin inhibition will allow recovery of plaque-associated synapse loss. We found that in plaque bearing transgenic mice, short term (1 week) FK506 treatment results in an amelioration of dendritic spine loss. We also observe an effect on spine morphology in wild-type mice with FK506 treatment. These data show that systemic FK506 administration, and hence calcineurin inhibition, may be neuroprotective for amyloid beta induced synaptic alterations. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Rozkalne, Anete; Hyman, Bradley T.; Spires-Jones, Tara L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
RP Hyman, BT (reprint author), 114 16th St, Charlestown, MA 02129 USA.
EM bhyman@partners.org
OI Spires-Jones, Tara/0000-0003-2530-0598
FU Alzheimer's disease Drug Discovery Foundation/Association for
Frontotemporal Dementias [P50 AG005134, AG08487]; [K99 AG033670-01A1]
FX This work was supported by K99 AG033670-01A1, Alzheimer's disease Drug
Discovery Foundation/Association for Frontotemporal Dementias, P50
AG005134, AG08487.
NR 34
TC 32
Z9 35
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 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD MAR
PY 2011
VL 41
IS 3
BP 650
EP 654
DI 10.1016/j.nbd.2010.11.014
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 718JZ
UT WOS:000287118700007
PM 21134458
ER
PT J
AU Greenberg, SM
Frosch, MP
AF Greenberg, Steven M.
Frosch, Matthew P.
TI Life imitates art Anti-amyloid antibodies and inflammatory cerebral
amyloid angiopathy
SO NEUROLOGY
LA English
DT Editorial Material
ID BETA
C1 [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM sgreenberg@partners.org
NR 10
TC 13
Z9 13
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR 1
PY 2011
VL 76
IS 9
BP 772
EP 773
DI 10.1212/WNL.0b013e31820e7bce
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 728JE
UT WOS:000287869600004
PM 21357829
ER
PT J
AU Gao, XA
Chen, HL
Schwarzschild, MA
Ascherio, A
AF Gao, Xiang
Chen, Honglei
Schwarzschild, Michael A.
Ascherio, Alberto
TI Use of ibuprofen and risk of Parkinson disease
SO NEUROLOGY
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NONNARCOTIC ANALGESIC USE; WOMEN;
METAANALYSIS; NSAIDS; QUESTIONNAIRE; CONSUMPTION; CAFFEINE; SMOKING;
TARGET
AB Background: Neuroinflammation may contribute to the pathogenesis of Parkinson disease (PD). Use of nonsteroidal anti-inflammatory drugs (NSAID) in general, and possibly ibuprofen in particular, has been shown to be related to lower PD risk in previous epidemiologic studies.
Methods: We prospectively examined whether use of ibuprofen or other NSAIDs is associated with lower PD risk among 136,197 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) free of PD at baseline (1998 for NHS and 2000 for HPFS). NSAIDs use was assessed via questionnaire. Results were combined in a meta-analysis with those of published prospective investigations.
Results: We identified 291 incident PD cases during 6 years of follow-up. Users of ibuprofen had a significantly lower PD risk than nonusers (relative risk [RR], adjusted for age, smoking, caffeine, and other covariates = 0.62; 95% confidence interval [CI] 0.42-0.93; p = 0.02). There was a dose-response relationship between tablets of ibuprofen taken per week and PD risk (p trend = 0.01). In contrast, PD risk was not significantly related to use of aspirin (RR = 0.99; 95% CI 0.78-1.26), other NSAIDs (RR = 1.26; 95% CI 0.86-1.84), or acetaminophen (RR = 0.86; 95% CI 0.62-1.18). Similar results were obtained in the meta-analyses: the pooled RR was 0.73 (95% CI 0.63-0.85; p < 0.0001) for ibuprofen use, whereas use of other types of analgesics was not associated with lower PD risk.
Conclusions: The association between use of ibuprofen and lower PD risks, not shared by other NSAIDs or acetaminophen, suggests ibuprofen should be further investigated as a potential neuroprotective agent against PD. Neurology (R) 2011; 76: 863-869
C1 [Gao, Xiang; Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Gao, Xiang] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Gao, XA (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM xiang.gao@channing.harvard.edu
OI Chen, Honglei/0000-0003-3446-7779
FU NIH/NINDS [R01 NS048517]; NIH [K24NS060991]; US Department of Defense;
Michael J. Fox Foundation; Parkinson Disease Foundation; RJG Parkinson's
Disease Foundation; American Parkinson Disease Association; American
Federation for Aging Research
FX Supported by NIH/NINDS grant R01 NS048517, NIH K24NS060991, and in part
by the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences. None of the sponsors participated in the
design of this study or in the collection, analysis, or interpretation
of the data.; Dr. Gao has received research support from the NIH/NINDS.
Dr. Chen has received intramural funding from the NIH. Dr. Schwarzschild
has received research support from the NIH/NINDS, the US Department of
Defense, the Michael J. Fox Foundation, the Parkinson Disease
Foundation, the RJG Parkinson's Disease Foundation, the American
Parkinson Disease Association, and the American Federation for Aging
Research. Dr. Ascherio serves on a scientific advisory board for the
Michael J. Fox Foundation; serves on the editorial boards of Neurology
(R), Annals of Neurology, and the American Journal of Epidemiology; has
received speaker honoraria from Merck Serono; and receives research
support from the NIH, the US Department of Defense, and the Michael J.
Fox Foundation.
NR 41
TC 101
Z9 103
U1 1
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR
PY 2011
VL 76
IS 10
BP 863
EP 869
DI 10.1212/WNL.0b013e31820f2d79
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 731NZ
UT WOS:000288117500007
PM 21368281
ER
PT J
AU Numis, AL
Major, P
Montenegro, MA
Muzykewicz, DA
Pulsifer, MB
Thiele, EA
AF Numis, A. L.
Major, P.
Montenegro, M. A.
Muzykewicz, D. A.
Pulsifer, M. B.
Thiele, E. A.
TI Identification of risk factors for autism spectrum disorders in tuberous
sclerosis complex
SO NEUROLOGY
LA English
DT Article
ID MRI FINDINGS; CHILDREN; TSC1; ABNORMALITIES; IMPAIRMENT; MUTATIONS;
LOCATION; FAMILIES; EPILEPSY; SEIZURES
AB Objective: The purpose of this study was to assess the prevalence of and to identify epidemiologic, genetic, electrophysiologic, and neuroanatomic risk factors for autism spectrum disorders (ASD) in a cohort of patients with tuberous sclerosis complex (TSC).
Methods: A total of 103 patients with TSC were evaluated for ASD. A retrospective review of patients' records was performed, including mutational analysis. EEG reports were analyzed for the presence of ictal and interictal epileptiform features. Brain MRI scans were evaluated for TSC neuropathology, including tuber burden.
Results: Of the 103 patients with TSC, 40% were diagnosed with an ASD. On univariate analysis, patients with ASD were less likely to have mutations in the TSC1 gene. Patients with ASD also had an earlier age at seizure onset and more frequent seizures. On EEG, those with ASD had a significantly greater amount of interictal epileptiform features in the left temporal lobe only. On MRI, there were no differences in the regional distribution of tuber burden, although those with TSC2 and ASD had a higher prevalence of cyst-like tubers.
Conclusions: The development of ASD in TSC is not well understood. Given our findings, ASD may be associated with persistent seizure activity early in development in particular brain regions, such as those responsible for social perception and communication in the left temporal lobe. The presence of cyst-like tubers on MRI could provide a structural basis or marker for ASD pathology in TSC, although studies assessing their effect on cortical function are needed. Neurology (R) 2011;76:981-987
C1 [Numis, A. L.; Major, P.; Muzykewicz, D. A.; Thiele, E. A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Psychol Assessment Ctr, Boston, MA 02114 USA.
RP Thiele, EA (reprint author), Carol & James Herscot Ctr Tuberous Sclerosis Comp, 175 Cambridge St,Suite 340, Boston, MA 02114 USA.
EM ethiele@partners.org
FU Carol and James Herscot Center for Tuberous Sclerosis Complex [NIH
5P01NS024279]; Doris Duke Charitable Foundation; Lundbeck Inc.; NIH;
Tuberous Sclerosis Alliance; UCB
FX Supported by the Carol and James Herscot Center for Tuberous Sclerosis
Complex, NIH 5P01NS024279, and the Doris Duke Charitable Foundation
(A.L.N.).; Dr. Numis, Dr. Major, Dr. Montenegro, D. A. Muzykewicz, and
Dr. Pulsifer report no disclosures. Dr. Thiele serves on the Board of
Directors of the Tuberous Sclerosis Alliance and on scientific advisory
boards for the Angelman Syndrome Foundation and the Charlie Foundation;
serves on the speakers' bureau for and has received funding for travel
and speaker honoraria from UCB; serves as a consultant for Lundbeck
Inc.; and receives research support from Lundbeck Inc., the NIH, and the
Tuberous Sclerosis Alliance.
NR 40
TC 71
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U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR
PY 2011
VL 76
IS 11
BP 981
EP 987
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 734WK
UT WOS:000288371800012
PM 21403110
ER
PT J
AU Montine, TJ
Peskind, ER
Quinn, JF
Wilson, AM
Montine, KS
Galasko, D
AF Montine, Thomas J.
Peskind, Elaine R.
Quinn, Joseph F.
Wilson, Angela M.
Montine, Kathleen S.
Galasko, Douglas
TI Increased Cerebrospinal Fluid F-2-Isoprostanes are Associated with Aging
and Latent Alzheimer's Disease as Identified by Biomarkers
SO NEUROMOLECULAR MEDICINE
LA English
DT Article
DE Alzheimer's disease; Cerebrospinal fluid; Biomarkers; A beta(42); Tau;
F-2-isoprostanes
ID MILD COGNITIVE IMPAIRMENT; IN-VIVO; AMYLOID DEPOSITION;
LIPID-PEROXIDATION; OXIDATIVE STRESS; OLDER-ADULTS; BRAIN; AD;
F-4-NEUROPROSTANES; NEUROPATHOLOGY
AB Alzheimer's disease (AD) is a common age-related chronic illness with latent, prodrome, and fully symptomatic dementia stages. Increased free radical injury to regions of brain is one feature of prodrome and dementia stages of AD; however, it also is associated with advancing age. This raises the possibility that age-related free radical injury to brain might be caused in part or in full by latent AD. We quantified free radical injury in the central nervous system with cerebrospinal fluid (CSF) F-2-isoprostanes (IsoPs) in 421 clinically normal individuals and observed a significant increase over the adult human lifespan (P < 0.001). Using CSF amyloid (A) beta(42) and tau, we defined normality using results from 28 clinically normal individuals < 50 years old, and then stratified 74 clinically normal subjects a parts per thousand yen60 years into those with CSF that had normal CSF A beta(42) and tau (n = 37); abnormal CSF A beta(42) and tau, the biomarker signature of AD (n = 24); decreased A beta(42) only (n = 4); or increased tau only (n = 9). Increased CSF F-2-IsoPs were present in clinically normal subjects with the biomarker signature of AD (P < 0.05) and those subjects with increased CSF tau (P < 0.001). Finally, we analyzed the relationship between age and CSF F-2-IsoPs for those clinically normal adults with normal CSF (n = 37) and those with abnormal CSF A beta(42) and/or tau (n = 37); only those with normal CSF demonstrated a significant increase with age (P < 0.01). These results show that CSF F-2-IsoPs increased across the human lifespan and that this age-related increase in free radical injury to brain persisted after culling those with laboratory evidence of latent AD.
C1 [Montine, Thomas J.; Wilson, Angela M.; Montine, Kathleen S.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR USA.
[Galasko, Douglas] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
RP Montine, TJ (reprint author), Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
EM tmontine@u.washington.edu
FU NIH [AG05131, AG05136]; Fidelity Foundation; Nancy and Buster Alvord
Endowment
FX This work was supported by grants from the NIH (AG05131 and AG05136),
the Fidelity Foundation, and the Nancy and Buster Alvord Endowment.
NR 41
TC 32
Z9 32
U1 1
U2 9
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1535-1084
J9 NEUROMOL MED
JI Neuromol. Med.
PD MAR
PY 2011
VL 13
IS 1
BP 37
EP 43
DI 10.1007/s12017-010-8126-6
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 726VB
UT WOS:000287753400012
PM 20632131
ER
PT J
AU Ritchey, M
Bessette-Symons, B
Hayes, SM
Cabeza, R
AF Ritchey, Maureen
Bessette-Symons, Brandy
Hayes, Scott M.
Cabeza, Roberto
TI Emotion processing in the aging brain is modulated by semantic
elaboration
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Affective; Valence; Functional MRI; Neuroimaging; Elderly; Levels of
processing
ID AGE-RELATED DIFFERENCES; EVENT-RELATED FMRI; OLDER-ADULTS; PREFRONTAL
CORTEX; FUNCTIONAL NEUROANATOMY; NEURAL MECHANISMS; COGNITIVE CONTROL;
NEGATIVE IMAGES; SOURCE MEMORY; ANGRY FACES
AB The neural correlates of emotion processing have been shown to vary with age: older adults (OAs) exhibit increased frontal activations and, under some circumstances, decreased amygdala activations relative to young adults (YAs) during emotion processing. Some of these differences are additionally modulated by valence, with age-related biases toward positive versus negative stimuli, and are thought to depend on OAs' capacity for controlled elaboration. However, the role of semantic elaboration in mediating valence effects in the aging brain has not yet been explicitly tested. In the present study, YAs and OAs were scanned while they viewed negative, neutral, and positive pictures during either a deep, elaborative task or a shallow, perceptual task. fMRI results reveal that emotion-related activity in the amygdala is preserved in aging and insensitive to elaboration demands. This study provides novel evidence that differences in valence processing are modulated by elaboration: relative to YAs, OAs show enhanced activity in the medial prefrontal cortex (PFC) and ventrolateral PFC in response to positive versus negative stimuli, but only during elaborative processing. These positive valence effects are predicted by individual differences in executive function in OAs for the deep but not shallow task. Finally, psychophysiological interaction analyses reveal age effects on valence-dependent functional connectivity between medial PFC and ventral striatum, as well as age and task effects on medial PFC-retrosplenial cortex interactions. Altogether, these findings provide support for the hypothesis that valence shifts in the aging brain are mediated by controlled processes such as semantic elaboration, self-referential processing, and emotion regulation. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Ritchey, Maureen; Cabeza, Roberto] Duke Univ, Ctr Cognit Neurosci, Durham, NC 27708 USA.
[Ritchey, Maureen; Cabeza, Roberto] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA.
[Bessette-Symons, Brandy] Ithaca Coll, Dept Psychol, Ithaca, NY USA.
[Hayes, Scott M.] VA Boston Healthcare Syst, Neuroimaging Ctr, Boston, MA USA.
[Hayes, Scott M.] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA.
[Hayes, Scott M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
RP Ritchey, M (reprint author), Duke Univ, Ctr Cognit Neurosci, Box 90999,LSRC Bldg, Durham, NC 27708 USA.
EM maureen.ritchey@duke.edu
RI Frank, David/E-8213-2012;
OI Ritchey, Maureen/0000-0002-5957-3642
FU National Institute on Aging [R01 AG019731, R01 AG23770, R01 AG34580, F32
AG029738]; National Institute of Mental Health [F31 MH085384]; National
Institute of Neurological Disorders and Stroke [R01 NS41328]
FX This work was supported by the National Institute on Aging [grant
numbers R01 AG019731, R01 AG23770, and R01 AG34580 awarded to RC and F32
AG029738 awarded to SMH], the National Institute of Mental Health [F31
MH085384 awarded to MR], and the National Institute of Neurological
Disorders and Stroke [R01 NS41328]. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of NIH, NIA, NINDS, or NIMH.
NR 65
TC 23
Z9 25
U1 2
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD MAR
PY 2011
VL 49
IS 4
SI SI
BP 640
EP 650
DI 10.1016/j.neuropsychologia.2010.09.009
PG 11
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 753GZ
UT WOS:000289761600008
PM 20869375
ER
PT J
AU Morse, L
AF Morse, Linda
TI Henry Kaplan and the Story of Hodgkin's Disease
SO ONCOLOGY NURSING FORUM
LA English
DT Book Review
C1 [Morse, Linda] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
RP Morse, L (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2011
VL 38
IS 2
BP 239
EP 240
PG 2
WC Oncology; Nursing
SC Oncology; Nursing
GA 736DM
UT WOS:000288470700019
ER
PT J
AU Stacy, RC
Jakobiec, FA
Sutula, FC
AF Stacy, Rebecca C.
Jakobiec, Frederick A.
Sutula, Francis C.
TI Recurrent Conjunctival Dermoid Cyst With Reactive Lymphoid Hyperplasia
SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID CLASSIFICATION; MANAGEMENT
AB Conjunctival dermoid cysts are a rare subtype of dermoid cyst usually presenting in adulthood. The authors report a case of a recurrent conjunctival dermoid cyst with reactive lymphoid hyperplasia that was immunohistochemically demonstrated to be polyclonal. Follicular centers that were present within the cyst wall were negative for Bcl-2 and positive for the immunohistochemical markers CD20, Bcl-6, CD10, and Ki67, which helped to differentiate the lesion from a follicular lymphoma. The lesion did not recur after 14 months of follow-up.
C1 [Stacy, Rebecca C.; Jakobiec, Frederick A.; Sutula, Francis C.] Massachusetts Eye & Ear Infirm, Boston, MA 02116 USA.
RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02116 USA.
EM fred_jakobiec@meei.harvard.edu
FU Heed Foundation
FX Supported in part by the Heed Foundation (to R.C.S.).
NR 7
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0740-9303
J9 OPHTHAL PLAST RECONS
JI Ophthalmic Plast. Reconstr. Surg.
PD MAR-APR
PY 2011
VL 27
IS 2
BP E28
EP E30
DI 10.1097/IOP.0b013e3181c6873a
PG 3
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 730BL
UT WOS:000288003800029
PM 20562661
ER
PT J
AU Brauner, SC
Berry, JL
Pye, J
Lee, EG
Rhee, DJ
AF Brauner, Stacey C.
Berry, Jesse L.
Pye, James
Lee, Edwin G.
Rhee, Douglas J.
TI Effect of Saline Conditions on the Tensile Strength of Ophthalmic
Sutures
SO OPHTHALMIC SURGERY LASERS & IMAGING
LA English
DT Article
ID ABSORBABLE SUTURES; STRABISMUS SURGERY; MUSCLE SURGERY
AB BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the tensile strength of sutures commonly used for ophthalmic surgery and the role of physiologically balanced saline comparable to the ocular environment to material failure.
MATERIALS AND METHODS: Ophthalmic sutures (9-0 and 10-0 nylon, 7-0 and 8-0 polyglactin 910, and 10-0 polypropylene) were tested using a tensiometer. Wet conditions were defined by soaking the suture in balanced salt solution for 24 hours or 7 days prior to testing.
RESULTS: The 9-0 nylon was approximately 30% stronger than 10-0 nylon (P < .01), whereas 7-0 polyglactin was 60% and 85% stronger than 8-0 polyglactin under dry and 24 hours of wet conditions (P = .0014 and .004), respectively. There was no difference in tensile strength between 10-0 nylon and polypropylene sutures. The 8-0 polyglactin suture lost 11% of tensile strength after 7 days of saline exposure.
CONCLUSION: The relative difference of suture strength between the difference gauge sutures is not a simple relationship to differences in the diameter. Tensile strength was not affected by saline conditions for the nylon, polypropylene, and 7-0 polyglactin sutures. The 8-0 polyglactin suture had a decrease in tensile strength after 7 days of exposure to saline. Surgeons should be aware of this limitation with 8-0 polyglactin.
C1 [Brauner, Stacey C.; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA.
[Berry, Jesse L.] LAC USC Med Ctr, Doheny Eye Inst, Los Angeles, CA USA.
[Pye, James; Lee, Edwin G.] Beaver Visitec Int, Waltham, MA USA.
RP Rhee, DJ (reprint author), 243 Charles St, Boston, MA 02114 USA.
EM Dougrhee@aol.com
OI Berry, Jesse/0000-0002-8907-9100
NR 10
TC 0
Z9 0
U1 0
U2 4
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1542-8877
J9 OPHTHAL SURG LAS IM
JI Ophthalmic Surg. Lasers Imaging
PD MAR-APR
PY 2011
VL 42
IS 2
DI 10.3928/15428877-20101124-01
PG 4
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 959PS
UT WOS:000305325900009
ER
PT J
AU Sun, JK
Aiello, LP
Cavallerano, JD
Stockman, M
Miller, KM
Qin, HJ
Beck, RW
Glassman, AR
AF Sun, Jennifer K.
Aiello, Lloyd Paul
Cavallerano, Jerry D.
Stockman, Margaret
Miller, Kellee M.
Qin, Haijing
Beck, Roy W.
Glassman, Adam R.
CA Diabetic Retinopathy Clinical Res
TI Visual Acuity Testing Using Autorefraction or Pinhole Occluder Compared
with a Manual Protocol Refraction in Individuals with Diabetes
SO OPHTHALMOLOGY
LA English
DT Article
ID COMPUTERIZED METHOD; POWER VECTORS; REPEATABILITY; RETINOPATHY;
ADAPTATION; ERROR
AB Purpose: To compare visual acuity (VA) scores obtained after autorefraction or using a pinhole occluder to scores obtained after refraction according to a standard clinical research protocol.
Design: Prospective, comparative case series.
Participants: One hundred ten study participants (209 eyes) with diabetes mellitus and a broad range of diabetic retinopathy severity and VA.
Methods: We measured VA after autorefraction by a Topcon KR-8000 autorefractor as well as after a Diabetic Retinopathy Clinical Research Network (DRCR.net) protocol manual refraction. The order of testing was randomized and examiners were masked to the source of each refraction. A second VA measurement, utilizing an identical DRCR.net manual refraction, was made in a subset of eyes (n = 144; 69%) to establish test-retest variability for comparison purposes. All eyes underwent VA testing using a pinhole occluder.
Main Outcome Measures: Best corrected VA as measured by the Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Test (E-ETDRS).
Results: In all eyes, the median E-ETDRS VA letter score (EVA) obtained after manual refraction (MR-EVA) was 69 (Snellen equivalent 20/40), ranging from 4 to 93 (20/800 to 20/16). The median MR-EVA was slightly better than the median EVA obtained after autorefraction (AR-EVA), with a median difference (AR-EVA - MR-EVA) of -1 letter (25th, 75th percentiles, -4, 2 letters). The absolute difference between AR-EVA and MR-EVA was similar to the test-retest variability of MR-EVA alone. In contrast, MR-EVA was better than EVA obtained using a pinhole occluder (PH-EVA; median PH-EVA - MR-EVA, -4 letters [-9, 0]), and had significantly less test-retest variability (P < 0.001). Generally, the spherical equivalent of autorefraction was slightly more hyperopic (or less myopic) than the spherical equivalent of manual refraction (median difference, +0.25 diopters [0, +0.63]).
Conclusions: Given the substantial time and effort required for training and certification of study protocol refractionists, and the similarity between AR-EVA and MR-EVA, further evaluation of autorefraction, but not pinhole occluder testing, as an alternative to the current clinical research gold standard of ETDRS protocol manual refraction in study participants with diabetic retinopathy is warranted.
C1 [Miller, Kellee M.; Qin, Haijing; Beck, Roy W.; Glassman, Adam R.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
[Sun, Jennifer K.; Aiello, Lloyd Paul; Cavallerano, Jerry D.; Stockman, Margaret] Harvard Univ, Sch Med, Beetham Eye Inst, Boston, MA USA.
[Sun, Jennifer K.; Aiello, Lloyd Paul; Cavallerano, Jerry D.; Stockman, Margaret] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Ophthalmol,Eye Res Sect, Boston, MA 02115 USA.
RP Miller, KM (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA.
EM drcrstat4@jaeb.org
FU National Eye Institute; National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health, Department of Health and
Human Services [EY14231, EY14229, EY018817]
FX Supported through a cooperative agreement from the National Eye
Institute and the National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health, Department of Health and
Human Services EY14231, EY14229, EY018817.
NR 16
TC 6
Z9 6
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2011
VL 118
IS 3
BP 537
EP 542
DI 10.1016/j.ophtha.2010.07.022
PG 6
WC Ophthalmology
SC Ophthalmology
GA 729QA
UT WOS:000287964400018
PM 20947171
ER
PT J
AU Litvack, JR
Mace, J
Smith, TL
AF Litvack, Jamie R.
Mace, Jess
Smith, Timothy L.
TI Role of Depression in Outcomes of Endoscopic Sinus Surgery
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
DE sinusitis; depression; quality of life; disease severity; endoscopic
sinus surgery; outcomes
ID QUALITY-OF-LIFE; PATIENT HEALTH QUESTIONNAIRE; CHRONIC RHINOSINUSITIS;
MYOCARDIAL-INFARCTION; HEART-FAILURE; PRIME-MD; SYMPTOMS; DISEASE;
IMPACT; SEVERITY
AB Objective. To prospectively measure the prevalence and effect of symptomatic depression on chronic rhinosinusitis (CRS) patients' quality of life (QOL), disease severity, and outcomes of endoscopic sinus surgery (ESS).
Study Design. Prospective cohort study.
Setting. Academic, tertiary care center.
Subjects and Methods. Seventy-six patients with CRS were enrolled prior to ESS and followed postoperatively for a mean (SD) of 13.3 (5.4) months. Lund-Mackay computed tomography score, Lund-Kennedy endoscopy score, Patient Health Questionnaire-9 (PHQ-9), 2 disease-specific QOL instruments (Rhinosinusitis Disability Index [RSDI] and Chronic Sinusitis Survey [CSS]), and 1 general QOL instrument (Medical Outcomes Study Short Form-36 [SF-36]) were measured. Differences in outcome scores were analyzed using univariate and multivariate analyses.
Results. Only 7 (9.2%) patients reported a history of depression, but 19 (25.0%) patients scored in the range of moderate or severe depression on the PHQ-9. Mean (SD) preoperative scores were significantly worse in depressed patients on the RSDI (62.7 [18.2] vs 45.3 [16.3]; P < .001) and 7 of 8 SF-36 domains (all P <= .011). Patients with depression significantly improved on both disease-specific QOL instruments (mean [SD] change; RSDI: 33.5 [24.7], P = .017; CSS: 25.0 [20.9], P = .012) and 3 SF-36 domains (all P <= .050). Postoperative change scores were not significantly different from patients without depression on the RSDI, CSS, or SF-36. Severity of depression significantly improved postoperatively in depressed patients (preoperative PHQ-9 scores: 13.4 [2.0] vs 6.1 [4.5], P = .017).
Conclusion. CRS patients with depression had worse baseline QOL than other CRS patients but experienced comparable postoperative improvement in QOL after ESS. Interestingly, depression severity significantly improved after ESS.
C1 [Mace, Jess; Smith, Timothy L.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Oregon Sinus Ctr, Portland, OR 97239 USA.
[Litvack, Jamie R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
RP Smith, TL (reprint author), Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Oregon Sinus Ctr, 3181 SW Sam Jackson Pk Rd,PV-01, Portland, OR 97239 USA.
EM smithtim@ohsu.edu
FU Oregon Health & Science University [T32 DC5945]; American Academy of
Otolaryngology-Head & Neck Surgery Foundation; NIH/NIDCD [R01 DC005805]
FX Dr. Litvack was supported by a T32 NIH Training Grant at Oregon Health &
Science University during this study (T32 DC5945). Partial funding was
supported for this project by the American Academy of
Otolaryngology-Head & Neck Surgery Foundation Health Service Research
Grant, 2008-09. Dr Smith and Mr Mace were grant funded by the NIH/NIDCD
R01 DC005805 (principal investigator: T.L. Smith).
NR 27
TC 31
Z9 32
U1 0
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
EI 1097-6817
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD MAR
PY 2011
VL 144
IS 3
BP 446
EP 451
DI 10.1177/0194599810391625
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 808RZ
UT WOS:000293997400020
PM 21493211
ER
PT J
AU Morasco, BJ
Gritzner, S
Lewis, L
Oldham, R
Turk, DC
Dobscha, SK
AF Morasco, Benjamin J.
Gritzner, Susan
Lewis, Lynsey
Oldham, Robert
Turk, Dennis C.
Dobscha, Steven K.
TI Systematic review of prevalence, correlates, and treatment outcomes for
chronic non-cancer pain in patients with comorbid substance use disorder
SO PAIN
LA English
DT Review
DE Chronic pain; Substance use disorder; Treatment outcomes; Opioids;
Systematic review; Quality of life
ID LOW-BACK-PAIN; CHRONIC NONMALIGNANT PAIN; TERM OPIOID THERAPY;
DRUG-RELATED BEHAVIORS; PRIMARY-CARE; IMMPACT RECOMMENDATIONS;
MEDICATION MISUSE; CLINICAL-TRIALS; ALCOHOL-ABUSE; RISK-FACTORS
AB Recent data suggest that comorbid substance use disorders (SUDs) are common among chronic non-cancer pain (CNCP) patients; however, prevalence rates vary across studies and findings are limited regarding treatment options for CNCP patients with comorbid SUD. The purpose of this systematic review is to assess the prevalence, associated demographic and clinical characteristics, and treatment outcomes for CNCP patients with comorbid SUD. We conducted searches from Ovid MEDLINE, PsychINFO, and PubMED from 1950 through February 2010 and retrieved the references. Thirty-eight studies met inclusion criteria and provided data that addressed our key questions. Three to forty-eight percent of CNCP patients have a current SUD. There are no demographic or clinical factors that consistently differentiate CNCP patients with comorbid SUD from patients without SUD, though SUD patients appear to be at greater risk for aberrant medication-related behaviors. CNCP patients with SUD are more likely to be prescribed opioid medications and at higher doses than CNCP patients without a history of SUD. CNCP patients with comorbid SUD do not significantly differ in their responses to treatment compared to CNCP patients without SUD, though the quality of this evidence is low. Limited data are available to identify predictors of treatment outcome. Although clinical experience and research suggests that SUDs are common among CNCP patients, only limited data are available to guide clinicians who treat this population. Research is needed to increase understanding of the prevalence, correlates, and responses to treatment of CNCP patients with comorbid SUDs. Published by Elsevier B. V. on behalf of International Association for the Study of Pain.
C1 [Morasco, Benjamin J.; Gritzner, Susan; Lewis, Lynsey; Oldham, Robert; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
[Morasco, Benjamin J.; Oldham, Robert; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA.
[Gritzner, Susan] Univ Pacific, Sch Profess Psychol, Stockton, CA 95211 USA.
[Turk, Dennis C.] Univ Washington Sch Med, Dept Anesthesiol & Pain Med, Seattle, WA USA.
[Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Med & Psychiat, Portland, OR USA.
RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM benjamin.morasco@va.gov
FU National Institute on Drug Abuse [K23DA023467]; Endo; Johnson Johnson;
Philips Respironics; National Institutes of Health; Eli Lilly; Empi;
Pfizer; SK LifeScience
FX This study was supported in part by award K23DA023467 from the National
Institute on Drug Abuse to Dr. Morasco. During the past 12 months, Dr.
Turk has received research support from Endo, Johnson & Johnson, Philips
Respironics, and the National Institutes of Health, and consulting fees
from Eli Lilly, Empi, Johnson & Johnson, Pfizer, Philips Respironics,
and SK LifeScience. He is also a Special Government Employee of the US
Food and Drug Administration. We appreciate the assistance of Mark
Helfand, M. D., Devan Kansagara, M. D., and Roger Chou, M. D., for help
in drafting or editing the key questions, Michele Freeman, M. P. H. for
technical assistance, and research librarians Rose Campbell and Andrew
Hamilton for developing the literature search strategies. The content of
this manuscript is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health, Department of Veterans Affairs, US Food and Drug Administration,
or another private entity.
NR 65
TC 48
Z9 50
U1 1
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD MAR
PY 2011
VL 152
IS 3
BP 488
EP 497
DI 10.1016/j.pain.2010.10.009
PG 10
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 719GZ
UT WOS:000287192200009
PM 21185119
ER
PT J
AU Sosenko, JM
Mahon, J
Rafkin, L
Lachin, JM
Krause-Steinrauf, H
Krischer, JP
Cuthbertson, D
Palmer, JP
Thompson, C
Greenbaum, CJ
Skyler, JS
AF Sosenko, Jay M.
Mahon, Jeffrey
Rafkin, Lisa
Lachin, John M.
Krause-Steinrauf, Heidi
Krischer, Jeffrey P.
Cuthbertson, David
Palmer, Jerry P.
Thompson, Clinton
Greenbaum, Carla J.
Skyler, Jay S.
CA Diabet Prevention Trial-Type 1 Grp
TrialNet Study Grp
TI A comparison of the baseline metabolic profiles between Diabetes
Prevention Trial-Type 1 and TrialNet Natural History Study participants
SO PEDIATRIC DIABETES
LA English
DT Article
DE C-peptide; glucose; prevention; trials; T1D
ID ISLET-CELL ANTIBODIES; INSULIN; MELLITUS; RISK; AUTOANTIBODIES;
SPECIFICITIES; RELATIVES; ANTIGEN; ONSET
AB Objective: We assessed whether differing autoantibody screening criteria for type 1 diabetes (T1D) prevention trials result in different baseline metabolic profiles of those who screen positive.
Methods: Diabetes Prevention Trial-Type 1 (DPT-1) participants were screened for islet cell autoantibodies, whereas TrialNet Natural History Study (TNNHS) participants were screened for biochemical autoantibodies. In both studies, those determined to be autoantibody positive underwent baseline oral glucose tolerance tests (OGTTs) in which glucose and C-peptide were measured.
Results: The percentage of those with an OGTT in the diabetic range was higher among the DPT-1 participants (10.0% of 956 vs. 6.4% of 645, p < 0.01). In a logistic regression analysis with adjustments for age and gender, the difference persisted (p < 0.01). Among those in the non-diabetic range (n = 860 for DPT-1 and n = 604 for the TNNHS), glucose levels were similar at all time points, except for higher fasting glucose levels in the TNNHS participants (p < 0.001). There was a higher percentage of impaired fasting glucose (IFG) in the TNNHS participants (10.9 vs. 6.7%, p < 0.01); however, with adjustments for age and gender, there was no longer a significant difference. There was no significant difference in the percentages with impaired glucose tolerance. C-peptide levels were much lower in the DPT-1 cohort at all OGTT time points (p < 0.001 for all).
Discussion: Differing criteria for autoantibody screening can result in marked differences in the baseline metabolic profiles of prospective participants of T1D prevention trials.
C1 [Sosenko, Jay M.] Univ Miami, Miller Sch Med, Dept Med, Div Endocrinol, Miami, FL 33101 USA.
[Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 3K7, Canada.
[Lachin, John M.; Krause-Steinrauf, Heidi; Thompson, Clinton] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[Krischer, Jeffrey P.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA.
[Cuthbertson, David] Univ S Florida, Pediatr Epidemiol Ctr, Tampa, FL USA.
[Palmer, Jerry P.] Univ Washington, Div Endocrinol & Metab, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Greenbaum, Carla J.] Benaroya Res Inst, Seattle, WA USA.
RP Sosenko, JM (reprint author), Univ Miami, Miller Sch Med, Dept Med, Div Endocrinol, POB 016960, Miami, FL 33101 USA.
EM jsosenko@med.miami.edu
RI Skyler, Jay/F-4211-2016;
OI Lachin, John/0000-0001-9838-2841
FU National Institutes of Health through the National Institute of Diabetes
and Digestive and Kidney Diseases; National Institute of Allergy and
Infectious Diseases; National Institute of Child Health and Human
Development; General Clinical Research Centers; Juvenile Diabetes
Research Foundation International; ADA
FX TrialNet is funded by the National Institutes of Health through the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institute of Allergy and Infectious Diseases, National
Institute of Child Health and Human Development, and General Clinical
Research Centers Program; the Juvenile Diabetes Research Foundation
International; and the ADA.
NR 17
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1399-543X
J9 PEDIATR DIABETES
JI Pediatr. Diabetes
PD MAR
PY 2011
VL 12
IS 2
BP 85
EP 90
DI 10.1111/j.1399-5448.2010.00662.x
PG 6
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA 726DZ
UT WOS:000287700300003
PM 20522170
ER
PT J
AU Rouhani, S
Meloney, L
Ahn, R
Nelson, BD
Burke, TF
AF Rouhani, Shada
Meloney, Laura
Ahn, Roy
Nelson, Brett D.
Burke, Thomas F.
TI Alternative Rehydration Methods: A Systematic Review and Lessons for
Resource-Limited Care
SO PEDIATRICS
LA English
DT Review
DE dehydration; critically ill children; diarrhea; international child
health; intravenous rehydration
ID INTRAOSSEOUS INFUSION; NASOGASTRIC REHYDRATION; INTRAVENOUS REHYDRATION;
ACUTE DIARRHEA; ACUTE GASTROENTERITIS; SEVERE DEHYDRATION;
RANDOMIZED-TRIAL; ORAL REHYDRATION; CHILDREN; RESUSCITATION
AB OBJECTIVE: Dehydration is a significant threat to the health of children worldwide and a major cause of death in resource-scarce settings. Although multiple studies have revealed that oral and intravenous (IV) methods for rehydration in nonsevere dehydration are nearly equally effective, little is known about effectiveness beyond these 2 techniques. With this systematic review we analyzed the effectiveness of nonoral and nonintravenous methods of rehydration.
METHODS: The Medline, Cochrane, Global Health, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched for articles on intraosseous (IO), nasogastric (NG), intraperitoneal (IP), subcutaneous (hypodermoclysis), and rectal (proctoclysis) rehydration through December 2009. Only human pediatric studies that included data on the effectiveness or complications of these methods were included.
RESULTS: The search identified 38 articles that met the inclusion criteria: 12 articles on NG, 16 on IO, 7 on IP, 3 on subcutaneous, and none on rectal rehydration. NG rehydration was as effective as IV rehydration for moderate-to-severe dehydration. IO rehydration was effective and easy to obtain, although only 1 randomized trial was identified. IP rehydration had some benefit for moderate dehydration, although none of the trials had control groups. Limited data were available on subcutaneous rehydration, and only 1 case series showed benefit.
CONCLUSIONS: NG rehydration should be considered second-line therapy, after oral rehydration, particularly in resource-limited environments. IO rehydration seems to be an effective alternative when IV access is not readily obtainable. Additional evidence is needed before IP and subcutaneous rehydration can be endorsed. Pediatrics 2011;127:e748-e757
C1 [Rouhani, Shada; Meloney, Laura; Ahn, Roy; Nelson, Brett D.; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA.
[Rouhani, Shada] Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Progra, Boston, MA 02115 USA.
[Ahn, Roy; Burke, Thomas F.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Nelson, Brett D.; Burke, Thomas F.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Nelson, Brett D.; Burke, Thomas F.] MassGen Hosp Children, Div Global Hlth, Boston, MA USA.
RP Rouhani, S (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, 5 Emerson Pl,Suite 100, Boston, MA 02114 USA.
EM srouhani@partners.org
OI Nelson, Brett/0000-0002-5049-1798
NR 48
TC 13
Z9 13
U1 1
U2 4
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2011
VL 127
IS 3
BP E748
EP E757
DI 10.1542/peds.2010-0952
PG 10
WC Pediatrics
SC Pediatrics
GA 728AI
UT WOS:000287845400027
PM 21321023
ER
PT J
AU Dai, TH
Kharkwal, GB
Zhao, J
St Denis, TG
Wu, QH
Xia, YM
Huang, LY
Sharma, SK
d'Enfert, C
Hamblin, MR
AF Dai, Tianhong
Kharkwal, Gitika B.
Zhao, Jie
St Denis, Tyler G.
Wu, Qiuhe
Xia, Yumin
Huang, Liyi
Sharma, Sulbha K.
d'Enfert, Christophe
Hamblin, Michael R.
TI Ultraviolet-C Light for Treatment of Candida albicans Burn Infection in
Mice
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID PSEUDOMONAS-AERUGINOSA; WOUND-INFECTION; MICROORGANISMS; ONYCHOMYCOSIS;
COLONIZATION; DISINFECTION; INACTIVATION; BIOFILMS
AB Burn patients are at high risk of invasive fungal infections, which are a leading cause of morbidity, mortality, and related expense exacerbated by the emergence of drug resistant fungal strains. In this study, we investigated the use of UVC light (254 nm) for the treatment of yeast Candida albicans infection in mouse third degree burns. In vitro studies demonstrated that UVC could selectively kill the pathogenic C. albicans compared with a normal mouse keratinocyte cell line in a light exposure dependent manner. A mouse model of chronic C. albicans infection in non-lethal third degree burns was developed. The C. albicans strain was stably transformed with a version of the Gaussia princeps luciferase gene that allowed real-time bioluminescence imaging of the progression of C. albicans infection. UVC treatment with a single exposure carried out on day 0 (30 min postinfection) gave an average 2.16-log(10)-unit (99.2%) loss of fungal luminescence when 2.92 J cm-2 UVC had been delivered, while UVC 24 h postinfection gave 1.94-log(10)-unit (95.8%) reduction of fungal luminescence after 6.48 J cm-2. Statistical analysis demonstrated that UVC treatment carried out on both day 0 and day 1 significantly reduced the fungal bioburden of infected burns. UVC was found to be superior to a topical antifungal drug, nystatin cream. UVC was tested on normal mouse skin and no gross damage was observed 24 h after 6.48 J cm-2. DNA lesions (cyclobutane pyrimidine dimers) were observed by immunofluorescence in normal mouse skin immediately after a 6.48 J cm-2 UVC exposure, but the lesions were extensively repaired at 24 h after UVC exposure.
C1 [Dai, Tianhong; Kharkwal, Gitika B.; Zhao, Jie; St Denis, Tyler G.; Wu, Qiuhe; Xia, Yumin; Huang, Liyi; Sharma, Sulbha K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Dai, Tianhong; Kharkwal, Gitika B.; Wu, Qiuhe; Huang, Liyi; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[St Denis, Tyler G.] John Jay High Sch, Cross River, NY USA.
[Wu, Qiuhe] Shandong Univ, Jinan Cent Hosp, Jinan 250100, Peoples R China.
[Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning, Peoples R China.
[d'Enfert, Christophe] Unite Biol & Pathogenicite Fong, Paris, France.
[d'Enfert, Christophe] USC2019, INRA, Paris, France.
[Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM hamblin@helix.mgh.harvard.edu
OI d'Enfert, Christophe/0000-0002-6235-3886; Hamblin,
Michael/0000-0001-6431-4605
FU NIH [RO1 AI050875]; US Air Force [FA9550-04-1-0079]; Bullock-Wellman
Fellowship Award; Airlift Research Foundation [109421]
FX This work was supported by the NIH (grant RO1 AI050875 to M. R. H.) and
US Air Force MFEL Program (FA9550-04-1-0079). T. D. was partially
supported by a Bullock-Wellman Fellowship Award and an Airlift Research
Foundation Extremity Trauma Research Grant (grant 109421).
NR 33
TC 12
Z9 13
U1 1
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0031-8655
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD MAR-APR
PY 2011
VL 87
IS 2
BP 342
EP 349
DI 10.1111/j.1751-1097.2011.00886.x
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 728JU
UT WOS:000287871200012
PM 21208209
ER
PT J
AU Goebel, M
Stengel, A
Lambrecht, NWG
Sachs, G
AF Goebel, M.
Stengel, A.
Lambrecht, N. W. G.
Sachs, G.
TI Selective gene expression by rat gastric corpus epithelium
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE transcriptome; stomach
ID PROTEIN DISULFIDE-ISOMERASE; ACID-SECRETION; HELICOBACTER-PYLORI;
PARIETAL-CELLS; MESSENGER-RNA; MOLECULAR CHARACTERIZATION;
ALCOHOL-DEHYDROGENASE; OXYNTIC MUCOSA; MOUSE STOMACH; ECL CELLS
AB Goebel M, Stengel A, Lambrecht NW, Sachs G. Selective gene expression by rat gastric corpus epithelium. Physiol Genomics 43: 237-254, 2011. First published December 21, 2010; doi:10.1152/physiolgenomics.00193.2010.-The gastrointestinal (GI) tract is divided into several segments that have distinct functional properties, largely absorptive. The gastric corpus is the only segment thought of as largely secretory. Microarray hybridization of the gastric corpus mucosal epithelial cells was used to compare gene expression with other segments of the columnar GI tract followed by statistical data subtraction to identify genes selectively expressed by the rat gastric corpus mucosa. This provides a means of identifying less obvious specific functions of the corpus in addition to its secretion-related genes. For example, important properties found by this GI tract comparative transcriptome reflect the energy demand of acid secretion, a role in lipid metabolism, the large variety of resident neuroendocrine cells, responses to damaging agents and transcription factors defining differentiation of its epithelium. In terms of overlap of gastric corpus genes with the rest of the GI tract, the distal small bowel appears to express many of the gastric corpus genes in contrast to proximal small and large bowel. This differential map of gene expression by the gastric corpus epithelium will allow a more detailed description of major properties of the gastric corpus and may lead to the discovery of gastric corpus cell differentiation genes and those mis-regulated in gastric carcinomas.
C1 [Goebel, M.; Stengel, A.; Sachs, G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Lambrecht, N. W. G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Lambrecht, N. W. G.; Sachs, G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
[Sachs, G.] W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Los Angeles, CA 90073 USA.
RP Lambrecht, NWG (reprint author), VA Long Beach Hlth Care Syst, Bldg 1,Rm 200M,E 7th St 09-113, Long Beach, CA 90822 USA.
EM Nils.Lambrecht2@va.gov
OI Lambrecht, Nils/0000-0002-1275-1384
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK-058333, DK-053642]; US Department of Veterans Affairs; German
Research Foundation [STE 1765/1-1, GO 1718/1-1]
FX This work was supported by National Institute of Diabetes and Digestive
and Kidney Diseases Grants DK-058333 (G. Sachs) and DK-053642 (G.
Sachs), the US Department of Veterans Affairs (G. Sachs), and German
Research Foundation Grants STE 1765/1-1 (A. Stengel) and Grant GO
1718/1-1 (M. Goebel).
NR 92
TC 5
Z9 5
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD MAR
PY 2011
VL 43
IS 5
BP 237
EP 254
DI 10.1152/physiolgenomics.00193.2010
PG 18
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 735ZI
UT WOS:000288458900001
PM 21177383
ER
PT J
AU Kim, S
Putrino, D
Ghosh, S
Brown, EN
AF Kim, Sanggyun
Putrino, David
Ghosh, Soumya
Brown, Emery N.
TI A Granger Causality Measure for Point Process Models of Ensemble Neural
Spiking Activity
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID TRAIN DATA-ANALYSIS; SPATIOTEMPORAL CORRELATIONS; STATISTICAL
ASSESSMENT; NEURONS; NETWORK; CONNECTIVITY; CORTEX
AB The ability to identify directional interactions that occur among multiple neurons in the brain is crucial to an understanding of how groups of neurons cooperate in order to generate specific brain functions. However, an optimal method of assessing these interactions has not been established. Granger causality has proven to be an effective method for the analysis of the directional interactions between multiple sets of continuous-valued data, but cannot be applied to neural spike train recordings due to their discrete nature. This paper proposes a point process framework that enables Granger causality to be applied to point process data such as neural spike trains. The proposed framework uses the point process likelihood function to relate a neuron's spiking probability to possible covariates, such as its own spiking history and the concurrent activity of simultaneously recorded neurons. Granger causality is assessed based on the relative reduction of the point process likelihood of one neuron obtained excluding one of its covariates compared to the likelihood obtained using all of its covariates. The method was tested on simulated data, and then applied to neural activity recorded from the primary motor cortex (MI) of a Felis catus subject. The interactions present in the simulated data were predicted with a high degree of accuracy, and when applied to the real neural data, the proposed method identified causal relationships between many of the recorded neurons. This paper proposes a novel method that successfully applies Granger causality to point process data, and has the potential to provide unique physiological insights when applied to neural spike trains.
C1 [Kim, Sanggyun; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Putrino, David; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Ghosh, Soumya] Univ Western Australia, QEII Med Ctr, Ctr Neuromuscular & Neurol Disorders, Nedlands, WA 6009, Australia.
[Brown, Emery N.] Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Kim, S (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA.
EM sgkim@neurostat.mit.edu
OI Putrino, David/0000-0002-2232-3324
FU NIH [DP1-OD003646, R01-EB006385]
FX This work was supported by NIH Grants DP1-OD003646 and
R01-EB006385(http://www.nih.gov). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
TC 55
Z9 55
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAR
PY 2011
VL 7
IS 3
AR e1001110
DI 10.1371/journal.pcbi.1001110
PG 13
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 743CU
UT WOS:000288995500017
PM 21455283
ER
PT J
AU Krishnaswamy, P
Brown, EN
Herr, HM
AF Krishnaswamy, Pavitra
Brown, Emery N.
Herr, Hugh M.
TI Human Leg Model Predicts Ankle Muscle-Tendon Morphology, State, Roles
and Energetics in Walking
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID SKELETAL-MUSCLE; MOTOR; BIOMECHANICS; ELECTROMYOGRAPHY; EXOSKELETONS;
LOCOMOTION; EFFICIENCY; SIGNAL
AB A common feature in biological neuromuscular systems is the redundancy in joint actuation. Understanding how these redundancies are resolved in typical joint movements has been a long-standing problem in biomechanics, neuroscience and prosthetics. Many empirical studies have uncovered neural, mechanical and energetic aspects of how humans resolve these degrees of freedom to actuate leg joints for common tasks like walking. However, a unifying theoretical framework that explains the many independent empirical observations and predicts individual muscle and tendon contributions to joint actuation is yet to be established. Here we develop a computational framework to address how the ankle joint actuation problem is resolved by the neuromuscular system in walking. Our framework is founded upon the proposal that a consideration of both neural control and leg muscle-tendon morphology is critical to obtain predictive, mechanistic insight into individual muscle and tendon contributions to joint actuation. We examine kinetic, kinematic and electromyographic data from healthy walking subjects to find that human leg muscle-tendon morphology and neural activations enable a metabolically optimal realization of biological ankle mechanics in walking. This optimal realization (a) corresponds to independent empirical observations of operation and performance of the soleus and gastrocnemius muscles, (b) gives rise to an efficient load-sharing amongst ankle muscle-tendon units and (c) causes soleus and gastrocnemius muscle fibers to take on distinct mechanical roles of force generation and power production at the end of stance phase in walking. The framework outlined here suggests that the dynamical interplay between leg structure and neural control may be key to the high walking economy of humans, and has implications as a means to obtain insight into empirically inaccessible features of individual muscle and tendons in biomechanical tasks.
C1 [Krishnaswamy, Pavitra; Brown, Emery N.; Herr, Hugh M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Herr, Hugh M.] MIT, Media Lab, Cambridge, MA 02139 USA.
RP Krishnaswamy, P (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM hherr@mit.edu
FU NIH [DP1 OD003646]; MIT Media Lab [2736448, 6895867]
FX This work was supported by the NIH Pioneer Award DP1 OD003646 (to ENB)
and the MIT Media Lab (Consortia Accounts 2736448 and 6895867). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 41
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U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAR
PY 2011
VL 7
IS 3
AR e1001107
DI 10.1371/journal.pcbi.1001107
PG 16
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 743CU
UT WOS:000288995500014
PM 21445231
ER
PT J
AU Neale, BM
Rivas, MA
Voight, BF
Altshuler, D
Devlin, B
Orho-Melander, M
Kathiresan, S
Purcell, SM
Roeder, K
Daly, MJ
AF Neale, Benjamin M.
Rivas, Manuel A.
Voight, Benjamin F.
Altshuler, David
Devlin, Bernie
Orho-Melander, Marju
Kathiresan, Sekar
Purcell, Shaun M.
Roeder, Kathryn
Daly, Mark J.
TI Testing for an Unusual Distribution of Rare Variants
SO PLOS GENETICS
LA English
DT Article
ID AMINO-ACID SUBSTITUTIONS; GENOME-WIDE ASSOCIATION; COMMON DISEASES;
PLASMA-LEVELS; CHOLESTEROL; ALLELES; PCSK9; POLYMORPHISMS; MUTATIONS;
GENES
AB Technological advances make it possible to use high-throughput sequencing as a primary discovery tool of medical genetics, specifically for assaying rare variation. Still this approach faces the analytic challenge that the influence of very rare variants can only be evaluated effectively as a group. A further complication is that any given rare variant could have no effect, could increase risk, or could be protective. We propose here the C-alpha test statistic as a novel approach for testing for the presence of this mixture of effects across a set of rare variants. Unlike existing burden tests, C-alpha, by testing the variance rather than the mean, maintains consistent power when the target set contains both risk and protective variants. Through simulations and analysis of case/control data, we demonstrate good power relative to existing methods that assess the burden of rare variants in individuals.
C1 [Neale, Benjamin M.; Rivas, Manuel A.; Voight, Benjamin F.; Kathiresan, Sekar; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Neale, Benjamin M.; Rivas, Manuel A.; Voight, Benjamin F.; Altshuler, David; Kathiresan, Sekar; Purcell, Shaun M.; Daly, Mark J.] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Devlin, Bernie] Univ Pittsburgh Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Orho-Melander, Marju] Malmo Univ Hosp, Dept Clin Sci Malmo Diabet & Cardiovasc Dis, Genet Epidemiol CRC, Malmo, Sweden.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Purcell, Shaun M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
RP Neale, BM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM bneale@broadinstitute.org; Kathryn.roeder@gmail.com;
mjdaly@chgr.mgh.harvard.edu
RI Voight, Benjamin/F-1775-2011; Sincan, Murat /A-3794-2010; Altshuler,
David/A-4476-2009
OI Altshuler, David/0000-0002-7250-4107
FU NIH [HL087676, EY11309, NS059727, DK072041]; NIH/NEIHS [NS059727];
NIH/NHBLI [HL087676, DK072041]; NIH/NIMH [NS059727, MH057881, MH089025,
MH089208]; Autism Speaks
FX This work was supported by NIH grants HL087676, EY11309, NS059727, and
DK072041; NIH/NEIHS grant NS059727; NIH/NHBLI grants DK072041 and
HL087676; NIH/NIMH grants NS059727, MH057881, MH089025, and MH089208;
and Autism Speaks grant for the Autism Genome Project. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 29
TC 258
Z9 269
U1 4
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2011
VL 7
IS 3
AR e1001322
DI 10.1371/journal.pgen.1001322
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 743DD
UT WOS:000288996600004
PM 21408211
ER
PT J
AU Speliotes, EK
Yerges-Armstrong, LM
Wu, J
Hernaez, R
Kim, LJ
Palmer, CD
Gudnason, V
Eiriksdottir, G
Garcia, ME
Launer, LJ
Nalls, MA
Clark, JM
Mitchell, BD
Shuldiner, AR
Butler, JL
Tomas, M
Hoffmann, U
Hwang, SJ
Massaro, JM
O'Donnell, CJ
Sahani, DV
Salomaa, V
Schadt, EE
Schwartz, SM
Siscovick, DS
Voight, BF
Carr, JJ
Feitosa, MF
Harris, TB
Fox, CS
Smith, AV
Kao, WHL
Hirschhorn, JN
Borecki, IB
AF Speliotes, Elizabeth K.
Yerges-Armstrong, Laura M.
Wu, Jun
Hernaez, Ruben
Kim, Lauren J.
Palmer, Cameron D.
Gudnason, Vilmundur
Eiriksdottir, Gudny
Garcia, Melissa E.
Launer, Lenore J.
Nalls, Michael A.
Clark, Jeanne M.
Mitchell, Braxton D.
Shuldiner, Alan R.
Butler, Johannah L.
Tomas, Marta
Hoffmann, Udo
Hwang, Shih-Jen
Massaro, Joseph M.
O'Donnell, Christopher J.
Sahani, Dushyant V.
Salomaa, Veikko
Schadt, Eric E.
Schwartz, Stephen M.
Siscovick, David S.
Voight, Benjamin F.
Carr, J. Jeffrey
Feitosa, Mary F.
Harris, Tamara B.
Fox, Caroline S.
Smith, Albert V.
Kao, W. H. Linda
Hirschhorn, Joel N.
Borecki, Ingrid B.
CA NASH CRN
GIANT Consortium
MAGIC Investigators
GOLD Consortium
TI Genome-Wide Association Analysis Identifies Variants Associated with
Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic
Traits
SO PLOS GENETICS
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; TRIGLYCERIDE LEVELS; LOCI; HEART; RISK; DESIGN;
ADULTS; STEATOHEPATITIS; PNPLA3; SUSCEPTIBILITY
AB Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (similar to 26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and similar to 2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<56 10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.
C1 [Speliotes, Elizabeth K.; Butler, Johannah L.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.; Butler, Johannah L.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Speliotes, Elizabeth K.; Voight, Benjamin F.; Hirschhorn, Joel N.] Broad Inst, Cambridge, MA USA.
[Yerges-Armstrong, Laura M.; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD USA.
[Wu, Jun; Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
[Hernaez, Ruben; Clark, Jeanne M.; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hernaez, Ruben; Clark, Jeanne M.] Johns Hopkins Univ Hosp, Div Gen Internal Med, Baltimore, MD 21287 USA.
[Hernaez, Ruben] Washington Hosp Ctr, Dept Internal Med, Washington, DC USA.
[Kim, Lauren J.; Garcia, Melissa E.; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Palmer, Cameron D.; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Palmer, Cameron D.; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Palmer, Cameron D.; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Gudnason, Vilmundur; Eiriksdottir, Gudny; Smith, Albert V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Nalls, Michael A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Clark, Jeanne M.; Kao, W. H. Linda] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, GRECC, Baltimore, MD 21218 USA.
[Tomas, Marta] Inst Municipal Invest Med, E-08003 Barcelona, Spain.
[Tomas, Marta] CIBER Epidemiol & Salud Publ, Barcelona, Spain.
[Hoffmann, Udo; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hoffmann, Udo; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Hwang, Shih-Jen; Massaro, Joseph M.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Massaro, Joseph M.] Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Salomaa, Veikko] Natl Publ Hlth Inst, Chron Dis Epidemiol Unit, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
[Schadt, Eric E.] Pacific Biosci, Menlo Pk, CA USA.
[Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Carr, J. Jeffrey] Wake Forest Univ Sch Med, Dept Radiol Sci, Winston Salem, NC USA.
[Carr, J. Jeffrey] Wake Forest Univ Sch Med, Dept Internal Med Cardiol, Winston Salem, NC USA.
[Carr, J. Jeffrey] Wake Forest Univ Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Speliotes, EK (reprint author), Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
EM espeliot@med.umich.edu; iborecki@wustl.edu
RI Ripatti, Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Meitinger,
Thomas/O-1318-2015; Prokopenko, Inga/H-3241-2014; Macciardi,
Fabio/N-3768-2014; Aben, Katja/G-9686-2016; Carr, John/A-1938-2012;
Smith, Albert/K-5150-2015; kinnunen, leena/B-7059-2012; Bochud,
Murielle/A-3981-2010; Visvikis-Siest, Sophie/H-2324-2014; Schwarz,
Peter/B-5127-2013; Naitza, Silvia/D-5620-2017; Feitosa,
Mary/K-8044-2012; Colaus, PsyColaus/K-6607-2013; Hernaez,
Ruben/C-4039-2014; Kiemeney, Lambertus/D-3357-2009; Singleton,
Andrew/C-3010-2009; Voight, Benjamin/F-1775-2011; Brunner,
Eric/H-2114-2011; Ridderstrale, Martin/F-7678-2012; Elliott,
Amanda/G-5120-2012; Rudan, Igor/I-1467-2012; Palmer, Lyle/K-3196-2014;
Witte, Daniel/C-1722-2008; Gudnason, Vilmundur/K-6885-2015;
OI Ripatti, Samuli/0000-0002-0504-1202; Polasek, Ozren/0000-0002-5765-1862;
Prokopenko, Inga/0000-0003-1624-7457; Macciardi,
Fabio/0000-0003-0537-4266; Aben, Katja/0000-0002-0214-2147; Carr,
John/0000-0002-4398-8237; Smith, Albert/0000-0003-1942-5845; kinnunen,
leena/0000-0001-8739-4812; Bochud, Murielle/0000-0002-5727-0218;
Visvikis-Siest, Sophie/0000-0001-8104-8425; Schwarz,
Peter/0000-0001-6317-7880; Feitosa, Mary/0000-0002-0933-2410; Seedorf,
Udo/0000-0003-4652-5358; Massaro, Joseph/0000-0002-2682-4812; Thiering,
Elisabeth/0000-0002-5429-9584; Lango Allen, Hana/0000-0002-7803-8688;
Willems van Dijk, Ko/0000-0002-2172-7394; Esko,
Tonu/0000-0003-1982-6569; Pichler, Irene/0000-0001-8251-0757; Magi,
Reedik/0000-0002-2964-6011; Kivimaki, Mika/0000-0002-4699-5627; Hernaez,
Ruben/0000-0002-1518-4020; Kiemeney, Lambertus/0000-0002-2368-1326;
Rudan, Igor/0000-0001-6993-6884; Palmer, Lyle/0000-0002-1628-3055;
Witte, Daniel/0000-0002-0769-2922; Gudnason,
Vilmundur/0000-0001-5696-0084; Zgaga, Lina/0000-0003-4089-9703; Zeggini,
Eleftheria/0000-0003-4238-659X; Luben, Robert/0000-0002-5088-6343;
Scherag, Andre/0000-0002-9406-4704; Melzer, David/0000-0002-0170-3838;
Forouhi, Nita/0000-0002-5041-248X; John, Ulrich/0000-0003-0587-5298;
Jorgensen, Torben/0000-0001-9453-2830; Watkins,
Hugh/0000-0002-5287-9016; Visscher, Peter/0000-0002-2143-8760; Marmot,
Michael/0000-0002-2431-6419; Mitchell, Braxton/0000-0003-4920-4744;
Ouwehand, Willem/0000-0002-7744-1790; Lawlor, Debbie
A/0000-0002-6793-2262; Johansson, Asa/0000-0002-2915-4498; de Geus,
Eco/0000-0001-6022-2666
FU NIH [T32 DK07191-32, F32 DK079466-01, NIH K23DK080145-01, R01DK075787,
N01-AG-12100, K01 DK067207, R01 AG18728, R01HL088119, U01 HL72515, U01
HL084756, T32AG000262, F32AR059469]; Icelandic Heart Association;
Althingi (the Icelandic Parliament); Diabetes Research and Training
Center of Maryland [P60 DK079637]; Nutrition and Obesity Research Center
of Maryland [P30DK072488]; American Diabetes Association [7-07-MN-08];
NIDDK [R01DK075681]; NHLBI [R01HL087700]; National Heart, Lung, and
Blood Institute [N01-HC-25195]; Affymetrix for genotyping services
[N02-HL-6-4278]; National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) [U01DK061718, U01DK061728, U01DK061731, U01DK061732,
U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713];
General Clinical Research Centers or Clinical and Translational Science
[UL1RR024989, M01RR000750, M01RR00188, ULRR02413101, M01RR000827,
UL1RR02501401, M01RR000065, M01RR020359]; US National Institutes of
Health (NIH); National Heart, Lung, and Blood Institute; Generalitat de
Catalunya [2007BP-B100068]; Red HERACLES, ISCIII [RD06/0009]
FX This work was partially supported by NIH grants T32 DK07191-32 to Daniel
Podolsky (for EKS), F32 DK079466-01 to EKS, NIH K23DK080145-01 to EKS,
and R01DK075787 to JNH. The AGES-Reykjavik Study is funded by NIH
contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd
(the Icelandic Heart Association), and the Althingi (the Icelandic
Parliament). The Old Order Amish Study was supported by NIH research
grants K01 DK067207, R01 AG18728, R01HL088119, U01 HL72515, and U01
HL084756. Partial funding was also provided by the Diabetes Research and
Training Center of Maryland (P60 DK079637) and the Nutrition and Obesity
Research Center of Maryland (P30DK072488). LMY-A was supported by NIH
training grants T32AG000262 and F32AR059469. RH was supported by the
American Diabetes Association Mentor-Based Postdoctoral Fellowship
Program (7-07-MN-08). The NHLBI Family Heart Study was supported by
NIDDK R01DK075681 (to IBB) and NHLBI R01HL087700. This research was
conducted in part using data and resources from the Framingham Heart
Study of the National Heart Lung and Blood Institute of the National
Institutes of Health and Boston University School of Medicine. The
analyses reflect intellectual input and resource development from the
Framingham Heart Study investigators participating in the SNP Health
Association Resource (SHARe) project. This work was partially supported
by the National Heart, Lung, and Blood Institute's Framingham Heart
Study (Contract No. N01-HC-25195) and its contract with Affymetrix for
genotyping services (Contract No. N02-HL-6-4278). The Nonalcoholic
Steatohepatitis Clinical Research Network (NASH CRN) is supported by the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
(grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734,
U01DK061737, U01DK061738, U01DK061730, U01DK061713). Several clinical
centers use support from General Clinical Research Centers or Clinical
and Translational Science Awards in conduct of NASH CRN Studies (grants
UL1RR024989, M01RR000750, M01RR00188, ULRR02413101, M01RR000827,
UL1RR02501401, M01RR000065, M01RR020359). The MIGen study was funded by
the US National Institutes of Health (NIH) and National Heart, Lung, and
Blood Institute's STAMPEED genomics research program. MT was supported
by the Beatriu de Pinos postdoctoral fellowship, Generalitat de
Catalunya (2007BP-B100068, MT), and Red HERACLES, ISCIII (RD06/0009).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 50
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U1 2
U2 49
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2011
VL 7
IS 3
AR e1001324
DI 10.1371/journal.pgen.1001324
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 743DD
UT WOS:000288996600006
PM 21423719
ER
PT J
AU Colantonio, AD
Bimber, BN
Neidermyer, WJ
Reeves, RK
Alter, G
Altfeld, M
Johnson, RP
Carrington, M
O'Connor, DH
Evans, DT
AF Colantonio, Arnaud D.
Bimber, Benjamin N.
Neidermyer, William J., Jr.
Reeves, R. Keith
Alter, Galit
Altfeld, Marcus
Johnson, R. Paul
Carrington, Mary
O'Connor, David H.
Evans, David T.
TI KIR Polymorphisms Modulate Peptide-Dependent Binding to an MHC Class I
Ligand with a Bw6 Motif
SO PLOS PATHOGENS
LA English
DT Article
ID NATURAL-KILLER-CELLS; IMMUNOGLOBULIN-LIKE RECEPTOR; SIMIAN
IMMUNODEFICIENCY VIRUS; SELECTIVE DOWN-REGULATION; HLA-B; INHIBITORY
RECEPTORS; RHESUS MACAQUES; CRYSTAL-STRUCTURE; CUTTING EDGE; HEPATITIS-C
AB Molecular interactions between killer immunoglobulin-like receptors (KIRs) and their MHC class I ligands play a central role in the regulation of natural killer (NK) cell responses to viral pathogens and tumors. Here we identify Mamu-A1*00201 (Mamu-A*02), a common MHC class I molecule in the rhesus macaque with a canonical Bw6 motif, as a ligand for Mamu-KIR3DL05. Mamu-A1*00201 tetramers folded with certain SIV peptides, but not others, directly stained primary NK cells and Jurkat cells expressing multiple allotypes of Mamu-KIR3DL05. Differences in binding avidity were associated with polymorphisms in the D0 and D1 domains of Mamu-KIR3DL05, whereas differences in peptide-selectivity mapped to the D1 domain. The reciprocal exchange of the third predicted MHC class I-contact loop of the D1 domain switched the specificity of two Mamu-KIR3DL05 allotypes for different Mamu-A1*00201-peptide complexes. Consistent with the function of an inhibitory KIR, incubation of lymphocytes from Mamu-KIR3DL05(+) macaques with target cells expressing Mamu-A1*00201 suppressed the degranulation of tetramer-positive NK cells. These observations reveal a previously unappreciated role for D1 polymorphisms in determining the selectivity of KIRs for MHC class I-bound peptides, and identify the first functional KIR-MHC class I interaction in the rhesus macaque. The modulation of KIR-MHC class I interactions by viral peptides has important implications to pathogenesis, since it suggests that the immunodeficiency viruses, and potentially other types of viruses and tumors, may acquire changes in epitopes that increase the affinity of certain MHC class I ligands for inhibitory KIRs to prevent the activation of specific NK cell subsets.
C1 [Colantonio, Arnaud D.; Neidermyer, William J., Jr.; Evans, David T.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA.
[Bimber, Benjamin N.; O'Connor, David H.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Dept Pathol & Lab Med, Madison, WI USA.
[Reeves, R. Keith; Johnson, R. Paul] New England Primate Res Ctr, Div Immunol, Southborough, MA USA.
[Alter, Galit; Altfeld, Marcus; Johnson, R. Paul; Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Alter, Galit; Altfeld, Marcus; Johnson, R. Paul; Carrington, Mary] Harvard Univ, Boston, MA 02115 USA.
[Carrington, Mary] NCI Frederick, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
RP Colantonio, AD (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA.
EM devans@hms.harvard.edu
OI o'connor, david/0000-0003-2139-470X
FU Public Health Service [AI063993, AI071306, RR000168]; Elizabeth Glaser
Pediatric AIDS Foundation; NIH [HHSN261200800001E]
FX This work was supported by Public Health Service grants AI063993,
AI071306 and RR000168. DTE is an Elizabeth Glaser Scientist supported by
the Elizabeth Glaser Pediatric AIDS Foundation. This project was also
supported in part by intramural NIH funding to the NCI under contract
number HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the DHHS, nor does mention
of trade names, commercial products, or organizations imply endorsement
by the U.S. Government. The funders had no role in the study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 64
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Z9 25
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2011
VL 7
IS 3
AR e1001316
DI 10.1371/journal.ppat.1001316
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 743CQ
UT WOS:000288994900010
PM 21423672
ER
PT J
AU Chan, WM
Dicianno, BE
AF Chan, Wendy M.
Dicianno, Brad E.
TI Virtual Socialization in Adults With Spina Bifida
SO PM&R
LA English
DT Article
ID QUALITY-OF-LIFE; YOUNG-ADULTS; HYDROCEPHALUS; ADOLESCENTS; ADJUSTMENT;
DISABILITY; MOBILITY; CHILDREN; HEALTH; WORLD
AB Objective: To use spina bifida (SB) as a model of chronic physical disability to study the associations of virtual socialization, friendships, and quality of life (QOL) in adults.
Design: Cross-sectional survey.
Setting: Subjects were recruited from residential living facilities, outpatient clinics, and the University of Pittsburgh Medical Center (UPMC) research registry.
Patients: Inclusion criteria were age between 18 and 80 years and clinical diagnoses of SB cystica (myelomeningocele) and hydrocephalus. The exclusion criterion was the diagnosis of SB occulta. Sixty-three eligible adults were enrolled, and all completed the study.
Methods: The survey via questionnaire was performed in person or over the telephone.
Main Outcome Measurements: Data collected included the World Health Organization's Medical Outcomes Study 26-item Short Form, Economic Self-Sufficiency from the Craig Handicap Assessment and Reporting Technique Short Form, virtual socializing habits, and number of friends. Three linear regression models were performed, each with a unique dependent variable: number of friends, psychological QOL, or social QOL. The following independent variables were included in all models: age, gender, ethnicity, economic self-sufficiency, marital status, education level, lesion level, health status, user group, collection method, and time spent virtually socializing. In addition, each regression model included the dependent variables from the other 2 models in its independent variables.
Results: Increased degree of virtual socialization (VS) was associated with a greater number of friends (P = .003, r = .684). Mean (standard deviation) numbers of friends by VS groups were the following: users, n = 4.9 +/- 2.7; semi-users, n = 3.8 +/- 2.7; and nonusers, n = 2.1 +/- 2.3, which represent a 2.3 times greater number of friends between the users and nonusers. The effect of virtual socialization on QOL was also positive, however, not statistically significant.
Conclusions: People with chronic physical disabilities, such as SB, are at high risk for peer rejection and long-term social avoidance. Users of the most immersive forms of virtual socialization, have more real world friends than both semi-users and nonusers. Any form of VS, whether immersive or real time, may improve the opportunity for meaningful social encounters. Prospective intervention studies are needed to elucidate whether a causal positive relationship between virtual socialization and friendships exists. Further research is needed to clarify virtual socialization's impact on QOL; however, the upward trend in all 4 domains of QOL across user groups suggests similar potential benefits. PM R 2011;3:219-225
C1 [Dicianno, Brad E.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Adult Spina Bifida Clin, Pittsburgh, PA 15260 USA.
[Dicianno, Brad E.] VA Pittsburgh HealthCare Syst, Pittsburgh, PA USA.
[Chan, Wendy M.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA.
RP Dicianno, BE (reprint author), Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Adult Spina Bifida Clin, 201 Kaufmann Bldg,3471 5th Ave, Pittsburgh, PA 15260 USA.
EM dicianno@pitt.edu
OI Dicianno, Brad/0000-0003-0738-0192
FU Human Engineering Research Laboratories
FX This research benefited from the support of Annmarie Kelleher MS, OTR/L,
ATP, CCRP, and Stacy Eckstein BS, MT(ASCP) from the Human Engineering
Research Laboratories.
NR 38
TC 4
Z9 4
U1 3
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAR
PY 2011
VL 3
IS 3
BP 219
EP 225
DI 10.1016/j.pmrj.2010.12.002
PG 7
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 961AX
UT WOS:000305437400006
PM 21402368
ER
PT J
AU Nguyen, RT
Borg-Stein, J
McInnis, K
AF Nguyen, Rosalyn T.
Borg-Stein, Joanne
McInnis, Kelly
TI Applications of Platelet-Rich Plasma in Musculoskeletal and Sports
Medicine: An Evidence-Based Approach
SO PM&R
LA English
DT Review
ID ANTERIOR CRUCIATE LIGAMENT; AUTOLOGOUS BLOOD INJECTION; TOTAL KNEE
ARTHROPLASTY; BIODEGRADABLE GELATIN HYDROGEL; RANDOMIZED
CONTROLLED-TRIAL; HEPATOCYTE GROWTH-FACTOR; HUMAN ENDOTHELIAL-CELLS;
IN-VITRO; CONDITIONED SERUM; ACHILLES-TENDON
AB This article aims to provide a comprehensive review of the current literature that pertains to the therapeutic use of autologous platelet-rich plasma (PRP). The basic science literature regarding the role of growth factors in mediating the healing process and the laboratory data from in vitro and in vivo studies that evaluated PRP are reviewed. Subsequently, the current evidence regarding PRP efficacy from animal models, human surgical studies, and human clinical studies is presented. A critical analysis of the literature follows, and the article concludes with the authors' perspectives on the state of PRP as a potentially efficacious bioregenerative treatment option for musculoskeletal and sports medicine applications. The relevant articles in this review were obtained via PubMed literature searches for PRP publications that pertain to musculoskeletal and sports medicine conditions. This article is not intended to be a formal meta-analysis. PM R 2011;3:226-250
C1 [Nguyen, Rosalyn T.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Newton Wellesley Hosp,Dept Phys Med & Rehabil, Boston, MA 02115 USA.
[Nguyen, Rosalyn T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Borg-Stein, Joanne] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Wellesley & Newton Wellesley Hosp, Wellesley, MA USA.
[McInnis, Kelly] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Sachusetts Gen Hosp, Boston, MA USA.
RP Nguyen, RT (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Newton Wellesley Hosp,Dept Phys Med & Rehabil, Boston, MA 02115 USA.
EM rtnsportsmd@gmail.com
NR 118
TC 45
Z9 49
U1 0
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAR
PY 2011
VL 3
IS 3
BP 226
EP 250
DI 10.1016/j.pmrj.2010.11.007
PG 25
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 961AX
UT WOS:000305437400007
PM 21402369
ER
PT J
AU Hiratsuka, S
Goel, S
Kamoun, WS
Maru, Y
Fukumura, D
Duda, DG
Jain, RK
AF Hiratsuka, Sachie
Goel, Shom
Kamoun, Walid S.
Maru, Yoshiro
Fukumura, Dai
Duda, Dan G.
Jain, Rakesh K.
TI Endothelial focal adhesion kinase mediates cancer cell homing to
discrete regions of the lungs via E-selectin up-regulation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE metastasis; permeability
ID GROWTH-FACTOR; BONE-MARROW; METASTASIS FORMATION; BREAST-CANCER; MYELOID
CELLS; IN-VIVO; ANGIOGENESIS; MICE; VEGF; INFLAMMATION
AB Primary tumors secrete factors that alter the microenvironment of distant organs, rendering those organs as fertile soil for subsequent metastatic cancer cell colonization. Although the lungs are exposed to these factors ubiquitously, lung metastases usually develop as a series of discrete lesions. The underlining molecular mechanisms of the formation of these discrete lesions are not understood. Here we show that primary tumors induce formation of discrete foci of vascular hyperpermeability in premetastatic lungs. This is mediated by endothelial cell-focal adhesion kinase (FAK), which up-regulates E-selectin, leading to preferential homing of metastatic cancer cells to these foci. Suppression of endothelial-FAK or E-selectin activity attenuates the number of cancer cells homing to these foci. Thus, localized activation of endothelial FAK and E-selectin in the lung vasculature mediates the initial homing of metastatic cancer cells to specific foci in the lungs.
C1 [Hiratsuka, Sachie; Goel, Shom; Kamoun, Walid S.; Fukumura, Dai; Duda, Dan G.; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA 02114 USA.
[Maru, Yoshiro] Tokyo Womens Med Univ, Dept Pharmacol, Tokyo 1628666, Japan.
RP Fukumura, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA 02114 USA.
EM dai@steele.mgh.harvard.edu; duda@steele.mgh.harvard.edu;
jain@steele.mgh.harvard.edu
FU Dyax; AstraZeneca; MedImmune; AstraZeneca/MedImmune; Astellas-Fibrogen;
SynDevRx; Regeneron; Genzyme; Morphosys; Noxxon Pharma; National
Institutes of Health [R01-CA085140, R01-CA115767, P01-CA080124,
R01-CA126642]; Federal Share/National Cancer Institute; R01-CA096915;
The Scholarship Fund; Fulbright Postgraduate Award; American Society of
Clinical Oncology; Susan G. Komen Postdoctoral Research Fellowship;
Department of Defence [W81XWH-10-1-0016]
FX R.K.J. received commercial research grants from Dyax, AstraZeneca, and
MedImmune; consultant fees from AstraZeneca/MedImmune, Dyax,
Astellas-Fibrogen, SynDevRx, Regeneron, Genzyme, Morphosys, and Noxxon
Pharma; and a speaker honorarium from Genzyme. R.K.J. owns stock in
SynDevRx. No reagents or funding from these companies was used in these
studies. There is no significant financial or other competing interest
in the work.; We thank B. Seed and I. Garkavstev for helpful comments;
L. Benjamin for providing VE-cadherin-tTA mice; R. Lee for providing the
FRNK vector; L. Wu for help with transgenic mice; M. Dawson, P. Huang,
M. Lee, C. Smith, and K. Kinzel for help in performing these
experiments; and M. Ancukiewicz for statistical analysis. This study was
supported by National Institutes of Health Grants R01-CA085140,
R01-CA115767, P01-CA080124, R01-CA126642, and Federal Share/National
Cancer Institute Proton Beam Program Income (to R.K.J.), and
R01-CA096915 (to D.F.). S.H. is supported by The Scholarship Fund to
Study Abroad, Japan. S.G. is supported by a Fulbright Postgraduate Award
and an American Society of Clinical Oncology Young Investigator Award.
W.S.K. is the recipient of a Susan G. Komen Postdoctoral Research
Fellowship. R.K.J. is the recipient of the Department of Defence Breast
Cancer Research Innovator Award W81XWH-10-1-0016.
NR 43
TC 48
Z9 50
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 1
PY 2011
VL 108
IS 9
BP 3725
EP 3730
DI 10.1073/pnas.1100446108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 728AD
UT WOS:000287844400054
PM 21321210
ER
PT J
AU Reddy, R
Fleet-Michaliszyn, S
Condray, R
Yao, JK
Keshavan, MS
Reddy, R
AF Reddy, R.
Fleet-Michaliszyn, S.
Condray, R.
Yao, J. K.
Keshavan, M. S.
Reddy, R.
TI Reduction in perseverative errors with adjunctive ethyl-eicosapentaenoic
acid in patients with schizophrenia: Preliminary study
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Schizophrenia; Omega-3 fatty acid; Eicosapentaenoic acid; WCST;
Executive function
ID PLACEBO-CONTROLLED TRIAL; CELL MEMBRANE DYNAMICS; COGNITIVE DYSFUNCTION;
FATTY-ACIDS; ANTIPSYCHOTIC MEDICATIONS; 1ST-EPISODE SCHIZOPHRENIA;
NEUROCOGNITIVE DEFICITS; MEMORY PERFORMANCE; EXECUTIVE FUNCTION;
OMEGA-3-FATTY-ACIDS
AB Introduction: Patients with schizophrenia have significant cognitive deficits, generally resistant to conventional treatment. This preliminary study examined the effects of ethyl-eicosapentanoate (EPA) on an executive function in early course patients.
Patients and methods: Patients with schizophrenia were given, after an informed consent, 2 g of an EPA daily for 24 weeks, in an open-label study. The Wisconsin Card Sort Test (WCST) was administered at baseline, weeks 4, 12 and 24.
Results: The 27 patients, with a mean duration of illness of 4.2 years, were all receiving atypical antipsychotics; treatment remained unchanged for the study. Perseverative errors - the key measure derived from WCST - were significantly reduced from the baseline mean of 28.2 to 18.4 errors at week 24. Positive symptoms also improved significantly. There were no correlations between EPA levels and any clinical or other neuropsychological measures.
Conclusion: These findings suggest that an EPA has procognitive effects for patients with schizophrenia, but controlled trials are required. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Reddy, R.; Condray, R.; Yao, J. K.; Reddy, R.] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
[Reddy, R.] Univ Toledo, Sch Med, Toledo, OH 43606 USA.
[Fleet-Michaliszyn, S.] Univ Arizona, Tucson, AZ USA.
[Condray, R.; Yao, J. K.; Reddy, R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Keshavan, M. S.] Harvard Univ, Boston, MA 02115 USA.
RP Reddy, R (reprint author), Univ Pittsburgh, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM reddyr@upmc.edu
FU NIMH [MH-46118, MH-58141, MH-45203]; VA Research Career Scientist Award;
NIH/NCRR/GCRC [M01 RR00056]
FX Sources of support: this publication was supported by funds received
from NIMH Grants MH-46118 (RR), MH-58141 (JKY) and MH-45203 (MSK), VA
Research Career Scientist Award (JKY), and the NIH/NCRR/GCRC Grant #M01
RR00056.
NR 54
TC 9
Z9 9
U1 2
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
EI 1532-2823
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD MAR-APR
PY 2011
VL 84
IS 3-4
BP 79
EP 83
DI 10.1016/j.plefa.2010.12.001
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 727EJ
UT WOS:000287780100002
PM 21211955
ER
PT J
AU Hermanrud, CE
Lucas, CL
Sykes, M
Huang, CA
Wang, ZR
AF Hermanrud, Christina E.
Lucas, Carrie L.
Sykes, Megan
Huang, Christene A.
Wang, Zhirui
TI Expression and purification of soluble murine CD40L monomers and
polymers in yeast Pichia pastoris
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Murine CD40L; Pichia pastoris; Yeast expression; Purification
ID T CELL IMMUNOTOXIN; LIGAND; RECIPIENTS; TRIMER
AB The anti-murine CD40L monoclonal antibody MR1 has been widely used in immunology research to block the CD40-CD40L interaction for induction of transplantation tolerance and to abrogate autoimmune diseases. The availability of recombinant CD40L with high binding capacity for MR1 would provide a valuable immunologic research tool. In this study, we constructed the single chain murine soluble CD40L monomer, dimer, trimer and successfully expressed them in yeast Pichia pastoris under the control of the alcohol oxidase promoter. The secreted single chain murine soluble CD40L monomers, dimers, and trimers were initially enriched through histidine tag capture by Ni-Sepharose 6 fast flow resin and further purified on a cation exchange resin. Purity reached more than 95% for the monomer and dimer forms and more than 90% for the trimer. Protein yield following purification was 16 mg/L for the monomer and dimer, and 8 mg/L for the trimer. ELISA analysis demonstrated that the CD40L dimers and trimers correctly folded in conformations exposing the MR1 antigenic determinant. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Huang, Christene A.] Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Sch Med,MGH E, Boston, MA 02129 USA.
[Hermanrud, Christina E.; Huang, Christene A.; Wang, Zhirui] MGH DF HCC Recombinant Prot Express & Purificat C, Boston, MA USA.
RP Huang, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Sch Med,MGH E, Bldg 149-6117C,13th St, Boston, MA 02129 USA.
EM christene.huang@tbrc.mgh.harvard.edu; zhirui.wang@tbrc.mgh.harvard.edu
FU Massachusetts General Hospital (MGH); Department of Surgery; Amelia
Peabody Foundation; MGH Executive Committee on Research;
Dana-Farber/Harvard Cancer Center (DF/HCC); NIH [R01HL049915]
FX The authors would like to gratefully acknowledge the Massachusetts
General Hospital (MGH), Department of Surgery, Amelia Peabody Foundation
and MGH Executive Committee on Research for equipment funding; and the
Dana-Farber/Harvard Cancer Center (DF/HCC) for start up funds to
establish a new Recombinant Protein Expression and Purification (RPrEP)
Core Facility. We also acknowledge the support and guidance of Dr. David
H. Sachs, Scientific Co-Director of the newly formed DF/HCC RPrEP Core
Facility at MGH. The work was supported by NIH Grant R01HL049915 (MS).
NR 19
TC 4
Z9 4
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD MAR
PY 2011
VL 76
IS 1
BP 115
EP 120
DI 10.1016/j.pep.2010.11.006
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 705WH
UT WOS:000286170900017
PM 21074618
ER
PT J
AU Rajagopal, MU
Hathout, Y
MacDonald, TJ
Kieran, MW
Gururangan, S
Blaney, SM
Phillips, P
Packer, R
Gordish-Dressman, H
Rood, BR
AF Rajagopal, Meena U.
Hathout, Yetrib
MacDonald, Tobey J.
Kieran, Mark W.
Gururangan, Sri
Blaney, Susan M.
Phillips, Peter
Packer, Roger
Gordish-Dressman, Heather
Rood, Brian R.
TI Proteomic profiling of cerebrospinal fluid identifies prostaglandin D2
synthase as a putative biomarker for pediatric medulloblastoma: A
pediatric brain tumor consortium study
SO PROTEOMICS
LA English
DT Article
DE 2-DE; Biomedicine; CSF proteomics; Medulloblastoma; Prostaglandin
synthase
ID CENTRAL-NERVOUS-SYSTEM; BETA-TRACE PROTEIN; BIOLOGICAL VARIATION;
MASS-SPECTROMETRY; APOLIPOPROTEIN-E; CANCER; QUANTIFICATION; CLUSTERIN;
MARKER; CSF
AB The aims of this study were to demonstrate the feasibility of centrally collecting and processing high-quality cerebrospinal fluid (CSF) samples for proteomic studies within a multi-center consortium and to identify putative biomarkers for medulloblastoma in CSF. We used 2-DE to investigate the CSF proteome from 33 children with medulloblastoma and compared it against the CSF proteome from 25 age-matched controls. Protein spots were subsequently identified by a combination of in-gel tryptic digestion and MALDI-TOF TOF MS analysis. On average, 160 protein spots were detected by 2-DE and 76 protein spots corresponding to 25 unique proteins were identified using MALDI-TOF. Levels of prostaglandin D2 synthase (PGD2S) were found to be six-fold decreased in the tumor samples versus control samples (p < 0.00001). These data were further validated using ELISA. Close examination of PGD2S spots revealed the presence of complex sialylated carbohydrates at residues Asn(78) and Asn(87). Total PGD2S levels are reduced six-fold in the CSF of children with medulloblastoma most likely representing a host response to the presence of the tumor. In addition, our results demonstrate the feasibility of performing proteomic studies on CSF samples collected from patients at multiple institutions within the consortium setting.
C1 [MacDonald, Tobey J.; Rood, Brian R.] Childrens Natl Med Ctr, Ctr Canc & Immunol, Washington, DC 20010 USA.
[Rajagopal, Meena U.; Hathout, Yetrib; Gordish-Dressman, Heather] Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA.
[Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Blaney, Susan M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
RP Rood, BR (reprint author), Childrens Natl Med Ctr, Ctr Canc & Immunol, Washington, DC 20010 USA.
EM brood@cnmc.org
RI MacDonald, Tobey/D-4554-2013;
OI Gordish-Dressman, Heather/0000-0002-2330-5427; Kieran,
Mark/0000-0003-2184-7692
FU NIH [U01 CA81457, 1P30HD40677, 5R24 HD050846]; American Lebanese Syrian
Associated Charities; The Childhood Brain Tumor Foundation; The Becca's
Run Fund; The Schlobohm Family; Friends of Ian
FX The authors acknowledge the support of James M. Boyett PhD, Executive
Director of the Operations and Biostatistics Center for the PBTC, Larry
E. Kun MD, Chair of the PBTC, Dana Wallace MS, Stacye Richardson MS,
Stewart Goldman MD, Ian Pollack MD, and Andreas Ekefjard of Ludesi. This
work was supported in part by NIH grant U01 CA81457 for the PBTC, the
American Lebanese Syrian Associated Charities, The Childhood Brain Tumor
Foundation, The Becca's Run Fund, The Schlobohm Family, and Friends of
Ian. This work was also partially supported by NIH core grants
1P30HD40677 and 5R24 HD050846.
NR 40
TC 19
Z9 22
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD MAR
PY 2011
VL 11
IS 5
BP 935
EP 943
DI 10.1002/pmic.201000198
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 731VK
UT WOS:000288137300010
PM 21271676
ER
PT J
AU Reise, SP
Ventura, J
Keefe, RSE
Baade, LE
Gold, JM
Green, MF
Kern, RS
Mesholam-Gately, R
Nuechterlein, KH
Seidman, LJ
Bilder, R
AF Reise, Steven P.
Ventura, Joseph
Keefe, Richard S. E.
Baade, Lyle E.
Gold, James M.
Green, Michael F.
Kern, Robert S.
Mesholam-Gately, Raquelle
Nuechterlein, Keith H.
Seidman, Larry J.
Bilder, Robert
TI Bifactor and Item Response Theory Analyses of Interviewer Report Scales
of Cognitive Impairment in Schizophrenia
SO PSYCHOLOGICAL ASSESSMENT
LA English
DT Article
DE item response theory; CGI-CogS; SCoRS; schizophrenia and cognitive
deficits; computerized adaptive testing
ID CLINICAL-TRIALS; RATING-SCALE; DIMENSIONALITY; RELIABILITY; VALIDITY;
BATTERY; MODELS
AB A psychometric analysis of 2 interview-based measures of cognitive deficits was conducted: the 21-item Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS; Ventura et al., 2008), and the 20-item Schizophrenia Cognition Rating Scale (SCoRS; Keefe et al., 2006), which were administered on 2 occasions to a sample of people with schizophrenia. Traditional psychometrics, bifactor analysis, and item response theory methods were used to explore item functioning and dimensionality and to compare instruments. Despite containing similar item content, responses to the CGI-CogS demonstrated superior psychometric properties (e.g., higher item intercorrelations, better spread of ratings across response categories) relative to the SCoRS. The authors argue that these differences arise mainly from the differential use of prompts and how the items are phrased and scored. Bifactor analysis demonstrated that although both measures capture a broad range of cognitive functioning (e.g., working memory, social cognition), the common variance on each is overwhelmingly explained by a single general factor. Item response theory analyses of the combined pool of 41 items showed that measurement precision is peaked in the mild to moderate range of cognitive impairment. Finally, simulated adaptive testing revealed that only about 10 to 12 items are necessary to achieve latent trait level estimates with reasonably small standard errors for most individuals. This suggests that these interview-based measures of cognitive deficits could be shortened without loss of measurement precision.
C1 [Reise, Steven P.; Nuechterlein, Keith H.; Bilder, Robert] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Ventura, Joseph; Green, Michael F.; Kern, Robert S.; Nuechterlein, Keith H.; Bilder, Robert] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Keefe, Richard S. E.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA.
[Baade, Lyle E.] Univ Kansas, Sch Med, Lawrence, KS 66045 USA.
[Gold, James M.] Univ Maryland, Maryland Psychiat Res Ctr, Sch Med, Baltimore, MD 21201 USA.
[Green, Michael F.; Kern, Robert S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Mesholam-Gately, Raquelle; Seidman, Larry J.] Harvard Univ, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Beth Israel Deaconess Med Ctr,Dept Psychiat,Med S, Cambridge, MA 02138 USA.
RP Reise, SP (reprint author), Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
EM reise@psych.ucla.edu
RI Bilder, Robert/A-8894-2008
OI Bilder, Robert/0000-0001-5085-7852
FU NIDA NIH HHS [RL1 DA024853, RL1 DA024853-04, RL1DA024853]; NIDCR NIH HHS
[UL1 DE019580-05, UL1 DE019580, UL1-DE019580]; NIMH NIH HHS
[1R21MH073971, MH37705, N01MH22006, P50 MH066286, R01 MH037705, R21
MH073971, R21 MH073971-01A2, R21 MH073971-02]
NR 34
TC 21
Z9 23
U1 2
U2 12
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1040-3590
EI 1939-134X
J9 PSYCHOL ASSESSMENT
JI Psychol. Assess.
PD MAR
PY 2011
VL 23
IS 1
BP 245
EP 261
DI 10.1037/a0021501
PG 17
WC Psychology, Clinical
SC Psychology
GA 729KT
UT WOS:000287949200021
PM 21381848
ER
PT J
AU Kranick, SM
Gorrindo, T
Hallett, M
AF Kranick, Sarah M.
Gorrindo, Tristan
Hallett, Mark
TI Psychogenic Movement Disorders and Motor Conversion: A Roadmap for
Collaboration Between Neurology and Psychiatry
SO PSYCHOSOMATICS
LA English
DT Article
ID COGNITIVE-BEHAVIORAL THERAPY; CLINICAL-FEATURES; DISSOCIATIVE DISORDER;
SYMPTOMS; TREMOR; TRIAL; PHENOMENOLOGY; PARKINSONISM; MANAGEMENT;
PROGNOSIS
AB Background: There are a host of vague terms to describe psychologically-mediated symptoms that mimic neurological disease, such as "functional," "non-organic," "psychogenic," or "medically unexplained." None of these terms has a direct translation in psychiatric classification, and psychiatrists are often fixed with patients who do not believe in a psychological origin for their symptoms. Objective: Within the framework of psychogenic movement disorders, we discuss the roadblocks to effective collaboration and treatment in these patients and the current state of the literature regarding diagnosis and treatment. Results: We describe the approach to these patients from the perspective of neurology and psychiatry illustrating the differences in terminology and categorization. Conclusion: Psychogenic movement disorders represent a unique opportunity for these fields to collaborate in the care of a potentially curable but significantly disabling disorder. (Psychosomatics 2011: 52:109-116)
C1 [Kranick, Sarah M.; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Gorrindo, Tristan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Kranick, SM (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10-7D42,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA.
EM sarah.kranick@nih.gov
FU NINDS
FX This research was supported in part by the NINDS Intramural Program.
NR 51
TC 13
Z9 13
U1 1
U2 8
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD MAR-APR
PY 2011
VL 52
IS 2
BP 109
EP 116
PG 8
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 741RF
UT WOS:000288881100002
PM 21397102
ER
PT J
AU Lindsay, AC
Sussner, KM
Greaney, ML
Peterson, KE
AF Lindsay, Ana C.
Sussner, Katarina M.
Greaney, Mary L.
Peterson, Karen E.
TI Latina Mothers' Beliefs and Practices Related to Weight Status, Feeding,
and the Development of Child Overweight
SO PUBLIC HEALTH NURSING
LA English
DT Article
DE beliefs; childhood overweight; feeding practices; Latino
ID LOW-INCOME MOTHERS; MEXICAN-AMERICAN MOTHERS; PRESCHOOL-AGED CHILDREN;
PHYSICAL-ACTIVITY; EATING BEHAVIOR; OBESIGENIC FAMILIES; IMMIGRANT
STATUS; SOCIAL-CONTEXT; OBESITY; HEALTH
AB Objective
To examine maternal beliefs and practices related to weight status, child feeding, and child overweight in the Latino culture that may contribute to the rising rates of overweight among preschool Latino children in the United States.
Design and Sample
This 2-phase qualitative study relies on data obtained in 6 focus groups with a total of 31 primarily Spanish-speaking, low-income mothers, followed by 20 individual, in-depth interviews with women participating in a health promotion educational program.
Measures
Child-feeding beliefs, practices, and weight status perceptions were elicited.
Results
The findings indicated that most respondents reported personal struggles with weight gain, particularly during and after pregnancy, and were concerned that their children would become obese. Although subjects understood the health and social consequences related to overweight, many discussed the pressures of familial and cultural influences endorsing a "chubby child."
Conclusions
Education and interventions that incorporate "culturally mediated" pathways to address mothers' feeding practices are essential for the prevention and control of childhood overweight among low-income Latinos. Nurses should be aware of the social and cultural influences on Latina mothers' beliefs and practices related to weight status and feeding practices and address these in their education approaches to prevent childhood overweight and obesity with this population group.
C1 [Lindsay, Ana C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Sussner, Katarina M.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA.
[Greaney, Mary L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Peterson, Karen E.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth, Ann Arbor, MI 48109 USA.
RP Lindsay, AC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2, Boston, MA 02115 USA.
EM alindsay@hsph.harvard.edu
FU National Cancer Institute [R03 CA108347-01]
FX We are thankful to the staff of the WIC Program at the Massachusetts
Department of Public Health and the mothers who participated in this
study. This study was supported by a grant from the National Cancer
Institute, R03 CA108347-01, for which Ana Lindsay, D. D. S., M. P. H.,
Dr.P.H., is Principal Investigator.
NR 53
TC 36
Z9 38
U1 1
U2 19
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0737-1209
J9 PUBLIC HEALTH NURS
JI Public Health Nurs.
PD MAR-APR
PY 2011
VL 28
IS 2
BP 107
EP 118
DI 10.1111/j.1525-1446.2010.00906.x
PG 12
WC Public, Environmental & Occupational Health; Nursing
SC Public, Environmental & Occupational Health; Nursing
GA 726QA
UT WOS:000287740000002
PM 21442018
ER
PT J
AU Ding, A
Eisenberg, JD
Pandharipande, PV
AF Ding, Alexander
Eisenberg, Jonathan D.
Pandharipande, Pari V.
TI The Economic Burden of Incidentally Detected Findings
SO RADIOLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Economic burden; Incidental findings; Imaging; CT colonography
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; EXTRACOLONIC FINDINGS; CT
COLONOGRAPHY; COST-EFFECTIVENESS; COLORECTAL-CANCER; LUNG-CANCER;
EXTRACARDIAC FINDINGS; MUTATION CARRIERS; IMPACT; MR
AB Practitioners in all medical disciplines recognize the high frequency of incidentally detected findings. Although some findings are discovered on physical examination, an increasing majority are detected at imaging performed for another indication. With increasing federal scrutiny on the net value of imaging services, the costs and benefits of incidental findings need to be more rigorously quantified. In this article, the authors examine current related work on imaging expenditures for incidental findings and provide a framework for future investigations that will efficiently and substantially advance the knowledge in this field.
C1 [Eisenberg, Jonathan D.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA 02114 USA.
[Pandharipande, Pari V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM pari@mgh-ita.org
FU NCI NIH HHS [K07 CA133097, K07 CA133097-02]
NR 42
TC 17
Z9 17
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 0033-8389
J9 RADIOL CLIN N AM
JI Radiol. Clin. N. Am.
PD MAR
PY 2011
VL 49
IS 2
BP 257
EP +
DI 10.1016/j.rcl.2010.11.004
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 738EX
UT WOS:000288623500004
PM 21333777
ER
PT J
AU Shanbhogue, AK
Prasad, SR
Takahashi, N
Vikram, R
Sahani, DV
AF Shanbhogue, Alampady K.
Prasad, Srinivasa R.
Takahashi, Naoki
Vikram, Raghunandan
Sahani, Dushyant V.
TI Recent Advances in Cytogenetics and Molecular Biology of Adult
Hepatocellular Tumors: Implications for Imaging and Management
SO RADIOLOGY
LA English
DT Review
ID FOCAL NODULAR HYPERPLASIA; GLYCOGEN-STORAGE-DISEASE; GROWTH-FACTOR-II;
HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; ORAL-CONTRACEPTIVE USE; PRIMARY
LIVER-CANCER; C VIRUS-INFECTION; MAGNETIC-RESONANCE; FIBROLAMELLAR
CARCINOMA; UNITED-STATES
AB Focal nodular hyperplasia (FNH), hepatocellular adenoma (HCA), and hepatocellular carcinoma (HCC) compose hepatocellular neoplasms that occur in adults. These tumors demonstrate characteristic epidemiologic and histopathologic features and clinical and imaging manifestations. HCAs are monoclonal neoplasms characterized by increased predilection to hemorrhage or rupture and occasional transformation to HCC. On the other hand, FNH is a polyclonal tumorlike lesion that occurs in response to increased perfusion and has an indolent clinical course. Up to 90% of HCCs occur in the setting of cirrhosis. Chronic viral hepatitis (hepatitis B and hepatitis C) infection and metabolic syndrome are major risk factors that can induce HCCs in nonfibrotic liver. Recent advances in pathology and genetics have led to better understanding of the histogenesis, natural history, and molecular events that determine specific oncologic pathways used by these neoplasms. HCAs are now believed to result from specific genetic mutations involving TCF1 (transcription factor 1 gene), IL6ST (interleukin 6 signal transducer gene), and CTNNB1 (beta catenin-1 gene); FNHs are characterized by an "imbalance" of angiopoietin. While the beta catenin signaling pathway is associated with well-and moderately differentiated HCCs, mutations involving p53 (tumor protein 53 gene), MMP14 (matrix metalloproteinase 14 gene), and RhoC (Ras homolog gene family, member C) are associated with larger tumor size, higher tumor grade with resultant shortened tumor-free survival, and poor prognosis. Fibrolamellar carcinoma (FLC), a unique HCC subtype, exhibits genomic homogeneity that partly explains its better overall prognosis. On the basis of recent study results involving cytogenetics and oncologic pathways of HCCs, novel drugs that act against molecular targets are being developed. Indeed, sorafenib (a multikinase inhibitor) is currently being used in the successful treatment of patients with advanced HCC. Characterization of genetic abnormalities and genotype-phenotype correlations in adult hepatocellular tumors provides better understanding of tumor pathology and biology, imaging findings, prognosis, and response to molecular therapeutics. (C)RSNA, 2011
C1 [Shanbhogue, Alampady K.; Prasad, Srinivasa R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[Vikram, Raghunandan] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA.
[Takahashi, Naoki] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Prasad, SR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM prasads@uthscsa.edu
FU GE Healthcare; Bracco Diagnostics
FX A.K.S. Financial activities related to the present article: none to
disclose. Financial activities not related to the present article: none
to disclose. Other relationships: none to disclose. S.R.P. Financial
activities related to the present article: none to disclose. Financial
activities not related to the present article: none to disclose. Other
relationships: none to disclose. N.T. Financial activities related to
the present article: none to disclose. Financial activities not related
to the present article: none to disclose. Other relationships: none to
disclose. R.V. Financial activities related to the present article: none
to disclose. Financial activities not related to the present article:
none to disclose. Other relationships: none to disclose. D.V.S.
Financial activities related to the present article: Institution
received a grant from GE Healthcare; received consulting fee or
honorarium from Bracco Diagnostics. Financial activities not related to
the present article: none to disclose. Other relationships: none to
disclose.
NR 156
TC 26
Z9 30
U1 0
U2 5
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAR
PY 2011
VL 258
IS 3
BP 673
EP 693
DI 10.1148/radiol.10100376
PG 21
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 724JX
UT WOS:000287573100004
PM 21339346
ER
PT J
AU Uppal, R
Catana, C
Ay, I
Benner, T
Sorensen, AG
Caravan, P
AF Uppal, Ritika
Catana, Ciprian
Ay, Ilknur
Benner, Thomas
Sorensen, A. Gregory
Caravan, Peter
TI Bimodal Thrombus Imaging: Simultaneous PET/MR Imaging with a
Fibrin-targeted Dual PET/MR Probe-Feasibility Study in Rat Model
SO RADIOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; IRON-OXIDE NANOPARTICLES; MR CONTRAST
AGENT; IN-VIVO; CORONARY-THROMBOSIS; PULMONARY EMBOLI; SWINE MODEL;
EP-2104R; SCANNER
AB Purpose: To image thrombus by using magnetic resonance (MR) imaging and positron emission tomography (PET) simultaneously in a rat arterial thrombus model with a dual PET/MR probe.
Materials and Methods: Animal studies were approved by the institutional animal use committee. A dual PET/MR probe was synthesized by means of partial exchange of gadolinium for copper 64 ((64)Cu) in the fibrin-targeted MR probe EP-2104R. A preformed 25-mm thrombus was injected into the right internal carotid artery of a rat. Imaging was performed with a clinical 3.0-T MR imager with an MR-compatible human PET imager. Rats (n = 5) were imaged prior to and after systemic administration of the dual probe by using simultaneous PET/MR. The organ distribution of (64)Cu and gadolinium was determined ex vivo (n = 8), 2 hours after injection by using well counting and inductively coupled plasma mass spectrometry, respectively. Signal intensity ratios (SIRs) between the thrombus-containing and contralateral vessel were computed from PET images and MR data before and after probe administration.
Results: The dual probe was synthesized with greater than 98% radiochemical purity. Thrombus enhancement was observed in all five animals at both MR (SIR([postprobe])/SIR([preprobe]) = 1.71 +/- 0.35, P = .0053) and PET (SIR = 1.85 +/- 0.48, P = .0087) after injection of the dual PET/MR probe. Ex vivo analysis at 2 hours after injection showed the highest (64)Cu and gadolinium concentrations, after the excretory organs (kidney and liver), to be in the thrombus.
Conclusion: A fibrin-targeted dual PET/MR probe enables simultaneous, direct MR and PET imaging of thrombus. (C)RSNA, 2010
C1 [Uppal, Ritika; Catana, Ciprian; Ay, Ilknur; Benner, Thomas; Sorensen, A. Gregory; Caravan, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Caravan, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM caravan@nmr.mgh.harvard.edu
FU MIND Institute; T32 Ruth L. Kirschstein National Research Service
[5T32CA009502]; National Institutes of Health [5T32CA009502, EB009062,
EB009783, NS38477, P41-RR14075]; NIH; National Cancer Institute; Medical
Research Council; Massachusetts General Hospital
FX Supported in part by the MIND Institute. I.A. supported by a T32 Ruth L.
Kirschstein National Research Service Award (5T32CA009502).; This
research was supported by the National Institutes of Health (grants
EB009062, EB009783, NS38477, 5T32CA009502, and P41-RR14075).; R.U. No
potential conflicts of interest to disclose. C.C. No potential conflicts
of interest to disclose. I.A. No potential conflicts of interest to
disclose. T.B. Financial activities related to the present article:
institution received an NIH grant. Financial activities not related to
the present article: is a consultant for Siemens Medical. Other
relationships: none to disclose. A.G.S. Financial activities related to
the present article: institution received grant from National Cancer
Institute. Financial activities not related to the present article:
money paid to institution for board membership for ACR-Image Metrix (no
compensation); author is a consultant for BayerScheringPharma, Bristol
Meyers Squibb, Biogenldec, Merrimack Pharmaceuticals, Olea Medical,
Mitsubishi Pharm, GE Healthcare, Regeneron, Siemens Medical, and NIH;
author and institution are consultants for Novartis, Roche, Takeda, and
AstraZeneca; author provides expert testimony for Kit; institution
receives grants from NIH and Medical Research Council; author receives
payment for lectures from New York University and ACR-Image Metrix;
institution has patent with Massachusetts General Hospital; author and
institution receive royalties from Massachusetts General Hospital;
author has Catalyst Medical and Breakaway Imaging stock; author receives
travel accommodations from Oxford University and Aarhus University.
Other relationships: none to disclose. A full listing of A.G.S.'s
competing interests is available at http://www.biomarkers.org/. P.C.
Financial activities related to the present article: institution
received NIH grant. Financial activities not related to the present
article: is a consultant for Lantheus Medical Imaging and Epix
Pharmaceuticals; has Catalyst Medical stock. Other relationships: none
to disclose.
NR 37
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PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAR
PY 2011
VL 258
IS 3
BP 812
EP 820
DI 10.1148/radiol.10100881
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 724JX
UT WOS:000287573100018
PM 21177389
ER
PT J
AU Spampinato, MV
Rumboldt, Z
Hosker, RJ
Mintzer, JE
AF Spampinato, Maria Vittoria
Rumboldt, Zoran
Hosker, Robert J.
Mintzer, Jacobo E.
CA Alzheimer's Dis Neuroimaging
TI Apolipoprotein E and Gray Matter Volume Loss in Patients with Mild
Cognitive Impairment and Alzheimer Disease
SO RADIOLOGY
LA English
DT Article
ID VOXEL-BASED MORPHOMETRY; CEREBROSPINAL-FLUID TAU; E EPSILON-4 ALLELE; E
GENOTYPE; TRANSGENIC MICE; CHOLINERGIC DEFICITS; CORTICAL THICKNESS;
AMYLOID DEPOSITION; CLINICAL-DIAGNOSIS; TACRINE THERAPY
AB Purpose: To examine the influence of apoliprotein E epsilon 4 allele (APOE 4) carrier status on disease progression by evaluating the rate of regional gray matter (GM) volume loss and disease severity in patients with newly diagnosed Alzheimer disease (AD) and stable amnestic mild cognitive impairment (MCI).
Materials and Methods: This study was approved by the institutional review board and was HIPAA compliant. All subjects or their legal representatives gave informed consent for participation. Ninety-five subjects (63 male; average age, 77.1 years; age range, 58-91 years; 51 APOE4 carriers; 44 noncarriers) with either documented MCI to AD conversion or stable amnestic MCI underwent three yearly magnetic resonance imaging examinations. Voxel-based morphometry for image postprocessing and Clinical Dementia Rating (CDR) scale for cognitive assessment were used.
Results: In APOE 4 carriers, GM volume loss affected the hippocampi, temporal and parietal lobes, right caudate nucleus, and insulae in patients with MCI to AD conversion and the insular and temporal lobes in patients in whom MCI was stable. In subjects who were not APOE 4 carriers, there was no significant GM volume change. There were no differences in CDR scores between APOE 4 carriers and noncarriers.
Conclusion: APOE 4 carriers with cognitive decline undergo faster GM atrophy than do noncarriers. The involvement of APOE 4 in the progression of hippocampal atrophy, neocortical atrophy, or both has potential important implications for diagnosis and therapeutic approaches in patients with AD and should be considered in clinical trials. The present results and the results of prior studies indicate that the rate of hippocampal and neocortical atrophy is greater in association with APOE 4 in nondemented elderly subjects, subjects with MCI, and those with AD. (C)RSNA, 2010
C1 [Spampinato, Maria Vittoria; Rumboldt, Zoran; Hosker, Robert J.] Med Univ S Carolina, Dept Radiol & Radiol Sci, Charleston, SC 29425 USA.
[Mintzer, Jacobo E.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Spampinato, MV (reprint author), Med Univ S Carolina, Dept Radiol & Radiol Sci, 96 Jonathan Lucas St,MSC 323, Charleston, SC 29425 USA.
EM spampin@musc.edu
RI Scharre, Douglas/E-4030-2011
FU Bracco Diagnostics; Bayer; Siemens; National Institute on Aging
FX M.V.S. Financial activities related to the present article: none to
disclose. Financial activities not related to the present article: none
to disclose. Other relationships: institution received compensation from
Bayer HealthCare and Bracco Diagnostics. Z.R. Financial activities
related to the present article: none to disclose. Financial activities
not related to the present article: none to disclose. Other
relationships: is a consultant for Bracco Diagnostics; provides research
support for Bracco Diagnostics, Bayer, and Siemens. R.J.H. No potential
conflicts of interest to disclose. J.E.M. Financial activities related
to the present article: institution received funding from National
Institute on Aging. Financial activities not related to the present
article: is on the board of ADNI. Other relationships: none to disclose.
NR 53
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PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAR
PY 2011
VL 258
IS 3
BP 843
EP 852
DI 10.1148/radiol.10100307
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 724JX
UT WOS:000287573100021
PM 21163916
ER
PT J
AU Hricak, H
Brenner, DJ
Adelstein, SJ
Frush, DP
Hall, EJ
Howell, RW
McCollough, CH
Mettler, FA
Pearce, MS
Suleiman, OH
Thrall, JH
Wagner, LK
AF Hricak, Hedvig
Brenner, David J.
Adelstein, S. James
Frush, Donald P.
Hall, Eric J.
Howell, Roger W.
McCollough, Cynthia H.
Mettler, Fred A.
Pearce, Mark S.
Suleiman, Orhan H.
Thrall, James H.
Wagner, Louis K.
TI Managing Radiation Use in Medical Imaging : A Multifaceted Challenge
SO RADIOLOGY
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; CARDIAC COMPUTED-TOMOGRAPHY; FLUOROSCOPICALLY
GUIDED PROCEDURES; CORONARY-ARTERY-DISEASE; MULTISLICE HELICAL CT;
MULTIDETECTOR-ROW CT; LOW-DOSE RADIATION; BREAST-CANCER;
IONIZING-RADIATION; DECISION-SUPPORT
AB This special report aims to inform the medical community about the many challenges involved in managing radiation exposure in a way that maximizes the benefit-risk ratio. The report discusses the state of current knowledge and key questions in regard to sources of medical imaging radiation exposure, radiation risk estimation, dose reduction strategies, and regulatory options.
C1 [Hricak, Hedvig] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
[Brenner, David J.; Hall, Eric J.] Columbia Univ, Ctr Radiol Res, Med Ctr, New York, NY 10032 USA.
[Adelstein, S. James] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Frush, Donald P.] Duke Med Ctr, Div Pediat Radiol, Durham, NC USA.
[Howell, Roger W.] UMDNJ New Jersey Med Sch Canc Ctr, Dept Radiol, Newark, NJ USA.
[McCollough, Cynthia H.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Mettler, Fred A.] Univ New Mexico, Dept Radiol, Albuquerque, NM 87131 USA.
[Pearce, Mark S.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Suleiman, Orhan H.] US FDA, Off New Drugs, Silver Spring, MD USA.
[Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Wagner, Louis K.] Univ Texas Med Sch Houston, Dept Diagnost & Intervent Imaging, Houston, TX USA.
RP Hricak, H (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave,Suite C-278, New York, NY 10021 USA.
EM mullnea@mskcc.org
RI Frush, Donald/M-6457-2015
OI Frush, Donald/0000-0002-6928-4465
FU NASA [NNJO5H138G]; DOE [SC0001634]; Siemens Medical Solutions; American
College of Radiology
FX E.J.H. Financial activities related to the present article:
institutional grants from NASA NNJO5H138G and DOE-SC0001634. Financial
activities not related to the present article: is paid for consultancy
(teaching) elsewhere, is paid for employment as professor emeritus at
Columbia University, is paid for expert testimony for several court
cases, and receives payment for lectures including service on speakers
bureaus teaching residents, receives royalties for textbook, receives
institutional grants for payment for development of educational
presentations, receives money for stock or stock options as part of
retirement portfolio, receives money for travel, accommodations, meeting
expenses for resident lectures. Other relationships: none to disclose.;
C.H.M. Financial activities related to the present article: received
institutional payment for travel expenses to the National Academies of
Science sponsored Beebe Symposium in December 2009. Financial activities
not related to the present article: received research grant related to
CT imaging from Siemens Medical Solutions. Other relationships: none to
disclose.; Financial activities not related to the present article:
receives a stipend for service as board chair from American College of
Radiology
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PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAR
PY 2011
VL 258
IS 3
BP 889
EP 905
DI 10.1148/radiol.10101157
PG 17
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 724JX
UT WOS:000287573100026
PM 21163918
ER
PT J
AU Sparks, TN
Ecker, JE
Janakiraman, V
AF Sparks, Teresa N.
Ecker, Jeff E.
Janakiraman, Vanitha
TI How Do Global Cesarean Rates Compare to Those in Massachusetts by
Ethnicity
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Sparks, Teresa N.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T058
BP 88A
EP 88A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700063
ER
PT J
AU Selesniemi, K
Lee, HJ
Tilly, JL
AF Selesniemi, Kaisa
Lee, Ho-Joon
Tilly, Jonathan L.
TI Aging-Related Increases in Oocyte Aneuploidy and Spindle Assembly
Defects Are Prevented by Dietary Caloric Restriction (CR) or Pgc-1-alpha
Gene Inactivation
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Selesniemi, Kaisa; Lee, Ho-Joon; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T-099
BP 100A
EP 100A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700104
ER
PT J
AU Kulkarni-Datar, K
Guo, LK
Zhang, L
Zuckerberg, LR
Foster, R
Rueda, BR
AF Kulkarni-Datar, Kashmira
Guo, Lankai
Zhang, Ling
Zuckerberg, Lawrence R.
Foster, Rosemary
Rueda, Bo R.
TI Comparing Stem Cell Populations in Normal, Hyperplastic and
Carcinomatous Endometrium in Wild Type and PTEN Deficient Mice
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Kulkarni-Datar, Kashmira; Guo, Lankai; Zhang, Ling; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Zuckerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kulkarni-Datar, Kashmira; Zuckerberg, Lawrence R.; Foster, Rosemary; Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
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PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2011
VL 18
IS 3
SU S
MA T127
BP 108A
EP 108A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700130
ER
PT J
AU White, YAR
Woods, DC
Guo, L
Rueda, BR
Tilly, JL
AF White, Yvonne A. R.
Woods, Dori C.
Guo, Lankai
Rueda, Bo R.
Tilly, Jonathan L.
TI The Cables1 Gene Is a Key Regulator of Oogonial Stem Cell (OSC) Mitotic
Activity in Adult Mouse Ovaries
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [White, Yvonne A. R.; Woods, Dori C.; Guo, Lankai; Rueda, Bo R.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
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PD MAR
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MA O055
BP 172A
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SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721700358
ER
PT J
AU Chattergoon, NN
Louey, S
Giraud, GD
Thornburg, KL
AF Chattergoon, Natasha N.
Louey, Samantha
Giraud, George D.
Thornburg, Kent L.
TI Thyroid Hormone Deprivation Disrupts the IGF-I System in the Fetal Heart
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Chattergoon, Natasha N.; Louey, Samantha; Giraud, George D.; Thornburg, Kent L.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA.
[Giraud, George D.] Portland VA Med Ctr, Portland, OR USA.
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PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
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PD MAR
PY 2011
VL 18
IS 3
SU S
MA F115
BP 205A
EP 205A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701042
ER
PT J
AU Lannon, BM
Cole, L
Yeh, J
AF Lannon, Benjamin M.
Cole, Lawrence
Yeh, John
TI Familial Human Chorionic Gonadotropin Syndrome: A Case Report
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Lannon, Benjamin M.; Yeh, John] Harvard Univ, Sch Med, BIDMC, Boston, MA USA.
[Cole, Lawrence] Univ New Mexico, Albuquerque, NM 87131 USA.
NR 0
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PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
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PD MAR
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SU S
MA F286
BP 256A
EP 256A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701213
ER
PT J
AU Imudia, AN
White, YAR
Woods, DC
Tanaka, Y
Tilly, JL
AF Imudia, Anthony N.
White, Yvonne A. R.
Woods, Dori C.
Tanaka, Yoshihiro
Tilly, Jonathan L.
TI Genetic Analysis of Mouse Embryonic Stem Cells (ESC), Primordial Germ
Cells (PGC) and Postnatal Oogonial Stem Cells (OSC) Reveals a
Progressive Germline Differentiation Profile
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Imudia, Anthony N.; White, Yvonne A. R.; Woods, Dori C.; Tanaka, Yoshihiro; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
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U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
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IS 3
SU S
MA F298
BP 259A
EP 260A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701225
ER
PT J
AU Lannon, BM
Rhee, J
Zimon, AE
AF Lannon, Benjamin M.
Rhee, Julie
Zimon, Alison E.
TI Characteristics of Couples Donating Cryopreserved Embryos for Human
Embryonic Stem Cell Research
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Lannon, Benjamin M.; Rhee, Julie; Zimon, Alison E.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA.
[Lannon, Benjamin M.; Zimon, Alison E.] Boston IVF, Waltham, MA USA.
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PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
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PD MAR
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IS 3
SU S
MA F-301
BP 260A
EP 260A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701228
ER
PT J
AU Satirapod, C
Wang, N
Niikura, Y
Wright, DL
Toth, TL
Tilly, JL
AF Satirapod, Chonthicha
Wang, Ning
Niikura, Yuichi
Wright, Diane L.
Toth, Thomas L.
Tilly, Jonathan L.
TI Human Seminal Fluid Contains a Factor That Enhances Postnatal Oogenesis
in Adult Female Mice
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Satirapod, Chonthicha; Wang, Ning; Niikura, Yuichi; Wright, Diane L.; Toth, Thomas L.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
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PD MAR
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SU S
MA F-304
BP 261A
EP 262A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701231
ER
PT J
AU Wang, N
Satirapod, C
Tilly, JL
AF Wang, Ning
Satirapod, Chonthicha
Tilly, Jonathan L.
TI Suicide Gene-Based Targeted Cell Ablation Confirms a Critical Role for
Oogonial Stem Cells (OSC) in Maintaining the Adult Ovarian Oocyte Pool
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Wang, Ning; Satirapod, Chonthicha; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
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PD MAR
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VL 18
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SU S
MA F-305
BP 262A
EP 262A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701232
ER
PT J
AU Woods, DC
White, YAR
Niikura, Y
Tilly, JL
AF Woods, Dori C.
White, Yvonne A. R.
Niikura, Yuichi
Tilly, Jonathan L.
TI Embryonic Stem Cell (ESC)-Derived Granulosa Cells Participate in
Follicle Formation In Vitro and In Vivo.
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Woods, Dori C.; White, Yvonne A. R.; Niikura, Yuichi; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
NR 0
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PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
J9 REPROD SCI
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PD MAR
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MA F-307
BP 262A
EP 262A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701234
ER
PT J
AU Henry, DE
Goldfarb, I
Dumont, O
Barth, W
AF Henry, Dana E.
Goldfarb, Ilona
Dumont, Olivia
Barth, William
TI Inadvertent Hysterotomy Extension at Cesarean Delivery and Risk of
Preterm Birth in the Next Pregnancy
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Henry, Dana E.; Goldfarb, Ilona; Dumont, Olivia; Barth, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol, Boston, MA USA.
NR 0
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PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
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PD MAR
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SU S
MA S043
BP 307A
EP 307A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701385
ER
PT J
AU Bahado-Singh, RO
Filetti, L
Imudia, A
Awonuga, A
Kruger, M
AF Bahado-Singh, Ray O.
Filetti, Lusia
Imudia, Anthony
Awonuga, Awoniyi
Kruger, Michael
TI Late Onset Post Partum Preeclampsia: Are There Different Subtypes
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Bahado-Singh, Ray O.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA.
NR 0
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PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
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SU S
MA S189
BP 349A
EP 349A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701529
ER
PT J
AU Panda, B
Panda, A
Abrahams, VM
Norwitz, ER
Stanic-Kostic, A
Shaw, AC
AF Panda, Britta
Panda, Alexander
Abrahams, Vikki M.
Norwitz, Errol R.
Stanic-Kostic, Aleksandar
Shaw, Albert C.
TI Dendritic Cells in the Circulation of Women with Preeclampsia
Demonstrate a Pro-Inflammatory Bias
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Panda, Britta; Stanic-Kostic, Aleksandar] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA.
[Panda, Alexander; Abrahams, Vikki M.; Shaw, Albert C.] Yale Univ, New Haven, CT USA.
[Norwitz, Errol R.] Tufts Univ, Tufts Med Ctr, Boston, MA 02111 USA.
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PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
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MA S217
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SC Obstetrics & Gynecology; Reproductive Biology
GA 778RE
UT WOS:000291721701557
ER
PT J
AU Castelino, FV
Goldberg, H
Dellaripa, PF
AF Castelino, Flavia V.
Goldberg, Hilary
Dellaripa, Paul F.
TI The impact of rheumatological evaluation in the management of patients
with interstitial lung disease
SO RHEUMATOLOGY
LA English
DT Article
DE Interstitial lung disease; CTD-related interstitial lung disease;
Quality of care
ID CONNECTIVE-TISSUE DISEASE; RHEUMATOID-ARTHRITIS; REVISED CRITERIA;
CLASSIFICATION; PNEUMONIA; COMMUNITY; SMOKING
AB Methods. Our multi-disciplinary ILD group evaluated 50 patients referred to our tertiary care practice over a 12-month period. Evaluation consisted of independent assessments by a pulmonologist and rheumatologist, including complete history and physical examination, review of laboratory data, as well as review of imaging and pathological specimens in conjunction with a radiologist and pathologist experienced in ILD. Therapy was initiated or changed in collaboration with the referring physicians.
Results. Mean age was 65 years for patients with rheumatic or CTD-related ILD (CTD-ILD) and 70 years for those with idiopathic pulmonary fibrosis (IPF). The final diagnosis after evaluation in the clinic was 25 patients with CTD-ILD, 15 patients with IPF and 10 patients with other forms of lung disease. Of the patients with a final diagnosis of CTD-ILD, 28% were referred with a diagnosis of IPF. Among those referred with CTD-ILD, 36% had their diagnosis changed to an alternate CTD-ILD. In total, the diagnosis was changed in 54% of patients who presented to the ILD clinic. Changes in therapy occurred in 80% of patients with CTD-ILD and in 27% of patients with IPF.
Conclusion. A multi-disciplinary ILD clinic offers patients an innovative mode of health-care delivery that can enhance diagnosis, affect treatment regimens and improve quality of care. Rheumatologists play a significant role in the clinical care of these patients and should evaluate all patients with ILD.
C1 [Castelino, Flavia V.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol, Boston, MA 02114 USA.
[Goldberg, Hilary] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA.
[Dellaripa, Paul F.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA.
RP Castelino, FV (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA.
EM fcastelino@partners.org
FU Genentech; Novartis Pharmaceuticals Corp.; Wyeth Pharmaceuticals; Gilead
Sciences, Inc.
FX Disclosure statement: P.F.D. has participated as a clinical investigator
in a study supported by Genentech and a project with Gilead. A project
with Gilead H. G. has been a site PI for multicenter clinical trials
funded by Novartis Pharmaceuticals Corp., Wyeth Pharmaceuticals, Gilead
Sciences, Inc. and Genentech. The other author has declared no conflicts
of interest.
NR 20
TC 20
Z9 20
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD MAR
PY 2011
VL 50
IS 3
BP 489
EP 493
DI 10.1093/rheumatology/keq233
PG 5
WC Rheumatology
SC Rheumatology
GA 726SE
UT WOS:000287745600009
PM 20685802
ER
PT J
AU Baker-LePain, JC
Nakamura, MC
Shepherd, J
von Scheven, E
AF Baker-LePain, Julie C.
Nakamura, Mary C.
Shepherd, John
von Scheven, Emily
TI Assessment of bone remodelling in childhood-onset systemic lupus
erythematosus
SO RHEUMATOLOGY
LA English
DT Article
DE Bone turnover; Systemic lupus erythematosus; Children; Cytokines;
Interferon
ID RESISTANT ACID-PHOSPHATASE; JUVENILE RHEUMATOID-ARTHRITIS; CHRONIC
KIDNEY-DISEASE; MINERAL-DENSITY; IDIOPATHIC ARTHRITIS; KNEE
OSTEOARTHRITIS; PREMENOPAUSAL WOMEN; NUTRITIONAL-STATUS;
INTERFERON-BETA; GROWTH FAILURE
AB Methods. Ninety subjects with SLE aged 8-22 years underwent yearly measurements of height, bone age, bone turnover markers, serum Type I IFNs, SLEDAI and BMD. Predictors of bone turnover were examined using serum osteocalcin as a marker of bone formation and both serum tartrate-resistant acid phosphatase (TRAP) and urine N-telopeptide (NTx) as markers of bone resorption.
Results. Subjects demonstrated short stature, high BMI and bone age delay. A spine BMD Z-score of less than -2.0 was seen in 16.1% of subject visits. Serum osteocalcin was negatively correlated with glucocorticoid dose (Spearman rank correlation coefficient R = -0.34, P < 0.0001) but was not associated with SLEDAI after adjustment for confounders. Serum TRAP was negatively associated with SLEDAI, even after controlling for confounders (P = 0.04). Similar results were obtained for urine NTx. There was a negative association between TRAP and serum IFN-beta (P = 0.03).
Conclusions. In this population of children and young adults with moderate lupus disease activity, glucocorticoid dose was a negative predictor of bone formation, whereas lupus disease activity was not. Interestingly, lupus disease activity was a negative predictor of bone resorption, suggesting that lupus disease activity is not the primary factor contributing to the bone deficits of childhood-onset SLE. The potential protective role of IFN-beta and the effects of SLE treatment on bone loss require further study.
C1 [von Scheven, Emily] Univ Calif San Francisco, Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA.
[Baker-LePain, Julie C.; Nakamura, Mary C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Nakamura, Mary C.] San Francisco VA Med Ctr, Dept Rheumatol, San Francisco, CA USA.
[Shepherd, John] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
RP von Scheven, E (reprint author), Univ Calif San Francisco, Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA.
EM evonsche@peds.ucsf.edu
FU National Institutes of Health/National Center for Research Resources
UCSF-Clinical and Translational Science Institute [UL1 RR024131];
NIH/NCRR [16319]; NIH [AR007304]; Department of Veterans' Affairs
FX Funding: This publication was supported by National Institutes of
Health/National Center for Research Resources UCSF-Clinical and
Translational Science Institute Grant Number UL1 RR024131 and NIH/NCRR
grant number 16319. Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the NIH.
J.C.B.-L. was supported by NIH Academic Rheumatology and Clinical
Immunology Training Grant Number AR007304. M.C.N. was supported by the
Department of Veterans' Affairs.
NR 42
TC 10
Z9 10
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD MAR
PY 2011
VL 50
IS 3
BP 611
EP 619
DI 10.1093/rheumatology/keq307
PG 9
WC Rheumatology
SC Rheumatology
GA 726SE
UT WOS:000287745600025
PM 21098573
ER
PT J
AU Kern, RS
Gold, JM
Dickinson, D
Green, MF
Nuechterlein, KH
Baade, LE
Keefe, RSE
Mesholam-Gately, RI
Seidman, LJ
Lee, C
Sugar, CA
Marder, SR
AF Kern, Robert S.
Gold, James M.
Dickinson, Dwight
Green, Michael F.
Nuechterlein, Keith H.
Baade, Lyle E.
Keefe, Richard S. E.
Mesholam-Gately, Raquelle I.
Seidman, Larry J.
Lee, Cathy
Sugar, Catherine A.
Marder, Stephen R.
TI The MCCB impairment profile for schizophrenia outpatients: Results from
the MATRICS psychometric and standardization study
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE MCCB; Cognition; Schizophrenia; Profile
ID CONSENSUS COGNITIVE BATTERY; WORK PERFORMANCE; MEMORY; REHABILITATION;
NEUROCOGNITION; IDENTIFICATION; METAANALYSIS; 1ST-EPISODE; PREDICTORS
AB The MATRICS Psychometric and Standardization Study was conducted as a final stage in the development of the MATRICS Consensus Cognitive Battery (MCCB). The study included 176 persons with schizophrenia or schizoaffective disorder and 300 community residents. Data were analyzed to examine the cognitive profile of clinically stable schizophrenia patients on the MCCB. Secondarily, the data were analyzed to identify which combination of cognitive domains and corresponding cut-off scores best discriminated patients from community residents, and patients competitively employed vs. those not. Raw scores on the ten MCCB tests were entered into the MCCB scoring program which provided age- and gender-corrected T-scores on seven cognitive domains. To test for between-group differences, we conducted a 2 (group) x 7 (cognitive domain) MANOVA with follow-up independent t-tests on the individual domains. Classification and regression trees (CART) were used for the discrimination analyses. Examination of patient T-scores across the seven cognitive domains revealed a relatively compact profile with T-scores ranging from 33.4 for speed of processing to 39.3 for reasoning and problem-solving. Speed of processing and social cognition best distinguished individuals with schizophrenia from community residents: speed of processing along with visual leaming and attention/vigilance optimally distinguished patients competitively employed from those who were not. The cognitive profile findings provide a standard to which future studies can compare results from other schizophrenia samples and related disorders; the classification results point to specific areas and levels of cognitive impairment that may advance work rehabilitation efforts. Published by Elsevier B.V.
C1 [Kern, Robert S.; Green, Michael F.; Nuechterlein, Keith H.; Sugar, Catherine A.; Marder, Stephen R.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Kern, Robert S.; Green, Michael F.; Marder, Stephen R.] VISN 22 Mental Illness Res, Dept Vet Affairs, Los Angeles, CA USA.
[Kern, Robert S.; Green, Michael F.; Marder, Stephen R.] Ctr Clin, Los Angeles, CA USA.
[Gold, James M.] Univ Maryland Baltimore, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD USA.
[Dickinson, Dwight] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Baade, Lyle E.] Univ Kansas, Sch Med, Wichita, KS 67214 USA.
[Keefe, Richard S. E.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA.
[Mesholam-Gately, Raquelle I.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat,Publ Psychiat Div, Beth Israel Deaconess Med Ctr,Massachusetts Menta, Boston, MA 02115 USA.
[Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lee, Cathy; Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare Ctr, MIRECC 210 A,Bldg 210,Room 116,11301 Wilshire Blv, Los Angeles, CA 90073 USA.
EM rkern@ucla.edu
FU National Institute for Mental Health [N01MH22006]
FX Funding for the MATRICS Initiative was provided through Contract
N01MH22006 from the National Institute for Mental Health to the
University of California, Los Angeles (Dr. Marder, PI; Dr. Green, Co-PI;
Dr. Fenton, Project Officer). Funding for this study came from an Option
(Dr. Green, PI; Dr. Nuechterlein, Co-PI) to the NIMH MATRICS Initiative.
The NIMH had no further role in study design; in the collection,
analysis and interpretation of data; in the writing of the report; and
in the decision to submit the paper for publication.
NR 29
TC 65
Z9 68
U1 5
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAR
PY 2011
VL 126
IS 1-3
BP 124
EP 131
DI 10.1016/j.schres.2010.11.008
PG 8
WC Psychiatry
SC Psychiatry
GA 743NS
UT WOS:000289025700018
PM 21159492
ER
PT J
AU Sousse, LE
Yamamoto, Y
Enkhbaatar, P
Rehberg, SW
Wells, SM
Leonard, S
Traber, MG
Yu, YM
Cox, RA
Hawkins, HK
Traber, LD
Herndon, DN
Traber, DL
AF Sousse, Linda E.
Yamamoto, Yusuke
Enkhbaatar, Perenlei
Rehberg, Sebastian W.
Wells, Sandra M.
Leonard, Scott
Traber, Maret G.
Yu, Yong-Ming
Cox, Robert A.
Hawkins, Hal K.
Traber, Lillian D.
Herndon, David N.
Traber, Daniel L.
TI ACUTE LUNG INJURY-INDUCED COLLAGEN DEPOSITION IS ASSOCIATED WITH
ELEVATED ASYMMETRIC DIMETHYLARGININE AND ARGINASE ACTIVITY
SO SHOCK
LA English
DT Article
DE Fibrosis; NO synthase; oxidative stress; arginine metabolism
ID SMOKE-INHALATION INJURY; NITRIC-OXIDE SYNTHASE; CIGARETTE-SMOKE; BURN
INJURY; SHEEP; EXPRESSION; INHIBITOR; CELLS; DIMETHYLAMINOHYDROLASE;
MALONDIALDEHYDE
AB Evidence suggests that lung structure and function are partly maintained by a balance between the competing arginine-metabolizing enzymes arginase and nitric oxide (NO) synthase. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. It is metabolized by dimethylarginine dimethylaminohydrolase 2 (DDAH-2), which is oxidant-sensitive. The mechanism that induces excess lung collagen deposition in burned patients has not yet been explored. Our objective was to investigate the role of ADMA and the arginase pathway in acute lung injury. An ovine model for burn and smoke inhalation injury was used to assess excess lung collagen deposition. Sheep were deeply anesthetized during the injury, mechanically ventilated, resuscitated with fluid, and killed after either 2 or 3 weeks. Lungs were assessed histologically and biochemically for collagen content, arginase activity, lipid peroxidation product and antioxidant concentration, and protein concentrations. Plasma was assessed for amino acid and nitrate/nitrite concentrations. Burn and inhalation injury resulted in significantly reduced pulmonary function and increased lung collagen deposition. These physiological changes were associated with significantly increased lung arginase activity, collagen synthesis precursor ornithine aminotransferase, and ornithine decarboxylase, which is associated with cell proliferation. Significant decreases in plasma nitrate/nitrite after injury were associated with increased lung ADMA concentrations and decreased DDAH-2 expression. The decreased DDAH-2 expression was associated with significantly increased lipid peroxidation product and decreased antioxidant content in the lung. These data support that excess lung collagen deposition and reduced pulmonary function in acute lung injury after burn and inhalation injury are mediated through the arginase pathway.
C1 [Sousse, Linda E.; Yamamoto, Yusuke; Enkhbaatar, Perenlei; Rehberg, Sebastian W.; Cox, Robert A.; Hawkins, Hal K.; Traber, Lillian D.; Traber, Daniel L.] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA.
[Sousse, Linda E.; Yamamoto, Yusuke; Enkhbaatar, Perenlei; Rehberg, Sebastian W.; Cox, Robert A.; Hawkins, Hal K.; Traber, Lillian D.; Traber, Daniel L.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Wells, Sandra M.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Environm Agr & Occupat Hlth, Omaha, NE USA.
[Leonard, Scott; Traber, Maret G.] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA.
[Yu, Yong-Ming] MassGen Hosp Children, Burn Unit, Boston, MA USA.
[Herndon, David N.] Shriners Hosp Children, Burn Unit, Galveston, TX 77550 USA.
RP Traber, DL (reprint author), Univ Texas Med Branch, Dept Anesthesiol, 301 Univ Blvd,Route 1102, Galveston, TX 77555 USA.
EM dltraber@utmb.edu
OI Traber, Maret/0000-0002-2892-4024
FU National Institute of General Medical Science [GM66312, GM60668];
National Heart, Lung, and Blood Institute [R00HL088550]; Shrine
Hospitals for Children (SHC) [8541, 8450]
FX This work was supported by Grants GM66312 and GM60668 from the National
Institute of General Medical Science, Grant R00HL088550 from the
National Heart, Lung, and Blood Institute, and Grants 8541 and 8450 from
the Shrine Hospitals for Children (SHC). The contents of this
publication are solely the responsibility of the authors and do not
necessarily represent the official views of the NIH or the SHC.
NR 35
TC 11
Z9 11
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
J9 SHOCK
JI Shock
PD MAR
PY 2011
VL 35
IS 3
BP 282
EP 288
DI 10.1097/SHK.0b013e3181fddd82
PG 7
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA 727DT
UT WOS:000287778500010
PM 20938379
ER
PT J
AU Nehra, D
Goldstein, AM
AF Nehra, Deepika
Goldstein, Allan M.
TI Intestinal malrotation: Varied clinical presentation from infancy
through adulthood
SO SURGERY
LA English
DT Article
ID MIDGUT MALROTATION; SURGICAL-MANAGEMENT; VOLVULUS; ROTATION; ANOMALIES;
NONROTATION; OBSTRUCTION; MORBIDITY; AGE; CT
AB Background. The purpose of this study was to determine the incidence and clinical presentation of intestinal malrotation from infancy through adulthood by examining the experience of a single institution caring for patients of all ages with this condition.
Methods. We conducted a retrospective review on all patients diagnosed with intestinal malrotation at Massachusetts General Hospital between 1992 and 2009. Patient demographics, clinical history, diagnostic tests, operative procedures, and outcome variables were recorded. Patients were divided into 3 age groups: infants (< 1 year), children (1-18 years), and adults (18 years).
Results. We identified 170 patients, of whom 31% were infants, 21% were children, and 48% were adults. Infants nearly always presented with emesis (93%), whereas adults most commonly presented with abdominal pain (87%), and less often with emesis (37%) or nausea (31%). The incidence of volvulus declined with age, from 37% to 22% to 12%, in each of the 3 age groups, respectively. Although infants were most often diagnosed within hours or days of symptom onset, 59% of children and 32% of adults experienced symptoms fir years before diagnosis. Upper gastrointestinal series was the most common imaging study performed in infants and children, but was replaced by abdominal computed tomography in adults. All infants and children underwent a Ladd's procedure, compared with only 61% of adults. The majority of patients experienced resolution of symptoms after operative intervention, although this decreased slightly with age.
Conclusion. Intestinal malrotation can occur in patients of any age and, in contrast with traditional teaching, nearly half of these patients may present during adulthood. An increased awareness of this entity and an understanding of its varied presentation at different ages may reduce time to diagnosis and improve patient outcome. (Surgery 2011;149:386-93.)
C1 [Nehra, Deepika] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA.
RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Warren 1153, Boston, MA 02114 USA.
EM agoldstein@partners.org
NR 36
TC 35
Z9 40
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD MAR
PY 2011
VL 149
IS 3
BP 386
EP 393
DI 10.1016/j.surg.2010.07.004
PG 8
WC Surgery
SC Surgery
GA 731MQ
UT WOS:000288111500012
PM 20719352
ER
PT J
AU Viswanathan, J
Haapasalo, A
Bottcher, C
Miettinen, R
Kurkinen, KMA
Lu, A
Thomas, A
Maynard, CJ
Romano, D
Hyman, BT
Berezovska, O
Bertram, L
Soininen, H
Dantuma, NP
Tanzi, RE
Hiltunen, M
AF Viswanathan, Jayashree
Haapasalo, Annakaisa
Bottcher, Claudia
Miettinen, Riitta
Kurkinen, Kaisa M. A.
Lu, Alice
Thomas, Anne
Maynard, Christa J.
Romano, Donna
Hyman, Bradley T.
Berezovska, Oksana
Bertram, Lars
Soininen, Hilkka
Dantuma, Nico P.
Tanzi, Rudolph E.
Hiltunen, Mikko
TI Alzheimer's Disease-Associated Ubiquilin-1 Regulates Presenilin-1
Accumulation and Aggresome Formation
SO TRAFFIC
LA English
DT Article
DE beta-amyloid precursor protein; high-molecular-weight forms; PEN-2;
proteasomal degradation; transcript variant
ID AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE ACTIVITY; BETA-APP;
PROTEASOME; UBIQUITINATION; IDENTIFICATION; DEGRADATION;
ENDOPROTEOLYSIS; AGGREGATION; INTERACTS
AB The Alzheimer's disease (AD)-associated ubiquilin-1 regulates proteasomal degradation of proteins, including presenilin (PS). PS-dependent gamma-secretase generates beta-amyloid (A beta) peptides, which excessively accumulate in AD brain. Here, we have characterized the effects of naturally occurring ubiquilin-1 transcript variants (TVs) on the levels and subcellular localization of PS1 and other gamma-secretase complex components and subsequent gamma-secretase function in human embryonic kidney 293, human neuroblastoma SH-SY5Y and mouse primary cortical cells. Full-length ubiquilin-1 TV1 and TV3 that lacks the proteasome-interaction domain increased full-length PS1 levels as well as induced accumulation of high-molecular-weight PS1 and aggresome formation. Accumulated PS1 colocalized with TV1 or TV3 in the aggresomes. Electron microscopy indicated that aggresomes containing TV1 or TV3 were targeted to autophagosomes. TV1- and TV3-expressing cells did not accumulate other unrelated proteasome substrates, suggesting that the increase in PS1 levels was not because of a general impairment of the ubiquitin-proteasome system. Furthermore, PS1 accumulation and aggresome formation coincided with alterations in A beta levels, particularly in cells overexpressing TV3. These effects were not related to altered gamma-secretase activity or PS1 binding to TV3. Collectively, our results indicate that specific ubiquilin-1 TVs can cause PS1 accumulation and aggresome formation, which may impact AD pathogenesis or susceptibility.
C1 [Viswanathan, Jayashree; Haapasalo, Annakaisa; Miettinen, Riitta; Kurkinen, Kaisa M. A.; Soininen, Hilkka; Hiltunen, Mikko] Univ Eastern Finland, Dept Neurol, Inst Clin Med, Kuopio, Finland.
[Viswanathan, Jayashree; Haapasalo, Annakaisa; Miettinen, Riitta; Kurkinen, Kaisa M. A.; Soininen, Hilkka; Hiltunen, Mikko] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
[Bottcher, Claudia; Maynard, Christa J.; Dantuma, Nico P.] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
[Miettinen, Riitta] CNServices Ltd, Kuopio, Finland.
[Lu, Alice; Romano, Donna; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA.
[Lu, Alice; Romano, Donna; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Thomas, Anne; Hyman, Bradley T.; Berezovska, Oksana] Harvard Univ, Massachusetts Alzheimer Dis Res Ctr, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Sch Med, Charlestown, MA USA.
[Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, Berlin, Germany.
RP Hiltunen, M (reprint author), Univ Eastern Finland, Dept Neurol, Inst Clin Med, Kuopio, Finland.
EM mikko.hiltunen@uef.fi
RI Bertram, Lars/K-3889-2015;
OI Bertram, Lars/0000-0002-0108-124X; Dantuma, Nico/0000-0002-6090-4170;
Chadchankar, Jayashree/0000-0002-0189-569X
FU EC [MEST-CT-2005-019217]; Health Research Council of the Academy of
Finland; EVO of Kuopio University Hospital [5772708]; Nordic Centre of
Excellence in Neurodegeneration; Sigrid Juselius Foundation; Swedish
Research Council; Wenner-Gren Foundation; NIH [AG15379]; Cure
Alzheimer's Fund; NIA
FX This study was supported by EC FP6, MEST-CT-2005-019217 (to J. V.), the
Health Research Council of the Academy of Finland (to A. H., H. S. and
M. H.), EVO grant 5772708 of Kuopio University Hospital (to H. S.), the
Nordic Centre of Excellence in Neurodegeneration (to N. P. D., H. S. and
M. H.), Sigrid Juselius Foundation (to M. H.), the Swedish Research
Council (to N. P. D.), the Wenner-Gren Foundation (to C. B.), NIH
AG15379 grant (to O. B.) and 'Cure Alzheimer's Fund' and NIA (to R. T.).
The authors wish to thank Dr Stefan Lichtenthaler
(Adolf-Butenandt-Institute, Ludwig-Maximilians-University) for the
generous gift of the HEK293-AP-APP cells, Dr Samuel E. Gandy (Mount
Sinai School of Medicine, New York, NY) for kindly providing the Ab14
antibody and Dr Garry Wong (A.I. Virtanen Institute for Molecular
Sciences, University of Eastern Finland) for revising the language of
the manuscript.
NR 45
TC 36
Z9 42
U1 0
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD MAR
PY 2011
VL 12
IS 3
BP 330
EP 348
DI 10.1111/j.1600-0854.2010.01149.x
PG 19
WC Cell Biology
SC Cell Biology
GA 719IS
UT WOS:000287199000008
PM 21143716
ER
PT J
AU Glasgow, R
Emmons, KM
AF Glasgow, Russ
Emmons, Karen M.
TI The public health need for patient-reported measures and health
behaviors in electronic health records: a policy statement of the
Society of Behavioral Medicine
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
C1 [Glasgow, Russ] Kaiser Permanente Colorado, Denver, CO USA.
[Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02215 USA.
RP Emmons, KM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW601, Boston, MA 02215 USA.
EM karen_m_emmons@dfci.harvard.edu
NR 6
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD MAR
PY 2011
VL 1
IS 1
BP 108
EP 109
DI 10.1007/s13142-011-0017-3
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V39LG
UT WOS:000209411900018
PM 24073037
ER
PT J
AU Bruner, DW
Hanisch, LJ
Reeve, BB
Trotti, AM
Schrag, D
Sit, L
Mendoza, TR
Minasian, L
O'Mara, A
Denicoff, AM
Rowland, JH
Montello, M
Geoghegan, C
Abernethy, AP
Clauser, SB
Castro, K
Mitchell, SA
Burke, L
Trentacosti, AM
Basch, EM
AF Bruner, Deborah Watkins
Hanisch, Laura J.
Reeve, Bryce B.
Trotti, Andy M.
Schrag, Deborah
Sit, Laura
Mendoza, Tito R.
Minasian, Lori
O'Mara, Ann
Denicoff, Andrea M.
Rowland, Julia H.
Montello, Michael
Geoghegan, Cindy
Abernethy, Amy P.
Clauser, Steven B.
Castro, Kathleen
Mitchell, Sandra A.
Burke, Laurie
Trentacosti, Ann Marie
Basch, Ethan M.
TI Stakeholder perspectives on implementing the National Cancer Institute's
patient-reported outcomes version of the Common Terminology Criteria for
Adverse Events (PRO-CTCAE)
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Patient-reported outcomes; Symptoms; adverse events; Oncology; Cancer;
Clinical trials; Toxicity; safety; Tolerability; Comparative
effectiveness research; Cooperative groups; National Cancer Institute
AB The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the "PRO-CTCAE." The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI's cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty-eight percent felt that patients in clinical trials would be willing to self-report adverse symptoms at clinic visits via computer, and 68% felt patients would self-report weekly from home via the internet or an automated telephone system. Lack of computers and limited space and personnel were seen as potential barriers to in-clinic self-reporting, but these were judged to be surmountable with adequate funding. The PRO-CTCAE items and software are viewed by a majority of survey respondents as a means to improve adverse event data quality and comprehensiveness, enhance clinical decision-making, and foster patient-clinician communication. Research is ongoing to assess the measurement properties and feasibility of implementing this measure in cancer clinical trials.
C1 [Bruner, Deborah Watkins] Univ Penn, Abramson Canc Ctr, Sch Nursing, Philadelphia, PA 19104 USA.
[Hanisch, Laura J.] Univ Penn, Abramson Canc Ctr, Canc Control & Outcomes Program, Philadelphia, PA 19104 USA.
[Reeve, Bryce B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Lineberger Comprehens Canc Ctr, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA.
[Trotti, Andy M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Schrag, Deborah] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA.
[Sit, Laura; Basch, Ethan M.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Grp, New York, NY 10065 USA.
[Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA.
[Minasian, Lori] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[O'Mara, Ann] NCI, Palliat Care Res Community Oncol & Prevent Trial, Canc Prevent Div, Bethesda, MD 20892 USA.
[Denicoff, Andrea M.] NCI, Clin Invest Branch, CTEP, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,DHHS, Bethesda, MD 20892 USA.
[Montello, Michael] NCI, Clin Trials Technol, Bethesda, MD 20892 USA.
[Geoghegan, Cindy] Breast Canc Network Strength, Chicago, IL 60603 USA.
[Abernethy, Amy P.] Duke Univ, Med Ctr, Sch Med, Dept Med, Durham, NC 27710 USA.
[Clauser, Steven B.; Castro, Kathleen; Mitchell, Sandra A.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Burke, Laurie; Trentacosti, Ann Marie] US FDA, Study Endpoints & Label Dev, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Basch, EM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Grp, 307 E 63rd St,2nd Floor, New York, NY 10065 USA.
EM basche@mskcc.org
OI Abernethy, Amy/0000-0001-6930-8722
FU National Cancer Institute [HHSN261200800043C]
FX This work was supported by the National Cancer Institute under contract
HHSN261200800043C awarded to Dr. Ethan Basch, PI.
NR 26
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U1 0
U2 2
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD MAR
PY 2011
VL 1
IS 1
BP 110
EP 122
DI 10.1007/s13142-011-0025-3
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V39LG
UT WOS:000209411900019
PM 24073038
ER
PT J
AU Varghese, M
Zhao, W
Wang, J
Cheng, A
Qian, XJ
Chaudhry, A
Ho, L
Pasinetti, GM
AF Varghese, Merina
Zhao, Wei
Wang, Jun
Cheng, Alice
Qian, Xianjuan
Chaudhry, Amna
Ho, Lap
Pasinetti, Giulio Maria
TI MITOCHONDRIAL BIOENERGETICS IS DEFECTIVE IN PRESYMPTOMATIC TG2576 AD
MICE
SO TRANSLATIONAL NEUROSCIENCE
LA English
DT Article
DE Alzheimer's disease; Amyloid; Dementia; Energy Metabolism; Memory;
Mitochondria; Oxidative phosphorylation; Oxygen Consumption; Tg2576
ID DEHYDROGENASE COMPLEX ACTIVITY; ALZHEIMERS-DISEASE BRAIN;
CYTOCHROME-C-OXIDASE; MOUSE MODEL; PYRUVATE-DEHYDROGENASE; SYNAPTIC
MITOCHONDRIA; TRANSGENIC MICE; PROTEIN; MEMORY; ACCUMULATION
AB Alzheimer's disease (AD) is an age-related dementia, with the pathological hallmarks of neuritic plaques and neurofibrillary tangles, brain atrophy and loss of synaptic terminals. Dysfunctional mitochondrial bioenergetics is implicated as a contributing factor to the cognitive decline observed in AD. We hypothesized that, in the presence of the AD neurotoxic peptide beta-amyloid, mitochondrial respiration is impaired early in synaptic terminals, which are vital to cognitive performance, preferentially in cognitive centers of the brain. We compared oxygen consumption in synaptosomal and perikaryal mitochondria prepared from the cerebral cortex and cerebellum of wild type (WT) and AD transgenic Tg2576 mice. Compared to WT mice, Tg2576 mice showed decreased mitochondrial respiration in the cerebral cortex specifically in synaptosomal fraction, while the perikaryal mitochondria were unaffected. Neither mitochondrial fraction was affected in the cerebellum of Tg2576 mice as compared to WT. The occurrence of a bioenergetic defect in synaptic terminals of mice over-expressing mutant beta-amyloid, in particular in an area of the brain important to cognition, points to an early role of mitochondrial defects in the onset of cognitive deficits in AD.
C1 [Varghese, Merina; Zhao, Wei; Wang, Jun; Cheng, Alice; Qian, Xianjuan; Chaudhry, Amna; Ho, Lap; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
[Varghese, Merina; Zhao, Wei; Wang, Jun; Cheng, Alice; Qian, Xianjuan; Ho, Lap; Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Educ & Clin Ctr, Bronx, NY 10468 USA.
RP Varghese, M (reprint author), Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
EM giulio.pasinetti@mssm.edu
OI Varghese, Merina/0000-0002-1517-3903
FU National Institutes of Health (NIH) [AG02219]; Department of Veterans
Affairs
FX We are grateful to Dr David B. Hicks for technical assistance. This
project was funded by grants from the National Institutes of Health (NIH
AG02219 Project 2) and the Department of Veterans Affairs.
NR 23
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U1 1
U2 4
PU VERSITA
PI WARSAW
PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND
SN 2081-3856
J9 TRANSL NEUROSCI
JI Transl. Neurosci.
PD MAR
PY 2011
VL 2
IS 1
BP 1
EP 5
DI 10.2478/s13380-011-0011-8
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 873MD
UT WOS:000298886500001
ER
PT J
AU Ning, MM
Lo, EH
AF Ning, MingMing
Lo, Eng H.
TI Opportunities and Challenges in Omics (vol 1, pg 233, 2010)
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Correction
C1 [Ning, MingMing; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Res Lab, Clin Prote Res Ctr, Boston, MA 02114 USA.
[Ning, MingMing; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Clin Prote Res Ctr, Res Lab, Boston, MA 02114 USA.
[Ning, MingMing; Lo, Eng H.] Harvard Univ, Sch Med, Boston, MA USA.
RP Ning, MM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Res Lab, Clin Prote Res Ctr, Boston, MA 02114 USA.
EM Ning@hms.harvard.edu; Lo@helix.mgh.harvard.edu
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-4483
J9 TRANSL STROKE RES
JI Transl. Stroke Res.
PD MAR
PY 2011
VL 2
IS 1
BP 128
EP 128
DI 10.1007/s12975-010-0058-9
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 943YB
UT WOS:000304162800016
PM 24323589
ER
PT J
AU Flynn, RL
Zou, L
AF Flynn, Rachel Litman
Zou, Lee
TI ATR: a master conductor of cellular responses to DNA replication stress
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
ID INTERSTRAND CROSS-LINK; S-PHASE CHECKPOINT; FANCONI-ANEMIA PATHWAY;
CHROMATIN REMODELING COMPLEX; HOLLIDAY JUNCTION RESOLVASE; DAMAGE
CHECKPOINT; STRANDED-DNA; MONOUBIQUITINATED FANCD2; SIGNALING PATHWAYS;
POLYMERASE-ALPHA
AB The integrity of the genome is constantly challenged by intrinsic and extrinsic genotoxic stresses that damage DNA. The cellular responses to DNA damage are orchestrated by DNA damage signaling pathways, also known as DNA damage checkpoints. These signaling pathways play crucial roles in detecting DNA damage, regulating DNA repair and coordinating DNA repair with other cellular processes. In vertebrates, the ATM- and Rad3-related (ATR) kinase plays a key role in the response to a broad spectrum of DNA damage and DNA replication stress. Here, we will discuss the recent findings on how ATR is activated by DNA damage and how it protects the genome against interference with DNA replication.
C1 [Flynn, Rachel Litman; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
[Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
EM zou.lee@mgh.harvard.edu
FU National Institutes of Health [GM076388]; American Cancer Society
[0902501]
FX L.Z. is supported by a National Institutes of Health grant (GM076388)
and is an Ellison New Scholar on Aging. R.L.F. is supported by an
American Cancer Society fellowship 0902501. We thank Dr. Bunsyo Shiotani
for helpful comments and apologize to our colleagues whose work we could
not cover owing to length constrains.
NR 100
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U1 0
U2 16
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD MAR
PY 2011
VL 36
IS 3
BP 133
EP 140
DI 10.1016/j.tibs.2010.09.005
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 740WE
UT WOS:000288824300002
PM 20947357
ER
PT J
AU Garcia-Garcia, F
De la Herran-Arita, AK
Juarez-Aguilar, E
Regalado-Santiago, C
Millan-Aldaco, D
Blanco-Centurion, C
Drucker-Colin, R
AF Garcia-Garcia, Fabio
De la Herran-Arita, Alberto K.
Juarez-Aguilar, Enrique
Regalado-Santiago, Citlalli
Millan-Aldaco, Diana
Blanco-Centurion, Carlos
Drucker-Colin, Rene
TI Growth hormone improves hippocampal adult cell survival and counteracts
the inhibitory effect of prolonged sleep deprivation on cell
proliferation
SO BRAIN RESEARCH BULLETIN
LA English
DT Article
DE BrdU; Cell proliferation; Neuroprotection; Neuronal survival; Growth
hormone
ID SLOW-WAVE SLEEP; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; DENTATE
GYRUS; FACTOR-I; RAT HYPOTHALAMUS; DEFICIENT ADULTS; GENE-EXPRESSION;
REM-SLEEP; NEUROGENESIS
AB Sleep deprivation (SD) produces numerous deleterious changes in brain cells, including apoptosis. It has been demonstrated that growth hormone (GH) stimulates cell growth and counteracts apoptosis, although this anti-apoptotic effect has not been tested against SD. To determine the protective effect of GH administration on cell proliferation and survival in the dentate gyrus (DG) of the hippocampus after sleep deprivation: we injected Wistar adult rats with a low dose of recombinant human GH (rhGH 5 ng/kg) per seven days and then we gently sleep deprived the animals for 48 consecutive hours. 5-Bromodeoxiuridine (BrdU) was administered to assess cell proliferation after the GH treatment and NeuN was used as marker of cell fate. Our results indicate that GH produced a three fold increase in the number of BrdU positive cells within the DG [Control = 1044 +/- 106.38 cells, rhGH = 2952 +/- 99.84 cells, P < 0.011. In contrast, 48 h of SD significantly reduced cell proliferation but this effect was antagonized by the GH administration [SD = 540 +/- 18.3 cells, rhGH + SD = 1116 +/- 84.48 cells, P < 0.004]. Paradoxically, SD and GH administration increased cell survival separately but no significantly compared with control animals. However, cell survival was increased in animals treated with rhGH + SD compared to rats injected with saline solution [P < 0.04]. Within the survival cells, the percentage of neurons was higher in SD animals [95%] compared with saline group, while this percentage (NeuN positive cells) was increased in animals treated with rhGH + SD [120%] compared with rhGH [25%] alone. Our findings indicate that CH strongly promotes cell proliferation in the adult brain and also protects the hippocampal neuronal precursors against the deleterious effect of prolonged sleep loss. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Garcia-Garcia, Fabio; Juarez-Aguilar, Enrique; Regalado-Santiago, Citlalli] Univ Veracruzana, Dept Biomed, Inst Ciencias Salud, Xalapa 91190, Veracruz, Mexico.
[De la Herran-Arita, Alberto K.; Millan-Aldaco, Diana; Drucker-Colin, Rene] Univ Nacl Autonoma Mexico, Dept Neurociencias, Inst Fisiol Celular, Mexico City 04510, DF, Mexico.
[Blanco-Centurion, Carlos] Harvard Univ, Sch Med, Dept Neurol, Boston VA Healthcare Syst, Boston, MA 02132 USA.
RP Garcia-Garcia, F (reprint author), Univ Veracruzana, Dept Biomed, Inst Ciencias Salud, Av Luis Castelazo Ayala S-N, Xalapa 91190, Veracruz, Mexico.
EM fgarcia@uv.mx
OI Garcia-Garcia, Fabio/0000-0002-3756-9845
FU PROMEP [UVER-PTC-118]
FX This work was supported by a grant from PROMEP UVER-PTC-118. The authors
wish to thank Marcela Palomero-Rivero for technical assistance.
NR 65
TC 13
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U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD FEB 28
PY 2011
VL 84
IS 3
BP 252
EP 257
DI 10.1016/j.brainresbull.2011.01.003
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 741SV
UT WOS:000288885800009
PM 21256199
ER
PT J
AU Wang, TJ
AF Wang, Thomas J.
TI Usefulness of Novel Screening Tests for Cardiovascular Disease
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID CORONARY-HEART-DISEASE; RISK PREDICTION; BIOMARKERS; EVENTS
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA.
EM tjwang@partners.org
NR 13
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD FEB 28
PY 2011
VL 171
IS 4
BP 284
EP 285
DI 10.1001/archinternmed.2010.543
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 728FD
UT WOS:000287858900002
PM 21357802
ER
PT J
AU Munshi, MN
Segal, AR
Suhl, E
Staum, E
Desrochers, L
Sternthal, A
Giusti, J
McCartney, R
Lee, Y
Bonsignore, P
Weinger, K
AF Munshi, Medha N.
Segal, Alissa R.
Suhl, Emmy
Staum, Elizabeth
Desrochers, Laura
Sternthal, Adrianne
Giusti, Judy
McCartney, Richard
Lee, Yishan
Bonsignore, Patricia
Weinger, Katie
TI Frequent Hypoglycemia Among Elderly Patients With Poor Glycemic Control
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID OLDER-ADULTS; ASSOCIATION; PERFORMANCE
AB Background: Episodes of hypoglycemia are particularly dangerous in the older population. To reduce the risk of hypoglycemia, relaxation of the standard hemoglobin A(1c) (HbA(1c)) goals has been proposed for frail elderly patients. However, the risk of hypoglycemia in this population with higher HbA(1c) levels is unknown.
Methods: Patients 69 years or older with HbA(1C) values of 8% or greater were evaluated with blinded continuous glucose monitoring for 3 days.
Results: Forty adults (mean [SD] age, 75 [5] years; HbA1C value, 9.3% [1.3%]; diabetes duration, 22 [14] years; 28 patients [70%] with type 2 diabetes mellitus; and 37 [93%] using insulin) were evaluated. Twenty-six patients (65%) experienced 1 or more episodes of hypoglycemia (glucose level < 70 mg/dL). Among these, 12 (46%) experienced a glucose level below 50 mg/dL and 19 (73%), a level below 60 mg/dL. The average number of episodes was 4; average duration, 46 minutes. Eighteen patients (69%) had at least 1 nocturnal episode (10 PM to 6 AM). Of the total of 102 hypoglycemic episodes, 95 (93%) were unrecognized by finger-stick glucose measurements performed 4 times a day or by symptoms.
Conclusions: Hypoglycemic episodes are common in older adults with poor glycemic control. Raising HbA(1C) goals may not be adequate to prevent hypoglycemia in this population.
C1 [Munshi, Medha N.; Segal, Alissa R.; Staum, Elizabeth] Joslin Diabet Ctr, Sect Adult Diabet, Boston, MA 02215 USA.
[Suhl, Emmy; Sternthal, Adrianne; Giusti, Judy; Lee, Yishan] Joslin Diabet Ctr, Sect Clin Behav & Outcome Res, Boston, MA 02215 USA.
[Munshi, Medha N.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA.
[Munshi, Medha N.; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA.
[Segal, Alissa R.] Massachusetts Coll Pharm & Hlth Sci, Dept Pharm Practice, Boston, MA USA.
[Desrochers, Laura] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA.
[Bonsignore, Patricia] Valley Med Grp, Diabet Program, Amherst, MA USA.
RP Munshi, MN (reprint author), Joslin Diabet Ctr, Sect Adult Diabet, 1 Joslin Pl, Boston, MA 02215 USA.
EM medha.munshi@joslin.harvard.edu
FU American Diabetes Association [1-07-CR-40]; Department of Defense
Peer-Reviewed Medical Research Program of the Office of the
Congressionally Directed Medical Research [W81XWH-07-1-0282]; Graetz
Foundation; National Institute of Diabetes and Digestive and Kidney
Diseases [P30 NIDDK36836, R01 NIDDK060115]
FX This study was supported in part by grant 1-07-CR-40 from a clinical
research award from the American Diabetes Association (Dr Munshi), grant
W81XWH-07-1-0282 from the Department of Defense Peer-Reviewed Medical
Research Program of the Office of the Congressionally Directed Medical
Research Programs (Dr Munshi), and by grants from the Graetz Foundation
(Dr Munshi), and grants P30 NIDDK36836 (Joslin Diabetes Center) and R01
NIDDK060115 (Dr Weinger) from the National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 14
TC 53
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U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD FEB 28
PY 2011
VL 171
IS 4
BP 362
EP 364
DI 10.1001/archinternmed.2010.539
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 728FD
UT WOS:000287858900019
PM 21357814
ER
PT J
AU Petnicki-Ocwieja, T
DeFrancesco, AS
Chung, E
Darcy, CT
Bronson, RT
Kobayashi, KS
Hu, LT
AF Petnicki-Ocwieja, Tanja
DeFrancesco, Alicia S.
Chung, Erin
Darcy, Courtney T.
Bronson, Roderick T.
Kobayashi, Koichi S.
Hu, Linden T.
TI Nod2 Suppresses Borrelia burgdorferi Mediated Murine Lyme Arthritis and
Carditis through the Induction of Tolerance
SO PLOS ONE
LA English
DT Article
ID INNATE IMMUNE ACTIVATION; TOLL-LIKE RECEPTOR-2; NF-KAPPA-B;
CROHNS-DISEASE; STREPTOCOCCUS-PNEUMONIAE; INFLAMMATORY RESPONSES;
LEGIONELLA-PNEUMOPHILA; CYTOKINE INDUCTION; ADAPTIVE IMMUNITY;
HOST-DEFENSE
AB The internalization of Borrelia burgdorferi, the causative agent of Lyme disease, by phagocytes is essential for an effective activation of the immune response to this pathogen. The intracellular, cytosolic receptor Nod2 has been shown to play varying roles in either enhancing or attenuating inflammation in response to different infectious agents. We examined the role of Nod2 in responses to B. burgdorferi. In vitro stimulation of Nod2 deficient bone marrow derived macrophages (BMDM) resulted in decreased induction of multiple cytokines, interferons and interferon regulated genes compared with wild-type cells. However, B. burgdorferi infection of Nod2 deficient mice resulted in increased rather than decreased arthritis and carditis compared to control mice. We explored multiple potential mechanisms for the paradoxical response in in vivo versus in vitro systems and found that prolonged stimulation with a Nod2 ligand, muramyl dipeptide (MDP), resulted in tolerance to stimulation by B. burgdorferi. This tolerance was lost with stimulation of Nod2 deficient cells that cannot respond to MDP. Cytokine patterns in the tolerance model closely paralleled cytokine profiles in infected Nod2 deficient mice. We propose a model where Nod2 has an enhancing role in activating inflammation in early infection, but moderates inflammation after prolonged exposure to the organism through induction of tolerance.
C1 [Petnicki-Ocwieja, Tanja; DeFrancesco, Alicia S.; Chung, Erin; Darcy, Courtney T.; Hu, Linden T.] Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA USA.
[Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Petnicki-Ocwieja, T (reprint author), Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA USA.
EM lhu@tuftsmedicalcenter.org
RI Hu, Linden/L-6314-2016
OI Hu, Linden/0000-0003-1659-5558
FU [R01AI071107]; [R56AI80646]; [T32AI007329]
FX This work was supported by R01AI071107 ( L. T. H.), R56AI80646 ( L. T.
H.), and T32AI007329 (T.P.O.). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 69
TC 15
Z9 15
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 28
PY 2011
VL 6
IS 2
AR e17414
DI 10.1371/journal.pone.0017414
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729EM
UT WOS:000287931400071
PM 21387014
ER
PT J
AU Westover, MB
Westover, KD
Bianchi, MT
AF Westover, M. Brandon
Westover, Kenneth D.
Bianchi, Matt T.
TI Significance testing as perverse probabilistic reasoning
SO BMC MEDICINE
LA English
DT Article
ID GENERAL MEDICAL JOURNALS; P-VALUE FALLACY; BAYESIAN METHODS;
DECISION-MAKING; GENETIC ASSOCIATIONS; CLINICAL-RESEARCH; HEART-FAILURE;
STATISTICS; INFERENCE; TRIALS
AB Truth claims in the medical literature rely heavily on statistical significance testing. Unfortunately, most physicians misunderstand the underlying probabilistic logic of significance tests and consequently often misinterpret their results. This near-universal misunderstanding is highlighted by means of a simple quiz which we administered to 246 physicians at two major academic hospitals, on which the proportion of incorrect responses exceeded 90%. A solid understanding of the fundamental concepts of probability theory is becoming essential to the rational interpretation of medical information. This essay provides a technically sound review of these concepts that is accessible to a medical audience. We also briefly review the debate in the cognitive sciences regarding physicians' aptitude for probabilistic inference.
C1 [Westover, M. Brandon; Bianchi, Matt T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Westover, Kenneth D.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
RP Westover, MB (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM mwestover@partners.org
NR 137
TC 10
Z9 10
U1 4
U2 25
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD FEB 28
PY 2011
VL 9
AR 20
DI 10.1186/1741-7015-9-20
PG 20
WC Medicine, General & Internal
SC General & Internal Medicine
GA 763NF
UT WOS:000290565300001
PM 21356064
ER
PT J
AU Zuleger, CL
Macklin, MD
Bostwick, BL
Pei, QL
Newton, MA
Albertini, MR
AF Zuleger, Cindy L.
Macklin, Michael D.
Bostwick, Bret L.
Pei, Qinglin
Newton, Michael A.
Albertini, Mark R.
TI In vivo 6-thioguanine-resistant T cells from melanoma patients have
public TCR and share TCR beta amino acid sequences with
melanoma-reactive T cells
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE T cell receptor; CDR3 sequencing; Tumor immunity; Hypoxanthine-guanine;
phosphoribosyltransferase
ID MYELIN BASIC-PROTEIN; PERIPHERAL-BLOOD; RECEPTOR REPERTOIRE; LYMPHOCYTE
RECOGNITION; MULTIPLE-SCLEROSIS; MUTANT FREQUENCY; ANTIGEN RECEPTOR;
SELF-ANTIGEN; ALPHA-CHAIN; INFLUENZA-A
AB vivo hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient T cells (MT) from melanoma patients are enriched for T cells with in vivo clonal amplifications that traffic between blood and tumor tissues. Melanoma is thus a model cancer to test the hypothesis that in vivo MT from cancer patients can be used as immunological probes for immunogenic tumor antigens. MT were obtained by 6-thioguanine (TG) selection of lymphocytes from peripheral blood and tumor tissues, and wild-type T cells (WT) were obtained analogously without TG selection. cDNA sequences of the T cell receptor beta chains (TRB) were used as unambiguous biomarkers of in vivo clonality and as indicators of T cell specificity. Public TRB were identified in MT from the blood and tumor of different melanoma patients. Such public TRB were not found in normal control MT or WT. As an indicator of T cell specificity for melanoma, the > 2600 MT and WT TRB, including the public TRB from melanoma patients, were compared to a literature-derived empirical database of > 1270 TRB from melanoma-reactive T cells. Various degrees of similarity, ranging from 100% conservation to 3-amino acid motifs (3-mer), were found between both melanoma patient MT and WT TRBs and the empirical database. The frequency of 3-mer and 4-mer TRB matching to the empirical database was significantly higher in MT compared with WT in the tumor (p = 0.0285 and p = 0.006, respectively). In summary, in vivo MT from melanoma patients contain public TRB as well as T cells with specificity for characterized melanoma antigens. We conclude that in vivo MT merit study as novel probes for uncharacterized immunogenic antigens in melanoma and other malignancies. Published by Elsevier B.V.
C1 [Albertini, Mark R.] Univ Wisconsin, Dept Med, Carbone Canc Ctr, Madison, WI 53792 USA.
[Pei, Qinglin; Newton, Michael A.] Univ Wisconsin, Dept Stat, Madison, WI 53792 USA.
[Bostwick, Bret L.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53792 USA.
[Newton, Michael A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53792 USA.
[Albertini, Mark R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP Albertini, MR (reprint author), Univ Wisconsin, Dept Med, Carbone Canc Ctr, 600 Highland Ave,K6-530, Madison, WI 53792 USA.
EM mralbert@wisc.edu
FU National Cancer Institute [P30 CA014520]; Gretchen and Andrew Dawes
Melanoma Research Fund; Ann's Hope Foundation; Steve Leuthold Family;
Tim Eagle Memorial
FX This material is based on work supported in part by the Department of
Veterans Affairs, Veterans Health Administration, Office of Research and
Development, Biomedical Laboratory Research and Development Service;
grant P30 CA014520 from the National Cancer Institute; the Gretchen and
Andrew Dawes Melanoma Research Fund; Ann's Hope Foundation; the Jay Van
Sloan Memorial from the Steve Leuthold Family; and the Tim Eagle
Memorial. The funding sources had no involvement in the study design; in
the collection, analysis and interpretation of data; in the writing of
the manuscript; or in the decision to submit the manuscript for
publication. We also thank Drs. David Mahvi, Sharon Weber, and Tracey
Weigel for identifying appropriate surgical specimens; Ms. Susi Nehls
for assistance with manuscript preparation; and Dr. Richard Albertini
for stimulating discussions. The authors have no financial or other
conflicts of interests to disclose related to this publication. The
contents do not represent the views of the Dept of Veterans Affairs or
the United States Government.
NR 56
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD FEB 28
PY 2011
VL 365
IS 1-2
BP 76
EP 86
DI 10.1016/j.jim.2010.12.007
PG 11
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 738DW
UT WOS:000288620600008
PM 21182840
ER
PT J
AU Yeh, HD
Smoot, E
Schoenfeld, DA
Markmann, JF
AF Yeh, Heidi
Smoot, Elizabeth
Schoenfeld, David A.
Markmann, James F.
TI Geographic Inequity in Access to Livers for Transplantation
SO TRANSPLANTATION
LA English
DT Article
DE Liver transplantation; Allocation; Geographic variation; Organ demand;
Listings per capita
ID ORGAN ALLOCATION; MELD SCORE; SURVIVAL; MODEL; DISEASE; SYSTEM; IMPACT;
RATES
AB Background. Liver transplantation offers life-saving therapy for patients with decompensated liver disease or T2 hepatocellular carcinomas. In the United States, deceased donor livers are primarily allocated by Model for End-Stage Liver Disease (MELD) score within each of the country's more than 50 donation service areas (DSAs). Variation in DSA size, population, and organ availability have engendered concern that unequal access to deceased donor livers across DSAs contributes to geographic variability in outcome.
Methods. To determine the extent to which DSA variability in organ availability correlated with combined waitlist and posttransplant mortality, we analyzed retrospectively national waitlist and posttransplant data for a 7-year period after implementation of the current MELD-based allocation system.
Results. Marked variation among DSAs was evident in death rate (3.3-fold), transplant rate (20-fold), and mean transplant MELD (> 10 points). Death rate correlated with organ availability was assessed by transplant rate and transplant MELD. DSAs with low organ availability included the country's largest cities, had more new listings per capita, larger waitlists, more transplant centers per DSA, and a higher proportion of black and Asian patients. DSAs of organ shortage were also characterized by more frequent dual listing at another transplant center, more living donor liver transplants, and increased average length of the transplant admission.
Conclusions. Geographic differences in deceased donor organ availability contribute to variation in overall death rate of liver transplant patients, shape the clinical practice of transplant, and influence the resources consumed per transplant. Geographic variation in organ access results primarily from rates of listing rather than donation. Our findings highlight the need to restructure organ distribution areas to achieve equal access to deceased donor livers for transplantation in the United States.
C1 [Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA.
[Smoot, Elizabeth; Schoenfeld, David A.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
RP Markmann, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Div, 5th Floor,White Bldg,55 Fruit St, Boston, MA 02114 USA.
EM JMarkmann@partners.org
FU NCATS NIH HHS [UL1 TR000170]
NR 27
TC 68
Z9 68
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD FEB 27
PY 2011
VL 91
IS 4
BP 479
EP 486
DI 10.1097/TP.0b013e3182066275
PG 8
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 718MR
UT WOS:000287127600019
PM 21200366
ER
PT J
AU Guo, CG
Alt, FW
Giallourakis, C
AF Guo, Chunguang
Alt, Frederick W.
Giallourakis, Cosmas
TI PAIRing for Distal Igh Locus V(D)J Recombination
SO IMMUNITY
LA English
DT Editorial Material
ID HEAVY-CHAIN GENE; B-CELL; IMMUNOGLOBULIN; GENERATION; REPERTOIRE;
SEGMENTS
AB In this issue of Immunity Ebert et al. (2011) defined the lineage- and stage-specific Pax5-dependent cis-sequences termed PAIR elements in the distal region of the mouse heavy chain immunoglobulin locus (Igh). These sequences may have a role in long-range IgH V(D)J recombination.
C1 [Guo, Chunguang; Alt, Frederick W.; Giallourakis, Cosmas] Harvard Univ, Immune Dis Inst, Howard Hughes Med Inst, Childrens Hosp,Dept Genet,Med Sch, Boston, MA 02115 USA.
[Giallourakis, Cosmas] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Alt, FW (reprint author), Harvard Univ, Immune Dis Inst, Howard Hughes Med Inst, Childrens Hosp,Dept Genet,Med Sch, 300 Longwood Ave, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
FU NIAID NIH HHS [R01 AI020047]
NR 10
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD FEB 25
PY 2011
VL 34
IS 2
BP 139
EP 141
DI 10.1016/j.immuni.2011.02.010
PG 3
WC Immunology
SC Immunology
GA 729YD
UT WOS:000287989500002
PM 21349424
ER
PT J
AU Nagashima, K
Shumway, SD
Sathyanarayanan, S
Chen, AH
Dolinski, B
Xu, YY
Keilhack, H
Thi, N
Wiznerowicz, M
Li, LX
Lutterbach, BA
Chi, A
Paweletz, C
Allison, T
Yan, YW
Munshi, SK
Klippel, A
Kraus, M
Bobkova, EV
Deshmukh, S
Xu, ZW
Mueller, U
Szewczak, AA
Pan, BS
Richon, V
Pollock, R
Blume-Jensen, P
Northrup, A
Andersen, JN
AF Nagashima, Kumiko
Shumway, Stuart D.
Sathyanarayanan, Sriram
Chen, Albert H.
Dolinski, Brian
Xu, Youyuan
Keilhack, Heike
Thi Nguyen
Wiznerowicz, Maciej
Li, Lixia
Lutterbach, Bart A.
Chi, An
Paweletz, Cloud
Allison, Timothy
Yan, Youwei
Munshi, Sanjeev K.
Klippel, Anke
Kraus, Manfred
Bobkova, Ekaterina V.
Deshmukh, Sujal
Xu, Zangwei
Mueller, Uwe
Szewczak, Alexander A.
Pan, Bo-Sheng
Richon, Victoria
Pollock, Roy
Blume-Jensen, Peter
Northrup, Alan
Andersen, Jannik N.
TI Genetic and Pharmacological Inhibition of PDK1 in Cancer Cells
CHARACTERIZATION OF A SELECTIVE ALLOSTERIC KINASE INHIBITOR
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SMALL-MOLECULE INHIBITORS; HUMAN BREAST-CANCER;
3-PHOSPHOINOSITIDE-DEPENDENT KINASE-1; PHOSPHATIDYLINOSITOL 3-KINASE;
STRUCTURAL MECHANISM; SIGNAL-TRANSDUCTION; TUMOR-SUPPRESSOR; TYROSINE
KINASE; DRUG DISCOVERY; AGC KINASES
AB Phosphoinositide-dependent kinase 1 (PDK1) is a critical activator of multiple prosurvival and oncogenic protein kinases and has garnered considerable interest as an oncology drug target. Despite progress characterizing PDK1 as a therapeutic target, pharmacological support is lacking due to the prevalence of nonspecific inhibitors. Here, we benchmark literature and newly developed inhibitors and conduct parallel genetic and pharmacological queries into PDK1 function in cancer cells. Through kinase selectivity profiling and x-ray crystallographic studies, we identify an exquisitely selective PDK1 inhibitor (compound 7) that uniquely binds to the inactive kinase conformation (DFG-out). In contrast to compounds 1-5, which are classical ATP-competitive kinase inhibitors (DFG-in), compound 7 specifically inhibits cellular PDK1 T-loop phosphorylation (Ser-241), supporting its unique binding mode. Interfering with PDK1 activity has minimal antiproliferative effect on cells growing as plastic-attached monolayer cultures (i.e. standard tissue culture conditions) despite reduced phosphorylation of AKT, RSK, and S6RP. However, selective PDK1 inhibition impairs anchorage-independent growth, invasion, and cancer cell migration. Compound 7 inhibits colony formation in a subset of cancer cell lines (four of 10) and primary xenograft tumor lines (nine of 57). RNAi-mediated knockdown corroborates the PDK1 dependence in cell lines and identifies candidate biomarkers of drug response. In summary, our profiling studies define a uniquely selective and cell-potent PDK1 inhibitor, and the convergence of genetic and pharmacological phenotypes supports a role of PDK1 in tumorigenesis in the context of three-dimensional in vitro culture systems.
C1 [Nagashima, Kumiko; Shumway, Stuart D.; Sathyanarayanan, Sriram; Chen, Albert H.; Dolinski, Brian; Xu, Youyuan; Keilhack, Heike; Thi Nguyen; Wiznerowicz, Maciej; Li, Lixia; Lutterbach, Bart A.; Chi, An; Paweletz, Cloud; Klippel, Anke; Kraus, Manfred; Bobkova, Ekaterina V.; Deshmukh, Sujal; Xu, Zangwei; Mueller, Uwe; Szewczak, Alexander A.; Pan, Bo-Sheng; Richon, Victoria; Pollock, Roy; Blume-Jensen, Peter; Northrup, Alan; Andersen, Jannik N.] Merck Res Labs, Boston, MA 02115 USA.
[Allison, Timothy; Yan, Youwei; Munshi, Sanjeev K.] Merck & Co Inc, West Point, PA 19486 USA.
RP Andersen, JN (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, 44 Binney St, Boston, MA 02115 USA.
EM jannik_andersen@dfci.harvard.edu
NR 71
TC 37
Z9 38
U1 1
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 25
PY 2011
VL 286
IS 8
BP 6433
EP 6448
DI 10.1074/jbc.M110.156463
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 723AB
UT WOS:000287476400054
PM 21118801
ER
PT J
AU Parchman, ML
Scoglio, CM
Schumm, P
AF Parchman, Michael L.
Scoglio, Caterina M.
Schumm, Phillip
TI Understanding the implementation of evidence-based care: A structural
network approach
SO IMPLEMENTATION SCIENCE
LA English
DT Article
ID HEALTH-CARE; DISSEMINATION; INNOVATION; DIFFUSION; BEHAVIOR; SPREAD
AB Background: Recent study of complex networks has yielded many new insights into phenomenon such as social networks, the internet, and sexually transmitted infections. The purpose of this analysis is to examine the properties of a network created by the 'co-care' of patients within one region of the Veterans Health Affairs.
Methods: Data were obtained for all outpatient visits from 1 October 2006 to 30 September 2008 within one large Veterans Integrated Service Network. Types of physician within each clinic were nodes connected by shared patients, with a weighted link representing the number of shared patients between each connected pair. Network metrics calculated included edge weights, node degree, node strength, node coreness, and node betweenness. Log-log plots were used to examine the distribution of these metrics. Sizes of k core networks were also computed under multiple conditions of node removal.
Results: There were 4,310,465 encounters by 266,710 shared patients between 722 provider types (nodes) across 41 stations or clinics resulting in 34,390 edges. The number of other nodes to which primary care provider nodes have a connection (172.7) is 42% greater than that of general surgeons and two and one-half times as high as cardiology. The log-log plot of the edge weight distribution appears to be linear in nature, revealing a 'scale-free' characteristic of the network, while the distributions of node degree and node strength are less so. The analysis of the k-core network sizes under increasing removal of primary care nodes shows that about 10 most connected primary care nodes play a critical role in keeping the k-core networks connected, because their removal disintegrates the highest k-core network.
Conclusions: Delivery of healthcare in a large healthcare system such as that of the US Department of Veterans Affairs (VA) can be represented as a complex network. This network consists of highly connected provider nodes that serve as 'hubs' within the network, and demonstrates some 'scale-free' properties. By using currently available tools to explore its topology, we can explore how the underlying connectivity of such a system affects the behavior of providers, and perhaps leverage that understanding to improve quality and outcomes of care.
C1 [Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Family & Community Med Dept, San Antonio, TX 78229 USA.
[Parchman, Michael L.] S Texas Vet Healthcare Syst, VERDICT Hlth Serv Res Program 11C6, San Antonio, TX 78229 USA.
[Scoglio, Caterina M.; Schumm, Phillip] Kansas State Univ, Elect & Comp Engn Dept, Manhattan, KS 66506 USA.
RP Parchman, ML (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Family & Community Med Dept, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM parchman@uthscsa.edu
OI Parchman, Michael/0000-0001-7129-2889
FU National Academies Keck Futures Initiative (NAKFI) [CS15]; Department of
Veterans Affairs, Veterans Health Administration, Health Services
Research and Development Service
FX Funding for this study provided by the National Academies Keck Futures
Initiative (NAKFI CS15) and the Department of Veterans Affairs, Veterans
Health Administration, Health Services Research and Development Service.
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 31
TC 10
Z9 10
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD FEB 24
PY 2011
VL 6
AR 14
DI 10.1186/1748-5908-6-14
PG 10
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 734LJ
UT WOS:000288335300001
PM 21349194
ER
PT J
AU Tsibris, AMN
Shepard, JAO
Zukerberg, LR
AF Tsibris, Athe M. N.
Shepard, Jo-Anne O.
Zukerberg, Lawrence R.
TI Case 6-2011: A 77-Year-Old Man with Dyspnea, Weakness, and Diaphoresis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HUMAN GRANULOCYTIC EHRLICHIOSIS; UNITED-STATES;
ANAPLASMA-PHAGOCYTOPHILUM; SURVEILLANCE; INFECTION; FEVER; BLOOD
C1 [Tsibris, Athe M. N.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Tsibris, Athe M. N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Shepard, Jo-Anne O.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Zukerberg, Lawrence R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Tsibris, AMN (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
NR 24
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 24
PY 2011
VL 364
IS 8
BP 759
EP 767
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 725NP
UT WOS:000287652500013
PM 21345106
ER
PT J
AU Benz, EJ
AF Benz, Edward J., Jr.
TI Newborn Screening for alpha-Thalassemia - Keeping Up with Globalization
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Benz, EJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 4
TC 7
Z9 7
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 24
PY 2011
VL 364
IS 8
BP 770
EP 771
DI 10.1056/NEJMe1013338
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 725NP
UT WOS:000287652500015
PM 21345108
ER
PT J
AU Hornick, JL
Shapiro, GI
Antonescu, CR
AF Hornick, Jason L.
Shapiro, Geoffrey I.
Antonescu, Cristina R.
TI More on Crizotinib REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID INFLAMMATORY MYOFIBROBLASTIC TUMOR
C1 [Hornick, Jason L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Antonescu, Cristina R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Hornick, JL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM geoffrey_shapiro@dfci.harvard.edu
NR 5
TC 0
Z9 0
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 FEB 24
PY 2011
VL 364
IS 8
BP 778
EP 779
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 725NP
UT WOS:000287652500022
ER
PT J
AU Iafrate, AJ
Kwak, E
Clark, JW
AF Iafrate, A. John
Kwak, Eunice
Clark, Jeffrey W.
TI More on Crizotinib REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Iafrate, A. John; Kwak, Eunice; Clark, Jeffrey W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM ekwak@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 24
PY 2011
VL 364
IS 8
BP 778
EP 778
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 725NP
UT WOS:000287652500021
ER
PT J
AU Kiessling, MK
Oberholzer, PA
Mondal, C
Karpova, MB
Zipser, MC
Lin, WM
Girardi, M
MacConaill, LE
Kehoe, SM
Hatton, C
French, LE
Garraway, LA
Polier, G
Suss, D
Klemke, CD
Krammer, PH
Gulow, K
Dummer, R
AF Kiessling, Michael K.
Oberholzer, Patrick A.
Mondal, Chandrani
Karpova, Maria B.
Zipser, Marie C.
Lin, William M.
Girardi, Michael
MacConaill, Laura E.
Kehoe, Sarah M.
Hatton, Charlie
French, Lars E.
Garraway, Levi A.
Polier, Gernot
Suess, Dorothee
Klemke, Claus-Detlev
Krammer, Peter H.
Guelow, Karsten
Dummer, Reinhard
TI High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS
mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK
signaling cascade
SO BLOOD
LA English
DT Article
ID T-CELL LYMPHOMA; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; AZD6244
ARRY-142886; RAS MUTATIONS; LUNG-CANCER; KINASE; GENES; LEUKEMIA;
DISEASE
AB Cutaneous T-cell lymphomas (CTCLs) are malignancies of skin-homing lymphoid cells, which have so far not been investigated thoroughly for common oncogenic mutations. We screened 90 biopsy specimens from CTCL patients (41 mycosis fungoides, 36 Sezary syndrome, and 13 non-mycosis fungoides/Sezary syndrome CTCL) for somatic mutations using OncoMap technology. We detected oncogenic mutations for the RAS pathway in 4 of 90 samples. One mycosis fungoides and one pleomorphic CTCL harbored a KRAS(G13D) mutation; one Sezary syndrome and one CD30(+) CTCL harbored a NRAS(Q61K) amino acid change. All mutations were found in stage IV patients (4 of 42) who showed significantly decreased overall survival compared with stage IV patients without mutations (P = .04). In addition, we detected a NRAS(Q61K) mutation in the CTCL cell line Hut78. Knockdown of NRAS by siRNA induced apoptosis in mutant Hut78 cells but not in CTCL cell lines lacking RAS mutations. The NRASQ61K mutation sensitized Hut78 cells toward growth inhibition by the MEK inhibitors U0126, AZD6244, and PD0325901. Furthermore, we found that MEK inhibitors exclusively induce apoptosis in Hut78 cells. Taken together, we conclude that RAS mutations are rare events at a late stage of CTCL, and our preclinical results suggest that such late-stage patients profit from MEK inhibitors. (Blood. 2011;117(8):2433-2440)
C1 [Oberholzer, Patrick A.; Karpova, Maria B.; Zipser, Marie C.; French, Lars E.; Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
[Kiessling, Michael K.; Polier, Gernot; Suess, Dorothee; Krammer, Peter H.; Guelow, Karsten] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Oberholzer, Patrick A.; MacConaill, Laura E.; Hatton, Charlie; Garraway, Levi A.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA.
[Oberholzer, Patrick A.; Mondal, Chandrani; MacConaill, Laura E.; Kehoe, Sarah M.; Hatton, Charlie; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Oberholzer, Patrick A.; Mondal, Chandrani; MacConaill, Laura E.; Kehoe, Sarah M.; Hatton, Charlie; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Lin, William M.; Girardi, Michael] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
[Klemke, Claus-Detlev] Univ Heidelberg, Univ Med Ctr Mannheim, Dept Dermatol Venerol & Allergol, D-6800 Mannheim, Germany.
RP Dummer, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland.
EM k.guelow@dkfz.de; reinhard.dummer@usz.ch
FU Novartis Foundation; Julius Muller Foundation; Gottfried and Julia
Bangerter-Rhyner Foundation; Wilhelm Sander Foundation; Bayer Schering
Pharma AG; Skin Cancer Foundation; Yale Cancer Center; American Skin
Association; Yale School of Medicine Fellowship; Helmholtz Alliance
Immunotherapy of Cancer [HA202]
FX P.A.O. and L.A.G. were supported by the Novartis Foundation. M.B.K. was
supported by the Julius Muller Foundation. M.C.Z. was supported by the
Gottfried and Julia Bangerter-Rhyner Foundation. M.K.K. was supported by
the Wilhelm Sander Foundation and Bayer Schering Pharma AG. W.M.L. and
M.G. were supported by the Skin Cancer Foundation and the Yale Cancer
Center Swebelius Fund. W.M.L. was also supported by the American Skin
Association and the Yale School of Medicine Fellowship Program. K.G. and
P.H.K. were supported by the Helmholtz Alliance Immunotherapy of Cancer
(HA202).
NR 50
TC 40
Z9 42
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 24
PY 2011
VL 117
IS 8
BP 2433
EP 2440
DI 10.1182/blood-2010-09-305128
PG 8
WC Hematology
SC Hematology
GA 726DK
UT WOS:000287698800024
PM 21209378
ER
PT J
AU Engers, DW
Field, JR
Le, U
Zhou, Y
Bolinger, JD
Zamorano, R
Blobaum, AL
Jones, CK
Jadhav, S
Weaver, CD
Conn, PJ
Lindsley, CW
Niswender, CM
Hopkins, CR
AF Engers, Darren W.
Field, Julie R.
Le, Uyen
Zhou, Ya
Bolinger, Julie D.
Zamorano, Rocio
Blobaum, Anna L.
Jones, Carrie K.
Jadhav, Satyawan
Weaver, C. David
Conn, P. Jeffrey
Lindsley, Craig W.
Niswender, Colleen M.
Hopkins, Corey R.
TI Discovery, Synthesis, and Structure-Activity Relationship Development of
a Series of N-(4-Acetamido)phenylpicolinamides as Positive Allosteric
Modulators of Metabotropic Glutamate Receptor 4 (mGlu(4)) with CNS
Exposure in Rats
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PARKINSONS-DISEASE; MGLUR4; PHARMACOLOGY; MECHANISM; PAMS
AB Herein we report the discovery, synthesis, and evaluation of a series of N-(4-acetamido)-phenylpico-linamides as positive allosteric modulators of mGlu(4). Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats.
C1 [Engers, Darren W.; Field, Julie R.; Le, Uyen; Zhou, Ya; Bolinger, Julie D.; Zamorano, Rocio; Blobaum, Anna L.; Jones, Carrie K.; Jadhav, Satyawan; Weaver, C. David; Conn, P. Jeffrey; Lindsley, Craig W.; Niswender, Colleen M.; Hopkins, Corey R.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA.
[Engers, Darren W.; Zhou, Ya; Zamorano, Rocio; Blobaum, Anna L.; Jones, Carrie K.; Jadhav, Satyawan; Conn, P. Jeffrey; Lindsley, Craig W.; Niswender, Colleen M.; Hopkins, Corey R.] Vanderbilt Univ, Med Ctr, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA.
[Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA.
[Lindsley, Craig W.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA.
[Weaver, C. David; Conn, P. Jeffrey] Vanderbilt Univ, Vanderbilt Inst Chem Biol, Nashville, TN 37232 USA.
[Engers, Darren W.; Lindsley, Craig W.; Hopkins, Corey R.] Vanderbilt Specialized Chem Ctr Accelerated Probe, Nashville, TN 37232 USA.
RP Niswender, CM (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, 2213 Garland Ave, Nashville, TN 37232 USA.
EM colleen.niswender@vanderbilt.edu; corey.r.hopkins@vanderbilt.edu
RI Conn, Peter/D-7848-2012; Zhou, Ya/F-1220-2013
FU National Institute of Mental Health, National Institute of Neurological
Disorders and Stroke; Michael J. Fox Foundation; Vanderbilt Department
of Pharmacology; Vanderbilt Institute of Chemical Biology
FX We thank Emily L. Days, Tasha Nalywajko, Cheryl A. Austin, and Michael
Baxter Williams for their critical contributions to the HTS portion of
the project. In addition, we thank Katrina Brewer, Ryan Morrison, and
Matt Mulder for technical assistance with the PK assays and Chris
Denicola, Nathan Kett, and Sichen Chang for the purification of
compounds utilizing the mass-directed HPLC system. This work was
supported by the National Institute of Mental Health, National Institute
of Neurological Disorders and Stroke, the Michael J. Fox Foundation, the
Vanderbilt Department of Pharmacology, and the Vanderbilt Institute of
Chemical Biology. Vanderbilt is a member of the MLPCN and houses the
Vanderbilt Specialized Chemistry Center for Accelerated Probe
Development (NIH/MLPCN; 5U54MH084659-02).
NR 19
TC 22
Z9 22
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 24
PY 2011
VL 54
IS 4
BP 1106
EP 1110
DI 10.1021/jm101271s
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 721FE
UT WOS:000287338200019
PM 21247167
ER
PT J
AU Lodato, S
Rouaux, C
Quast, KB
Jantrachotechatchawan, C
Studer, M
Hensch, TK
Arlotta, P
AF Lodato, Simona
Rouaux, Caroline
Quast, Kathleen B.
Jantrachotechatchawan, Chanati
Studer, Michele
Hensch, Takao K.
Arlotta, Paola
TI Excitatory Projection Neuron Subtypes Control the Distribution of Local
Inhibitory Interneurons in the Cerebral Cortex
SO NEURON
LA English
DT Article
ID CORTICAL GABAERGIC INTERNEURONS; TANGENTIAL MIGRATION; IN-VIVO;
IMMUNOREACTIVE NEURONS; GANGLIONIC EMINENCE; CELLULAR-PATTERNS;
CORPUS-CALLOSUM; NERVOUS-SYSTEM; ADULT MICE; MOUSE
AB In the mammalian cerebral cortex, the developmental events governing the integration of excitatory projection neurons and inhibitory interneurons into balanced local circuitry are poorly understood. We report that different subtypes of projection neurons uniquely and differentially determine the laminar distribution of cortical interneurons. We find that in Fezf2(-/-) cortex, the exclusive absence of subcerebral projection neurons and their replacement by callosal projection neurons cause distinctly abnormal lamination of interneurons and altered GABAergic inhibition. In addition, experimental generation of either corticofugal neurons or callosal neurons below the cortex is sufficient to recruit cortical interneurons to these ectopic locations. Strikingly, the identity of the projection neurons generated, rather than strictly their birthdate, determines the specific types of interneurons recruited. These data demonstrate that in the neocortex individual populations of projection neurons cell-extrinsically control the laminar fate of interneurons and the assembly of local inhibitory circuitry.
C1 [Jantrachotechatchawan, Chanati; Arlotta, Paola] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Jantrachotechatchawan, Chanati; Arlotta, Paola] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Lodato, Simona; Rouaux, Caroline; Jantrachotechatchawan, Chanati; Arlotta, Paola] Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
[Lodato, Simona; Rouaux, Caroline; Jantrachotechatchawan, Chanati; Arlotta, Paola] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Quast, Kathleen B.; Hensch, Takao K.] Harvard Univ, Dept Mol & Cellular Biol, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Studer, Michele] INSERM, U636, F-06108 Nice, France.
[Studer, Michele] Univ Nice Sophia Antipolis, Lab Genet Dev Normal & Pathol, F-06108 Nice, France.
[Lodato, Simona; Studer, Michele] European Sch Mol Med SEMM, Naples, Italy.
RP Arlotta, P (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
EM paola_arlotta@hms.harvard.edu
RI Studer, Michele/P-4580-2016; Lodato, Simona/A-3525-2017
OI Studer, Michele/0000-0001-7105-2957; Lodato, Simona/0000-0001-6498-2590
FU NIH [NS062849, 1DP1 OD 003699-01]; Harvard Stem Cell Institute; Ellison
Medical Foundation; European School of Molecular Medicine; ALS
Association
FX We would like to thank Jeffrey Macklis and Bradley Molyneaux for
reagents and insightful advice; Antonio Simeone, Antonio Baldini, and
Tommaso Russo for serving on S.L.'s dissertation committee and for their
comments; Oscar Mann for critical input during early stages of this
study; Tracy Pearse-Young for sharing the APP shRNA construct and for
help with electroporations in the rat; Roberto Rusconi for support with
cell counting; Jeffrey Macklis, Verne Caviness, Eiman Azim, Giulio
Srubek Tomassy, Feng Zhang, and Anne Goodwin for their careful reading
of the manuscript and comments; Robert Hevner, Carlos Lois, John
Rubenstein, Vassilis Pachnis, and Andre Goffinet for generous sharing of
antibodies, cDNA clones, and expression vectors; Yuchio Yanagawa for
sharing the GAD67::GFP mice; Alyssa Meleski, Amanda Merlino, and Zachary
Trayes-Gibson for outstanding technical support; and Claudio Mare for
schematic drawings. This work was partially supported by grants from the
NIH (NS062849) and the Harvard Stem Cell Institute to P.A. and the NIH
Director's Pioneer Award (1DP1 OD 003699-01) and Ellison Medical
Foundation to T.K.H. S.L. was partially supported by a predoctoral
fellowship from the European School of Molecular Medicine (S.E.M.M.) and
C.R. was partially supported by a Milton-Safenowitz postdoctoral
fellowship from the ALS Association.
NR 67
TC 73
Z9 73
U1 3
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD FEB 24
PY 2011
VL 69
IS 4
BP 763
EP 779
DI 10.1016/j.neuron.2011.01.015
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA 735KO
UT WOS:000288413200017
PM 21338885
ER
PT J
AU Leykum, LK
Palmer, R
Lanham, H
Jordan, M
McDaniel, RR
Noel, PH
Parchman, M
AF Leykum, Luci K.
Palmer, Ray
Lanham, Holly
Jordan, Michelle
McDaniel, Reuben R.
Noel, Polly H.
Parchman, Michael
TI Reciprocal learning and chronic care model implementation in primary
care: results from a new scale of learning in primary care
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID DECISION-SUPPORT-SYSTEM; CHRONIC ILLNESS CARE; CLINICAL-PRACTICE;
HEALTH-CARE; MANAGEMENT; COMPLEXITY; ORGANIZATIONS; IMPROVEMENT;
GUIDELINES; DELIVERY
AB Background: Efforts to improve the care of patients with chronic disease in primary care settings have been mixed. Application of a complex adaptive systems framework suggests that this may be because implementation efforts often focus on education or decision support of individual providers, and not on the dynamic system as a whole. We believe that learning among clinic group members is a particularly important attribute of a primary care clinic that has not yet been well-studied in the health care literature, but may be related to the ability of primary care practices to improve the care they deliver. To better understand learning in primary care settings by developing a scale of learning in primary care clinics based on the literature related to learning across disciplines, and to examine the association between scale responses and chronic care model implementation as measured by the Assessment of Chronic Illness Care (ACIC) scale.
Methods: Development of a scale of learning in primary care setting and administration of the learning and ACIC scales to primary care clinic members as part of the baseline assessment in the ABC Intervention Study. All clinic clinicians and staff in forty small primary care clinics in South Texas participated in the survey.
Results: We developed a twenty-two item learning scale, and identified a five-item subscale measuring the construct of reciprocal learning (Cronbach alpha 0.79). Reciprocal learning was significantly associated with ACIC total and sub-scale scores, even after adjustment for clustering effects.
Conclusions: Reciprocal learning appears to be an important attribute of learning in primary care clinics, and its presence relates to the degree of chronic care model implementation. Interventions to improve reciprocal learning among clinic members may lead to improved care of patients with chronic disease and may be relevant to improving overall clinic performance.
C1 [Leykum, Luci K.; Palmer, Ray; Lanham, Holly; Noel, Polly H.; Parchman, Michael] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Leykum, Luci K.; Lanham, Holly; Noel, Polly H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Palmer, Ray; Parchman, Michael] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA.
[Jordan, Michelle] Arizona State Univ, Mary Lou Fulton Teachers Coll, Phoenix, AZ USA.
[Lanham, Holly; McDaniel, Reuben R.] Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA.
RP Leykum, LK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
EM Leykum@uthscsa.edu
RI Jordan, Michelle/K-8757-2012;
OI Parchman, Michael/0000-0001-7129-2889
FU National Institute of Health (NIDDK) [R18DK075692]; Department of
Veterans Affairs, Veterans Health Administration, Health Services
Research and Development Service; South Texas Veterans Health Care
System; IC2 Institute of the University of Texas at Austin
FX The research reported here was supported by the National Institute of
Health (NIDDK Grant R18DK075692) and the Department of Veterans Affairs,
Veterans Health Administration, Health Services Research and Development
Service. Investigator salary support is provided through this funding,
and through the South Texas Veterans Health Care System. Dr. McDaniel
receives support from the IC2 Institute of the University of
Texas at Austin. The views expressed in this article are those of the
authors and do not necessarily reflect the position or policy of the
Department of Veterans Affairs.
NR 58
TC 12
Z9 12
U1 1
U2 10
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 FEB 23
PY 2011
VL 11
AR 44
DI 10.1186/1472-6963-11-44
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 730JU
UT WOS:000288030400001
PM 21345225
ER
PT J
AU Hackett, TA
Barkat, TR
O'Brien, BMJ
Hensch, TK
Polley, DB
AF Hackett, Troy A.
Barkat, Tania Rinaldi
O'Brien, Barbara M. J.
Hensch, Takao K.
Polley, Daniel B.
TI Linking Topography to Tonotopy in the Mouse Auditory Thalamocortical
Circuit
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MEDIAL GENICULATE-BODY; RECEPTIVE-FIELD PLASTICITY; DORSAL COCHLEAR
NUCLEUS; RESPONSE-SPECIFIC BANDS; HEARING-LOSS; IN-VITRO;
FUNCTIONAL-ORGANIZATION; CORTICOFUGAL MODULATION; SYNAPTIC-TRANSMISSION;
SPECTRAL INTEGRATION
AB The mouse sensory neocortex is reported to lack several hallmark features of topographic organization such as ocular dominance and orientation columns in primary visual cortex or fine-scale tonotopy in primary auditory cortex (AI). Here, we re-examined the question of auditory functional topography by aligning ultra-dense receptive field maps from the auditory cortex and thalamus of the mouse in vivo with the neural circuitry contained in the auditory thalamocortical slice in vitro. We observed precisely organized tonotopic maps of best frequency (BF) in the middle layers of AI and the anterior auditory field as well as in the ventral and medial divisions of the medial geniculate body (MGBv and MGBm, respectively). Tracer injections into distinct zones of the BF map in AI retrogradely labeled topographically organized MGBv projections and weaker, mixed projections from MGBm. Stimulating MGBv along the tonotopic axis in the slice produced an orderly shift of voltage-sensitive dye (VSD) signals along the AI tonotopic axis, demonstrating topography in the mouse thalamocortical circuit that is preserved in the slice. However, compared with BF maps of neuronal spiking activity, the topographic order of subthreshold VSD maps was reduced in layer IV and even further degraded in layer II/III. Therefore, the precision of AI topography varies according to the source and layer of the mapping signal. Our findings further bridge the gap between in vivo and in vitro approaches for the detailed cellular study of auditory thalamocortical circuit organization and plasticity in the genetically tractable mouse model.
C1 [Polley, Daniel B.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Eaton Peabody Lab, Boston, MA 02114 USA.
[Hackett, Troy A.; O'Brien, Barbara M. J.] Vanderbilt Univ, Sch Med, Dept Hearing & Speech Sci, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA.
[Barkat, Tania Rinaldi; Hensch, Takao K.] Harvard Univ, Ctr Brain Sci, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
RP Polley, DB (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM Daniel_polley@meei.harvard.edu
OI Polley, Daniel/0000-0002-5120-2409
FU National Institutes of Health [DC009836, DC04318]; Core Research for
Evolutional Science and Technology, Japan Science & Technology Agency;
Human Frontiers Science Program
FX This work was supported by National Institutes of Health Grants DC009836
(D. B. P.) and DC04318 (T. A. H.); Core Research for Evolutional Science
and Technology, Japan Science & Technology Agency (T. K. H.); the Human
Frontiers Science Program (T. K. H.); and the Harvard Society of Fellows
(T. R. B.). We thank Michelle Young and Dr. Vivek Khatri for technical
assistance and fruitful discussion.
NR 93
TC 64
Z9 64
U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 23
PY 2011
VL 31
IS 8
BP 2983
EP 2995
DI 10.1523/JNEUROSCI.5333-10.2011
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 725TX
UT WOS:000287670100027
PM 21414920
ER
PT J
AU Haun, JB
Castro, CM
Wang, R
Peterson, VM
Marinelli, BS
Lee, H
Weissleder, R
AF Haun, Jered B.
Castro, Cesar M.
Wang, Rui
Peterson, Vanessa M.
Marinelli, Brett S.
Lee, Hakho
Weissleder, Ralph
TI Micro-NMR for Rapid Molecular Analysis of Human Tumor Samples
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID BREAST-CANCER; LUNG-CANCER; NEOADJUVANT CHEMOTHERAPY; CLINICAL-TRIALS;
CELL DETECTION; CORE BIOPSIES; IN-VIVO; NANOTECHNOLOGY; NANOPARTICLE;
ONCOLOGY
AB Although tumor cells obtained from human patients by image-guided intervention are a valuable source for diagnosing cancer, conventional means of analysis are limited. Here, we report the development of a quantitative micro-NMR (nuclear magnetic resonance) system for rapid, multiplexed analysis of human tumors. We implemented the technology in a clinical setting to analyze cells obtained by fine-needle aspirates from suspected lesions in 50 patients and validated the results in an independent cohort of another 20 patients. Single fine-needle aspirates yielded sufficient numbers of cells to enable quantification of multiple protein markers in all patients within 60 min. Moreover, using a four-protein signature, we report a 96% accuracy for establishing a cancer diagnosis, surpassing conventional clinical analyses by immunohistochemistry. Our results also show that protein expression patterns decay with time, underscoring the need for rapid sampling and diagnosis close to the patient bedside. We also observed a surprising degree of heterogeneity in protein expression both across the different patient samples and even within the same tumor, which has important implications for molecular diagnostics and therapeutic drug targeting. Our quantitative point-of-care micro-NMR technique shows potential for cancer diagnosis in the clinic.
C1 [Haun, Jered B.; Castro, Cesar M.; Peterson, Vanessa M.; Marinelli, Brett S.; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
[Castro, Cesar M.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Wang, Rui] Massachusetts Gen Hosp, MGH Biostat Ctr, Boston, MA 02114 USA.
[Wang, Rui] Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA.
[Peterson, Vanessa M.] MIT, Cambridge, MA 02139 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
EM rweissleder@mgh.harvard.edu
FU NCI NIH HHS [F32 CA144139-02, P50 CA127003, P50 CA127003-05, T32
CA079443, T32 CA079443-10, U54 CA119349, U54 CA119349-05, F32 CA144139];
NHLBI NIH HHS [U01 HL080731, U01 HL080731-05, UO1 HL080731]; NIBIB NIH
HHS [R01 EB004626, R01 EB004626-07, R01 EB010011, R01 EB010011-03]
NR 54
TC 87
Z9 88
U1 1
U2 38
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 23
PY 2011
VL 3
IS 71
AR 71ra16
DI 10.1126/scitranslmed.3002048
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795JZ
UT WOS:000292971800003
PM 21346169
ER
PT J
AU Bourdette, D
Yadav, V
AF Bourdette, Dennis
Yadav, Vijayshree
TI The radiologically isolated syndrome revisited When is it presymptomatic
multiple sclerosis?
SO NEUROLOGY
LA English
DT Editorial Material
ID DIAGNOSTIC-CRITERIA
C1 [Bourdette, Dennis; Yadav, Vijayshree] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Bourdette, Dennis] Portland VA Med Ctr, VA Multiple Sclerosis Ctr Excellence W, Portland, OR USA.
RP Bourdette, D (reprint author), Oregon Hlth & Sci Univ, Dept Neurol L226, Portland, OR 97239 USA.
EM bourdett@ohsu.edu
NR 11
TC 6
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD FEB 22
PY 2011
VL 76
IS 8
BP 680
EP 681
DI 10.1212/WNL.0b013e31820e7769
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 724KH
UT WOS:000287574500005
PM 21270414
ER
PT J
AU Moskowitz, MA
Waeber, C
AF Moskowitz, Michael A.
Waeber, Christian
TI Remote Ischemic Preconditioning Making the Brain More Tolerant, Safely
and Inexpensively
SO CIRCULATION
LA English
DT Editorial Material
DE Editorials; acute stroke; brain; cerebral ischemia; postconditioning
ID RANDOMIZED CONTROLLED-TRIAL; CEREBRAL-ISCHEMIA; INJURY; MECHANISMS;
SURGERY; STROKE; RATS
C1 [Moskowitz, Michael A.; Waeber, Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA USA.
RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, CNY149-6403,149 13th St, Charlestown, MA 02129 USA.
EM moskowitz@helix.mgh.harvard.edu
RI Waeber, Christian/A-8333-2009
OI Waeber, Christian/0000-0001-6078-0027
NR 21
TC 9
Z9 9
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 22
PY 2011
VL 123
IS 7
BP 709
EP 711
DI 10.1161/CIRCULATIONAHA.110.009688
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 724PF
UT WOS:000287588000008
PM 21300956
ER
PT J
AU Wang, TY
White, JA
Tricoci, P
Giugliano, RP
Zeymer, U
Harrington, RA
Montalescot, G
James, SK
Van de Werf, F
Armstrong, PW
Braunwald, E
Califf, RM
Newby, LK
AF Wang, Tracy Y.
White, Jennifer A.
Tricoci, Pierluigi
Giugliano, Robert P.
Zeymer, Uwe
Harrington, Robert A.
Montalescot, Gilles
James, Stefan K.
Van de Werf, Frans
Armstrong, Paul W.
Braunwald, Eugene
Califf, Robert M.
Newby, L. Kristin
TI Upstream Clopidogrel Use and the Efficacy and Safety of Early
Eptifibatide Treatment in Patients With Acute Coronary Syndrome An
Analysis From the Early Glycoprotein IIb/IIIa Inhibition in Patients
With Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) Trial
SO CIRCULATION
LA English
DT Article
DE platelets; anticoagulants; eptifibatide; clopidogrel; acute coronary
syndrome
ID WAVE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; PLATELET INHIBITION;
INTERNATIONAL PERSPECTIVE; CARDIAC-CATHETERIZATION; STENT IMPLANTATION;
GLOBAL REGISTRY; INTERVENTION; REACTIVITY; OUTCOMES
AB Background-In the Early Glycoprotein IIb/IIIa Inhibition in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial, routine preangiography eptifibatide use was not superior to delayed provisional use but led to more bleeding. This analysis examines efficacy and safety of early eptifibatide in the setting of concurrent upstream clopidogrel use.
Methods and Results-In EARLY-ACS, clopidogrel use and timing were determined by treating physicians, but randomization to early eptifibatide versus placebo was stratified by the intent to use upstream clopidogrel. Among 9166 non-ST-elevation acute coronary syndrome patients who underwent coronary angiography, intent to use upstream clopidogrel was declared in 6895 (75%), and 7068 (77%) received upstream clopidogrel. After multivariable adjustment, intended upstream clopidogrel use did not differentially influence the effect of early eptifibatide on the primary end point of 96-hour death/myocardial infarction/recurrent ischemia requiring urgent revascularization/thrombotic bailout (interaction P = 0.988). Early eptifibatide use reduced 30-day death/myocardial infarction among patients with intended upstream clopidogrel (adjusted odds ratio 0.85; 95% confidence interval 0.73 to 0.99) but not among those without intended upstream clopidogrel use (adjusted odds ratio 1.02; 95% confidence interval 0.80 to 1.30). However, the clopidogrel by randomized treatment interaction term was not significant (P = 0.23). Thrombolysis in Myocardial Infarction major bleeding risk was increased with early eptifibatide in the setting of upstream clopidogrel use. Results were similar using actual clopidogrel treatment strata.
Conclusions-Routine early eptifibatide use, compared with delayed provisional use, may be associated with lower 30-day ischemic risk in non-ST-elevation acute coronary syndrome patients also treated with clopidogrel before angiography. The benefit-risk ratio of intensive platelet inhibition with combined early use of antiplatelet agents needs further evaluation in prospective randomized trials.
C1 [Wang, Tracy Y.; White, Jennifer A.; Tricoci, Pierluigi; Harrington, Robert A.; Newby, L. Kristin] Duke Clin Res Inst, Durham, NC 27705 USA.
[Giugliano, Robert P.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
[Zeymer, Uwe] Herzzentrum Ludwigshafen, Ludwigshafen, Germany.
[Montalescot, Gilles] Hop La Pitie Salpetriere, Inst Cardiol, Paris, France.
[James, Stefan K.] Univ Uppsala Hosp, Uppsala, Sweden.
[Van de Werf, Frans] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium.
[Van de Werf, Frans] Leuven Coordinating Ctr, Louvain, Belgium.
[Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada.
[Califf, Robert M.] Duke Translat Med Inst, Durham, NC USA.
RP Wang, TY (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.
EM tracy.wang@duke.edu
FU Schering-Plough Inc; Merck Pharmaceuticals; Bristol-Myers;
Squibb/Sanofi; Schering-Plough; Medicines Company; Heartscape; Canyon
Pharmaceuticals; Eli Lilly/Daiichi-Sankyo Alliance; Merck & Co Inc
through the Duke Clinical Research Institute; Daiichi-Sankyo;
Schering-Plough (now Merck); Bristol-Myers Squibb; Boston Scientific;
Centocor; Cordis; Eli-Lilly; Federation Franccaise de Cardiologie;
Fondation de France; Guerbet Medical; INSERM; ITC Edison; Medtronic;
Pfizer; Sanofi-Aventis Group; Societe Franccaise de Cardiologie;
Accumetrics; Bayer; Boehringer-Ingelheim; Eisai; Menarini; MSD;
Novartis; Portola; Sanofi-Aventis; Roche; Merck; Boehringer Ingelheim
(Canada) Ltd; Sanofi-Aventis Canada; Schering-Plough Research Institute;
Scios Inc/Ortho-Biotech; GlaxoSmithKline; Portola Pharmaceutical Inc;
Uppsala Clinical Research Center; Merck Company Inc; Merck Co Inc
FX The EARLY ACS trial and this work were funded by research grants from
Schering-Plough Inc and Merck Pharmaceuticals.; Dr Wang has received
research grants from Bristol-Myers Squibb/Sanofi Partnership,
Schering-Plough, The Medicines Company, Heartscape, Canyon
Pharmaceuticals, and Eli Lilly/Daiichi-Sankyo Alliance. Dr Tricoci has
received research grants from Merck & Co Inc through the Duke Clinical
Research Institute and is on the advisory board for Merck & Co Inc. Dr
Giugliano has received research grant support from Daiichi-Sankyo and
Schering-Plough, honoraria from Schering-Plough, Bristol-Myers Squib,
and Sanofi-Aventis and is on the advisory board for Schering-Plough and
Merck & Co Inc. Dr Zeymer has received research grants from
Schering-Plough (now Merck). Dr Harrington has received research funding
from and consults with Schering-Plough (now Merck). A complete listing
of Dr Harrington's relationships with industry is available at
http://www.dcri.duke.edu/research/coi.jsp. Dr Montalescot has received
research grants (to his institution) from Bristol-Myers Squibb, Boston
Scientific, Centocor, Cordis, Eli-Lilly, Federation Franccaise de
Cardiologie, Fondation de France, Guerbet Medical, INSERM, ITC Edison,
Medtronic, Pfizer, Sanofi-Aventis Group, and Societe Franccaise de
Cardiologie and consulting or lecture fees from Accumetrics,
Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb,
Daiichi-Sankyo, Eisai, Eli-Lilly, Menarini, MSD, Novartis, Portola,
Sanofi-Aventis Group, Schering-Plough, and The Medicines Company. Dr
James has received research grants and speaker fees from AstraZeneca,
Sanofi-Aventis, Bristol-Myers Squibb, Eli Lilly, and Schering-Plough. Dr
Van de Werf has received research grants from Schering-Plough (now
Merck) and Roche and advisory board and speaker's fees from
Schering-Plough, Merck, and Roche. Dr Armstrong has provided consulting
or other services that generate personal income to Sanofi-Aventis,
Bristol-Myers Squibb Canada, Merck Frosst Canada Ltd, Abbott
Laboratories, GlaxoSmithKline, Bristol-Myers Squibb/Pfizer, Regado
Biosciences, and F. Hoffmann-La Roche Ltd and has received research
grants or contracts from Boehringer Ingelheim (Canada) Ltd,
Sanofi-Aventis Canada, Eli Lilly, Schering-Plough Research Institute,
Scios Inc/Ortho-Biotech, GlaxoSmithKline, Portola Pharmaceutical Inc,
Uppsala Clinical Research Center and AstraZeneca, and Merck & Company
Inc that partially support his university salary and/or research
projects. Dr Braunwald is chair of the TIMI Study Group at the Brigham
and Women's Hospital, which receives (or has received within the past 24
months) grant support for the TIMI Study Group from the following
pharmaceutical companies (all >$10 000): Eli Lilly, Merck & Co Inc,
Schering-Plough Research Institute, and Daiichi-Sankyo. Dr Braunwald has
also participated occasionally (maximum 2 to 3 times/y) in
symposia/advisory board meetings/consultancies for the following
companies, for which he receives an honorarium (always >$10 000) and
reimbursement of travel-related expenses: Daiichi-Sankyo, Eli Lilly,
Merck & Co Inc, and Schering-Plough. Dr Califf has received research
funding from and consulted for Schering-Plough (now Merck; all
consulting funds donated to not-for-profit organizations). A complete
listing of Dr Califf's relationships with industry is available at
http://www.dcri.duke.edu/research/coi.jsp. Dr Newby has received
research grants from Schering-Plough and Merck & Co Inc through the Duke
Clinical Research Institute and consulting honoraria from
Schering-Plough. A complete listing of Dr. Newby's relationships with
industry is available at http://www.dcri.duke.edu/research/coi.jsp.; J
White reports no conflicts.
NR 32
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 22
PY 2011
VL 123
IS 7
BP 722
EP 730
DI 10.1161/CIRCULATIONAHA.110.958041
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 724PF
UT WOS:000287588000011
PM 21300952
ER
PT J
AU Fonarow, GC
Smith, EE
Saver, JL
Reeves, MJ
Bhatt, DL
Grau-Sepulveda, MV
Olson, DM
Hernandez, AF
Peterson, ED
Schwamm, LH
AF Fonarow, Gregg C.
Smith, Eric E.
Saver, Jeffrey L.
Reeves, Mathew J.
Bhatt, Deepak L.
Grau-Sepulveda, Maria V.
Olson, DaiWai M.
Hernandez, Adrian F.
Peterson, Eric D.
Schwamm, Lee H.
TI Timeliness of Tissue-Type Plasminogen Activator Therapy in Acute
Ischemic Stroke Patient Characteristics, Hospital Factors, and Outcomes
Associated With Door-to-Needle Times Within 60 Minutes
SO CIRCULATION
LA English
DT Article
DE hospital performance; mortality; registries; stroke; thrombolytics
ID RT-PA STROKE; INTRAVENOUS THROMBOLYSIS; POOLED ANALYSIS; CARE;
GUIDELINES; ALTEPLASE; NINDS; RECOMMENDATIONS; ESTABLISHMENT; EXPERIENCE
AB Background-The benefits of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke are time dependent, and guidelines recommend an arrival to treatment initiation (door-to-needle) time of <= 60 minutes.
Methods and Results-Data from acute ischemic stroke patients treated with tPA within 3 hours of symptom onset in 1082 hospitals participating in the Get With the Guidelines-Stroke Program from April 1, 2003, to September 30, 2009 were studied to determine frequency, patient and hospital characteristics, and temporal trends in patients treated with door-to-needle times <= 60 minutes. Among 25 504 ischemic stroke patients treated with tPA, door-to-needle time was <= 60 minutes in only 6790 (26.6%). Patient factors most strongly associated with door-to-needle time <= 60 minutes were younger age, male gender, white race, or no prior stroke. Hospital factors associated with <= 60 minute door-to-needle time included greater annual volumes of tPA-treated stroke patients. The proportion of patients with door-to-needle times <= 60 minutes varied widely by hospital (0% to 79.2%) and increased from 19.5% in 2003 to 29.1% in 2009 (P < 0.0001). Despite similar stroke severity, in-hospital mortality was lower (adjusted odds ratio, 0.78; 95% confidence interval, 0.69 to 0.90; P < 0.0003) and symptomatic intracranial hemorrhage was less frequent (4.7% versus 5.6%; P < 0.0017) for patients with door-to-needle times <= 60 minutes compared with patients with door-to-needle times <= 60 minutes.
Conclusions-Fewer than one-third of patients treated with intravenous tPA had door-to-needle times <= 60 minutes, with only modest improvement over the past 6.5 years. These findings support the need for a targeted initiative to improve the timeliness of reperfusion in acute ischemic stroke. (Circulation. 2011; 123: 750-758.)
C1 [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA.
[Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada.
[Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiol VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA.
[Grau-Sepulveda, Maria V.; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Fonarow, GC (reprint author), Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, 10833 LeConte Ave,Room 47-123 CHS, Los Angeles, CA 90095 USA.
EM gfonarow@mednet.ucla.edu
RI Hernandez, Adrian F./A-7818-2016;
OI Saver, Jeffrey/0000-0001-9141-2251; Schwamm, Lee/0000-0003-0592-9145;
Hernandez, Adrian F./0000-0003-3387-9616; Smith,
Eric/0000-0003-3956-1668
FU Bristol-Myers; Squib/Sanofi Pharmaceutical; AHA Pharmaceutical
Roundtable [0675060N]; Boeringher-Ingelheim; Merck; National Institutes
of Health; NIH (NINDS) [R01 NS062028]; Canadian Stroke Network; Canadian
Institutes of Health Research; Heart and Stroke Foundation of Canada;
Michigan Stroke Registry; AstraZeneca; Bristol-Myers Squibb; Eisai;
Sanofi Aventis; Medicines Co.; Johnson Johnson; Lilly; Merck-Schering
Plough
FX The GWTG-Stroke program is provided by the AHA/ASA. The GWTG-Stroke
program is currently supported in part by a charitable contribution from
Bristol-Myers Squib/Sanofi Pharmaceutical Partnership and the AHA
Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past
through support from Boeringher-Ingelheim and Merck. The industry
sponsors had no role in the design and conduct of the study; the
collection, management, analysis, and interpretation of the data; or the
preparation, review, or approval of the manuscript.; Dr Fonarow receives
research support from the National Institutes of Health; served as a
consultant to Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and
Sanofi-Aventis; received honoraria from Pfizer, Merck, Schering Plough,
Bristol Myers Squibb, and Sanofi-Aventis; and is an employee of the
University of California, which holds a patent on retriever devices for
stroke. Dr Fonarow had full access to all of the data in the study and
takes responsibility for the integrity of the data and the accuracy of
the data analysis. Dr Smith serves as a member of the GWTG Science
Subcommittee; receives research support from the NIH (NINDS R01
NS062028), Canadian Stroke Network, Canadian Institutes of Health
Research, and Heart and Stroke Foundation of Canada; and has served on
an advisory board for Genentech. Dr Saver serves as a member of the GWTG
Science Subcommittee and as a scientific consultant regarding trial
design and conduct to CoAxia, Concentric Medical, Talacris, Ferrer,
Photothera, Brainsgate, Sygnis, and Ev3; received lecture honoraria from
Ferrer; and is an employee of the University of California, which holds
a patent on retriever devices for stroke. Dr Reeves receives salary
support from the Michigan Stroke Registry and serves as a member of the
AHA's GWTG Quality Improvement Subcommittee. Dr Bhatt receives research
support from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi Aventis,
and The Medicines Co. Dr Grau-Sepulveda is a member of the Duke Clinical
Research Institute, which serves as the AHA GWTG data coordinating
center. Drs Olson and Hernandez are members of the Duke Clinical
Research Institute, which serves as the AHA GWTG Data Coordinating
Center. Dr Hernandez is a recipient of an AHA Pharmaceutical Roundtable
grant (0675060N); has received a research grant from Johnson & Johnson;
and has received honorarium from AstraZeneca and Amgen. Dr Peterson has
received research grants from Lilly, Johnson & Johnson, and
Bristol-Myers Squibb, Sanofi-Aventis, and Merck-Schering Plough
partnership. Dr Peterson serves as principal investigator of the Data
Analytic Center for AHAs GWTG. Dr Schwamm serves as chair of the AHA
GWTG Steering Committee; serves as a consultant to the Research Triangle
Institute and to the Massachusetts Department of Public Health; and
serves on the Steering Committee for Lundbeck's DIAS4 clinical trial.
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 22
PY 2011
VL 123
IS 7
BP 750
EP U184
DI 10.1161/CIRCULATIONAHA.110.974675
PG 11
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 724PF
UT WOS:000287588000014
PM 21311083
ER
PT J
AU Tamietto, M
de Gelder, B
AF Tamietto, Marco
de Gelder, Beatrice
TI Sentinels in the visual system
SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE
LA English
DT Editorial Material
C1 [Tamietto, Marco; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
[de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[de Gelder, Beatrice] Harvard Univ, Sch Med, Boston, MA USA.
RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
EM degelder@nmr.mgh.harvard.edu
OI Tamietto, Marco/0000-0002-8815-8499
NR 15
TC 1
Z9 1
U1 0
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5153
J9 FRONT BEHAV NEUROSCI
JI Front. Behav. Neurosci.
PD FEB 22
PY 2011
VL 5
AR 6
DI 10.3389/fnbeh.2011.00006
PG 2
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA V29VN
UT WOS:000208776000001
PM 21373367
ER
PT J
AU Dell'Italia, LJ
AF Dell'Italia, Louis J.
TI The Forgotten Left Ventricle in Right Ventricular Pressure Overload
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE atrophy; pulmonary hypertension; right ventricular failure
ID CONTRACTILE FUNCTION; HYPERTENSION; HEARTS
C1 [Dell'Italia, Louis J.] Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA.
RP Dell'Italia, LJ (reprint author), UAB, Ctr Heart Failure Res, Div Cardiol, 434 BMR2,1530 3rd Ave S, Birmingham, AL 35294 USA.
EM loudell@uab.edu
NR 7
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 22
PY 2011
VL 57
IS 8
BP 929
EP 930
DI 10.1016/j.jacc.2010.08.647
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 725NB
UT WOS:000287650900008
PM 21329839
ER
PT J
AU Fifer, KM
Qadir, S
Subramanian, S
Vijayakumar, J
Figueroa, AL
Quynh, AT
Hoffman, U
Brady, TJ
Tawakol, A
AF Fifer, Kenneth M.
Qadir, Sadia
Subramanian, Sharath
Vijayakumar, Jayanthi
Figueroa, Amparo L.
Quynh A. Truong
Hoffman, Udo
Brady, Thomas J.
Tawakol, Ahmed
TI Positron Emission Tomography Measurement of Periodontal
F-18-Fluorodeoxyglucose Uptake Is Associated With Histologically
Determined Carotid Plaque Inflammation
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE atherosclerosis; carotid; inflammation; periodontal; PET
ID CORONARY-HEART-DISEASE; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE;
SYSTEMIC INFLAMMATION; ATHEROMATOUS PLAQUES; COMPUTED-TOMOGRAPHY;
VASCULAR-DISEASE; FDG-PET; ATHEROSCLEROSIS; PATHOGENS
AB Objectives This study aimed to test the hypothesis that metabolic activity within periodontal tissue (a possible surrogate for periodontal inflammation) predicts inflammation in a remote atherosclerotic vessel, utilizing F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging.
Background Several lines of evidence establish periodontal disease as an important risk factor for atherosclerosis. FDG-PET imaging is an established method for measuring metabolic activity in human tissues and blood vessels.
Methods One hundred twelve patients underwent FDG-PET imaging 92 +/- 5 min after FDG administration (13 to 25 mCi). Periodontal FDG uptake was measured by obtaining standardized uptake values from the periodontal tissue of each patient, and the ratio of periodontal to background (blood) activity was determined (TBR). Standardized uptake value measurements were obtained in the carotid and aorta as well as in a venous structure. Localization of periodontal, carotid, and aortic activity was facilitated by PET coregistration with computed tomography or magnetic resonance imaging. A subset of 16 patients underwent carotid endarterectomy within 1 month of PET imaging, during which atherosclerotic plaques were removed and subsequently stained with anti-CD68 antibodies to quantify macrophage infiltration. Periodontal FDG uptake was compared with carotid plaque macrophage infiltration.
Results Periodontal FDG uptake (TBR) is associated with carotid TBR (R = 0.64, p < 0.0001), as well as aortic TBR (R = 0.38; p = 0.029). Moreover, a strong relationship was observed between periodontal TBR and histologically assessed inflammation within excised carotid artery plaques (R = 0.81, p < 0.001).
Conclusions FDG-PET measurements of metabolic activity within periodontal tissue correlate with macrophage infiltration within carotid plaques. These findings provide direct evidence for an association between periodontal disease and atherosclerotic inflammation. (J Am Coll Cardiol 2011;57:971-6) (C) 2011 by the American College of Cardiology Foundation
C1 [Fifer, Kenneth M.; Quynh A. Truong; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, Boston, MA 02114 USA.
[Fifer, Kenneth M.; Qadir, Sadia; Subramanian, Sharath; Vijayakumar, Jayanthi; Figueroa, Amparo L.; Quynh A. Truong; Hoffman, Udo; Brady, Thomas J.; Tawakol, Ahmed] Harvard Univ, Sch Med, Boston, MA USA.
[Qadir, Sadia; Subramanian, Sharath; Vijayakumar, Jayanthi; Figueroa, Amparo L.; Quynh A. Truong; Hoffman, Udo; Brady, Thomas J.; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Imaging, Boston, MA 02114 USA.
RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM atawakol@partners.org
NR 49
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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 FEB 22
PY 2011
VL 57
IS 8
BP 971
EP 976
DI 10.1016/j.jacc.2010.09.056
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 725NB
UT WOS:000287650900013
PM 21329844
ER
PT J
AU Zhou, XH
Wong, LL
Karakoti, AS
Seal, S
McGinnis, JF
AF Zhou, Xiaohong
Wong, Lily L.
Karakoti, Ajay S.
Seal, Sudipta
McGinnis, James F.
TI Nanoceria Inhibit the Development and Promote the Regression of
Pathologic Retinal Neovascularization in the Vldlr Knockout Mouse
SO PLOS ONE
LA English
DT Article
ID DENSITY LIPOPROTEIN RECEPTOR; ENDOTHELIAL GROWTH-FACTOR; OXIDATIVE
STRESS; ANGIOMATOUS PROLIFERATION; RETINITIS-PIGMENTOSA; NADPH OXIDASE;
SUBRETINAL NEOVASCULARIZATION; PHOTORECEPTOR DEGENERATION; MACULAR
DEGENERATION; MODEL
AB Many neurodegenerative diseases are known to occur and progress because of oxidative stress, the presence of reactive oxygen species (ROS) in excess of the cellular defensive capabilities. Age related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration share oxidative stress as a common node upstream of the blinding effects of these diseases. Knockout of the Vldlr gene results in a mouse that develops intraretinal and subretinal neovascular lesions within the first month of age and is an excellent model for a form of AMD called retinal angiomatous proliferation (RAP). Cerium oxide nanoparticles (nanoceria) catalytically scavenge ROS by mimicking the activities of superoxide dismutase and catalase. A single intravitreal injection of nanoceria into the Vldlr-/- eye was shown to inhibit: the rise in ROS in the Vldlr-/- retina, increases in vascular endothelial growth factor (VEGF) in the photoreceptor layer, and the formation of intraretinal and subretinal neovascular lesions. Of more therapeutic interest, injection of nanoceria into older mice (postnatal day 28) resulted in the regression of existing vascular lesions indicating that the pathologic neovessels require the continual production of excessive ROS. Our data demonstrate the unique ability of nanoceria to prevent downstream effects of oxidative stress in vivo and support their therapeutic potential for treatment of neurodegenerative diseases such as AMD and DR.
C1 [Zhou, Xiaohong; Wong, Lily L.; Karakoti, Ajay S.; Seal, Sudipta; McGinnis, James F.] Univ Oklahoma, Coll Med, Dept Ophthalmol, Dean McGee Eye Inst, Oklahoma City, OK 73190 USA.
[Karakoti, Ajay S.; Seal, Sudipta] Univ Cent Florida, Adv Mat Proc Anal Ctr, Mech Mat Aerosp Engn Nanosci & Technol Ctr, Orlando, FL 32816 USA.
[McGinnis, James F.] Oklahoma Ctr Neurosci, Dept Ophthalmol & Cell Biol, Oklahoma City, OK USA.
RP Zhou, XH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab, Boston, MA 02115 USA.
EM lily-wong@ouhsc.edu; james-mcginnis@ouhsc.edu
RI Wong, Lily/D-7737-2011
OI Wong, Lily/0000-0003-0569-3398
FU NIH [P30-EY12190, COBRE-P20 RR017703, R21EY018306, R01EY018724]; FFB
[C-NP-0707-0404-UOK08]; NSF [CBET-0708172]; OCAST [HR06-075];
Presbyterian Health Foundation; Research to Prevent Blindness; RPB
FX This work was supported by grants from: NIH: P30-EY12190, COBRE-P20
RR017703, R21EY018306, R01EY018724; FFB (http://www.blindness.org/):
C-NP-0707-0404-UOK08; NSF: CBET-0708172;
OCAST(http://www.ok.gov/ocast/Programs/Oklahoma_Health_Research_(OHR)/in
dex.html): HR06-075, and unrestricted funds from Presbyterian Health
Foundation (http://www.phfokc.com/research.htm) and Research to Prevent
Blindness (http://www.rpbusa.org/rpb/) (RPB). JFM is a recipient of an
RPB Senior Scientific Investigator Award. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 22
PY 2011
VL 6
IS 2
AR e16733
DI 10.1371/journal.pone.0016733
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 725PA
UT WOS:000287656600014
PM 21364932
ER
PT J
AU Kveraga, K
Ghuman, AS
Kassam, KS
Aminoff, EA
Hamalainen, MS
Chaumon, M
Bar, M
AF Kveraga, Kestutis
Ghuman, Avniel Singh
Kassam, Karim S.
Aminoff, Elissa A.
Haemaelaeinen, Matti S.
Chaumon, Maximilien
Bar, Moshe
TI Early onset of neural synchronization in the contextual associations
network
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE phase locking; oscillations; beta; visual cognition
ID PARAHIPPOCAMPAL PLACE AREA; MEDIAL TEMPORAL-LOBES; VISUAL OBJECT
RECOGNITION; TOP-DOWN FACILITATION; RETROSPLENIAL CORTEX; MEMORY
RETRIEVAL; SCENE PERCEPTION; PHASE SYNCHRONIZATION; ORBITOFRONTAL
CORTEX; CORTICAL NETWORKS
AB Objects are more easily recognized in their typical context. However, is contextual information activated early enough to facilitate the perception of individual objects, or is contextual facilitation caused by postperceptual mechanisms? To elucidate this issue, we first need to study the temporal dynamics and neural interactions associated with contextual processing. Studies have shown that the contextual network consists of the parahippocampal, retrosplenial, and medial prefrontal cortices. We used functional MRI, magnetoencephalography, and phase synchrony analyses to compare the neural response to stimuli with strong or weak contextual associations. The context network was activated in functional MRI and preferentially synchronized in magnetoencephalography (MEG) for stimuli with strong contextual associations. Phase synchrony increased early (150-250 ms) only when it involved the parahippocampal cortex, whereas retrosplenial-medial prefrontal cortices synchrony was enhanced later (300-400 ms). These results describe the neural dynamics of context processing and suggest that context is activated early during object perception.
C1 [Kveraga, Kestutis; Haemaelaeinen, Matti S.; Chaumon, Maximilien; Bar, Moshe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Kveraga, Kestutis; Haemaelaeinen, Matti S.; Bar, Moshe] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Ghuman, Avniel Singh] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Kassam, Karim S.] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA.
[Aminoff, Elissa A.] Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA.
[Chaumon, Maximilien] Boston Coll, Dept Psychol, Chestnut Hill, MA 02459 USA.
[Bar, Moshe] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Kveraga, K (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM kestas@nmr.mgh.harvard.edu
RI Hamalainen, Matti/C-8507-2013;
OI Aminoff, Elissa/0000-0002-6455-8930; Ghuman, Avniel/0000-0003-1746-4656
FU National Institute of Mental Health [K01-MH084011]; National Institutes
of Health [NS50615, EY019477]; National Science Foundation [0842947]
FX This research was supported by National Institute of Mental Health Grant
K01-MH084011 (to K.K.), National Institutes of Health Grants NS50615 and
EY019477 (to M.B.), and National Science Foundation Grant 0842947 (to
M.B.).
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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 FEB 22
PY 2011
VL 108
IS 8
BP 3389
EP 3394
DI 10.1073/pnas.1013760108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 724ML
UT WOS:000287580400059
PM 21300869
ER
PT J
AU Shamis, Y
Hewitt, KJ
Carlson, MW
Margvelashvilli, M
Dong, SM
Kuo, CK
Daheron, L
Egles, C
Garlick, JA
AF Shamis, Yulia
Hewitt, Kyle J.
Carlson, Mark W.
Margvelashvilli, Mariam
Dong, Shumin
Kuo, Catherine K.
Daheron, Laurence
Egles, Christophe
Garlick, Jonathan A.
TI Fibroblasts derived from human embryonic stem cells direct development
and repair of 3D human skin equivalents
SO STEM CELL RESEARCH & THERAPY
LA English
DT Article
ID KERATINOCYTES IN-VITRO; STROMAL CELLS; GROWTH; DIFFERENTIATION; CULTURE;
REEPITHILIALIZATION; REGENERATION; PHENOTYPE; FEEDERS; SUPPORT
AB Introduction: Pluripotent, human stem cells hold tremendous promise as a source of progenitor and terminally differentiated cells for application in future regenerative therapies. However, such therapies will be dependent upon the development of novel approaches that can best assess tissue outcomes of pluripotent stem cell-derived cells and will be essential to better predict their safety and stability following in vivo transplantation.
Methods: In this study we used engineered, human skin equivalents (HSEs) as a platform to characterize fibroblasts that have been derived from human embryonic stem (hES) cell. We characterized the phenotype and the secretion profile of two distinct hES-derived cell lines with properties of mesenchymal cells (EDK and H9-MSC) and compared their biological potential upon induction of differentiation to bone and fat and following their incorporation into the stromal compartment of engineered, HSEs.
Results: While both EDK and H9-MSC cell lines exhibited similar morphology and mesenchymal cell marker expression, they demonstrated distinct functional properties when incorporated into the stromal compartment of HSEs. EDK cells displayed characteristics of dermal fibroblasts that could support epithelial tissue development and enable re-epithelialization of wounds generated using a 3D tissue model of cutaneous wound healing, which was linked to elevated production of hepatocyte growth factor (HGF). Lentiviral shRNA-mediated knockdown of HGF resulted in a dramatic decrease of HGF secretion from EDK cells that led to a marked reduction in their ability to promote keratinocyte proliferation and re-epithelialization of cutaneous wounds. In contrast, H9-MSCs demonstrated features of mesenchymal stem cells (MSC) but not those of dermal fibroblasts, as they underwent multilineage differentiation in monolayer culture, but were unable to support epithelial tissue development and repair and produced significantly lower levels of HGF.
Conclusions: Our findings demonstrate that hES-derived cells could be directed to specified and alternative mesenchymal cell fates whose function could be distinguished in engineered HSEs. Characterization of hES-derived mesenchymal cells in 3D, engineered HSEs demonstrates the utility of this tissue platform to predict the functional properties of hES-derived fibroblasts before their therapeutic transplantation.
C1 [Shamis, Yulia; Hewitt, Kyle J.; Garlick, Jonathan A.] Tufts Univ, Sackler Sch Grad Biomed Sci, Sch Med, Program Cell Mol & Dev Biol, Boston, MA 02111 USA.
[Carlson, Mark W.; Margvelashvilli, Mariam; Dong, Shumin; Egles, Christophe; Garlick, Jonathan A.] Tufts Univ, Sch Dent Med, Dept Oral & Maxillofacial Pathol, Boston, MA 02111 USA.
[Kuo, Catherine K.] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA.
[Daheron, Laurence] Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02114 USA.
RP Garlick, JA (reprint author), Tufts Univ, Sackler Sch Grad Biomed Sci, Sch Med, Program Cell Mol & Dev Biol, 136 Harrison Ave, Boston, MA 02111 USA.
EM Jonathan.Garlick@tufts.edu
OI EGLES, Christophe/0000-0003-0982-7752
FU National Institute for Dental Research (NIDCR) [DE017413]
FX We thank Dr. Addy Alt-Holland, Cathy X. Zhao, and Adam G. Sowalsky for
their contributions during the progress of this work and Judith Edwards
for assistance in the preparation of the manuscript. This work was
supported by grant #DE017413 to JAG from National Institute for Dental
Research (NIDCR).
NR 37
TC 20
Z9 21
U1 0
U2 17
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-6512
J9 STEM CELL RES THER
JI Stem Cell Res. Ther.
PD FEB 21
PY 2011
VL 2
AR 10
DI 10.1186/scrt51
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 794HL
UT WOS:000292886000001
PM 21338517
ER
PT J
AU Moteabbed, M
Espana, S
Paganetti, H
AF Moteabbed, M.
Espana, S.
Paganetti, H.
TI Monte Carlo patient study on the comparison of prompt gamma and PET
imaging for range verification in proton therapy
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; IN-BEAM; IRRADIATION; DELIVERY; SYSTEM;
DISTRIBUTIONS; FEASIBILITY; SIMULATIONS; DESIGN; CAMERA
AB The purpose of this work was to compare the clinical adaptation of prompt gamma (PG) imaging and positron emission tomography (PET) as independent tools for non-invasive proton beam range verification and treatment validation. The PG range correlation and its differences with PET have been modeled for the first time in a highly heterogeneous tissue environment, using different field sizes and configurations. Four patients with different tumor locations (head and neck, prostate, spine and abdomen) were chosen to compare the site-specific behaviors of the PG and PET images, using both passive scattered and pencil beam fields. Accurate reconstruction of dose, PG and PET distributions was achieved by using the planning computed tomography (CT) image in a validated GEANT4-based Monte Carlo code capable of modeling the treatment nozzle and patient anatomy in detail. The physical and biological washout phenomenon and decay half-lives for PET activity for the most abundant isotopes such as C-11, O-15, N-13, P-30 and K-38 were taken into account in the data analysis. The attenuation of the gamma signal after traversing the patient geometry and respective detection efficiencies were estimated for both methods to ensure proper comparison. The projected dose, PG and PET profiles along many lines in the beam direction were analyzed to investigate the correlation consistency across the beam width. For all subjects, the PG method showed on average approximately 10 times higher gamma production rates than the PET method before, and 60 to 80 times higher production after including the washout correction and acquisition time delay. This rate strongly depended on tissue density and elemental composition. For broad passive scattered fields, it was demonstrated that large differences exist between PG and PET signal falloff positions and the correlation with the dose distribution for different lines in the beam direction. These variations also depended on the treatment site and the particular subject. Thus, similar to PET, direct range verification with PG in passive scattering is not easily viable. However, upon development of an optimized 3D PG detector, indirect range verification by comparing measured and simulated PG distributions (currently being explored for the PET method) would be more beneficial because it can avoid the inherent biological challenges of the PET imaging. The improved correlation of PG and PET with dose when using pencil beams was evident. PG imaging was found to be potentially advantageous especially for small tumors in the presence of high tissue heterogeneities. Including the effects of detector acceptance and efficiency may hold PET superior in terms of the amplitude of the detected signal (depending on the future development of PG detection technology), but the ability to perform online measurements and avoid signal disintegration (due to washout) with PG are important factors that can outweigh the benefits of higher detection sensitivity.
C1 [Moteabbed, M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Moteabbed, M (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM mmoteabbed@partners.org
RI Espana, Samuel/E-9240-2010
OI Espana, Samuel/0000-0001-9092-4597
FU NIH/NCI [P01 CA-21239]; Massachusetts General Hospital, 'Proton Therapy
Research and Treatment Center' [C06 CA059267]
FX The project was supported by NIH/NCI P01 CA-21239 'Proton Therapy
Research' and by the Federal Share of program income earned by
Massachusetts General Hospital on C06 CA059267, 'Proton Therapy Research
and Treatment Center'.
NR 29
TC 64
Z9 64
U1 2
U2 19
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 FEB 21
PY 2011
VL 56
IS 4
BP 1063
EP 1082
DI 10.1088/0031-9155/56/4/012
PG 20
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 714HX
UT WOS:000286800800012
PM 21263174
ER
PT J
AU Wen, PY
van den Bent, MJ
Macdonald, DR
Tsien, C
Vogelbaum, MA
Chang, SM
AF Wen, Patrick Y.
van den Bent, Martin J.
Macdonald, David R.
Tsien, Christina
Vogelbaum, Michael A.
Chang, Susan M.
TI Baseline Preadjuvant Magnetic Resonance Imaging for Response Assessment
and for Planning Radiotherapy in Glioblastoma Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID HIGH-GRADE GLIOMAS
C1 [Wen, Patrick Y.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA.
[Wen, Patrick Y.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[van den Bent, Martin J.] Erasmus Univ Hosp Rotterdam, Daniel den Hoed Canc Ctr, Neurooncol Unit, Rotterdam, Netherlands.
[Macdonald, David R.] Univ Western Ontario, London Reg Canc Program, London, ON, Canada.
[Tsien, Christina] Univ Michigan, Med Ctr, Ann Arbor, MI USA.
[Vogelbaum, Michael A.] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA.
[Chang, Susan M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Wen, PY (reprint author), Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2011
VL 29
IS 6
BP E149
EP E149
DI 10.1200/JCO.2010.33.1215
PG 1
WC Oncology
SC Oncology
GA 722OP
UT WOS:000287444000011
ER
PT J
AU Oberoi, D
Matthews, LD
Cairns, IH
Emrich, D
Lobzin, V
Lonsdale, CJ
Morgan, EH
Prabu, T
Vedantham, H
Wayth, RB
Williams, A
Williams, C
White, SM
Allen, G
Arcus, W
Barnes, D
Benkevitch, L
Bernardi, G
Bowman, JD
Briggs, FH
Bunton, JD
Burns, S
Cappallo, RC
Clark, MA
Corey, BE
Dawson, M
DeBoer, D
De Gans, A
deSouza, L
Derome, M
Edgar, RG
Elton, T
Goeke, R
Gopalakrishna, MR
Greenhill, LJ
Hazelton, B
Herne, D
Hewitt, JN
Kamini, PA
Kaplan, DL
Kasper, JC
Kennedy, R
Kincaid, BB
Kocz, J
Koeing, R
Kowald, E
Lynch, MJ
Madhavi, S
McWhirter, SR
Mitchell, DA
Morales, MF
Ng, A
Ord, SM
Pathikulangara, J
Rogers, AEE
Roshi, A
Salah, JE
Sault, RJ
Schinckel, A
Shankar, NU
Srivani, KS
Stevens, J
Subrahmanyan, R
Thakkar, D
Tingay, SJ
Tuthill, J
Vaccarella, A
Waterson, M
Webster, RL
Whitney, AR
AF Oberoi, Divya
Matthews, Lynn D.
Cairns, Iver H.
Emrich, David
Lobzin, Vasili
Lonsdale, Colin J.
Morgan, Edward H.
Prabu, T.
Vedantham, Harish
Wayth, Randall B.
Williams, Andrew
Williams, Christopher
White, Stephen M.
Allen, G.
Arcus, Wayne
Barnes, David
Benkevitch, Leonid
Bernardi, Gianni
Bowman, Judd D.
Briggs, Frank H.
Bunton, John D.
Burns, Steve
Cappallo, Roger C.
Clark, M. A.
Corey, Brian E.
Dawson, M.
DeBoer, David
De Gans, A.
deSouza, Ludi
Derome, Mark
Edgar, R. G.
Elton, T.
Goeke, Robert
Gopalakrishna, M. R.
Greenhill, Lincoln J.
Hazelton, Bryna
Herne, David
Hewitt, Jacqueline N.
Kamini, P. A.
Kaplan, David L.
Kasper, Justin C.
Kennedy, Rachel
Kincaid, Barton B.
Kocz, Jonathan
Koeing, R.
Kowald, Errol
Lynch, Mervyn J.
Madhavi, S.
McWhirter, Stephen R.
Mitchell, Daniel A.
Morales, Miguel F.
Ng, A.
Ord, Stephen M.
Pathikulangara, Joseph
Rogers, Alan E. E.
Roshi, Anish
Salah, Joseph E.
Sault, Robert J.
Schinckel, Antony
Shankar, N. Udaya
Srivani, K. S.
Stevens, Jamie
Subrahmanyan, Ravi
Thakkar, D.
Tingay, Steven J.
Tuthill, J.
Vaccarella, Annino
Waterson, Mark
Webster, Rachel L.
Whitney, Alan R.
TI FIRST SPECTROSCOPIC IMAGING OBSERVATIONS OF THE SUN AT LOW RADIO
FREQUENCIES WITH THE MURCHISON WIDEFIELD ARRAY PROTOTYPE
SO ASTROPHYSICAL JOURNAL LETTERS
LA English
DT Article
DE instrumentation: interferometers; radiation mechanisms: non-thermal;
Sun: corona; Sun: radio radiation
ID SOLAR CORONA; IMAGES; FLARE; MHZ
AB We present the first spectroscopic images of solar radio transients from the prototype for the Murchison Widefield Array, observed on 2010 March 27. Our observations span the instantaneous frequency band 170.9-201.6 MHz. Though our observing period is characterized as a period of "low" to "medium" activity, one broadband emission feature and numerous short-lived, narrowband, non-thermal emission features are evident. Our data represent a significant advance in low radio frequency solar imaging, enabling us to follow the spatial, spectral, and temporal evolution of events simultaneously and in unprecedented detail. The rich variety of features seen here reaffirms the coronal diagnostic capability of low radio frequency emission and provides an early glimpse of the nature of radio observations that will become available as the next generation of low-frequency radio interferometers come online over the next few years.
C1 [Oberoi, Divya; Matthews, Lynn D.; Lonsdale, Colin J.; Benkevitch, Leonid; Cappallo, Roger C.; Corey, Brian E.; Derome, Mark; Kennedy, Rachel; Kincaid, Barton B.; McWhirter, Stephen R.; Rogers, Alan E. E.; Salah, Joseph E.; Whitney, Alan R.] MIT, Haystack Observ, Westford, MA 01886 USA.
[Cairns, Iver H.; Lobzin, Vasili; Thakkar, D.] Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia.
[Emrich, David; Wayth, Randall B.; Arcus, Wayne; Herne, David; Lynch, Mervyn J.; Tingay, Steven J.; Waterson, Mark] Curtin Univ, Curtin Inst Radio Astron, Perth, WA, Australia.
[Morgan, Edward H.; Williams, Christopher; Goeke, Robert; Hewitt, Jacqueline N.] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
[Prabu, T.; Vedantham, Harish; Gopalakrishna, M. R.; Kamini, P. A.; Madhavi, S.; Roshi, Anish; Shankar, N. Udaya; Srivani, K. S.; Subrahmanyan, Ravi] Raman Res Inst, Bangalore 560080, Karnataka, India.
[Williams, Andrew] Univ Western Australia, Perth Observ, Perth, WA 6009, Australia.
[White, Stephen M.] USAF, Res Lab, Kirtland, NM USA.
[Allen, G.; Bunton, John D.; DeBoer, David; deSouza, Ludi; Elton, T.; Ng, A.; Pathikulangara, Joseph; Schinckel, Antony; Stevens, Jamie; Tuthill, J.] CSIRO Astron & Space Sci, Epping, NSW, Australia.
[Barnes, David] Swinburne Univ Technol, Ctr Astrophys & Supercomp, Melbourne, Vic, Australia.
[Bernardi, Gianni; Greenhill, Lincoln J.; Kasper, Justin C.; Mitchell, Daniel A.; Ord, Stephen M.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
[Bowman, Judd D.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ USA.
[Briggs, Frank H.; Dawson, M.; De Gans, A.; Kocz, Jonathan; Kowald, Errol; Vaccarella, Annino; Waterson, Mark] Australian Natl Univ, Res Sch Astron & Astrophys, Canberra, ACT, Australia.
[Burns, Steve] Burns Ind Inc, Nashua, NH USA.
[Clark, M. A.; Edgar, R. G.] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA.
[DeBoer, David; Kennedy, Rachel] Univ Calif Berkeley, Berkeley Astron Dept, Berkeley, CA 94720 USA.
[Edgar, R. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hazelton, Bryna; Morales, Miguel F.] Univ Washington, Dept Phys, Seattle, WA 98195 USA.
[Kaplan, David L.] Univ Wisconsin, Dept Phys, Milwaukee, WI USA.
[Roshi, Anish] Natl Radio Astron Observ, Green Bank, WV USA.
[Sault, Robert J.; Webster, Rachel L.] Univ Melbourne, Sch Phys, Melbourne, Vic, Australia.
RP Oberoi, D (reprint author), MIT, Haystack Observ, Westford, MA 01886 USA.
RI Bunton, John/A-4944-2008; Astronomy & Astrophysics Group, Raman Res
Institute/D-4046-2012; M, Manjunath/N-4000-2014; Kasper,
Justin/D-1152-2010; Wayth, Randall/B-2444-2013; Tingay,
Steven/B-5271-2013; Emrich, David/B-7002-2013; Waterson,
Mark/B-7352-2013; Ord, Stephen/C-6138-2013; Subrahmanyan,
Ravi/D-4889-2012; Williams, Andrew/K-2931-2013; Udayashankar ,
N/D-4901-2012
OI Cairns, Iver/0000-0001-6978-9765; M, Manjunath/0000-0001-8710-0730;
Kocz, Jonathon/0000-0003-0249-7586; Kasper, Justin/0000-0002-7077-930X;
Wayth, Randall/0000-0002-6995-4131; Emrich, David/0000-0002-4058-1837;
Waterson, Mark/0000-0002-0192-2686; Williams,
Andrew/0000-0001-9080-0105;
FU Commonwealth Government of Australia; Western Australian State
government; U.S. National Science Foundation [AST-0457585, PHY-0835713];
Australian Research Council [LE0775621, LE0882938]; U.S. Air Force
Office of Scientific Research [FA9550-0510247]; National Collaborative
Infrastructure Strategy; Australian federal government via Astronomy
Australia Limited; Smithsonian Astrophysical Observatory; MIT School of
Science; Raman Research Institute; Australian National University; iVEC;
Initiative in Innovative Computing; NVIDIA; International Centre for
Radio Astronomy Research, a Joint Venture of Curtin University
FX This work uses data obtained from the Murchison Radioastronomy
Observatory (MRO), jointly funded by the Commonwealth Government of
Australia and Western Australian State government. The MRO is managed by
the CSIRO, who also provides operational support to the MWA. We
acknowledge the Wajarri Yamatji people as the traditional owners of the
Observatory site. Support came from the U.S. National Science Foundation
(grants AST-0457585 and PHY-0835713), the Australian Research Council
(grants LE0775621 and LE0882938), the U.S. Air Force Office of
Scientific Research (grant FA9550-0510247), the National Collaborative
Infrastructure Strategy, funded by the Australian federal government via
Astronomy Australia Limited, the Smithsonian Astrophysical Observatory,
the MIT School of Science, the Raman Research Institute, The Australian
National University, iVEC, the Initiative in Innovative Computing and
NVIDIA sponsored Center for Excellence at Harvard, and the International
Centre for Radio Astronomy Research, a Joint Venture of Curtin
University, and The University of Western Australia funded by the
Western Australian State government.
NR 17
TC 15
Z9 15
U1 1
U2 11
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 2041-8205
J9 ASTROPHYS J LETT
JI Astrophys. J. Lett.
PD FEB 20
PY 2011
VL 728
IS 2
AR L27
DI 10.1088/2041-8205/728/2/L27
PG 7
WC Astronomy & Astrophysics
SC Astronomy & Astrophysics
GA 715YI
UT WOS:000286931200003
ER
PT J
AU Ciaranello, AL
Lockman, S
Freedberg, KA
Hughes, M
Chu, J
Currier, J
Wood, R
Holmes, CB
Pillay, S
Conradie, F
McIntyre, J
Losina, E
Walensky, RP
AF Ciaranello, Andrea L.
Lockman, Shahin
Freedberg, Kenneth A.
Hughes, Michael
Chu, Jennifer
Currier, Judith
Wood, Robin
Holmes, Charles B.
Pillay, Sandy
Conradie, Francesca
McIntyre, James
Losina, Elena
Walensky, Rochelle P.
CA CEPAC Int OCTANE Investigators
TI First-line antiretroviral therapy after single-dose nevirapine exposure
in South Africa: a cost-effectiveness analysis of the OCTANE trial
SO AIDS
LA English
DT Article
DE antiretroviral therapy; cost-effectiveness; HIV; mother-to-child
transmission; single-dose nevirapine
ID RESOURCE-LIMITED SETTINGS; HIV-INFECTED ADULTS; COTE-DIVOIRE; WOMEN;
RITONAVIR; OUTCOMES; LOPINAVIR/RITONAVIR; TRANSMISSION; INTRAPARTUM;
ZIDOVUDINE
AB Background: The OCTANE trial reports superior outcomes of lopinavir/ritonavir vs. nevirapine-based antiretroviral therapy (ART) among women previously exposed to single-dose nevirapine to prevent mother-to-child HIV transmission. However, lopinavir/ritonavir is 12 times costlier than nevirapine.
Methods: We used a computer model, with OCTANE and local data, to simulate HIV-infected, single-dose nevirapine-exposed women in South Africa. Outcomes of three alternative ART sequences were projected: no ART (for comparison), first-line nevirapine, and first-line lopinavir/ritonavir. OCTANE data included mean age (31 years) and CD4 cell count (135/mu l); median time since single-dose nevirapine (17 months); and 24-week viral suppression efficacy for first-line ART (nevirapine: 85%, lopinavir/ritonavir: 97%). Outcomes included life expectancy, per-person costs (2008 US$), and incremental cost-effectiveness ratios.
Results: With no ART, projected life expectancy was 1.6 years and per-person cost was $2980. First-line nevirapine increased life expectancy (15.2 years) and cost ($13 990; cost-effectiveness ratio: $810/year of life saved versus no ART). First-line lopinavir/ritonavir further increased life expectancy to 16.3 years and cost to $15 630 (cost-effectiveness ratio: $1520/year of life saved versus first-line nevirapine). First-line lopinavir/ritonavir cost-effectiveness was sensitive to prevalence of nevirapine-resistant virus at ART initiation, time from single-dose nevirapine exposure to ART initiation (6-12, 12-24, or > 24 months), second-line ART efficacies, and outcomes after 24 weeks on ART.
Conclusions: First-line lopinavir/ritonavir-based ART is very cost-effective in single-dose nevirapine-exposed, South African women similar to OCTANE participants. Lopinavir/ritonavir should be initiated in women with known nevirapine resistance or single-dose nevirapine exposure less than 12 months prior, or in whom such information is unknown. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Ciaranello, Andrea L.; Lockman, Shahin; Walensky, Rochelle P.] Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Publ Hlth, Boston, MA 02114 USA.
[Ciaranello, Andrea L.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Div Infect Dis, Sch Publ Hlth, Boston, MA 02114 USA.
[Lockman, Shahin] Harvard Univ, Div Immunol & Infect Dis, Sch Publ Hlth, Boston, MA 02114 USA.
[Freedberg, Kenneth A.; Chu, Jennifer; Losina, Elena; Walensky, Rochelle P.] Harvard Univ, Div Gen Med, Sch Publ Hlth, Boston, MA 02114 USA.
[Freedberg, Kenneth A.] Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Ctr AIDS Res, Boston, MA 02114 USA.
[Hughes, Michael] Harvard Univ, Ctr Biostat AIDS Res, Sch Publ Hlth, Boston, MA 02114 USA.
[Currier, Judith] Univ Calif Los Angeles, Div Infect Dis, Los Angeles, CA USA.
[Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
[Holmes, Charles B.] Off Global AIDS Coordinator, Washington, DC USA.
[Pillay, Sandy] Nelson Mandela Sch Med, Infect Dis Unit, Durban, South Africa.
[Conradie, Francesca] Univ Witwatersrand, Johannesburg, South Africa.
[McIntyre, James] Anova Hlth Inst, Johannesburg, South Africa.
[Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Orthoped Surg, Boston, MA USA.
[Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Ciaranello, AL (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Publ Hlth, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM aciaranello@partners.org
RI Anglaret, Xavier/F-7333-2013;
OI Walensky, Rochelle P./0000-0002-8795-379X; Lipsitch,
Marc/0000-0003-1504-9213
FU National Institute of Allergy and Infectious Disease [K01 AI078754, K24
AI56933, K24 AI062476, R01 AI058736, R01 HD044391, P30 AI 60354, R01 AI
69453]; Adult AIDS Clinical Trials Group [U01 AI068636, U01 AI069424];
Statistical and Data Management Center for the AIDS Clinical Trials
Group [U01 AI68634]; Comprehensive International Program for Research on
AIDS in South Africa [U19 AI53217]; Elizabeth Glaser Pediatric AIDS
Foundation; NIAID [U01 AI06836, AI68634]; General Clinical Research
Centers (GCRC) of the National Center for Research Resources; Boehringer
Ingelheim; Glaxo SmithKline
FX Funding for this work was provided by the National Institute of Allergy
and Infectious Disease [K01 AI078754 (A.L.C.), K24 AI56933 (J. Currier),
K24 AI062476 (K.A.F.), R01 AI058736 (K.A.F., R.P.W., A.L.C., R.W., J.
Chu, E.L.), R01 HD044391 (S.L.), P30 AI 60354 (A.L.C.), R01 AI 69453
(J.M.)]; the Adult AIDS Clinical Trials Group [U01 AI068636 (A.L.C.,
K.A.F., R.P.W.), U01 AI069424 (J. Currier), Statistical and Data
Management Center for the AIDS Clinical Trials Group (U01 AI68634
(M.D.H.)]; the Comprehensive International Program for Research on AIDS
in South Africa [U19 AI53217 (R.W..)]; and the Elizabeth Glaser
Pediatric AIDS Foundation (A.L.C., K.A.F., J. Chu, R.P.W.).; The OCTANE
trial is registered on ClinicalTrials.gov (NCT 00089505) and supported
by NIAID (U01 AI06836, AI68634) and the General Clinical Research
Centers (GCRC) of the National Center for Research Resources. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of NIAID or the National
Institutes of Health.; Michael Hughes is a paid member of Data and
Safety Monitoring Boards for the following manufacturers of
antiretroviral therapy: Boehringer Ingelheim, Pfizer, Tibotec. James
McIn-tyre has received speaker's honoraria from Abbott Pharmaceuticals,
and research funding, travel grants and speaker's honoraria from
Boehringer Ingelheim and Glaxo SmithKline. All other authors have no
conflicts of interest to disclose.
NR 50
TC 18
Z9 18
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD FEB 20
PY 2011
VL 25
IS 4
BP 479
EP 492
DI 10.1097/QAD.0b013e3283428cbe
PG 14
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 716LN
UT WOS:000286970300010
PM 21293199
ER
PT J
AU Choueiri, TK
Mayer, EL
Je, YJ
Rosenberg, JE
Nguyen, PL
Azzi, GR
Bellmunt, J
Burstein, HJ
Schutz, FAB
AF Choueiri, Toni K.
Mayer, Erica L.
Je, Youjin
Rosenberg, Jonathan E.
Nguyen, Paul L.
Azzi, Georges R.
Bellmunt, Joaquim
Burstein, Harold J.
Schutz, Fabio A. B.
TI Congestive Heart Failure Risk in Patients With Breast Cancer Treated
With Bevacizumab
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; INHIBITOR SUNITINIB; PHASE-III; METAANALYSIS;
CARDIOTOXICITY; HYPERTENSION; CHEMOTHERAPY; DOCETAXEL; BIAS
AB Purpose
Bevacizumab is a treatment option in patients with metastatic breast cancer. Congestive heart failure (CHF) has been reported, although the overall incidence and relative risk (RR) of this complication remains unclear. We performed an up-to-date, comprehensive meta-analysis to determine the risk of serious CHF in patients with breast cancer receiving bevacizumab.
Methods
The databases of Medline were searched for articles from 1966 to March 2010. Abstracts presented at the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium meetings were also searched for relevant clinical trials. Eligible studies include randomized trials with bevacizumab in patients with breast cancer. Adequate reporting of safety profile data was required for inclusion. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% CIs by using random-effects models.
Results
A total of 3,784 patients were included. Overall incidence results for high-grade CHF in bevacizumab- and placebo-treated patients were 1.6% (95% CI, 1.0% to 2.6%) and 0.4% (95% CI, 0.2% to 1.0%), respectively. The RR of CHF in bevacizumab-treated patients was 4.74 (95% CI, 1.66 to 11.18; P = .001) compared with placebo-treated ones. In subgroup analyses, there were no significant differences in CHF incidence or risk between patients treated with low-dose (2.5 mg/kg) versus high-dose (5 mg/kg) bevacizumab or among patients treated with different chemotherapy regimens. No evidence of publication bias was observed.
Conclusion
This is the first comprehensive report to show that bevacizumab is associated with an increased risk of significant heart failure in patients with breast cancer. J Clin Oncol 29: 632-638. (C) 2011 by American Society of Clinical Oncology
C1 [Schutz, Fabio A. B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Univ Hosp Mar, Inst Municipal Invest Med, Barcelona, Spain.
RP Schutz, FAB (reprint author), Dana Farber Canc Inst, 44 Binney St Dana 1230, Boston, MA 02115 USA.
EM FabioA_Schutz@dfci.harvard.edu
FU Jonathan E. Rosenberg; GlaxoSmithKline; sanofi-aventis; Novartis
FX Research Funding: Jonathan E. Rosenberg, GlaxoSmithKline,
sanofi-aventis, Novartis
NR 30
TC 129
Z9 135
U1 1
U2 3
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 FEB 20
PY 2011
VL 29
IS 6
BP 632
EP 638
DI 10.1200/JCO.2010.31.9129
PG 7
WC Oncology
SC Oncology
GA 722OP
UT WOS:000287444000019
PM 21205755
ER
PT J
AU Ruan, J
Martin, P
Furman, RR
Lee, SM
Cheung, K
Vose, JM
LaCasce, A
Morrison, J
Elstrom, R
Ely, S
Chadburn, A
Cesarman, E
Coleman, M
Leonard, JP
AF Ruan, Jia
Martin, Peter
Furman, Richard R.
Lee, Shing M.
Cheung, Ken
Vose, Julie M.
LaCasce, Ann
Morrison, Julia
Elstrom, Rebecca
Ely, Scott
Chadburn, Amy
Cesarman, Ethel
Coleman, Morton
Leonard, John P.
TI Bortezomib Plus CHOP-Rituximab for Previously Untreated Diffuse Large
B-Cell Lymphoma and Mantle Cell Lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; PROSPECTIVE
RANDOMIZED-TRIAL; PROGRESSION-FREE SURVIVAL; EUROPEAN MCL NETWORK;
PHASE-II; CLINICAL-TRIALS; ELDERLY-PATIENTS; MOLECULAR SUBTYPES; R-CHOP
AB Purpose
The proteasome inhibitor bortezomib may enhance activity of chemoimmunotherapy in lymphoma. We evaluated dose-escalated bortezomib plus standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (R) in patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).
Patients and Methods
Seventy-six subjects with untreated DLBCL (n = 40) and MCL (n = 36) received standard CHOP every 21 days (CHOP-21) with R plus bortezomib at 0.7 mg/m(2) (n = 4), 1.0 mg/m(2) (n = 9), or 1.3 mg/m(2) (n = 63) on days 1 and 4 for six cycles.
Results
Median age was 63 years (range, 20 to 87), and International Prognostic Index (IPI) scores were generally unfavorable (39% with IPI of 2, and 49% with IPI of 3 to 5), as were Mantle Cell Lymphoma International Prognostic Index scores in patients with MCL (28% intermediate risk and 39% high risk). Toxicity was manageable, including neuropathy in 49 subjects (8% grade 2 and 4% grade 3) and grade 3/4 anemia (13%), neutropenia (41%), and thrombocytopenia (25%). For DLBCL, the evaluable overall response rate (ORR) was 100% with 86% complete response (CR)/CR unconfirmed (CRu; n = 35). Intent-to-treat (ITT, n = 40) ORR was 88% with 75% CR/CRu, 2-year progression-free survival (PFS) of 64% (95% CI, 47% to 77%) and 2-year overall survival (OS) of 70% (95% CI, 53% to 82%). For MCL, the evaluable ORR was 91% with 72% CR/CRu (n = 32). The ITT (n = 36) ORR was 81% with 64% CR/CRu, 2-year PFS 44% (95% CI, 27% to 60%) and 2-year OS 86% (95% CI, 70% to 94%). IPI and MIPI correlated with survival in DLBCL and MCL, respectively. Unlike in DLBCL treated with R-CHOP alone, nongerminal center B cell (non-GCB) and GCB subtypes had similar outcomes.
Conclusion
Bortezomib with R-CHOP-21 can be safely administered and may enhance outcomes, particularly in non-GCB DLBCL, justifying randomized studies.
C1 [Leonard, John P.] Weill Cornell Med Coll, Ctr Lymphoma & Myeloma, New York, NY 10065 USA.
New York Presbyterian Hosp, New York, NY USA.
Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
Univ Nebraska, Med Ctr, Omaha, NE USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Leonard, JP (reprint author), Weill Cornell Med Coll, Ctr Lymphoma & Myeloma, 525 E 68th St,Starr 340, New York, NY 10065 USA.
EM jpleonar@med.cornell.edu
FU Millennium Pharmaceuticals; Lymphoma Research Foundation; Lymphoma
Foundation; American Society of Clinical Oncology Career Development
Award; Genentech; Millennium
FX Supported in part by Millennium Pharmaceuticals, grants from the
Lymphoma Research Foundation (J.P.L.) and the Lymphoma Foundation
(J.P.L.), and an American Society of Clinical Oncology Career
Development Award (J.R.).; Research Funding: Richard R. Furman,
Genentech, Millennium; Julie M. Vose, Genentech, Millennium; John P.
Leonard, Genentech, Millennium
NR 46
TC 142
Z9 148
U1 0
U2 8
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 FEB 20
PY 2011
VL 29
IS 6
BP 690
EP 697
DI 10.1200/JCO.2010.31.1142
PG 8
WC Oncology
SC Oncology
GA 722OP
UT WOS:000287444000027
PM 21189393
ER
PT J
AU Petrocca, F
Lieberman, J
AF Petrocca, Fabio
Lieberman, Judy
TI Promise and Challenge of RNA Interference-Based Therapy for Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; DOUBLE-STRANDED-RNA; CELL-CYCLE ARREST;
DOWN-REGULATION; IN-VIVO; CAENORHABDITIS-ELEGANS; MIR-34A CONTRIBUTES;
NONHUMAN-PRIMATES; OVARIAN-CANCER; TUMOR-GROWTH
AB Cancer therapeutics still fall far short of our goals for treating patients with locally advanced or metastatic disease. Until recently, almost all cancer drugs were crude cytotoxic agents that discriminate poorly between cancer cells and normally dividing cells. The development of targeted biologics that recognize tumor cell surface antigens and of specific inhibitors of pathways dysregulated in cancer cells or normal cellular pathways on which a cancer cell differentially depends has provided hope for converting our increasing understanding of cellular transformation into intelligently designed anticancer therapeutics. However, new drug development is painfully slow, and the pipeline of new therapeutics is thin. The discovery of RNA interference (RNAi), a ubiquitous cellular pathway of gene regulation that is dysregulated in cancer cells, provides an exciting opportunity for relatively rapid and revolutionary approaches to cancer drug design. Small RNAs that harness the RNAi machinery may become the next new class of drugs for treating a variety of diseases. Although it has only been 9 years since RNAi was shown to work in mammalian cells, about a dozen phase I to III clinical studies have already been initiated, including four for cancer. So far there has been no unexpected toxicity and suggestions of benefit in one phase II study. However, the obstacles for RNAi-based cancer therapeutics are substantial. This article will discuss how the endogenous RNAi machinery might be harnessed for cancer therapeutics, why academic researchers and biotech and pharmaceutical companies are so excited, and what the obstacles are and how they might be overcome.
C1 Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Lieberman, J (reprint author), 200 Longwood Ave,WAB 255, Boston, MA 02115 USA.
EM lieberman@idi.harvard.edu
RI Lieberman, Judy/A-2717-2015
FU Department of Defense [W81XWH-09-1-0058]; GlaxoSmithKline-Immune Disease
Institute
FX Supported by Department of Defense Breast Cancer Research Program Grant
No. W81XWH-09-1-0058 (J.L.) and fellowship (F.P.) and by a
GlaxoSmithKline-Immune Disease Institute Alliance research grant (J.L.).
NR 81
TC 66
Z9 71
U1 0
U2 19
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 FEB 20
PY 2011
VL 29
IS 6
BP 747
EP 754
DI 10.1200/JCO.2009.27.6287
PG 8
WC Oncology
SC Oncology
GA 722OP
UT WOS:000287444000035
PM 21079135
ER
PT J
AU Nalls, MA
Plagnol, V
Hernandez, DG
Sharma, M
Sheerin, UM
Saad, M
Simon-Sanchez, J
Schulte, C
Lesage, S
Sveinbjornsdottir, S
Arepalli, S
Barker, R
Ben-Shlomo, Y
Berendse, HW
Berg, D
Bhatia, K
de Bie, RMA
Biffi, A
Bloem, B
Bochdanovits, Z
Bonin, M
Bras, JM
Brockmann, K
Brooks, J
Burn, DJ
Charlesworth, G
Chen, HL
Chinnery, PF
Chong, S
Clarke, CE
Cookson, MR
Cooper, JM
Corvol, JC
Counsell, C
Damier, P
Dartigues, JF
Deloukas, P
Deuschl, G
Dexter, DT
van Dijk, KD
Dillman, A
Durif, F
Durr, A
Edkins, S
Evans, JR
Foltynie, T
Gao, JJ
Gardner, M
Gibbs, JR
Goate, A
Gray, E
Guerreiro, R
Gustafsson, O
Harris, C
van Hilten, JJ
Hofman, A
Hollenbeck, A
Holton, J
Hu, M
Huang, XM
Huber, H
Hudson, G
Hunt, SE
Huttenlocher, J
Illig, T
Jonsson, PV
Lambert, JC
Langford, C
Lees, A
Lichtner, P
Limousin, P
Lopez, G
Lorenz, D
McNeill, A
Moorby, C
Moore, M
Morris, HR
Morrison, KE
Mudanohwo, E
O'Sullivan, SS
Pearson, J
Perlmutter, JS
Petursson, H
Pollak, P
Post, B
Potter, S
Ravina, B
Revesz, T
Riess, O
Rivadeneira, F
Rizzu, P
Ryten, M
Sawcer, S
Schapira, A
Scheffer, H
Shaw, K
Shoulson, I
Sidransky, E
Smith, C
Spencer, CCA
Stefansson, H
Stockton, JD
Strange, A
Talbot, K
Tanner, CM
Tashakkori-Ghanbaria, A
Tison, F
Trabzuni, D
Traynor, BJ
Uitterlinden, AG
Velseboer, D
Vidailhet, M
Walker, R
van de Warrenburg, B
Wickremaratchi, M
Williams, N
Williams-Gray, CH
Winder-Rhodes, S
Stefansson, K
Martinez, M
Hardy, J
Heutink, P
Brice, A
Gasser, T
Singleton, AB
Wood, NW
AF Nalls, Michael A.
Plagnol, Vincent
Hernandez, Dena G.
Sharma, Manu
Sheerin, Una-Marie
Saad, Mohamad
Simon-Sanchez, Javier
Schulte, Claudia
Lesage, Suzanne
Sveinbjornsdottir, Sigurlaug
Arepalli, Sampath
Barker, Roger
Ben-Shlomo, Yoav
Berendse, Henk W.
Berg, Daniela
Bhatia, Kailash
de Bie, Rob M. A.
Biffi, Alessandro
Bloem, Bas
Bochdanovits, Zoltan
Bonin, Michael
Bras, Jose M.
Brockmann, Kathrin
Brooks, Janet
Burn, David J.
Charlesworth, Gavin
Chen, Honglei
Chinnery, Patrick F.
Chong, Sean
Clarke, Carl E.
Cookson, Mark R.
Cooper, J. Mark
Corvol, Jean Christophe
Counsell, Carl
Damier, Philippe
Dartigues, Jean-Francois
Deloukas, Panos
Deuschl, Guenther
Dexter, David T.
van Dijk, Karin D.
Dillman, Allissa
Durif, Frank
Duerr, Alexandra
Edkins, Sarah
Evans, Jonathan R.
Foltynie, Thomas
Gao, Jianjun
Gardner, Michelle
Gibbs, J. Raphael
Goate, Alison
Gray, Emma
Guerreiro, Rita
Gustafsson, Omar
Harris, Clare
van Hilten, Jacobus J.
Hofman, Albert
Hollenbeck, Albert
Holton, Janice
Hu, Michele
Huang, Xuemei
Huber, Heiko
Hudson, Gavin
Hunt, Sarah E.
Huttenlocher, Johanna
Illig, Thomas
Jonsson, Palmi V.
Lambert, Jean-Charles
Langford, Cordelia
Lees, Andrew
Lichtner, Peter
Limousin, Patricia
Lopez, Grisel
Lorenz, Delia
McNeill, Alisdair
Moorby, Catriona
Moore, Matthew
Morris, Huw R.
Morrison, Karen E.
Mudanohwo, Ese
O'Sullivan, Sean S.
Pearson, Justin
Perlmutter, Joel S.
Petursson, Hjoervar
Pollak, Pierre
Post, Bart
Potter, Simon
Ravina, Bernard
Revesz, Tamas
Riess, Olaf
Rivadeneira, Fernando
Rizzu, Patrizia
Ryten, Mina
Sawcer, Stephen
Schapira, Anthony
Scheffer, Hans
Shaw, Karen
Shoulson, Ira
Sidransky, Ellen
Smith, Colin
Spencer, Chris C. A.
Stefansson, Hreinn
Stockton, Joanna D.
Strange, Amy
Talbot, Kevin
Tanner, Carlie M.
Tashakkori-Ghanbaria, Avazeh
Tison, Francois
Trabzuni, Daniah
Traynor, Bryan J.
Uitterlinden, Andre G.
Velseboer, Daan
Vidailhet, Marie
Walker, Robert
van de Warrenburg, Bart
Wickremaratchi, Mirdhu
Williams, Nigel
Williams-Gray, Caroline H.
Winder-Rhodes, Sophie
Stefansson, Kari
Martinez, Maria
Hardy, John
Heutink, Peter
Brice, Alexis
Gasser, Thomas
Singleton, Andrew B.
Wood, Nicholas W.
CA Int Parkinson Dis Genomics Consort
Wellcome Trust Case-Control Consor
TI Imputation of sequence variants for identification of genetic risks for
Parkinson's disease: a meta-analysis of genome-wide association studies
SO LANCET
LA English
DT Article
ID SYNAPTOTAGMIN-XI; COMMON; LOCI; SUSCEPTIBILITY; MUTATIONS; SUGGESTS;
REGION; STK39; SNCA
AB Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease.
Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated.
Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5x10(-8)). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BSTI, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7-69-3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23-2.83) compared with 1.00 in the lowest quintile of disease risk.
Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.
C1 [Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20837 USA.
[Plagnol, Vincent; Wood, Nicholas W.] UCL Genet Inst, London, England.
[Hernandez, Dena G.; Sheerin, Una-Marie; Bhatia, Kailash; Bras, Jose M.; Charlesworth, Gavin; Gardner, Michelle; Gibbs, J. Raphael; Guerreiro, Rita; Ryten, Mina; Trabzuni, Daniah; Hardy, John; Wood, Nicholas W.] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Sharma, Manu] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
[Sharma, Manu] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany.
[Saad, Mohamad] CPTP, INSERM, U563, Toulouse, France.
[Saad, Mohamad; Martinez, Maria] Univ Toulouse 3, F-31062 Toulouse, France.
[Simon-Sanchez, Javier; Bochdanovits, Zoltan; Rizzu, Patrizia; Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands.
[Lesage, Suzanne; Corvol, Jean Christophe; Duerr, Alexandra] INSERM, UMR S975, Paris, France.
[Lesage, Suzanne] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Paris, France.
[Lesage, Suzanne; Corvol, Jean Christophe; Duerr, Alexandra] CNRS, Paris, France.
[Sveinbjornsdottir, Sigurlaug] Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland.
[Sveinbjornsdottir, Sigurlaug] MEHT Broomfield Hosp, Dept Neurol, Chelmsford, Essex, England.
[Sveinbjornsdottir, Sigurlaug] Univ London, Queen Mary Coll, London, England.
[Barker, Roger] Univ Cambridge, Addenbrookes Hosp, Dept Neurol, Cambridge CB2 2QQ, England.
[Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, Bristol BS8 1TH, Avon, England.
[Berendse, Henk W.; van Dijk, Karin D.] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands.
[Berendse, Henk W.; van Dijk, Karin D.] Vrije Univ Amsterdam Med Ctr, Alzheimers Ctr, Amsterdam, Netherlands.
[de Bie, Rob M. A.; Velseboer, Daan] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands.
[Biffi, Alessandro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Biffi, Alessandro] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Bloem, Bas; Post, Bart; van de Warrenburg, Bart] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, NL-6525 ED Nijmegen, Netherlands.
[Bonin, Michael; Petursson, Hjoervar; Riess, Olaf] Univ Tubingen, Inst Human Genet, Dept Med Genet, Tubingen, Germany.
[Burn, David J.] Newcastle Univ, Clin Ageing Res Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Chen, Honglei] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC USA.
[Chinnery, Patrick F.; Hudson, Gavin] Newcastle Univ, Sch Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Clarke, Carl E.; Moorby, Catriona; Morrison, Karen E.] Univ Birmingham, Sch Clin & Expt Med, Birmingham, W Midlands, England.
[Clarke, Carl E.] Sandwell & W Birmingham Hosp NHS Trust, City Hosp, Dept Neurol, Birmingham, W Midlands, England.
[Cooper, J. Mark; McNeill, Alisdair; Schapira, Anthony] UCL Inst Neurol, Dept Clin Neurosci, London, England.
[Corvol, Jean Christophe] Hop La Pitie Salpetriere, INSERM, CIC 9503, Paris, France.
[Counsell, Carl] Univ Aberdeen, Div Appl Hlth Sci, Populat Hlth Sect, Aberdeen, Scotland.
[Damier, Philippe] CHU Nantes, CIC0004, Serv Neurol, F-44035 Nantes 01, France.
[Dartigues, Jean-Francois] Univ Victor Segalen, INSERM, U897, Bordeaux, France.
[Deloukas, Panos; Edkins, Sarah; Gray, Emma; Hunt, Sarah E.; Potter, Simon; Tashakkori-Ghanbaria, Avazeh] Wellcome Trust Sanger Inst, Cambridge, England.
[Deuschl, Guenther] Univ Kiel, Univ Klinikum Schleswig Holstein, Neurol Klin, Kiel, Germany.
[Dexter, David T.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Parkinsons Dis Res Grp, London, England.
[Durif, Frank] Hop Gabriel Montpied, Serv Neurol, Clermont Ferrand, France.
[Duerr, Alexandra] Hop La Pitie Salpetriere, AP HP, Paris, France.
[Evans, Jonathan R.; Langford, Cordelia] Cambridge Ctr Brain Repair, Cambridge, England.
[Gustafsson, Omar] Oslo Univ Hosp, deCODE Genet, N-0407 Oslo, Norway.
[Gustafsson, Omar] Oslo Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway.
[van Hilten, Jacobus J.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Hollenbeck, Albert] AARP, Washington, DC USA.
[Holton, Janice] UCL Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England.
[Hu, Michele] John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Bioengn, Hershey, PA 17033 USA.
[Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Jonsson, Palmi V.] Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland.
[Lambert, Jean-Charles] INSERM, U744, F-59045 Lille, France.
[Lambert, Jean-Charles] Univ Lille Nord, Inst Pasteur Lille, Lille, France.
[Lichtner, Peter] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Limousin, Patricia] Inst Neurol, Sobell Dept, Unit Funct Neurosurg, London WC1N 3BG, England.
[Lopez, Grisel] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD USA.
[Morris, Huw R.] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales.
[Morrison, Karen E.] Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp, Dept Neurosci, Birmingham, W Midlands, England.
[Mudanohwo, Ese] UCL Inst Neurol, Neurogenet Unit, London, England.
[Perlmutter, Joel S.] Washington Univ, Dept Neurol Radiol & Neurobiol, St Louis, MO 63130 USA.
[Pollak, Pierre] CHU Grenoble, Serv Neurol, F-38043 Grenoble, France.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Sawcer, Stephen] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
[Scheffer, Hans] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Shoulson, Ira] Univ Rochester, Dept Neurol, Rochester, NY USA.
[Smith, Colin; Walker, Robert] Univ Edinburgh, Dept Pathol, Edinburgh, Midlothian, Scotland.
[Spencer, Chris C. A.; Strange, Amy] Wellcome Trust Ctr Human Genet, Oxford, England.
[Talbot, Kevin] Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England.
[Tanner, Carlie M.] Parkinsons Inst & Clin Ctr, Dept Clin Res, Sunnyvale, CA USA.
[Tison, Francois] Hop Haut Leveque, Serv Neurol, Pessac, France.
[Vidailhet, Marie] Univ Paris 06, INSERM, UMR S975, CNRS,UMR 7225, F-75252 Paris 05, France.
[Wickremaratchi, Mirdhu] Cardiff Univ, Dept Neurol, Cardiff, S Glam, Wales.
[Williams-Gray, Caroline H.] Addenbrookes Hosp, Dept Neurol, Cambridge, England.
[Winder-Rhodes, Sophie] Univ Cambridge, Dept Psychiat, Cambridge CB2 1TN, England.
[Winder-Rhodes, Sophie] Univ Cambridge, MRC, Cambridge CB2 1TN, England.
[Winder-Rhodes, Sophie] Univ Cambridge, Wellcome Trust Behav & Clin Neurosci Inst, Cambridge CB2 1TN, England.
[Martinez, Maria] INSERM, U563, F-75654 Paris 13, France.
[Brice, Alexis] Univ Paris 06, Pitie Salpetriere Hosp, AP HP, CNRS,UMR 7225,INSERM,UMR S975, F-75252 Paris 05, France.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20837 USA.
EM singleta@mail.nih.gov
RI Morris, Huw/B-8527-2008; Bloem, Bastiaan/E-3812-2010; Charlesworth,
Gavin/B-5895-2011; Singleton, Andrew/C-3010-2009; turton,
miranda/F-4682-2011; Holton, Janice/F-6831-2011; Talbot, Kevin
/F-7361-2011; Guerreiro, Rita/A-1327-2011; Plagnol, Vincent/A-5667-2011;
mcneill, alisdair/B-1267-2012; O'Sullivan, Sean/C-9333-2012; Hardy,
John/C-2451-2009; Lees, Andrew/A-6605-2009; Scheffer, Hans/E-4644-2012;
Traynor, Bryan/G-5690-2010; Deloukas, Panos/B-2922-2013; Bras,
Jose/A-1428-2011; Cooper, J Mark/D-5826-2013; Deuschl,
Gunther/A-7986-2010; lambert, jean-charles/F-8787-2013; Wood,
Nicholas/C-2505-2009; LICEND, CEMND/F-1296-2015; Bloem,
B.R./H-8013-2014; Trabzuni, Daniah/C-4034-2012; Rivadeneira,
Fernando/O-5385-2015; van de Warrenburg, Bart/D-1935-2010; Lambert,
jean-charles/A-9553-2014; Martinez, Maria/B-3111-2013; corvol,
jean-christophe/I-6387-2012; Revesz, Tamas/A-8732-2010; Hudson,
Gavin/E-7117-2017;
OI Morris, Huw/0000-0002-5473-3774; Holton, Janice/0000-0002-3882-5249;
O'Sullivan, Sean/0000-0002-0583-7956; Scheffer,
Hans/0000-0002-2986-0915; Deloukas, Panos/0000-0001-9251-070X; Cooper, J
Mark/0000-0002-3007-3054; Wood, Nicholas/0000-0002-9500-3348; Trabzuni,
Daniah/0000-0003-4826-9570; Rivadeneira, Fernando/0000-0001-9435-9441;
Lambert, jean-charles/0000-0003-0829-7817; Bhatia,
Kailash/0000-0001-8185-286X; Chen, Honglei/0000-0003-3446-7779;
Martinez, Maria/0000-0003-2180-4537; corvol,
jean-christophe/0000-0001-7325-0199; Revesz, Tamas/0000-0003-2501-0259;
Walker, Robert/0000-0001-7383-7846; Bras, Jose/0000-0001-8186-0333;
Schulte, Claudia/0000-0003-4006-1265; Plagnol,
Vincent/0000-0002-5597-9215; Stefansson, Hreinn/0000-0002-9331-6666
FU deCODE; Eisai; Merck-Serono; Cephalon; Novartis; National Institute on
Aging, National Institute of Neurological Disorders and Stroke, National
Institute of Environmental Health Sciences; National Human Genome
Research Institute of the National Institutes of Health, Department of
Health and Human Services [Z01-AG000949-02, Z01-ES101986]; US Department
of Defense [W81XWH-09-2-0128]; National Institutes of Health [NS057105,
RA024992]; American Parkinson disease Association (APDA); Barnes Jewish
Hospital Foundation; Greater St Louis Chapter of the APDA;
Hersenstichting Nederland; Neuroscience Campus Amsterdam; section of
medical genomics; Prinses Beatrix Fonds; Forschungszentrum fur Umwelt
und Gesundheit; German National Genome Network (German Ministry for
Education and Research) [01GS08134]; German Federal Ministry of
Education and Research [NGFN 01GR0468]; Helmholtz Alliance Mental Health
in an Ageing Society [HA-215]; Helmholtz Association; French National
Agency of Research [ANR-08-MNP-012]; Landspitali University Hospital;
Icelandic Research Council; European Community [PIAP-GA-2008-230596];
Wellcome Trust [083948/Z/07/Z]; Medical Research Council; Wellcome Trust
disease centre [WT089698/Z/09/Z]; Parkinson's UK [8047, J-0804]; Medical
Research Council [G0700943]; Department of Health's National Institute
for Health Research Biomedical Research Centres; Wellcome Trust/Medical
Research Council [WT089698]; Parkinson's Disease Consortium (UKPDC)
FX KSt has received grants from deCODE. JH has received consulting fees or
honoraria from Eisai and his institute has received consulting fees or
honoraria from Merck-Serono. TG has received consultancy fees from
Cephalon and Merck-Serono; grants from Novartis; payments for lectures
including service on speakers' bureaus from Boehringer Ingelheim,
Merck-Serono, UCB, and Valeant; and holds patents NGFN2 and KASPP. MAN,
VP, DGH, MSh, U-MS, MSa, JS-S, CS, SL, SS, KS, MM, PH, ABr, ABS, and NWW
declare that they have no conflicts of interest.; This work was
supported by the Intramural Research Programs of the National Institute
on Aging, National Institute of Neurological Disorders and Stroke,
National Institute of Environmental Health Sciences, and National Human
Genome Research Institute of the National Institutes of Health,
Department of Health and Human Services (project numbers Z01-AG000949-02
and Z01-ES101986). This work was also supported by the US Department of
Defense (award number W81XWH-09-2-0128); National Institutes of Health
(grants NS057105 and RA024992); American Parkinson disease Association
(APDA); Barnes Jewish Hospital Foundation; Greater St Louis Chapter of
the APDA; Hersenstichting Nederland; Neuroscience Campus Amsterdam; and
the section of medical genomics, the Prinses Beatrix Fonds. The KORA
(Cooperative Research in the Region of Augsburg) research platform was
started and financed by the Forschungszentrum fur Umwelt und Gesundheit,
which is funded by the German Federal Ministry of Education, Science,
Research, and Technology and by the State of Bavaria. This study was
also funded by the German National Genome Network (NGENplus number
01GS08134, German Ministry for Education and Research); by the German
Federal Ministry of Education and Research (NGFN 01GR0468, PopGen); and
01EW0908 in the frame of ERA-NET NEURON and Helmholtz Alliance Mental
Health in an Ageing Society (HA-215), which was funded by the Initiative
and Networking Fund of the Helmholtz Association. The French GWAS work
was supported by the French National Agency of Research
(ANR-08-MNP-012). This study was also sponsored by the Landspitali
University Hospital Research Fund (grant to SSv); Icelandic Research
Council (grant to SSv); and European Community Framework Programme 7,
People Programme, and IAPP on novel genetic and phenotypic markers of
Parkinson's disease and Essential Tremor (MarkMD), contract number
PIAP-GA-2008-230596 MarkMD (to HP and JHu). We used the Biowulf Linux
cluster at the National Institutes of Health, Bethesda, MD, USA, and DNA
panels, samples, and clinical data from the National Institute of
Neurological Disorders and Stroke Human Genetics Resource Center DNA and
Cell Line Repository. People who contributed samples are acknowledged in
descriptions of every panel on the repository website. We thank The
French Parkinson's Disease Genetics Study Group: Y Agid, M Anheim, A-M
Bonnet, M Borg, A Brice, E Broussolle, J-C Corvol, P Damier, A Destee, A
Darr, F Durif, S Klebe, E Lohmann, M Martinez, P Pollak, O Rascol, F
Tison, C Tranchant, M Venn, F Viallet, and M Vidailhet. We also thank
the members of the French 3C Consortium: Annick Alperovitch, Claudine
Berr, Christophe Tzourio, and Philippe Amouyel for allowing us souse
part of the 3C cohort; and D Zelenika for support in generating the
genome-wide molecular data. We used genome-wide association data
generated by the Wellcome Trust Case-Control Consortium 2 (WTCCC2) from
UK patients with Parkinson's disease and UK control individuals from the
1958 Birth Cohort and National Blood Service. Genotyping of UK
replication cases on ImmunoChip was part of the WTCCC2 project, which
was funded by the Wellcome Trust (083948/Z/07/Z). UK population control
data was made available through WTCCC1. This study was supported by the
Medical Research Council and Wellcome Trust disease centre (grant
WT089698/Z/09/Z to NW, J Ha, and ASc). This study was also supported by
Parkinson's UK (grants 8047 and J-0804) and the Medical Research Council
(G0700943). We thank Jeffrey Barrett for assistance with the design of
the ImmunoChip.; DNA extration work that was done in the UK was
undertaken at University College London Hospitals, University College
London, who received a proportion of funding from the Department of
Health's National Institute for Health Research Biomedical Research
Centres funding. This study was supported in part by the Wellcome
Trust/Medical Research Council Joint Call in Neurodegeneration award
(WT089698) to the Parkinson's Disease Consortium (UKPDC), whose members
are from the UCL Institute of Neurology, University of Sheffield, and
the Medical Research Council Protein Phosphorylation Unit at the
University of Dundee.
NR 35
TC 382
Z9 384
U1 10
U2 78
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 FEB 19
PY 2011
VL 377
IS 9766
BP 641
EP 649
DI 10.1016/S0140-6736(10)62345-8
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 727DB
UT WOS:000287776600033
ER
PT J
AU Banz, VM
Paul, K
de Moya, M
Zimmermann, H
Candinas, D
Exadaktylos, AK
AF Banz, Vanessa M.
Paul, Katrin
de Moya, Marc
Zimmermann, Heinz
Candinas, Daniel
Exadaktylos, Aristomenis K.
TI Ignoring non-specific abdominal pain in emergency department patients
may be related to decreased quality of life
SO SWISS MEDICAL WEEKLY
LA English
DT Article
DE abdominal pain; prospective survey; emergency medicine; pain
ID LOW-BACK-PAIN; ABNORMAL ILLNESS BEHAVIOR; MAJOR DEPRESSION; SYMPTOMS;
POPULATION; HEALTH; SOMATIZATION; PREVALENCE; DISORDERS; ANXIETY
AB QUESTIONS UNDER STUDY: Patients suffering from chronic pain have a high prevalence of depression, resulting in a significant impact on overall quality of life. Our aim was to investigate how long term acute non-specific abdominal pain (NSAP) affected overall physical and mental well-being in patients admitted to our emergency department (ED).
METHODS: All patients discharged from the ED with NSAP between 06/2007 and 06/2008 were included for follow up. Current health and well-being was evaluated using the SF-36 (R) health questionnaire. Ordinal linear regression models were chosen to separately assess variables influencing SF-36 (R) outcome, with adjustment for age and gender.
Results were expressed as differences of means with corresponding 95% confidence intervals and p-values. RESULTS: Of the 200 patients included (57% female, mean age 33 years), 53 (26.5%) still suffered from NSAP after a 12.5-month mean follow up. Patients with persistent NSAP suffered more from chronic pain (26.4%) or known psychiatric illnesses (15.1%) than unaffected patients (p < 0.001 and p = 0.028). Mental (MCS) and physical component scores (PCS) were significantly worse in patients suffering from persistent NSAP, even when adjusted for confounding factors including chronic pain syndromes, pre-existing psychiatric illnesses, other concomitant comorbidities and previous abdominal surgery (p < 0.001 for both scores). Other risk factors included chronic pain syndromes, pre-existing psychiatric illnesses, other concomitant comorbidities and previous abdominal surgery.
CONCLUSIONS: NSAP persistence may be associated with a decreased quality of life. Emphasis should be put on providing early counselling and support, with the aim of minimising the long term detrimental side effects of NSAP.
C1 [Banz, Vanessa M.; Candinas, Daniel] Univ Hosp Bern, Inselspital, Dept Visceral Surg & Med, CH-3010 Bern, Switzerland.
[Banz, Vanessa M.; Paul, Katrin; Zimmermann, Heinz; Candinas, Daniel; Exadaktylos, Aristomenis K.] Univ Bern, CH-3010 Bern, Switzerland.
[Paul, Katrin; Zimmermann, Heinz; Exadaktylos, Aristomenis K.] Univ Hosp Bern, Inselspital, Dept Emergency Med, CH-3010 Bern, Switzerland.
[de Moya, Marc] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg Surg Crit Care, Boston, MA USA.
RP Banz, VM (reprint author), Univ Hosp Bern, Inselspital, Dept Visceral Surg & Med, CH-3010 Bern, Switzerland.
EM vanessa.banz@insel.ch
NR 27
TC 3
Z9 3
U1 3
U2 4
PU E M H SWISS MEDICAL PUBLISHERS LTD
PI MUTTENZ
PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND
SN 1424-7860
J9 SWISS MED WKLY
JI Swiss Med. Wkly.
PD FEB 18
PY 2011
VL 141
AR w13167
DI 10.4414/smw.2011.13167
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 756EF
UT WOS:000289993800003
PM 21337174
ER
PT J
AU Jiang, H
Shukla, A
Wang, XL
Chen, WY
Bernstein, BE
Roeder, RG
AF Jiang, Hao
Shukla, Abhijit
Wang, Xiaoling
Chen, Wei-yi
Bernstein, Bradley E.
Roeder, Robert G.
TI Role for Dpy-30 in ES Cell-Fate Specification by Regulation of H3K4
Methylation within Bivalent Domains
SO CELL
LA English
DT Article
ID EMBRYONIC STEM-CELLS; ELEGANS DOSAGE COMPENSATION; HISTONE H3;
DEVELOPMENTAL REGULATORS; CHROMATIN SIGNATURES; GROUP PROTEINS;
POLYCOMB; PLURIPOTENT; DIFFERENTIATION; TRITHORAX
AB Histone H3K4 methylation is associated with active genes and, along with H3K27 methylation, is part of a bivalent chromatin mark that typifies poised developmental genes in embryonic stem cells (ESCs). However, its functional roles in ESC maintenance and differentiation are not established. Here we show that mammalian Dpy-30, a core subunit of the SET1/MLL histone methyltransferase complexes, modulates H3K4 methylation in vitro, and directly regulates chromosomal H3K4 trimethylation (H3K4me3) throughout the mammalian genome. Depletion of Dpy-30 does not affect ESC self-renewal, but significantly alters the differentiation potential of ESCs, particularly along the neural lineage. The differentiation defect is accompanied by defects in gene induction and in H3K4 methylation at key developmental loci. Our results strongly indicate an essential functional role for Dpy-30 and SET1/MLL complex-mediated H3K4 methylation, as a component of the bivalent mark, at developmental genes during the ESC fate transitions.
C1 [Jiang, Hao; Wang, Xiaoling; Chen, Wei-yi; Roeder, Robert G.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10065 USA.
[Shukla, Abhijit; Bernstein, Bradley E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Shukla, Abhijit; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Shukla, Abhijit; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Roeder, RG (reprint author), Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10065 USA.
EM roeder@mail.rockefeller.edu
RI Wang, Xiaoling/D-4208-2013
FU Tri-Institutional Starr Stem Cell Scholars fellowship; NIH [DK071900];
Starr Cancer Consortium [I2-A88]; Leukemia and Lymphoma Society
[7132-08]
FX We are grateful to Yali Dou for baculoviruses encoding RbBP5, WDR5 and
Ash2L, Cristina Hughes (David Allis lab), and Eric McIntush (Bethyl
Laboratories) for Dpy-30 antibody, Joanna Wysocka for WDR5 antibody,
Aaron Goldberg (David Allis lab) for LIF, Shannon Lauberth and Zhanyun
Tang for providing supporting data, Zheng-Yuan Fu for technical
assistance, Esther Rheinbay, Jing Wang and Xiaojian Sun for data
analyses, and Bing Ren (UCSD) and Xiangdong Lu for insightful
discussions of the project. H.J. and W.-Y.C. are Leukemia and Lymphoma
Society Fellows. X. W. is a recipient of a Tri-Institutional Starr Stem
Cell Scholars fellowship. This work was supported by NIH (DK071900),
Starr Cancer Consortium (I2-A88), and Leukemia and Lymphoma Society
(7132-08) grants to R.G.R.
NR 44
TC 140
Z9 150
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 18
PY 2011
VL 144
IS 4
BP 513
EP 525
DI 10.1016/j.cell.2011.01.020
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 722ZC
UT WOS:000287473100007
PM 21335234
ER
PT J
AU Pellegrini, M
Calzascia, T
Toe, JG
Preston, SP
Lin, AE
Elford, AR
Shahinian, A
Lang, PA
Lang, KS
Morre, M
Assouline, B
Lahl, K
Sparwasser, T
Tedder, TF
Paik, JH
DePinho, RA
Basta, S
Ohashi, PS
Mak, TW
AF Pellegrini, Marc
Calzascia, Thomas
Toe, Jesse G.
Preston, Simon P.
Lin, Amy E.
Elford, Alisha R.
Shahinian, Arda
Lang, Philipp A.
Lang, Karl S.
Morre, Michel
Assouline, Brigitte
Lahl, Katharina
Sparwasser, Tim
Tedder, Thomas F.
Paik, Ji-hye
DePinho, Ronald A.
Basta, Sameh
Ohashi, Pamela S.
Mak, Tak W.
TI IL-7 Engages Multiple Mechanisms to Overcome Chronic Viral Infection and
Limit Organ Pathology
SO CELL
LA English
DT Article
ID CD4(+) T-CELLS; IN-VIVO; LYMPHOID-TISSUE; HOST-DEFENSE; INTERLEUKIN-22;
ACTIVATION; EXPANSION; INFLAMMATION; PERSISTENCE; HEPATOCYTES
AB Understanding the factors that impede immune responses to persistent viruses is essential in designing therapies for HIV infection. Mice infected with LCMV clone-13 have persistent high-level viremia and a dysfunctional immune response. Interleukin-7, a cytokine that is critical for immune development and homeostasis, was used here to promote immunity toward clone-13, enabling elucidation of the inhibitory pathways underlying impaired antiviral immune response. Mechanistically, IL-7 down-regulated a critical repressor of cytokine signaling, Socs3, resulting in amplified cytokine production, increased T cell effector function and numbers, and viral clearance. IL-7 enhanced thymic output to expand the naive T cell pool, including T cells that were not LCMV specific. Additionally, IL-7 promoted production of cytoprotective IL-22 that abrogated liver pathology. The IL-7-mediated effects were dependent on endogenous IL-6. These attributes of IL-7 have profound implications for its use as a therapeutic in the treatment of chronic viral diseases.
C1 [Pellegrini, Marc; Calzascia, Thomas; Lin, Amy E.; Elford, Alisha R.; Shahinian, Arda; Lang, Philipp A.; Lang, Karl S.; Ohashi, Pamela S.; Mak, Tak W.] Univ Hlth Network, Dept Med Biophys, Campbell Family Canc Res Inst, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada.
[Pellegrini, Marc; Calzascia, Thomas; Lin, Amy E.; Elford, Alisha R.; Shahinian, Arda; Lang, Philipp A.; Lang, Karl S.; Ohashi, Pamela S.; Mak, Tak W.] Univ Hlth Network, Dept Immunol, Campbell Family Canc Res Inst, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada.
[Pellegrini, Marc; Toe, Jesse G.; Preston, Simon P.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia.
[Pellegrini, Marc] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3050, Australia.
[Morre, Michel; Assouline, Brigitte] Cytheris Inc, F-92130 Issy Les Moulineaux, France.
[Lahl, Katharina] Stanford Univ, Lab Immunol & Vasc Biol, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Sparwasser, Tim] Ctr Expt & Clin Infect Res, Inst Infect Immunol, TWINCORE, D-30625 Hannover, Germany.
[Tedder, Thomas F.] Duke Univ, Dept Immunol, Med Ctr, Durham, NC 27708 USA.
[Paik, Ji-hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med Oncol,Dept Med,Dana Farber Canc Inst, Boston, MA 02115 USA.
[Paik, Ji-hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Basta, Sameh] Queens Univ, Dept Microbiol & Immunol, Kingston, ON K7L 396, Canada.
RP Ohashi, PS (reprint author), Univ Hlth Network, Dept Med Biophys, Campbell Family Canc Res Inst, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada.
EM pohashi@uhnres.utoronto.ca
RI Pellegrini, Marc/F-7670-2014; Lang, Karl/R-2505-2016
FU Canadian Institute for Health Research [CIHR-MOP-106529]; Terry Fox
Cancer Foundation National Cancer Institute of Canada; Boninchi
Foundation (Geneva, Switzerland); National Cancer Institute of Canada;
Irvington Institute with the Cancer Research Institute (New York, NY);
Australian National Health and Medical Research Council; Natural
Sciences and Engineering Research Council of Canada; Ontario Ministry of
Health and Long Term Care (OMOHLTC)
FX Dr. Mandana Nikpour assisted with statistical analyses. Marina Zaitseva
contributed to the analysis of thymic emigrants; Alain Lamarre, Paul
Jolicoeur, and Michel Nussenzweig provided reagents and mice. This work
was supported by a Canadian Institute for Health Research grant to T. W.
M. and P.S.O. (CIHR-MOP-106529) and a Terry Fox Cancer Foundation
National Cancer Institute of Canada grant to T. W. M. T. C. was
supported by the Boninchi Foundation (Geneva, Switzerland) and The Terry
Fox Foundation through an award from the National Cancer Institute of
Canada. M. P. was supported through an Irvington Institute Fellowship
with the Cancer Research Institute (New York, NY) and an Australian
National Health and Medical Research Council Fellowship. S. B receives
support from the Natural Sciences and Engineering Research Council of
Canada. P.S.O. holds a Canada Research Chair in autoimmunity and tumor
immunity. This research was also funded, in part, by the Ontario
Ministry of Health and Long Term Care (OMOHLTC). The views expressed do
not necessarily reflect those of the OMOHLTC.
NR 48
TC 143
Z9 147
U1 1
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 18
PY 2011
VL 144
IS 4
BP 601
EP 613
DI 10.1016/j.cell.2011.01.011
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 722ZC
UT WOS:000287473100014
PM 21295337
ER
PT J
AU Fung, H
Demple, B
AF Fung, Hua
Demple, Bruce
TI Distinct Roles of Ape1 Protein in the Repair of DNA Damage Induced by
Ionizing Radiation or Bleomycin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BASE EXCISION-REPAIR; DOUBLE-STRAND-BREAK; HUMAN APURINIC/APYRIMIDINIC
ENDONUCLEASE; HUMAN CELL-EXTRACTS; SINGLE-STRAND; ABASIC SITES;
IN-VITRO; SACCHAROMYCES-CEREVISIAE; CLUSTERED DAMAGE; CANCER
AB Ionizing radiation (IR) and bleomycin (BLM) are used to treat various types of cancers. Both agents generate cytotoxic double strand breaks (DSB) and abasic (apurinic/apyrimidinic (AP)) sites in DNA. The human AP endonuclease Ape1 acts on abasic or 3'-blocking DNA lesions such as those generated by IR or BLM. We examined the effect of siRNA-mediated Ape1 suppression on DNA repair and cellular resistance to IR or BLM in human B-lymphoblastoid TK6 cells and HCT116 colon tumor cells. Partial Ape1 deficiency (similar to 30% of normal levels) sensitized cells more dramatically to BLM than to IR cytotoxicity. In both cases, expression of the unrelated yeast AP endonuclease, Apn1, largely restored resistance. Ape1 deficiency increased DNA AP site accumulation due to IR treatment but reduced the number of DSB. In contrast, for BLM, there were more DSB under Ape1 deficiency, with little change in the accumulation of AP sites. Although the role of Ape1 in generating DSB was greater for IR, the enzyme facilitated removal of AP sites, which may mitigate the cytotoxic effects of IR. In contrast, BLM generates scattered AP sites, and the DSB have 3'-phosphoglycolate termini that require Ape1 processing. These DSB persist under Ape1 deficiency. Apoptosis induced by BLM (but not by IR) under Ape1 deficiency was partially p53-dependent, more dramatically in TK6 than HCT116 cells. Thus, Ape1 suppression or inhibition may be a more efficacious adjuvant for BLM than for IR cancer therapy, particularly for tumors with a functional p53 pathway.
C1 [Demple, Bruce] SUNY Stony Brook, Dept Pharmacol Sci, Sch Med, Stony Brook, NY 11794 USA.
[Fung, Hua] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Demple, B (reprint author), SUNY Stony Brook, Dept Pharmacol Sci, Sch Med, Stony Brook, NY 11794 USA.
EM bruce@pharm.stonybrook.edu
FU National Institutes of Health [R01 GM040000]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01 GM040000 (to B. D.).
NR 60
TC 39
Z9 39
U1 1
U2 5
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 FEB 18
PY 2011
VL 286
IS 7
BP 4968
EP 4977
DI 10.1074/jbc.M110.146498
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 719SY
UT WOS:000287230600005
PM 21081487
ER
PT J
AU Riese, MJ
Grewal, J
Das, J
Zou, T
Patil, V
Chakraborty, AK
Koretzky, GA
AF Riese, Matthew J.
Grewal, Jashanpreet
Das, Jayajit
Zou, Tao
Patil, Vineet
Chakraborty, Arup K.
Koretzky, Gary A.
TI Decreased Diacylglycerol Metabolism Enhances ERK Activation and Augments
CD8(+) T Cell Functional Responses
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CBL-B; KINASE-ZETA; HOMEOSTATIC PROLIFERATION; RAS ACTIVATION; IN-VIVO;
POSITIVE SELECTION; ANTIGEN; PROTEIN; ALPHA; NAIVE
AB Modulation of T cell receptor signal transduction in CD8(+) T cells represents a novel strategy toward enhancing the immune response to tumor. Recently, levels of guanine exchange factors, RasGRP and SOS, within T cells have been shown to represent a key determinant in the regulation of the analog to the digital activation threshold of Ras. One important for regulating activation levels of RasGRP is diacylglycerol (DAG), and its levels are influenced by diacylglycerol kinase-zeta (DGK zeta), which metabolizes DAG into phosphatidic acid, terminating DAG-mediated Ras signaling. We sought to determine whether DGK zeta-deficient CD8(+) T cells demonstrated enhanced in vitro responses in a manner predicted by the current model of Ras activation and to evaluate whether targeting this threshold confers enhanced CD8(+) T cell responsiveness to tumor. We observed that DGK zeta-deficient CD8(+) T cells conform to most predictions of the current model of how RasGRP levels influence Ras activation. But our results differ in that the EC50 value of stimulation is not altered for any T cell receptor stimulus, a finding that suggests a further degree of complexity to how DGK zeta deficiency affects signals important for Ras and ERK activation. Additionally, we found that DGK zeta-deficient CD8(+) T cells demonstrate enhanced responsiveness in a subcutaneous lymphoma model, implicating the analog to a digital conversion threshold as a novel target for potential therapeutic manipulation.
C1 [Koretzky, Gary A.] Univ Penn, Dept Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Riese, Matthew J.] Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Koretzky, Gary A.] Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA.
[Das, Jayajit] Nationwide Childrens Hosp, Battelle Ctr Math Med, Columbus, OH 43205 USA.
[Das, Jayajit] Ohio State Univ, Dept Pediat, Columbus, OH 43205 USA.
[Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Koretzky, Gary A.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] Massachusetts Gen Hosp, Ragon Inst, MIT, Charlestown, MA 02129 USA.
RP Koretzky, GA (reprint author), 413 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA.
EM koretzky@mail.med.upenn.edu
RI Das, Jayajit/E-2951-2011
FU National Institutes of Health
FX This work was supported, in whole or in part, by a National Institutes
of Health grant.
NR 46
TC 24
Z9 24
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 FEB 18
PY 2011
VL 286
IS 7
BP 5254
EP 5265
DI 10.1074/jbc.M110.171884
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 719SY
UT WOS:000287230600034
PM 21138839
ER
PT J
AU Lee, KH
Liu, YJ
Biswas, A
Ogawa, C
Kobayashi, KS
AF Lee, Kyoung-Hee
Liu, Yuen-Joyce
Biswas, Amlan
Ogawa, Chikako
Kobayashi, Koichi S.
TI A Novel Aminosaccharide Compound Blocks Immune Responses by Toll-like
Receptors and Nucleotide-binding Domain, Leucine-rich Repeat Proteins
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; BLAU-SYNDROME; BACTERIAL
PEPTIDOGLYCAN; REGULATORY ROLES; CARD15 MUTATIONS; CROHNS-DISEASE;
CUTTING EDGE; MURINE MODEL; STRANDED-RNA
AB Toll-like receptors (TLRs) and nucleotide-binding domain, leucine-rich repeat (NLR) proteins are two major forms of innate immune receptors that trigger inflammatory responses by various biological mechanisms such as cytokine production, recruitment of inflammatory cells, or activation of adaptive immunity. Although the innate immune system is designed to fight against infectious pathogens, excessive activation of TLR or NLR signaling pathways may lead to unwarranted inflammation with hazardous outcomes, including septic shock or inflammatory diseases. As part of the search for effective therapeutics to regulate these responses, here we show that a novel aminosaccharide compound, named DFK1012, inhibits immune responses caused by TLR and NLR activation. Treatment with DFK1012, but not its derivatives DFK845 or DFK846, strongly inhibited pro-inflammatory cytokine production upon stimulation via either TLR or NLR proteins in macrophages. Importantly, we have not observed cytotoxicity in any range of its working concentration. Treatment with DFK1012 did not interfere with TLR- or NLR-induced activation of p38 and JNK, phosphorylation/degradation of I kappa B, and subsequent nuclear translocation of NF-kappa B subunit p65, suggesting that the inhibitory activity of DFK1012 is not due to the suppression of downstream signaling. Indeed, DFK1012 did not impair transcription of pro-inflammatory cytokine genes but rather promoted post-translational degradation of pro-inflammatory cytokines. Therefore, DFK1012 is a novel anti-inflammatory compound that drives proteolysis of proinflammatory cytokines induced by TLR and NLR stimulation. DFK1012 may represent a novel class of potential therapeutic agents aimed at the treatment of inflammatory disorders.
C1 [Lee, Kyoung-Hee; Liu, Yuen-Joyce; Biswas, Amlan; Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Lee, Kyoung-Hee; Biswas, Amlan; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Ogawa, Chikako] Eisai Res Inst, Andover, MA 01810 USA.
RP Kobayashi, KS (reprint author), 1420A,44 Binney St, Boston, MA 02115 USA.
EM Koichi_Kobayashi@dfci.harvard.edu
FU Eisai Research Institute under Dana-Farber Cancer Institute [2696, CRF
734]; Cancer Research Institute; Claudia Adams Barr Award
FX This work was supported by the Eisai Research Institute under the
Sponsored Research Agreement (Dana-Farber Cancer Institute Agreement
Number Reference 2696/Eisai Research Institute CRF 734).; A recipient of
the Investigator Award from the Cancer Research Institute and the
Claudia Adams Barr Award.
NR 59
TC 7
Z9 7
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 18
PY 2011
VL 286
IS 7
BP 5727
EP 5735
DI 10.1074/jbc.M110.108001
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 719SY
UT WOS:000287230600081
PM 21138842
ER
PT J
AU Nagaike, T
Logan, C
Hotta, I
Rozenblatt-Rosen, O
Meyerson, M
Manley, JL
AF Nagaike, Takashi
Logan, Charlotte
Hotta, Ikuko
Rozenblatt-Rosen, Orit
Meyerson, Matthew
Manley, James L.
TI Transcriptional Activators Enhance Polyadenylation of mRNA Precursors
SO MOLECULAR CELL
LA English
DT Article
ID POLYMERASE-II ELONGATION; 3' UNTRANSLATED REGIONS; B-CELL
DIFFERENTIATION; PAF1 COMPLEX; TUMOR-SUPPRESSOR;
SACCHAROMYCES-CEREVISIAE; IN-VIVO; GENE-EXPRESSION; HISTONE H3; PROTEIN
AB Polyadenylation of mRNA precursors is frequently coupled to transcription by RNA polymerase II. Although this coupling is known to involve interactions with the C-terminal domain of the RNA polymerase II largest subunit, the possible role of other factors is not known. Here we show that a prototypical transcriptional activator, GAL4-VP16, stimulates transcription-coupled polyadenylation in vitro. In the absence of GAL4-VP16, specifically initiated transcripts accumulated but little polyadenylation was observed, while in its presence polyadenylation was strongly enhanced. We further show that this stimulation requires the transcription elongation-associated PAF complex (PAF1c), as PAF1c depletion blocked GAL4-VP16-stimulated polyadenylation. Furthermore, knockdown of PAF subunits by siRNA resulted in decreased 3' cleavage, and nuclear export, of mRNA in vivo. Finally, we show that GAL4-VP16 interacts directly with PAF1c and recruits it to DNA templates. Our results indicate that a transcription activator can stimulate transcription-coupled 3' processing and does so via interaction with PAF1c.
C1 [Nagaike, Takashi; Logan, Charlotte; Hotta, Ikuko; Manley, James L.] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
[Rozenblatt-Rosen, Orit; Meyerson, Matthew] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
[Rozenblatt-Rosen, Orit; Meyerson, Matthew] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA.
RP Manley, JL (reprint author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
EM jlm2@columbia.edu
RI Meyerson, Matthew/E-7123-2012
FU National Institutes of Health [R01 GM28983]
FX We thank Nishta Rao for preparing HeLa nuclear extract. We are grateful
to Dr. Jerry Workman and Dr. Russ Carstens for providing 5SG5E4 plasmid
and pIRES-puro3 plasmid, respectively. We also thank Dr. Bin Tian for
communicating results prior to publication. This study was supported by
National Institutes of Health grant R01 GM28983 to J.L.M.
NR 56
TC 53
Z9 57
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD FEB 18
PY 2011
VL 41
IS 4
BP 409
EP 418
DI 10.1016/j.molcel.2011.01.022
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 727BW
UT WOS:000287773300006
PM 21329879
ER
PT J
AU Rodgers, JT
Vogel, RO
Puigserver, P
AF Rodgers, Joseph T.
Vogel, Rutger O.
Puigserver, Pere
TI Clk2 and B56 beta Mediate Insulin-Regulated Assembly of the PP2A
Phosphatase Holoenzyme Complex on Akt
SO MOLECULAR CELL
LA English
DT Article
ID PROTEIN-KINASE-B; PHOSPHORYLATION; ACTIVATION; SUBUNIT; AKT/PKB;
SENSITIVITY; INHIBITION; METABOLISM; RESISTANCE; ATTENUATE
AB Akt mediates important cellular decisions involved in growth, survival, and metabolism. The mechanisms by which Akt is phosphorylated and activated in response to growth factors or insulin have been extensively studied, but the molecular regulatory components and dynamics of Akt attenuation are poorly understood. Here we show that a downstream target of insulin-induced Akt activation, Clk2, triggers Akt dephosphorylation through the PP2A phosphatase complex. Clk2 phosphorylates the PP2A regulatory subunit B56 beta (PPP2R5B, B'beta), which is a critical regulatory step in the assembly of the PP2A holoenzyme complex on Akt leading to dephosphorylation of both S473 and T308 Akt sites. Since Akt plays a pivotal role in cellular signaling, these results have important implications for our understanding of Akt regulation in many biological processes.
C1 [Rodgers, Joseph T.; Vogel, Rutger O.; Puigserver, Pere] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Rodgers, Joseph T.; Vogel, Rutger O.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
RP Puigserver, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM pere_puigserver@dfci.harvard.edu
FU Ellison Medical Foundation; American Diabetes Association; U.S.
Department of Defense; National Institutes of Health (NIH) [RO1,
DK069966]; American Heart Association; Energy4All Foundation
FX We would like to thank Christine Chin for technical assistance,
Francisca Vazquez and Zachary Gerhart-Hines for careful reviewing of
this manuscript, and Bruce Spiegelman and all members of the Puigserver
lab for discussions relating to this project. A special thanks to David
Virshup for supplying 856 plasmids and antibodies. These studies were
supported in part by an Ellison Medical Foundation New Scholar Award,
American Diabetes Association, U.S. Department of Defense, and National
Institutes of Health (NIH) RO1, DK069966 (to P.P.); an American Heart
Association Predoctoral fellowship (to J.T.R.); and the Energy4All
Foundation (to fly.). J.T.R. and R.V. performed experiments and analyzed
data, and J.T.R. and P.P. designed experiments, analyzed data, and wrote
the manuscript.
NR 30
TC 32
Z9 37
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD FEB 18
PY 2011
VL 41
IS 4
BP 471
EP 479
DI 10.1016/j.molcel.2011.02.007
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 727BW
UT WOS:000287773300011
PM 21329884
ER
PT J
AU Fu, J
Ghali, BW
Lozynsky, AJ
Oral, E
Muratoglu, OK
AF Fu, Jun
Ghali, Bassem W.
Lozynsky, Andrew J.
Oral, Ebru
Muratoglu, Orhun K.
TI Wear resistant UHMWPE with high toughness by high temperature melting
and subsequent radiation cross-linking
SO POLYMER
LA English
DT Article
DE High temperature melting; Radiation cross-linking; Low wear
ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; ALPHA-TOCOPHEROL;
IRRADIATED UHMWPE; UNITED-STATES; VITAMIN-E; OXIDATION; COMPONENTS;
CRYSTALS
AB The goal of this study was to create wear resistant ultra high molecular weight polyethylene (UHMWPE) with improved strength and toughness. It was previously demonstrated that high temperature melting (HIM) of UHMWPE at 280-320 degrees C improved its toughness without detrimentally affecting its wear resistance. We hypothesized that radiation cross-linking after high temperature melting could further improve the wear resistance of UHMWPE, and the loss in toughness by radiation cross-linking could be compensated by the improved toughness achieved by the high temperature melting prior to irradiation. In this work, we demonstrated that irradiation after HTM generated UHMWPE with improved toughness compared to the irradiated UHMWPEs without HIM, partly due to the low cross-link density of irradiated HIM UHMWPE. At a given cross-link density, irradiated HTM UHMWPEs showed higher wear resistance than irradiated UHMWPE. Therefore, successive HTM and radiation cross-linking strategy is promising to create UHMWPE materials with low wear and improved mechanical properties for total joint implants. (C) 2011 Published by Elsevier Ltd.
C1 [Fu, Jun; Ghali, Bassem W.; Lozynsky, Andrew J.; Oral, Ebru; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
[Fu, Jun; Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA.
RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St, Boston, MA 02114 USA.
EM eoral@partners.org
RI Fu, Jun/C-1648-2012
OI Fu, Jun/0000-0002-8723-1439
NR 26
TC 10
Z9 14
U1 0
U2 22
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0032-3861
J9 POLYMER
JI Polymer
PD FEB 17
PY 2011
VL 52
IS 4
BP 1155
EP 1162
DI 10.1016/j.polymer.2011.01.017
PG 8
WC Polymer Science
SC Polymer Science
GA 722WV
UT WOS:000287466900031
ER
PT J
AU Kaufman, DS
Zietman, AL
Dahl, DM
Harisinghani, MG
Wu, CL
AF Kaufman, Donald S.
Zietman, Anthony L.
Dahl, Douglas M.
Harisinghani, Mukesh G.
Wu, Chin-Lee
TI Case 5-2011: A 65-Year-Old Man with Hematuria after Treatment for
Prostate Cancer ANATOMICAL DIAGNOSIS
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ADENOCARCINOMA; BRACHYTHERAPY; RADIOTHERAPY; OUTCOMES
C1 [Kaufman, Donald S.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
[Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Dahl, Douglas M.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kaufman, Donald S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Zietman, Anthony L.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA.
[Dahl, Douglas M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Kaufman, DS (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
NR 11
TC 1
Z9 1
U1 1
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 17
PY 2011
VL 364
IS 7
BP 667
EP 675
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 722BW
UT WOS:000287406000014
PM 21323545
ER
PT J
AU Cao, Y
Staropoli, JF
Biswas, S
Espinola, JA
MacDonald, ME
Lee, JM
Cotman, SL
AF Cao, Yi
Staropoli, John F.
Biswas, Sunita
Espinola, Janice A.
MacDonald, Marcy E.
Lee, Jong-Min
Cotman, Susan L.
TI Distinct Early Molecular Responses to Mutations Causing vLINCL and JNCL
Presage ATP Synthase Subunit C Accumulation in Cerebellar Cells
SO PLOS ONE
LA English
DT Article
ID NEURONAL CEROID-LIPOFUSCINOSIS; LINK BATTEN-DISEASE; TRANSMEMBRANE
PROTEIN; LYSOSOMAL STORAGE; CLN3 PROTEIN; PATHWAY; MOUSE; EXPRESSION;
TRAFFICKING; DEFICIENCY
AB Variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), caused by CLN6 mutation, and juvenile neuronal ceroid lipofuscinosis (JNCL), caused by CLN3 mutation, share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and CbCln6(nclf/nclf) cerebellar cells and compared them to wild-type and CbCln3(Delta ex7/8/Delta ex7/8) cerebellar cells. CbCln6(nclf/nclf) cells and CbCln3(Delta ex7/8/Delta ex7/8) cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6(nclf/nclf) cells, while fluid-phase endocytosis and LysoTracker (R) labeled vesicles were decreased in both CbCln6(nclf/nclf) and CbCln3(Delta ex7/8/Delta ex7/8) cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3(Delta ex7/8) and Cln6(nclf) mutations. Thus, these data support the hypothesis that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival.
C1 [Cao, Yi; Staropoli, John F.; Biswas, Sunita; Espinola, Janice A.; MacDonald, Marcy E.; Lee, Jong-Min; Cotman, Susan L.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Cao, Y (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
EM cotman@helix.mgh.harvard.edu
FU Batten Disease Support and Research Association; National Institute of
Neurological Disorders and Stroke, National Institutes of Health
[NS33648]; National Tay-Sachs and Allied Diseases Association;
Massachusetts Alzheimer's Disease Research Center; Harvard
NeuroDiscovery Center; Dubai-Harvard Foundation for Medical Research
FX This study was funded by the Batten Disease Support and Research
Association (www.bdsra.org; Postdoctoral Fellowships to Y.C. and S.B.,
Grant to S.L.C.), by the National Institute of Neurological Disorders
and Stroke, National Institutes of Health (www.ninds.nih.gov; NS33648,
to M.E.M.), the National Tay-Sachs and Allied Diseases Association
(www.ntsad.org; to S.L.C.), the Massachusetts Alzheimer's Disease
Research Center and Harvard NeuroDiscovery Center Pilot Study Grants
Program (madrc.mgh.harvard.edu; to S.L.C.) and the Dubai-Harvard
Foundation for Medical Research (www.dhfmr.hms.harvard.edu; to S.L.C.).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 57
TC 24
Z9 24
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 17
PY 2011
VL 6
IS 2
AR e17118
DI 10.1371/journal.pone.0017118
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 723BX
UT WOS:000287482300030
PM 21359198
ER
PT J
AU Sarantopoulos, S
Stevenson, KE
Kim, HT
Washel, WS
Bhuiya, NS
Cutler, CS
Alyea, EP
Ho, VT
Soiffer, RJ
Antin, JH
Ritz, J
AF Sarantopoulos, Stefanie
Stevenson, Kristen E.
Kim, Haesook T.
Washel, Whitney S.
Bhuiya, Nazmim S.
Cutler, Corey S.
Alyea, Edwin P.
Ho, Vincent T.
Soiffer, Robert J.
Antin, Joseph H.
Ritz, Jerome
TI Recovery of B-cell homeostasis after rituximab in chronic
graft-versus-host disease
SO BLOOD
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; BONE-MARROW-TRANSPLANTATION; LIVED
PLASMA-CELLS; RHEUMATOID-ARTHRITIS; LYMPHOCYTE STIMULATOR; TISSUE
AUTOANTIGENS; DEPLETION THERAPY; ACTIVATING FACTOR; PERIPHERAL-BLOOD;
IMMUNE-SYSTEM
AB Investigation of the effects of rituximab (anti-CD20) on B-cell-activating factor of the tumor necrosis factor family (BAFF) and B cells would better define the significance of B-cell homeostasis in chronic graft-versus-host disease (cGVHD) pathophysiology. We studied 20 cGVHD patients at a median of 25 months after rituximab treatment when most patients had recovered total B-cell numbers. A total of 55% of patients had stable/improved cGVHD, and total B-cell numbers in these patients were significantly higher compared with rituximab-unresponsive patients. Although total B-cell number did not differ significantly between cGVHD groups before rituximab, there was a proportional increase in B-cell precursors in patients who later had stable/improved cGVHD. After rituximab, BAFF levels increased in all patients. Coincident with B-cell recovery in the stable/ improved group, BAFF/B-cell ratios and CD27(+) B-cell frequencies decreased significantly. The peripheral B-cell pool in stable/improved cGVHD patients was largely composed of naive IgD(+) B cells. By contrast, rituximab-unresponsive cGVHD patients had persistent elevation of BAFF and a predominance of circulating B cells possessing an activated BAFF-R(Lo)CD20(Lo) cell surface phenotype. Thus, naive B-cell reconstitution and decreased BAFF/B-cell ratios were associated with clinical response after rituximab in cGVHD. Our findings begin to delineate B-cell homeostatic mechanisms important for human immune tolerance. (Blood. 2011;117(7):2275-2283)
C1 [Sarantopoulos, Stefanie] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Stevenson, Kristen E.; Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Washel, Whitney S.; Bhuiya, Nazmim S.; Cutler, Corey S.; Alyea, Edwin P.; Ho, Vincent T.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Washel, Whitney S.; Bhuiya, Nazmim S.; Cutler, Corey S.; Alyea, Edwin P.; Ho, Vincent T.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Ritz, Jerome] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA.
RP Sarantopoulos, S (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295, Chapel Hill, NC 27599 USA.
EM stefanie_sarantopoulos@med.unc.edu
OI Ritz, Jerome/0000-0001-5526-4669
FU National Marrow Donor Program; Jock and Bunny Adams Research and
Education Endowment; Ted and Eileen Pasquarello Research Fund; National
Institutes of Health [AI29530, CA142106, K12CA087723]
FX This work was supported by the National Marrow Donor Program Amy
Strelzer Manasevit Award, the Jock and Bunny Adams Research and
Education Endowment, the Ted and Eileen Pasquarello Research Fund, and
the National Institutes of Health (grants AI29530, CA142106, and
K12CA087723).
NR 49
TC 55
Z9 58
U1 3
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 17
PY 2011
VL 117
IS 7
BP 2275
EP 2283
DI 10.1182/blood-2010-10-307819
PG 9
WC Hematology
SC Hematology
GA 722OB
UT WOS:000287440900030
PM 21097674
ER
PT J
AU Sahin, E
Colla, S
Liesa, M
Moslehi, J
Muller, FL
Guo, MR
Cooper, M
Kotton, D
Fabian, AJ
Walkey, C
Maser, RS
Tonon, G
Foerster, F
Xiong, R
Wang, YA
Shukla, SA
Jaskelioff, M
Martin, ES
Heffernan, TP
Protopopov, A
Ivanova, E
Mahoney, JE
Kost-Alimova, M
Perry, SR
Bronson, R
Liao, RL
Mulligan, R
Shirihai, OS
Chin, L
DePinho, RA
AF Sahin, Erguen
Colla, Simona
Liesa, Marc
Moslehi, Javid
Mueller, Florian L.
Guo, Mira
Cooper, Marcus
Kotton, Darrell
Fabian, Attila J.
Walkey, Carl
Maser, Richard S.
Tonon, Giovanni
Foerster, Friedrich
Xiong, Robert
Wang, Y. Alan
Shukla, Sachet A.
Jaskelioff, Mariela
Martin, Eric S.
Heffernan, Timothy P.
Protopopov, Alexei
Ivanova, Elena
Mahoney, John E.
Kost-Alimova, Maria
Perry, Samuel R.
Bronson, Roderick
Liao, Ronglih
Mulligan, Richard
Shirihai, Orian S.
Chin, Lynda
DePinho, Ronald A.
TI Telomere dysfunction induces metabolic and mitochondrial compromise
SO NATURE
LA English
DT Article
ID HEART-FAILURE; STEM-CELLS; HEPATOCELLULAR-CARCINOMA; P53; MICE; DAMAGE;
LEADS; COACTIVATORS; PGC-1-ALPHA; BIOGENESIS
AB Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1 alpha and PGC-1 beta, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1a expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1 alpha and PGC-1 beta promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere-p53-PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction.
C1 [Sahin, Erguen; Colla, Simona; Mueller, Florian L.; Maser, Richard S.; Tonon, Giovanni; Foerster, Friedrich; Xiong, Robert; Wang, Y. Alan; Shukla, Sachet A.; Jaskelioff, Mariela; Martin, Eric S.; Heffernan, Timothy P.; Protopopov, Alexei; Ivanova, Elena; Mahoney, John E.; Kost-Alimova, Maria; Perry, Samuel R.; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Sahin, Erguen; Colla, Simona; Moslehi, Javid; Mueller, Florian L.; Maser, Richard S.; Tonon, Giovanni; Foerster, Friedrich; Jaskelioff, Mariela; Martin, Eric S.; Chin, Lynda; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Liesa, Marc; Kotton, Darrell; Shirihai, Orian S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Moslehi, Javid; Liao, Ronglih; DePinho, Ronald A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Guo, Mira] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Cooper, Marcus] Univ Massachusetts, Div Cardiovasc Med, Worcester, MA 01605 USA.
[Fabian, Attila J.; Mulligan, Richard; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Walkey, Carl] Univ Melbourne, St Vincents Hosp, St Vincents Inst, Victoria 3065, Australia.
[Walkey, Carl] Univ Melbourne, St Vincents Hosp, Dept Med, Victoria 3065, Australia.
[Bronson, Roderick] Harvard Univ, Sch Med, Rodent Histopathol Lab, Boston, MA 02115 USA.
RP DePinho, RA (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
EM ron_depinho@dfci.harvard.edu
RI Maser, Richard/B-2970-2012;
OI Liesa Roig, Marc/0000-0002-5909-8570; Kotton,
Darrell/0000-0002-9604-8476; Walkley, Carl/0000-0002-4784-9031; Colla,
Simona/0000-0001-6583-8910
FU Deutsche Forschungsgemeinschaft; NIH National Cancer Institute; Robert
A. and Renee E. Belfer Foundation; Ellison Foundation; American Cancer
Society; Fundacion Ramon Areces
FX We thank C. Bianchi, J. Moriarty, K. Marmon and E. Thompson for
excellent mouse husbandry and care. We are grateful to B. Spiegelman, P.
Puigserver, J. E. Dominy and J. L. Estall for providing Ad-PGC-1 alpha
and Ad-GFP virus and helpful comments on the manuscript. We thank G. I.
Evan for the p53-ER construct. We appreciate input, critical comments
and helpful discussions from many DePinho/Chin lab members, in
particular A.-J. Chen, C. Khoo, R. Carrasco, A. Kimmelman, S. Quayle, D.
Liu and R. Wiedemeyer. We acknowledge the services of the Mouse
Metabolism Cores at Yale (NIH/NIDDK U24 DK-59635) and at Baylor College
of Medicine (BCM) and the BCM Diabetes & Endocrinology Research Center
(DERC) grant (P30 DK079638). E.S. was supported by the Deutsche
Forschungsgemeinschaft and this work and R.A.D. are supported by R01 and
U01 grants from the NIH National Cancer Institute and the Robert A. and
Renee E. Belfer Foundation. R.A.D. was supported by an Ellison
Foundation for Medical Research Senior Scholar and an American Cancer
Society Research Professor award. M.L. is a recipient of a postdoctoral
fellowship from Fundacion Ramon Areces.
NR 45
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U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD FEB 17
PY 2011
VL 470
IS 7334
BP 359
EP 365
DI 10.1038/nature09787
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 722CS
UT WOS:000287409100034
PM 21307849
ER
PT J
AU Bookman, EB
Langehorne, AA
Eckfeldt, JH
Glass, KC
Jarvik, GP
Klag, M
Koski, G
Motulsky, A
Wilfond, B
Manolio, TA
Fabsitz, RR
Luepker, RV
AF Bookman, Ebony B.
Langehorne, Aleisha A.
Eckfeldt, John H.
Glass, Kathleen C.
Jarvik, Gail P.
Klag, Michael
Koski, Greg
Motulsky, Arno
Wilfond, Benjamin
Manolio, Teri A.
Fabsitz, Richard R.
Luepker, Russell V.
TI Comment on "Multidimensional Results Reporting to Participants in
Genomic Studies: Getting It Right"
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Letter
ID WORKING GROUP
C1 [Bookman, Ebony B.; Manolio, Teri A.; Fabsitz, Richard R.] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Langehorne, Aleisha A.] NHLBI, Biomed Res Training Program Underrepresented, Bethesda, MD 20892 USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Glass, Kathleen C.] McGill Univ, Dept Human Genet & Pediat, Montreal, PQ H3G 1Y6, Canada.
[Klag, Michael] Johns Hopkins Univ, Dept Internal Med, Baltimore, MD 21205 USA.
[Koski, Greg] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA.
[Jarvik, Gail P.] Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA.
[Motulsky, Arno] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Wilfond, Benjamin] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Luepker, Russell V.] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA.
RP Bookman, EB (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
EM ebony.bookman@nih.gov
RI Jarvik, Gail/N-6476-2014
OI Jarvik, Gail/0000-0002-6710-8708
NR 3
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U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 16
PY 2011
VL 3
IS 70
AR 70le1
DI 10.1126/scitranslmed.3001516
PG 1
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795JW
UT WOS:000292971500005
PM 21325615
ER
PT J
AU Gollub, RL
Kong, J
AF Gollub, Randy L.
Kong, Jian
TI For Placebo Effects in Medicine, Seeing Is Believing
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID INDUCED EXPECTATIONS; CONTROLLED-TRIALS; HUMAN BRAIN; PAIN; MECHANISMS;
ACUPUNCTURE; ANALGESIA; FMRI; DISSOCIATION; ANTICIPATION
AB The gold standard for determining the efficacy of biomedical therapies is the detection of a significant difference between the therapeutic effects of an active pharmacological agent or procedure and a matched inert placebo in a randomized controlled trial. Detecting this difference has become a challenge for medicine, especially for outcomes that are based on patient self-rated scales. Yet factors that contribute to placebo responses have received scant attention. In this issue of Science Translational Medicine, Bingel et al. report on an example of how noninvasive whole-brain imaging contributes to our understanding of brain-based placebo effects. Here we highlight ways in which neuroimaging is catalyzing a revolution in society's perspective of placebo effects by providing a compelling visualization of how brain activities that reflect a person's thoughts, feelings, and past experiences can enhance or antagonize his or her response to a medical treatment.
C1 [Gollub, Randy L.; Kong, Jian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA.
RP Gollub, RL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA.
EM rgollub@partners.org
OI Gollub, Randy L./0000-0002-9434-4044
NR 35
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U1 0
U2 13
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 16
PY 2011
VL 3
IS 70
AR 70ps5
DI 10.1126/scitranslmed.3002120
PG 5
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795JW
UT WOS:000292971500002
PM 21325616
ER
PT J
AU Cooke, CR
Joo, MJ
Anderson, SM
Lee, TA
Udris, EM
Johnson, E
Au, DH
AF Cooke, Colin R.
Joo, Min J.
Anderson, Stephen M.
Lee, Todd A.
Udris, Edmunds M.
Johnson, Eric
Au, David H.
TI The validity of using ICD-9 codes and pharmacy records to identify
patients with chronic obstructive pulmonary disease
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
DE Chronic Obstructive Pulmonary Disease; Statistical Models; Epidemiology;
Veterans; Sensitivity and Specificity; Logistic Models
ID ARTIFICIAL NEURAL-NETWORKS; INHALED CORTICOSTEROIDS;
LOGISTIC-REGRESSION; ADMINISTRATIVE DATABASES; MEDICAID POPULATION;
AIRWAY-OBSTRUCTION; COPD; MORTALITY; BURDEN; DIAGNOSIS
AB Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.
Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC < 0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria.
Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of >= 1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: >= 6 albuterol MDI, >= 3 ipratropium MDI, >= 1 outpatient ICD-9 code, >= 1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).
Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.
C1 [Cooke, Colin R.] Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
[Cooke, Colin R.] Univ Michigan, Robert Wood Johnson Fdn Clin Scholars Program, Ann Arbor, MI 48109 USA.
[Joo, Min J.; Lee, Todd A.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL USA.
[Joo, Min J.] Univ Illinois, Sect Pulm Crit Care Sleep & Allergy, Chicago, IL USA.
[Anderson, Stephen M.; Udris, Edmunds M.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Lee, Todd A.] Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL USA.
[Lee, Todd A.] Univ Illinois, Coll Pharm, Ctr Pharmacoecon Res, Chicago, IL USA.
[Johnson, Eric] Grp Hlth Res Inst, Seattle, WA USA.
[Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
RP Cooke, CR (reprint author), Univ Michigan, Div Pulm & Crit Care Med, 6312 Med Sci Bldg 1,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM cookecr@umich.edu; joo@uic.edu; stephen.anderson@va.gov;
todd.lee@va.gov; Ed.Udris@va.gov; johnson.ex@ghc.org;
dau@u.washington.edu
OI Cooke, Colin/0000-0001-9713-5371
FU Department of Veterans Affairs, Health Services Research and Development
(DHA); American Lung Association [CI-51755-N]; American Thoracic
Society; Robert Wood Johnson Foundation; University of Michigan COPE
FX This study was supported by the Department of Veterans Affairs, Health
Services Research and Development (DHA), American Lung Association
(CI-51755-N) awarded to DHA, the American Thoracic Society Fellow Career
Development Award (CRC), and the Robert Wood Johnson Foundation Clinical
Scholar's Program (CRC). The funding bodies had no role in study design
analysis, interpretation and writing of the manuscript, and in the
decision to submit the manuscript for publication. The authors would
also like to acknowledge the referees for their thoughtful contributions
to the manuscript.; This article was made available as Open Access with
the support of the University of Michigan COPE Fund,
http://lib.umich.edu/cope
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U2 2
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 FEB 16
PY 2011
VL 11
AR 37
DI 10.1186/1472-6963-11-37
PG 25
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 730JS
UT WOS:000288030200001
PM 21324188
ER
PT J
AU Wang, LX
Million, M
Rivier, J
Rivier, C
Craft, N
Stenzel-Poore, MP
Tache, Y
AF Wang, Lixin
Million, Mulugeta
Rivier, Jean
Rivier, Catherine
Craft, Noah
Stenzel-Poore, Mary P.
Tache, Yvette
TI CRF Receptor Antagonist Astressin-B Reverses and Prevents Alopecia in
CRF Over-Expressing Mice
SO PLOS ONE
LA English
DT Article
ID CORTICOTROPIN-RELEASING HORMONE; HAIR-GROWTH; TRANSGENIC MICE;
DIFFERENTIAL EXPRESSION; CUTANEOUS EXPRESSION; STRESS-RESPONSE; MOUSE
MODELS; HPA AXIS; SKIN; UROCORTIN
AB Corticotropin-releasing factor (CRF) signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE)-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 mu g/mouse) injected peripherally once a day for 5 days in 4-9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF2 receptor antagonist, astressin(2)-B had moderate effect on pigmentation, but not on hair regrowth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress.
C1 [Wang, Lixin; Million, Mulugeta; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Div Digest Dis,Dept Med,CURE, Los Angeles, CA 90095 USA.
[Wang, Lixin; Million, Mulugeta; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, Los Angeles, CA 90095 USA.
[Rivier, Jean; Rivier, Catherine] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, San Diego, CA 92138 USA.
[Craft, Noah] Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, Div Dermatol,Dept Med,Los Angeles Biomed Res Inst, Torrance, CA USA.
[Craft, Noah] Univ Calif Los Angeles, David Geffen Sch Med, Harbor UCLA Med Ctr, Div Infect Dis,Dept Med,Los Angeles Biomed Res In, Torrance, CA USA.
[Stenzel-Poore, Mary P.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
RP Wang, LX (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Div Digest Dis,Dept Med,CURE, Los Angeles, CA 90095 USA.
EM milllionmulugeta@mednet.ucla.edu
FU Department of Veterans Affairs; NIH [R01 DK-57238, R21 DK-068155, RO1
DK-078676, R01 DK-33061, P50 DK-64539, DK PO1-26741]
FX This work was supported by the Research Career Scientist Award,
Department of Veterans Affairs (Y. Tache); and the following NIH grants:
R01 DK-57238 (Y. Tache); R21 DK-068155 and RO1 DK-078676 (M. Million);
R01 DK-33061 (Y. Tache, M. Million); P50 DK-64539 (Y. Tache, M.
Million); DK PO1-26741 (J. Rivier). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 16
PY 2011
VL 6
IS 2
AR e16377
DI 10.1371/journal.pone.0016377
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721YC
UT WOS:000287392700017
PM 21359208
ER
PT J
AU Bello, AK
Thadhani, R
Hemmelgarn, B
Klarenbach, S
Gill, J
Chan, C
Zimmerman, D
Holmes, D
Cembrowski, G
Opgenorth, D
Sibrian, R
Karkhaneh, M
Tiv, S
Wiebe, N
Tonelli, M
AF Bello, Aminu K.
Thadhani, Ravi
Hemmelgarn, Brenda
Klarenbach, Scott
Gill, John
Chan, Christopher
Zimmerman, Deborah
Holmes, Daniel
Cembrowski, George
Opgenorth, Dawn
Sibrian, Rafael
Karkhaneh, Mohammad
Tiv, Sophanny
Wiebe, Natasha
Tonelli, Marcello
TI Design and implementation of the canadian kidney disease cohort study
(CKDCS): A prospective observational study of incident hemodialysis
patients
SO BMC NEPHROLOGY
LA English
DT Article
ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; PERITONEAL-DIALYSIS;
ADMINISTRATIVE DATA; PRACTICE PATTERNS; CLINICAL-RESEARCH;
UNITED-STATES; HEALTH; OUTCOMES; CLASSIFICATION
AB Background: Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD).
Methods/Design: The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions.
Preliminary Results: Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice.
Discussion: The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future.
C1 [Bello, Aminu K.; Klarenbach, Scott; Opgenorth, Dawn; Sibrian, Rafael; Karkhaneh, Mohammad; Tiv, Sophanny; Wiebe, Natasha; Tonelli, Marcello] Univ Alberta, Dept Med, Edmonton, AB, Canada.
[Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Hemmelgarn, Brenda] Univ Calgary, Dept Med, Calgary, AB, Canada.
[Gill, John] Univ British Columbia, Div Nephrol, Vancouver, BC, Canada.
[Chan, Christopher] Univ Toronto, Univ Hlth Network, Div Nephrol, Toronto, ON, Canada.
[Zimmerman, Deborah] Univ Ottawa, Dept Med, Ottawa, ON, Canada.
[Holmes, Daniel] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada.
[Cembrowski, George] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada.
RP Tonelli, M (reprint author), Univ Alberta, Dept Med, Edmonton, AB, Canada.
EM mtonelli@ualberta.ca
RI Hemmelgarn, Brenda/I-6894-2012; Bello, Aminu/D-2213-2013; Klarenbach,
Scott/E-7731-2013; Tonelli, Marcello/B-3028-2009
OI Klarenbach, Scott/0000-0002-8611-1056;
FU Canadian Institutes of Health Research (CIHR); Abbott Laboratories;
Alberta Heritage Foundation for Medical Research; Northern Alberta Renal
Program
FX The CKDCS is being funded by the Canadian Institutes of Health Research
(CIHR), Abbott Laboratories, Alberta Heritage Foundation for Medical
Research, and the Northern Alberta Renal Program.
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2369
J9 BMC NEPHROL
JI BMC Nephrol.
PD FEB 16
PY 2011
VL 12
AR 10
DI 10.1186/1471-2369-12-10
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 946MT
UT WOS:000304356700002
PM 21324196
ER
PT J
AU Joynt, KE
Orav, EJ
Jha, AK
AF Joynt, Karen E.
Orav, E. John
Jha, Ashish K.
TI Thirty-Day Readmission Rates for Medicare Beneficiaries by Race and Site
of Care
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID QUALITY-OF-CARE; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED
CONTROLLED-TRIAL; CONGESTIVE-HEART-FAILURE; SAFETY-NET HOSPITALS; DUTY
HOUR REFORM; BLACK PATIENTS; TRANSITIONS INTERVENTION; ADMINISTRATIVE
DATA; RACIAL DISPARITIES
AB Context Understanding whether and why there are racial disparities in readmissions has implications for efforts to reduce readmissions.
Objective To determine whether black patients have higher odds of readmission than white patients and whether these disparities are related to where black patients receive care.
Design Using national Medicare data, we examined 30-day readmissions after hospitalization for acute myocardial infarction (MI), congestive heart failure (CHF), and pneumonia. We categorized hospitals in the top decile of proportion of black patients as minority-serving. We determined the odds of readmission for black patients compared with white patients at minority-serving vs non-minority-serving hospitals.
Setting and Participants Medicare Provider Analysis Review files of more than 3.1 million Medicare fee-for-service recipients who were discharged from US hospitals in 2006-2008.
Main Outcome Measure Risk-adjusted odds of 30-day readmission.
Results Overall, black patients had higher readmission rates than white patients (24.8% vs 22.6%, odds ratio [OR], 1.13; 95% confidence interval [CI], 1.11-1.14; P<.001); patients from minority-serving hospitals had higher readmission rates than those from non-minority-serving hospitals (25.5% vs 22.0%, OR, 1.23; 95% CI, 1.20-1.27; P<.001). Among patients with acute MI and using white patients from non-minority-serving hospitals as the reference group (readmission rate 20.9%), black patients from minority-serving hospitals had the highest readmission rate (26.4%; OR, 1.35; 95% CI, 1.28-1.42), while white patients from minority-serving hospitals had a 24.6% readmission rate (OR, 1.23; 95% CI, 1.18-1.29) and black patients from non-minority-serving hospitals had a 23.3% readmission rate (OR, 1.20; 95% CI, 1.16-1.23; P<.001 for each); patterns were similar for CHF and pneumonia. The results were unchanged after adjusting for hospital characteristics including markers of caring for poor patients.
Conclusion Among elderly Medicare recipients, black patients were more likely to be readmitted after hospitalization for 3 common conditions, a gap that was related to both race and to the site where care was received. JAMA. 2011;305(7):675-681 www.jama.com
C1 [Joynt, Karen E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Joynt, Karen E.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA.
RP Joynt, KE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.
EM kjoynt@partners.org
FU National Institutes of Health, Brigham and Women's Hospital, Division of
Cardiovascular Medicine [T32HL007604-24]
FX Dr Joynt was supported by National Institutes of Health Training Grant
T32HL007604-24, Brigham and Women's Hospital, Division of Cardiovascular
Medicine.
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U2 27
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 16
PY 2011
VL 305
IS 7
BP 675
EP 681
DI 10.1001/jama.2011.123
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 721NH
UT WOS:000287361100018
PM 21325183
ER
PT J
AU Irving, S
Moore, DR
Liberman, MC
Sumner, CJ
AF Irving, Samuel
Moore, David R.
Liberman, M. Charles
Sumner, Christian J.
TI Olivocochlear Efferent Control in Sound Localization and
Experience-Dependent Learning
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID AUDITORY SPACE; ELECTRICAL-STIMULATION; HEARING IMPAIRMENT; BINAURAL
HEARING; OPTIC TECTUM; PLASTICITY; FERRETS; NOISE; INNERVATION;
MODULATION
AB Efferent auditory pathways have been implicated in sound localization and its plasticity. We examined the role of the olivocochlear system (OC) in horizontal sound localization by the ferret and in localization learning following unilateral earplugging. Under anesthesia, adult ferrets underwent olivocochlear bundle section at the floor of the fourth ventricle, either at the midline or laterally (left). Lesioned and control animals were trained to localize 1 s and 40 ms amplitude-roved broadband noise stimuli from one of 12 loudspeakers. Neither type of lesion affected normal localization accuracy. All ferrets then received a left earplug and were tested and trained over 10 d. The plug profoundly disrupted localization. Ferrets in the control and lateral lesion groups improved significantly during subsequent training on the 1 s stimulus. No improvement (learning) occurred in the midline lesion group. Markedly poorer performance and failure to learn was observed with the 40 ms stimulus in all groups. Plug removal resulted in a rapid resumption of normal localization in all animals. Insertion of a subsequent plug in the right ear produced similar results to left earplugging. Learning in the lateral lesion group was independent of the side of the lesion relative to the earplug. Lesions in all reported cases were verified histologically. The results suggest the OC system is not needed for accurate localization, but that it is involved in relearning localization during unilateral conductive hearing loss.
C1 [Irving, Samuel; Moore, David R.; Sumner, Christian J.] Inst Hearing Res, MRC, Nottingham NG7 2RD, England.
[Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Liberman, M. Charles] Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02114 USA.
RP Sumner, CJ (reprint author), Inst Hearing Res, MRC, Univ Pk, Nottingham NG7 2RD, England.
EM chris@ihr.mrc.ac.uk
FU Medical Research Council; National Institute on Deafness and Other
Communication Disorders [R01 DC 0188, P30 05209]
FX Research was supported by the Medical Research Council and by the
National Institute on Deafness and Other Communication Disorders (Grants
R01 DC 0188 and P30 05209 to M.C.L.).
NR 33
TC 32
Z9 32
U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 16
PY 2011
VL 31
IS 7
BP 2493
EP 2501
DI 10.1523/JNEUROSCI.2679-10.2011
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 721XZ
UT WOS:000287392400018
PM 21325517
ER
PT J
AU Kalia, LV
Kalia, SK
Chau, H
Lozano, AM
Hyman, BT
McLean, PJ
AF Kalia, Lorraine V.
Kalia, Suneil K.
Chau, Hien
Lozano, Andres M.
Hyman, Bradley T.
McLean, Pamela J.
TI Ubiquitinylation of alpha-Synuclein by Carboxyl Terminus
Hsp70-Interacting Protein (CHIP) Is Regulated by Bcl-2-Associated
Athanogene 5 (BAG5)
SO PLOS ONE
LA English
DT Article
ID HEAT-SHOCK PROTEINS; DEPENDENT E3 LIGASE; PARKINSONS-DISEASE; LEWY
BODIES; MOLECULAR CHAPERONES; NUCLEOTIDE EXCHANGE; COCHAPERONE BAG2;
QUALITY-CONTROL; CELL-DEATH; DEGRADATION
AB Parkinson's disease (PD) is a common neurodegenerative condition in which abnormalities in protein homeostasis, or proteostasis, may lead to accumulation of the protein alpha-synuclein (alpha-syn). Mutations within or multiplications of the gene encoding alpha-syn are known to cause genetic forms of PD and polymorphisms in the gene are recently established risk factors for idiopathic PD. alpha-syn is a major component of Lewy bodies, the intracellular proteinaceous inclusions which are pathological hallmarks of most forms of PD. Recent evidence demonstrates that alpha-syn can self associate into soluble oligomeric species and implicates these alpha-syn oligomers in cell death. We have previously shown that carboxyl terminus of Hsp70-interacting protein (CHIP), a co-chaperone molecule with E3 ubiquitin ligase activity, may reduce the levels of toxic alpha-syn oligomers. Here we demonstrate that alpha-syn is ubiquitinylated by CHIP both in vitro and in cells. We find that the products from ubiquitinylation by CHIP include both monoubiquitinylated and polyubiquitinylated forms of alpha-syn. We also demonstrate that CHIP and alpha-syn exist within a protein complex with the co-chaperone bcl-2-associated athanogene 5 (BAG5) in brain. The interaction of CHIP with BAG5 is mediated by Hsp70 which binds to the tetratricopeptide repeat domain of CHIP and the BAG domains of BAG5. The Hsp70-mediated association of BAG5 with CHIP results in inhibition of CHIP E3 ubiquitin ligase activity and subsequently reduces alpha-syn ubiquitinylation. Furthermore, we use a luciferase-based protein-fragment complementation assay of alpha-syn oligomerization to investigate regulation of alpha-syn oligomers by CHIP in living cells. We demonstrate that BAG5 mitigates the ability of CHIP to reduce alpha-syn oligomerization and that non-ubiquitinylated alpha-syn has an increased propensity for oligomerization. Thus, our results identify CHIP as an E3 ubiquitin ligase of alpha-syn and suggest a novel function for BAG5 as a modulator of CHIP E3 ubiquitin ligase activity with implications for CHIP-mediated regulation of alpha-syn oligomerization.
C1 [Kalia, Lorraine V.; Kalia, Suneil K.; Hyman, Bradley T.; McLean, Pamela J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Kalia, Lorraine V.] Univ Toronto, Div Neurol, Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada.
[Kalia, Suneil K.; Lozano, Andres M.] Univ Toronto, Div Neurosurg, Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada.
[Kalia, Lorraine V.; Kalia, Suneil K.; Chau, Hien; Lozano, Andres M.] Univ Toronto, Div Brain Imaging & Behav Syst Neurosci, Toronto Western Res Inst, Univ Hlth Network, Toronto, ON, Canada.
RP Kalia, LV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
EM lorraine.kalia@utoronto.ca
FU NIH/NINDS [NS 063963]; Michael J. Fox Foundation
FX This work was supported by NIH/NINDS grant NS 063963 and research grants
from the Michael J. Fox Foundation. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 62
TC 52
Z9 55
U1 2
U2 21
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 16
PY 2011
VL 6
IS 2
AR e14695
DI 10.1371/journal.pone.0014695
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721YC
UT WOS:000287392700008
PM 21358815
ER
PT J
AU Traugott, KA
Maxwell, PR
Green, K
Frei, C
Lewis, JS
AF Traugott, Kristi A.
Maxwell, Pamela R.
Green, Kay
Frei, Christopher
Lewis, James S., II
TI Effects of therapeutic drug monitoring criteria in a computerized
prescriber-order-entry system on the appropriateness of vancomycin level
orders
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
DE Antibiotics; Blood levels; Computers; Dosage; Medication orders;
Prescribing; Protocols; Rational therapy; Vancomycin
AB Purpose. The effects of therapeutic drug monitoring (TDM) criteria in a computerized prescriber-order-entry (CPOE) system on the appropriateness of orders for vancomycin levels were evaluated.
Methods. Vancomycin TDM criteria were developed and implemented in a CPOE system. These criteria were displayed via a pop-up alert message when vancomycin levels were ordered and included directions for appropriate timing and justification for routine monitoring. Data for two groups of adult inpatients who had vancomycin levels ordered before and after criteria implementation were compared. Medical records were retrospectively reviewed for these patients to collect information regarding patient demographics, vancomycin dosage and indication, concurrent antibiotics and nephrotoxic agents during vancomycin therapy, length of stay, duration of vancomycin therapy, and number of vancomycin levels drawn, The primary outcome was the percent change in appropriate vancomycin levels ordered after criteria implementation.
Results. A total of 200 patients were analyzed, 100 in each group. The percentage of appropriate orders for vancomycin levels significantly increased after criteria implementation (from 58% to 68%, p = 0.02). The greatest effect on appropriateness occurred with the first level ordered (52% versus 70% in the preimplementation and postimplementation groups, respectively; p = 0.01). The majority of inappropriate levels were due to improper timing of sample collections, accounting for 55% of the inappropriate levels evaluated.
Conclusion. A significant increase in the number of appropriately ordered and drawn serum vancomycin levels occurred after implementation of TDM criteria in the hospital's CPOE system. The majority of orders that were deemed inappropriate were due to improper timing of laboratory collection.
C1 [Traugott, Kristi A.] Ochsner Hlth Syst, New Orleans, LA 70121 USA.
[Traugott, Kristi A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Frei, Christopher] Univ Texas Austin, Coll Pharm, Pharmacotherapy Div, Austin, TX 78712 USA.
[Frei, Christopher] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA.
[Frei, Christopher] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA.
RP Traugott, KA (reprint author), Ochsner Hlth Syst, 1514 Jefferson Highway, New Orleans, LA 70121 USA.
EM ktraugott@ochsner.org
NR 18
TC 13
Z9 13
U1 1
U2 5
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 FEB 15
PY 2011
VL 68
IS 4
BP 347
EP 352
DI 10.2146/ajhp090661
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 858CC
UT WOS:000297772500012
PM 21289330
ER
PT J
AU Astor, TL
AF Astor, Todd L.
TI RNA Interference, RSV, and Lung Transplantation A Promising Future for
siRNA Therapeutics
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID RESPIRATORY SYNCYTIAL VIRUS; DENDRITIC CELLS; RIBAVIRIN; POTENT;
INDUCTION; INFECTION
C1 Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA.
RP Astor, TL (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA.
NR 21
TC 6
Z9 7
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD FEB 15
PY 2011
VL 183
IS 4
BP 427
EP 428
DI 10.1164/rccm.201009-1488ED
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 724IE
UT WOS:000287568500004
PM 21325081
ER
PT J
AU Rodriguez, AE
Vigo, CF
Delacasa, A
Mieres, J
Fernandez-Pereira, C
Bernardi, V
Bettinoti, M
Rodriguez-Granillo, AM
Rodriguez-Granillo, G
Santaera, O
Curotto, V
Rubilar, B
Tronge, J
Palacios, IF
Antoniucci, D
AF Rodriguez, Alfredo E.
Vigo, Cesar F.
Delacasa, Alejandro
Mieres, Juan
Fernandez-Pereira, Carlos
Bernardi, Victor
Bettinoti, Marcelo
Rodriguez-Granillo, Alfredo M.
Rodriguez-Granillo, Gaston
Santaera, Omar
Curotto, Valeria
Rubilar, Bibiana
Tronge, Jorge
Palacios, Igor F.
Antoniucci, David
CA EUCATAX Investigators
TI Efficacy and Safety of a Double-Coated Paclitaxel-Eluting Coronary
Stent: The EUCATAX Trial
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE percutaneous coronary intervention (PCI); restenosis (RSTN); acute
coronary syndrome (ACS); drug delivery (DDEL); quantitative coronary
angiography (QCA)
ID BARE-METAL STENTS; RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; ARTERY
LESIONS; POLYMER; LONG; IMPLANTATION; REGISTRY; REVASCULARIZATION;
THROMBOSIS
AB Objectives: The aim of this study was the comparison of a new double-coated paclitaxel-eluting coronary stent with bare-metal stent (BMS) in patients undergoing percutaneous coronary intervention. Background: Stent coating with biodegradable polymers as a platform for elution of drugs has the potential for complete elution of drugs and for decreasing the risk of late complications. Methods: Multicenter randomized trial comparing a paclitaxel-eluting stent (PES) coated with a biodegradable polymer and glycocalyx with the equivalent BMS. We randomly assigned 422 patients with de novo coronary lesions to PES (211 patients) or to BMS (211 patients). Primary end point was target vessel failure (TVF) defined as cardiac death, myocardial infarction, and target vessel revascularization. Clinical secondary end points were target vessel revascularization, target lesion revascularization, stent thrombosis (ST), and major adverse cardiovascular events (MACE). Angiographic secondary end points were late loss and binary restenosis. Results: At 1 year of follow-up, TVF rate was 9.5% in the PES group and 17.1% in the BMS group (P = 0.02), and MACE rate was 10% in PES and 19% in BMS arm (P = 0.009). All other secondary end points were reached but ST. ST rate was low and similar in both study arms. Conclusions: The study shows that patients treated with PES with dual coating technology had significantly lower incidence of TVF and MACE than those treated with BMS design; however, longer follow-up should be necessary to assess true advantages of this technology compared with the previous one. (C) 2010 Wiley-Liss, Inc.
C1 [Rodriguez, Alfredo E.; Mieres, Juan; Fernandez-Pereira, Carlos; Curotto, Valeria; Rubilar, Bibiana] Sanatorio Otamendi, Cardiac Unit, Buenos Aires, DF, Argentina.
[Vigo, Cesar F.] Sanatorio Del Salvador, Intervent Cardiol, Cordoba, Argentina.
[Delacasa, Alejandro] Sanatorio Belgrano, Intervent Cardiol, Buenos Aires, DF, Argentina.
[Mieres, Juan] Sanatorio Los Lomas, Intervent Cardiol, Buenos Aires, DF, Argentina.
[Fernandez-Pereira, Carlos; Tronge, Jorge] Clin IMA, Intervent Cardiol & Cardiol Dept, Buenos Aires, DF, Argentina.
[Bernardi, Victor] Clin Sol, Buenos Aires, DF, Argentina.
[Bettinoti, Marcelo] Sanatorio Guemes Hosp Privado, Intervent Cardiol, Buenos Aires, DF, Argentina.
[Rodriguez, Alfredo E.; Rodriguez-Granillo, Alfredo M.; Rodriguez-Granillo, Gaston] CECI, Buenos Aires, DF, Argentina.
[Palacios, Igor F.] Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA.
[Antoniucci, David] Careggi Hosp, Div Cardiovasc, Florence, Italy.
RP Rodriguez, AE (reprint author), Callao 1441 4B C1024AAA, Buenos Aires, DF, Argentina.
EM rodriguezalfredo.e@gmail.com
FU Eucatech AG, Reinhelfeden, Germany
FX Grant sponsor: Eucatech AG, Reinhelfeden, Germany.
NR 23
TC 6
Z9 6
U1 0
U2 3
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 FEB 15
PY 2011
VL 77
IS 3
BP 335
EP 342
DI 10.1002/ccd.22769
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 725QD
UT WOS:000287659800003
PM 20824769
ER
PT J
AU Lacadie, SA
Zon, LI
AF Lacadie, Scott A.
Zon, Leonard I.
TI The ERGonomics of hematopoietic stem cell self-renewal
SO GENES & DEVELOPMENT
LA English
DT Article
DE ERG; ETS family transcription factors; Gata2; hematopoietic development;
hematopoietic stem cells; Runx1; self-renewal
ID TRANSCRIPTION FACTOR GATA-2; AORTIC ENDOTHELIUM; PRIMITIVE
HEMATOPOIESIS; PROGENITOR CELLS; PROSTATE-CANCER; FACTOR ERG;
DIFFERENTIATION; TRANSITION; ONCOGENE; SCREEN
AB Stem cells make more of themselves by self-renewing cell divisions. In the February 1, 2011, issue of Genes & Development, Taoudi and colleagues (pp. 251-262) show an essential role for the ETS transcription factor ERG in the self-renewal of embryonic hematopoietic stem cells. A model is presented in which the redundant functions of GATA2 and RUNX1 in self-renewal are under direct control of ERG.
C1 [Zon, Leonard I.] Harvard Univ, Harvard Stem Cell Inst,Childrens Hosp, Howard Hughes Med Inst,Dana Farber Canc Inst, Stem Cell Program,Div Hematol Oncol,Sch Med, Boston, MA 02115 USA.
RP Zon, LI (reprint author), Harvard Univ, Harvard Stem Cell Inst,Childrens Hosp, Howard Hughes Med Inst,Dana Farber Canc Inst, Stem Cell Program,Div Hematol Oncol,Sch Med, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
NR 45
TC 3
Z9 3
U1 0
U2 1
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD FEB 15
PY 2011
VL 25
IS 4
BP 289
EP 293
DI 10.1101/gad.2031511
PG 5
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 721OT
UT WOS:000287365000001
PM 21325129
ER
PT J
AU Diop-Frimpong, B
Chauhan, VP
Krane, S
Boucher, Y
Jain, RK
AF Diop-Frimpong, Benjamin
Chauhan, Vikash P.
Krane, Stephen
Boucher, Yves
Jain, Rakesh K.
TI Losartan inhibits collagen I synthesis and improves the distribution and
efficacy of nanotherapeutics in tumors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE drug delivery; matrix modifier; thrombospondin-1; transforming growth
factor beta; transport
ID GROWTH-FACTOR-BETA; CONVERTING-ENZYME-INHIBITORS; INTERSTITIAL FLUID
PRESSURE; TYPE-1 RECEPTOR BLOCKADE; MOUSE MODEL; PANCREATIC-CANCER;
RENAL INJURY; SOLID TUMORS; BLOOD-FLOW; ANGIOTENSIN
AB The dense collagen network in tumors significantly reduces the penetration and efficacy of nanotherapeutics. We tested whether losartan-a clinically approved angiotensin II receptor antagonist with noted antifibrotic activity-can enhance the penetration and efficacy of nanomedicine. We found that losartan inhibited collagen I production by carcinoma-associated fibroblasts isolated from breast cancer biopsies. Additionally, it led to a dose-dependent reduction in stromal collagen in desmoplastic models of human breast, pancreatic, and skin tumors in mice. Furthermore, losartan improved the distribution and therapeutic efficacy of intratumorally injected oncolytic herpes simplex viruses. Finally, it also enhanced the efficacy of i.v. injected pegylated liposomal doxorubicin (Doxil). Thus, losartan has the potential to enhance the efficacy of nanotherapeutics in patients with desmoplastic tumors.
C1 [Diop-Frimpong, Benjamin; Chauhan, Vikash P.; Boucher, Yves; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
[Diop-Frimpong, Benjamin; Chauhan, Vikash P.; Krane, Stephen; Boucher, Yves; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Diop-Frimpong, Benjamin] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Diop-Frimpong, Benjamin; Chauhan, Vikash P.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Krane, Stephen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Boucher, Y (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA.
EM yves@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu
RI Chauhan, Vikash/H-8172-2013
OI Chauhan, Vikash/0000-0001-9126-2302
FU Dyax; AstraZeneca; Medimmune; AstraZeneca/Medimmune; Astellas-Fibrogen;
Regeneron; Genzyme; Morphosys; Noxxon Pharma; US National Cancer
Institute [P01CA80124, R01CA85140, R01CA98706]; Department of Defense
[W91ZSQ7342N607, W81XWH-10-1-0016]
FX R.K.J. received commercial research grants from Dyax, AstraZeneca, and
Medimmune; consultant fees from AstraZeneca/Medimmune, Dyax,
Astellas-Fibrogen, Regeneron, Genzyme, Morphosys, and Noxxon Pharma; and
a speaker honorarium from Genzyme. R.K.J. owns stock in SynDevRx. No
reagents or funding from these companies was used in these studies.
There is no significant financial or other competing interest in the
work.; We acknowledge Drs. N. Kirkpatrick, D. Lacorre, and R. Guang for
help in planning experiments, Dr. T. Stylianopoulos for help with
manuscript preparation, and Dr. L. Fisher (National Institute of Dental
Research) for kindly providing the LF-67 antibody. We thank Eve Smith
and Sylvie Roberge for their technical assistance. This work was
supported by US National Cancer Institute grants to R.K.J. (P01CA80124
and R01CA85140) and Y.B. (R01CA98706) and a Department of Defense Breast
Cancer research fellowship to B.D.-F. (W91ZSQ7342N607) and innovator
award to R.K.J. (W81XWH-10-1-0016).
NR 54
TC 143
Z9 145
U1 5
U2 49
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 FEB 15
PY 2011
VL 108
IS 7
BP 2909
EP 2914
DI 10.1073/pnas.1018892108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721TB
UT WOS:000287377000054
PM 21282607
ER
PT J
AU Chui, KKH
Wenger, JB
Cohen, SA
Naumova, EN
AF Chui, Kenneth K. H.
Wenger, Julia B.
Cohen, Steven A.
Naumova, Elena N.
TI Visual Analytics for Epidemiologists: Understanding the Interactions
Between Age, Time, and Disease with Multi-Panel Graphs
SO PLOS ONE
LA English
DT Article
ID INFECTIOUS-DISEASES; PUBLIC-HEALTH; UNITED-STATES; SEASONALITY;
SURVEILLANCE; MORTALITY; INFLUENZA; TEMPERATURE; POPULATION; PNEUMONIA
AB Background: Visual analytics, a technique aiding data analysis and decision making, is a novel tool that allows for a better understanding of the context of complex systems. Public health professionals can greatly benefit from this technique since context is integral in disease monitoring and biosurveillance. We propose a graphical tool that can reveal the distribution of an outcome by time and age simultaneously.
Methodology/Principal Findings: We introduce and demonstrate multi-panel (MP) graphs applied in four different settings: U.S. national influenza-associated and salmonellosis-associated hospitalizations among the older adult population (>= 65 years old), 1991-2004; confirmed salmonellosis cases reported to the Massachusetts Department of Public Health for the general population, 2004-2005; and asthma-associated hospital visits for children aged 0-18 at Milwaukee Children's Hospital of Wisconsin, 1997-2006. We illustrate trends and anomalies that otherwise would be obscured by traditional visualization techniques such as case pyramids and time-series plots.
Conclusion/Significance: MP graphs can weave together two vital dynamics-temporality and demographics-that play important roles in the distribution and spread of diseases, making these graphs a powerful tool for public health and disease biosurveillance efforts.
C1 [Chui, Kenneth K. H.; Cohen, Steven A.] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA.
[Wenger, Julia B.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Naumova, Elena N.] Tufts Univ, Sch Engn, Dept Civil & Environm Engn, Medford, MA 02155 USA.
RP Chui, KKH (reprint author), Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA.
EM kenneth.chui@tufts.edu
RI Naumova, Elena/C-5954-2011;
OI Naumova, Elena/0000-0002-9562-4734
FU National Institutes of Health (NIH) National Institute of Allergy and
Infectious Diseases (NIAID) [U19 AI062627, N01 AI-50032]
FX The research was supported by National Institutes of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID) grants U19
AI062627 and N01 AI-50032. The funders had no roles in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 9
Z9 9
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 15
PY 2011
VL 6
IS 2
AR e14683
DI 10.1371/journal.pone.0014683
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721QH
UT WOS:000287369200002
PM 21347221
ER
PT J
AU Arif, SA
Mitchell, MM
AF Arif, Sally A.
Mitchell, Melissa M.
TI Iloperidone: A new drug for the treatment of schizophrenia
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
DE Absorption; Antipsychotic agents; Dosage; Drugs; availability;
Iloperidone; Mechanism of action; Pharmacogenetics; Pharmacokinetics;
Schizophrenia; Toxicity
ID ANTIPSYCHOTIC ILOPERIDONE; SAFETY PROFILE; RATING-SCALE; EFFICACY;
AGENTS; TOLERABILITY; METABOLITES; DISORDERS; RECEPTORS; BINDING
AB Purpose. The pharmacology, pharmacokinetics, pharmacogenomics, clinical efficacy, and safety and tolerability profile of iloperidone for the treatment of schizophrenia are reviewed.
Summary. Iloperidone is an atypical antipsychotic that recently received marketing approval from the Food and Drug Administration for the acute treatment of schizophrenia. Iloperidone is a pure antagonist and the first antipsychotic to have pharmacogenomic studies indicate predictive response based on six identified polymorphisms. Pharmacokinetic studies have determined that iloperidone is well absorbed orally, with a bioavailability of 96%. Phase II and III clinical trials have shown iloperidone to improve symptoms of schizophrenia, based on the Positive and Negative Symptom Scale, Brief Psychiatric Rating Scale, and Clinical Global Impressions Severity scores (p < 0.05). Iloperidone has established tolerability at recommended dosages of up to 24 mg daily; however, the dosage must be slowly increased over seven days, and twice-daily administration is required to avoid orthostatic hypotension. The most common adverse effects associated with iloperidone were dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight gain. Safety studies have also found that iloperidone increases the risk of Q-Tc interval prolongation, similar to that seen with ziprasidone. Minimal changes in glucose and lipid abnormalities were seen in short-term (4- and 6-week) and long-term (52-week) studies, indicating a low chance of metabolic disturbance with iloperidone. Conclusion. Iloperidone may be a viable and safe option for the treatment of schizophrenia in adult patients, especially for patients who cannot tolerate other antipsychotic agents. However, iloperidone lacks a clear benefit over other antipsychotic agents.
C1 [Arif, Sally A.] Midwestern Univ, Chicago Coll Pharm, Downers Grove, IL 60515 USA.
[Arif, Sally A.; Mitchell, Melissa M.] Long Isl Univ, Arnold & Marie Schwartz Coll Pharm & Hlth Sci, Brooklyn, NY USA.
[Arif, Sally A.] James J Peters Vet Affairs Med Ctr, Dept Pharm, Bronx, NY USA.
[Mitchell, Melissa M.] Riverside Cty Reg Med Ctr, Moreno Valley, CA USA.
[Mitchell, Melissa M.] St Vincents Hosp, Dept Pharm, New York, NY USA.
RP Arif, SA (reprint author), Midwestern Univ, Chicago Coll Pharm, 555 31st St, Downers Grove, IL 60515 USA.
EM sarif@midwestern.edu
NR 41
TC 14
Z9 15
U1 0
U2 7
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 FEB 15
PY 2011
VL 68
IS 4
BP 301
EP 308
DI 10.2146/ajhp100079
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 858CC
UT WOS:000297772500006
PM 21289324
ER
PT J
AU Gajic, O
Dabbagh, O
Park, PK
Adesanya, A
Chang, SY
Hou, P
Anderson, H
Hoth, JJ
Mikkelsen, ME
Gentile, NT
Gong, MN
Talmor, D
Bajwa, E
Watkins, TR
Festic, E
Yilmaz, M
Iscimen, R
Kaufman, DA
Esper, AM
Sadikot, R
Douglas, I
Sevransky, J
Malinchoc, M
AF Gajic, Ognien
Dabbagh, Ousama
Park, Pauline K.
Adesanya, Adebola
Chang, Steven Y.
Hou, Peter
Anderson, Harry, III
Hoth, J. Jason
Mikkelsen, Mark E.
Gentile, Nina T.
Gong, Michelle N.
Talmor, Daniel
Bajwa, Ednan
Watkins, Timothy R.
Festic, Emir
Yilmaz, Murat
Iscimen, Remzi
Kaufman, David A.
Esper, Annette M.
Sadikot, Ruxana
Douglas, Ivor
Sevransky, Jonathan
Malinchoc, Michael
CA US Critical Illness Injury Trials
TI Early Identification of Patients at Risk of Acute Lung Injury Evaluation
of Lung Injury Prediction Score in a Multicenter Cohort Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE respiratory distress syndrome; adult; prevention; prediction model;
acute respiratory failure
ID RESPIRATORY-DISTRESS-SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; MAJOR
NONCARDIAC SURGERY; INTENSIVE-CARE-UNIT; CLINICAL PREDICTORS; VENTILATOR
SETTINGS; ACUTE-PANCREATITIS; RELEVANT OUTCOMES; CONTROLLED-TRIAL;
SEVERITY SCORES
AB Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies.
Objectives: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS).
Methods: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions.
Measurements and Main Results: Twenty-two hospitals enrolled 5,584 patients at risk All developed a median of 2 (interquartile range 1-4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80(95% confidence interval, 0.78-0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9-5.7).
Conclusions: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772).
C1 [Gajic, Ognien; Malinchoc, Michael] Mayo Clin, Rochester, MN 55905 USA.
[Dabbagh, Ousama] Univ Missouri, Columbia, MO USA.
[Park, Pauline K.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Adesanya, Adebola] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Chang, Steven Y.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
[Hou, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Anderson, Harry, III] Wright State Univ, Boonshoft Sch Med, Dayton, OH 45435 USA.
[Anderson, Harry, III] Miami Valley Hosp, Dayton, OH USA.
[Hoth, J. Jason] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Mikkelsen, Mark E.] Univ Penn, Philadelphia, PA 19104 USA.
[Gentile, Nina T.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA.
[Gong, Michelle N.] Mt Sinai Sch Med, New York, NY USA.
[Talmor, Daniel] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Bajwa, Ednan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Watkins, Timothy R.] Univ Washington, Harborview, WA USA.
[Festic, Emir] Mayo Clin, Jacksonville, FL 32224 USA.
[Yilmaz, Murat] Akdeniz Univ, Antalyia, Turkey.
[Iscimen, Remzi] Uludag Univ, Bursa, Turkey.
[Kaufman, David A.] Bridgeport Hosp, New Haven, CT USA.
[Esper, Annette M.] Emory Univ, Atlanta, GA 30322 USA.
[Sadikot, Ruxana] Univ Illinois, Chicago, IL USA.
[Douglas, Ivor] Univ Colorado, Denver, CO 80202 USA.
[Sevransky, Jonathan] Johns Hopkins Univ, Baltimore, MD USA.
RP Gajic, O (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA.
EM gajic.ognjen@mayo.edu
OI Douglas, Ivor/0000-0002-4541-1431
FU National Institute of Health [HL78743-01A1, 1 KL2 RR024151]; Mayo Clinic
Critical Care Research Committee; Sanofi-Aventis; Bristol Myer
Squib/Pfizer; University Of Missouri; Vital Therapies; Maquet, Inc.; Eli
Lilly; Artisan Pharma; Walker; Allen; Grice; Ammons; NIH; American Lung
Association; American College of Surgeons; Vapotherm in industry
FX The study was supported in part by grants from the National Institute of
Health: HL78743-01A1 and 1 KL2 RR024151 (O.G.) and the Mayo Clinic
Critical Care Research Committee.; Author Disclosure: O.G. does not have
a financial relationship with a commercial entity that has an interest
in the subject of this manuscript. O.D. received $1,001-85,000 from
Sanofi-Aventis in lecture fees and $10,001-$50,000 from Bristol Myer
Squib/Pfizer in industry-sponsored grants paid to the University Of
Missouri. P.K.P. received up to $1,000 from Bayer for serving as a
consultant and $10,001-$50,000 from Vital Therapies for serving as a
co-investigator in industry-sponsored grants. A.A. received up to $1,000
from Maquet, Inc. in consultancy fees. S.Y.C. received $50,001-$100,000
from Eli Lilly as both the PI and the National Coordinator for a
clinical trial and $10,001 $50,000 from Artisan Pharma as the PI for a
study that has just closed in industry-sponsored grants. P.H. does not
have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. H.A. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. J.J.H. received $1,001-$5,000 from
Walker, Allen, Grice, Ammons, and Foy LLP for serving as an expert
witness and more than $100,001 from the NIH, $50,001-$100,000 from the
American Lung Association, and more than $100,001 from the American
College of Surgeons in sponsored grants;. M.E.M. received
$50,001-8100,000 from the NIH as a T32 cardiopulmonary grant funding
during M.E.M.'s fellowship;. N.T.G. received $10,001-850,000 from
Vapotherm in industry-sponsored grants for a research studyand more than
$100,001 fro the NIH in sponsored grants,. M.N.G. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. D.T. received $1,001 $5,000 from Elcam
Medical for serving as a member of a scientific advisory board until
2009. E.B. received more than $100,001 from the NIH in sponsored grants
as a K23 grant,. T.R.W. received more than $100,001 from the NIH in
sponsored grants as a 1K23GM086729 (career development award);. E.F.
does not have a financial relationship with a commercial entity that has
an interest in the subject of this manuscript. M.Y. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. R.I. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. D.A.K. received $10,001 $50,000 from the
Port Authority of NY and NJ, up to $1,000 from Goldberg Segalla LLP,
$1,001 $5,000 from Burton Schulte Weekley McLaughlin & Beytin for
serving as an expert witness, and $1,001-$5,000 from UpToDate in
royalties. A.M.E. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. R.S. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. I.D. received $10,001-$50,000 from Eli Lilly for serving on
a scientific advisory board (study steering committee), more than
$100,001 from the NIH as a research grant for lung injury and ARDS
research, and $10,001-$50,000 from the Canadian CC Trials Group as a
research grant for lung injury and ARDS research;. J.S. received
$1,001-$5,000 from Idaho Technology in consultancy fees, more than
$100,001 from the NIH in sponsored grants, and $5,001-$10,000 from
Critical Care Medicine as a journal section editor. M.M. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript.
NR 53
TC 173
Z9 184
U1 2
U2 10
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD FEB 15
PY 2011
VL 183
IS 4
BP 462
EP 470
DI 10.1164/rccm.201004-0549OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 724IE
UT WOS:000287568500010
PM 20802164
ER
PT J
AU Levine, S
Biswas, C
Dierov, J
Barsotti, R
Shrager, JB
Taitan, N
Sonnad, S
Kucharchzuk, JC
Kaiser, LR
Singhal, S
Budak, MT
AF Levine, Sanford
Biswas, Chhanda
Dierov, Jamil
Barsotti, Robert
Shrager, Joseph B.
Taitan Nguyen
Sonnad, Seema
Kucharchzuk, John C.
Kaiser, Larry R.
Singhal, Sunil
Budak, Murat T.
TI Increased Proteolysis, Myosin Depletion, and Atrophic AKT-FOXO Signaling
in Human Diaphragm Disuse
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE AKT; FOXO; ubiquitination; proteasome; myosin heavy chains
ID SKELETAL-MUSCLE ATROPHY; MECHANICAL VENTILATION; OXIDATIVE STRESS;
PROTEIN-DEGRADATION; DYSFUNCTION; PATHWAYS; PHOSPHORYLATION; ACTIVATION;
PROTEASOME; CACHEXIA
AB Rationale: Patients on mechanical ventilation who exhibit diaphragm inactivity for a prolonged time (case subjects) develop decreases in diaphragm force-generating capacity accompanied by diaphragm myofiber atrophy.
Objectives: Our objectives were to test the hypotheses that increased proteolysis by the ubiquitin-proteasome pathway, decreases in myosin heavy chain (MyHC) levels, and atrophic AKT-FOXO signaling play major roles in eliciting these pathological changes associated with diaphragm disuse.
Methods: Biopsy specimens were obtained from the costal diaphragms of 18 case subjects before harvest (cases) and compared with intraoperative specimens from the diaphragms of 11 patients undergoing surgery for benign lesions or localized lung cancer (control subjects). Case subjects had diaphragm inactivity and underwent mechanical ventilation for 18 to 72 hours, whereas this state in controls was limited to 2 to 4 hours.
Measurements and Main Results: With respect to proteolysis in cytoplasm fractions, case diaphragms exhibited greater levels of ubiquitinated-protein conjugates, increased activity of the 265 proteasome, and decreased levels of MyHCs and a-actin. With respect to atrophic signaling in nuclear fractions, case diaphragms exhibited decreases in phosphorylated AKT, phosphorylated FOXO1, increased binding to consensus DNA sequence for Atrogin-1 and MuRF-1, and increased supershift of DNA-FOXO1 complexes with specific antibodies against FOXO1, as well as increased Atrogin-1 and MuRF-1 transcripts in whole myofiber lysates.
Conclusions: Our findings suggest that increased activity of the ubiquitin-proteasome pathway, marked decreases in MyHCs, and atrophic AKT-FOXO signaling play important roles in eliciting the myofiber atrophy and decreases in diaphragm force generation associated with prolonged human diaphragm disuse.
C1 [Levine, Sanford; Biswas, Chhanda; Dierov, Jamil; Shrager, Joseph B.; Taitan Nguyen; Sonnad, Seema; Kucharchzuk, John C.; Kaiser, Larry R.; Singhal, Sunil; Budak, Murat T.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
[Levine, Sanford; Biswas, Chhanda; Barsotti, Robert; Shrager, Joseph B.; Budak, Murat T.] Univ Penn, Penn Muscle Inst, Philadelphia, PA 19104 USA.
[Levine, Sanford] Gift Life Donor Program, Philadelphia, PA USA.
[Levine, Sanford; Biswas, Chhanda; Dierov, Jamil; Shrager, Joseph B.; Taitan Nguyen; Singhal, Sunil; Budak, Murat T.] Dept Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA 19104 USA.
[Levine, Sanford; Biswas, Chhanda; Dierov, Jamil; Shrager, Joseph B.; Taitan Nguyen; Singhal, Sunil; Budak, Murat T.] Dept Vet Affairs Med Ctr, Med Res Serv, Philadelphia, PA 19104 USA.
[Barsotti, Robert] Philadelphia Coll Osteopath Med, Philadelphia, PA USA.
[Shrager, Joseph B.] Palo Alto Vet Affairs Med Ctr, Palo Alto, CA USA.
[Shrager, Joseph B.] Stanford Univ, Dept Cardiothorac Surg, Palo Alto, CA 94304 USA.
[Kaiser, Larry R.] Univ Texas Hlth Sci Ctr Houston, Off President, Houston, TX USA.
RP Levine, S (reprint author), 1495 Wesleys Run, Gladwyne, PA 19035 USA.
EM sdlevine@mail.med.upenn.edu
RI Budak, Murat/I-8358-2013
OI Budak, Murat/0000-0002-5059-9651
FU NHLBI [R01-HL-078834]; Ventalis, Inc.; GlaxoSmithKline; Imedex;
aparoscopic Institute of Gynecologic Oncology; Hall; Hieatt; Connelly;
NIH
FX Supported by NHLBI grant R01-HL-078834 (S.L.).; S.L. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. C.B. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. I.D. does not have a financial relationship
with a commercial entity that has an interest in the subject of this
manuscript. R.B. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript. J.B.S. was employed by Projects in Knowledge for development
of an online lung cancer course, received $1,001-$5,000 from Ventalis,
Inc. in consultancy fees as own founders stock, $1,001 $5,000 from
GlaxoSmithKline for serving on the MAGRIT study advisory board,
51,001-55,000 from Imedex and $1,001 $5,000 from Laparoscopic Institute
of Gynecologic Oncology in lecture fees, $1,001 $5,000 from Hall,
Hieatt, and Connelly, LLP for serving as an expert witness on legal case
reviews, 510,001-550,000 from the NIH in sponsored grants as a
coinvestigator on R01, and more than $100,001 from the Merit Review
Board in sponsored grants for serving as a PI on a Merit Review Grant.
T.N. does not have a financial relationship with a commercial entity
that has an interest in the subject of this manuscript. S.S. does not
have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. J.C.K. does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript. L.R.K. does not have a financial
relationship with a commercial entity that has an interest in the
subject of this manuscript. S.S. does not have a financial relationship
with a commercial entity that has an interest in the subject of this
manuscript. M.T.B. does not have a financial relationship with a
commercial entity that has an interest in the subject of this
manuscript.
NR 40
TC 63
Z9 65
U1 1
U2 7
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD FEB 15
PY 2011
VL 183
IS 4
BP 483
EP 490
DI 10.1164/200910-1487OC
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 724IE
UT WOS:000287568500012
PM 20833824
ER
PT J
AU Kelley, AS
Ettner, SL
Morrison, RS
Du, QL
Wenger, NS
Sarkisian, CA
AF Kelley, Amy S.
Ettner, Susan L.
Morrison, R. Sean
Du, Qingling
Wenger, Neil S.
Sarkisian, Catherine A.
TI Determinants of Medical Expenditures in the Last 6 Months of Life
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID QUALITY-OF-CARE; REGIONAL-VARIATIONS; PATIENT PREFERENCES; TREATMENT
INTENSITY; END; DISABILITY; CANCER; DEATH; AGE; HOSPITALIZATION
AB Background: End-of-life medical expenditures exceed costs of care during other years, vary across regions, and are likely to be unsustainable. Identifying determinants of expenditure variation may reveal opportunities for reducing costs.
Objective: To identify patient-level determinants of Medicare expenditures at the end of life and to determine the contributions of these factors to expenditure variation while accounting for regional characteristics. It was hypothesized that race or ethnicity, social support, and functional status are independently associated with treatment intensity and controlling for regional characteristics, and that individual characteristics account for a substantial proportion of expenditure variation.
Design: Using data from the Health and Retirement Study, Medicare claims, and The Dartmouth Atlas of Health Care, relationships were modeled between expenditures and patient and regional characteristics.
Setting: United States, 2000 to 2006.
Participants: 2394 Health and Retirement Study decedents aged 65.5 years or older.
Measurements: Medicare expenditures in the last 6 months of life were estimated in a series of 2-level multivariable regression models that included patient, regional, and patient and regional characteristics.
Results: Decline in function (rate ratio [RR], 1.64 [95% CI, 1.46 to 1.83]); Hispanic ethnicity (RR, 1.50 [CI, 1.22 to 1.85]); black race (RR, 1.43 [CI, 1.25 to 1.64]); and certain chronic diseases, including diabetes (RR, 1.16 [CI, 1.06 to 1.27]), were associated with higher expenditures. Nearby family (RR, 0.90 [CI, 0.82 to 0.98]) and dementia (RR, 0.78 CI, 0.71 to 0.87]) were associated with lower expenditures, and advance care planning had no association. Regional characteristics, including end-of-life practice patterns (RR, 1.09 [CI, 1.06 to 1.14]) and hospital beds per capita (RR, 1.01 [CI, 1.00 to 1.02]), were associated with higher expenditures. Patient characteristics explained 10% of overall variance and retained statistically significant relationships with expenditures after regional characteristics were controlled for.
Limitation: The study limitations include the decedent sample, proxy informants, and a large proportion of unexplained variation.
Conclusion: Patient characteristics, such as functional decline, race or ethnicity, chronic disease, and nearby family, are important determinants of expenditures at the end of life, independent of regional characteristics.
C1 [Kelley, Amy S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Los Angeles, CA USA.
RP Kelley, AS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA.
EM amy.kelley@mssm.edu
FU Brookdale Foundation; National Institute on Aging [K24 AG022345];
National Palliative Care Research Center; Veterans Affairs Greater Los
Angeles Healthcare System Geriatric Research Education Clinical Center
FX Grant Support: By the Brookdale Foundation. Dr. Kelley is a Brookdale
Leadership in Aging Fellow. Dr. Morrison is the recipient of a MidCareer
Investigator Award in Patient-Oriented Research (K24 AG022345) from the
National Institute on Aging and is supported by the National Palliative
Care Research Center. Dr. Sarkisian is supported by the Veterans Affairs
Greater Los Angeles Healthcare System Geriatric Research Education
Clinical Center.
NR 49
TC 63
Z9 63
U1 4
U2 23
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD FEB 15
PY 2011
VL 154
IS 4
BP 235
EP W78
DI 10.7326/0003-4819-154-4-201102150-00004
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 720VF
UT WOS:000287310000015
PM 21320939
ER
PT J
AU Qaseem, A
Humphrey, LL
Chou, R
Snow, V
Shekelle, P
AF Qaseem, Amir
Humphrey, Linda L.
Chou, Roger
Snow, Vincenza
Shekelle, Paul
CA Amer Coll Phys
TI Use of Intensive Insulin Therapy for the Management of Glycemic Control
in Hospitalized Patients: A Clinical Practice Guideline From the
American College of Physicians
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID CRITICALLY-ILL PATIENTS; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED
CONTROLLED-TRIAL; TYPE-2 DIABETES-MELLITUS; GLUCOSE-INSULIN;
CARDIAC-SURGERY; ISCHEMIC-STROKE; OLDER PATIENTS; HYPERGLYCEMIA;
HYPOGLYCEMIA
AB Description: The American College of Physicians (ACP) developed this guideline to present the evidence for the link between the use of intensive insulin therapy to achieve different glycemic targets and health outcomes in hospitalized patients with or without diabetes mellitus.
Methods: Published literature on this topic was identified by using MEDLINE and the Cochrane Library. Additional articles were obtained from systematic reviews and the reference lists of pertinent studies, reviews, and editorials, as well as by consulting experts; unpublished studies on ClinicalTrials.gov were also identified. The literature search included studies published from 1950 through March 2009. Searches were limited to English-language publications. The primary outcomes of interest were short-term mortality and hypoglycemia. This guideline grades the evidence and recommendations by using the ACP clinical practice guidelines grading system.
Recommendation 1: ACP recommends not using intensive insulin therapy to strictly control blood glucose in non-surgical intensive care unit (SICU)/medical intensive care unit (MICU) patients with or without diabetes mellitus (Grade: strong recommendation, moderate-quality evidence).
Recommendation 2: ACP recommends not using intensive insulin therapy to normalize blood glucose in SICU/MICU patients with or without diabetes mellitus (Grade: strong recommendation, high-quality evidence).
Recommendation 3: ACP recommends a target blood glucose level of 7.8 to 11.1 mmol/L (140 to 200 mg/dL) if insulin therapy is used in SICU/MICU patients (Grade: weak recommendation, moderate-quality evidence).
C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA.
Pfizer, Collegeville, PA USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Portland VA Med Ctr, Portland, OR USA.
W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA.
RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA.
EM aqaseem@acponline.org
FU ACP operating budget; Agency for Healthcare Research and Quality
FX Financial support for the development of this guideline comes
exclusively from the ACP operating budget.; Any financial and
nonfinancial conflicts of interest of the group members were declared,
discussed, and resolved. Dr. Vincenza Snow was an employee of the
American College of Physicians at the time of the writing of this
guideline. Dr. Snow: Employment: American College of Physicians, Pfizer.
Dr. Shekelle: Grants/grants pending (money to institution): Agency for
Healthcare Research and Quality; Royalties: UpToDate. Disclosures can
also be viewed at
www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-272
5.
NR 59
TC 131
Z9 145
U1 3
U2 14
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD FEB 15
PY 2011
VL 154
IS 4
BP 260
EP W81
DI 10.7326/0003-4819-154-4-201102150-00007
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 720VF
UT WOS:000287310000018
PM 21320941
ER
PT J
AU Kansagara, D
Fu, RW
Freeman, M
Wolf, F
Helfand, M
AF Kansagara, Devan
Fu, Rongwei
Freeman, Michele
Wolf, Fawn
Helfand, Mark
TI Intensive Insulin Therapy in Hospitalized Patients: A Systematic Review
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Review
ID CRITICALLY-ILL PATIENTS; BLOOD-GLUCOSE CONTROL; TIGHT GLYCEMIC CONTROL;
ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; PREDICTIVE
CONTROL ALGORITHM; CLINICAL-PRACTICE GUIDELINES; DEPENDENT
DIABETES-MELLITUS; CARDIAC SURGICAL-PROCEDURES; STERNAL WOUND-INFECTION
AB Background: The benefits and harms of intensive insulin therapy (IIT) titrated to strict glycemic targets in hospitalized patients remain uncertain.
Purpose: To evaluate the benefits and harms of IIT in hospitalized patients.
Data Sources: MEDLINE and Cochrane Database of Systematic Reviews from 1950 to January 2010, reference lists, experts, and unpublished sources.
Study Selection: English-language randomized, controlled trials comparing protocols titrated to strict or less strict glycemic targets.
Data Extraction: Two reviewers independently abstracted data from each study on sample, setting, glycemic control interventions, glycemic targets, mean glucose levels achieved, and outcomes. Results were grouped by patient population or setting. A random-effects model was used to combine trial data on short-term mortality (<= 28 days), long-term mortality (90 or 180 days), infection, length of stay, and hypoglycemia. The Grading of Recommendations Assessment, Development, and Evaluation system was used to rate the overall body of evidence for each outcome.
Data Synthesis: In a meta-analysis of 21 trials in intensive care unit, perioperative care, myocardial infarction, and stroke or brain injury settings, IIT did not affect short-term mortality (relative risk, 1.00 [95% CI, 0.94 to 1.07]). No consistent evidence showed that IIT reduced long-term mortality, infection rates, length of stay, or the need for renal replacement therapy. No evidence of benefit from IIT was reported in any hospital setting, although the best evidence for lack of benefit was in intensive care unit settings. Data combined from 10 trials showed that IIT was associated with a high risk for severe hypoglycemia (relative risk, 6.00 [CI, 4.06 to 8.87]; P < 0.001). Risk for IIT-associated hypoglycemia was increased in all hospital settings.
Limitations: Methodological shortcomings and inconsistencies limit the data in perioperative care, myocardial infarction, and stroke or brain injury settings. Differences in insulin protocols and patient and hospital characteristics may affect generalizability across treatment settings.
Conclusion: No consistent evidence demonstrates that IIT targeted to strict glycemic control compared with less strict glycemic control improves health outcomes in hospitalized patients. Furthermore, IIT is associated with an increased risk for severe hypoglycemia.
C1 [Kansagara, Devan] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Portland Diabet & Endocrinol Ctr, Portland, OR 97239 USA.
RP Kansagara, D (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, 3710 SW US Vet Hosp Rd,Mailcode R&D 71, Portland, OR 97239 USA.
EM kansagar@ohsu.edu
FU Department of Veterans Affairs, Veterans Health Administration [ESP
05-225, 01-0206]; American College of Physicians
FX Financial Support: By the Department of Veterans Affairs, Veterans
Health Administration (VHA Project ESP 05-225, VA #01-0206). The
American College of Physicians provided funding for the preparation of
this manuscript.
NR 143
TC 86
Z9 94
U1 4
U2 14
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD FEB 15
PY 2011
VL 154
IS 4
BP 268
EP W89
DI 10.7326/0003-4819-154-4-201102150-00008
PG 23
WC Medicine, General & Internal
SC General & Internal Medicine
GA 720VF
UT WOS:000287310000019
PM 21320942
ER
PT J
AU Hallahan, B
Newell, J
Soares, JC
Brambilla, P
Strakowski, SM
Fleck, DE
Kieseppa, T
Altshuler, LL
Fornito, A
Malhi, GS
McIntosh, AM
Yurgelun-Todd, DA
Labar, KS
Sharma, V
MacQueen, GM
Murray, RM
McDonald, C
AF Hallahan, Brian
Newell, John
Soares, Jair C.
Brambilla, Paolo
Strakowski, Stephen M.
Fleck, David E.
Kieseppa, Tuula
Altshuler, Lori L.
Fornito, Alex
Malhi, Gin S.
McIntosh, Andrew M.
Yurgelun-Todd, Deborah A.
Labar, Kevin S.
Sharma, Verinder
MacQueen, Glenda M.
Murray, Robin M.
McDonald, Colm
TI Structural Magnetic Resonance Imaging in Bipolar Disorder: An
International Collaborative MegaAnalysis of Individual Adult Patient
Data
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 8th International Conference on Bipolar Disorder
CY JUN 25-27, 2009
CL Pittsburgh, PA
SP NIMH
DE Amygdala; bipolar disorder; hippocampus; lateral ventricles; lithium;
mega-analysis
ID SUBGENUAL PREFRONTAL CORTEX; TEMPORAL-LOBE STRUCTURES; BRAIN
GRAY-MATTER; HIPPOCAMPAL VOLUME; MOOD DISORDERS; WHITE-MATTER; LITHIUM
TREATMENT; BASAL GANGLIA; HEALTHY-INDIVIDUALS; NEUROTROPHIC FACTOR
AB Background: There is substantial inconsistency in results of brain structural magnetic resonance imaging studies in adult bipolar disorder. This is likely consequent upon limited statistical power of studies together with their clinical and methodological heterogeneity. The current study was undertaken to perform an international collaborative mega-analysis of regional volumetric measurements of individual patient and healthy subject data, to optimize statistical power, detect case-control differences, assess the association of psychotropic medication usage with brain structural variation, and detect other possible sources of heterogeneity.
Methods: Eleven international research groups contributed published and unpublished data on 321 individuals with bipolar disorder land 442 healthy subjects. We used linear mixed effects regression models to evaluate differences in brain structure between patient groups.
Results: Individuals with bipolar disorder had increased right lateral ventricular, left temporal lobe, and right putamen volumes. Bipolar patients taking lithium displayed significantly increased hippocampal and amygdala volume compared with patients not treated with lithium and healthy comparison subjects. Cerebral volume reduction was significantly associated with illness duration in bipolar individuals.
Conclusions: The application of mega-analysis to bipolar disorder imaging identified lithium use and illness duration as substantial and consistent sources of heterogeneity, with lithium use associated with regionally specific increased brain volume.
C1 [Hallahan, Brian; McDonald, Colm] Natl Univ Ireland Galway, Dept Psychiat, Inst Clin Sci, Galway, Ireland.
Natl Univ Ireland Galway, Hlth Res Board, Clin Res Facil, Galway, Ireland.
[Newell, John] Natl Univ Ireland Galway, Sch Math Stat & Appl Math, Galway, Ireland.
[Brambilla, Paolo] Univ N Carolina, Sch Med, Dept Psychiat, Ctr Excellence Res & Treatment Bipolar Disorders, Chapel Hill, NC USA.
[Brambilla, Paolo] Univ Udine, DPMSC, Sect Psychiat, I-33100 Udine, Italy.
IRCCS E Medea, Inst Sci, Udine, Italy.
[Strakowski, Stephen M.; Fleck, David E.] Univ Cincinnati, Coll Med, Div Bipolar Disorder Res, Cincinnati, OH USA.
[Strakowski, Stephen M.; Fleck, David E.] Univ Cincinnati, Coll Med, Ctr Imaging Res, Cincinnati, OH USA.
[Kieseppa, Tuula] Univ Helsinki, Cent Hosp, Natl Inst Hlth & Welf, Dept Mental Hlth & Alcohol Res, Helsinki, Finland.
Univ Helsinki, Dept Psychiat, Cent Hosp, Helsinki, Finland.
[Altshuler, Lori L.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, W Los Angeles Healthcare Ctr, Los Angeles, CA USA.
Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Fornito, Alex] Univ Cambridge, Addenbrookes Hosp, Brain Mapping Unit, Dept Psychiat, Cambridge CB2 2QQ, England.
Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Natl Neurosci Facil, Melbourne, Vic 3010, Australia.
[Malhi, Gin S.] Univ Sydney, Discipline Psychol Med, Sydney, NSW 2006, Australia.
[McIntosh, Andrew M.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.
[Yurgelun-Todd, Deborah A.] Univ Utah, Dept Psychiat, Utahs Sch Med, Cognit Imaging Lab,Brain Inst, Salt Lake City, UT USA.
[Labar, Kevin S.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[Labar, Kevin S.] Duke Univ, Med Ctr, Ctr Cognit Neurosci, Durham, NC USA.
[Sharma, Verinder] Univ Western Ontario, Dept Psychiat, Reg Mental Hlth Care London, London, ON N6A 3K7, Canada.
[MacQueen, Glenda M.] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
[Murray, Robin M.; McDonald, Colm] Inst Psychiat, Div Psychol Med, London, England.
[Soares, Jair C.] Univ Texas Hlth Sci Ctr, Ctr Excellence Mood Disorders, Houston, TX USA.
Harris Cty Psychiat Ctr, Houston, TX USA.
RP Hallahan, B (reprint author), Natl Univ Ireland, Dept Psychiat, Inst Clin Sci, Galway, Ireland.
EM brian.hallahan@nuigalway.ie
RI McIntosh, Andrew/B-9379-2008; McDonald, Colm/C-1430-2009; Murray,
Robin/F-8658-2012; Alex, Fornito/N-8214-2013;
OI McIntosh, Andrew/0000-0002-0198-4588; Murray, Robin/0000-0003-0829-0519;
Alex, Fornito/0000-0001-9134-480X; Newell, John/0000-0001-7685-6655;
Hallahan, Brian/0000-0003-0518-9757
NR 72
TC 123
Z9 125
U1 1
U2 25
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD FEB 15
PY 2011
VL 69
IS 4
BP 326
EP 335
DI 10.1016/j.biopsych.2010.08.029
PG 10
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 718JV
UT WOS:000287118300006
PM 21030008
ER
PT J
AU Hutton, J
Walker, LG
Gilbert, FJ
Evans, DG
Eeles, R
Kwan-Lim, GE
Thompson, D
Pointon, LJ
Sharp, DM
Leach, MO
AF Hutton, J.
Walker, L. G.
Gilbert, F. J.
Evans, D. G.
Eeles, R.
Kwan-Lim, G. E.
Thompson, D.
Pointon, L. J.
Sharp, D. M.
Leach, M. O.
CA High Risk Study
TI Psychological impact and acceptability of magnetic resonance imaging and
X-ray mammography: the MARIBS Study
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE MARIBS; psychology; MRI; anxiety; breast cancer
ID HIGH FAMILIAL RISK; BREAST-CANCER; NATIONAL MULTICENTER; HOSPITAL
ANXIETY; DEPRESSION SCALE; GENETIC RISK; WOMEN; MRI; HISTORY;
PERFORMANCE
AB BACKGROUND: As part of the Magnetic Resonance Imaging for Breast Screening (MARIBS), Study women with a family history of breast cancer were assessed psychologically to determine the relative psychological impact and acceptability of annual screening using magnetic resonance imaging (MRI) and conventional X-ray mammography (XRM).
METHODS: Women were assessed psychologically at baseline (4 weeks before MRI and XRM), immediately before, and immediately after, both MRI and XRM, and at follow-up (6 weeks after the scans).
RESULTS: Overall, both procedures were found to be acceptable with high levels of satisfaction (MRI, 96.3% and XRM, 97.7%; NS) and low levels of psychological morbidity throughout, particularly at 6-week follow-up. Low levels of self-reported distress were reported for both procedures (MRI, 13.5% and XRM, 7.8%), although MRI was more distressing (P = 0.005). Similarly, higher anticipatory anxiety was reported before MRI than before XRM (P = 0.003). Relative to XRM, MRI-related distress was more likely to persist at 6 weeks after the scans in the form of intrusive MRI-related thoughts (P = 0.006) and total MRI-related distress (P = 0.014). More women stated that they intended to return for XRM (96.3%) than for MRI (88%; P < 0.0005). These effects were most marked for the first year of screening, although they were also statistically significant in subsequent years.
CONCLUSION: Given the proven benefits of MRI in screening for breast cancer in this population, these data point to the urgent need to provide timely information and support to women undergoing MRI. British Journal of Cancer (2011) 104, 578-586. doi:10.1038/bjc.2011.1 www.bjcancer.com (C) 2011 Cancer Research UK
C1 [Hutton, J.] N Lanarkshire Council, Motherwell ML1 1JE, Lanark, Scotland.
[Walker, L. G.; Sharp, D. M.] Univ Hull, Postgrad Med Inst, Inst Rehabil, Kingston Upon Hull HU3 2PG, Yorks, England.
[Walker, L. G.; Sharp, D. M.] Hull York Med Sch, Kingston Upon Hull HU3 2PG, Yorks, England.
[Gilbert, F. J.] Univ Aberdeen, Aberdeen Biomed Imaging Ctr, Aberdeen AB25 2ZD, Scotland.
[Evans, D. G.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester M13 9WL, Lancs, England.
[Eeles, R.; Kwan-Lim, G. E.; Leach, M. O.] Canc Res UK Clin Magnet Resonance Res Grp, Inst Canc Res, Sutton SM2 5PT, Surrey, England.
[Eeles, R.; Kwan-Lim, G. E.; Leach, M. O.] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England.
[Thompson, D.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 8RN, England.
[Pointon, L. J.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA.
RP Hutton, J (reprint author), N Lanarkshire Council, 73-77 Merry St, Motherwell ML1 1JE, Lanark, Scotland.
EM huttonJe@northlan.gov.uk
RI leach, martin/C-2248-2008;
OI leach, martin/0000-0002-0756-5368; Eeles, Rosalind/0000-0002-3698-6241;
Evans, Gareth/0000-0002-8482-5784
FU UK Medical Research Council [G960413]; NHS funding as an NIHR Biomedical
Research Centre; CRUK; EPSRC Cancer Imaging Centre; MRC; Department of
Health (England) [C1060/A10334]; NIHR
FX The study is a UK-wide collaboration of 22 genetics centres, and their
associated MRI and Mammography Departments. We acknowledge the vital
contributions of clinical colleagues, radiographers, nurses, clerical
staff, physicists, and engineers. A special thank you is extended to the
women and their surgeons and oncologists who referred them, without whom
the study would not have been possible. The national study is supported
by a grant from the UK Medical Research Council (G960413). The cost of
the MRI studies is paid for by subvention funding for research from the
UK National Health Service. The protocol is based, in part, on
developments supported by Cancer Research UK and the Yorkshire Cancer
Research Campaign. Contributions towards training and education have
been made by Schering Healthcare (Burgess Hill, UK) and Oracle Education
(Bracknell, UK). We thank Myriad Genetics (Saltlake, UT, USA) for doing
the anonymous genetic testing and Paula Smith for doing the risk
calculations for the Genetic Eligibility Panel. The Institute of Cancer
Research (ICR) receives NHS funding as an NIHR Biomedical Research
Centre. The ICR Imaging Centre receives support from the CRUK and EPSRC
Cancer Imaging Centre funding in association with the MRC and Department
of Health (England) grant C1060/A10334. DGE is supported by an NIHR
grant to the Biomedical Research Centre, Manchester.
NR 29
TC 9
Z9 9
U1 1
U2 6
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 FEB 15
PY 2011
VL 104
IS 4
BP 578
EP 586
DI 10.1038/bjc.2011.1
PG 9
WC Oncology
SC Oncology
GA 728ZY
UT WOS:000287915600006
PM 21326245
ER
PT J
AU Ellisen, LW
AF Ellisen, Leif W.
TI PARP Inhibitors in Cancer Therapy: Promise, Progress, and Puzzles
SO CANCER CELL
LA English
DT Editorial Material
ID POLY(ADP-RIBOSE) POLYMERASE; TUMORS
C1 [Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM ellisen@helix.mgh.harvard.edu
FU NCI NIH HHS [P30 CA006516-44S2, P30 CA006516]
NR 10
TC 26
Z9 29
U1 1
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 FEB 15
PY 2011
VL 19
IS 2
BP 165
EP 167
DI 10.1016/j.ccr.2011.01.047
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 727BE
UT WOS:000287771500005
PM 21316599
ER
PT J
AU Frank, NY
Schatton, T
Kim, S
Zhan, QA
Wilson, BJ
Ma, J
Saab, KR
Osherov, V
Widlund, HR
Gasser, M
Waaga-Gasser, AM
Kupper, TS
Murphy, GF
Frank, MH
AF Frank, Natasha Y.
Schatton, Tobias
Kim, Soo
Zhan, Qian
Wilson, Brian J.
Ma, Jie
Saab, Karim R.
Osherov, Veronika
Widlund, Hans R.
Gasser, Martin
Waaga-Gasser, Ana-Maria
Kupper, Thomas S.
Murphy, George F.
Frank, Markus H.
TI VEGFR-1 Expressed by Malignant Melanoma-Initiating Cells Is Required for
Tumor Growth
SO CANCER RESEARCH
LA English
DT Article
ID CANCER STEM-CELLS; VASCULOGENIC MIMICRY; IN-VIVO; ANGIOGENESIS;
RECEPTOR; CHEMORESISTANCE; IDENTIFICATION; ABCB5; CD133
AB \ Melanoma growth is driven by malignant melanoma-initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member ABCB5. ABCB5(+) melanoma subpopulations have been shown to over-express the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE1 and are associated with CD31(-) vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5(+) MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5(+) tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced the expression of CD144 in ABCB5(+) subpopulations that constitutively expressed VEGFR-1 but not in ABCB5(-) bulk populations that were predominantly VEGFR-1(-). In vivo, melanoma-specific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5(+) VM morphology and inhibited ABCB5(+) VM-associated production of the secreted melanoma mitogen laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by >90%). Our results show that VEGFR-1 function in MMIC regulates VM and associated laminin production and show that this function represents one mechanism through which MMICs promote tumor growth. Cancer Res; 71(4); 1474-85. (c) 2011 AACR.
C1 [Frank, Natasha Y.; Schatton, Tobias; Kim, Soo; Wilson, Brian J.; Ma, Jie; Saab, Karim R.; Osherov, Veronika; Frank, Markus H.] Childrens Hosp Boston, Transplantat Res Ctr, Boston, MA 02115 USA.
[Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Frank, Natasha Y.] Boston VA Healthcare Syst, Dept Med, Boston, MA USA.
[Schatton, Tobias; Wilson, Brian J.; Ma, Jie; Saab, Karim R.; Widlund, Hans R.; Kupper, Thomas S.; Frank, Markus H.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Zhan, Qian; Murphy, George F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Gasser, Martin; Waaga-Gasser, Ana-Maria] Univ Wurzburg, Dept Surg, Wurzburg, Germany.
RP Frank, MH (reprint author), Childrens Hosp Boston, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA.
EM gmurphy@rics.bwh.harvard.edu; mfrank@rics.bwh.harvard.edu
RI Frank, Markus/O-1625-2014
OI Frank, Markus/0000-0002-1312-0488
FU NIH/NCI [1RO1CA113796, 1R01CA138231, 2P50CA093683-06A20006]; NIH/NINDS
[KO8NS051349]
FX This work was supported by funds provided by the NIH/NCI (grants
1RO1CA113796 and 1R01CA138231 to M.H. Frank and grant
2P50CA093683-06A20006 to T.S. Kupper, M.H. Frank, and G.F. Murphy) and
the NIH/NINDS (grant KO8NS051349 to N.Y. Frank).
NR 46
TC 65
Z9 73
U1 2
U2 13
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2011
VL 71
IS 4
BP 1474
EP 1485
DI 10.1158/0008-5472.CAN-10-1660
PG 12
WC Oncology
SC Oncology
GA 721KP
UT WOS:000287352600029
PM 21212411
ER
PT J
AU Clair, DG
Hopkins, LN
Mehta, M
Kasirajan, K
Schermerhorn, M
Schonholz, C
Kwolek, CJ
Eskandari, MK
Powell, RJ
Ansel, GM
AF Clair, Daniel G.
Hopkins, L. Nelson
Mehta, Manish
Kasirajan, Karthikeshwar
Schermerhorn, Marc
Schoenholz, Claudio
Kwolek, Christopher J.
Eskandari, Mark K.
Powell, Richard J.
Ansel, Gary M.
CA EMPiRe Clinical Study
TI Neuroprotection During Carotid Artery Stenting Using the GORE Flow
Reversal System: 30-Day Outcomes in the EMPiRE Clinical Study
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE angioplasty; carotid arteries; embolism; stents; stroke
ID SURGICAL-RISK PATIENTS; CEREBRAL PROTECTION DEVICES; EMBOLIC PROTECTION;
DISTAL PROTECTION; ENDOVASCULAR TREATMENT; FILTERWIRE EX/EZ; CAPTURE
REGISTRY; RANDOMIZED-TRIAL; BEACH TRIAL; ANGIOPLASTY
AB Background: Each of the embolic protection devices used in carotid artery stenting (CAS) has advantages and disadvantages. The prospective, multicenter, single-arm EMPiRE Clinical Study investigated a proximally placed device (GORE Flow Reversal System) that provides distal neuroprotection during CAS by reversing blood flow in the internal carotid artery, thereby directing emboli away from the brain. Methods: The study evaluated 30-day outcomes in 245 pivotal high-surgical-risk patients (mean age, 70 years; 32% symptomatic; 16% >= 80-years old) with carotid stenosis who underwent CAS using the flow reversal system. The primary endpoint was a major adverse event (MAE; stroke, death, myocardial infarction, or transient ischemic attack) within 30 days of CAS. The MAE rate was compared with an objective performance criterion (OPC) derived from CAS studies that included embolic protection. Results: The MAE rate was 4.5% (11 patients; P = 0.002 compared with the OPC). The stroke and death rate was 2.9%. No patient had a major ischemic stroke. Six patients (2.4%) had intolerance to flow reversal. The death and stroke rates in the symptomatic, asymptomatic, and octogenarian subgroups were 2.6, 3, and 2.6%, respectively, meeting American Heart Association guidelines for carotid endarterectomy. Conclusion: The stroke and death rate in this study was among the lowest in CAS trials. The results indicate that the flow reversal system is safe and effective when used for neuroprotection during CAS and that it provides benefits in a broad patient population. (C) 2010 Wiley-Liss, Inc.
C1 [Clair, Daniel G.] Cleveland Clin, Lerner Coll Med, Dept Vasc Surg, Inst Heart & Vasc, Cleveland, OH 44135 USA.
[Hopkins, L. Nelson] SUNY Buffalo, Buffalo, NY 14260 USA.
[Hopkins, L. Nelson] Toshiba Stroke Ctr, Buffalo, NY USA.
[Mehta, Manish] Albany Vasc Grp, Albany, NY USA.
[Kasirajan, Karthikeshwar] Emory Univ Hosp, Atlanta, GA 30322 USA.
[Schermerhorn, Marc] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Schoenholz, Claudio] Med Univ S Carolina, Charleston, SC 29425 USA.
[Kwolek, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Eskandari, Mark K.] NW Mem Hosp, Chicago, IL 60611 USA.
[Powell, Richard J.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Ansel, Gary M.] Riverside Methodist Hosp, Columbus, OH 43214 USA.
RP Clair, DG (reprint author), Cleveland Clin, Lerner Coll Med, Dept Vasc Surg, Inst Heart & Vasc, 9500 Euclid Ave,H32, Cleveland, OH 44135 USA.
EM CLAIRD@ccf.org
NR 51
TC 63
Z9 64
U1 1
U2 8
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 FEB 15
PY 2011
VL 77
IS 3
BP 420
EP 429
DI 10.1002/ccd.22789
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 725QD
UT WOS:000287659800017
PM 20853365
ER
PT J
AU Neal, JW
Shaw, AT
AF Neal, Joel W.
Shaw, Alice T.
TI One Allele's Loss Is Another's Gain: Alterations of NKX2-8 in Non-Small
Cell Lung Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
AB Large-scale genetic changes such as loss or gain of chromosomes are important drivers of solid tumor carcinogenesis. Recent technological advances in genomic profiling have allowed quantitative detection of gene copy numbers, leading to identification of the 14q13.3 gene locus as functionally important in non-small cell lung cancers. Clin Cancer Res; 17(4); 638-9. (C) 2010 AACR.
C1 [Shaw, Alice T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Ctr Thorac Canc, Boston, MA 02114 USA.
[Neal, Joel W.] Stanford Canc Ctr, Stanford, CA USA.
RP Shaw, AT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp Canc Ctr, Ctr Thorac Canc, Profess Off Bldg 222, Boston, MA 02114 USA.
EM ashaw1@partners.org
FU Novartis; AztraZeneca
FX A. Shaw, commercial research grant, Novartis, AztraZeneca; consultant,
Pfizer, Millennium.
NR 9
TC 0
Z9 0
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 FEB 15
PY 2011
VL 17
IS 4
BP 638
EP 639
DI 10.1158/1078-0432.CCR-10-3081
PG 2
WC Oncology
SC Oncology
GA 728ZM
UT WOS:000287913200002
PM 21163872
ER
PT J
AU Diamond, JR
Bastos, BR
Hansen, RJ
Gustafson, DL
Eckhardt, SG
Kwak, EL
Pandya, SS
Fletcher, GC
Pitts, TM
Kulikowski, GN
Morrow, M
Arnott, J
Bray, MR
Sidor, C
Messersmith, W
Shapiro, GI
AF Diamond, Jennifer R.
Bastos, Bruno R.
Hansen, Ryan J.
Gustafson, Daniel L.
Eckhardt, S. Gail
Kwak, Eunice L.
Pandya, Shuchi S.
Fletcher, Graham C.
Pitts, Todd M.
Kulikowski, Gillian N.
Morrow, Mark
Arnott, Jamie
Bray, Mark R.
Sidor, Carolyn
Messersmith, Wells
Shapiro, Geoffrey I.
TI Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of ENMD-2076,
a Novel Angiogenic and Aurora Kinase Inhibitor, in Patients with
Advanced Solid Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RENAL-CELL CARCINOMA; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER;
BEVACIZUMAB; SUNITINIB; TARGETS; HYPERTENSION; SORAFENIB
AB Purpose: ENMD-2076 is a unique orally bioavailable Aurora kinase and VEGFR inhibitor. The purpose of this phase 1 study of ENMD-2076 was to determine the MTD, pharmacokinetic, and pharmacodynamic profiles and preliminary antitumor activity.
Experimental Design: Patients with refractory advanced solid malignancies were treated with ENMD-2076 orally with continuous once daily dosing. Doses from 60 to 200 mg/m(2) were evaluated using a standard 3 (to 4) + 3 design. Pharmacokinetic parameters were studied on days 1, 28, and 30 to 35 of cycle 1. Expanded MTD cohorts included patients with ovarian cancer, colorectal cancer, and refractory solid tumors.
Results: A total of 67 patients (46 F, 21M; ages 30-76) entered the study. Dose levels of 60, 80, 120, 200, and 160 mg/m(2) were evaluated. Two patients experienced grade 3 hypertension at 200 mg/m(2), and additional grade 3 neutropenia events limited tolerability at this dose. An intermediate dose of 160 mg/m(2) was determined to be the MTD. The most common drug-related adverse events included hypertension, nausea/vomiting, and fatigue. The pharmacokinetics of ENMD-2076 were characterized by a rapid absorption phase (T(max) 3-7.8 hours), a t(1/2) of 27.3 to 38.3 hours after a single dose, and dose proportional exposure. Decreased plasma sVEGFR2 was observed posttreatment. Two patients with platinum refractory/resistant ovarian cancer had RECIST partial responses.
Conclusions: ENMD-2076 was well tolerated, had a linear pharmacokinetic profile, and showed promising antitumor activity, particularly in ovarian cancer. The recommended phase 2 dose of ENMD-2076 is 160 mg/m(2) administered orally once daily with continuous dosing. Clin Cancer Res; 17(4); 849-60. (C) 2010 AACR.
C1 [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA.
[Diamond, Jennifer R.; Eckhardt, S. Gail; Pitts, Todd M.; Kulikowski, Gillian N.; Morrow, Mark; Messersmith, Wells] Univ Colorado Denver, Aurora, CO USA.
[Hansen, Ryan J.; Gustafson, Daniel L.] Colorado State Univ, Anim Canc Ctr, Ft Collins, CO 80523 USA.
[Kwak, Eunice L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pandya, Shuchi S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Fletcher, Graham C.; Arnott, Jamie; Bray, Mark R.; Sidor, Carolyn] EntreMed Inc, Toronto, ON, Canada.
[Arnott, Jamie; Bray, Mark R.; Sidor, Carolyn] EntreMed Inc, Durham, NC USA.
RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Early Drug Dev Ctr, 44 Binney St, Boston, MA 02115 USA.
EM geoffrey_shapiro@dfci.harvard.edu
FU EntreMed, Inc. [NCT00658671]; Colorado State University
FX Supported by EntreMed, Inc. (NCT00658671), including a Sponsored
Research Agreement with Colorado State University for performance of
pharmacokinetics.
NR 37
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U1 0
U2 5
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 FEB 15
PY 2011
VL 17
IS 4
BP 849
EP 860
DI 10.1158/1078-0432.CCR-10-2144
PG 12
WC Oncology
SC Oncology
GA 728ZM
UT WOS:000287913200024
PM 21131552
ER
PT J
AU Quek, R
Wang, QA
Morgan, JA
Shapiro, GI
Butrynski, JE
Ramaiya, N
Huftalen, T
Jederlinic, N
Manola, J
Wagner, AJ
Demetri, GD
George, S
AF Quek, Richard
Wang, Qian
Morgan, Jeffrey A.
Shapiro, Geoffrey I.
Butrynski, James E.
Ramaiya, Nikhil
Huftalen, Tarsha
Jederlinic, Nicole
Manola, Judith
Wagner, Andrew J.
Demetri, George D.
George, Suzanne
TI Combination mTOR and IGF-1R Inhibition: Phase I Trial of Everolimus and
Figitumumab in Patients with Advanced Sarcomas and Other Solid Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MONOCLONAL-ANTIBODY CP-751,871; GROWTH-FACTOR RECEPTOR; MAMMALIAN
TARGET; PATHWAY; FIBROBLASTS; ACTIVATION; SUNITINIB; CARCINOMA; CANCER;
CELLS
AB Purpose: Preclinical models demonstrate synergistic antitumor activity with combination blockade of mTOR and IGF-1R signaling. We aimed to determine the safety, tolerability, and recommended phase II dose (RP2D) of the combination of figitumumab, a fully human IgG2 anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody (Pfizer) and the mTOR inhibitor, everolimus (Novartis). Pharmacokinetics and preliminary antitumor effects of the combination were evaluated.
Experimental Design: Phase I trial in patients with advanced sarcomas and other solid tumors. Initial cohort combined full phase 2 dose figitumumab (20 mg/kg IV every 21 days) with full dose everolimus (10 mg orally once daily). Intercohort dose de-escalation was planned for unacceptable toxicities. Dose modifications were allowed beyond cycle 1.
Results: NoDLTs were observed in the initial cohort during cycle one, therefore full dose figitumumab and everolimus was declared the RP2D. In total, 21 patients were enrolled on study. Most toxicities were grade 1 or 2, and were similar to reported toxicities of the single agents. Mucositis was the most frequently observed grade 3 toxicity. Median time on study was 104 days (range 17-300). Of 18 patients evaluable for response, best response was partial response in 1 patient with malignant solitary fibrous tumor and, stable disease in 15 patients. There were no apparent pharmacokinetic interactions between everolimus and figitumumab.
Conclusions: Combination figitumumab plus everolimus at full doses appears safe and well tolerated with no unexpected toxicities. Dose reductions in everolimus may be required after prolonged drug administration. This regimen exhibits interesting antitumor activity warranting further investigation. Clin Cancer Res; 17(4); 871-9. (C) 2010 AACR.
C1 [Quek, Richard; Morgan, Jeffrey A.; Butrynski, James E.; Huftalen, Tarsha; Jederlinic, Nicole; Wagner, Andrew J.; George, Suzanne] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
[Wang, Qian; Manola, Judith] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA.
[Ramaiya, Nikhil] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
[Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA.
RP George, S (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 44 Binney St, Boston, MA 02115 USA.
EM suzanne_george@dfci.harvard.edu
FU Novartis; Pfizer; Genentech; Arqule; Exelixis; Ariad
FX SG has received research funding from, and have served in a consultant
or advisory role for Novartis and Pfizer. AJW has received research
funding from Genentech, Prolexys, Arqule, and Exelixis, and have served
in a consultant or advisory role for Genentech. GDD has received
research funding from Novartis, Pfizer, and Ariad; served in a
consultant or advisory role for Novartis, Pfizer, Ariad, Amgen, and
Genentech; received honoraria from Novartis, Pfizer; and has provided
expert testimony for Novartis, Pfizer, and Ariad. All other authors
declared no conflicts of interest.; Research drugs and pharmacokinetic
assay support were provided by Novartis and Pfizer.
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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 FEB 15
PY 2011
VL 17
IS 4
BP 871
EP 879
DI 10.1158/1078-0432.CCR-10-2621
PG 9
WC Oncology
SC Oncology
GA 728ZM
UT WOS:000287913200026
PM 21177764
ER
PT J
AU Zhu, AX
Duda, DG
Ancukiewicz, M
di Tomaso, E
Clark, JW
Miksad, R
Fuchs, CS
Ryan, DP
Jain, RK
AF Zhu, Andrew X.
Duda, Dan G.
Ancukiewicz, Marek
di Tomaso, Emmanuelle
Clark, Jeffrey W.
Miksad, Rebecca
Fuchs, Charles S.
Ryan, David P.
Jain, Rakesh K.
TI Exploratory Analysis of Early Toxicity of Sunitinib in Advanced
Hepatocellular Carcinoma Patients: Kinetics and Potential Biomarker
Value
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PHASE-II TRIAL; SKIN TOXICITY; GROWTH-FACTOR; BEVACIZUMAB; SORAFENIB;
BLOOD; TUMOR; INHIBITORS; CANCER; VEGF
AB Purpose: Sunitinib-a multitargeted tyrosine kinase inhibitor-can modulate circulating inflammatory factors in cancer patients that may be relevant for hepatocellular carcinoma (HCC) progression. However, a recent phase III study of sunitinib in HCC was halted due to its toxicity. Here, we studied the early kinetics of adverse events after sunitinib, and explored their association with circulating proteins and clinical outcome in advanced HCC in a single-arm phase II study.
Experimental Design: Toxicity was evaluated every two weeks during the first cycle of therapy. Biomarker changes from baseline were tested after adjusting for multiple comparisons. Correlation between toxicities and overall survival (OS) or time-to-tumor progression (TTP) was evaluated in a Cox model using log-transformed levels or change in biomarkers, after stratifying by stage and adjusting for baseline level.
Results: Myeloid and lymphoid blood cell counts decreased by 20% to 50% after sunitinib treatment (P < 0.05 for all). The extent of the early decrease in neutrophils and monocytes, and the development of nonhematologic toxicities (i.e., skin toxicities), were significantly associated with both OS and TTP (P < 0.05). Changes in circulating cells significantly associated with specific changes in plasma biomarkers (i.e., changes in platelets with changes in VEGF-C and soluble-VEGFR3; changes in neutrophils with changes in IL-8, TNF-alpha, and soluble-VEGFR2).
Conclusions: The adverse effects of sunitinib, particularly on the hematopoietic system, may be rapid and appear directly related to its activity in HCC. This exploratory study suggests that early hematopoietic toxicities may potentially predict outcome in advanced HCC after sunitinib treatment. Clin Cancer Res; 17(4); 918-27. (C) 2010 AACR.
C1 [Zhu, Andrew X.; Clark, Jeffrey W.; Ryan, David P.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
[Duda, Dan G.; Ancukiewicz, Marek; di Tomaso, Emmanuelle; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Duda, Dan G.; Ancukiewicz, Marek; di Tomaso, Emmanuelle; Miksad, Rebecca; Fuchs, Charles S.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA.
[Miksad, Rebecca] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 55 Fruit St,LH-POB,Room 232, Boston, MA 02114 USA.
EM azhu@partners.org
OI Miksad, Rebecca/0000-0003-3194-5122
FU Pfizer; National Institutes of Health [P01CA80124, R01CA115767]; Federal
Share/NCI Proton Beam Program Income; Harvard Clinical and Translational
Science Center [M01-RR-01066]
FX A.X. Zhu: consultant/advisory board, Genentech, Bayer Pharmaceuticals,
Pfizer. E. di Tomaso: current employment, Novartis. C. S. Fuchs:
consultant/advisory board, Bristol-Myers Squibb, Merck, Roche, Amgen,
Genentech, Alynylam, Imclone Systems, Genomic Health; commercial
research grant, Pfizer. D. P. Ryan: honorarium, Genentech. R. K. Jain:
commercial research grant, Dyax, AstraZeneca, and MedImmune;
consultant/advisory board, AstraZeneca, Dyax, Astellas-Fibrogen,
Regeneron, SynDevRx, Genzyme, Morphosys, and Noxxon Pharma; speaker
honorarium, Genzyme; stock ownership, SynDevRx. D. G. Duda, J. W. Clark,
R. Miksad, and M. Ancukiewicz reported no potential conflicts of
interest.; This study was supported by Pfizer (A. X. Zhu) and
correlative studies were supported in part by National Institutes of
Health Grants P01CA80124, R01CA115767, and Federal Share/NCI Proton Beam
Program Income (R. K. Jain) and by Grant M01-RR-01066, Harvard Clinical
and Translational Science Center.
NR 36
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U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD FEB 15
PY 2011
VL 17
IS 4
BP 918
EP 927
DI 10.1158/1078-0432.CCR-10-0515
PG 10
WC Oncology
SC Oncology
GA 728ZM
UT WOS:000287913200031
PM 20843836
ER
PT J
AU Kenny, EE
Kim, M
Gusev, A
Lowe, JK
Salit, J
Smith, JG
Kovvali, S
Kang, HM
Newton-Cheh, C
Daly, MJ
Stoffel, M
Altshuler, DM
Friedman, JM
Eskin, E
Breslow, JL
Pe'er, I
AF Kenny, Eimear E.
Kim, Minseung
Gusev, Alexander
Lowe, Jennifer K.
Salit, Jacqueline
Smith, J. Gustav
Kovvali, Sirisha
Kang, Hyun Min
Newton-Cheh, Christopher
Daly, Mark J.
Stoffel, Markus
Altshuler, David M.
Friedman, Jeffrey M.
Eskin, Eleazar
Breslow, Jan L.
Pe'er, Itsik
TI Increased power of mixed models facilitates association mapping of 10
loci for metabolic traits in an isolated population
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL;
CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; QUANTITATIVE TRAITS; FOUNDER
POPULATION; COMPLEX TRAITS; WHOLE-GENOME; LINKAGE DISEQUILIBRIUM;
VARIANCE-COMPONENTS
AB The potential benefits of using population isolates in genetic mapping, such as reduced genetic, phenotypic and environmental heterogeneity, are offset by the challenges posed by the large amounts of direct and cryptic relatedness in these populations confounding basic assumptions of independence. Wehave evaluated four representative specialized methods for association testing in the presence of relatedness; (i) within-family (ii) within-and between-family and (iii) mixed-models methods, using simulated traits for 2906 subjects with known genome-wide genotype data from an extremely isolated population, the Island of Kosrae, Federated States of Micronesia. We report that mixed models optimally extract association information from such samples, demonstrating 88% power to rank the true variant as among the top 10 genome-wide with 56% achieving genome-wide significance, a > 80% improvement over the other methods, and demonstrate that population isolates have similar power to non-isolate populations for observing variants of known effects. We then used the mixed-model method to reanalyze data for 17 published phenotypes relating to metabolic traits and electrocardiographic measures, along with another 8 previously unreported. We replicate nine genome-wide significant associations with known loci of plasma cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, thyroid stimulating hormone, homocysteine, C-reactive protein and uric acid, with only one detected in the previous analysis of the same traits. Further, we leveraged shared identity-by-descent genetic segments in the region of the uric acid locus to fine-map the signal, refining the known locus by a factor of 4. Finally, we report a novel associations for height (rs17629022, P < 2.1 x 10(-8)).
C1 [Kenny, Eimear E.; Kim, Minseung; Gusev, Alexander; Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA.
[Kenny, Eimear E.; Salit, Jacqueline; Friedman, Jeffrey M.; Breslow, Jan L.] Rockefeller Univ, New York, NY 10065 USA.
[Lowe, Jennifer K.; Kovvali, Sirisha; Daly, Mark J.; Altshuler, David M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Lowe, Jennifer K.; Daly, Mark J.; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Smith, J. Gustav; Newton-Cheh, Christopher; Altshuler, David M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kang, Hyun Min] Univ Michigan, Bioinformat Grad Program, Ann Arbor, MI 48109 USA.
[Stoffel, Markus] Swiss Fed Inst Technol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
[Eskin, Eleazar] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA.
[Eskin, Eleazar] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90024 USA.
RP Pe'er, I (reprint author), Columbia Univ, Dept Comp Sci, 450 Comp Sci Bldg,500 W 120th St,Mailcode 0401, New York, NY 10027 USA.
EM itsik@cs.columbia.edu
RI Altshuler, David/A-4476-2009; Breslow, Jan/B-7544-2008; Eskin,
Eleazar/J-9187-2012
OI Altshuler, David/0000-0002-7250-4107; Eskin, Eleazar/0000-0003-1149-4758
FU Starr Foundation; Howard Hughes Medical Institute; National Heart, Lung
and Blood Institute [080025]; Doris Duke Charitable Foundation;
Burroughs Wellcome Fund Career Award; Women & Science fellowship;
National Science Foundation [CAREER 0845677, EMT 0829882]
FX This work was supported by grants from the Starr Foundation and Howard
Hughes Medical Institute for all measurement of metabolic traits and
genotypes. Measurements of electrocardiographic traits in Kosrae were
supported by a K23 from the National Heart, Lung and Blood Institute
(grant number 080025), a Doris Duke Charitable Foundation Clinical
Scientist Development Award and a Burroughs Wellcome Fund Career Award
for Medical Scientists to CNC. Support from a Women & Science fellowship
was provided to EEK. Support from the National Science Foundation (grant
numbers CAREER 0845677, EMT 0829882) was provided to IP.
NR 69
TC 12
Z9 13
U1 0
U2 1
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 FEB 15
PY 2011
VL 20
IS 4
BP 827
EP 839
DI 10.1093/hmg/ddq510
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 709VL
UT WOS:000286469400017
PM 21118897
ER
PT J
AU Eccleston, J
Yan, C
Yuan, K
Alt, FW
Selsing, E
AF Eccleston, Jennifer
Yan, Catherine
Yuan, Karen
Alt, Frederick W.
Selsing, Erik
TI Mismatch Repair Proteins MSH2, MLH1, and EXO1 Are Important for
Class-Switch Recombination Events Occurring in B Cells That Lack
Nonhomologous End Joining
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CYTIDINE DEAMINASE AID; SINGLE-STRANDED-DNA; SOMATIC HYPERMUTATION;
ANTIBODY DIVERSIFICATION; LIGASE-IV; MICE; MECHANISM; TRANSLOCATIONS;
DEFICIENCY; ABSENCE
AB In the absence of core nonhomologous end-joining (NHEJ) factors, Ab gene class-switch recombination (CSR) uses an alternative end-joining (A-EJ) pathway to recombine switch (S) region DNA breaks. Previous reports showing decreased S-junction microhomologies in MSH2-deficient mice and an exonuclease 1 (EXO1) role in yeast microhomology-mediated end joining suggest that mismatch repair (MMR) proteins might influence A-EJ-mediated CSR. We have directly investigated whether MMR proteins collectively or differentially influence the A-EJ mechanism of CSR by analyzing CSR in mice deficient in both XRCC4 and individual MMR proteins. We find CSR is reduced and that Igh locus chromosome breaks are reduced in the MMR/XRCC4 double-deficient B cells compared with B cells deficient in XRCC4 alone, suggesting MMR proteins function upstream of double-strand break formation to influence CSR efficiency in these cells. Our results show that MLH1, EXO1, and MSH2 are all important for efficient A-EJ-mediated CSR, and we propose that MMR proteins convert DNA nicks and point mutations into dsDNA breaks for both C-NHEJ and A-EJ pathways of CSR. We also find Mlh1-XRCC4(-) B cells have an increased frequency of direct S junctions, suggesting that MLH1 proteins may have additional functions that influence A-EJ-mediated CSR. The Journal of Immunology, 2011, 186: 2336-2343.
C1 [Eccleston, Jennifer; Yuan, Karen; Selsing, Erik] Tufts Univ, Sch Med, Dept Pathol, Program Immunol, Boston, MA 02111 USA.
[Yan, Catherine] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Expt Pathol, Boston, MA 02115 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Selsing, E (reprint author), Tufts Univ, Sch Med, Dept Pathol, Program Immunol, 150 Harrison Ave, Boston, MA 02111 USA.
EM erik.selsing@tufts.edu
FU National Institutes of Health [AI24465, AI077595]; Eshe Foundation
FX This work was supported by National Institutes of Health Grants AI24465
(to E.S.) and AI077595 (to F.W.A.) and by the Eshe Foundation.
NR 45
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Z9 15
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2011
VL 186
IS 4
BP 2336
EP 2343
DI 10.4049/jimmunol.1003104
PG 8
WC Immunology
SC Immunology
GA 715KF
UT WOS:000286882700054
PM 21242524
ER
PT J
AU Triant, VA
Grinspoon, SK
AF Triant, Virginia A.
Grinspoon, Steven K.
TI Immune Dysregulation and Vascular Risk in HIV-Infected Patients:
Implications for Clinical Care
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID T-CELL COUNT; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS; EVENTS; IMMUNODEFICIENCY;
INTERRUPTION; MEN
C1 [Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nut Metab, Boston, MA 02114 USA.
[Triant, Virginia A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nut Metab, 55 Fruit St,Longfellow 207, Boston, MA 02114 USA.
EM sgrinspoon@partners.org
FU NIAID NIH HHS [K01 AI073109]; NIDDK NIH HHS [K24 DK064545]
NR 22
TC 7
Z9 7
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 15
PY 2011
VL 203
IS 4
BP 439
EP 441
DI 10.1093/infdis/jiq084
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 709VE
UT WOS:000286468700002
PM 21220778
ER
PT J
AU Manzano-Fernandez, S
Januzzi, JL
Boronat-Garcia, M
Bonaque-Gonzalez, JC
Truong, QA
Pastor-Perez, FJ
Munoz-Esparza, C
Pastor, P
Albaladejo-Oton, MD
Casas, T
Valdes, M
Pascual-Figal, DA
AF Manzano-Fernandez, Sergio
Januzzi, James L., Jr.
Boronat-Garcia, Miguel
Carlos Bonaque-Gonzalez, Juan
Truong, Quynh A.
Pastor-Perez, Francisco J.
Munoz-Esparza, Carmen
Pastor, Patricia
Albaladejo-Oton, Maria D.
Casas, Teresa
Valdes, Mariano
Pascual-Figal, Domingo A.
TI beta-Trace Protein and Cystatin C as Predictors of Long-Term Outcomes in
Patients With Acute Heart Failure
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE acute heart failure; beta-trace protein; cystatin C; prognosis
ID PROSTAGLANDIN-D-SYNTHASE; GLOMERULAR-FILTRATION-RATE; RENAL-FUNCTION;
INDEPENDENT PREDICTOR; NATRIURETIC PEPTIDE; RISK STRATIFICATION; SERUM
CONCENTRATION; PROGNOSTIC VALUE; ELDERLY PERSONS; GAMMA-TRACE
AB Objectives The purpose of this study was to evaluate the prognostic importance of novel markers of renal dysfunction among patients with acutely destabilized heart failure (ADHF).
Background beta-trace protein (BTP) and cystatin C are newer biomarkers for renal dysfunction; the prognostic importance of these tests, particularly BTP, relative to standard measures of renal function remains unclear.
Methods A total of 220 consecutive hospitalized patients with ADHF were prospectively studied. Blood samples were collected on presentation. In-hospital worsening renal function, as well as mortality and/or heart failure (HF) hospitalization, over a median follow-up period of 500 days was examined as a function of BTP or cystatin C concentrations; results were compared with creatinine, estimated glomerular filtration rate, and blood urea nitrogen.
Results Neither BTP nor cystatin C was associated with worsening renal function during the index hospitalization. A total of 116 patients (53%) either died or were hospitalized for HF during follow-up. Those with adverse outcomes had higher BTP (1.04 mg/l [range 0.80 to 1.49 mg/l] vs. 0.88 mg/l [range 0.68 to 1.17 mg/l], p = 0.003) and cystatin C (1.29 mg/l [range 1.00 to 1.71 mg/l] vs. 1.03 mg/l [range 0.86 to 1.43 mg/l], p = 0.001). After multivariable adjustment, both BTP (hazard ratio: 1.41, 95% confidence interval: 1.06 to 1.88; p = 0.018) and cystatin C (hazard ratio: 1.50, 95% confidence interval: 1.13 to 2.01; p = 0.006) were significant predictors of death/HF hospitalization, whereas serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen were no longer significant. In patients with an estimated glomerular filtration rate >60 ml/min/1.73 m(2), elevated concentrations of BTP and cystatin C were still associated with significantly higher risk of adverse clinical events (p < 0.05). Net reclassification index analysis suggested cystatin C and BTP deliver comparable information regarding prognosis.
Conclusions Among patients hospitalized with ADHF, BTP and cystatin C predict risk of death and/or HF hospitalization and are superior to standard measures of renal function for this indication. (J Am Coll Cardiol 2011; 57: 849-58) (C) 2011 by the American College of Cardiology Foundation
C1 [Januzzi, James L., Jr.; Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Manzano-Fernandez, Sergio; Carlos Bonaque-Gonzalez, Juan; Pastor-Perez, Francisco J.; Munoz-Esparza, Carmen; Valdes, Mariano; Pascual-Figal, Domingo A.] Univ Hosp Virgen de la Arrixaca, Dept Cardiol, Murcia, Spain.
[Boronat-Garcia, Miguel; Albaladejo-Oton, Maria D.; Casas, Teresa] Univ Hosp Virgen de la Arrixaca, Dept Biochem, Murcia, Spain.
[Pastor, Patricia] Univ Hosp Virgen de la Arrixaca, Dept Gen Surg, Murcia, Spain.
RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,32 Fruit St, Boston, MA 02114 USA.
EM JJanuzzi@partners.org
RI Pascual Figal, Domingo /B-3794-2008
OI Pascual Figal, Domingo /0000-0002-4993-9540
FU Roche Diagnostics; Siemens; Critical Diagnostics
FX Dr. Januzzi, Jr, has received grant support from Roche Diagnostics,
Siemens, and Critical Diagnostics; has served as a consultant to Roche
Diagnostics and Critical Diagnostics; and has received speaking fees
from Roche Diagnostics and Siemens. Dr. Pascual-Figal has received grant
support from Roche Diagnostics. All other authors have reported that
they have no relationships to disclose.
NR 46
TC 39
Z9 42
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 15
PY 2011
VL 57
IS 7
BP 849
EP 858
DI 10.1016/j.jacc.2010.08.644
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 718MK
UT WOS:000287126700014
PM 21310322
ER
PT J
AU Tinaz, S
Courtney, MG
Stern, CE
AF Tinaz, Sule
Courtney, Maureen G.
Stern, Chantal E.
TI Focal Cortical and Subcortical Atrophy in Early Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE MRI; orbitofrontal cortex; emotional dysregulation; cognition
ID HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; HUNTINGTONS-DISEASE;
ALZHEIMERS-DISEASE; COORDINATE SYSTEM; DEMENTIA; BRAIN; SEGMENTATION
AB Neurodegeneration in clinically manifest Parkinson's disease affects the substantia nigra pars compacta, and gradually spreads to the limbic cortices and the neocortex. We used MRI imaging coupled with automated surface reconstruction and segmentation methods to examine cortical thickness and subcortical volumes in nondemented, early-stage Parkinson's disease patients compared to matched healthy control participants. These methods, which have been previously used to document cortical thickness changes in patients with Alzheimer's disease and Huntington's disease but not Parkinson's disease, use MR signal intensity information and the geometric constraints of the cortical and subcortical structures for an accurate tissue classification. Parkinson's disease patients were matched to the control group in psychomotor processing speed and executive functioning, but showed higher anxiety state scores. Our results demonstrated focal cortical thinning in the Parkinson's disease group in the orbitofrontal cortex, ventrolateral prefrontal cortex, and occipito-parietal areas. Subcortically, striatal volume loss was noted. These results demonstrate that both cortical and subcortical structural changes occur at relatively early stages of the disease, and are discussed in terms of the emotional dysregulation that occurs early on in patients with Parkinson's disease. (C) 2010 Movement Disorder Society
C1 [Tinaz, Sule; Courtney, Maureen G.; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA.
[Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Tinaz, S (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St,Room 109, Boston, MA 02215 USA.
EM aysesule.tinaz@nih.gov
FU NIMH [R21 MH066213]; Athinoula A. Martinos Center for Biomedical Imaging
[NCRR P41 RR14075]
FX The study was supported by NIMH award R21 MH066213, and the Athinoula A.
Martinos Center for Biomedical Imaging award (NCRR P41 RR14075).
NR 39
TC 47
Z9 47
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD FEB 15
PY 2011
VL 26
IS 3
BP 436
EP 441
DI 10.1002/23453
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 748UU
UT WOS:000289418900010
PM 21462259
ER
PT J
AU Kimberly, WT
Sheth, KN
AF Kimberly, W. Taylor
Sheth, Kevin N.
TI Approach to Severe Hemispheric Stroke
SO NEUROLOGY
LA English
DT Article
ID MIDDLE CEREBRAL-ARTERY; ISCHEMIC-STROKE; INFARCTION; PREDICTORS;
CRANIECTOMY; MANAGEMENT
C1 [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA.
[Sheth, Kevin N.] Univ Maryland, Med Ctr, Dept Neurol, Div Neurocrit Care & Stroke, Baltimore, MD 21201 USA.
RP Sheth, KN (reprint author), 110 S Paca St,3rd Floor, Baltimore, MD 21201 USA.
EM ksheth@som.umaryland.edu
FU Harvard-MIT Clinical Investigator Training Program; American Academy of
Neurology Foundation; Brainscope
FX Dr. Kimberly has received research support from the Harvard-MIT Clinical
Investigator Training Program and the American Academy of Neurology
Foundation (Clinical Research Fellowship). Dr. Sheth serves on the
editorial boards of Frontiers in Hospitalist Neurology and Neurology
Today; receives publishing royalties for Blueprints Clinical Cases in
Neurology (Lippincott Williams & Wilkins, 2006); and has received
research support from Brainscope and the American Academy of Neurology
Foundation (Clinical Research Fellowship).
NR 15
TC 11
Z9 12
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD FEB 15
PY 2011
VL 76
IS 7
SU 2
BP S50
EP S56
DI 10.1212/WNL.0b013e31820c35f4
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 721NT
UT WOS:000287362300009
PM 21321352
ER
PT J
AU Gesta, S
Bezy, O
Mori, MA
Macotela, Y
Lee, KY
Kahn, CR
AF Gesta, Stephane
Bezy, Olivier
Mori, Marcelo A.
Macotela, Yazmin
Lee, Kevin Y.
Kahn, C. Ronald
TI Mesodermal developmental gene Tbx15 impairs adipocyte differentiation
and mitochondrial respiration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE thiazolidinedione; bioenergetics profile; Oil Red O
ID VISCERAL ADIPOSE-TISSUE; BODY-FAT DISTRIBUTION; IN-VIVO; OBESITY;
METABOLISM; GLUCOSE; ORIGIN; CELLS; IDENTIFICATION; ADIPOGENESIS
AB Increased intraabdominal (visceral) fat is associated with a high risk of diabetes and metabolic syndrome. We have previously shown that the mesodermal developmental transcription factor Tbx15 is highly differentially expressed between visceral and subcutaneous (s.c.) fat in both humans and rodents, and in humans visceral fat Tbx15 expression is decreased in obesity. Here we show that, in mice, Tbx15 is 260-fold more highly expressed in s.c. preadipocytes than in epididymal preadipocytes. Overexpression of Tbx15 in 3T3-L1 preadipocytes impairs adipocyte differentiation and decreases triglyceride content. This defect in differentiation can be corrected by stimulating cells with the PPAR. agonist rosiglitazone (Rosi). However, triglyceride accumulation remains decreased by similar to 50%, due to a decrease in basal lipogenic rate and increase in basal lipolytic rate. 3T3-L1 preadipocytes overexpressing Tbx15 also have a 15% reduction in mitochondrial mass and a 28% reduction in basal mitochondrial respiration (P = 0.004) and ATP turnover (P = 0.02), and a 45% (P = 0.003) reduction in mitochondrial respiratory capacity. Thus, differential expression of Tbx15 between fat depots plays an important role in the interdepot differences in adipocyte differentiation, triglyceride accumulation, and mitochondrial function that may contribute to the risk of diabetes and metabolic disease.
C1 [Gesta, Stephane; Bezy, Olivier; Mori, Marcelo A.; Macotela, Yazmin; Lee, Kevin Y.; Kahn, C. Ronald] Harvard Univ, Sch Med, Dept Integrat Physiol & Metab, Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Dept Integrat Physiol & Metab, Joslin Diabet Ctr, Boston, MA 02215 USA.
EM c.ronald.kahn@joslin.harvard.edu
FU National Institutes of Health [DK82659, DK60837]; Diabetes and
Endocrinology Research Center [DK36836]; Eli Lilly foundation; Loveman
foundation
FX This work was supported in part by National Institutes of Health Grants
DK82659 and DK60837, Diabetes and Endocrinology Research Center Grant
DK36836, the Mary K. Iacocca Professorship, and grants from the Eli
Lilly and Loveman foundations.
NR 43
TC 31
Z9 31
U1 1
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 FEB 15
PY 2011
VL 108
IS 7
BP 2771
EP 2776
DI 10.1073/pnas.1019704108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721TB
UT WOS:000287377000031
PM 21282637
ER
PT J
AU Green, MR
Monti, S
Dalla-Favera, R
Pasqualucci, L
Walsh, NC
Schmidt-Supprian, M
Kutok, JL
Rodig, SJ
Neuberg, DS
Rajewsky, K
Golub, TR
Alt, FW
Shipp, MA
Manis, JP
AF Green, Michael R.
Monti, Stefano
Dalla-Favera, Riccardo
Pasqualucci, Laura
Walsh, Nicole C.
Schmidt-Supprian, Marc
Kutok, Jeffery L.
Rodig, Scott J.
Neuberg, Donna S.
Rajewsky, Klaus
Golub, Todd R.
Alt, Frederick W.
Shipp, Margaret A.
Manis, John P.
TI Signatures of murine B-cell development implicate Yy1 as a regulator of
the germinal center-specific program
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID TRANSCRIPTION FACTORS; GENE-EXPRESSION; BCL-2 EXPRESSION; BINDING;
APOPTOSIS; LINEAGE; MECHANISM; LYMPHOMAS; NETWORKS; PROTEINS
AB We utilized gene expression profiling of a comprehensive panel of purified developmentally defined normal murine B cells to identify unique transcriptional signatures for each subset. To elucidate transcription factor activities that function in a stage-specific fashion, we used gene sets that share transcription factor targets and found that germinal center B cells had a robust enrichment of up-regulated and down-regulated signatures compared with the other B-cell subsets. Notably, we found Yy1 and its targets to be central regulators of the germinal center B (GCB)-specific transcriptional program with binding of Yy1 to select signature genes in GCB cells, and translation of the Yy1 signatures to human GCB cells. We then tested whether our newly generated, stage-specific transcriptional signatures could be used to link murine lymphoma models to stages of normal B-cell development. Although each of the molecularly defined murine lymphoma models conserved certain stage-specific features of normal B-cell development, there was a significant alteration of the normal differentiation signature following malignant transformation. These findings offer important tools and insights for elucidating differences between normal and malignant B cells.
C1 [Green, Michael R.; Rajewsky, Klaus; Alt, Frederick W.; Shipp, Margaret A.; Manis, John P.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Green, Michael R.; Neuberg, Donna S.; Golub, Todd R.; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Monti, Stefano; Golub, Todd R.] Broad Inst, Cambridge, MA 02142 USA.
[Dalla-Favera, Riccardo; Pasqualucci, Laura] Columbia Univ, New York, NY 10032 USA.
[Walsh, Nicole C.; Golub, Todd R.; Alt, Frederick W.; Manis, John P.] Childrens Hosp, Boston, MA 02115 USA.
[Schmidt-Supprian, Marc; Rajewsky, Klaus; Alt, Frederick W.] Immune Dis Inst, Boston, MA 02115 USA.
[Kutok, Jeffery L.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Golub, Todd R.; Alt, Frederick W.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu; margaret_shipp@dfci.harvard.edu;
john.manis@childrens.harvard.edu
RI Schmidt-Supprian, Marc/F-5893-2011; Green, Michael/F-3482-2013;
OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Green,
Michael/0000-0001-6309-9472; Monti, Stefano/0000-0002-9376-0660
FU National Institutes of Health [CA92625]
FX We thank Drs. Carlo Croce, Fritz Melchers, Max Cooper, and Barry
Sleckman for critical review of this manuscript. This work was supported
by National Institutes of Health Grant CA92625. F. W. A. and T. G. are
Investigators of The Howard Hughes Medical Institute.
NR 42
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Z9 23
U1 1
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 15
PY 2011
VL 108
IS 7
BP 2873
EP 2878
DI 10.1073/pnas.1019537108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721TB
UT WOS:000287377000048
PM 21282644
ER
PT J
AU Ahmad, R
Rajabi, H
Kosugi, M
Joshi, MD
Alam, M
Vasir, B
Kawano, T
Kharbanda, S
Kufe, D
AF Ahmad, Rehan
Rajabi, Hasan
Kosugi, Michio
Joshi, Maya Datt
Alam, Maroof
Vasir, Baldev
Kawano, Takeshi
Kharbanda, Surender
Kufe, Donald
TI MUC1-C Oncoprotein Promotes STAT3 Activation in an Autoinductive
Regulatory Loop
SO SCIENCE SIGNALING
LA English
DT Article
ID NF-KAPPA-B; GROWTH-FACTOR RECEPTOR; SIGNAL TRANSDUCER; UNPHOSPHORYLATED
STAT3; RESPONSIVE ELEMENT; CARCINOMA-CELLS; BREAST-CANCER; JAK-STAT;
TRANSCRIPTION-3; PROTEIN
AB Signal transducer and activator of transcription 3 (STAT3) is activated in human breast cancer and other malignancies. Mucin 1 (MUC1) is a heterodimeric cell surface glycoprotein that is overexpressed in human carcinomas and, like STAT3, promotes cell survival and induces transformation. We found that in breast cancer cells, the MUC1 carboxyl-terminal receptor subunit (MUC1-C) associates with the gp130-Janus-activated kinase 1 (JAK1)-STAT3 complex. The MUC1-C cytoplasmic domain interacted directly with JAK1 and STAT3, and MUC1-C was necessary for JAK1-mediated STAT3 activation. In turn, MUC1-C and activated STAT3 occupied the promoter of MUC1, and MUC1-C contributed to STAT3-mediated activation of MUC1 transcription. The MUC1-C inhibitor GO-201 blocked the MUC1-C interaction with STAT3, thereby decreasing MUC1-C and STAT3 occupancy on the MUC1 and STAT3 promoters and activation of STAT3 target genes, including MUC1 itself. These findings indicate that MUC1-C promotes STAT3 activation and that MUC1-C and STAT3 function in an autoinductive loop that may play a role in cancer cell survival.
C1 [Ahmad, Rehan; Rajabi, Hasan; Kosugi, Michio; Joshi, Maya Datt; Alam, Maroof; Vasir, Baldev; Kawano, Takeshi; Kharbanda, Surender; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Kufe, D (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 Funding: This work was supported by grants CA97098, CA42802, and
CA100707 awarded by the National Cancer Institute.
NR 50
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Z9 41
U1 0
U2 8
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 FEB 15
PY 2011
VL 4
IS 160
AR ra9
DI 10.1126/scisignal.2001426
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 721KF
UT WOS:000287351300001
PM 21325207
ER
PT J
AU Carlson, CM
Kirby, KA
Casadei, MA
Partin, MR
Kistler, CE
Walter, LC
AF Carlson, Charlotte M.
Kirby, Katharine A.
Casadei, Michele A.
Partin, Melissa R.
Kistler, Christine E.
Walter, Louise C.
TI Lack of Follow-up After Fecal Occult Blood Testing in Older Adults
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID PRIMARY-CARE PHYSICIANS; COMPLETE DIAGNOSTIC EVALUATION;
COLORECTAL-CANCER; COMORBIDITY INDEX; ELDERLY-PATIENTS; COLON
EVALUATION; NATIONAL-SURVEY; HEALTH-CARE; PATIENT; VETERANS
AB Background: It is unclear whether lack of follow-up after screening fecal occult blood testing (FOBT) in older adults is due to screening patients whose comorbidity or preferences do not permit follow-up vs failure to complete follow-up in healthy patients.
Methods: A prospective cohort study of 2410 patients 70 years or older screened with FOBT was conducted at 4 Veteran Affairs (VA) medical centers from January 1 to December 31, 2001. The main outcome measure was receipt of follow-up within 1 year of FOBT based on national VA and Medicare data. For patients with positive FOBT results, age and Charlson comorbidity scores were evaluated as potential predictors of receiving a complete colon evaluation (colonoscopy or sigmoidoscopy plus barium enema), and medical records were reviewed to determine reasons for lack of follow-up.
Results: A total of 212 patients (9%) had positive FOBT results; 42% received a complete colon evaluation within 1 year. Age and comorbidity were not associated with receipt of a complete follow-up, which was similar among patients 70 to 74 years old with a Charlson score of 0 compared with patients 80 years or older with a Charlson score of 1 or higher (48% vs 41%; P=.28). The VA site, number of positive FOBT cards, and number of VA outpatient visits were predictors. Of 122 patients who did not receive a complete follow-up within 1 year, 38% had documentation that comorbidity or preferences did not permit follow-up, and over the next 5 years 76% never received a complete follow-up.
Conclusions: While follow-up after positive FOBT results was low regardless of age or comorbidity, screening patients in whom complete evaluation would not be pursued substantially contributes to lack of follow-up. Efforts to improve follow-up should address the full chain of decision making, including decisions to screen and decisions to follow up.
C1 [Carlson, Charlotte M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Kirby, Katharine A.; Casadei, Michele A.; Kistler, Christine E.; Walter, Louise C.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA.
[Partin, Melissa R.] Univ Minnesota, Ctr Chron Dis Outcomes Res, Minneapolis VA Med Ctr, Minneapolis, MN 55455 USA.
[Partin, Melissa R.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
RP Walter, LC (reprint author), VA Med Ctr 181G, Div Geriatr, 4150 Clement St, San Francisco, CA 94121 USA.
EM Louise.Walter@ucsf.edu
FU VA Health Services Research and Development [IIR-04-427]; National
Cancer Institute [1R01CA134425]; Center for Chronic Disease Outcomes
Research [HFP 98-001]; [AG000212-16]
FX Dr Walter is supported by a VA Health Services Research and Development
grant IIR-04-427 and by grant 1R01CA134425 from the National Cancer
Institute and is a Robert Wood Johnson Physician Faculty Scholar. Dr
Kistler is supported by a T-32 Training Grant AG000212-16. Dr Partin is
supported by the Center for Chronic Disease Outcomes Research, VA Health
Services Research and Development grant HFP 98-001.
NR 37
TC 18
Z9 18
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD FEB 14
PY 2011
VL 171
IS 3
BP 249
EP 256
DI 10.1001/archinternmed.2010.372
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 721CI
UT WOS:000287328700012
PM 20937917
ER
PT J
AU Milane, L
Duan, ZF
Amiji, M
AF Milane, Lara
Duan, Zhenfeng
Amiji, Mansoor
TI Role of hypoxia and glycolysis in the development of multi-drug
resistance in human tumor cells and the establishment of an orthotopic
multi-drug resistant tumor model in nude mice using hypoxic
pre-conditioning
SO CANCER CELL INTERNATIONAL
LA English
DT Article
ID DRUG-RESISTANCE; CANCER-CELLS; INDUCIBLE FACTOR-1; AEROBIC GLYCOLYSIS;
THERAPY; WARBURG; METASTASIS; INHIBITORS; OXYGEN; GENES
AB Background: The development of multi-drug resistant (MDR) cancer is a significant challenge in the clinical treatment of recurrent disease. Hypoxia is an environmental selection pressure that contributes to the development of MDR. Many cancer cells, including MDR cells, resort to glycolysis for energy acquisition. This study aimed to explore the relationship between hypoxia, glycolysis, and MDR in a panel of human breast and ovarian cancer cells. A second aim of this study was to develop an orthotopic animal model of MDR breast cancer.
Methods: Nucleic and basal protein was extracted from a panel of human breast and ovarian cancer cells; MDR cells and cells pre-exposed to either normoxic or hypoxic conditions. Western blotting was used to assess the expression of MDR markers, hypoxia inducible factors, and glycolytic proteins. Tumor xenografts were established in the mammary fat pad of nu/nu mice using human breast cancer cells that were pre-exposed to either hypoxic or normoxic conditions. Immunohistochemistry was used to assess the MDR character of excised tumors.
Results: Hypoxia induces MDR and glycolysis in vitro, but the cellular response is cell-line specific and duration dependent. Using hypoxic, triple-negative breast cancer cells to establish 100 mm(3) tumor xenografts in nude mice is a relevant model for MDR breast cancer.
Conclusion: Hypoxic pre-conditiong and xenografting may be used to develop a multitude of orthotopic models for MDR cancer aiding in the study and treatment of the disease.
C1 [Milane, Lara; Amiji, Mansoor] Northeastern Univ, Sch Pharm, Dept Pharmaceut Sci, Boston, MA 02115 USA.
[Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA.
RP Amiji, M (reprint author), Northeastern Univ, Sch Pharm, Dept Pharmaceut Sci, 360 Huntington Ave, Boston, MA 02115 USA.
EM m.amiji@neu.edu
RI Amiji, Mansoor/A-4365-2014
OI Amiji, Mansoor/0000-0001-6170-881X
FU National Cancer Institute, National Institutes of Health [R01 CA 119617,
R01 CA 119617S1, R21 CA- 135594]
FX This study was supported by the National Cancer Institute, National
Institutes of Health through grants R01 CA 119617 and R01 CA 119617S1
(ARRA Supplement), and R21 CA- 135594. Husain Attarwala is kindly
thanked for assistance with the animal model development and in vivo
studies.
NR 55
TC 33
Z9 36
U1 0
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2867
J9 CANCER CELL INT
JI Cancer Cell Int.
PD FEB 14
PY 2011
VL 11
AR 3
DI 10.1186/1475-2867-11-3
PG 16
WC Oncology
SC Oncology
GA 728CR
UT WOS:000287852200001
PM 21320311
ER
PT J
AU Leritz, EC
Salat, DH
Williams, VJ
Schnyer, DM
Rudolph, JL
Lipsitz, L
Fischl, B
McGlinchey, RE
Milberg, WP
AF Leritz, Elizabeth C.
Salat, David H.
Williams, Victoria J.
Schnyer, David M.
Rudolph, James L.
Lipsitz, Lewis
Fischl, Bruce
McGlinchey, Regina E.
Milberg, William P.
TI Thickness of the human cerebral cortex is associated with metrics of
cerebrovascular health in a normative sample of community dwelling older
adults
SO NEUROIMAGE
LA English
DT Article
DE Aging; Cerebrovascular health; Cerebrovascular risk; Cortical thickness;
Brain structure
ID WHITE-MATTER LESIONS; MEDIAL TEMPORAL-LOBE; MILD COGNITIVE IMPAIRMENT;
MAGNETIC-RESONANCE IMAGES; SYSTOLIC BLOOD-PRESSURE; SURFACE-BASED
ANALYSIS; 6-YEAR FOLLOW-UP; ALZHEIMERS-DISEASE; CORTICAL SURFACE;
RISK-FACTORS
AB We examined how wide ranges in levels of risk factors for cerebrovascular disease are associated with thickness of the human cerebral cortex in 115 individuals ages 43-83 with no cerebrovascular or neurologic history. Cerebrovascular risk factors included blood pressure, cholesterol, body mass index, creatinine, and diabetes-related factors. Variables were submitted into a principal components analysis that confirmed four orthogonal factors (blood pressure, cholesterol, cholesterol/metabolic and glucose). T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness. Increasing blood pressure factor scores were associated with numerous regions of reduced thickness. Increasing glucose scores were modestly associated with areas of regionally decreased thickness. Increasing cholesterol scores, in contrast, were associated with thicker cortex across the whole brain. All findings were primarily independent of age. These results provide evidence that normal and moderately abnormal levels of parameters used to assess cerebrovascular health may impact brain structure, even in the absence of cerebrovascular disease. Our data have important implications for the clinical management of vascular health, as well as for what is currently conceptualized as "normal aging" as they suggest that subclinical levels of risk may impact cortical gray matter before a disease process is evident. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Leritz, Elizabeth C.; Salat, David H.; Williams, Victoria J.; Rudolph, James L.; McGlinchey, Regina E.; Milberg, William P.] VA Boston Healthcare Syst, GRECC, Boston, MA USA.
[Leritz, Elizabeth C.; Williams, Victoria J.; Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Leritz, Elizabeth C.; Salat, David H.; Lipsitz, Lewis; McGlinchey, Regina E.; Milberg, William P.] Harvard Univ, Sch Med, Boston, MA USA.
[Leritz, Elizabeth C.; Salat, David H.; Williams, Victoria J.; Fischl, Bruce] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Fischl, Bruce] MIT, CSAIL HST, Cambridge, MA 02139 USA.
[Lipsitz, Lewis] Beth Israel Deaconess Med Ctr, Gerontol Div, Hebrew Senior Life Inst Aging Res, Boston, MA 02215 USA.
[Schnyer, David M.] Univ Texas Austin, Austin, TX 78712 USA.
RP Leritz, EC (reprint author), 150 S Huntington Ave,GRECC 182 JP, Boston, MA 02130 USA.
EM bleritz@nmr.mgh.harvard.edu
RI McGlinchey, Regina/R-1971-2016;
OI Kennedy, Kristen/0000-0001-5373-9026
FU National Institute of Neurologic Disorders and Stroke [K23NS062148,
K23NS06214802S1, R01NS052585]; National Institute of Nursing Research
[R01NR010827]; National Institute on Aging [P60AG08812, P01AG004390,
K01AG24898, AG02238]; Medical Research Service VA; National Institutes
of Health through the Roadmap for Medical Research [P41-RR14075,
BIRN002, U24 RR021382, R01EB006758, U54 EB005149]
FX This work was supported by the National Institute of Neurologic
Disorders and Stroke (grant numbers K23NS062148, K23NS06214802S1 and
R01NS052585); the National Institute of Nursing Research (grant number
R01NR010827), the National Institute on Aging (grant numbers P60AG08812,
P01AG004390, K01AG24898 and AG02238); and by Medical Research Service VA
Merit Review Awards to William Milberg and Regina McGlinchey. Further
support was provided in part by the National Center for Research
Resources (grant number P41-RR14075), and the NCRR BIRN Morphometric
Project (grant numbers BIRN002 and U24 RR021382), the National Institute
for Biomedical Imaging and Bioengineering (grant number R01EB006758), as
well as the Mental Illness and Neuroscience Discovery (MIND) Institute,
and is part of the National Alliance for Medical Image Computing
(NAMIC), funded by the National Institutes of Health through the Roadmap
for Medical Research (grant number U54 EB005149). Additional support was
provided by The Autism & Dyslexia Project funded by the Ellison Medical
Foundation. The authors would like to thank Marge Ahlquist for her
assistance with BP collection and phlebotomy on all participants.
NR 72
TC 49
Z9 49
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 14
PY 2011
VL 54
IS 4
BP 2659
EP 2671
DI 10.1016/j.neuroimage.2010.10.050
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 710FH
UT WOS:000286495800012
PM 21035552
ER
PT J
AU Chan, AM
Halgren, E
Marinkovic, K
Cash, SS
AF Chan, Alexander M.
Halgren, Eric
Marinkovic, Ksenija
Cash, Sydney S.
TI Decoding word and category-specific spatiotemporal representations from
MEG and EEG
SO NEUROIMAGE
LA English
DT Article
DE Language; Semantic category; Machine learning; Decoding; MEG; EEG
ID CONCEPTUAL KNOWLEDGE; BRAIN POTENTIALS; DISTRIBUTED ACCOUNT; NEURAL
BASIS; LANGUAGE; DYNAMICS; MAGNETOENCEPHALOGRAPHY; ELECTROENCEPHALOGRAM;
ORGANIZATION; RECOGNITION
AB The organization and localization of lexico-semantic information in the brain has been debated for many years. Specifically, lesion and imaging studies have attempted to map the brain areas representing living versus nonliving objects, however, results remain variable. This may be due, in part, to the fact that the univariate statistical mapping analyses used to detect these brain areas are typically insensitive to subtle, but widespread, effects. Decoding techniques, on the other hand, allow for a powerful multivariate analysis of multichannel neural data. In this study, we utilize machine-learning algorithms to first demonstrate that semantic category, as well as individual words, can be decoded from EEG and MEG recordings of subjects performing a language task. Mean accuracies of 76% (chance = 50%) and 83% (chance = 20%) were obtained for the decoding of living vs. nonliving category or individual words respectively. Furthermore, we utilize this decoding analysis to demonstrate that the representations of words and semantic category are highly distributed both spatially and temporally. In particular, bilateral anterior temporal, bilateral inferior frontal, and left inferior temporal-occipital sensors are most important for discrimination. Successful intersubject and intermodality decoding shows that semantic representations between stimulus modalities and individuals are reasonably consistent. These results suggest that both word and category-specific information are present in extracranially recorded neural activity and that these representations may be more distributed, both spatially and temporally, than previous studies suggest. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Chan, Alexander M.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Chan, Alexander M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Halgren, Eric; Marinkovic, Ksenija] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
RP Chan, AM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Thier 423,55 Fruit St, Boston, MA 02114 USA.
EM amchan@mit.edu
FU NDSEG Fellowship; Frank H. Buck Scholarship; Rappaport Fellowship; NIH
[NS18741]
FX This work was supported by an NDSEG Fellowship and a Frank H. Buck
Scholarship to AMC and a Rappaport Fellowship to SSC. Overall support
was provided by NIH grant NS18741. We thank J.M. Baker, A.R. Dykstra,
C.J. Keller, F.E. McAllister, H. McAllister, N. Dehghani, J. Cormier,
L.R. Hochberg, R. Zepeda, J. Donoghue, C. Sherman, C. Raclin, I.
Sukhotinsky, S.S. Hou, and G.C. Sing for their helpful comments.
NR 54
TC 45
Z9 45
U1 2
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD FEB 14
PY 2011
VL 54
IS 4
BP 3028
EP 3039
DI 10.1016/j.neuroimage.2010.10.073
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 710FH
UT WOS:000286495800044
PM 21040796
ER
PT J
AU Tao, H
Manak, JR
Sowers, L
Mei, X
Kiyonari, H
Abe, T
Dandaleh, NS
Yang, TA
Wu, S
Chen, S
Fox, MH
Gurnett, C
Montine, T
Bird, T
Shaffer, LG
Rosenfeld, JA
McConne, J
Madan-Khetarpal, S
Berry-Kravis, E
Griesbach, H
Saneto, RP
Scott, MP
Antic, D
Reed, J
Boland, R
Ehaideb, SN
El-Shanti, H
Mahajan, VB
Ferguson, PJ
Axelrod, JD
Lehesjoki, AE
Fritzsch, B
Slusarski, DC
Wemmie, J
Ueno, N
Bassuk, AG
AF Tao, Hirotaka
Manak, J. Robert
Sowers, Levi
Mei, Xue
Kiyonari, Hiroshi
Abe, Takaya
Dandaleh, Nader S.
Yang, Tian
Wu, Shu
Chen, Shan
Fox, Mark H.
Gurnett, Christina
Montine, Thomas
Bird, Thomas
Shaffer, Lisa G.
Rosenfeld, Jill A.
McConne, Juliann
Madan-Khetarpal, Suneeta
Berry-Kravis, Elizabeth
Griesbach, Hilary
Saneto, Russell P.
Scott, Matthew P.
Antic, Dragana
Reed, Jordan
Boland, Riley
Ehaideb, Salleh N.
El-Shanti, Hatem
Mahajan, Vinit B.
Ferguson, Polly J.
Axelrod, Jeffrey D.
Lehesjoki, Anna-Elina
Fritzsch, Bernd
Slusarski, Diane C.
Wemmie, John
Ueno, Naoto
Bassuk, Alexander G.
TI Mutations in Prickle Orthologs Cause Seizures in Flies, Mice, and Humans
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID PROGRESSIVE MYOCLONUS EPILEPSY; PLANAR CELL POLARITY;
DROSOPHILA-MELANOGASTER; NEURON MIGRATION; MOUSE PRICKLE1; GENE;
ZEBRAFISH; GASTRULATION; MOVEMENTS; CHANNEL
AB Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution.
C1 [Tao, Hirotaka; Ueno, Naoto] Natl Inst Basic Biol, Div Morphogenesis, Okazaki, Aichi 4448585, Japan.
[Manak, J. Robert; Mei, Xue; Yang, Tian; Reed, Jordan; Boland, Riley; Ehaideb, Salleh N.; Fritzsch, Bernd; Slusarski, Diane C.] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA.
[Sowers, Levi; Wu, Shu; Chen, Shan; Fox, Mark H.; El-Shanti, Hatem; Ferguson, Polly J.; Bassuk, Alexander G.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA.
[Kiyonari, Hiroshi; Abe, Takaya] RIKEN Ctr Dev Biol, Lab Anim Resources & Genet Engn, Chuo Ku, Kobe, Hyogo 650047, Japan.
[Dandaleh, Nader S.] Univ Iowa, Dept Neurosurg, Carver Coll Med, Iowa City, IA 52242 USA.
[Gurnett, Christina] Washington Univ, Dept Neurol, St Louis, MO 63310 USA.
[Montine, Thomas] Univ Washington, Dept Pathol, Seattle, WA 98104 USA.
[Bird, Thomas] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98104 USA.
[Shaffer, Lisa G.; Rosenfeld, Jill A.] Signature Genom Labs, Spokane, WA 99202 USA.
[McConne, Juliann; Madan-Khetarpal, Suneeta] Childrens Hosp Pittsburgh UPMC, Pittsburgh, PA 15224 USA.
[Berry-Kravis, Elizabeth] Rush Presbyterian St Lukes Med Ctr, Dept Pediat, Chicago, IL 60612 USA.
[Berry-Kravis, Elizabeth] Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Berry-Kravis, Elizabeth] Rush Presbyterian St Lukes Med Ctr, Dept Biochem, Chicago, IL 60612 USA.
[Saneto, Russell P.] Seattle Childrens Hosp, Div Pediat Neurol, Seattle, WA 98105 USA.
[Scott, Matthew P.; Antic, Dragana] Stanford Univ, Sch Med, Dept Dev Biol, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Scott, Matthew P.; Antic, Dragana] Stanford Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Scott, Matthew P.; Antic, Dragana] Stanford Univ, Sch Med, Dept Bioengn, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Antic, Dragana; Axelrod, Jeffrey D.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[El-Shanti, Hatem] Shafallah Med Genet Ctr, Doha 33123, Qatar.
[Mahajan, Vinit B.] Univ Iowa, Dept Ophthalmol & Visual Sci, Carver Coll Med, Iowa City, IA 52242 USA.
[Lehesjoki, Anna-Elina] Univ Helsinki, Folkhalsan Inst Genet, FIN-00014 Helsinki, Finland.
[Lehesjoki, Anna-Elina] Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland.
[Wemmie, John] Univ Iowa, Dept Psychiat, Ia City, IA 52242 USA.
[Wemmie, John] Univ Iowa, Dept Neurosurg, Neurosci Program, Roy J & Lucille A Carver Coll Med, Ia City, IA 52242 USA.
[Wemmie, John] Dept Vet Affairs Med Ctr, Iowa City, IA 52242 USA.
[Ueno, Naoto] Grad Univ Adv Studies SOKENDAI, Dept Basic Biol, Sch Life Sci, Okazaki, Aichi 4448585, Japan.
RP Ueno, N (reprint author), Natl Inst Basic Biol, Div Morphogenesis, 38 Nishigonaka, Okazaki, Aichi 4448585, Japan.
EM nueno@nibb.ac.jp; alexander-bassuk@uiowa.edu
RI Kiyonari, Hiroshi/N-7936-2015; EL-SHANTI, HATEM/Q-4932-2016;
OI EL-SHANTI, HATEM/0000-0001-6230-8316; Fritzsch,
Bernd/0000-0002-4882-8398
FU National Institutes of Health [R01 NS064159, 3R01NS064159-02S1, R01
GM059823, RO1 CA112369, P50 AG05136, 1R21NS058309-01A1]; VA; Howard
Hughes Medical Institute
FX This work was supported by National Institutes of Health grants R01
NS064159 and 3R01NS064159-02S1 (to A.G.B.), R01 GM059823 (to J.D.A.),
RO1 CA112369 (to D.C.S.), and P50 AG05136 (to T.M.), by
1R21NS058309-01A1 (to J.W.), by a VA Merit Review Award (to J.W.), and
by a grant from the Howard Hughes Medical Institute (to M.S.). We thank
Jeff Murray, Jeff Neul, Val Sheffield, Bev Davidson, Zoha Kibar, Heather
Mefford, and Sam Berkovic for their thoughtful reviews. We thank Jeff
Murray for access to the CEPH-HGD samples and Taqman assay. L.G.S. and
J.A.R. are employed by Signature Genomics Laboratories.
NR 57
TC 46
Z9 50
U1 0
U2 6
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 FEB 11
PY 2011
VL 88
IS 2
BP 138
EP 149
DI 10.1016/j.ajhg.2010.12.012
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 725YZ
UT WOS:000287684100002
PM 21276947
ER
PT J
AU Jang, C
Choi, JK
Kim, E
Park, ES
Wasco, W
Buxbaum, JD
Kim, YS
Choi, EK
AF Jang, Changhwan
Choi, Jin-Kyu
Kim, EunYoung
Park, Eun-Su
Wasco, Wilma
Buxbaum, Joseph D.
Kim, Yong-Sun
Choi, Eun-Kyoung
TI Calsenilin is degraded by the ubiquitin-proteasome pathway
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Calsenilin; Proteasome; Ubiquitin
ID CAPACITATIVE CALCIUM-ENTRY; ALZHEIMERS-DISEASE; ENDOPLASMIC-RETICULUM;
MEDIATED DEGRADATION; PROTEIN-DEGRADATION; POTASSIUM CHANNELS;
PRESENILIN; CALSENILIN/DREAM/KCHIP3; MODULATION; EXPRESSION
AB Calsenilin, a neuronal calcium binding protein that has been shown to have multiple functions in the cell, interacts with presenilin 1 (PS1) and presenilin 2 (PS2), represses gene transcription and binds to A-type voltage-gated potassium channels. In addition, increased levels of calsenilin are observed in the brains of Alzheimer's disease and epilepsy patients. The present study was designed to investigate the molecular mechanism of calsenilin degradation pathways in cultured cells. Here, we demonstrate that inhibition of the ubiquitin-proteasomal pathway (UPP) but not lysosomal pathway markedly increased the expression levels of calsenilin. Immunofluorescence analysis revealed that following proteasomal inhibition calsenilin accumulated in the endoplasmic reticulum (ER) and Golgi, while lysosomal inhibition had no effect on calsenilin localization. In addition, we found the change of subcellular localization of PS1 from diffuse pattern to punctuate staining pattern in the ER and perinuclear region in the presence of calsenilin. These findings suggest that calsenilin degradation is primarily mediated by the UPP and that impairment in the UPP may contribute to the involvement of calsenilin in disease-associated neurodegeneration. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Choi, Eun-Kyoung] Hallym Univ, Ilsong Inst Life Sci, Lab Cellular Aging & Neurodegenerat, Anyang 431060, Gyeonggi Do, South Korea.
[Jang, Changhwan; Kim, Yong-Sun] Hallym Univ, Coll Med, Dept Microbiol, Chunchon, South Korea.
[Wasco, Wilma] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA.
[Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat & Neurobiol, Lab Mol Neuropsychiat, New York, NY 10029 USA.
RP Choi, EK (reprint author), Hallym Univ, Ilsong Inst Life Sci, Lab Cellular Aging & Neurodegenerat, 1605-4 Gwanyang Dong, Anyang 431060, Gyeonggi Do, South Korea.
EM ekchoi@hallym.ac.kr
OI Buxbaum, Joseph/0000-0001-8898-8313
FU Ministry of Education, Science and Technology [2010-0001262]; Korean
Government (MOEHRD) [KRF-2006-331-E00287]
FX We thank Drs. J.H. Boo and H.S. Hong for helpful discussions and Dr. W.
Xia for providing WT PSI cDNA. This research was supported by Basic
Science Research Program through the National Research Foundation of
Korea (NRF) funded by the Ministry of Education, Science and Technology
(2010-0001262) and the Korea Research Foundation grant funded by Korean
Government (MOEHRD, Basic Research Promotion Fund)
[KRF-2006-331-E00287].
NR 36
TC 4
Z9 4
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD FEB 11
PY 2011
VL 405
IS 2
BP 180
EP 185
DI 10.1016/j.bbrc.2010.12.137
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 725EH
UT WOS:000287627500006
PM 21216226
ER
PT J
AU Nichols, FC
Yao, XD
Bajrami, B
Downes, J
Finegold, SM
Knee, E
Gallagher, JJ
Housley, WJ
Clark, RB
AF Nichols, Frank C.
Yao, Xudong
Bajrami, Bekim
Downes, Julia
Finegold, Sydney M.
Knee, Erica
Gallagher, James J.
Housley, William J.
Clark, Robert B.
TI Phosphorylated Dihydroceramides from Common Human Bacteria Are Recovered
in Human Tissues
SO PLOS ONE
LA English
DT Article
ID PORPHYROMONAS-GINGIVALIS LIPIDS; SYSTEMIC INNATE IMMUNITY;
RHEUMATOID-ARTHRITIS; MICROBIOTA; PERIODONTITIS; ASSOCIATION; DISEASE
AB Novel phosphorylated dihydroceramide (PDHC) lipids produced by the periodontal pathogen Porphyromonas gingivalis include phosphoethanolamine (PE DHC) and phosphoglycerol dihydroceramides (PG DHC) lipids. These PDHC lipids mediate cellular effects through Toll-like receptor 2 (TLR2) including promotion of IL-6 secretion from dendritic cells and inhibition of osteoblast differentiation and function in vitro and in vivo. The PE DHC lipids also enhance (TLR2)-dependent murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. The unique non-mammalian structures of these lipids allows for their specific quantification in bacteria and human tissues using multiple reaction monitoring (MRM)-mass spectrometry (MS). Synthesis of these lipids by other common human bacteria and the presence of these lipids in human tissues have not yet been determined. We now report that synthesis of these lipids can be attributed to a small number of intestinal and oral organisms within the Bacteroides, Parabacteroides, Prevotella, Tannerella and Porphyromonas genera. Additionally, the PDHCs are not only present in gingival tissues, but are also present in human blood, vasculature tissues and brain. Finally, the distribution of these TLR2-activating lipids in human tissues varies with both the tissue site and disease status of the tissue suggesting a role for PDHCs in human disease.
C1 [Nichols, Frank C.; Knee, Erica] Univ Connecticut, Sch Dent Med, Dept Oral Hlth & Diagnost Sci, Farmington, CT 06032 USA.
[Yao, Xudong; Bajrami, Bekim] Univ Connecticut, Dept Chem, Storrs, CT USA.
[Downes, Julia; Finegold, Sydney M.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA.
[Gallagher, James J.] Univ Connecticut, Sch Med, Dept Surg, Farmington, CT 06032 USA.
[Gallagher, James J.] Connecticut Vasc Inst, Hartford, CT USA.
[Housley, William J.; Clark, Robert B.] Univ Connecticut, Sch Med, Dept Immunol, Farmington, CT 06032 USA.
[Housley, William J.; Clark, Robert B.] Univ Connecticut, Sch Med, Dept Med, Farmington, CT 06032 USA.
RP Nichols, FC (reprint author), Univ Connecticut, Sch Dent Med, Dept Oral Hlth & Diagnost Sci, Farmington, CT 06032 USA.
EM nichols@nso.uchc
FU National Multiple Sclerosis Society [RG4070-A-6]
FX This work was supported by a grant from the National Multiple Sclerosis
Society (RG4070-A-6). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 21
TC 10
Z9 11
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 11
PY 2011
VL 6
IS 2
AR e16771
DI 10.1371/journal.pone.0016771
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721OO
UT WOS:000287364500005
PM 21347306
ER
PT J
AU El Saleeby, CM
Grottkau, BE
Friedmann, AM
Westra, SJ
Sohani, AR
AF El Saleeby, Chadi M.
Grottkau, Brian E.
Friedmann, Alison M.
Westra, Sjirk J.
Sohani, Aliyah R.
TI Case 4-2011: A 4-Year-Old Boy with Back Pain and Hypercalcemia B
lymphoblastic leukemia, not otherwise specified
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ORTHOPEDIC MANIFESTATIONS; PEDIATRIC-PATIENTS; BONE PAIN; CHILDREN;
MANAGEMENT; ARTHRITIS; LYMPHOMA; CRLF2
C1 [El Saleeby, Chadi M.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hosp Med & Infect Dis, Boston, MA 02114 USA.
[Grottkau, Brian E.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Orthoped Surg, Boston, MA 02114 USA.
[Friedmann, Alison M.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Oncol, Boston, MA 02114 USA.
[Westra, Sjirk J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[El Saleeby, Chadi M.; Friedmann, Alison M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Grottkau, Brian E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Westra, Sjirk J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP El Saleeby, CM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hosp Med & Infect Dis, Boston, MA 02114 USA.
FU Harvard Medical School Office of Continuing Education
FX This case was presented at the postgraduate course Primary Care
Pediatrics, sponsored by the Harvard Medical School Office of Continuing
Education.
NR 35
TC 4
Z9 4
U1 0
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 10
PY 2011
VL 364
IS 6
BP 552
EP 562
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 718QH
UT WOS:000287139900012
PM 21306242
ER
PT J
AU Giralt, SA
Horowitz, M
Weisdorf, D
Cutler, C
AF Giralt, Sergio A.
Horowitz, Mary
Weisdorf, Daniel
Cutler, Corey
TI Review of Stem-Cell Transplantation for Myelodysplastic Syndromes in
Older Patients in the Context of the Decision Memo for Allogeneic
Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome
Emanating From the Centers for Medicare and Medicaid Services
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; DAILY INTRAVENOUS
BUSULFAN; PROGNOSTIC SCORING SYSTEM; IDENTICAL SIBLING DONOR; HIGH-RISK;
CONDITIONING REGIMEN; PREDICTING SURVIVAL; CLINICAL-OUTCOMES; UNRELATED
DONORS
AB Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem-cell disorders that result in varying degrees of cytopenia and risk of transformation into acute leukemia. Allogeneic stem-cell transplantation (SCT) is the only known cure for this disease. The treatment is routinely used for younger patients, but only a minority of patients older than the age of 60 undergo this procedure. The overall MDS incidence is 3.3 per 100,000, but the incidence in patients older than age 70 is between 15 and 50 per 100,000. The median age at presentation is 76 years. Medicare-age patients 65 or older represent 80% of the total population receiving an MDS diagnosis. In the United States, one of the obstacles to SCT for older patients with MDS has been lack of third party reimbursement. On August 4, 2010, the Centers for Medicare and Medicaid Services released their Decision Memo for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Myelodysplastic Syndrome. This memo states: "Allogeneic HSCT for MDS is covered by Medicare only for beneficiaries with MDS participating in an approved clinical study that meets the criteria below ... . " In this review, we will summarize what is known regarding the role of allogeneic SCT in older patients as well as other elements that should be included within clinical trials that can provide the evidence necessary to demonstrate that allogeneic SCT should be a covered benefit for Medicare beneficiaries. J Clin Oncol 29:566-572. (C) 2011 by American Society of Clinical Oncology
C1 [Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplant Program, New York, NY 10065 USA.
Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA.
Univ Minnesota, Minneapolis, MN USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Giralt, SA (reprint author), Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplant Program, 1275 York Ave,Box 235, New York, NY 10065 USA.
EM giralts@mskcc.org
FU NHLBI NIH HHS [U10 HL069315]
NR 70
TC 12
Z9 13
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 10
PY 2011
VL 29
IS 5
BP 566
EP 572
DI 10.1200/JCO.2010.32.1919
PG 7
WC Oncology
SC Oncology
GA 717XX
UT WOS:000287082900022
PM 21220586
ER
PT J
AU Ross, DS
AF Ross, Douglas S.
TI Radioiodine Therapy for Hyperthyroidism.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MULTINODULAR TOXIC GOITER; DOSE I-131 THERAPY; GRAVES-DISEASE;
RADIOACTIVE IODINE; ANTITHYROID DRUGS; THYROID-NODULES; FOLLOW-UP;
CANCER INCIDENCE; OPHTHALMOPATHY; LONG
AB A 37-year-old woman presented with palpitations, tremulousness, shortness of breath, and a 9-kg (20-lb) weight loss, and received a diagnosis of Graves' hyperthyroidism. At the time of diagnosis, she had mild proptosis, no diplopia, and no signs of eye inflammation. Her thyroid gland was two times the normal size and non-nodular. Her initial serum triiodothyronine (T(3)) concentration was 655 ng per deciliter (9.2 nmol per liter), and her free thyroxine (T(4)) concentration was 5.7 ng per deciliter (73 pmol per liter). She was treated with methimazole for a year, and her thyroid tests became normal. She discontinued the methimazole 10 weeks before the current presentation with recurrent palpitations and tremulousness. Her serum T(3) concentration is 345 ng per deciliter (5.4 nmol per liter), and her free T(4) concentration is 2.8 ng per deciliter (36.0 pmol per liter). The patient does not smoke. She has a 3-year-old daughter and wishes to become pregnant again. Her endocrinologist recommends radioiodine ablation of her thyroid.
C1 Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA.
RP Ross, DS (reprint author), Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA.
NR 49
TC 42
Z9 54
U1 1
U2 18
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 FEB 10
PY 2011
VL 364
IS 6
BP 542
EP 550
DI 10.1056/NEJMct1007101
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 718QH
UT WOS:000287139900008
PM 21306240
ER
PT J
AU Ng, S
Fanta, C
Okam, M
Bhatt, AS
AF Ng, Samuel
Fanta, Christopher
Okam, Maureen
Bhatt, Ami S.
TI NK-Cell and B-Cell Deficiency with a Thymic Mass
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Ng, Samuel; Fanta, Christopher; Okam, Maureen] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bhatt, Ami S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Ng, S (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM asbhatt@partners.org
NR 5
TC 4
Z9 4
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 10
PY 2011
VL 364
IS 6
BP 586
EP 588
DI 10.1056/NEJMc1012485
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 718QH
UT WOS:000287139900041
PM 21306273
ER
PT J
AU Li, Q
Haigis, KM
McDaniel, A
Harding-Theobald, E
Kogan, SC
Akagi, K
Wong, JCY
Braun, BS
Wolff, L
Jacks, T
Shannon, K
AF Li, Qing
Haigis, Kevin M.
McDaniel, Andrew
Harding-Theobald, Emily
Kogan, Scott C.
Akagi, Keiko
Wong, Jasmine C. Y.
Braun, Benjamin S.
Wolff, Linda
Jacks, Tyler
Shannon, Kevin
TI Hematopoiesis and leukemogenesis in mice expressing oncogenic Nras(G12D)
from the endogenous locus
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; K-RAS ONCOGENE; SOMATIC ACTIVATION; N-RAS;
MYELOPROLIFERATIVE DISORDER; ERYTHROID-DIFFERENTIATION; CONDITIONAL
EXPRESSION; SIGNAL-TRANSDUCTION; HYPERACTIVE RAS; HUMAN CANCER
AB NRAS is frequently mutated in hematologic malignancies. We generated Mx1-Cre, Lox-STOP-Lox (LSL)-Nras(G12D) mice to comprehensively analyze the phenotypic, cellular, and biochemical consequences of endogenous oncogenic Nras expression in hematopoietic cells. Here we show that Mx1-Cre, LSL-Nras(G12D) mice develop an indolent myeloproliferative disorder but ultimately die of a diverse spectrum of hematologic cancers. Expressing mutant Nras in hematopoietic tissues alters the distribution of hematopoietic stem and progenitor cell populations, and Nras mutant progenitors show distinct responses to cytokine growth factors. Injecting Mx1-Cre, LSL-Nras(G12D) mice with the MOL4070LTR retrovirus causes acute myeloid leukemia that faithfully recapitulates many aspects of human NRAS-associated leukemias, including cooperation with deregulated Evi1 expression. The disease phenotype in Mx1-Cre, LSL-Nras(G12D) mice is attenuated compared with Mx1-Cre, LSL-Kras(G12D) mice, which die of aggressive myeloproliferative disorder by 4 months of age. We found that endogenous Kras(G12D) expression results in markedly elevated Ras protein expression and Ras-GTP levels in Mac1(+) cells, whereas Mx1-Cre, LSL-Nras(G12D) mice show much lower Ras protein and Ras-GTP levels. Together, these studies establish a robust and tractable system for interrogating the differential properties of oncogenic Ras proteins in primary cells, for identifying candidate cooperating genes, and for testing novel therapeutic strategies. (Blood. 2011; 117(6): 2022-2032)
C1 [McDaniel, Andrew; Harding-Theobald, Emily; Wong, Jasmine C. Y.; Braun, Benjamin S.; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
[Li, Qing] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA.
[Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA.
[Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
[Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94158 USA.
[Kogan, Scott C.; Shannon, Kevin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.
[Akagi, Keiko] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol, Columbus, OH 43210 USA.
[Akagi, Keiko] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol, Columbus, OH 43210 USA.
[Akagi, Keiko] Ohio State Univ, Ctr Comprehens Canc, Dept Med Genet, Columbus, OH 43210 USA.
[Wolff, Linda] NCI, Cellular Oncol Lab, Frederick, MD 21701 USA.
[Jacks, Tyler] MIT, Ctr Canc Res, Cambridge, MA 02139 USA.
[Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Shannon, K (reprint author), Univ Calif San Francisco, Dept Pediat, Helen Diller Family Canc Res Bldg,1450 3rd St,Rm, San Francisco, CA 94158 USA.
EM shannonk@peds.ucsf.edu
FU National Institutes of Health [U01 CA84221, R37 CA72614, K01 CA118425,
K08 CA134649, K08 CA119105, T32 CA129583]; Leukemia & Lymphoma Society;
Jeffrey and Karen Peterson Family Foundation; Frank A. Campini
Foundation; National Cancer Institute Center for Cancer Research
FX This work was supported by the National Institutes of Health (grants U01
CA84221, R37 CA72614, K01 CA118425, K08 CA134649, K08 CA119105, and T32
CA129583), the Leukemia & Lymphoma Society, the Jeffrey and Karen
Peterson Family Foundation, and the Frank A. Campini Foundation. T.J. is
an Investigator of the Howard Hughes Medical Institute. S.C.K. is a
Leukemia & Lymphoma Society Scholar. The Intramural Research Program of
the National Cancer Institute Center for Cancer Research supports
research in the laboratory of L.W.
NR 46
TC 56
Z9 57
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 10
PY 2011
VL 117
IS 6
BP 2022
EP 2032
DI 10.1182/blood-2010-04-280750
PG 11
WC Hematology
SC Hematology
GA 719HA
UT WOS:000287192300039
PM 21163920
ER
PT J
AU Bejar, R
Levine, R
Ebert, BL
AF Bejar, Rafael
Levine, Ross
Ebert, Benjamin L.
TI Unraveling the Molecular Pathophysiology of Myelodysplastic Syndromes
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID ACUTE MYELOID-LEUKEMIA; THERAPY-RELATED MYELODYSPLASIA; CHRONIC
MYELOMONOCYTIC LEUKEMIA; FAMILIAL PLATELET DISORDER; METHYLTRANSFERASE
GENE EZH2; AML1/RUNX1 POINT MUTATIONS; CHROMOSOME 5Q DELETION;
THROMBOCYTOSIS RARS-T; UNIPARENTAL DISOMY; C-CBL
AB Somatically acquired genetic abnormalities lead to the salient features that define myelodysplastic syndromes (MDS): clonal hematopoiesis, aberrant differentiation, peripheral cytopenias, and risk of progression to acute myeloid leukemia. Although specific karyotypic abnormalities have been linked to MDS for decades, more recent findings have demonstrated the importance of mutations within individual genes, focal alterations that are not apparent by standard cytogenetics, and aberrant epigenetic regulation of gene expression. The spectrum of genetic abnormalities in MDS implicates a wide range of molecular mechanisms in the pathogenesis of these disorders, including activation of tyrosine kinase signaling, genomic instability, impaired differentiation, altered ribosome function, and changes in the bone marrow microenvironment. Specific alterations present in individual patients with MDS may explain much of the heterogeneity in clinical phenotype associated with this disease and can predict prognosis and response to therapy. Elucidation of the full complement of genetic causes of MDS promises profound insight into the biology of the disease, improved classification and prognostic scoring schemes, and the potential for novel targeted therapies with molecular predictors of response. J Clin Oncol 29:504-515. (c) 2011 by American Society of Clinical Oncology
C1 [Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Stem Cell Inst, Cambridge, MA USA.
Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10021 USA.
RP Ebert, BL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Karp Res Bldg,CHRB 05-211,1 Blackfan Cir, Boston, MA 02115 USA.
EM bebert@partners.org
FU GlaxoSmithKline
FX Benjamin L. Ebert, GlaxoSmithKline
NR 139
TC 150
Z9 156
U1 0
U2 12
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 FEB 10
PY 2011
VL 29
IS 5
BP 504
EP 515
DI 10.1200/JCO.2010.31.1175
PG 12
WC Oncology
SC Oncology
GA 717XX
UT WOS:000287082900016
PM 21220588
ER
PT J
AU Uemura, K
Farner, KC
Nasser-Ghodsi, N
Jones, P
Berezovska, O
AF Uemura, Kengo
Farner, Katherine C.
Nasser-Ghodsi, Navine
Jones, Phill
Berezovska, Oksana
TI Reciprocal relationship between APP positioning relative to the membrane
and PS1 conformation
SO MOLECULAR NEURODEGENERATION
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; NONSTEROIDAL
ANTIINFLAMMATORY DRUGS; GAMMA-SECRETASE ACTIVITY; A-BETA;
STRUCTURAL-CHANGES; PRESENILIN; MUTATIONS; MECHANISM; TARGET
AB Background: Several familial Alzheimer disease (FAD) mutations within the transmembrane region of the amyloid precursor protein (APP) increase the A beta(42/40) ratio without increasing total A beta production. In the present study, we analyzed the impact of FAD mutations and g-secretase modulators (GSMs) that alter the A beta(42/40) ratio on APP C-terminus (CT) positioning relative to the membrane, reasoning that changes in the alignment of the APP intramembranous domain and presenilin 1 (PS1) may impact the PS1/gamma-secretase cleavage site on APP.
Results: By using a Forster resonance energy transfer (FRET)-based technique, fluorescent lifetime imaging microscopy (FLIM), we show that A beta(42/40) ratio-modulating factors which target either APP substrate or PS1/gamma-secretase affect proximity of the APP-CT to the membrane and change PS1 conformation.
Conclusions: Thus, we propose that there is a reciprocal relationship between APP-CT positioning relative to the membrane and PS1 conformation, suggesting that factors that modulate either APP positioning in the membrane or PS1 conformation could be exploited therapeutically.
C1 [Farner, Katherine C.; Nasser-Ghodsi, Navine; Jones, Phill; Berezovska, Oksana] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA 02129 USA.
[Uemura, Kengo] Kyoto Univ, Grad Sch Med, Kyoto 6068501, Japan.
RP Berezovska, O (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, Charlestown, MA 02129 USA.
EM oberezovska@partners.org
FU [AG026593]; [AG15379]
FX We are grateful to Dr. Bradley T. Hyman for helpful discussions, to Ms.
Mary Banks for technical assistance, to Drs. Koo (UCSD) and DeStrooper
(VIB, Belgium) for PS1/2 dko and APP/APLP2 dko MEF cells, respectively;
and to Dr. Wolfe (BWH, Boston) for HP. This work was supported by
AG026593 and AG15379 (OB).
NR 46
TC 11
Z9 12
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1326
J9 MOL NEURODEGENER
JI Mol. Neurodegener.
PD FEB 10
PY 2011
VL 6
AR 15
DI 10.1186/1750-1326-6-15
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 729EO
UT WOS:000287931600001
PM 21310068
ER
PT J
AU Berger, MF
Lawrence, MS
Demichelis, F
Drier, Y
Cibulskis, K
Sivachenko, AY
Sboner, A
Esgueva, R
Pflueger, D
Sougnez, C
Onofrio, R
Carter, SL
Park, K
Habegger, L
Ambrogio, L
Fennell, T
Parkin, M
Saksena, G
Voet, D
Ramos, AH
Pugh, TJ
Wilkinson, J
Fisher, S
Winckler, W
Mahan, S
Ardlie, K
Baldwin, J
Simons, JW
Kitabayashi, N
MacDonald, TY
Kantoff, PW
Chin, L
Gabriel, SB
Gerstein, MB
Golub, TR
Meyerson, M
Tewari, A
Lander, ES
Getz, G
Rubin, MA
Garraway, LA
AF Berger, Michael F.
Lawrence, Michael S.
Demichelis, Francesca
Drier, Yotam
Cibulskis, Kristian
Sivachenko, Andrey Y.
Sboner, Andrea
Esgueva, Raquel
Pflueger, Dorothee
Sougnez, Carrie
Onofrio, Robert
Carter, Scott L.
Park, Kyung
Habegger, Lukas
Ambrogio, Lauren
Fennell, Timothy
Parkin, Melissa
Saksena, Gordon
Voet, Douglas
Ramos, Alex H.
Pugh, Trevor J.
Wilkinson, Jane
Fisher, Sheila
Winckler, Wendy
Mahan, Scott
Ardlie, Kristin
Baldwin, Jennifer
Simons, Jonathan W.
Kitabayashi, Naoki
MacDonald, Theresa Y.
Kantoff, Philip W.
Chin, Lynda
Gabriel, Stacey B.
Gerstein, Mark B.
Golub, Todd R.
Meyerson, Matthew
Tewari, Ashutosh
Lander, Eric S.
Getz, Gad
Rubin, Mark A.
Garraway, Levi A.
TI The genomic complexity of primary human prostate cancer
SO NATURE
LA English
DT Article
ID MYELOID-LEUKEMIA GENOME; GENE FUSIONS; ANDROGEN RECEPTOR;
TUMOR-SUPPRESSOR; HUMAN BREAST; PTEN; PROGRESSION; REARRANGEMENTS;
MUTATION; PATHWAY
AB Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, 'copy-neutral') rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2-ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.
C1 [Demichelis, Francesca; Esgueva, Raquel; Pflueger, Dorothee; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y.; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
[Berger, Michael F.; Lawrence, Michael S.; Cibulskis, Kristian; Sivachenko, Andrey Y.; Sougnez, Carrie; Onofrio, Robert; Carter, Scott L.; Ambrogio, Lauren; Fennell, Timothy; Parkin, Melissa; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Pugh, Trevor J.; Wilkinson, Jane; Fisher, Sheila; Winckler, Wendy; Mahan, Scott; Ardlie, Kristin; Baldwin, Jennifer; Chin, Lynda; Gabriel, Stacey B.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Garraway, Levi A.] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA.
[Berger, Michael F.; Lawrence, Michael S.; Cibulskis, Kristian; Sivachenko, Andrey Y.; Sougnez, Carrie; Onofrio, Robert; Carter, Scott L.; Ambrogio, Lauren; Fennell, Timothy; Parkin, Melissa; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Pugh, Trevor J.; Wilkinson, Jane; Fisher, Sheila; Winckler, Wendy; Mahan, Scott; Ardlie, Kristin; Baldwin, Jennifer; Chin, Lynda; Gabriel, Stacey B.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Garraway, Levi A.] MIT, Cambridge, MA 02142 USA.
[Demichelis, Francesca] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10021 USA.
[Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
[Sboner, Andrea; Gerstein, Mark B.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Sboner, Andrea; Habegger, Lukas; Gerstein, Mark B.] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
[Ramos, Alex H.; Pugh, Trevor J.; Kantoff, Philip W.; Chin, Lynda; Meyerson, Matthew; Lander, Eric S.; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Pugh, Trevor J.; Kantoff, Philip W.; Chin, Lynda; Meyerson, Matthew; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Simons, Jonathan W.] Prostate Canc Fdn, Santa Monica, CA 90401 USA.
[Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Gerstein, Mark B.] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
[Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Golub, Todd R.; Meyerson, Matthew; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Tewari, Ashutosh] Weill Cornell Med Coll, Inst Prostate Canc, Dept Urol, New York, NY 10065 USA.
[Tewari, Ashutosh] Weill Cornell Med Coll, Lefrak Ctr Robot Surg, New York, NY 10065 USA.
[Tewari, Ashutosh] New York Presbyterian Hosp, New York, NY 10065 USA.
[Lander, Eric S.] 9 Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
RP Rubin, MA (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
EM rubinma@med.cornell.edu; levi_garraway@dfci.harvard.edu
RI Sboner, Andrea/C-6487-2008; Meyerson, Matthew/E-7123-2012; Drier,
Yotam/K-5208-2012;
OI Sboner, Andrea/0000-0001-6915-3070; Drier, Yotam/0000-0003-1725-2995;
Rubin, Mark/0000-0002-8321-9950; Demichelis,
Francesca/0000-0002-8266-8631
FU Prostate Cancer Foundation/Movember; Howard Hughes Medical Institute;
National Human Genome Research Institute; Kohlberg Foundation; National
Cancer Institute (NCI); NCI Early Detection Research Network; National
Institutes of Health; Department of Defense; Dana-Farber/Harvard Cancer
Center [2 P50 CA090381-11]; Starr Cancer Consortium
FX We thank R. Leung and all members of the Broad Institute Sequencing
Platform. This work was supported by the Prostate Cancer
Foundation/Movember (T. R. G., M. A. R., L. A. G.), the Howard Hughes
Medical Institute (T. R. G.), the National Human Genome Research
Institute (S. B. G., E. S. L.), the Kohlberg Foundation (P. W. K., L. A.
G.), the National Cancer Institute (NCI; F. D., M. A. R., M. M.), the
NCI Early Detection Research Network (M. A. R.), the National Institutes
of Health (L. A. G.), the Department of Defense (F. D.), the
Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE grant 2 P50
CA090381-11 (P. W. K.), and the Starr Cancer Consortium (M. F. B., F.
D., M. A. R., L.A.G.).
NR 50
TC 601
Z9 614
U1 7
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 FEB 10
PY 2011
VL 470
IS 7333
BP 214
EP 220
DI 10.1038/nature09744
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200035
PM 21307934
ER
PT J
AU Ding, ZH
Wu, CJ
Chu, GC
Xiao, YH
Ho, D
Zhang, JF
Perry, SR
Labrot, ES
Wu, XQ
Lis, R
Hoshida, Y
Hiller, D
Hu, BL
Jiang, S
Zheng, HW
Stegh, AH
Scott, KL
Signoretti, S
Bardeesy, N
Wang, YA
Hill, DE
Golub, TR
Stampfer, MJ
Wong, WH
Loda, M
Mucci, L
Chin, L
DePinho, RA
AF Ding, Zhihu
Wu, Chang-Jiun
Chu, Gerald C.
Xiao, Yonghong
Ho, Dennis
Zhang, Jingfang
Perry, Samuel R.
Labrot, Emma S.
Wu, Xiaoqiu
Lis, Rosina
Hoshida, Yujin
Hiller, David
Hu, Baoli
Jiang, Shan
Zheng, Hongwu
Stegh, Alexander H.
Scott, Kenneth L.
Signoretti, Sabina
Bardeesy, Nabeel
Wang, Y. Alan
Hill, David E.
Golub, Todd R.
Stampfer, Meir J.
Wong, Wing H.
Loda, Massimo
Mucci, Lorelei
Chin, Lynda
DePinho, Ronald A.
TI SMAD4-dependent barrier constrains prostate cancer growth and metastatic
progression
SO NATURE
LA English
DT Article
ID PHYSICIANS HEALTH; TGF-BETA; EXPRESSION; PTEN; SMAD4; DIFFERENTIATION;
TRANSCRIPTION; INACTIVATION; OSTEOPONTIN; APOPTOSIS
AB Effective clinical management of prostate cancer (PCA) has been challenged by significant intratumoural heterogeneity on the genomic and pathological levels and limited understanding of the genetic elements governing disease progression(1). Here, we exploited the experimental merits of the mouse to test the hypothesis that pathways constraining progression might be activated in indolent Pten-null mouse prostate tumours and that inactivation of such progression barriers in mice would engender a metastasis-prone condition. Comparative transcriptomic and canonical pathway analyses, followed by biochemical confirmation, of normal prostate epithelium versus poorly progressive Pten-null prostate cancers revealed robust activation of the TGF beta/BMP-SMAD4 signalling axis. The functional relevance of SMAD4 was further supported by emergence of invasive, metastatic and lethal prostate cancers with 100% penetrance upon genetic deletion of Smad4 in the Pten-null mouse prostate. Pathological and molecular analysis as well as transcriptomic knowledge-based pathway profiling of emerging tumours identified cell proliferation and invasion as two cardinal tumour biological features in the metastatic Smad4/Pten-null PCA model. Follow-on pathological and functional assessment confirmed cyclin D1 and SPP1 as key mediators of these biological processes, which together with PTEN and SMAD4, form a four-gene signature that is prognostic of prostate-specific antigen (PSA) biochemical recurrence and lethal metastasis in human PCA. This model-informed progression analysis, together with genetic, functional and translational studies, establishes SMAD4 as a key regulator of PCA progression in mice and humans.
C1 [Ding, Zhihu; Wu, Chang-Jiun; Chu, Gerald C.; Xiao, Yonghong; Ho, Dennis; Perry, Samuel R.; Labrot, Emma S.; Hu, Baoli; Jiang, Shan; Zheng, Hongwu; Stegh, Alexander H.; Scott, Kenneth L.; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Ding, Zhihu; Wu, Chang-Jiun; Chu, Gerald C.; Xiao, Yonghong; Ho, Dennis; Perry, Samuel R.; Labrot, Emma S.; Wu, Xiaoqiu; Lis, Rosina; Hu, Baoli; Jiang, Shan; Zheng, Hongwu; Stegh, Alexander H.; Scott, Kenneth L.; Wang, Y. Alan; Loda, Massimo; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ding, Zhihu; Wu, Chang-Jiun; Ho, Dennis; Zheng, Hongwu; Stegh, Alexander H.; Scott, Kenneth L.; Hill, David E.; Chin, Lynda; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Ding, Zhihu; Wu, Chang-Jiun; Ho, Dennis; Zheng, Hongwu; Stegh, Alexander H.; Scott, Kenneth L.; Chin, Lynda; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Chu, Gerald C.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Zhang, Jingfang] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA.
[Wu, Xiaoqiu; Lis, Rosina; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Hoshida, Yujin; Golub, Todd R.] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.
[Hoshida, Yujin; Golub, Todd R.] Harvard Univ, Cambridge, MA 02142 USA.
[Hiller, David; Wong, Wing H.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
[Signoretti, Sabina] Dana Farber Harvard Canc Ctr, Renal Canc Program, Boston, MA 02115 USA.
[Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA.
[Hill, David E.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Chin, Lynda] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Stampfer, Meir J.; Mucci, Lorelei] 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.
[Stampfer, Meir J.; Mucci, Lorelei] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
RP DePinho, RA (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
EM lynda_chin@dfci.harvard.edu; ron_depinho@dfci.harvard.edu
RI Hill, David/B-6617-2011;
OI Zheng, Hongwu/0000-0002-5823-4913
FU Damon Runyon Cancer Research Foundation; National Science Foundation;
Helen Hay Whitney Foundation; Multiple Myeloma Research Foundation;
Belfer Institute for Applied Cancer Science (NCI) [U01-CA84313]; DF/HCC
SPORE in Prostate Cancer [P50 CA090381-08]; National Cancer Institute
[RO1CA131945, P50 CA90381, RO1 5R01CA136578, R01CA141298]; Linda and
Arthur Gelb Center for Translational Research; Prostate Cancer
Foundation
FX The authors are grateful to the late W. Gerald for providing the primary
gene expression data and clinical outcome files13. We thank
S. Zhou for excellent mouse husbandry and care, B. Xiong and G. Tonon
for bioinformatic assistance, and S. Jia, J. M. Stommel, J. Paik, M. Kim
and A. C. Kimmelman for helpful discussion. We thank M. Vidal, the
Ellison Foundation and DFCI ISR for support of ORF cloning efforts, R.
Maser for MSCV-puro-v5 gateway vector, W. Hahn for shRNA constructs. We
thank the DF/HCC Specialized Histopathology Core and the DF/HCC Tissue
Microarray and Imaging core for the TMA IHC staining; the DFCI/BWH
Center for Molecular Oncologic Pathology (CMOP) for the quantification
of the IHC. Z.D was supported by the Damon Runyon Cancer Research
Foundation. D. H. was supported by a graduate fellowship from the
National Science Foundation. H.Z. was supported by the Helen Hay Whitney
Foundation. Y.A.W. was supported by the Multiple Myeloma Research
Foundation. This work is supported by the Belfer Institute for Applied
Cancer Science, NCI U01-CA84313 (L. C. and R. A. D.), DF/HCC SPORE in
Prostate Cancer P50 CA090381-08 (Z.D.), the National Cancer Institute
(M. L. RO1CA131945 and P50 CA90381, L. M. RO1 5R01CA136578, M. S.
R01CA141298), and the Linda and Arthur Gelb Center for Translational
Research (M. L.). R. A. D. was supported by an American Cancer Society
Research Professorship and L. M. was supported by the Prostate Cancer
Foundation.
NR 33
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U1 3
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD FEB 10
PY 2011
VL 470
IS 7333
BP 269
EP +
DI 10.1038/nature09677
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 718RQ
UT WOS:000287144200046
PM 21289624
ER
PT J
AU Oberaigner, W
Buchberger, W
Frede, T
Daniaux, M
Knapp, R
Marth, C
Siebert, U
AF Oberaigner, Willi
Buchberger, Wolfgang
Frede, Thomas
Daniaux, Martin
Knapp, Rudolf
Marth, Christian
Siebert, Uwe
TI Introduction of organised mammography screening in tyrol: results of a
one-year pilot phase
SO BMC PUBLIC HEALTH
LA English
DT Article
ID BREAST-CANCER MORTALITY; SERVICES TASK-FORCE; FINLAND; US; REDUCTION;
AUSTRIA; PROGRAM; TRENDS
AB Background: Efficiency and efficacy of organised mammography screening programs have been proven in large randomised trials. But every local implementation of mammography screening has to check whether the well established quality standards are met. Therefore it was the aim of this study to analyse the most common quality indices after introducing organised mammography screening in Tyrol, Austria, in a smooth transition from the existing system of opportunistic screening.
Methods: In June 2007, the system of opportunistic mammography screening in Tyrol was changed to an organised system by introducing a personal invitation system, a training program, a quality assurance program and by setting up a screening database. All procedures are noted in a written protocol. Most EU recommendations for organised mammography screening were followed, except double reading. All women living in Tyrol and covered by social insurance are now invited for a mammography, in age group 40-59 annually and in age group 60-69 biannually. Screening mammography is offered mainly by radiologists in private practice. We report on the results of the first year of piloting organised mammography screening in two counties in Tyrol.
Results: 56,432 women were invited. Estimated participation rate was 34.5% at one year of follow-up (and 55.5% at the second year of follow-up); 3.4% of screened women were recalled for further assessment or intermediate screening within six months. Per 1000 mammograms nine biopsies were performed and four breast cancer cases detected (N = 68). Of invasive breast cancer cases 34.4% were <= 10 mm in size and 65.6% were node-negative. In total, six interval cancer cases were detected during one year of follow-up; this is 19% of the background incidence rate.
Conclusions: In the Tyrolean breast cancer screening program, a smooth transition from a spontaneous to an organised mammography screening system was achieved in a short time and with minimal additional resources. One year after introduction of the screening program, most of the quality indicators recommended by the European guidelines had been reached.
However, it will be necessary to introduce double reading, to change the rule for BI-RADS 3, and to concentrate on actions toward improving the participation rate.
C1 [Oberaigner, Willi] Tyrolean State Hosp Ltd, Dept Clin Epidemiol, Canc Registry Tyrol, Innsbruck, Austria.
[Oberaigner, Willi; Buchberger, Wolfgang; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Inst Publ Hlth Med Decis Making & Hlth Technol As, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Hall In Tirol, Austria.
[Oberaigner, Willi; Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Innsbruck, Austria.
[Buchberger, Wolfgang] TILAK, Innsbruck, Austria.
[Frede, Thomas; Daniaux, Martin] Innsbruck Med Univ, Dept Radiol, Innsbruck, Austria.
[Knapp, Rudolf] Kufstein Cty Hosp, Dept Radiol, Kufstein, Austria.
[Marth, Christian] Innsbruck Med Univ, Dept Obstet & Gynecol, Innsbruck, Austria.
[Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA.
[Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Inst Technol Assessment, Sch Med, Boston, MA USA.
[Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Oberaigner, W (reprint author), Tyrolean State Hosp Ltd, Dept Clin Epidemiol, Canc Registry Tyrol, Innsbruck, Austria.
EM willi.oberaigner@tilak.at
FU ONCOTYROL Center for Personal Cancer Medicine; Federal Ministry for
Transport Innovation and Technology (BMVIT); Federal Ministry of
Economics and Labour (BMWA); Tyrolean Future Foundation (TZS); UMIT -
University for Health Sciences; Medical Informatics and Technology;
Innsbruck Medical University; Tyrolean Health Insurance Fund; Tyrolean
Health Company
FX This work was supported by the ONCOTYROL Center for Personal Cancer
Medicine. ONCOTYROL is a COMET Center funded by the Federal Ministry for
Transport Innovation and Technology (BMVIT) and the Federal Ministry of
Economics and Labour (BMWA), the Tyrolean Future Foundation (TZS) and
the Land of Styria represented by the Styrian Business Promotion Agency
(SFG) and supported by UMIT - University for Health Sciences, Medical
Informatics and Technology, Innsbruck Medical University, Tyrolean
Health Insurance Fund and Tyrolean Health Company.
NR 29
TC 3
Z9 3
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD FEB 9
PY 2011
VL 11
AR 91
DI 10.1186/1471-2458-11-91
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 730XH
UT WOS:000288070200001
PM 21306614
ER
PT J
AU Soto, O
Cros, D
AF Soto, Oscar
Cros, Didier
TI Direct Corticospinal Control of Force Derivative
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MAGNETIC BRAIN-STIMULATION; HUMAN MOTOR CORTEX; DORSAL INTEROSSEOUS
MUSCLE; 2 DIFFERENT VIEWS; TRANSCRANIAL STIMULATION; ISOMETRIC
CONTRACTIONS; CORTICOMOTONEURONAL CM; VOLUNTARY CONTRACTION;
CORTICAL-NEURONS; MOVEMENT
AB During simultaneous generation of static and dynamic forces, motor cortical signals only predict the dynamic components, suggesting a key role in the coding of force changes. However, such a role is obscured by uncertainties regarding the representation of dynamic force signals in corticospinal outputs. We used transcranial magnetic stimulation (TMS) of the motor cortex in humans during a task that dissociated the direction of instantaneous net force and that of force derivative. The direction of TMS-evoked force outputs was closely associated with that of the force derivative, and had no relationship with that of the net force generated simultaneously, even though the magnitude of the instantaneous net force largely exceeded that of the force derivative. This observation supports the hypothesis that during dynamic force generation, the motor cortex and the corticospinal system assume a pivotal role in coding the direction of force changes, through selective recruitment of spinal motoneurons.
C1 [Soto, Oscar; Cros, Didier] Massachusetts Gen Hosp, Dept Neurol, Clin Neurophysiol Labs, Boston, MA 02114 USA.
RP Cros, D (reprint author), 1 Hawthorne Pl,Suite 103-7, Boston, MA 02114 USA.
EM dcros@partners.org
NR 44
TC 2
Z9 2
U1 0
U2 5
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 FEB 9
PY 2011
VL 31
IS 6
BP 1944
EP 1948
DI 10.1523/JNEUROSCI.0056-10.2011
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 721WV
UT WOS:000287389400003
PM 21307232
ER
PT J
AU Choy, HA
Kelley, MM
Croda, J
Matsunaga, J
Babbitt, JT
Ko, AI
Picardeau, M
Haake, DA
AF Choy, Henry A.
Kelley, Melissa M.
Croda, Julio
Matsunaga, James
Babbitt, Jane T.
Ko, Albert I.
Picardeau, Mathieu
Haake, David A.
TI The Multifunctional LigB Adhesin Binds Homeostatic Proteins with
Potential Roles in Cutaneous Infection by Pathogenic Leptospira
interrogans
SO PLOS ONE
LA English
DT Article
ID IMMUNOGLOBULIN-LIKE PROTEINS; STAPHYLOCOCCUS-AUREUS; CLUMPING FACTOR;
EXTRACELLULAR-MATRIX; MUCOSAL IMMUNOLOGY; CRYSTAL-STRUCTURE;
HUMAN-FIBRINOGEN; GENE-EXPRESSION; TISSUE-REPAIR; MODEL
AB Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9-11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats.
C1 [Choy, Henry A.; Matsunaga, James; Babbitt, Jane T.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Choy, Henry A.; Kelley, Melissa M.; Matsunaga, James; Babbitt, Jane T.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA.
[Croda, Julio; Ko, Albert I.] Brasilian Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, Salvador, BA, Brazil.
[Croda, Julio] Fed Univ Grande Dourados, Fac Hlth Sci, Dourados, MS, Brazil.
[Ko, Albert I.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Epidemiol Microbial Dis, New Haven, CT 06510 USA.
[Picardeau, Mathieu] Inst Pasteur, Unite Biol Spirochetes, Paris, France.
[Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA.
[Haake, David A.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA.
[Haake, David A.] Univ Calif Los Angeles, Dept Mol Genet Microbiol & Immunol, Los Angeles, CA USA.
RP Choy, HA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
EM hachoy@ucla.edu
RI Ko, Albert/P-2343-2015
FU National Institutes of Health [R01 AI34431, U01 AI088752, D43 TW00919,
R01 AI052473]; VA Medical Research Funds; Institut Pasteur, Paris,
France; French Ministry of Research [ANR-08-MIE-018]; Oswaldo Cruz
Foundation [PDTIS RVR05]
FX This study was supported by the National Institutes of Health (R01
AI34431, U01 AI088752, D43 TW00919, and R01 AI052473), VA Medical
Research Funds (to D. A. H.), the Institut Pasteur, Paris, France, the
French Ministry of Research (ANR-08-MIE-018), and the Fiocruz-Pasteur
Scientific Cooperation Agreement, Oswaldo Cruz Foundation (PDTIS RVR05).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 51
TC 27
Z9 28
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 9
PY 2011
VL 6
IS 2
AR e16879
DI 10.1371/journal.pone.0016879
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 721NN
UT WOS:000287361700049
PM 21347378
ER
PT J
AU Thankamony, SP
Sackstein, R
AF Thankamony, Sai P.
Sackstein, Robert
TI Enforced hematopoietic cell E- and L-selectin ligand (HCELL) expression
primes transendothelial migration of human mesenchymal stem cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE G-protein; selectin; cell therapeutics; regenerative medicine
ID BONE-MARROW; CHEMOKINE RECEPTORS; IN-VIVO; VASCULAR ENDOTHELIUM;
MULTISTEP PARADIGM; SHEAR-FLOW; CD44; ADHESION; SIGNALS; RAP1
AB According to the multistep model of cell migration, chemokine receptor engagement (step 2) triggers conversion of rolling interactions (step 1) into firm adhesion (step 3), yielding transendothelial migration. We recently reported that glycosyltransferase-programmed stereosubstitution (GPS) of CD44 on human mesenchymal stem cells (hMSCs) creates the E-selectin ligand HCELL (hematopoietic cell E-selectin/L-selectin ligand) and, despite absence of CXCR4, systemically administered HCELL(+)hMSCs display robust osteotropism visualized by intravital microscopy. Here we performed studies to define the molecular effectors of this process. We observed that engagement of hMSC HCELL with E-selectin triggers VLA-4 adhesiveness, resulting in shear-resistant adhesion to ligand VCAM-1. This VLA-4 activation is mediated via a Rac1/Rap1 GTPase signaling pathway, resulting in transendothelial migration on stimulated human umbilical vein endothelial cells without chemokine input. These findings indicate that hMSCs coordinately integrate CD44 ligation and integrin activation, circumventing chemokine-mediated signaling, yielding a step 2-bypass pathway of the canonical multistep paradigm of cell migration.
C1 [Thankamony, Sai P.; Sackstein, Robert] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Sackstein, Robert] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Thankamony, Sai P.; Sackstein, Robert] Harvard Univ, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA.
[Sackstein, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Sackstein, R (reprint author), Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA.
EM rsackstein@rics.bwh.harvard.edu
FU National Institutes of Health [HL073714, CA121335]
FX The authors appreciate the helpful advice of Drs. Tanya Mayadas, Xavier
Cullere, and Hans Widlund. This work was supported by National
Institutes of Health R01 Grants HL073714 and CA121335, and is dedicated
to the memory of Harold C. Sackstein.
NR 52
TC 41
Z9 41
U1 2
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 8
PY 2011
VL 108
IS 6
BP 2258
EP 2263
DI 10.1073/pnas.1018064108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 717YH
UT WOS:000287084500019
PM 21257905
ER
PT J
AU Abdelwahid, E
Smith, G
AF Abdelwahid, Eltyeb
Smith, Graham
TI Promising antiapoptotic effects of helix B-surface peptide (HBSP) for
treatment of heart diseases
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
ID ERYTHROPOIETIN; ACTIVATION
C1 [Abdelwahid, Eltyeb] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Smith, Graham] Queen Mary Univ London, Barts & Royal London Sch Med, London E1 4NS, England.
RP Abdelwahid, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
EM eltyeb.abdelwahid@cbrc2.mgh.harvard.edu
NR 5
TC 1
Z9 1
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 8
PY 2011
VL 108
IS 6
BP E17
EP E17
DI 10.1073/pnas.1012530108
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 717YH
UT WOS:000287084500001
PM 21278330
ER
PT J
AU O'Donoghue, ML
AF O'Donoghue, Michelle L.
TI CYP2C19 Genotype and Proton Pump Inhibitors in Clopidogrel-Treated
Patients Does It Take Two to Tango?
SO CIRCULATION
LA English
DT Editorial Material
DE Editorials; clopidogrel; proton pump inhibitors; CYP2C19, human
ID CARDIOVASCULAR EVENTS; TRIAL; OMEPRAZOLE; OUTCOMES; RISK
C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA.
RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA.
EM modonoghue@partners.org
NR 23
TC 6
Z9 6
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD FEB 8
PY 2011
VL 123
IS 5
BP 468
EP 470
DI 10.1161/CIRCULATIONAHA.110.006866
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 717CT
UT WOS:000287021300008
PM 21262991
ER
PT J
AU Deshpande, V
Nduaguba, A
Zimmerman, SM
Kehoe, SM
MacConaill, LE
Lauwers, GY
Ferrone, C
Bardeesy, N
Zhu, AX
Hezel, AF
AF Deshpande, Vikram
Nduaguba, Afamefuna
Zimmerman, Stephanie M.
Kehoe, Sarah M.
MacConaill, Laura E.
Lauwers, Gregory Y.
Ferrone, Cristina
Bardeesy, Nabeel
Zhu, Andrew X.
Hezel, Aram F.
TI Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma
SO BMC CANCER
LA English
DT Article
ID BILIARY-TRACT CANCERS; GROWTH-FACTOR-RECEPTOR; INTRAHEPATIC
CHOLANGIOCELLULAR CARCINOMA; TUMOR-SUPPRESSOR GENE; K-RAS; BETA-CATENIN;
MICROSATELLITE INSTABILITY; P53 OVEREXPRESSION; SOMATIC MUTATIONS;
BILE-DUCT
AB Background: The genetics of advanced biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined.
Methods: To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases.
Results: Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%). KRAS mutations were identified in 3 (13%) intra- hepatic cholangiocarcinomas and 1 (33%) perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma.
Conclusions: The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.
C1 [Deshpande, Vikram; Zimmerman, Stephanie M.; Lauwers, Gregory Y.; Ferrone, Cristina; Bardeesy, Nabeel; Zhu, Andrew X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kehoe, Sarah M.; MacConaill, Laura E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Nduaguba, Afamefuna; Hezel, Aram F.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14642 USA.
RP Zhu, AX (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM AZHU@PARTNERS.ORG; aram_hezel@urmc.rochester.edu
FU HHMI; NIH
FX This work was supported by grants from the HHMI (AFH), and AFH is
supported by an NIH K08 career development award.
NR 39
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U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD FEB 8
PY 2011
VL 11
AR 60
DI 10.1186/1471-2407-11-60
PG 7
WC Oncology
SC Oncology
GA 726RT
UT WOS:000287744500001
PM 21303542
ER
PT J
AU Wang, TJ
AF Wang, Thomas J.
TI Assessing the Role of Circulating, Genetic, and Imaging Biomarkers in
Cardiovascular Risk Prediction
SO CIRCULATION
LA English
DT Article
DE genetics; imaging; prevention; prognosis
ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; INTIMA-MEDIA THICKNESS;
ARTERY CALCIUM SCORE; BRAIN NATRIURETIC PEPTIDE; SERVICES TASK-FORCE;
CLINICAL-TRIAL DESIGNS; ALL-CAUSE MORTALITY; MIDDLE-AGED MEN;
ENDOTHELIAL DYSFUNCTION
C1 Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Wang, TJ (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, GRB-800,55 Fruit St, Boston, MA 02114 USA.
EM tjwang@partners.org
FU NHLBI NIH HHS [R01 HL083197, R01 HL083197-04, R01 HL086875, R01
HL086875-04, R01 HL098283, R01 HL098283-03, R01-HL-083197,
R01-HL-083875, R01-HL098283]; NIDDK NIH HHS [R01 DK081572, R01
DK081572-03, R01-DK-081572]
NR 121
TC 112
Z9 117
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 8
PY 2011
VL 123
IS 5
BP 551
EP 565
DI 10.1161/CIRCULATIONAHA.109.912568
PG 15
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 717CT
UT WOS:000287021300019
PM 21300963
ER
PT J
AU Held, C
Asenblad, N
Bassand, JP
Becker, RC
Cannon, CP
Claeys, MJ
Harrington, RA
Horrow, J
Husted, S
James, SK
Mahaffey, KW
Nicolau, JC
Scirica, BM
Storey, RF
Vintila, M
Ycas, J
Wallentin, L
AF Held, Claes
Asenblad, Nils
Bassand, Jean Pierre
Becker, Richard C.
Cannon, Christopher P.
Claeys, Marc J.
Harrington, Robert A.
Horrow, Jay
Husted, Steen
James, Stefan K.
Mahaffey, Kenneth W.
Nicolau, Jose C.
Scirica, Benjamin M.
Storey, Robert F.
Vintila, Marius
Ycas, Joseph
Wallentin, Lars
TI Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes
Undergoing Coronary Artery Bypass Surgery Results From the PLATO
(Platelet Inhibition and Patient Outcomes) Trial
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE acute coronary syndromes; clopidogrel; coronary artery bypass grafting;
ticagrelor
ID ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; GRAFT-SURGERY; ASPIRIN;
MANAGEMENT; INTERVENTION; ANTAGONIST; THERAPY; SAFETY; CURE
AB Objectives The purpose of this study is to evaluate the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome undergoing coronary artery bypass graft surgery (CABG), as a post-randomization strategy.
Background Ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y(12)-receptor antagonist. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized 18,624 patients with acute coronary syndromes, ticagrelor compared with clopidogrel significantly reduced the risk of the primary composite end point of cardiovascular (CV) death, myocardial infarction, or stroke (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.77 to 0.92; p < 0.001). This report investigated the outcomes of patients treated with CABG during the trial.
Methods In total, 1,899 patients underwent CABG post-randomization. The protocol recommended ticagrelor/placebo to be withheld for 24 to 72 h and clopidogrel/placebo for 5 days preoperatively. In all, 1,261 patients underwent CABG and were receiving study drug treatment <7 days before surgery. The statistical analysis was based on events occurring from the CABG procedure until the end of the study, excluding 3 patients with CABG after study end.
Results In the 1,261 patient cohort, the relative reduction of primary composite end point at 12 months (10.6% [66 of 629] with ticagrelor versus 13.1% [79 of 629] with clopidogrel; HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.29) was consistent with the results of the whole trial. Total mortality was reduced from 9.7% (58 of 629) to 4.7% (29 of 629; HR: 0.49; 95% CI: 0.32 to 0.77; p < 0.01), CV death from 7.9% (47 of 629) to 4.1% (25 of 629; HR: 0.52; 95% CI: 0.32 to 0.85; p < 0.01), and non-CV death numerically from 2.0% to 0.7% (p = 0.07). There was no significant difference in CABG-related major bleeding between the randomized treatments.
Conclusions In the subgroup of patients undergoing CABG within 7 days after the last study drug intake, ticagrelor compared with clopidogrel was associated with a substantial reduction in total and CV mortality without excess risk of CABG-related bleeding. (J Am Coll Cardiol 2011;57:672-84) (C) 2011 by the American College of Cardiology Foundation
C1 [Held, Claes] Uppsala Univ, Dept Cardiol, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden.
[Held, Claes; Asenblad, Nils; James, Stefan K.; Wallentin, Lars] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden.
[Bassand, Jean Pierre] Univ Besancon, F-25030 Besancon, France.
[Becker, Richard C.; Harrington, Robert A.; Mahaffey, Kenneth W.] Duke Clin Res Inst, Durham, NC USA.
[Cannon, Christopher P.; Scirica, Benjamin M.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
[Claeys, Marc J.] Univ Hosp, Edegem, Belgium.
[Horrow, Jay; Ycas, Joseph] AstraZeneca Res & Dev, Wilmington, DE USA.
[Husted, Steen] Arhus Univ Hosp, Aarhus, Denmark.
[Nicolau, Jose C.] Univ Sao Paolo, Sch Med, Sao Paulo, Brazil.
[Storey, Robert F.] Univ Sheffield, Sheffield, S Yorkshire, England.
[Vintila, Marius] Carol Davila Univ Med Bucharest, Bucharest, Romania.
RP Held, C (reprint author), Uppsala Univ, Dept Cardiol, Uppsala Clin Res Ctr, Dag Hammarskjolds 14B, S-75185 Uppsala, Sweden.
EM claes.held@ucr.uu.se
RI Nicolau, Jose/E-1487-2012; 刘, 李陆/H-8469-2015;
OI Held, Claes/0000-0001-9402-7404
FU AstraZeneca
FX Carol Davila University of Medicine Bucharest, Bucharest, Romania. The
PLATO study was funded by AstraZeneca. For full author disclosures,
please see the end of this article.
NR 21
TC 191
Z9 204
U1 1
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 FEB 8
PY 2011
VL 57
IS 6
BP 672
EP 684
DI 10.1016/j.jacc.2010.10.029
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 715JH
UT WOS:000286880100006
PM 21194870
ER
PT J
AU Tallaj, JA
Cadeiras, M
AF Tallaj, Jose A.
Cadeiras, Martin
TI Mechanical Rescue of the Heart in Shock
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE assist devices; cardiogenic shock; heart failure; myocardial infarction
ID ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR ASSIST DEVICE;
CARDIOGENIC-SHOCK; COUNTERPULSATION; DYSFUNCTION; MORTALITY; EFFICACY;
FAILURE; SUPPORT; SAFETY
AB Cardiogenic shock (CS) is a state of extreme hypoperfusion owing to pump failure manifested by altered mental status, cool extremities, and/or renal failure. This hypoperfusion leads to release of catecholamines and other inflammatory mediators, which further perpetuates myocardial ischemia and injury, resulting in additional impairment in systemic and tissue perfusion. Any cause of acute severe cardiac failure may lead to CS.
C1 [Tallaj, Jose A.; Cadeiras, Martin] Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA.
[Tallaj, Jose A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA.
RP Tallaj, JA (reprint author), Univ Alabama, Dept Med, Div Cardiol, THT 338,1900 Univ Blvd, Birmingham, AL 35294 USA.
EM jtallaj@uab.edu
NR 13
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 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 8
PY 2011
VL 57
IS 6
BP 697
EP 699
DI 10.1016/j.jacc.2010.10.015
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 715JH
UT WOS:000286880100009
PM 21292128
ER
PT J
AU Van Dijk, KRA
Sperling, RA
AF Van Dijk, Koene R. A.
Sperling, Reisa A.
TI Defaulting on the default network Increased risk for dementia
SO NEUROLOGY
LA English
DT Editorial Material
ID INTRINSIC FUNCTIONAL CONNECTIVITY; MILD COGNITIVE IMPAIRMENT;
ALZHEIMERS-DISEASE; MODE; MRI; MEMORY
C1 [Sperling, Reisa A.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA 02115 USA.
[Van Dijk, Koene R. A.; Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Van Dijk, Koene R. A.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Sperling, Reisa A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Sperling, RA (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA.
EM reisa@rics.bwh.harvard.edu
RI Van Dijk, Koene/G-3317-2012;
OI Van Dijk, Koene/0000-0001-6137-4282; Kennedy,
Kristen/0000-0001-5373-9026
FU NIA NIH HHS [P01AG036694, R01AG027435]
NR 15
TC 4
Z9 4
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD FEB 8
PY 2011
VL 76
IS 6
BP 498
EP 500
DI 10.1212/WNL.0b013e31820af975
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 718MN
UT WOS:000287127100004
PM 21228298
ER
PT J
AU Wong, C
Stylianopoulos, T
Cui, JA
Martin, J
Chauhan, VP
Jiang, W
Popovic, Z
Jain, RK
Bawendi, MG
Fukumura, D
AF Wong, Cliff
Stylianopoulos, Triantafyllos
Cui, Jian
Martin, John
Chauhan, Vikash P.
Jiang, Wen
Popovic, Zoran
Jain, Rakesh K.
Bawendi, Moungi G.
Fukumura, Dai
TI Multistage nanoparticle delivery system for deep penetration into tumor
tissue
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE drug delivery; cancer therapy; nanomedicine
ID METASTATIC BREAST-CANCER; PHASE-III TRIAL; SOLID TUMORS; IN-VIVO;
INTERSTITIAL TRANSPORT; GELATIN NANOPARTICLES; EXTRACELLULAR-MATRIX;
SUBCUTANEOUS TUMORS; QUANTUM DOTS; DIFFUSION
AB Current Food and Drug Administration-approved cancer nanotherapeutics, which passively accumulate around leaky regions of the tumor vasculature because of an enhanced permeation and retention (EPR) effect, have provided only modest survival benefits. This suboptimal outcome is likely due to physiological barriers that hinder delivery of the nanotherapeutics throughout the tumor. Many of these nanotherapeutics are approximate to 100 nm in diameter and exhibit enhanced accumulation around the leaky regions of the tumor vasculature, but their large size hinders penetration into the dense collagen matrix. Therefore, we propose a multistage system in which 100-nm nanoparticles "shrink" to 10-nm nanoparticles after they extravasate from leaky regions of the tumor vasculature and are exposed to the tumor microenvironment. The shrunken nanoparticles can more readily diffuse throughout the tumor's interstitial space. This size change is triggered by proteases that are highly expressed in the tumor microenvironment such as MMP-2, which degrade the cores of 100-nm gelatin nanoparticles, releasing smaller 10-nm nanoparticles from their surface. We used quantum dots (QD) as a model system for the 10-nm particles because their fluorescence can be used to demonstrate the validity of our approach. In vitro MMP-2 activation of the multistage nanoparticles revealed that the size change was efficient and effective in the enhancement of diffusive transport. In vivo circulation half-life and intratumoral diffusion measurements indicate that our multistage nanoparticles exhibited both the long circulation half-life necessary for the EPR effect and the deep tumor penetration required for delivery into the tumor's dense collagen matrix.
C1 [Wong, Cliff; Cui, Jian; Popovic, Zoran; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Stylianopoulos, Triantafyllos; Martin, John; Chauhan, Vikash P.; Jiang, Wen; Jain, Rakesh K.; Fukumura, Dai] Massachusetts Gen Hosp, Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA.
[Stylianopoulos, Triantafyllos; Martin, John; Chauhan, Vikash P.; Jiang, Wen; Jain, Rakesh K.; Fukumura, Dai] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Bawendi, MG (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA.
EM mgb@mit.edu; dai@steele.mgh.harvard.edu
RI Chauhan, Vikash/H-8172-2013; Martin, John/L-6892-2016;
OI Chauhan, Vikash/0000-0001-9126-2302; Martin, John/0000-0002-9828-8203;
Stylianopoulos, Triantafyllos/0000-0002-3093-1696; Jiang,
Wen/0000-0001-9154-633X
FU Dyax; AstraZeneca; MedImmune; AstraZeneca/MedImmune; Astellas-Fibrogen;
Regeneron; Genzyme; MorphoSys; Noxxon Pharma; US National Cancer
Institute [R01-CA126642, R01-CA085140, R01-CA115767, P01-CA080124,
R01-CA096915]; MIT-Harvard NIH Center for Cancer Nanotechnology
Excellence [1U54-CA119349]; MIT DCIF [CHE-980806, DBI-9729592]; ISN
[W911NF-07-D-0004]; Susan G. Komen Foundation [KG091281]; US Department
of Defense [W81XWH-10-1-0016]
FX R.K.J. received commercial research grants from Dyax, AstraZeneca, and
MedImmune; consultant fees from AstraZeneca/MedImmune, Dyax,
Astellas-Fibrogen, Regeneron, Genzyme, MorphoSys, and Noxxon Pharma; and
a speaker honorarium from Genzyme. R.K.J. owns stock in SynDevRx. No
reagents or funding from these companies were used in these studies.
There is no significant financial or other competing interest in the
work.; We thank Patrick Boisvert for assistance with SEM imaging, Yves
Boucher for help with zymography, Peigen Huang for the direction of
gnotobiotic animal facility, Julia Kahn for animal model preparation,
Eve Smith for cancer cell line preparation, Lisa Marshall for assistance
with FCS, Li Miao for administrative support, Debby Pheasant for
assistance with DLS, and Elisabeth Shaw for assistance with XPS. We
thank Juwell Wu for assistance with image analysis and helpful
discussions. This research was supported by US National Cancer Institute
Grants R01-CA126642 (to R.K.J. and M.G.B.), R01-CA085140, R01-CA115767
(to R.K.J.), P01-CA080124 (to R.K.J. and D.F.), R01-CA096915 (to D.F.);
MIT-Harvard NIH Center for Cancer Nanotechnology Excellence Grant
1U54-CA119349 (to M.G.B.); MIT DCIF Grants CHE-980806 and DBI-9729592;
by ISN Grant W911NF-07-D-0004 (to M.G.B.); and The Susan G. Komen
Foundation Grant KG091281 (to T.S.). R.K.J. is a recipient of Innovator
Award W81XWH-10-1-0016 from the US Department of Defense Breast Cancer
Research Program.
NR 44
TC 334
Z9 339
U1 35
U2 273
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 FEB 8
PY 2011
VL 108
IS 6
BP 2426
EP 2431
DI 10.1073/pnas.1018382108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 717YH
UT WOS:000287084500048
PM 21245339
ER
PT J
AU Yu, M
Stott, S
Toner, M
Maheswaran, S
Haber, DA
AF Yu, Min
Stott, Shannon
Toner, Mehmet
Maheswaran, Shyamala
Haber, Daniel A.
TI Circulating tumor cells: approaches to isolation and characterization
SO JOURNAL OF CELL BIOLOGY
LA English
DT Review
ID BREAST-CANCER PATIENTS; RESISTANT PROSTATE-CANCER;
EPITHELIAL-MESENCHYMAL TRANSITION; MULTIPARAMETER FLOW-CYTOMETRY; HUMAN
PERIPHERAL-BLOOD; BONE-MARROW; LUNG-CANCER; FREE DNA; COLORECTAL-CANCER;
CARCINOMA-CELLS
AB Circulating tumor cells (CTCs) shed from primary and metastatic cancers are admixed with blood components and are thus rare, making their isolation and characterization a major technological challenge. CTCs hold the key to understanding the biology of metastasis and provide a biomarker to noninvasively measure the evolution of tumor genotypes during treatment and disease progression. Improvements in technologies to yield purer CTC populations amenable to better cellular and molecular characterization will enable a broad range of clinical applications, including early detection of disease and the discovery of biomarkers to predict treatment responses and disease progression.
C1 [Yu, Min; Haber, Daniel A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02129 USA.
[Yu, Min; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
[Stott, Shannon; Toner, Mehmet] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02129 USA.
RP Haber, DA (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02129 USA.
EM dhaber@partners.org
RI Zhou, Feng/E-9510-2011
FU Howard Hughes Medical Institute; NIBIB NIH HHS [P41 EB002503]
NR 110
TC 420
Z9 434
U1 33
U2 271
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD FEB 7
PY 2011
VL 192
IS 3
BP 373
EP 382
DI 10.1083/jcb.201010021
PG 10
WC Cell Biology
SC Cell Biology
GA 727DX
UT WOS:000287778900003
PM 21300848
ER
PT J
AU Wilken, R
Veena, MS
Wang, MB
Srivatsan, ES
AF Wilken, Reason
Veena, Mysore S.
Wang, Marilene B.
Srivatsan, Eri S.
TI Curcumin: A review of anti-cancer properties and therapeutic activity in
head and neck squamous cell carcinoma
SO MOLECULAR CANCER
LA English
DT Review
ID NF-KAPPA-B; BREAST-CANCER CELLS; MALIGNANT GLIOMA-CELLS;
LIPOSOME-ENCAPSULATED CURCUMIN; ISCHEMIA-REPERFUSION INJURY; TYROSINE
KINASE INHIBITOR; HUMAN NEUROBLASTOMA-CELLS; SOUTHWEST-ONCOLOGY-GROUP;
NITRIC-OXIDE SYNTHASE; PHASE-II TRIAL
AB Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-kappa B and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-alpha, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent.
C1 [Wilken, Reason; Veena, Mysore S.; Wang, Marilene B.; Srivatsan, Eri S.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA.
[Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Los Angeles, CA 90095 USA.
[Veena, Mysore S.; Srivatsan, Eri S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA.
RP Srivatsan, ES (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA.
EM esrivats@ucla.edu
FU VAGLAHS; West Los Angeles Surgical Education Research Center; NIH [R21
CA116826-01]; Veterans Administration, Washington, DC
FX We thank Eugene Han for help with figures. The study was supported by
funds from VAGLAHS, West Los Angeles Surgical Education Research Center,
NIH (R21 CA116826-01 to M. B. Wang) and Merit grant from the Veterans
Administration, Washington, DC (E.S. Srivatsan).
NR 217
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Z9 222
U1 13
U2 76
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD FEB 7
PY 2011
VL 10
AR 12
DI 10.1186/1476-4598-10-12
PG 19
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 729DX
UT WOS:000287929900001
PM 21299897
ER
PT J
AU Konry, T
Smolina, I
Yarmush, JM
Irimia, D
Yarmush, ML
AF Konry, Tania
Smolina, Irina
Yarmush, Joel M.
Irimia, Daniel
Yarmush, Martin L.
TI Ultrasensitive Detection of Low-Abundance Surface-Marker Protein Using
Isothermal Rolling Circle Amplification in a Microfluidic Nanoliter
Platform
SO SMALL
LA English
DT Article
ID SINGLE-MOLECULE DETECTION; ENZYMATIC AMPLIFICATION; DNA; POLYMERASE;
EXPRESSION; DROPLETS; CANCER; CELLS
AB With advances in immunology and cancer biology, there is an unmet need for increasingly sensitive systems to monitor the expression of specific cell markers for the development of new diagnostic and therapeutic tools. To address this challenge, a highly sensitive labeling method that translates antigen-antibody recognition processes into DNA detection events that can be greatly amplified via isothermal rolling circle amplification (RCA) is applied. By merging the single-molecule detection power of RCA reactions with microfluidic technology, it is demonstrated that the identification of specific protein markers can be achieved on tumor-cell surfaces in miniaturized nanoliter reaction droplets. Furthermore, this combined approach of signal amplification in a microfluidic format could extend the utility of existing methods by reducing sample and reagent consumption and enhancing the sensitivities and specificities for various applications, including early diagnosis of cancer.
C1 [Smolina, Irina] Boston Univ, Dept Biomed Engn, Ctr Adv Biotechnol, Boston, MA 02215 USA.
[Konry, Tania; Irimia, Daniel; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
[Konry, Tania; Irimia, Daniel; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Konry, Tania; Irimia, Daniel; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA.
[Yarmush, Martin L.] New York Methodist Hosp, Dept Anesthesiol, Brooklyn, NY 11215 USA.
RP Smolina, I (reprint author), Boston Univ, Dept Biomed Engn, Ctr Adv Biotechnol, 36 Cummington St, Boston, MA 02215 USA.
EM IReis@sbi.org; ismolina@bu.edu
OI Irimia, Daniel/0000-0001-7347-2082
FU NIH [1R21RR025371-01]
FX We thank Ajay Shah for slides preparation and Dr. Jon Edd and Dr. Erkin
Seker for technical assistance in the device operation. This work was
supported by a NIH research grant (1R21RR025371-01) to I.S.
NR 21
TC 31
Z9 34
U1 4
U2 38
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1613-6810
J9 SMALL
JI Small
PD FEB 7
PY 2011
VL 7
IS 3
BP 395
EP 400
DI 10.1002/smll.201001620
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 724WL
UT WOS:000287607000016
PM 21294269
ER
PT J
AU Yu, LY
Hales, CA
AF Yu, Lunyin
Hales, Charles A.
TI Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary
hypertension and vascular remodeling in rats
SO RESPIRATORY RESEARCH
LA English
DT Article
ID CELL-DERIVED FACTOR-1-ALPHA; HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS;
MIGRATION; RECRUITMENT; INHIBITION; MICE; ENGRAFTMENT; HEPARIN; BLOOD
AB Background: CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood.
Methods: In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats.
Results: We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP), ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S)) and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats.
Conclusions: The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment.
C1 [Yu, Lunyin; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA.
RP Yu, LY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA.
EM lyu3@partners.org
FU ATS/Pulmonary Hypertension Research Grant [PH-08-010]; NIH [HL39150];
Susannah Wood Fund
FX This work was supported by ATS/Pulmonary Hypertension Research Grant
PH-08-010 (L. Yu) and NIH grants HL39150 (C.A. Hales) and by Susannah
Wood Fund.
NR 50
TC 16
Z9 16
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-9921
J9 RESP RES
JI Respir. Res.
PD FEB 4
PY 2011
VL 12
AR 21
DI 10.1186/1465-9921-12-21
PG 11
WC Respiratory System
SC Respiratory System
GA 723RP
UT WOS:000287524800001
PM 21294880
ER
PT J
AU Radhakrishnan, H
Wu, WC
Boas, D
Franceschini, MA
AF Radhakrishnan, Harsha
Wu, Weicheng
Boas, David
Franceschini, Maria Angela
TI Study of neurovascular coupling by modulating neuronal activity with
GABA
SO BRAIN RESEARCH
LA English
DT Article
DE Neurovascular coupling; GABA; Diffuse optical imaging; Near infrared
spectroscopy; EEG; Somatosensory evoked potential
ID RAT SOMATOSENSORY CORTEX; CEREBRAL-BLOOD-FLOW; DIFFUSE OPTICAL
MEASUREMENT; NEAR-INFRARED SPECTROSCOPY; ACTIVITY-DEPENDENT INCREASES;
EVOKED-POTENTIALS; BARREL CORTEX; FUNCTIONAL MRI; HUMAN BRAIN;
HEMODYNAMIC-RESPONSES
AB Fundamental to the interpretation of neurovascular coupling is determining the neuronal activity that accounts for functional hyperemia. Recently, synaptic and not spiking activity has been found to be responsible for the hemodynamic response. Using pharmacological manipulation in rats, we want to further determine whether the cortical synaptic activity generated by the thalamic input or the subsequent synaptic activity related to secondary cortical processing is driving the hemodynamic response. In this study, we topically applied gamma-aminobutyric acid (GABA) in the somatosensory cortex and used electrical forepaw stimulation to evoke neural and vascular activity. In a group of 8 animals, using laminar electrophysiology, we verified that topical application of GABA for 20 mm does not affect layer IV synaptic activity but reduces subsequent activity in the supragranular and infragranular layers. In another group of 8 animals, we simultaneously measured the electrical and vascular responses with scalp electroencephalography (EEG) and diffuse optical imaging (DOI), respectively. We decomposed somatosensory evoked potentials (SEP) into three major components: P1, N1, and P2, where P1 represents the thalamic input activity originating in layer IV and N1 and P2 represent the subsequent cortical transmissions. We verified that GABA infusion in the somatosensory cortex does not significantly reduce the P1 SEP component but strongly reduces the N1 and P2 components. We found that GABA also elicits a large reduction in the hemodynamic responses, which correlate with the reduction in N1 and P2 components. These results suggest that the hemodynamic response is predominantly driven by cortico-cortical interactions and not by the initial thalamocortical activity in layer IV. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Radhakrishnan, Harsha; Wu, Weicheng; Boas, David; Franceschini, Maria Angela] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Photon Migrat Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
RP Radhakrishnan, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Photon Migrat Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, 149,13th St,Rm 2277, Charlestown, MA 02129 USA.
EM harsha@nmr.mgh.harvard.edu
RI Radhakrishnan, Harsha/K-5557-2012
FU US National Institutes of Health (NIH) [R01-EB001954]
FX We thank Anna Devor, Diego Contreras, and Bruce Jenkins for valuable
discussions and Michael Moskowitz and Nadege Roche for critical reading
of the manuscript. This research is supported by the US National
Institutes of Health (NIH) grant R01-EB001954.
NR 66
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD FEB 4
PY 2011
VL 1372
BP 1
EP 12
DI 10.1016/j.brainres.2010.11.082
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 720PX
UT WOS:000287293700001
PM 21145313
ER
PT J
AU Basu, U
Meng, FL
Keim, C
Grinstein, V
Pefanis, E
Eccleston, J
Zhang, TT
Myers, D
Wasserman, CR
Wesemann, DR
Januszyk, K
Gregory, RI
Deng, HT
Lima, CD
Alt, FW
AF Basu, Uttiya
Meng, Fei-Long
Keim, Celia
Grinstein, Veronika
Pefanis, Evangelos
Eccleston, Jennifer
Zhang, Tingting
Myers, Darienne
Wasserman, Caitlyn R.
Wesemann, Duane R.
Januszyk, Kurt
Gregory, Richard I.
Deng, Haiteng
Lima, Christopher D.
Alt, Frederick W.
TI The RNA Exosome Targets the AID Cytidine Deaminase to Both Strands of
Transcribed Duplex DNA Substrates
SO CELL
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; ANTIBODY DIVERSIFICATION ENZYME; CHROMOSOMAL
R-LOOPS; PROTEIN-KINASE-A; SOMATIC HYPERMUTATION; POLYMERASE-II;
B-CELLS; MECHANISM; REGIONS; PHOSPHORYLATION
AB Activation-induced cytidine deaminase (AID) initiates immunoglobulin (Ig) heavy-chain (IgH) class switch recombination (CSR) and Ig variable region somatic hypermutation (SHM) in B lymphocytes by deaminating cytidines on template and nontemplate strands of transcribed DNA substrates. However, the mechanism of AID access to the template DNA strand, particularly when hybridized to a nascent RNA transcript, has been an enigma. We now implicate the RNA exosome, a cellular RNA-processing/degradation complex, in targeting AID to both DNA strands. In B lineage cells activated for CSR, the RNA exosome associates with AID, accumulates on IgH switch regions in an AID-dependent fashion, and is required for optimal CSR. Moreover, both the cellular RNA exosome complex and a recombinant RNA exosome core complex impart robust AID-and transcription-dependent DNA deamination of both strands of transcribed SHM substrates in vitro. Our findings reveal a role for noncoding RNA surveillance machinery in generating antibody diversity.
C1 [Basu, Uttiya; Meng, Fei-Long; Eccleston, Jennifer; Zhang, Tingting; Myers, Darienne; Wasserman, Caitlyn R.; Wesemann, Duane R.; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Program Cellular & Mol Med,Dept Genet,Childrens H, Boston, MA 02115 USA.
[Basu, Uttiya; Meng, Fei-Long; Eccleston, Jennifer; Zhang, Tingting; Myers, Darienne; Wasserman, Caitlyn R.; Wesemann, Duane R.; Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston,Dept Genet, Boston, MA 02115 USA.
[Basu, Uttiya; Keim, Celia; Grinstein, Veronika; Pefanis, Evangelos] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Deng, Haiteng] Rockefeller Univ, Prote Res Ctr, New York, NY 10065 USA.
[Gregory, Richard I.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Harvard Stem Cell Inst,Childrens Hosp Boston, Boston, MA 02115 USA.
[Januszyk, Kurt; Lima, Christopher D.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Deng, Haiteng] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
RP Basu, U (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Program Cellular & Mol Med,Dept Genet,Childrens H, 300 Longwood Ave, Boston, MA 02115 USA.
EM ub2121@columbia.edu; alt@enders.tch.harvard.edu
OI Lima, Christopher/0000-0002-9163-6092
FU National Institute of Health [AI31541, GM079196]; Columbia University;
Regeneron Pharmaceuticals; Cancer Biology training grant [CA09503-23];
Leukemia Research Foundation
FX We thank Bjoern Schwer, Jason Rodriguez, Stephen Goff, Bruce Stillman,
and Tasuku Honjo for providing reagents and/or protocols. We also thank
Bjoern Schwer and Cosmas Giallourakis for critically reading the
manuscript. This work was supported by National Institute of Health
grants AI31541 (to F. W. A.) and GM079196 (to K.J. and C. D. L.); by
Trustees of Columbia University Faculty startup funds (to U. B.); and by
funds from Regeneron Pharmaceuticals (in support of E. P.). F.-L. M. is
a fellow of Cancer Research Institute of New York. C. K. was supported
by a Cancer Biology training grant CA09503-23. K.J. is a fellow of the
American Cancer Society (PF-10-236-01-RMC). U. B. is a Special Fellow of
the Leukemia and Lymphoma Society of America and the recipient of a New
Investigator Award from the Leukemia Research Foundation. F. W. A. is an
Investigator of the Howard Hughes Medical Institute.
NR 80
TC 131
Z9 140
U1 1
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 4
PY 2011
VL 144
IS 3
BP 353
EP 363
DI 10.1016/j.cell.2011.01.001
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 716MK
UT WOS:000286973100008
PM 21255825
ER
PT J
AU Koh, KP
Yabuuchi, A
Rao, S
Huang, Y
Cunniff, K
Nardone, J
Laiho, A
Tahiliani, M
Sommer, CA
Mostoslavsky, G
Lahesmaa, R
Orkin, SH
Rodig, SJ
Daley, GQ
Rao, A
AF Koh, Kian Peng
Yabuuchi, Akiko
Rao, Sridhar
Huang, Yun
Cunniff, Kerrianne
Nardone, Julie
Laiho, Asta
Tahiliani, Mamta
Sommer, Cesar A.
Mostoslavsky, Gustavo
Lahesmaa, Riitta
Orkin, Stuart H.
Rodig, Scott J.
Daley, George Q.
Rao, Anjana
TI Tet1 and Tet2 Regulate 5-Hydroxymethylcytosine Production and Cell
Lineage Specification in Mouse Embryonic Stem Cells
SO CELL STEM CELL
LA English
DT Article
ID DNA METHYLATION; SELF-RENEWAL; TRANSCRIPTIONAL NETWORK; MYELOID CANCERS;
GENOMIC DNA; 5-METHYLCYTOSINE; PLURIPOTENCY; CONVERSION; PROTEINS; ROLES
AB TET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras. Consistent with these findings, Tet1-depleted ESCs form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells. Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs.
C1 [Koh, Kian Peng; Huang, Yun; Tahiliani, Mamta; Lahesmaa, Riitta; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Yabuuchi, Akiko; Rao, Sridhar; Cunniff, Kerrianne; Orkin, Stuart H.; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Yabuuchi, Akiko; Rao, Sridhar; Cunniff, Kerrianne; Orkin, Stuart H.; Daley, George Q.] Harvard Stem Cell Inst, Dana Faber Canc Inst, Boston, MA 02115 USA.
[Nardone, Julie] Cell Signaling Technol, Bioinformat, Danvers, MA 01923 USA.
[Laiho, Asta; Lahesmaa, Riitta] Univ Turku, Turku Ctr Biotechnol, FI-20520 Turku, Finland.
[Laiho, Asta; Lahesmaa, Riitta] Abo Akad Univ, FI-20520 Turku, Finland.
[Sommer, Cesar A.; Mostoslavsky, Gustavo] Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Boston, MA 02118 USA.
[Sommer, Cesar A.; Mostoslavsky, Gustavo] Boston Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02118 USA.
[Orkin, Stuart H.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Rodig, Scott J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Daley, George Q.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Koh, Kian Peng; Huang, Yun; Tahiliani, Mamta; Lahesmaa, Riitta; Rao, Anjana] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
RP Rao, A (reprint author), La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
EM arao@idi.harvard.edu
RI Sommer, Cesar /H-9187-2013;
OI Huang, Yun/0000-0001-5950-9168
FU NIH [AI44432, CA42471, RC1-DA028422, RO1-DK70055, RO1-DK59279,
UO1-HL100001]; ARRA [RC2-HL102815]; Roche Foundation for Anemia
Research; Alex's Lemonade Stand; Harvard Stem Cell Institute; American
Heart Association; Academy of Finland; Sigrid Juselius Foundation;
Burroughs Wellcome Fund; Leukemia and Lymphoma Society; Johnson Johnson;
Verastem; Epizyme; iPierian; Solasia KK; MPM Capital, L.L.P.
FX We thank P. Gadue and G. Keller for CD4-Foxa2/GFP-Bry ESCs, C. Unitt and
staff at the Specialized Rodent Histopathology Services, Brigham and
Women's Hospital for mouse histology and GFP staining, P. Junni at the
Finnish Microarray and Sequencing Centre, Turku Centre for Biotechnology
for sample processing and array hybridization, and K. E. Waraska at the
Biopolymers facility, Harvard Medical School, for low-density
array-based q-PCR. This work was funded by NIH grants AI44432, CA42471,
and RC1-DA028422 (to A.R.); RO1-DK70055, RO1-DK59279, UO1-HL100001, and
special funds from the ARRA stimulus package RC2-HL102815 (to GOD); the
Roche Foundation for Anemia Research, Alex's Lemonade Stand, and the
Harvard Stem Cell Institute (to GOD); an American Heart Association
postdoctoral fellowship (to K.P.K); and grants from The Academy of
Finland and The Sigrid Juselius Foundation (to R.L.). G.Q.D. is an
affiliate member of the Broad Institute, a recipient of Clinical
Scientist Awards in Translational Research from the Burroughs Wellcome
Fund and the Leukemia and Lymphoma Society, and an investigator of the
Howard Hughes Medical Institute and the Manton Center for Orphan Disease
Research. G.Q.D. is a member of the scientific advisory boards and holds
stock in or receives consulting fees from the following companies:
Johnson & Johnson, Verastem, Epizyme, iPierian, Solasia KK, and MPM
Capital, L.L.P..
NR 48
TC 337
Z9 353
U1 7
U2 69
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 FEB 4
PY 2011
VL 8
IS 2
BP 200
EP 213
DI 10.1016/j.stem.2011.01.008
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 725GO
UT WOS:000287633400013
PM 21295276
ER
PT J
AU Sturzu, AC
Wu, SM
AF Sturzu, Anthony C.
Wu, Sean M.
TI Developmental and Regenerative Biology of Multipotent Cardiovascular
Progenitor Cells
SO CIRCULATION RESEARCH
LA English
DT Review
DE cardiovascular disease; stem cells; regeneration; cardiac development;
cardiomyocytes
ID CARDIAC STEM-CELLS; ADULT MAMMALIAN CARDIOMYOCYTES; BINDING CASSETTE
TRANSPORTER; EPICARDIUM-DERIVED CELLS; SIDE POPULATION CELLS;
MYOCARDIAL-INFARCTION; DEFINED FACTORS; SMOOTH-MUSCLE; BONE-MARROW;
IN-VIVO
AB Our limited ability to improve the survival of patients with heart failure is attributable, in part, to the inability of the mammalian heart to meaningfully regenerate itself. The recent identification of distinct families of multipotent cardiovascular progenitor cells from endogenous, as well as exogenous, sources, such as embryonic and induced pluripotent stem cells, has raised much hope that therapeutic manipulation of these cells may lead to regression of many forms of cardiovascular disease. Although the exact source and cell type remains to be clarified, our greater understanding of the scientific underpinning behind developmental cardiovascular progenitor cell biology has helped to clarify the origin and properties of diverse cells with putative cardiogenic potential. In this review, we highlight recent advances in the understanding of cardiovascular progenitor cell biology from embryogenesis to adulthood and their implications for therapeutic cardiac regeneration. We believe that a detailed understanding of cardiogenesis will inform future applications of cardiovascular progenitor cells in heart failure therapy and regenerative medicine. (Circ Res. 2011;108:353-364.)
C1 [Sturzu, Anthony C.; Wu, Sean M.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Wu, SM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, CPZN 3224 Simches Bldg,185 Cambridge St, Boston, MA 02114 USA.
EM smwu@partners.org
FU NIH [T32 HL07208-33, OD004411]; NIH/National Heart, Lung, and Blood
Institute [HL081086, HL100408]; Harvard Stem Cell Institute
FX A.C.S. is supported by NIH training grant T32 HL07208-33. S.M.W. is
supported by grants from the NIH/National Heart, Lung, and Blood
Institute (grants HL081086 and HL100408); NIH Director's New Innovator
Award (OD004411); and Harvard Stem Cell Institute.
NR 120
TC 41
Z9 45
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD FEB 4
PY 2011
VL 108
IS 3
BP 353
EP 364
DI 10.1161/CIRCRESAHA.110.227066
PG 12
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 715YB
UT WOS:000286930500012
PM 21293007
ER
PT J
AU da-Silva, WS
Ribich, S
Drigo, RAE
Castillo, M
Patti, ME
Bianco, AC
AF da-Silva, Wagner S.
Ribich, Scott
Arrojo e Drigo, Rafael
Castillo, Melany
Patti, Mary-Elizabeth
Bianco, Antonio C.
TI The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid
accelerate thyroid hormone activation and energy expenditure
SO FEBS LETTERS
LA English
DT Article
DE Thyroid hormone; Deiodinase; Chemical chaperone; Oxygen consumption;
Metabolism
ID TYPE-2 IODOTHYRONINE DEIODINASE; RETICULUM-ASSOCIATED DEGRADATION;
ADIPOSE-TISSUE; INSULIN; TRIIODOTHYRONINE; CONVERSION; THYROXINE;
APOPTOSIS; STRESS; CELLS
AB Exposure of cell lines endogenously expressing the thyroid hormone activating enzyme type 2 deiodinase (D2) to the chemical chaperones tauroursodeoxycholic acid (TUDCA) or 4-phenylbutiric acid (4-PBA) increases D2 expression, activity and T3 production. In brown adipocytes, TUDCA or 4-PBA induced T3-dependent genes and oxygen consumption (similar to 2-fold), an effect partially lost in D2 knockout cells. In wild type, but not in D2 knockout mice, administration of TUDCA lowered the respiratory quotient, doubled brown adipose tissue D2 activity and normalized the glucose intolerance associated with high fat feeding. Thus, D2 plays a critical role in the metabolic effects of chemical chaperones. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
C1 [da-Silva, Wagner S.; Ribich, Scott; Arrojo e Drigo, Rafael; Castillo, Melany; Bianco, Antonio C.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33143 USA.
[Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Bianco, AC (reprint author), 1400 NW 10th St,Suite 816, Miami, FL 33136 USA.
EM abianco@deiodinase.org
RI Bianco, Antonio/A-4965-2008; da Silva, Wagner/A-7835-2008; Arrojo e
Drigo, Rafael/F-6213-2010;
OI Bianco, Antonio/0000-0001-7737-6813; da Silva,
Wagner/0000-0002-0001-0386; Arrojo e Drigo, Rafael/0000-0001-7712-013X
FU NIDDK [DK65055]
FX We are grateful to John W. Harney for the outstanding technical
assistance. Grant support from NIDDK(DK65055). W.S.S. is a fellow of the
Pew Charitable Trusts Foundation.
NR 32
TC 18
Z9 18
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD FEB 4
PY 2011
VL 585
IS 3
BP 539
EP 544
DI 10.1016/j.febslet.2010.12.044
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 712HR
UT WOS:000286657700015
PM 21237159
ER
PT J
AU Ting, DT
Lipson, D
Paul, S
Brannigan, BW
Akhavanfard, S
Coffman, EJ
Contino, G
Deshpande, V
Iafrate, AJ
Letovsky, S
Rivera, MN
Bardeesy, N
Maheswaran, S
Haber, DA
AF Ting, David T.
Lipson, Doron
Paul, Suchismita
Brannigan, Brian W.
Akhavanfard, Sara
Coffman, Erik J.
Contino, Gianmarco
Deshpande, Vikram
Iafrate, A. John
Letovsky, Stan
Rivera, Miguel N.
Bardeesy, Nabeel
Maheswaran, Shyamala
Haber, Daniel A.
TI Aberrant Overexpression of Satellite Repeats in Pancreatic and Other
Epithelial Cancers
SO SCIENCE
LA English
DT Article
ID PERVASIVE TRANSCRIPTION; HUMAN GENOMES; SMALL RNAS; DIFFERENTIATION;
ELEMENTS; MOUSE; CELLS
AB Satellite repeats in heterochromatin are transcribed into noncoding RNAs that have been linked to gene silencing and maintenance of chromosomal integrity. Using digital gene expression analysis, we showed that these transcripts are greatly overexpressed in mouse and human epithelial cancers. In 8 of 10 mouse pancreatic ductal adenocarcinomas (PDACs), pericentromeric satellites accounted for a mean 12% (range 1 to 50%) of all cellular transcripts, a mean 40-fold increase over that in normal tissue. In 15 of 15 human PDACs, alpha satellite transcripts were most abundant and HSATII transcripts were highly specific for cancer. Similar patterns were observed in cancers of the lung, kidney, ovary, colon, and prostate. Derepression of satellite transcripts correlated with overexpression of the long interspersed nuclear element 1 (LINE-1) retrotransposon and with aberrant expression of neuroendocrine-associated genes proximal to LINE-1 insertions. The overexpression of satellite transcripts in cancer may reflect global alterations in heterochromatin silencing and could potentially be useful as a biomarker for cancer detection.
C1 [Ting, David T.; Paul, Suchismita; Brannigan, Brian W.; Akhavanfard, Sara; Coffman, Erik J.; Contino, Gianmarco; Deshpande, Vikram; Iafrate, A. John; Rivera, Miguel N.; Bardeesy, Nabeel; Maheswaran, Shyamala; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Ting, David T.; Paul, Suchismita; Brannigan, Brian W.; Akhavanfard, Sara; Coffman, Erik J.; Contino, Gianmarco; Deshpande, Vikram; Iafrate, A. John; Rivera, Miguel N.; Bardeesy, Nabeel; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
[Ting, David T.; Paul, Suchismita; Brannigan, Brian W.; Akhavanfard, Sara; Coffman, Erik J.; Contino, Gianmarco; Deshpande, Vikram; Iafrate, A. John; Rivera, Miguel N.; Bardeesy, Nabeel; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Ting, David T.; Paul, Suchismita; Brannigan, Brian W.; Akhavanfard, Sara; Coffman, Erik J.; Contino, Gianmarco; Deshpande, Vikram; Iafrate, A. John; Rivera, Miguel N.; Bardeesy, Nabeel; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Lipson, Doron; Letovsky, Stan] Helicos BioSci Corp, Cambridge, MA 02139 USA.
RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM haber@helix.mgh.harvard.edu
OI Contino, Gianmarco/0000-0001-5874-0405
FU Pancreatic Cancer Action Network-American Association for Cancer
Research; Warshaw Institute for Pancreatic Cancer Research; Fond.
Veronesi; Howard Hughes Medical Institute; National Cancer Institute
[CA129933]
FX This work was supported by a Pancreatic Cancer Action Network-American
Association for Cancer Research Fellowship and the Warshaw Institute for
Pancreatic Cancer Research (D.T.T.); Fond. Veronesi (G.C.); Howard
Hughes Medical Institute (D.A.H. and M.N.R.); and National Cancer
Institute CA129933 (D.A.H). We thank T. Raz, P. Kapranov, E. Giladi, and
J. Whetstine for helpful discussions and K. Haigis and K. Wong for
providing mouse colon and lung tumors, respectively. Massachusetts
General Hospital and the authors (D.A.H., D.L., S.M., D.T.T.) have filed
a patent application relating to detection of satellite and LINE
sequences in human cancers.
NR 23
TC 168
Z9 179
U1 2
U2 28
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 FEB 4
PY 2011
VL 331
IS 6017
BP 593
EP 596
DI 10.1126/science.1200801
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715ZE
UT WOS:000286933600056
PM 21233348
ER
PT J
AU Massimini, DF
Warner, JJP
Li, GA
AF Massimini, Daniel F.
Warner, Jon J. P.
Li, Guoan
TI Non-invasive determination of coupled motion of the scapula and
humerus-An in-vitro validation
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Shoulder; Kinematics; Fluoroscopy; Radiostereometric; Validation
ID PROFESSIONAL BASEBALL PITCHERS; GLENOHUMERAL JOINT KINEMATICS;
ARTICULAR-CARTILAGE CONTACT; GEOMETRIC IMAGE DISTORTION; TISSUE ARTIFACT
ASSESSMENT; SCAPULOHUMERAL RHYTHM; SHOULDER KINEMATICS; VIVO
MEASUREMENT; ELEVATION; TRANSLATION
AB Measuring the motion of the scapula and humerus with sub-millimeter levels of accuracy in six-degrees-of-freedom (6-DOF) is a challenging problem. The current methods to measure shoulder joint motion via the skin do not produce clinically significant levels of accuracy. Thus, the purpose of this study was to validate a non-invasive markerless dual fluoroscopic imaging system (DFIS) model-based tracking technique for measuring dynamic in-vivo shoulder kinematics. Our DFIS tracks the positions of bones based on their projected silhouettes to contours on recorded pairs of fluoroscopic images. For this study, we compared markerlessly tracking the bones of the scapula and humerus to track them with implanted titanium spheres using a radiostereometric analysis (RSA) while manually manipulating a cadaver specimen's arms. Additionally, we report the repeatability of the DFIS to track the scapula and humerus during dynamic shoulder motion. The difference between the markerless model-based tracking technique and the RSA was +/- 0.3 mm in translation and +/- 0.5 degrees in rotation. Furthermore, the repeatability of the markerless DFIS model-based tracking technique for the scapula and humerus was +/- 0.2 mm and +/- 0.4 degrees, respectively. The model-based tracking technique achieves an accuracy that is similar to an invasive RSA tracking technique and is highly suited for non-invasively studying the in-vivo motion of the shoulder. This technique could be used to investigate the scapular and humeral biomechanics in both healthy individuals and in patients with various pathologies under a variety of dynamic shoulder motions encountered during the activities of daily living. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Massimini, Daniel F.; Warner, Jon J. P.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA 02114 USA.
[Massimini, Daniel F.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, GRJ-1215,55 Fruit St, Boston, MA 02114 USA.
EM gli1@partners.org
RI Lempereur, Mathieu/G-5470-2012
NR 43
TC 18
Z9 18
U1 2
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
J9 J BIOMECH
JI J. Biomech.
PD FEB 3
PY 2011
VL 44
IS 3
BP 408
EP 412
DI 10.1016/j.jbiomech.2010.10.003
PG 5
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 724BL
UT WOS:000287551000008
PM 21055753
ER
PT J
AU Kim, JS
Fan, CY
Choi, D
Jang, IK
Lee, JM
Kim, TH
Park, SM
Paik, SI
Ko, YG
Hong, MK
Jang, Y
Chung, N
AF Kim, Jung-Sun
Fan, Chunyu
Choi, Donghoon
Jang, Ik-Kyung
Lee, Jung Myung
Kim, Tae Hoon
Park, Sang Min
Paik, Sung Il
Ko, Young-Guk
Hong, Myeong-Ki
Jang, Yangsoo
Chung, Namsik
TI Different patterns of neointimal coverage between acute coronary
syndrome and stable angina after various types of drug-eluting stents
implantation; 9-month follow-up optical coherence tomography study
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Acute coronary syndrome; Drug-eluting stent; Tomography; Optical
coherence
ID LARGE 2-INSTITUTIONAL COHORT; ROUTINE CLINICAL-PRACTICE;
MYOCARDIAL-INFARCTION; THROMBOSIS; PACLITAXEL; PLACEMENT
AB Background: Acute coronary syndrome (ACS) is an independent risk factor for late stent thrombosis which might be related to the impaired vascular healing after drug-eluting stent (DES) due to the disruption of plaques and thrombus formation. Therefore, we investigated the vascular response after various DES implantations between ACS and stable angina pectoris (SAP) using optical coherence tomography (OCT).
Methods: Ninety-one patients [49 ACS: 20 sirolimus-eluting (SES), 12 paclitaxel-eluting (PES) and 17 zotarolimus eluting stent (ZES) and 42 SAP: 15 SES, 12 PES and 15 ZES] underwent OCT at 9 months after stent implantation. Neointimal coverage and malapposition were evaluated in 21,939 struts in 2269-mm stented segments.
Results: In the ACS group, the incidence of uncovered and malapposed struts was significantly higher (8.9 +/- 13.7 vs 2.9 +/- 6.2%, p=0.01 and 2.2 +/- 5.6 vs 0.5 +/- 2.0%, p=0.02). Among the three DESs tested, SES showed a significantly higher rate of uncovered struts in the ACS group (17.3 +/- 13.4 vs 4.4 +/- 6.2%, p=0.003). PES had a trend toward higher rate of uncovered and malapposed struts in the ACS groups (6.7 +/- 7.6 vs 4.0 +/- 9.0%, p=0.13) while ZES was similar in both groups.
Conclusion: The patterns of neointimal coverage and malapposition at 9 months after DES implantation were different between ACS and SAP, and variable among the DES type between two groups. Therefore, the present study suggests that vascular response after DES implantation might be influenced by both clinical presentation and type of DES. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Kim, Jung-Sun; Choi, Donghoon; Lee, Jung Myung; Kim, Tae Hoon; Park, Sang Min; Paik, Sung Il; Ko, Young-Guk; Hong, Myeong-Ki; Jang, Yangsoo; Chung, Namsik] Yonsei Univ, Coll Med, Div Cardiol, Yonsei Cardiovasc Ctr, Seoul 120752, South Korea.
[Fan, Chunyu] ShanXi Med Univ, Hosp 1, Div Cardiol, Taiyuan, Peoples R China.
[Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
RP Choi, D (reprint author), Yonsei Univ, Coll Med, Div Cardiol, Yonsei Cardiovasc Ctr, 250 Seongsanno, Seoul 120752, South Korea.
EM cdhlyj@yuhs.ac
RI Jang, Yang Soo/D-4803-2012;
OI Kim, Tae-Hoon/0000-0003-4200-3456
FU Ministry of Health & Welfare, Republic of Korea [A085136]; Yonsei
University College of Medicine; Yonsei University; Cardiovascular
Research Center, Seoul, Korea
FX This study was supported by a grant of the Korea Health 21 R&D Project,
Ministry of Health & Welfare, Republic of Korea (A085136) and was
supported by a faculty research grant of Yonsei University College of
Medicine for 2007 and by Yonsei University Research Fund of 2007 and
Cardiovascular Research Center, Seoul, Korea.
NR 30
TC 25
Z9 29
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD FEB 3
PY 2011
VL 146
IS 3
BP 341
EP 346
DI 10.1016/j.ijcard.2009.07.012
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 709SA
UT WOS:000286460500015
PM 19709765
ER
PT J
AU Mitsiades, CS
AF Mitsiades, Constantine S.
TI How "immunomodulatory" are IMIDs?
SO BLOOD
LA English
DT Editorial Material
ID MULTIPLE-MYELOMA; LENALIDOMIDE; THALIDOMIDE
C1 Dana Farber Canc Inst, Boston, MA 02215 USA.
RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA.
NR 10
TC 9
Z9 9
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 3
PY 2011
VL 117
IS 5
BP 1440
EP 1441
DI 10.1182/blood-2010-11-317156
PG 3
WC Hematology
SC Hematology
GA 715WV
UT WOS:000286925500004
PM 21292783
ER
PT J
AU Mansoor, A
Pittaluga, S
Beck, PL
Wilson, WH
Ferry, JA
Jaffe, ES
AF Mansoor, Adnan
Pittaluga, Stefania
Beck, Paul L.
Wilson, Wyndham H.
Ferry, Judith A.
Jaffe, Elaine S.
TI NK-cell enteropathy: a benign NK-cell lymphoproliferative disease
mimicking intestinal lymphoma: clinicopathologic features and follow-up
in a unique case series
SO BLOOD
LA English
DT Article
ID NATURAL-KILLER-CELLS; DELTA T-CELL; CELIAC-DISEASE; ADAPTIVE IMMUNITY;
MUCOSAL; PROLIFERATION; SKIN; LYMPHOCYTES; DISORDER; INNATE
AB Intestinal T-cell and natural killer (NK)-cell lymphomas are clinically aggressive and can be challenging to diagnose in small endoscopic biopsies. We describe 8 patients in whom atypical NK-cell lymphoproliferative lesions mimicked NK-or T-cell lymphoma. The patients (2 men; 6 women; ages 27-68 years) presented with vague gastrointestinal symptoms with lesions involving stomach, duodenum, small intestine, and colon. At endoscopy, the lesions exhibited superficial ulceration, edema, and hemorrhage. Biopsies revealed a mucosal infiltrate of atypical cells with an NK-cell phenotype (CD56(+)/TIA-1(+)/Granzyme B(+)/cCD3(+)), which displaced but did not invade the glandular epithelium. Epstein-Barr virus-encoded RNA in situ hybridization was negative, and T-cell receptor-gamma gene rearrangement showed no evidence of a clonal process. Based on an original diagnosis of lymphoma, 3 patients received aggressive chemotherapy followed by autologous bone marrow transplantation in 2. Five patients were followed without treatment. However, no patient developed progressive disease or died of lymphoma (median follow-up, 30 months). Repeat endoscopies in 6 of 8 patients showed persistence or recurrence of superficial gastrointestinal lesions. This unique entity mimics intestinal and NK-/T-cell lymphomas on endoscopic biopsies and can result in erroneous diagnosis, leading to aggressive chemotherapy. We propose the term "NK-cell enteropathy" for this syndrome of as yet unknown etiology. (Blood. 2011; 117(5): 1447-1452)
C1 [Mansoor, Adnan] Calgary Lab Serv, Dept Pathol & Lab Med, Calgary, AB, Canada.
[Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Beck, Paul L.] Univ Calgary, Div Gastroenterol, Calgary, AB, Canada.
[Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Jaffe, ES (reprint author), NIH, Hematopathol Sect, Pathol Lab, 10 Ctr Dr,Bldg 10,Rm 2B42, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
FU Center for Cancer Research, National Cancer Institute
FX This work was supported by the intramural research budget of the Center
for Cancer Research, National Cancer Institute.
NR 39
TC 42
Z9 45
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 3
PY 2011
VL 117
IS 5
BP 1447
EP 1452
DI 10.1182/blood-2010-08-302737
PG 6
WC Hematology
SC Hematology
GA 715WV
UT WOS:000286925500009
PM 20966166
ER
PT J
AU Sivina, M
Hartmann, E
Kipps, TJ
Rassenti, L
Krupnik, D
Lerner, S
LaPushin, R
Xiao, LC
Huang, XL
Werner, L
Neuberg, D
Kantarjian, H
O'Brien, S
Wierda, WG
Keating, MJ
Rosenwald, A
Burger, JA
AF Sivina, Mariela
Hartmann, Elena
Kipps, Thomas J.
Rassenti, Laura
Krupnik, Diana
Lerner, Susan
LaPushin, Ruth
Xiao, Lianchun
Huang, Xuelin
Werner, Lillian
Neuberg, Donna
Kantarjian, Hagop
O'Brien, Susan
Wierda, William G.
Keating, Michael J.
Rosenwald, Andreas
Burger, Jan A.
TI CCL3 (MIP-1 alpha) plasma levels and the risk for disease progression in
chronic lymphocytic leukemia
SO BLOOD
LA English
DT Article
ID B-CELL LYMPHOMA; GENE MUTATION STATUS; T-CELLS; CD38 EXPRESSION;
SURVIVAL; RECEPTOR; CHEMOKINES; ANTIGEN; ZAP-70; MICROENVIRONMENT
AB B-cell receptor (BCR) signaling has been inferred as an important mechanism for disease progression in chronic lymphocytic leukemia (CLL) and other B-cell malignancies. In response to BCR activation, CLL cells secrete the chemokine CCL3, which fosters interactions between CLL cells and the leukemia micro-environment. CCL3 secretion correlates with expression of the 70-kDa zeta-associated protein (ZAP-70) and responsiveness of the CLL clone to BCR stimulation. Here, we measured CCL3 plasma levels by enzyme-linked immunosorbent assay (ELISA) in 351 CLL patients and examined CCL3 levels for associations with established prognostic markers and time from diagnosis to initial therapy. We found that CCL3 plasma concentrations were strongly associated with established prognostic markers. In a Cox proportional hazards regression model, CCL3 as well as established prognostic markers (immunoglobulin heavy chain variable-region mutation status, CD38 or ZAP-70 cytogenetics, clinical stage) were significantly associated with time to treatment. Multivariable analysis revealed that CCL3 (hazard ratio [HR] = 2.33, P < .0001), advanced clinical stage (HR = 2.75, P = .0025), poor risk cytogenetics (del 17p, HR = 2.38; del11q, HR = 2.36, P = .001), and CD38 expression (HR = 1.43, P = .023) were independent prognostic markers. Collectively, CCL3 is a novel, robust, and independent prognostic marker in CLL that can easily and reliably be measured by ELISA. CCL3 therefore should become useful for risk assessment in patients with CLL. (Blood. 2011; 117(5): 1662-1669)
C1 [Burger, Jan A.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Unit 428, Houston, TX 77230 USA.
[Hartmann, Elena; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany.
[Kipps, Thomas J.; Rassenti, Laura] Univ Calif San Diego, Dept Med, Chron Lymphocyt Leukemia Res Consortium, San Diego, CA 92103 USA.
[Kipps, Thomas J.; Rassenti, Laura] Univ Calif San Diego, Dept Med, Div Hematol Oncol, San Diego, CA 92103 USA.
[Xiao, Lianchun; Huang, Xuelin] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77230 USA.
[Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Burger, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Unit 428, POB 301402, Houston, TX 77230 USA.
EM jaburger@mdanderson.org
FU CLL Global Research Foundation; ASCO Career Development Award; National
Institutes of Health CLL Research Consortium [PO1-CA81534]
FX This work was supported by CLL Global Research Foundation grants (W.W.,
A.R., and J.B.), an ASCO Career Development Award (J.B.), and National
Institutes of Health CLL Research Consortium (grant PO1-CA81534).
NR 38
TC 59
Z9 60
U1 1
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD FEB 3
PY 2011
VL 117
IS 5
BP 1662
EP 1669
DI 10.1182/blood-2010-09-307249
PG 8
WC Hematology
SC Hematology
GA 715WV
UT WOS:000286925500033
PM 21115978
ER
PT J
AU Liu, FL
White, JA
Antonescu, C
Gusenleitner, D
Quackenbush, J
AF Liu, Fenglong
White, Joseph A.
Antonescu, Corina
Gusenleitner, Daniel
Quackenbush, John
TI GCOD - GeneChip Oncology Database
SO BMC BIOINFORMATICS
LA English
DT Article
ID RENAL-CELL CARCINOMA; EXPRESSION; NORMALIZATION; DIOXYGENASE; TUMOR
AB Background: DNA microarrays have become a nearly ubiquitous tool for the study of human disease, and nowhere is this more true than in cancer. With hundreds of studies and thousands of expression profiles representing the majority of human cancers completed and in public databases, the challenge has been effectively accessing and using this wealth of data.
Description: To address this issue we have collected published human cancer gene expression datasets generated on the Affymetrix GeneChip platform, and carefully annotated those studies with a focus on providing accurate sample annotation. To facilitate comparison between datasets, we implemented a consistent data normalization and transformation protocol and then applied stringent quality control procedures to flag low-quality assays.
Conclusion: The resulting resource, the GeneChip Oncology Database, is available through a publicly accessible website that provides several query options and analytical tools through an intuitive interface.
C1 [White, Joseph A.; Antonescu, Corina; Gusenleitner, Daniel; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Liu, Fenglong] Monsanto Co, Middleton, WI 53562 USA.
RP White, JA (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA.
EM jwhite@jimmy.harvard.edu
FU Dana-Farber Cancer Institute; NLM [5R01 LM008795-04]; NSF [DBI-0649614]
FX This research was supported by institutional funds from the Dana-Farber
Cancer Institute, NLM Grant # 5R01 LM008795-04, and NSF Grant #
DBI-0649614. We thank Priya Karanam (pkaranam@jimmy.harvard.edu) for
assistance with database maintenance and resolving data retrieval
issues.
NR 15
TC 10
Z9 10
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD FEB 3
PY 2011
VL 12
AR 46
DI 10.1186/1471-2105-12-46
PG 10
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 726QW
UT WOS:000287742200001
PM 21291543
ER
PT J
AU Shinagare, AB
Cunto-Amesty, G
Fennessy, FM
AF Shinagare, Atul B.
Cunto-Amesty, Gina
Fennessy, Fiona M.
TI Multiple inflammatory nodules: a differential diagnosis of new pulmonary
nodules in oncology patients
SO CANCER IMAGING
LA English
DT Article
DE Sarcoma; pulmonary nodules; inflammatory nodules
ID PSEUDOTUMOR
AB New pulmonary nodules in an oncology patient are often considered metastatic unless proven otherwise. However, the possibility of an inflammatory cause needs to be considered in this setting. Clinicopathologic correlation is always needed in such cases to establish a diagnosis, especially before initiating a new treatment. The multiplicity of inflammatory nodules in this case, in the form of multiple pulmonary nodules and a spinal soft tissue mass, can be a considerable diagnostic challenge. The potential ramifications of not being familiar with inflammatory pseudotumors and not knowing when to suggest it involve unnecessary and incorrect patient treatment including chemotherapy, and may have medicolegal implications for the radiologist. Therefore all radiologists, especially those involved in oncologic imaging, need to be aware of this entity.
C1 [Shinagare, Atul B.; Fennessy, Fiona M.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA.
[Shinagare, Atul B.; Fennessy, Fiona M.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Cunto-Amesty, Gina] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Shinagare, AB (reprint author), 33 Pond Ave,Apt B 514, Brookline, MA 02445 USA.
EM ashinagare@partners.org
NR 13
TC 1
Z9 1
U1 0
U2 0
PU E-MED
PI LONDON
PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND
SN 1470-7330
J9 CANCER IMAGING
JI Cancer Imaging
PD FEB 3
PY 2011
VL 10
IS 1
BP 205
EP 208
DI 10.1102/1470-7330.2010.0031
PG 4
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 826CG
UT WOS:000295328400001
PM 21300598
ER
PT J
AU Diep, CQ
Ma, DD
Deo, RC
Holm, TM
Naylor, RW
Arora, N
Wingert, RA
Bollig, F
Djordjevic, G
Lichman, B
Zhu, H
Ikenaga, T
Ono, F
Englert, C
Cowan, CA
Hukriede, NA
Handin, RI
Davidson, AJ
AF Diep, Cuong Q.
Ma, Dongdong
Deo, Rahul C.
Holm, Teresa M.
Naylor, Richard W.
Arora, Natasha
Wingert, Rebecca A.
Bollig, Frank
Djordjevic, Gordana
Lichman, Benjamin
Zhu, Hao
Ikenaga, Takanori
Ono, Fumihito
Englert, Christoph
Cowan, Chad A.
Hukriede, Neil A.
Handin, Robert I.
Davidson, Alan J.
TI Identification of adult nephron progenitors capable of kidney
regeneration in zebrafish
SO NATURE
LA English
DT Article
ID TRANSGENIC ZEBRAFISH; GENES; MORPHOGENESIS; PRONEPHROS; REPORTER
AB Loss of kidney function underlies many renal diseases(1). Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones(2,3). By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury(4,5), providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.
C1 [Diep, Cuong Q.; Ma, Dongdong; Deo, Rahul C.; Holm, Teresa M.; Naylor, Richard W.; Wingert, Rebecca A.; Cowan, Chad A.; Handin, Robert I.; Davidson, Alan J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Ma, Dongdong; Handin, Robert I.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Wingert, Rebecca A.; Cowan, Chad A.; Handin, Robert I.; Davidson, Alan J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Bollig, Frank; Englert, Christoph] Fritz Lipmann Inst, Leibniz Inst Age Res, D-07745 Jena, Germany.
[Zhu, Hao] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ikenaga, Takanori; Ono, Fumihito] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Englert, Christoph] Friedrich Schiller Univ, D-07743 Jena, Germany.
[Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Hukriede, Neil A.] Univ Pittsburgh, Sch Med, Dept Dev Biol, Pittsburgh, PA 15260 USA.
[Diep, Cuong Q.; Deo, Rahul C.; Holm, Teresa M.; Naylor, Richard W.; Arora, Natasha; Wingert, Rebecca A.; Djordjevic, Gordana; Lichman, Benjamin; Cowan, Chad A.; Davidson, Alan J.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
RP Davidson, AJ (reprint author), Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Auckland 1142, New Zealand.
EM a.davidson@auckland.ac.nz
OI Ikenaga, Takanori/0000-0002-7321-9703; Zhu, Hao/0000-0002-8417-9698;
Lichman, Benjamin/0000-0002-0033-1120
FU Harvard Stem Cell Institute; American Society of Nephrology; National
Institutes of Health/National Institute of Diabetes and Digestive and
Kidney Diseases [P50DK074030]
FX We thank E. C. Liao for help with suturing, and R. Ethier and L. Gyr for
zebrafish care. A.J.D. was supported by the Harvard Stem Cell Institute,
the American Society of Nephrology and the National Institutes of
Health/National Institute of Diabetes and Digestive and Kidney Diseases
(P50DK074030).
NR 23
TC 105
Z9 108
U1 2
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD FEB 3
PY 2011
VL 470
IS 7332
BP 95
EP U108
DI 10.1038/nature09669
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 715LQ
UT WOS:000286886400041
PM 21270795
ER
PT J
AU Miller, FG
Joffe, S
AF Miller, Franklin G.
Joffe, Steven
TI Equipoise and the Dilemma of Randomized Clinical Trials
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID METASTATIC COLORECTAL-CANCER; ESTROGEN PLUS PROGESTIN; THERAPEUTIC
MISCONCEPTION; 1ST-LINE CHEMOTHERAPY; RESPONSE RATES; BREAST-CANCER;
SURVIVAL; BENEFIT; MELANOMA; ETHICS
C1 [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
OI Joffe, Steven/0000-0002-0667-7384
NR 35
TC 78
Z9 78
U1 0
U2 8
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 FEB 3
PY 2011
VL 364
IS 5
BP 476
EP 480
DI 10.1056/NEJMsb1011301
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 715LL
UT WOS:000286885900016
PM 21288100
ER
PT J
AU Ferguson-Smith, AC
Patti, ME
AF Ferguson-Smith, Anne C.
Patti, Mary-Elizabeth
TI You Are What Your Dad Ate
SO CELL METABOLISM
LA English
DT Editorial Material
ID IN-UTERO; MAMMALS; DIET; RATS
AB Maternal nutrition and metabolism are critical determinants of adult offspring health. Recent reports describe adverse offspring outcomes associated with the father's diet, indicating nongenetic inheritance of paternal experience. Determining underlying mechanisms may require reconsideration of our understanding of the heritability of epigenetic states.
C1 [Ferguson-Smith, Anne C.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
[Ferguson-Smith, Anne C.] Singapore Inst Clin Sci, Brenner Ctr Mol Med, Singapore, Singapore.
[Patti, Mary-Elizabeth] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Patti, Mary-Elizabeth] Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Ferguson-Smith, AC (reprint author), Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3EG, England.
EM afsmith@mole.bio.cam.ac.uk; mary.elizabeth.patti@joslin.harvard.edu
RI Ferguson-Smith, Anne/G-7534-2011
NR 9
TC 38
Z9 39
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD FEB 2
PY 2011
VL 13
IS 2
BP 115
EP 117
DI 10.1016/j.cmet.2011.01.011
PG 3
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 722KR
UT WOS:000287431600001
PM 21284975
ER
PT J
AU Schleinitz, D
Kloting, N
Bottcher, Y
Wolf, S
Dietrich, K
Tonjes, A
Breitfeld, J
Enigk, B
Halbritter, J
Korner, A
Schon, MR
Jenkner, J
Tseng, YH
Lohmann, T
Dressler, M
Stumvoll, M
Bluher, M
Kovacs, P
AF Schleinitz, Dorit
Kloeting, Nora
Boettcher, Yvonne
Wolf, Sara
Dietrich, Kerstin
Toenjes, Anke
Breitfeld, Jana
Enigk, Beate
Halbritter, Jan
Koerner, Antje
Schoen, Michael R.
Jenkner, Jost
Tseng, Yu-Hua
Lohmann, Tobias
Dressler, Miriam
Stumvoll, Michael
Blueher, Matthias
Kovacs, Peter
TI Genetic and Evolutionary Analyses of the Human Bone Morphogenetic
Protein Receptor 2 (BMPR2) in the Pathophysiology of Obesity
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HAPLOTYPE RECONSTRUCTION; PHYLOGENETIC
ANALYSIS; MAXIMUM-LIKELIHOOD; INSULIN-SECRETION; DIABETES-MELLITUS;
POPULATION; EXPRESSION; VARIANTS; CELLS
AB Objective: Human bone morphogenetic protein receptor 2 (BMPR2) is essential for BMP signalling and may be involved in the regulation of adipogenesis. The BMPR2 locus has been suggested as target of recent selection in human populations. We hypothesized that BMPR2 might have a role in the pathophysiology of obesity.
Research Design and Methods: Evolutionary analyses (dN/dS, Fst, iHS) were conducted in vertebrates and human populations. BMPR2 mRNA expression was measured in 190 paired samples of visceral and subcutaneous adipose tissue. The gene was sequenced in 48 DNA samples. Nine representative single nucleotide polymorphisms (SNPs) were genotyped for subsequent association studies on quantitative traits related to obesity in 1830 German Caucasians. An independent cohort of 925 Sorbs was used for replication. Finally, relation of genotypes to mRNA in fat was examined.
Results: The evolutionary analyses indicated signatures of selection on the BMPR2 locus. BMPR2 mRNA expression was significantly increased both in visceral and subcutaneous adipose tissue of 37 overweight (BMI>25 and <30 kg/m(2)) and 80 obese (BMI>30 kg/m(2)) compared with 44 lean subjects (BMI<25 kg/m(2)) (P<0.001). In a case-control study including lean and obese subjects, two intronic SNPs (rs6717924, rs13426118) were associated with obesity (adjusted P<0.05). Combined analyses including the initial cohort and the Sorbs confirmed a consistent effect for rs6717924 (combined P=0.01) on obesity. Moreover, rs6717924 was associated with higher BMPR2 mRNA expression in visceral adipose tissue.
Conclusion: Combined BMPR2 genotype-phenotype-mRNA expression data as well as evolutionary aspects suggest a role of BMPR2 in the pathophysiology of obesity.
C1 [Schleinitz, Dorit; Dietrich, Kerstin; Breitfeld, Jana; Enigk, Beate; Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
[Kloeting, Nora; Boettcher, Yvonne; Wolf, Sara; Toenjes, Anke; Halbritter, Jan; Stumvoll, Michael; Blueher, Matthias] Univ Leipzig, Dept Med, Leipzig, Germany.
[Toenjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany.
[Koerner, Antje] Univ Leipzig, Univ Hosp Children & Adolescents, Leipzig, Germany.
[Schoen, Michael R.; Jenkner, Jost] Municipal Clin Karlsruhe, Clin Visceral Surg, Karlsruhe, Germany.
[Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Lohmann, Tobias; Dressler, Miriam] Municipal Clin, Dresden, Germany.
RP Schleinitz, D (reprint author), Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
EM bluma@medizin.uni-leipzig.de; peter.kovacs@medizin.uni-leipzig.de
RI Korner, Antje/B-3988-2015;
OI Korner, Antje/0000-0001-6001-0356; Schon, Michael/0000-0002-0698-4130
FU Federal Ministry of Education and Research, Competence Network Obesity
[FKZ 01GI0829]; NGFNplus [FKZ 01GI0827]; Deutsche Forschungsgemeinschaft
(DFG); German Diabetes Association [BL 833/1-1, Stu192/6-1, KO 3512/1-1,
KO 3880/1-1]; National Institutes of Health (USA) [R01 DK077097, P30
DK040561]; DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland)
FX This work was supported by grants from the Federal Ministry of Education
and Research, Competence Network Obesity (FKZ 01GI0829), the NGFNplus
(FKZ 01GI0827), Deutsche Forschungsgemeinschaft (DFG), the Clinical
Research Group "Atherobesity'' KFO 152 (projects BL 833/1-1 to MB, and
Stu192/6-1 (MS), KO 3512/1-1 to AK, KO 3880/1-1 to PK), from the German
Diabetes Association (to DS and PK), from the National Institutes of
Health (USA) grants R01 DK077097 and P30 DK040561 (to YHT) and DHFD
(Diabetes Hilfs- und Forschungsfonds Deutschland; to MS, PK, MB). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 36
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U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 2
PY 2011
VL 6
IS 2
AR e16155
DI 10.1371/journal.pone.0016155
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 717IF
UT WOS:000287036200008
PM 21311592
ER
PT J
AU Shervin, N
Dorrwachter, J
Bragdon, CR
Shervin, D
Zurakowski, D
Malchau, H
AF Shervin, Nina
Dorrwachter, Janet
Bragdon, Charles R.
Shervin, David
Zurakowski, David
Malchau, Henrik
TI Comparison of Paper and Computer-Based Questionnaire Modes for Measuring
Health Outcomes in Patients Undergoing Total Hip Arthroplasty
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID REPLACEMENT; PENCIL; SCORE
AB Background: Health status questionnaires are important, especially with the growing interest in outcome studies. However, these questionnaires continue to be administered in their original paper format. We hypothesized that total hip arthroplasty outcome data derived with computer-based questionnaires do not differ significantly from those derived with established paper-based formats.
Methods: From January 2006 to January 2007, the clinic schedules of four attending arthroplasty surgeons were screened weekly to identify patients who could potentially be included in the study. Charts were reviewed for subjects who were scheduled for or had received primary total hip arthroplasty. Patients were recruited during their office visit or when they attended a preoperative educational class, and five health status questionnaires (the Harris hip score, WOMAC [Western Ontario and McMaster Universities Osteoarthritis Index], SF-36 [Short Form-36], EQ-5D [EuroQol-5D], and UCLA [University of California at Los Angeles] activity score) were administered in three formats: paper, touch screen, and web-based. Repeated-measures analysis of variance and Pearson correlations were used to compare the questionnaire modes for the Harris hip score (normally distributed data), and the Friedman test and Spearman correlations were used to compare the modes for the other health status scores (non-normally distributed data). The study was designed with 90% power for detecting 10% differences between modes in the entire series of sixty-one patients and with 82% and 87% power in preoperative and postoperative subgroups, respectively.
Results: The mean age was sixty-three years, with thirty-seven male and twenty-four female patients in the study. Forty-seven hips (77%) had osteoarthritis as the primary diagnosis. No significant differences were detected, for any of the five health outcome systems, among the paper, touch screen, and web-based modes, and there were highly significant correlations among all questionnaire modes in the entire series of patients and in the preoperative and postoperative subgroups (p < 0.001).
Conclusions: The scores obtained with the paper, touch screen, and web-based modes of the five questionnaires demonstrated excellent agreement. Thus, touch screen and web-based formats can be used to collect and track patient outcome data. Use of electronic formats of these questionnaires will facilitate a more efficient and reliable data collection process.
C1 [Shervin, Nina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA.
RP Shervin, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Biomech & Biomat Lab, Jackson Bldg 1126,55 Fruit St, Boston, MA 02114 USA.
EM hmalchau@partners.org
NR 19
TC 18
Z9 18
U1 0
U2 3
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD FEB 2
PY 2011
VL 93A
IS 3
BP 285
EP 293
DI 10.2106/JBJS.I.01104
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 721DY
UT WOS:000287335000007
PM 21266642
ER
PT J
AU Courchesne, SL
Karch, C
Pazyra-Murphy, MF
Segal, RA
AF Courchesne, Stephanie L.
Karch, Christoph
Pazyra-Murphy, Maria F.
Segal, Rosalind A.
TI Sensory Neuropathy Attributable to Loss of Bcl-w
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SMALL-FIBER NEUROPATHY; CELL-CYCLE ENTRY; WALLERIAN DEGENERATION;
MITOCHONDRIAL FISSION; AXONAL DEGENERATION; GROWTH-FACTOR; APOPTOSIS;
DEATH; EXPRESSION; SURVIVAL
AB Small fiber sensory neuropathy is a common disorder in which progressive degeneration of small-diameter nociceptors causes decreased sensitivity to thermal stimuli and painful sensations in the extremities. In the majority of patients, the cause of small fiber sensory neuropathy is unknown, and treatment options are limited. Here, we show that Bcl-w (Bcl-2l2) is required for the viability of small fiber nociceptive sensory neurons. Bcl-w(-/-) mice demonstrate an adult-onset progressive decline in thermosensation and a decrease in nociceptor innervation of the epidermis. This denervation occurs without cell body loss, indicating that lack of Bcl-w results in a primary axonopathy. Consistent with this phenotype, we show that Bcl-w, in contrast to the closely related Bcl-2 and Bcl-xL, is enriched in axons of sensory neurons and that Bcl-w prevents the dying back of axons. Bcl-w(-/-) sensory neurons exhibit mitochondrial abnormalities, including alterations in axonal mitochondrial size, axonal mitochondrial membrane potential, and cellular ATP levels. Collectively, these data establish bcl-w(-/-) mice as an animal model of small fiber sensory neuropathy and provide new insight regarding the role of Bcl-w and of mitochondria in preventing axonal degeneration.
C1 [Courchesne, Stephanie L.; Karch, Christoph; Pazyra-Murphy, Maria F.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Courchesne, Stephanie L.; Karch, Christoph; Pazyra-Murphy, Maria F.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Courchesne, Stephanie L.; Karch, Christoph; Pazyra-Murphy, Maria F.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM rosalind_segal@dfci.harvard.edu
FU National Institutes of Health (NIH) [R01 NS050674, P30-HD-18655]
FX This work was supported by National Institutes of Health (NIH) Grant R01
NS050674 (R.A.S.). S.L.C. is a Stuart H.Q. and Victoria Quan Fellow at
Harvard Medical School. Confocal microscopy imaging was performed at the
Mental Retardation Developmental Disability Research Center Imaging
Core, Children's Hospital Boston (NIH Grant P30-HD-18655), and
stereology imaging was performed at the Harvard NeuroDiscovery Optical
Imaging Center. We thank Grant MacGregor (University of California,
Irvine, Irvine, California) for the generous gift of bcl-w-/-
mice. We thank members of Qiufu Ma's laboratory for helpful advice and
discussion. We thank Jennifer Kalscheuer, Danny Lee, and Aymeric Hans
for assistance, and Katharina Cosker and Sara Fenstermacher for
discussion and manuscript suggestions. The research that is the basis of
this paper was conducted before S.L.C. started employment at NIH.
NR 50
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U1 0
U2 3
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 FEB 2
PY 2011
VL 31
IS 5
BP 1624
EP 1634
DI 10.1523/JNEUROSCI.3347-10.2011
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 715WE
UT WOS:000286922100010
PM 21289171
ER
PT J
AU Miyazono, S
Isayama, T
Makino, CL
AF Miyazono, Sadaharu
Isayama, Tomoki
Makino, Clint L.
TI Vitamin A as an Activator and Sensitizing Chromophore for Rhodopsin
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 55th Annual Meeting of the Biophysical-Society
CY MAR 05-09, 2011
CL Baltimore, MD
SP Biophys Soc
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
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 FEB 2
PY 2011
VL 100
IS 3
SU 1
BP 22
EP 22
PG 1
WC Biophysics
SC Biophysics
GA 972PF
UT WOS:000306288600113
ER
PT J
AU Kural, C
Boulant, S
Kirchhausen, T
AF Kural, Comert
Boulant, Steeve
Kirchhausen, Tomas
TI Real-Time Imaging of Clathrin Dynamics in Three Dimensions
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 55th Annual Meeting of the Biophysical-Society
CY MAR 05-09, 2011
CL Baltimore, MD
SP Biophys Soc
C1 [Kural, Comert; Boulant, Steeve; Kirchhausen, Tomas] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA.
[Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
NR 0
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U1 0
U2 1
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 FEB 2
PY 2011
VL 100
IS 3
SU 1
BP 30
EP 30
PG 1
WC Biophysics
SC Biophysics
GA 972PF
UT WOS:000306288600155
ER
PT J
AU Wu, J
Ruas, JL
Estall, JL
Rasbach, KA
Choi, JH
Ye, L
Bostrom, P
Tyra, HM
Crawford, RW
Campbell, KP
Rutkowski, DT
Kaufman, RJ
Spiegelman, BM
AF Wu, Jun
Ruas, Jorge L.
Estall, Jennifer L.
Rasbach, Kyle A.
Choi, Jang Hyun
Ye, Li
Bostroem, Pontus
Tyra, Heather M.
Crawford, Robert W.
Campbell, Kevin P.
Rutkowski, D. Thomas
Kaufman, Randal J.
Spiegelman, Bruce M.
TI The Unfolded Protein Response Mediates Adaptation to Exercise in
Skeletal Muscle through a PGC-1 alpha/ATF6 alpha Complex
SO CELL METABOLISM
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; ER STRESS; CELL FUNCTION; TRANSCRIPTION;
PGC-1; COACTIVATORS; EXPRESSION; INCREASES; PATHWAYS; DISEASE
AB Exercise has been shown to be effective for treating obesity and type 2 diabetes. However, the molecular mechanisms for adaptation to exercise training are not fully understood. Endoplasmic reticulum (ER) stress has been linked to metabolic dysfunction. Here we show that the unfolded protein response (UPR), an adaptive response pathway that maintains ER homeostasis upon luminal stress, is activated in skeletal muscle during exercise and adapts skeletal muscle to exercise training. The transcriptional coactivator PGC-1 alpha, which regulates several exercise-associated aspects of skeletal muscle function, mediates the UPR in myotubes and skeletal muscle through coactivation of ATF6 alpha. Efficient recovery from acute exercise is compromised in ATF6 alpha(-/-) mice. Blocking ER-stress-related cell death via deletion of CHOP partially rescues the exercise intolerance phenotype in muscle-specific PGC-1 alpha KO mice. These findings suggest that modulation of the UPR through PGC1 alpha represents an alternative avenue to improve skeletal muscle function and achieve metabolic benefits.
C1 [Wu, Jun; Ruas, Jorge L.; Estall, Jennifer L.; Rasbach, Kyle A.; Choi, Jang Hyun; Ye, Li; Bostroem, Pontus; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wu, Jun; Ruas, Jorge L.; Estall, Jennifer L.; Rasbach, Kyle A.; Choi, Jang Hyun; Ye, Li; Bostroem, Pontus; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kaufman, Randal J.] Univ Michigan, Med Ctr, Dept Biol Chem, Ann Arbor, MI 48109 USA.
[Kaufman, Randal J.] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Tyra, Heather M.; Rutkowski, D. Thomas] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA.
[Crawford, Robert W.; Campbell, Kevin P.] Univ Iowa, Howard Hughes Med Inst, Carver Coll Med, Iowa City, IA 52242 USA.
[Crawford, Robert W.; Campbell, Kevin P.] Univ Iowa, Howard Hughes Med Inst, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA.
[Crawford, Robert W.; Campbell, Kevin P.] Univ Iowa, Howard Hughes Med Inst, Dept Neurol, Iowa City, IA 52242 USA.
[Crawford, Robert W.; Campbell, Kevin P.] Univ Iowa, Howard Hughes Med Inst, Dept Internal Med, Iowa City, IA 52242 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
RI Choi, Jang Hyun/B-3055-2012;
OI Ruas, Jorge/0000-0002-1110-2606
FU National Institutes of Health (NIH) [DK61562, DK54477, 1137, DK042394,
R01 HL052173, P01 HL057346]; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) [DK084058]; Wellstone Muscular
Dystrophy Cooperative Research Center [U54 NS053672]; Howard Hughes
Medical Institute; American Heart Association [POST2010078]
FX We thank Dina Laznik and Kevin Brannan for excellent technical
assistance. We thank Dr. Umut Ozcan for the adenovirus expressing ATF6
alpha N. We thank members of the Spiegelman laboratory for helpful
comments, especially Drs. Patrick Seale and Melin Khandekar. This work
was supported by National Institutes of Health (NIH) grants (to B.M.S.,
DK61562 and DK54477). Portions of this work were supported by NIH 1137
DK042394, R01 HL052173, and P01 HL057346 to R.J.K. and R01 DK084058 from
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) to D.T.R. This work was supported in part by the Senator Paul D.
Wellstone Muscular Dystrophy Cooperative Research Center grant 1 U54
NS053672 (to K.P.C.). K.P.C. is an investigator of the Howard Hughes
Medical Institute. J.W. was supported by a postdoctoral fellowship from
the American Heart Association (Founders Affiliate #09POST2010078). J.W.
and B.M.S. conceived and designed the experiments. J.W., J.L.R., J.L.E.,
K.A.R., J.H.C., L.Y., P.B., H.M.T., and R.W.C. performed the
experiments. J.W. and B.M.S. analyzed the data and wrote the paper. Work
with ATF6 alpha-/- and IRE1 alpha deleted myotubes was done
with the laboratory of R.J.K. Work with ATF6 alpha-/- mice
was done with the laboratories of K.P.C. and D.T.R.
NR 27
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U1 2
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD FEB 2
PY 2011
VL 13
IS 2
BP 160
EP 169
DI 10.1016/j.cmet.2011.01.003
PG 10
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 722KR
UT WOS:000287431600009
PM 21284983
ER
PT J
AU Axon, RN
Williams, MV
AF Axon, R. Neal
Williams, Mark V.
TI Hospital Readmission as an Accountability Measure
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID INPATIENT CARE; QUALITY; ASSOCIATION
C1 [Axon, R. Neal] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA.
[Axon, R. Neal] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC USA.
[Williams, Mark V.] Northwestern Univ, Feinberg Sch Med, Div Hosp Med, Chicago, IL 60611 USA.
RP Axon, RN (reprint author), 135 Rutledge Ave,MSC 591, Charleston, SC 29425 USA.
EM axon@musc.edu
NR 10
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U1 0
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 2
PY 2011
VL 305
IS 5
BP 504
EP 505
DI 10.1001/jama.2011.72
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 714LI
UT WOS:000286810700026
PM 21285430
ER
PT J
AU Holschneider, DP
Bradesi, S
Mayer, EA
AF Holschneider, Daniel P.
Bradesi, Sylvie
Mayer, Emeran A.
TI The role of experimental models in developing new treatments for
irritable bowel syndrome
SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Review
DE functional gastrointestinal disorders; intestinal transit; neuroimaging;
visceral pain
ID C-FOS EXPRESSION; 5-HT3 RECEPTOR ANTAGONIST; FUNCTIONAL GASTROINTESTINAL
DISORDERS; REGIONAL BRAIN ACTIVATION; KAPPA-AGONIST FEDOTOZINE;
ROBALZOTAN TARTRATE MONOHYDRATE; NOXIOUS COLORECTAL DISTENSION;
LUMBOSACRAL SPINAL-CORD; COLONIC DISTENSION; VISCERAL PAIN
AB Irritable bowel syndrome (IBS) is characterized by chronic, recurrent abdominal pain and altered bowel habits and is currently defined by symptom criteria and the absence of detectable organic disease. The underlying pathophysiology remains incompletely understood. Despite considerable efforts by the scientific community and the pharmaceutical industry to develop novel pharmacological treatments aimed at chronic visceral pain, the traditional approach to identifying and evaluating novel drugs for this target have largely failed to translate into effective IBS treatments. However, several novel drugs aimed at normalizing bowel movements have produced clinical effects, not only on the primary target, but also on pain and discomfort. While some of the commonly used experimental animal models for the pain dimension of IBS have some face and construct validity, the predictive validity of most of the models is either unknown, or has been disappointing. A reverse translational approach is proposed, which is based on identification and characterization of brain endophenotypes in patients, followed by translation of these endophenotypes for pharmacological studies in rodent models.
C1 [Holschneider, Daniel P.; Bradesi, Sylvie; Mayer, Emeran A.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
[Holschneider, Daniel P.] Univ So Calif, Dept Psychiat, Los Angeles, CA USA.
[Holschneider, Daniel P.] Univ So Calif, Dept Behav Sci Neurol Cell & Neurobiol, Los Angeles, CA USA.
[Bradesi, Sylvie; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, UCLA Ctr Neurobiol Stress, Los Angeles, CA 90024 USA.
[Bradesi, Sylvie; Mayer, Emeran A.] Univ Calif Los Angeles, Sch Med, Dept Physiol, UCLA Ctr Neurobiol Stress, Los Angeles, CA 90024 USA.
[Bradesi, Sylvie; Mayer, Emeran A.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, UCLA Ctr Neurobiol Stress, Los Angeles, CA 90024 USA.
RP Bradesi, S (reprint author), VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
EM sbradesi@ucla.edu
FU NIH [DK 48351, DK 64539, DA026597]
FX The work discussed in this paper is supported by NIH grants DK 48351, DK
64539, DA026597. The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials
discussed in the manuscript apart from those disclosed.
NR 133
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U2 3
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1747-4124
J9 EXPERT REV GASTROENT
JI Expert Rev. Gastroenterol. Hepatol.
PD FEB
PY 2011
VL 5
IS 1
BP 43
EP 57
DI 10.1586/EGH.10.88
PG 15
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 861SL
UT WOS:000298039400011
PM 21309671
ER
PT J
AU Biagtan, MJ
Viswanathan, RK
Mathur, SK
AF Biagtan, M. J.
Viswanathan, R. K.
Mathur, S. K.
TI The Chronic Urticaria Index as a Predictor of Responsiveness to Therapy
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Biagtan, M. J.; Viswanathan, R. K.; Mathur, S. K.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA.
[Mathur, S. K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB104
EP AB104
DI 10.1016/j.jaci.2010.12.417
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400400
ER
PT J
AU Blumenthal, KG
Patil, S
Ling, M
Long, A
AF Blumenthal, K. G.
Patil, S.
Ling, M.
Long, A.
TI The Importance of Vancomycin in Drug Rash with Eosinophilia and Systemic
Symptoms (DRESS) Syndrome
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Blumenthal, K. G.; Patil, S.; Ling, M.; Long, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB198
EP AB198
DI 10.1016/j.jaci.2010.12.787
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400769
ER
PT J
AU Ford, LS
Bloom, KA
Nowak-Wegrzyn, AH
Chase, AZ
Hertzberg, EH
Bencharitiwong, R
Shreffler, WG
Sampson, HA
AF Ford, L. S.
Bloom, K. A.
Nowak-Wegrzyn, A. H.
Chase, A. Z.
Hertzberg, E. H.
Bencharitiwong, R.
Shreffler, W. G.
Sampson, H. A.
TI Basophil Reactivity, IgE and IgG(4) Among Subjects with Various Levels
of Milk Tolerance
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol (AAAAI)
C1 [Ford, L. S.; Bloom, K. A.; Nowak-Wegrzyn, A. H.; Chase, A. Z.; Hertzberg, E. H.; Bencharitiwong, R.; Sampson, H. A.] Mt Sinai Sch Med, New York, NY USA.
[Shreffler, W. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB29
EP AB29
DI 10.1016/j.jaci.2010.12.125
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400109
ER
PT J
AU Ling, M
Begun, J
Patil, S
Hamilos, DL
AF Ling, M.
Begun, J.
Patil, S.
Hamilos, D. L.
TI Eosinophilic Cholangiopathy Presenting With Peripheral Eosinophilia and
Hepatic Mass
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Ling, M.; Begun, J.; Patil, S.; Hamilos, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB108
EP AB108
DI 10.1016/j.jaci.2010.12.433
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400415
ER
PT J
AU Lu, TX
Fabry, V
Lim, E
Cole, ET
Orkin, SH
Rothenberg, ME
AF Lu, T. X.
Fabry, V.
Lim, E.
Cole, E. T.
Orkin, S. H.
Rothenberg, M. E.
TI MicroRNA-21 Deficiency Leads to an Attenuated Asthma Response in Mice
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Lu, T. X.; Fabry, V.; Lim, E.; Cole, E. T.; Rothenberg, M. E.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Orkin, S. H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB220
EP AB220
DI 10.1016/j.jaci.2010.12.877
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400858
ER
PT J
AU Parikh, N
Verma, P
Lee, S
Klaustermeyer, WB
AF Parikh, N.
Verma, P.
Lee, S.
Klaustermeyer, W. B.
TI Inhaler Use and Effect on Asthma Control
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Parikh, N.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA.
[Verma, P.; Lee, S.; Klaustermeyer, W. B.] Univ Calif Los Angeles, Div Allergy Immunol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB159
EP AB159
DI 10.1016/j.jaci.2010.12.631
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400613
ER
PT J
AU Patil, S
Ling, M
Wilson, MT
Long, A
Hesterberg, P
Wong, JT
Banerji, A
AF Patil, S.
Ling, M.
Wilson, M. T.
Long, A.
Hesterberg, P.
Wong, J. T.
Banerji, A.
TI Repeat Skin Testing Improves Risk Stratification For Platinum-based
Chemotherapy Desensitizations
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Patil, S.; Ling, M.; Wilson, M. T.; Long, A.; Hesterberg, P.; Wong, J. T.; Banerji, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB143
EP AB143
DI 10.1016/j.jaci.2010.12.569
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400551
ER
PT J
AU Ruiter, B
Shreffler, WG
AF Ruiter, B.
Shreffler, W. G.
TI Human Dendritic Cells Stimulated with Peanut Extract Express High Levels
of RALDH2 and Induce RA-Sensitive Genes in Naive T Cells
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Ruiter, B.; Shreffler, W. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB263
EP AB263
DI 10.1016/j.jaci.2010.12.1047
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846401161
ER
PT J
AU Verma, P
Randhawa, I
Klaustermeyer, WB
AF Verma, P.
Randhawa, I.
Klaustermeyer, W. B.
TI Severe Geriatric Asthma: Efficacy of Omalizumab in a VA population
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Verma, P.; Klaustermeyer, W. B.] Univ Calif Los Angeles, Div Allergy Immunol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB160
EP AB160
DI 10.1016/j.jaci.2010.12.634
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400616
ER
PT J
AU Viswanathan, RK
Biagtan, MJ
Kelly, JT
Moss, MH
Mathur, SK
AF Viswanathan, R. K.
Biagtan, M. J.
Kelly, J. T.
Moss, M. H.
Mathur, S. K.
TI Phenotypic Profile of Potential Responders to Omalizumab in Chronic
Idiopathic Urticaria
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting
CY MAR 18-22, 2011
CL San Francisco, CA
SP Amer Acad Allergy Asthma & Immunol
C1 [Viswanathan, R. K.; Biagtan, M. J.; Kelly, J. T.; Moss, M. H.; Mathur, S. K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Mathur, S. K.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2011
VL 127
IS 2
SU S
BP AB103
EP AB103
DI 10.1016/j.jaci.2010.12.414
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 832YI
UT WOS:000295846400397
ER
PT J
AU Selinger, S
Restrepo, MI
Copeland, LA
Pugh, MJV
Nakashima, B
Downs, JR
Anzueto, A
Mortensen, EM
AF Selinger, Scott
Restrepo, Marcos I.
Copeland, Laurel A.
Pugh, Mary Jo V.
Nakashima, Brandy
Downs, John R.
Anzueto, Antonio
Mortensen, Eric M.
TI Pneumonia in the Elderly Hospitalized in the Department of Veteran
Affairs Health Care System
SO MILITARY MEDICINE
LA English
DT Article
ID COMMUNITY-ACQUIRED PNEUMONIA; VALIDATION; FACILITIES; MORTALITY;
OUTCOMES; THERAPY; IMPACT
AB Pneumonia is a major cause of hospital admissions and deaths worldwide. Our aim was to examine the trends in admissions for pneumonia in the Department of Veterans Affairs (VA). We examined data for the fiscal years 2002 through 2007 on patients aged 65 years and older hospitalized with pneumonia by using VA administrative databases. The numbers of hospital admissions for pneumonia were relatively stable during this period. However, length of hospital stay and 30- and 90-day mortality decreased during this period. The proportion of patients admitted to the intensive care unit remained relatively constant, but fewer received mechanical ventilation; there was substantial increase in noninvasive ventilation. In the VA, pneumonia-related admissions are being managed more effectively even as the overall number of admissions remains stable.
C1 [Selinger, Scott; Downs, John R.; Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Gen Internal Med, San Antonio, TX 78229 USA.
[Restrepo, Marcos I.; Copeland, Laurel A.; Pugh, Mary Jo V.; Nakashima, Brandy; Downs, John R.; Anzueto, Antonio; Mortensen, Eric M.] VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA.
[Copeland, Laurel A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
RP Selinger, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Gen Internal Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
RI Restrepo, Marcos/H-4442-2014;
OI Mortensen, Eric/0000-0002-3880-5563; Copeland,
Laurel/0000-0002-9478-0209
FU National Institute of Nursing Research [R01NR0I0828]; Department of
Veteran Affairs Veterans Integrated Service Network [17]; National
Health Institute [KL2 RR025766]; Veterans Health Administration
[MRP-05-145]
FX This project was supported by grant number R01NR0I0828 from the National
Institute of Nursing Research. Dr. Restrepo is supported by a Department
of Veteran Affairs Veterans Integrated Service Network 17 new faculty
grant and National Health Institute Grant KL2 RR025766. Dr. Copeland is
supported by Veterans Health Administration Grant MRP-05-145. The
funding agencies had no role in conducting the study or in the
preparation, review, or approval of the manuscript.
NR 21
TC 0
Z9 0
U1 0
U2 0
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
J9 MIL MED
JI Milit. Med.
PD FEB
PY 2011
VL 176
IS 2
BP 214
EP 217
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825BL
UT WOS:000295245800020
PM 21366087
ER
PT J
AU Stroffolini, T
Deuffic-Burban, S
Deltenre, P
Buti, M
Parkes, J
Muhlberger, N
Siebert, U
Moreno, C
Hatzakis, A
Rosenberg, W
Zeuzem, S
Mathurin, P
AF Stroffolini, T.
Deuffic-Burban, S.
Deltenre, P.
Buti, M.
Parkes, J.
Muehlberger, N.
Siebert, U.
Moreno, C.
Hatzakis, A.
Rosenberg, W.
Zeuzem, S.
Mathurin, P.
TI HCV burden in Europe: Impact of national treatment practices on future
HCV-related morbidity and mortality through a modeling approach
SO DIGESTIVE AND LIVER DISEASE
LA English
DT Meeting Abstract
C1 [Stroffolini, T.; Mathurin, P.] Policlin Umberto 1, Dipartimento Malattie Infett & Tropicali, Rome, Italy.
[Deuffic-Burban, S.] INSERM, U995, F-59045 Lille, France.
[Deuffic-Burban, S.; Mathurin, P.] Univ Lille Nord France, EA 2694, Lille, France.
[Deltenre, P.] CHU Lille, Hop Huriez, Serv Hepatogastroenterol, F-59037 Lille, France.
[Deltenre, P.] Hop Jolimont, Serv Hepatogastroenterol, Haine St Paul, Belgium.
[Buti, M.] Univ Valle Hebron, Gen Hosp, Liver Unit, Dept Internal Med Hepatol, Barcelona, Spain.
[Parkes, J.] Univ Southampton, Sch Med, Southampton, Hants, England.
[Muehlberger, N.; Siebert, U.] Univ Hlth Sci Med Informat & Technol, UMIT, Innsbruck, Austria.
[Siebert, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Moreno, C.] ULB, Hop Erasme, Dept Gastroenterol & Hepatopancreatol, Brussels, Belgium.
[Hatzakis, A.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
[Rosenberg, W.] UCL, Inst Hepatol, London, England.
[Zeuzem, S.] Goethe Univ Hosp, Frankfurt, Germany.
[Buti, M.] Inst Salud Carlos III, Ciber ehd, Barcelona, Spain.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1590-8658
J9 DIGEST LIVER DIS
JI Dig. Liver Dis.
PD FEB
PY 2011
VL 43
SU 2
BP S70
EP S70
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 808ZW
UT WOS:000294021500018
ER
PT J
AU Silver, AL
Yager, P
Purohit, P
Noviski, N
Hartnick, CJ
AF Silver, Amanda L.
Yager, Phoebe
Purohit, Prashant
Noviski, Natan
Hartnick, Christopher J.
TI Dexmedetomidine Use in Pediatric Airway Reconstruction
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article; Proceedings Paper
CT AAO-HNSF Annual Meeting and OTO EXPO
CY SEP 25-29, 2010
CL Boston, MA
SP AAO, HNSF
DE dexmedetomidine; pediatric; airway reconstruction; laryngotracheal
reconstruction; laryngeal cleft repair
ID PROPOFOL INFUSION SYNDROME; HIGH-DOSE DEXMEDETOMIDINE; LARYNGOTRACHEAL
RECONSTRUCTION; INTENSIVE-CARE; SEDATION
AB Objective. Assess the postoperative use of dexmedetomidine (Precedex) in pediatric patients following airway reconstruction.
Study Design. Historical cohort study.
Setting. Tertiary medical center. Subjects and Methods. A retrospective review of 24 children undergoing laryngotracheal reconstruction (LTR) or laryngeal cleft repair (LCR) was conducted. Twelve children were treated with standard sedation protocols where dexmedetomidine was administered in lieu of propofol (Diprivan); 12 age-, gender-, and procedure-matched controls were selected. Subjects were divided into groups based on duration of postoperative intubation for cross-comparison; group 1 was intubated <24 hours, group 2 was intubated 2 to 6 days, and group 3 was intubated 7 days or longer. Baseline heart rate and blood pressure measurements were compared to hourly measurements for the first 6 hours following initiation of dexmedetomidine or mechanical ventilation in the control group. Number of supportive respiratory interventions, adverse events, self-extubations, premature termination of dexmedetomidine, amount of muscle relaxants, agents to treat withdrawal, and length of stay were evaluated.
Results. Ten patients undergoing LTR and 2 patients undergoing LCR receiving dexmedetomidine were compared to 10 LTR and 2 LCR control patients. Overall, dexmedetomidine was well tolerated and without significant adverse effects, particularly in cases of short-term intubation or as a bridge to extubation.
Conclusion. In cases requiring short-term intubation following airway reconstruction, dexmedetomidine may offer a safe alternative to propofol by providing readily reversible sedation during the periextubation period. Further studies are needed to determine the safety, efficacy, dosing, and potential complications of longer term dexmedetomidine administration in pediatric airway reconstruction.
C1 [Silver, Amanda L.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Silver, Amanda L.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Yager, Phoebe; Noviski, Natan] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Purohit, Prashant] Univ Hawaii, Pediat Residency Program, Honolulu, HI 96822 USA.
RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM christopher_hartnick@meei.harvard.edu
NR 19
TC 5
Z9 6
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD FEB
PY 2011
VL 144
IS 2
BP 262
EP 267
DI 10.1177/0194599810391397
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 808RV
UT WOS:000293997000023
PM 21493428
ER
PT J
AU Taft, CT
Watkins, LE
Stafford, J
Street, AE
Monson, CM
AF Taft, Casey T.
Watkins, Laura E.
Stafford, Jane
Street, Amy E.
Monson, Candice M.
TI Posttraumatic Stress Disorder and Intimate Relationship Problems: A
Meta-Analysis
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE PTSD; intimate relationships; couples; trauma
ID VIETNAM COMBAT VETERANS; IRAQI FREEDOM VETERANS; TRAUMA-EXPOSED ADULTS;
PARTNER VIOLENCE; DOMESTIC VIOLENCE; CONFLICT-TACTICS; MARITAL
SATISFACTION; FORMER PRISONERS; SYMPTOMS; FAMILY
AB Objective: The authors conducted a meta-analysis of empirical studies investigating associations between indices of posttraumatic stress disorder (PTSD) and intimate relationship problems to empirically synthesize this literature. Method: A literature search using PsycINFO, Medline, Published International Literature on Traumatic Stress (PILOTS), and Dissertation Abstracts was performed. The authors identified 31 studies meeting inclusion criteria. Results: True score correlations (p) revealed medium-sized associations between PTSD and intimate relationship discord (p = .38, N = 7,973, K = 21), intimate relationship physical aggression perpetration (p = .42, N = 4,630, K = 19), and intimate relationship psychological aggression perpetration (p = .36, N = 1,501, K = 10). The strength of the association between PTSD and relationship discord was higher in military (vs. civilian) samples, and when the study was conducted in the United States (vs. other country), and the study represented a doctoral dissertation (vs. published article). The strength of the association between PTSD and physical aggression was higher in military (vs. civilian) samples, males (vs. females), community (vs. clinical) samples, studies examining PTSD symptom severity (vs. diagnosis), when the physical aggression measure focused exclusively on severe violence (vs. a more inclusive measure), and the study was published (vs. dissertation). For the PTSD psychological aggression association, 98% of the variance was accounted for by methodological artifacts such as sampling and measurement error; consequently, no moderators were examined in this relationship. Conclusions: Findings highlight a need for the examination of models explaining the relationship difficulties associated with PTSD symptomatology and interventions designed to treat problems in both areas.
C1 [Taft, Casey T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA.
[Taft, Casey T.; Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Stafford, Jane] Univ S Carolina, Dept Psychol, Aiken, SC USA.
[Street, Amy E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA.
[Monson, Candice M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada.
RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, 116B-4,150 S Huntington Ave, Boston, MA 02130 USA.
EM casey.taft@va.gov
FU NIMH NIH HHS [K08 MH7311701A2]
NR 73
TC 124
Z9 127
U1 13
U2 49
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD FEB
PY 2011
VL 79
IS 1
BP 22
EP 33
DI 10.1037/a0022196
PG 12
WC Psychology, Clinical
SC Psychology
GA 714ZD
UT WOS:000286849300003
PM 21261431
ER
PT J
AU Kovach, AE
Lam, Q
Dias-Santagata, D
Sadow, PM
AF Kovach, A. E.
Lam, Q.
Dias-Santagata, D.
Sadow, P. M.
TI Molecular Analysis of Adrenal Cortical Carcinomas in Clinical and
Histologic Context
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 577
BP 138A
EP 138A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000017
ER
PT J
AU Fan, XS
Chen, JY
Feng, AN
Wu, HY
Gold, JS
Huang, Q
AF Fan, X. S.
Chen, J. Y.
Feng, A. N.
Wu, H. Y.
Gold, J. S.
Huang, Q.
TI HER2 Protein Over-Expression in Proximal and Distal Gastric Cancers: An
Immunohistochemical and Clinicopathological Comparison Study of 957
Cases
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Nanjing Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China.
VA Boston Healthcare Syst, W Roxbury, MA USA.
Harvard Univ, Sch Med, W Roxbury, MA USA.
RI Gold, Jason/O-5112-2014
OI Gold, Jason/0000-0002-2925-4755
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 620
BP 148A
EP 148A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000060
ER
PT J
AU Huang, Q
Gold, JK
Wu, HY
Fan, XS
Feng, AN
Shi, J
AF Huang, Q.
Gold, J. K.
Wu, H. Y.
Fan, X. S.
Feng, A. N.
Shi, J.
TI Pancreatic Acinar-Like Adenocarcinoma of the Proximal Stomach Involving
the Esophagus in Chinese Patients: A Clinicopathological Study of 41
Cases from a Single High-Volume Hospital in China.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP US & Canadian Acad Pathol (USCAP)
C1 Nanjing Drum Tower Hosp, Nanjing, Peoples R China.
VA Boston Healthcare Syst, W Roxbury, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 640
BP 152A
EP 152A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000080
ER
PT J
AU Kim, A
Park, MK
Kim, KB
Kim, JY
Shin, N
Choi, KU
Park, DY
Lauwers, GY
AF Kim, A.
Park, M-K
Kim, K-B
Kim, J-Y
Shin, N.
Choi, K-U
Park, D. Y.
Lauwers, G. Y.
TI P53 Expression and Proliferation Index Measured by Ki-67 Immunostaining
in Gastric Pit Dysplasia.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Pusan Natl Univ Hosp, Pusan, South Korea.
Pusan Natl Univ, Sch Med, Pusan, South Korea.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 654
BP 156A
EP 156A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000094
ER
PT J
AU Lisovsky, M
Mino-Kenudson, M
Lefferts, J
Courville, E
Zaki, B
Calvo, LN
Hong, TS
Tsongalis, GJ
Lawyers, GY
Srivastava, A
AF Lisovsky, M.
Mino-Kenudson, M.
Lefferts, J.
Courville, E.
Zaki, B.
Calvo, L. N.
Hong, T. S.
Tsongalis, G. J.
Lawyers, G. Y.
Srivastava, A.
TI MGMT (O6-MethylguanineDNA Methyltransferase) Is Inactivated in a
Significant Subset of Distal Esophageal Adenocarcinomas: Implications
for Neoadjuvant Chemoradiation Therapy.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 660
BP 157A
EP 157A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000100
ER
PT J
AU Lisovsky, M
Jiang, Z
Lawyers, GY
AF Lisovsky, M.
Jiang, Z.
Lawyers, G. Y.
TI Oncofetal Protein IMP3 as a Predictor of Prognosis in Gastric
Adenocarcinoma.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
UMassMem Med Ctr, Worcester, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 659
BP 157A
EP 157A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000099
ER
PT J
AU Nosho, K
Dranoff, G
Fuchs, C
Ogino, S
AF Nosho, K.
Dranoff, G.
Fuchs, C.
Ogino, S.
TI Tumor-Infiltrating CD45RO+-Cell Density, but Not CD3+, CD8+, or
FOXP3+-Cell Density, Has a Prognostic Role in Colorectal Cancer,
Independent of Molecular Features
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 672
BP 160A
EP 160A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000112
ER
PT J
AU Ogino, S
Tanaka, N
Fuchs, C
AF Ogino, S.
Tanaka, N.
Fuchs, C.
TI Multivariate Negative Binomial Regression Identifies Length of
Colorectal Resection, Proximal Tumor Location, T3N0M0 Stage, Academic
Setting, and Tumor PIK3CA Mutation as Independent Predictors of Lymph
Node Count
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 675
BP 160A
EP 161A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000115
ER
PT J
AU Ogino, S
Fuchs, C
Huttenhower, C
AF Ogino, S.
Fuchs, C.
Huttenhower, C.
TI LINE-1 Extreme Hypomethylator Is a New Distinct Molecular Subtype
Associated with Young Age and Poor Prognosis: Bioinformatic Analysis of
1190 Colorectal Cancers
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 676
BP 161A
EP 162A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000116
ER
PT J
AU Rege, TA
Wagner, AJ
Corless, CL
Hornick, JL
AF Rege, T. A.
Wagner, A. J.
Corless, C. L.
Hornick, J. L.
TI "Pediatric-Type" Gastrointestinal Stromal Tumors in Adults: Distinctive
Histology Predicts Genotype and Clinical Behavior.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 690
BP 165A
EP 165A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000130
ER
PT J
AU Shimizu, M
Aida, J
Brown, IS
Greenson, JK
Jouret-Mourin, A
Kawachi, H
Lennerz, JK
Nagata, K
Takubo, K
Vieth, M
Lauwers, GY
AF Shimizu, M.
Aida, J.
Brown, I. S.
Greenson, J. K.
Jouret-Mourin, A.
Kawachi, H.
Lennerz, J. K.
Nagata, K.
Takubo, K.
Vieth, M.
Lauwers, G. Y.
TI Evaluation of Esophageal Biopsies for Squamous Intraepithelial
Neoplasia: Differences between Japan and the West.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Saitama Med Univ, Int Med Ctr, Hidaka, Japan.
Tokyo Metropolitan Inst Gerontol, Tokyo, Japan.
Sullivan Nicolaides Pathol, Brisbane, Qld, Australia.
Univ Michigan, Ann Arbor, MI 48109 USA.
Catholic Univ Louvain, B-1200 Brussels, Belgium.
Tokyo Med & Dent Univ, Tokyo, Japan.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Klinikum Bayreuth, Bayreuth, Germany.
RI Brown, Ian/R-7763-2016
OI Brown, Ian/0000-0001-6329-2547
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 701
BP 167A
EP 167A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000141
ER
PT J
AU Virk, RK
Lauwers, GY
Deshpande, V
AF Virk, R. K.
Lauwers, G. Y.
Deshpande, V.
TI The Significance of IGG4 in Inflammatory Bowel Disease
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 UMass Mem Med Ctr, Worcester, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 719
BP 172A
EP 172A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000159
ER
PT J
AU Wang, H
Chen, Y
Deshpande, V
AF Wang, H.
Chen, Y.
Deshpande, V.
TI Heterogeneity in Signaling Pathways of Gastrointestinal Neuroendocrine
Cell Tumors: A Critical Look at Notch Signaling Pathway
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
Univ Delaware, Newark, DE USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 721
BP 172A
EP 173A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000161
ER
PT J
AU Berger, MF
Lawrence, MS
Demichelis, F
Getz, G
Rubin, MA
Garraway, LA
AF Berger, M. F.
Lawrence, M. S.
Demichelis, F.
Getz, G.
Rubin, M. A.
Garraway, L. A.
TI Characterization of Complex Chromosomal Aberrations in Primary Prostate
Cancer Genomes
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Broad Inst, Weill Cornell Med Coll, Prostate Genome Consortium, Cambridge, England.
Weill Cornell Med Coll, New York, NY USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 752
BP 179A
EP 179A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000192
ER
PT J
AU Flavin, R
Hendrickson, W
Krunz, L
Judson, G
Lis, R
Bailey, D
Fiorentino, M
Finn, S
Martin, N
Stark, J
Pettersson, A
Sinnott, J
Penny, K
Fall, K
Giovannucci, E
Rubin, M
Kantoff, P
Stampfer, M
Loda, M
Mucci, L
AF Flavin, R.
Hendrickson, W.
Krunz, L.
Judson, G.
Lis, R.
Bailey, D.
Fiorentino, M.
Finn, S.
Martin, N.
Stark, J.
Pettersson, A.
Sinnott, J.
Penny, K.
Fall, K.
Giovannucci, E.
Rubin, M.
Kantoff, P.
Stampfer, M.
Loda, M.
Mucci, L.
TI SPINK1 Protein Expression and Prostate Cancer Progression
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Harvard Canc Ctr, Dana Farber Canc Inst, Boston, MA USA.
Weill Cornell Med Coll, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 810
BP 192A
EP 192A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000250
ER
PT J
AU He, W
Cheville, JC
Sadow, PM
Gopalan, A
Fine, SW
Al-Ahmadie, HA
Chen, Y
Oliva, E
Russo, P
Reuter, VE
Tickoo, SK
AF He, W.
Cheville, J. C.
Sadow, P. M.
Gopalan, A.
Fine, S. W.
Al-Ahmadie, H. A.
Chen, Y.
Oliva, E.
Russo, P.
Reuter, V. E.
Tickoo, S. K.
TI Pathologic Characteristics and Clinical Outcome of Renal Epithelioid
Angiomyolipoma: A Multi-Institutional Experience Based on Primary Tumor
Resections
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Mayo Clin, Rochester, MN USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 829
BP 196A
EP 197A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000269
ER
PT J
AU Kao, CS
Idrees, MT
Young, RH
Ulbright, TM
AF Kao, C-S
Idrees, M. T.
Young, R. H.
Ulbright, T. M.
TI Solid Pattern of Testicular Yolk Sac Tumor: A Morphologic and
Immunohistochemical Study of 52 Cases
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Indiana Univ, Sch Med, Indianapolis, IN USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 853
BP 202A
EP 202A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000293
ER
PT J
AU Pettersson, A
Flavin, R
Stark, J
Fiorentino, M
Pollak, A
Penney, K
Sesso, HD
Gleave, M
Bismar, TA
Perner, S
Finn, S
Rubin, MA
Ma, J
Giovannucci, E
Stampfer, M
Kantoff, P
Loda, M
Mucci, L
AF Pettersson, A.
Flavin, R.
Stark, J.
Fiorentino, M.
Pollak, A.
Penney, K.
Sesso, H. D.
Gleave, M.
Bismar, T. A.
Perner, S.
Finn, S.
Rubin, M. A.
Ma, J.
Giovannucci, E.
Stampfer, M.
Kantoff, P.
Loda, M.
Mucci, L.
TI TMPRSS2:ERG Rearrangement and Markers of Metabolic Signaling Pathways
Implicated in Prostate Carcinogenesis
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 [Pettersson, A.; Flavin, R.; Stark, J.; Fiorentino, M.; Pollak, A.; Penney, K.; Sesso, H. D.; Gleave, M.; Bismar, T. A.; Perner, S.; Finn, S.; Rubin, M. A.; Ma, J.; Giovannucci, E.; Stampfer, M.; Kantoff, P.; Loda, M.; Mucci, L.] Dana Farber Harvard Canc Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 917
BP 217A
EP 218A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000357
ER
PT J
AU Ryan, RJ
Wu, S
Borger, D
Iafrate, J
Wu, CL
Le, L
AF Ryan, R. J.
Wu, S.
Borger, D.
Iafrate, J.
Wu, C-L
Le, L.
TI The Lymphoma-Associated EZH2 Codon 641 Mutation Is Not Detected in
Localized Prostate Carcinoma
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 [Ryan, R. J.; Wu, S.; Borger, D.; Iafrate, J.; Wu, C-L; Le, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 933
BP 221A
EP 221A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000373
ER
PT J
AU Stampfer, MJ
Penney, K
Sinnott, J
Flavin, R
Stark, J
Finn, S
Giovannucci, E
Sesso, H
Loda, M
Mucci, L
Fiorentino, M
AF Stampfer, M. J.
Penney, K.
Sinnott, J.
Flavin, R.
Stark, J.
Finn, S.
Giovannucci, E.
Sesso, H.
Loda, M.
Mucci, L.
Fiorentino, M.
TI Does Gleason Grade Progress over Time?
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 [Stampfer, M. J.; Penney, K.; Sinnott, J.; Flavin, R.; Stark, J.; Finn, S.; Giovannucci, E.; Sesso, H.; Loda, M.; Mucci, L.; Fiorentino, M.] Dana Farber Harvard Canc Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 952
BP 225A
EP 225A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000392
ER
PT J
AU Stark, JR
Finn, SP
Ma, J
Sinnott, JA
Schumacher, F
Lis, R
Penney, KL
Kasperzyk, JL
Sesso, HD
Stampfer, MJ
Giovannucci, EL
Loda, M
Mucci, LA
AF Stark, J. R.
Finn, S. P.
Ma, J.
Sinnott, J. A.
Schumacher, F.
Lis, R.
Penney, K. L.
Kasperzyk, J. L.
Sesso, H. D.
Stampfer, M. J.
Giovannucci, E. L.
Loda, M.
Mucci, L. A.
TI Adiponectin Receptor 2 Expression Predicts Lethal Prostate Cancer
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Univ Dublin, Trin Coll, Dublin, Ireland.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Univ Calif Los Angeles, Keck Sch Med, Los Angeles, CA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 954
BP 226A
EP 226A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000394
ER
PT J
AU Al-Agha, OM
Huwait, HP
Chow, C
Yang, W
Senz, JE
Kalloger, SG
Huntsman, DH
Young, R
Gilks, CB
AF Al-Agha, O. M.
Huwait, H. P.
Chow, C.
Yang, W.
Senz, J. E.
Kalloger, S. G.
Huntsman, D. H.
Young, R.
Gilks, C. B.
TI Anti-FOXL2 Antibody Is a Sensitive and Specific Diagnostic Marker for
Ovarian Sex Cord-Stromal Tumors.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Vancouver Gen Hosp, Vancouver, BC, Canada.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 988
BP 234A
EP 234A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000428
ER
PT J
AU Azueta, A
Gatius, S
Velasco, A
Santacana, M
Pallares, J
Clarke, B
Oliva, E
Matias-Guiu, X
AF Azueta, A.
Gatius, S.
Velasco, A.
Santacana, M.
Pallares, J.
Clarke, B.
Oliva, E.
Matias-Guiu, X.
TI Dedifferentiated Carcinoma of the Endometrium and the Ovary: A Molecular
Study of 8 Cases.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Univ Lleida, Hosp Univ Arnau Vilanova, IRB Lleida, Lleida, Spain.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Toronto Gen Hosp, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 999
BP 236A
EP 236A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000439
ER
PT J
AU Biscuola, M
De Vijver, KV
Castilla, MA
Romero-Perez, L
Lopez-Garcia, MA
Palacios, J
Oliva, E
AF Biscuola, M.
De Vijver, K. Van
Castilla, M. A.
Romero-Perez, L.
Lopez-Garcia, M. A.
Palacios, J.
Oliva, E.
TI Molecular Alterations in Endometrial Carcinosarcomas (ECS).
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Hosp Univ Virgen Rocio IBIS, Inst Biomed Sevilla, Seville, Spain.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Romero-Perez, Laura/C-8314-2015; Castilla, M Angeles/C-9454-2015
OI Romero-Perez, Laura/0000-0003-3196-4382;
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1004
BP 237A
EP 238A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000444
ER
PT J
AU Castilla, MA
Moreno-Bueno, G
Romero-Perez, L
Van De Vijver, K
Biscuola, M
Lopez-Garcia, MA
Prat, J
Matias-Guiu, X
Cano, A
Oliva, E
Palacios, J
AF Castilla, M. A.
Moreno-Bueno, G.
Romero-Perez, L.
Van De Vijver, K.
Biscuola, M.
Lopez-Garcia, M. A.
Prat, J.
Matias-Guiu, X.
Cano, A.
Oliva, E.
Palacios, J.
TI Micro-RNA Signature of the Epithelial-Mesenchymal Transition in
Endometrial Carcinosarcoma.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Hosp Univ Virgen Rocio IBIS, Seville, Spain.
IdiPAZ Inst Invest La Paz, Inst Invest Biomed Alberto Sols CSIC UAM, Madrid, Spain.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Hosp San Pau, Barcelona, Spain.
Hosp Arnau Vilanova, Lleida, Spain.
RI Romero-Perez, Laura/C-8314-2015; Castilla, M Angeles/C-9454-2015
OI Romero-Perez, Laura/0000-0003-3196-4382;
NR 0
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1015
BP 240A
EP 240A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000455
ER
PT J
AU Chiang, S
Ali, R
Lee, CH
Gilks, B
Oliva, E
AF Chiang, S.
Ali, R.
Lee, C-H
Gilks, B.
Oliva, E.
TI Frequency of Known Translocations Detected by Fluorescence In Situ
Hybridization in Endometrial and Endometrioid Stromal Tumors (ESTs): A
Study of 57 Patients.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
BC Canc Agcy, Vancouver, BC, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1020
BP 241A
EP 241A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000460
ER
PT J
AU Chiang, S
Gilks, B
Huntsman, DG
Oliva, E
AF Chiang, S.
Gilks, B.
Huntsman, D. G.
Oliva, E.
TI Immunohistochemical and Mutational Analysis of FOXL2 in Uterine Tumors
Resembling Ovarian Sex-Cord Tumors.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
BC Canc Agcy, Vancouver, BC, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1021
BP 241A
EP 241A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000461
ER
PT J
AU Gilks, CB
Oliva, E
Soslow, R
AF Gilks, C. B.
Oliva, E.
Soslow, R.
TI Poor Interobserver Reproducibility in the Diagnosis of High-Grade
Endometrial Carcinoma
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Vancouver Gen Hosp, Vancouver, BC, Canada.
BC Childrens & Womens Hosp, Vancouver, BC, Canada.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1049
BP 248A
EP 248A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000489
ER
PT J
AU Karst, AM
Levanon, K
Hirsch, MS
Drapkin, R
AF Karst, A. M.
Levanon, K.
Hirsch, M. S.
Drapkin, R.
TI Transformation of Fallopian Tube Epithelial Cells Leads to High-Grade
Tumor Formation in a Xenograft Mouse Model
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Chaim Sheba Med Ctr, Sheba Canc Res Ctr, Ramat Gan, Israel.
Brigham & Womens Hosp, Ramat Gan, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1063
BP 249A
EP 249A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000495
ER
PT J
AU Karst, AM
Levanon, K
Duraisamy, S
Liu, JF
Hirsch, MS
Drapkin, R
AF Karst, A. M.
Levanon, K.
Duraisamy, S.
Liu, J. F.
Hirsch, M. S.
Drapkin, R.
TI Stathmin 1, a Marker of PI3K Pathway Activation and Regulator of
Microtubule Dynamics, Is Expressed in Early Serous Ovarian Carcinomas
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Chaim Sheba Med Ctr, Sheba Canc Res Ctr, Ramat Gan, Israel.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1064
BP 249A
EP 249A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000496
ER
PT J
AU Lim, D
Gilks, B
Longacre, T
Nucci, MR
Soslow, RA
Oliva, E
AF Lim, D.
Gilks, B.
Longacre, T.
Nucci, M. R.
Soslow, R. A.
Oliva, E.
TI Interobserver Variability in the Interpretation of Tumor Cell Necrosis
(TCN) in Uterine Leiomyosarcoma (LMS).
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Natl Univ Hlth Syst, Singapore, Singapore.
Vancouver Gen Hosp, Vancouver, BC, Canada.
Stanford Univ, Stanford, CA 94305 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1086
BP 256A
EP 256A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000526
ER
PT J
AU Lim, D
Wang, WL
Lee, CH
Dodge, T
Gilks, B
Oliva, E
AF Lim, D.
Wang, W-L
Lee, C-H
Dodge, T.
Gilks, B.
Oliva, E.
TI Old Versus New FIGO Staging Systems in Predicting Overall Survival in
Patients with Uterine Leiomyosarcoma: A Study of 86 Cases.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Natl Univ Hlth Syst, Singapore, Singapore.
Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
Vancouver Gen Hosp, Vancouver, BC, Canada.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1085
BP 256A
EP 256A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000525
ER
PT J
AU Ning, G
Laury, AR
Quick, CM
Hirsch, MS
Drapkin, R
Mehra, KK
Mehrad, M
McKeon, FD
Crum, CP
Xian, W
AF Ning, G.
Laury, A. R.
Quick, C. M.
Hirsch, M. S.
Drapkin, R.
Mehra, K. K.
Mehrad, M.
McKeon, F. D.
Crum, C. P.
Xian, W.
TI Co-Ordinated Dysregulation of PAX2, ALDH1 and EZH2 in Tubal Serous
Carcinogenesis.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Harvard Univ, Sch Med, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
St Lukes Roosevelt Hosp, New York, NY USA.
Washington Univ, St Louis, MO USA.
A Star Inst Med Biol, Singapore, Singapore.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1110
BP 262A
EP 262A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000550
ER
PT J
AU Tarragona, J
Santacana, M
Valls, J
Oliva, E
Palacios, J
Matias-Guiu, X
AF Tarragona, J.
Santacana, M.
Valls, J.
Oliva, E.
Palacios, J.
Matias-Guiu, X.
TI Stem Cell Marker Expression in Endometrial Carcinoma
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Univ Lleida, IRB Lleida, Hosp Univ Arnau Vilanova, Lleida, Spain.
Hosp Virgen Rocio, Seville, Spain.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1140
BP 268A
EP 268A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000580
ER
PT J
AU Zaino, R
Zhu, J
Abendroth, C
Yemelyanova, A
Oliva, E
Lim, D
Hagemann, IS
Montone, K
Delair, D
Saslow, R
AF Zaino, R.
Zhu, J.
Abendroth, C.
Yemelyanova, A.
Oliva, E.
Lim, D.
Hagemann, I. S.
Montone, K.
Delair, D.
Saslow, R.
TI Stage II Endometrial Carcinoma: Endocervical Gland Spread Is Not
Reproducibly Distinguished from Endocervical Stromal Invasion.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Johns Hopkins Med Ctr, Hershey Med Ctr, Baltimore, MD USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
U Penn, Philadelphia, PA USA.
Mem Sloan Kettering Canc Ctr, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1157
BP 272A
EP 272A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000597
ER
PT J
AU Courville, EL
Lew, M
Sadow, PM
AF Courville, E. L.
Lew, M.
Sadow, P. M.
TI Retrospective Review of Tonsil Specimens: Experiential Assessment of a
Clinical Practice.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1178
BP 277A
EP 277A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000618
ER
PT J
AU Carvajal, A
Sua, L
Silva, N
Pittaluga, S
Royo, C
Sargent, RL
Climent, F
Jacobs, SA
Delabie, J
Naresh, K
Bagg, A
Harris, NL
Swerdlow, SH
Jaffe, ES
Campo, E
AF Carvajal, A.
Sua, L.
Silva, N.
Pittaluga, S.
Royo, C.
Sargent, R. L.
Climent, F.
Jacobs, S. A.
Delabie, J.
Naresh, K.
Bagg, A.
Harris, N. L.
Swerdlow, S. H.
Jaffe, E. S.
Campo, E.
TI "In Situ" Mantle Cell Lymphoma (MCL), an Incidental Finding with an
Indolent Clinical Course
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Hosp Clin Barcelona, Barcelona, Spain.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ Pittsburgh, Pittsburgh, PA 15260 USA.
Oslo Univ Hosp, Oslo, Norway.
Hammersmith Hosp, London, England.
Hosp Univ Penn, Philadelphia, PA 19104 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NCI, Bethesda, MD 20892 USA.
RI Royo, Cristina/H-3193-2015
OI Royo, Cristina/0000-0002-1214-4656
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1228
BP 289A
EP 289A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000668
ER
PT J
AU Chiu, A
Chen, YB
Pinkus, GS
Hasserjian, RP
AF Chiu, A.
Chen, Y-B
Pinkus, G. S.
Hasserjian, R. P.
TI Acute Graft-Versus-Host Disease Is Associated with Increased Bone
Remodeling and Impaired B-Cell Development Suggesting Effects on the
Osteoblastic Niche.
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1237
BP 291A
EP 291A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000677
ER
PT J
AU Hasserjian, RP
Chi, YO
Hu, Y
Kluk, M
Attar, E
Wang, SA
AF Hasserjian, R. P.
Chi, Y. Ok
Hu, Y.
Kluk, M.
Attar, E.
Wang, S. A.
TI Therapy-Related Myelodysplastic Syndrome (MDS) Lacking High-Risk
Karyotype Resembles De Novo Disease and Differs from Conventional
Therapy-Related MDS
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
UMass Med Ctr, Worcester, MA USA.
UT MD Anderson Canc Ctr, Houston, TX USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1275
BP 300A
EP 300A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000715
ER
PT J
AU Katz, SG
LaBelle, JL
Godes, M
Fisher, JK
Bird, GH
Walensky, LD
AF Katz, S. G.
LaBelle, J. L.
Godes, M.
Fisher, J. K.
Bird, G. H.
Walensky, L. D.
TI Stapled BIM BH3 Helix Restores Apoptosis in BIM-Null Mantle Cell
Lymphoma
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1295
BP 304A
EP 305A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000735
ER
PT J
AU Nardi, V
Kluk, M
Attar, E
Winkfield, K
Hasserjian, RP
AF Nardi, V.
Kluk, M.
Attar, E.
Winkfield, K.
Hasserjian, R. P.
TI AML and MDS Following Radiation Therapy Are Similar to De Novo Disease
and Differ from Other Therapy-Related Myeloid Neoplasms
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1322
BP 309A
EP +
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000758
ER
PT J
AU Nardi, V
Rochelle-Keyes, H
Peterson, T
Loda, M
Rosina, L
Raje, N
Sohani, AR
Sabatini, DM
Hasserjian, RP
AF Nardi, V.
Rochelle-Keyes, H.
Peterson, T.
Loda, M.
Rosina, L.
Raje, N.
Sohani, A. R.
Sabatini, D. M.
Hasserjian, R. P.
TI Activation of the PI3K/Akt Pathway in Plasma Cell Myeloma Is Associated
with MAF and DEPTOR Overexpression and Favorable Response to Therapy
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 100th Annual Meeting of the United States and
Canadian-Academy-of-Pathology
CY FEB 26-MAR 04, 2011
CL San Antonio, TX
SP Canadian Acad Pathol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Whitehead Inst, Cambridge, MA 02142 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2011
VL 91
SU 1
MA 1323
BP 311A
EP 311A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 773CQ
UT WOS:000291285000763
ER
EF